WorldWideScience

Sample records for human cocaine cannabis

  1. Acute effects of cocaine and cannabis on response inhibition in humans: an ERP investigation.

    Science.gov (United States)

    Spronk, Desirée B; De Bruijn, Ellen R A; van Wel, Janelle H P; Ramaekers, Johannes G; Verkes, Robbert J

    2016-11-01

    Substance abuse has often been associated with alterations in response inhibition in humans. Not much research has examined how the acute effects of drugs modify the neurophysiological correlates of response inhibition, or how these effects interact with individual variation in trait levels of impulsivity and novelty seeking. This study investigated the effects of cocaine and cannabis on behavioural and event-related potential (ERP) correlates of response inhibition in 38 healthy drug using volunteers. A double-blind placebo-controlled randomized three-way crossover design was used. All subjects completed a standard Go/NoGo task after administration of the drugs. Compared with a placebo, cocaine yielded improved accuracy, quicker reaction times and an increased prefrontal NoGo-P3 ERP. Cannabis produced opposing results; slower reaction times, impaired accuracy and a reduction in the amplitude of the prefrontal NoGo-P3. Cannabis in addition decreased the amplitude of the parietally recorded P3, while cocaine did not affect this. Neither drugs specifically affected the N2 component, suggesting that pre-motor response inhibitory processes remain unaffected. Neither trait impulsivity nor novelty seeking interacted with drug-induced effects on measures of response inhibition. We conclude that acute drug effects on response inhibition seem to be specific to the later, evaluative stages of response inhibition. The acute effects of cannabis appeared less specific to response inhibition than those of cocaine. Together, the results show that the behavioural effects on response inhibition are reflected in electrophysiological correlates. This study did not support a substantial role of vulnerability personality traits in the acute intoxication stage. © 2015 Society for the Study of Addiction.

  2. Cannabis, Cocaine and the Wages of Prime Age Males

    NARCIS (Netherlands)

    van Ours, J.C.

    2005-01-01

    This paper uses a dataset collected among inhabitants of Amsterdam, to study whether wages of prime age male workers are affected by the use of cannabis and cocaine.The analysis shows that cocaine use and infrequent cannabis use do not affect wages.Frequent cannabis use has a negative wage effect.Th

  3. Acute effects of cocaine and cannabis on reversal learning as a function of COMT and DRD2 genotype.

    Science.gov (United States)

    Spronk, Desirée B; Van der Schaaf, Marieke E; Cools, Roshan; De Bruijn, Ellen R A; Franke, Barbara; van Wel, Janelle H P; Ramaekers, Johannes G; Verkes, Robbert J

    2016-01-01

    Long-term cannabis and cocaine use has been associated with impairments in reversal learning. However, how acute cannabis and cocaine administration affect reversal learning in humans is not known. In this study, we aimed to establish the acute effects of administration of cannabis and cocaine on valence-dependent reversal learning as a function of DRD2 Taq1A (rs1800497) and COMT Val108/158Met (rs4680) genotype. A double-blind placebo-controlled randomized 3-way crossover design was used. Sixty-one regular poly-drug users completed a deterministic reversal learning task under the influence of cocaine, cannabis, and placebo that enabled assessment of both reward- and punishment-based reversal learning. Proportion correct on the reversal learning task was increased by cocaine, but decreased by cannabis. Effects of cocaine depended on the DRD2 genotype, as increases in proportion correct were seen only in the A1 carriers, and not in the A2/A2 homozygotes. COMT genotype did not modulate drug-induced effects on reversal learning. These data indicate that acute administration of cannabis and cocaine has opposite effects on reversal learning. The effects of cocaine, but not cannabis, depend on interindividual genetic differences in the dopamine D2 receptor gene.

  4. Acute effects of cocaine and cannabis on response inhibition in humans: an ERP investigation

    NARCIS (Netherlands)

    Spronk, D.B.; De Bruijn, E.R.; van Wel, J.H.; Ramaekers, J.G.; Verkes, R.J.

    2016-01-01

    Substance abuse has often been associated with alterations in response inhibition in humans. Not much research has examined how the acute effects of drugs modify the neurophysiological correlates of response inhibition, or how these effects interact with individual variation in trait levels of impul

  5. [Renal and spleen infarction after massive consumption of cannabis and cocaine in a young man].

    Science.gov (United States)

    Le Guen, P-Y; Gestin, S; Plat, E; Quéhé, P; Bressollette, L

    2011-02-01

    Cannabis is the most widely consumed drug in the world, particularly among young subjects. Cocaine is the third leading illicit drug. Cases of renal infarction associated with combined consumption of cannabis and cocaine have been reported in the literature. We describe the case of a 24-year-old man who presented renal and spleen infarction after massive consumption of cannabis and cocaine. Both vascular events arose on healthy arteries. Etiological tests were negative leading to the conclusion that the events resulted from a toxic cause related to cannabis and cocaine consumption. Different mechanisms, potentially including thrombosis, might explain the association of cannabis and cocaine with vascular events. We suggest that a systematic search for cannabis and cocaine consumption among young victims of vascular disease might be useful.

  6. Psychedelic symptoms of cannabis and cocaine use as a function of trait impulsivity.

    Science.gov (United States)

    van Wel, J H P; Spronk, D B; Kuypers, K P C; Theunissen, E L; Toennes, S W; Verkes, R J; Ramaekers, J G

    2015-03-01

    Trait impulsivity has been linked to addiction in humans. It has been suggested that drug users with high trait impulsivity levels are more sensitive to subjective drug intoxication. This study assessed whether subjective response to drugs differs between drug users with normal or high levels of trait impulsivity. Regular drug users (N = 122) received doses of cocaine HCl, cannabis, and placebo in a three-way crossover study. Their mood, dissociative state, and psychedelic symptoms were measured with subjective rating scales (CADDS, Bowdle, POMS). Trait impulsivity was assessed with the Barratt Impulsiveness Scale. Cannabis increased dissociation and psychedelic state, as well as fatigue, confusion, depression and anxiety, and decreased arousal, positive mood, vigor, friendliness, and elation. Cocaine increased dissociation, psychedelic state, vigor, friendliness, elation, positive mood, anxiety and arousal, while decreasing fatigue. Only a few subjective items revealed a drug × trait impulsivity interaction, suggesting that psychedelic symptoms were most intense in high impulsivity subjects. Trait impulsiveness ratings were negatively correlated with ratings of vigor (r = -.197) and positively correlated with ratings of loss of thought control (r = .237) during cannabis intoxication. It is concluded that a broad association between trait impulsivity and psychedelic subjective drug experience appears to be absent. © The Author(s) 2015.

  7. Prediction of cannabis and cocaine use in adolescence using decision trees and logistic regression

    Directory of Open Access Journals (Sweden)

    Alfonso L. Palmer

    2010-01-01

    Full Text Available Spain is one of the European countries with the highest prevalence of cannabis and cocaine use among young people. The aim of this study was to investigate the factors related to the consumption of cocaine and cannabis among adolescents. A questionnaire was administered to 9,284 students between 14 and 18 years of age in Palma de Mallorca (47.1% boys and 52.9% girls whose mean age was 15.59 years. Logistic regression and decision trees were carried out in order to model the consumption of cannabis and cocaine. The results show the use of legal substances and committing fraudulence or theft are the main variables that raise the odds of consuming cannabis. In boys, cannabis consumption and a family history of drug use increase the odds of consuming cocaine, whereas in girls the use of alcohol, behaviours of fraudulence or theft and difficulty in some personal skills influence their odds of consuming cocaine. Finally, ease of access to the substance greatly raises the odds of consuming cocaine and cannabis in both genders. Decision trees highlight the role of consuming other substances and committing fraudulence or theft. The results of this study gain importance when it comes to putting into practice effective prevention programmes.

  8. Influence of thermal hair straightening on cannabis and cocaine content in hair.

    Science.gov (United States)

    Ettlinger, Jana; Yegles, Michel

    2016-08-01

    It has been shown that cosmetic treatment like bleaching and perming may lead to an important decrease of drugs of abuse content in hair. Currently, hair straightening has become a regular hair treatment especially for women. The aim of this preliminary study was to investigate the effect of in vitro treatment of hair with heat straightener on cannabis and cocaine concentrations in hair. 17 positive cannabis and 7 positive cocaine hair samples were treated in vitro with a hair straightener. During this treatment hair was put sequentially 30 times in contact with heated iron plates at 200°C during 2s corresponding to a total time of contact of 1min. THC and Cannabinol (CBN) were analysed in cannabis positive hair and cocaine, benzoylecgonin (BZE) and cocaethylene were analysed in cocaine positive hair. Analyses were performed with routine methods using GC/MS in electron impact mode. Regarding cannabis results a decrease of THC concentrations was found in 11 of 17 hair samples after thermal treatment, whereas in 6 cases an increase was shown. In all the hair samples CBN concentrations was explicitly higher after the in vitro treatment. Regarding cocaine results cocaine and cocaethylene concentrations decreased after treatment in all seven hair samples; in contrast, higher concentrations of BZE were determined. The strong increase of CBN and BZE content in hair after thermal treatments may be due to the fact that THC is converted by heat into CBN and cocaine into BZE, thus changing the respective ratios of the analysed substances. In conclusion, thermal straightening should be considered as other cosmetic hair treatments for a correct interpretation of hair results. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Cannabidiol, a Cannabis sativa constituent, inhibits cocaine-induced seizures in mice: Possible role of the mTOR pathway and reduction in glutamate release.

    Science.gov (United States)

    Gobira, Pedro H; Vilela, Luciano R; Gonçalves, Bruno D C; Santos, Rebeca P M; de Oliveira, Antonio C; Vieira, Luciene B; Aguiar, Daniele C; Crippa, José A; Moreira, Fabricio A

    2015-09-01

    Cannabidiol (CBD), a major non-psychotomimetic constituent of Cannabis sativa, has therapeutic potential for certain psychiatric and neurological disorders. Studies in laboratory animals and limited human trials indicate that CBD has anticonvulsant and neuroprotective properties. Its effects against cocaine neurotoxicity, however, have remained unclear. Thus, the present study tested the hypothesis that CBD protects against cocaine-induced seizures and investigated the underlying mechanisms. CBD (30 mg/kg) pre-treatment increased the latency and reduced the duration of cocaine (75 mg/kg)-induced seizures in mice. The CB1 receptor antagonist, AM251 (1 and 3mg/kg), and the CB2 receptor antagonist, AM630 (2 and 4 mg/kg), failed to reverse this protective effect, suggesting that alternative mechanisms are involved. Synaptosome studies with the hippocampus of drug-treated animals revealed that cocaine increases glutamate release, whereas CBD induces the opposite effect. Finally, the protective effect of this cannabinoid against cocaine-induced seizure was reversed by rapamycin (1 and 5mg/kg), an inhibitor of the mammalian target of rapamycin (mTOR) intracellular pathway. In conclusion, CBD protects against seizures in a model of cocaine intoxication. These effects possibly occur through activation of mTOR with subsequent reduction in glutamate release. CBD should be further investigated as a strategy for alleviating psychostimulant toxicity.

  10. Cannabis and cocaine decrease cognitive impulse control and functional corticostriatal connectivity in drug users with low activity DBH genotypes

    NARCIS (Netherlands)

    Ramaekers, J.G.; van Wel, J.H.; Spronk, D.; Franke, B.; Kenis, G.; Toennes, S.W.; Kuypers, K.P.; Theunissen, E.L.; Stiers, P.; Verkes, R.J.

    2016-01-01

    The dopamine beta-hydroxylase (DbetaH) enzyme transforms dopamine into noradrenaline. We hypothesized that individuals with low activity DBH genotypes (rs1611115 CT/TT) are more sensitive to the influence of cannabis and cocaine on cognitive impulse control and functional connectivity in the limbic

  11. High Suicide Risk after the Development of Cognitive and Working Memory Deficits Caused by Cannabis, Cocaine and Ecstasy Use

    Science.gov (United States)

    Pompili, Maurizio; Lester, David; Girardi, Paolo; Tatarelli, Roberto

    2007-01-01

    We report the case of attempted suicide by a 30-year-old man who had significant cognitive deficits that developed after at least three years of polysubstance use with cannabis, methylenedioxymethamphetamine (MDMA, "ecstasy") and cocaine. The patient reported increasing difficulties in his professional and interpersonal life which may have been…

  12. Cannabis and Breastfeeding

    Directory of Open Access Journals (Sweden)

    Aurélia Garry

    2009-01-01

    Full Text Available Cannabis is a drug derived from hemp plant, Cannabis sativa, used both as a recreational drug or as medicine. It is a widespread illegal substance, generally smoked for its hallucinogenic properties. Little is known about the adverse effects of postnatal cannabis exposure throw breastfeeding because of a lack of studies in lactating women. The active substance of cannabis is the delta 9 TetraHydroCannabinol (THC. Some studies conclude that it could decrease motor development of the child at one year of age. Therefore, cannabis use and abuse of other drugs like alcohol, tobacco, or cocaine must be contraindicated during breastfeeding. Mothers who use cannabis must stop breastfeeding, or ask for medical assistance to stop cannabis use in order to provide her baby with all the benefits of human milk.

  13. Human studies of cannabinoids and medicinal cannabis.

    Science.gov (United States)

    Robson, P

    2005-01-01

    Cannabis has been known as a medicine for several thousand years across many cultures. It reached a position of prominence within Western medicine in the nineteenth century but became mired in disrepute and legal controls early in the twentieth century. Despite unremitting world-wide suppression, recreational cannabis exploded into popular culture in the 1960s and has remained easily obtainable on the black market in most countries ever since. This ready availability has allowed many thousands of patients to rediscover the apparent power of the drug to alleviate symptoms of some of the most cruel and refractory diseases known to humankind. Pioneering clinical research in the last quarter of the twentieth century has given some support to these anecdotal reports, but the methodological challenges to human research involving a pariah drug are formidable. Studies have tended to be small, imperfectly controlled, and have often incorporated unsatisfactory synthetic cannabinoid analogues or smoked herbal material of uncertain composition and irregular bioavailability. As a result, the scientific evaluation of medicinal cannabis in humans is still in its infancy. New possibilities in human research have been opened up by the discovery of the endocannabinoid system, a rapidly expanding knowledge of cannabinoid pharmacology, and a more sympathetic political environment in several countries. More and more scientists and clinicians are becoming interested in exploring the potential of cannabis-based medicines. Future targets will extend beyond symptom relief into disease modification, and already cannabinoids seem to offer particular promise in the treatment of certain inflammatory and neurodegenerative conditions. This chapter will begin with an outline of the development and current status of legal controls pertaining to cannabis, following which the existing human research will be reviewed. Some key safety issues will then be considered, and the chapter will conclude with

  14. The effects of price and perceived quality on the behavioural economics of alcohol, amphetamine, cannabis, cocaine, and ecstasy purchases.

    Science.gov (United States)

    Goudie, Andrew J; Sumnall, Harry R; Field, Matt; Clayton, Hannah; Cole, Jon C

    2007-07-10

    Behavioural economic models of substance use describe the relationship between changes in unit price and consumption. However, these models rarely take account of the perceived quality (i.e. potency) of controlled drugs. Therefore we investigated the effects of both price and quality on the decision to purchase controlled drugs by polysubstance misusers. Forty current polysubstance misusers (29 males, 11 females; mean age 23.8) were recruited into the study. Participants were asked to hypothetically purchase drugs from a price list of alcohol, amphetamine, cannabis, cocaine and ecstasy at different levels of quality and price (i.e. better quality drugs cost more money). The disposable income available for those purchases was systematically varied in order to determine the impact of income on the decision to purchase drugs. Demand for both normal and strong alcohol was income inelastic. Demand for both poor and average quality cannabis and ecstasy was income inelastic, but demand for good quality cannabis and ecstasy was income elastic. The demand for poor quality cocaine was income inelastic, with the demand for both average and good quality cocaine being income elastic. Participants reported too few purchases of amphetamine, which precluded behavioural economic analysis. These results suggest that, like other goods, controlled drugs are purchased based upon the consumer's interpretations of their relative value. Therefore, it is probable that the purchase and subsequent use of controlled drugs by polysubstance misusers will be heavily influenced by the economic environment.

  15. Believability of Messages about Cannabis, Cocaine and Heroin among Never-Triers, Trier-Rejecters and Current Users of Cannabis

    Science.gov (United States)

    Jones, Sandra C.; Rossiter, John R.

    2004-01-01

    This paper examines the believability of strong warnings about the negative consequences of drug use among young adults in Australia who have never tried, currently use, or have tried and rejected cannabis. It finds that the strong warnings about cannabis are generally believed by never-triers. The same warnings are perceived by current users as…

  16. A comparison of independent depression and substance-induced depression in cannabis-, cocaine-, and opioid-dependent treatment seekers.

    Science.gov (United States)

    Dakwar, Elias; Nunes, Edward V; Bisaga, Adam; Carpenter, Kenneth C; Mariani, John P; Sullivan, Maria A; Raby, Wilfrid N; Levin, Frances R

    2011-01-01

    Depressive symptoms often coexist with substance use disorders (SUDs). The DSM-IV has identified two distinct categories for depression coexisting with SUDs-independent depression and substance-induced depression. While this distinction has important therapeutic and prognostic implications, it remains difficult to make in clinical practice; the differentiation is often guided by chronological and symptom severity criteria that patients may be unable to precisely provide. Furthermore, it is unclear whether the various substances commonly abused-cannabis, cocaine, and opioids-are equally associated with the two types of depression. Predictors, associations, and other markers may be helpful in guiding the diagnostic process. We, therefore, examined the differences between cannabis-, cocaine-, and opioid-dependent individuals contending with independent depression and those contending with substance-induced depression in regard to several variables, hypothesizing that independent depression is more commonly found in females, and that it is associated with higher symptom severity and psychiatric comorbidity. Cocaine-, cannabis-, and/or opioid-dependent, treatment-seeking individuals underwent a structured clinical interview for DSM-IV-TR disorders after providing consent at our clinical research site; those with co-existing primary depression or substance-induced depression diagnoses were provided with further questionnaires and were entered into this analysis (n= 242). Pair-wise comparisons were conducted between the groups classified as independent versus substance-induced depression with 2-by-2 tables and chi-square tests for dichotomous independent variables, and t-tests for continuous variables. Binomial logistic regression was performed in order to ascertain which of the variables were significant predictors. Women were more likely than men to have independent depression (pCannabis dependence was highly associated with independent depression (pdepression

  17. The role of endocannabinoid transmission in cocaine addiction.

    Science.gov (United States)

    Arnold, Jonathon C

    2005-06-01

    Research is beginning to outline a role for the endocannabinoid system in cocaine addiction. Human and animal studies indicate that exogenous cannabinoids modulate the acute rewarding effects of cocaine. These studies, however, cannot directly investigate the necessity of endocannabinoid transmission in cocaine addiction. Studies that do offer a direct assessment show that neither pharmacological antagonism nor deletion of the CB1 receptor alters the acute rewarding effects of cocaine. In contrast, CB1 receptors appear to be involved in the association of cocaine reward with environmental cues and reinstatement of cocaine self-administration. Together, these results point to CB1 receptor antagonists as potential anti-craving compounds in the treatment of cocaine addiction. Given the limitations of human population studies, animal research may be useful in discerning causal inferences between cannabis and cocaine use. While animal research suggests cannabis use may precipitate cocaine relapse, cross-sensitization between cannabinoids and cocaine has not been demonstrated and CB1 receptors do not mediate behavioral sensitization to cocaine. The effect of acute or chronic cocaine on endocannabinoid transmission in reward-related areas of the brain is relatively under-researched. Acute cocaine administration increases anandamide levels in the striatum, an effect that is mediated by dopamine D2-like receptors. Conversely, chronic cocaine exposure has no effect on anandamide, but decreases 2-arachidonylglycerol levels in the limbic forebrain. This review highlights research indicating that the endocannabinoid system may subserve certain aspects of cocaine addiction and suggests avenues for future investigation.

  18. Cocaine

    Science.gov (United States)

    Cocaine is a white powder. It can be snorted up the nose or mixed with water and injected with a needle. Cocaine can also be made into small white rocks, ... Crack is smoked in a small glass pipe. Cocaine speeds up your whole body. You may feel ...

  19. Cocaine

    Science.gov (United States)

    ... nerves, including seizures and strokes. How can a cocaine overdose be treated? Because cocaine overdose often leads to a heart attack, stroke, or ... severe paranoia with auditory hallucinations A person can overdose on cocaine, which can lead to death. Behavioral therapy may ...

  20. An application of item response theory analysis to alcohol, cannabis, and cocaine criteria in DSM-IV.

    Science.gov (United States)

    Langenbucher, James W; Labouvie, Erich; Martin, Christopher S; Sanjuan, Pilar M; Bavly, Lawrence; Kirisci, Levent; Chung, Tammy

    2004-02-01

    Item response theory (IRT) is supplanting classical test theory as the basis for measures development. This study demonstrated the utility of IRT for evaluating DSM-IV diagnostic criteria. Data on alcohol, cannabis, and cocaine symptoms from 372 adult clinical participants interviewed with the Composite International Diagnostic Interview--Expanded Substance Abuse Module (CIDI-SAM) were analyzed with Mplus (B. Muthen & L. Muthen, 1998) and MULTILOG (D. Thissen, 1991) software. Tolerance and legal problems criteria were dropped because of poor fit with a unidimensional model. Item response curves, test information curves, and testing of variously constrained models suggested that DSM-IV criteria in the CIDI-SAM discriminate between only impaired and less impaired cases and may not be useful to scale case severity. IRT can be used to study the construct validity of DSM-IV diagnoses and to identify diagnostic criteria with poor performance.

  1. Temperament and character traits associated with the use of alcohol, cannabis, cocaine, benzodiazepines, and hallucinogens: evidence from a large Brazilian web survey

    Directory of Open Access Journals (Sweden)

    Ricardo Schneider Jr.

    2015-03-01

    Full Text Available Objectives: To evaluate how personality traits are associated with occasional use, abuse, and dependence of alcohol, cannabis, cocaine, benzodiazepines, and hallucinogens in a large availability sample of adults via online questionnaires. Methods: The sample consisted of 8,646 individuals (24.7% men and 75.3% women who completed an anonymous web survey. Involvement with drugs and temperament/character traits were assessed through the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST and the Temperament and Character Inventory - Revised (TCI-R, respectively. Interactions among variables were analyzed using MANOVA with Bonferroni adjustment. Results: Novelty seeking was the trait most associated with increased involvement with alcohol, cannabis, and cocaine. There was a significant association between harm avoidance and benzodiazepine use. Persistence was lower in cannabis-, benzodiazepine-, and cocaine-dependent subjects, as well as in hallucinogen abusers. Self-directedness was reduced in dependents of all drug classes. No strong relationships were found between other temperament or character dimensions and the severity of drug use. Conclusions: Novelty seeking was associated with increased involvement with all drugs studied in this sample, although to a lesser extent with benzodiazepines and hallucinogens. The temperament and character profile for benzodiazepine use was different from that of other drugs due to the relationship with higher harm avoidance and self-transcendence and lower self-directedness.

  2. Toward a global view of alcohol, tobacco, cannabis, and cocaine use: findings from the WHO World Mental Health Surveys.

    Directory of Open Access Journals (Sweden)

    Louisa Degenhardt

    2008-07-01

    Full Text Available BACKGROUND: Alcohol, tobacco, and illegal drug use cause considerable morbidity and mortality, but good cross-national epidemiological data are limited. This paper describes such data from the first 17 countries participating in the World Health Organization's (WHO's World Mental Health (WMH Survey Initiative. METHODS AND FINDINGS: Household surveys with a combined sample size of 85,052 were carried out in the Americas (Colombia, Mexico, United States, Europe (Belgium, France, Germany, Italy, Netherlands, Spain, Ukraine, Middle East and Africa (Israel, Lebanon, Nigeria, South Africa, Asia (Japan, People's Republic of China, and Oceania (New Zealand. The WHO Composite International Diagnostic Interview (CIDI was used to assess the prevalence and correlates of a wide variety of mental and substance disorders. This paper focuses on lifetime use and age of initiation of tobacco, alcohol, cannabis, and cocaine. Alcohol had been used by most in the Americas, Europe, Japan, and New Zealand, with smaller proportions in the Middle East, Africa, and China. Cannabis use in the US and New Zealand (both 42% was far higher than in any other country. The US was also an outlier in cocaine use (16%. Males were more likely than females to have used drugs; and a sex-cohort interaction was observed, whereby not only were younger cohorts more likely to use all drugs, but the male-female gap was closing in more recent cohorts. The period of risk for drug initiation also appears to be lengthening longer into adulthood among more recent cohorts. Associations with sociodemographic variables were consistent across countries, as were the curves of incidence of lifetime use. CONCLUSIONS: Globally, drug use is not distributed evenly and is not simply related to drug policy, since countries with stringent user-level illegal drug policies did not have lower levels of use than countries with liberal ones. Sex differences were consistently documented, but are decreasing in more

  3. Cannabis and tolerance: acute drug impairment as a function of cannabis use history

    OpenAIRE

    Ramaekers, J. G.; van Wel, J.H.; D. B. Spronk; Toennes, S. W.; Kuypers, K. P. C.; Theunissen, E L; Verkes, R. J.

    2016-01-01

    Cannabis use history as predictor of neurocognitive response to cannabis intoxication remains subject to scientific and policy debates. The present study assessed the influence of cannabis on neurocognition in cannabis users whose cannabis use history ranged from infrequent to daily use. Drug users (N = 122) received acute doses of cannabis (300 mug/kg THC), cocaine HCl (300 mg) and placebo. Cocaine served as active control for demonstrating neurocognitive test sensitivity. Executive function...

  4. Probing cocaine-antibody interactions in buffer and human serum.

    Directory of Open Access Journals (Sweden)

    Muthu Ramakrishnan

    Full Text Available BACKGROUND: Despite progress in cocaine immunotherapy, the kinetic and thermodynamic properties of antibodies which bind to cocaine and its metabolites are not well understood. It is also not clear how the interactions between them differ in a complex matrix such as the serum present in the human body. In the present study, we have used microscale thermophoresis (MST, isothermal titration calorimetry (ITC, and surface plasmon resonance (SPR we have evaluated the affinity properties of a representative mouse monoclonal (mAb08 as well as those of polyclonal antibodies purified from vaccinated mouse and human patient serum. RESULTS: MST analysis of fluorescently tagged mAb08 binding to cocaine reveals an approximately 15 fold decrease in its equilibrium dissociation constant in 20-50% human serum compared with that in saline buffer. A similar trend was also found using enriched polyclonal antibodies purified from vaccinated mice and patient serum, for which we have used fluorescently tagged bovine serum albumin conjugated to succinyl norcocaine (BSA-SNC. This conjugate closely mimics both cocaine and the hapten used to raise these antibodies. The ITC data also revealed that cocaine has a moderate affinity of about 2 µM to 20% human serum and very little interaction with human serum albumin or nonspecific human IgG at that concentration range. In a SPR inhibition experiment, the binding of mAb08 to immobilized BSA-SNC was inhibited by cocaine and benzoylecgonine in a highly competitive manner, whereas the purified polyclonal antibodies from vaccinated humans and mice, revealed preferential selectivity to pharmacologically active cocaine but not to the inactive metabolite benzoylecgonine. We have also developed a simple binding model to simulate the challenges associated with cocaine immunotherapy using the variable quantitative and kinetic properties of the antibodies. CONCLUSIONS: High sensitivity calorimetric determination of antibody binding to

  5. Thinking high: the impact of cannabis on human cognition

    OpenAIRE

    Kowal, M.A.

    2016-01-01

    The research presented in this thesis focused on the effects of cannabis on mental functions and the brain. Specifically, the investigation aimed at exploring how cannabis affects creative thinking, awareness of errors, and the neurotransmitter dopamine among regular cannabis users. It was discovered that cannabis does not improve creativity and that it can decrease error awareness and impair dopaminergic functioning. Consequently, these findings allow for a better understanding of the nature...

  6. Thinking high : the impact of cannabis on human cognition

    NARCIS (Netherlands)

    Kowal, M.A.

    2016-01-01

    The research presented in this thesis focused on the effects of cannabis on mental functions and the brain. Specifically, the investigation aimed at exploring how cannabis affects creative thinking, awareness of errors, and the neurotransmitter dopamine among regular cannabis users. It was discovere

  7. Thinking high : the impact of cannabis on human cognition

    NARCIS (Netherlands)

    Kowal, M.A.

    2016-01-01

    The research presented in this thesis focused on the effects of cannabis on mental functions and the brain. Specifically, the investigation aimed at exploring how cannabis affects creative thinking, awareness of errors, and the neurotransmitter dopamine among regular cannabis users. It was discovere

  8. Mapping cocaine binding sites in human and baboon brain in vivo.

    Science.gov (United States)

    Fowler, J S; Volkow, N D; Wolf, A P; Dewey, S L; Schlyer, D J; Macgregor, R R; Hitzemann, R; Logan, J; Bendriem, B; Gatley, S J

    1989-01-01

    The first direct measurements of cocaine binding in the brain of normal human volunteers and baboons have been made by using positron emission tomography (PET) and tracer doses of [N-11C-methyl]-(-)-cocaine ([11C]cocaine). Cocaine's binding and release from brain are rapid with the highest regional uptake of carbon-11 occurring in the corpus striatum at 4-10 minutes after intravenous injection of labeled cocaine. This was followed by a clearance to half the peak value at about 25 minutes with the overall time course paralleling the previously documented time course of the euphoria experienced after intravenous cocaine administration. Blockade of the dopamine reuptake sites with nomifensine reduced the striatal but not the cerebellar uptake of [11C]cocaine in baboons indicating that cocaine binding is associated with the dopamine reuptake site in the corpus striatum. A comparison of labeled metabolites of cocaine in human and baboon plasma showed that while cocaine is rapidly metabolized in both species, the profile of labeled metabolites is different, with baboon plasma containing significant amounts of labeled carbon dioxide, and human plasma containing no significant labeled carbon dioxide. These studies demonstrate the feasibility of using [11C]cocaine and PET to map binding sites for cocaine in human brain, to monitor its kinetics, and to characterize its binding mechanism by using appropriate pharmacological challenges.

  9. Use of drugs of abuse in less than 30-year-old drivers killed in a road crash in France: a spectacular increase for cannabis, cocaine and amphetamines.

    Science.gov (United States)

    Mura, P; Chatelain, C; Dumestre, V; Gaulier, J M; Ghysel, M H; Lacroix, C; Kergueris, M F; Lhermitte, M; Moulsma, M; Pépin, G; Vincent, F; Kintz, P

    2006-07-13

    A collaborative study was conducted in France in order to determine the prevalence of cannabinoids, opiates, cocaine metabolites and amphetamines in blood samples from drivers killed in road accidents in 2003 and 2004 and to compare these values with those of a previous study performed during the period 2000-2001 involving 900 drivers. Blood samples were provided from 2003 under 30-year-old drivers, killed in a traffic accident. Drugs of abuse were determined by gas chromatography-mass spectrometry using the same analytical procedures in all the 12 laboratories. The most frequently observed compounds were by far cannabinoids, that tested positive in 39.6% of the total number of samples. Delta9 tetrahydrocannabinol (THC), the most active of the principle constituents in marijuana (cannabis sativa), was detected in the blood of 28.9% drivers and was the single drug of abuse in 80.2% of the positive cases. It was associated with amphetamines in 7.4% and with opiates and cocaine in 1.9 and 4.8%, respectively. Amphetamines were present in 3.1% of the total number of samples, cocaine metabolites in 3.0% and opiates in 3.5%. When comparing these results with those of a previous study performed 3 years before, a significant increase is observed for THC (28.9% versus 16.9%), cocaine metabolites (3.0% versus 0.2%) and amphetamines (3.1% versus 1.4%). This study demonstrates the critical necessity of implementing in France as soon as possible systematical roadside testing for drugs of abuse.

  10. Psychedelic symptoms of cannabis and cocaine use as a function of trait impulsivity

    NARCIS (Netherlands)

    Wel, J. van; Spronk, D.B.; Kuypers, K.; Theunissen, E.; Toennes, S.; Verkes, R.J.; Ramaekers, J.

    2015-01-01

    Trait impulsivity has been linked to addiction in humans. It has been suggested that drug users with high trait impulsivity levels are more sensitive to subjective drug intoxication. This study assessed whether subjective response to drugs differs between drug users with normal or high levels of

  11. Psychedelic symptoms of cannabis and cocaine use as a function of trait impulsivity

    NARCIS (Netherlands)

    Wel, J. van; Spronk, D.B.; Kuypers, K.; Theunissen, E.; Toennes, S.; Verkes, R.J.; Ramaekers, J.

    2015-01-01

    Trait impulsivity has been linked to addiction in humans. It has been suggested that drug users with high trait impulsivity levels are more sensitive to subjective drug intoxication. This study assessed whether subjective response to drugs differs between drug users with normal or high levels of tra

  12. Psychedelic symptoms of cannabis and cocaine use as a function of trait impulsivity

    NARCIS (Netherlands)

    Wel, J. van; Spronk, D.B.; Kuypers, K.; Theunissen, E.; Toennes, S.; Verkes, R.J.; Ramaekers, J.

    2015-01-01

    Trait impulsivity has been linked to addiction in humans. It has been suggested that drug users with high trait impulsivity levels are more sensitive to subjective drug intoxication. This study assessed whether subjective response to drugs differs between drug users with normal or high levels of tra

  13. [MEDICAL CANNABIS].

    Science.gov (United States)

    Naftali, Timna

    2016-02-01

    The cannabis plant has been known to humanity for centuries as a remedy for pain, diarrhea and inflammation. Current research is inspecting the use of cannabis for many diseases, including multiple sclerosis, epilepsy, dystonia, and chronic pain. In inflammatory conditions cannabinoids improve pain in rheumatoid arthritis and:pain and diarrhea in Crohn's disease. Despite their therapeutic potential, cannabinoids are not free of side effects including psychosis, anxiety, paranoia, dependence and abuse. Controlled clinical studies investigating the therapeutic potential of cannabis are few and small, whereas pressure for expanding cannabis use is increasing. Currently, as long as cannabis is classified as an illicit drug and until further controlled studies are performed, the use of medical cannabis should be limited to patients who failed conventional better established treatment.

  14. Effects of Cannabis Use on Human Behavior, Including Cognition, Motivation, and Psychosis: A Review.

    Science.gov (United States)

    Volkow, Nora D; Swanson, James M; Evins, A Eden; DeLisi, Lynn E; Meier, Madeline H; Gonzalez, Raul; Bloomfield, Michael A P; Curran, H Valerie; Baler, Ruben

    2016-03-01

    With a political debate about the potential risks and benefits of cannabis use as a backdrop, the wave of legalization and liberalization initiatives continues to spread. Four states (Colorado, Washington, Oregon, and Alaska) and the District of Columbia have passed laws that legalized cannabis for recreational use by adults, and 23 others plus the District of Columbia now regulate cannabis use for medical purposes. These policy changes could trigger a broad range of unintended consequences, with profound and lasting implications for the health and social systems in our country. Cannabis use is emerging as one among many interacting factors that can affect brain development and mental function. To inform the political discourse with scientific evidence, the literature was reviewed to identify what is known and not known about the effects of cannabis use on human behavior, including cognition, motivation, and psychosis.

  15. Chronic cannabis use is associated with impaired fear extinction in humans.

    Science.gov (United States)

    Papini, Santiago; Ruglass, Lesia M; Lopez-Castro, Teresa; Powers, Mark B; Smits, Jasper A J; Hien, Denise A

    2017-01-01

    The use of fear conditioning and extinction paradigms to examine intermediate phenotypes of anxiety and stress-related disorders has facilitated the identification of neurobiological mechanisms that underlie specific components of abnormal psychological functioning. Across species, acute pharmacologic manipulation of the endogenous cannabinoid system has provided evidence of its critical role in fear extinction, but the effects of chronic cannabis on extinction are relatively understudied. In rats, chronic cannabinoid administration impairs fear extinction in a drug-free state. Here we examine whether chronic cannabis use is associated with impaired fear extinction in humans. Participants were healthy chronic cannabis users (n = 20) and nonuser controls with minimal lifetime cannabis use (n = 20) matched on age, sex, and race who all screened negative for psychiatric disorders. A 2-day differential fear conditioning paradigm was used to test the hypothesis that chronic cannabis use would be associated with impaired extinction of the skin conductance response. Consistent with hypotheses, chronic cannabis use was associated with reduced within-session extinction of skin conductance response on Day 1 (d = 0.78), and between-session extinction on Day 2 (d = 0.76). Unexpectedly, cannabis use was also associated with reduced subjective differentiation between threat and safety stimuli during conditioning. Replication and translation of findings are necessary to test potential mechanisms directly and examine whether impairments can be reversed pharmacologically or after a period of cannabis abstinence. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  16. D3 dopamine and kappa opioid receptor alterations in human brain of cocaine-overdose victims.

    Science.gov (United States)

    Mash, D C; Staley, J K

    1999-06-29

    Cocaine is thought to be addictive because chronic use leads to molecular adaptations within the mesolimbic dopamine (DA) circuitry, which affects motivated behavior and emotion. Although the reinforcing effects of cocaine are mediated primarily by blockade of DA uptake, reciprocal signaling between DA and endogenous opioids has important implications for understanding cocaine dependence. We have used in vitro autoradiography and ligand binding to map D3 DA and kappa opioid receptors in the human brains of cocaine-overdose victims. The number of D3 binding sites was increased one-to threefold over the nucleus accumbens and ventromedial sectors of the caudate and putamen from cocaine-overdose victims, as compared to age-matched and drug-free control subjects. D3 receptor/cyclophilin mRNA ratios in the nucleus accumbens were increased sixfold in cocaine-overdose victims over control values, suggesting that cocaine exposure also affects the expression of D3 receptor mRNA. The number of kappa opioid receptors in the nucleus accumbens and other corticolimbic areas from cocaine fatalities was increased twofold as compared to control values. Cocaine-overdose victims exhibiting preterminal excited delirium had a selective upregulation of kappa receptors measured also in the amygdala. Understanding the complex regulatory profiles of DA and opioid synaptic markers that occur with chronic misuse of cocaine may suggest multitarget strategies for treating cocaine dependence.

  17. Dopamine D3 receptor-preferring agonist enhances the subjective effects of cocaine in humans.

    Science.gov (United States)

    Newton, Thomas F; Haile, Colin N; Mahoney, James J; Shah, Ravi; Verrico, Christopher D; De La Garza, Richard; Kosten, Thomas R

    2015-11-30

    Pramipexole is a D3 dopamine receptor-preferring agonist indicated for the treatment of Parkinson disease. Studies associate pramipexole with pathological gambling and impulse control disorders suggesting a role for D3 receptors in reinforcement processes. Clinical studies showed pramipexole decreased cocaine craving and reversed central deficits in individuals with cocaine use disorder. Preclinical studies have shown acute administration of pramipexole increases cocaine's reinforcing effects whereas other reports suggest chronic pramipexole produces tolerance to cocaine. In a randomized, double-blind, placebo-controlled study we examined the impact of pramipexole treatment on the subjective effects produced by cocaine in volunteers with cocaine use disorder. Volunteers received pramipexole titrated up to 3.0mg/d or placebo over 15 days. Participants then received intravenous cocaine (0, 20 and 40mg) on day 15. Cardiovascular and subjective effects were obtained with visual analog scales at time points across the session. Pramipexole alone increased peak heart rate following saline and diastolic blood pressure following cocaine. Pramipexole produced upwards of two-fold increases in positive subjective effects ratings following cocaine. These results indicate that chronic D3 receptor activation increases the subjective effects of cocaine in humans. Caution should be used when prescribing pramipexole to patients that may also use cocaine.

  18. Can ropinirole modulate reinforcing subjective effects of cocaine in humans?

    Directory of Open Access Journals (Sweden)

    Angelo Giovanni Icro eMaremmani

    2011-08-01

    Full Text Available In this study we evaluated, by means of the Cocaine Rush Visual Analogue Scale (CRVAS, the impact of ropinirole on the expected rush induced by cocaine in a group of heroin addicts abusing cocaine; the self-reported reaction to the rush blockade (if any on cocaine consumption, and the correlations between this self-reported reaction and individual, clinical and therapeutic parameters. Nineteen cocaine abuser heroin-dependent patients entered the study. Their experienced cocaine rush was 61.31±32.1% of the maximum effect previously experienced. Compared with their previous rush intensity 16 patients experienced significantly lower intensity, three the same intensity and none a higher intensity. In particular, two patients experienced a complete blockade of rush and reported a reduced use of cocaine. Fourteen patients experienced a partial blockade of cocaine rush; of these, nine reported they had reduced their use of cocaine. Ropinirole does diminish the subjective intensity of an expected cocaine rush, so interfering with the dynamics of reward, while supporting its possible use in the treatment of cocaine dependence.

  19. Online extraction LC-MS/MS method for the simultaneous quantitative confirmation of urine drugs of abuse and metabolites: amphetamines, opiates, cocaine, cannabis, benzodiazepines and methadone.

    Science.gov (United States)

    de Jager, Andrew D; Bailey, Neville L

    2011-09-01

    A rapid LC-MS/MS method for confirmatory testing of five major categories of drugs of abuse (amphetamine-type substances, opiates, cocaine, cannabis metabolites and benzodiazepines) in urine has been developed. All drugs of abuse mandated by the Australian/New Zealand Standard AS/NZS 4308:2008 are quantified in a single chromatographic run. Urine samples are diluted with a mixture of isotope labelled internal standards. An on-line trap-and-flush approach, followed by LC-ESI-MS/MS has been successfully used to process samples in a functioning drugs of abuse laboratory. Following injection of diluted urine samples, compounds retained on the trap cartridge are flushed onto a reverse-phase C18 HPLC column (5-μm particle size) with embedded hydrophylic functionality. A total chromatographic run-time of 15 min is required for adequate resolution. Automated quantitation software algorithms have been developed in-house using XML scripting to partially automate the identification of positive samples, taking into account ion ratio (IR) and retention times (Rt). The sensitivity of the assay was found to be adequate for the quantitation of drugs in urine at and below the confirmation cut-off concentrations prescribed by AS/NZS 4308:2008.

  20. Cocaine exposure impairs multilineage hematopoiesis of human hematopoietic progenitor cells mediated by the sigma-1 receptor [corrected].

    Science.gov (United States)

    Nixon, Christopher C; Schwartz, Brandon H; Dixit, Dhaval; Zack, Jerome A; Vatakis, Dimitrios N

    2015-03-02

    Prenatal exposure to cocaine is a significant source of fetal and neonatal developmental defects. While cocaine associated neurological and cardiac pathologies are well-documented, it is apparent that cocaine use has far more diverse physiological effects. It is known that in some cell types, the sigma-1 receptor mediates many of cocaine's cellular effects. Here we present a novel and concise investigation into the mechanism that underlies cocaine associated hematopoietic pathology. Indeed, this is the first examination of the effects of cocaine on hematopoiesis. We show that cocaine impairs multilineage hematopoiesis from human progenitors from multiple donors and tissue types. We go on to present the first demonstration of the expression of the sigma-1 receptor in human CD34 + human hematopoietic stem/progenitor cells. Furthermore, we demonstrate that these cocaine-induced hematopoietic defects can be reversed through sigma-1 receptor blockade.

  1. Functional MRI studies in human Ecstasy and cannabis users

    NARCIS (Netherlands)

    Jager, G.

    2006-01-01

    Cannabis and ecstasy are among the most widely used illicit drugs in the world. However, there are substantial concerns about their neurotoxic potential for brain and brain function. Despite previous research, some crucial questions regarding the causality, course and clinical relevance have remaine

  2. Rapid simultaneous determination of ephedrines, amphetamines, cocaine, cocaine metabolites, and opiates in human urine by GC-MS.

    Science.gov (United States)

    Saito, Takeshi; Mase, Hiroyasu; Takeichi, Sanae; Inokuchi, Sadaki

    2007-01-04

    This paper presents a simple and sensitive chromatographic procedure for the simultaneous determination and quantification of ephedrines, amphetamines, cocaine, cocaine metabolites, and opiates in human urine by gas chromatography-mass spectrometry. This method involves enzyme hydrolysis in the presence of a deuterated internal standard, liquid-liquid extraction, and derivatization with pentafluoropropionic anhydride and pentafluoropropanol. The recovery of each compound averaged at 65.8% or more. The limits of detection determined for each compound by using a 2-mL sample volume ranged from 5 to 50 ng/mL. The calibration curves were linear to 100 ng/mL for all compounds when determined using methamphetamine-d4 and MDMA-d5 as internal standards. This method was successfully applied for the analysis of urine samples suspected to contain intoxicants such as methamphetamine and heroin.

  3. Prevalence of DSM-IV and DSM-5 Alcohol, Cocaine, Opioid, and Cannabis Use Disorders in a Largely Substance Dependent Sample

    Science.gov (United States)

    Peer, Kyle; Rennert, Lior; Lynch, Kevin G.; Farrer, Lindsay; Gelernter, Joel; Kranzler, Henry R.

    2012-01-01

    BACKGROUND The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) will soon replace the DSM-IV, which has existed for nearly two decades. The changes in diagnostic criteria have important implications for research and for the clinical care of individuals with Substance Use Disorders (SUDs). METHODS We used the Semi-Structured Assessment for Drug Dependence and Alcoholism to evaluate the lifetime presence of DSM-IV abuse and dependence diagnoses and DSM-5 mild, moderate, or severe SUDs for alcohol, cocaine, opioids, and cannabis in a sample of 7,543 individuals recruited to participate in genetic studies of substance dependence. RESULTS Switches between diagnostic systems consistently resulted in a modestly greater prevalence for DSM-5 SUDs, based largely on the assignment of DSM-5 diagnoses to DSM-IV “diagnostic ophans” (i.e., individuals meeting one or two criteria for dependence and none for abuse, and thus not receiving a DSM-IV SUD diagnosis). The vast majority of these diagnostic switches were attributable to the requirement that only two of 11 criteria be met for a DSM-5 SUD diagnosis. We found evidence to support the omission from DSM-5 of the legal criterion due to its limited diagnostic utility. The addition of craving as a criterion in DSM-5 did not substantially affect the likelihood of an SUD diagnosis. CONCLUSION The greatest advantage of DSM-5 appears to be its ability to capture diagnostic orphans. In this sample, changes reflected in DSM-5 had a minimal impact on the prevalence of SUD diagnoses. PMID:22884164

  4. Reduced attentional scope in cocaine polydrug users

    NARCIS (Netherlands)

    Colzato, L.S.; van den Wildenberg, W.P.M.; Hommel, B.

    2009-01-01

    Cocaine is Europe's second preferred recreational drug after cannabis but very little is known about possible cognitive impairments in the upcoming type of recreational cocaine user (monthly consumption). We asked whether recreational use of cocaine impacts early attentional selection processes. Coc

  5. The genetics of complex human behaviour: Cannabis use, personality, sexuality and mating

    NARCIS (Netherlands)

    Verweij, K.J.H.

    2012-01-01

    I investigated the genetic and environmental etiology of individual differences in a variety of complex human behaviours, broadly captured within three domains - 1) cannabis use, 2) personality, and 3) sexuality and mating. Research questions and hypotheses are addressed with large community-based,

  6. The genetics of complex human behaviour: Cannabis use, personality, sexuality and mating

    NARCIS (Netherlands)

    Verweij, K.J.H.

    2012-01-01

    I investigated the genetic and environmental etiology of individual differences in a variety of complex human behaviours, broadly captured within three domains - 1) cannabis use, 2) personality, and 3) sexuality and mating. Research questions and hypotheses are addressed with large community-based,

  7. Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D. [Brookhaven National Lab., Upton, NY (United States)]|[State Univ. of New York, Stony Brook, NY (United States). Dept. of Psychiatry; Wang, G.J.; Fowler, J.S. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1999-05-28

    The reinforcing effects of cocaine and methylphenidate have been linked to their ability to block dopamine transporters (DAT). Though cocaine and methylphenidate have similar in vitro affinities for DAT the abuse of methylphenidate in humans is substantially lower than of cocaine. To test if differences in in vivo potency at the DAT between these two drugs could account for the differences in their abuse liability the authors compared the levels of DAT occupancies that they had previously reported separately for intravenous methylphenidate in controls and for intravenous cocaine in cocaine abusers. DAT occupancies were measured with Positron Emission Tomography using [{sup 11}C]cocaine, as a DAT ligand, in 8 normal controls for the methylphenidate study and in 17 active cocaine abusers for the cocaine study. The ratio of the distribution volume of [{sup 11}C]cocaine in striatum to that in cerebellum, which corresponds to Bmax/Kd+1, was used as measure of DAT availability. Parallel measures were obtained to assess the cardiovascular effects of these two drugs. Methylphenidate and cocaine produced comparable dose-dependent blockage of DAT with an estimated ED{sub 50} for methylphenidate of 0.07 mg/kg and for cocaine of 0.13 mg/kg. Both drugs induced similar increases in heart rate and blood pressure but the duration of the effects were significantly longer for methylphenidate than for cocaine.

  8. Cocaine: A Catalyst for Human Immunodeficiency Virus-Associated Dementia

    Directory of Open Access Journals (Sweden)

    Navneet K Dhillon

    2008-01-01

    Full Text Available Injection drug use has been recognized as a major risk factor for AIDS from the outset of the epidemic. Cocaine, one of the most widely abused drugs in the United States can both impair the functions of macrophages & CD4+ lymphocytes and also activate HIV-1 expression in these cells. Cocaine is a multifactorial agent that acts globally to impair the functioning of brain resident cells through multiple pathways. The drug not only promotes virus replication in macrophages, microglia and astrocytes, but can also upregulate CCR5 coreceptor, and reciprocally inhibit its ligands, thereby increasing virus infectivity. Cocaine is known to modulate astroglial function and activation. Cocaine causes a myriad of toxic responses in the neurons: a it synergizes with viral proteins, Tat and gp120 resulting in exacerbated neuronal apoptosis, b it causes calcium mobilization and, c generation of reactive oxygen species. Additionally, cocaine also exerts potent effects on microvascular permeability, thereby impacting the influx of virus-infected inflammatory cells in brain parenchyma. By amplifying the various arms of the toxic responses that characterize HIV-associated dementia (HAD, cocaine skews the balance in favor of the virus leading to accelerated progression and severity of dementia.

  9. Cannabis: evolution and ethnobotany

    National Research Council Canada - National Science Library

    Clarke, Robert Connell; Merlin, Mark David

    2013-01-01

    .... The culturally valuable and often irreplaceable goods derived from Cannabis deeply influenced the commercial, medical, ritual, and religious practices of cultures throughout the ages, and human...

  10. In vitro characterization of cocaine binding sites in human hair.

    Science.gov (United States)

    Joseph, R E; Tsai, W J; Tsao, L I; Su, T P; Cone, E J

    1997-09-01

    In vitro studies were performed to characterize [3H]cocaine binding to dark and light ethnic hair types. In vitro binding to hair was selective, was reversible and increased linearly with increasing hair concentration. Scatchard analyses revealed high-affinity (6-112 nM) and low-affinity (906-4433 nM) binding in hair. Competition studies demonstrated that the potencies of 3beta-(4-bromophenyl)tropane-2beta-carboxylic acid methyl ester, and 5-(4-chlorophenyl)-2,5-dihydro-3H-imidazol[2,1-alpha]isoindole-5-ol and 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane were similar to or less than that of (-)-cocaine. The potency of (-)-cocaine was 10-fold greater than that of (+)-cocaine at inhibiting radioligand specific binding to hair. Multivariate analysis indicated that significantly greater nonspecific and specific radioligand binding occurred in dark hair than in light hair. Multivariate analysis also demonstrated a significant ethnicity x sex effect on specific and nonspecific binding to hair. Greater radioligand binding occurred in male Africoid hair than in female Africoid hair and in all Caucasoid hair types. Melanin was considered the most likely binding site for cocaine in hair. Typically, the concentration of melanin is much greater in dark than in light hair. Scatchard analysis indicated that dark hair had a 5- to 43-fold greater binding capacity than light hair. Differences in radioligand binding between hair types appeared to be due to differences in the density of binding sites formed by melanin in hair.

  11. Detecting Cannabis Use on the Human Skin Surface via an Electronic Nose System

    Directory of Open Access Journals (Sweden)

    Andreas Voss

    2014-07-01

    Full Text Available The most commonly used drug testing methods are based on the analysis of hair and urine using gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry or immunoassay screening. These methods are time-consuming and partly expensive. One alternative method could be the application of an “electronic nose” (eNose. We have developed an eNose to detect directly on the human skin surface metabolic changes in the human body odor caused by cannabis consumption. Twenty cannabis-smoking and 20 tobacco-smoking volunteers were enrolled in this study. For the sensor signal data processing, two different methods were applied: Principle component analysis (PCA with discriminant analysis, and the method of pattern recognition with subsequent support vector machines (SVM processing. The PCA analysis achieved a correct classification of 70%, whereas the SVM obtained an accuracy of 92.5% (sensitivity 95%, specificity 90% between cannabis-consuming volunteers and tobacco-smoking subjects. This study shows evidence that a low-cost, portable and fast-working eNose system could be useful for health protection, security agencies and for forensic investigations. The ability to analyze human body odor with an eNose opens up a wide field for diagnosing other drugs and also various diseases.

  12. Brain Imaging Studies on the Cognitive, Pharmacological and Neurobiological Effects of Cannabis in Humans: Evidence from Studies of Adult Users.

    Science.gov (United States)

    Weinstein, Aviv; Livny, Abigail; Weizman, Abraham

    2016-01-01

    Cannabis is the most widely used illicit drug worldwide. Regular cannabis use has been associated with a range of acute and chronic mental health problems, such as anxiety, depression, psychotic symptoms and neurocognitive impairments and their neural mechanisms need to be examined. This review summarizes and critically evaluates brain-imaging studies of cannabis in recreational and regular cannabis users between January 2000 and January 2016. The search has yielded eligible 103 structural and functional studies. Regular use of cannabis results in volumetric, gray matter and white matter structural changes in the brain, in particular in the hippocampus and the amygdala. Regular use of cannabis affects cognitive processes such as attention, memory, inhibitory control, decision-making, emotional processing, social cognition and their associated brain areas. There is evidence that regular cannabis use leads to altered neural function during attention and working memory and that recruitment of activity in additional brain regions can compensate for it. Similar to other drugs of abuse, cannabis cues activated areas in the reward pathway. Pharmacological studies showed a modest increase in human striatal dopamine transmission after administration of THC in healthy volunteers. Regular cannabis use resulted in reduced dopamine transporter occupancy and reduced dopamine synthesis but not in reduced striatal D2/D3 receptor occupancy compared with healthy control participants. Studies also showed different effects of Δ-9 tetrahydrocannabinol (THC) and cannabidiol (CBD) on emotion, cognition and associated brain regions in healthy volunteers, whereby CBD protects against the psychoactive effects of THC. Brain imaging studies using selective high-affinity radioligands for the imaging of cannabinoid CB1 receptor availability in Positron Emission Tomography (PET) showed downregulation of CB1 in regular users of cannabis. In conclusion, regular use of the cannabinoids exerts

  13. Modeling of pharmacokinetics of cocaine in human reveals the feasibility for development of enzyme therapies for drugs of abuse.

    Directory of Open Access Journals (Sweden)

    Fang Zheng

    Full Text Available A promising strategy for drug abuse treatment is to accelerate the drug metabolism by administration of a drug-metabolizing enzyme. The question is how effectively an enzyme can actually prevent the drug from entering brain and producing physiological effects. In the present study, we have developed a pharmacokinetic model through a combined use of in vitro kinetic parameters and positron emission tomography data in human to examine the effects of a cocaine-metabolizing enzyme in plasma on the time course of cocaine in plasma and brain of human. Without an exogenous enzyme, cocaine half-lives in both brain and plasma are almost linearly dependent on the initial cocaine concentration in plasma. The threshold concentration of cocaine in brain required to produce physiological effects has been estimated to be 0.22±0.07 µM, and the threshold area under the cocaine concentration versus time curve (AUC value in brain (denoted by AUC2(∞ required to produce physiological effects has been estimated to be 7.9±2.7 µM·min. It has been demonstrated that administration of a cocaine hydrolase/esterase (CocH/CocE can considerably decrease the cocaine half-lives in both brain and plasma, the peak cocaine concentration in brain, and the AUC2(∞. The estimated maximum cocaine plasma concentration which a given concentration of drug-metabolizing enzyme can effectively prevent from entering brain and producing physiological effects can be used to guide future preclinical/clinical studies on cocaine-metabolizing enzymes. Understanding of drug-metabolizing enzymes is key to the science of pharmacokinetics. The general insights into the effects of a drug-metabolizing enzyme on drug kinetics in human should be valuable also in future development of enzyme therapies for other drugs of abuse.

  14. Platelet Activation in Human Immunodeficiency Virus Type-1 Patients Is Not Altered with Cocaine Abuse.

    Directory of Open Access Journals (Sweden)

    Michelle Kiebala

    Full Text Available Recent work has indicated that platelets, which are anucleate blood cells, significantly contribute to inflammatory disorders. Importantly, platelets also likely contribute to various inflammatory secondary disorders that are increasingly associated with Human Immunodeficiency Virus Type-1 (HIV infection including neurological impairments and cardiovascular complications. Indeed, HIV infection is often associated with increased levels of platelet activators. Additionally, cocaine, a drug commonly abused by HIV-infected individuals, leads to increased platelet activation in humans. Considering that orchestrated signaling mechanisms are essential for platelet activation, and that nuclear factor-kappa B (NF-κB inhibitors can alter platelet function, the role of NF-κB signaling in platelet activation during HIV infection warrants further investigation. Here we tested the hypothesis that inhibitory kappa B kinase complex (IKK activation would be central for platelet activation induced by HIV and cocaine. Whole blood from HIV-positive and HIV-negative individuals, with or without cocaine abuse was used to assess platelet activation via flow cytometry whereas IKK activation was analyzed by performing immunoblotting and in vitro kinase assays. We demonstrate that increased platelet activation in HIV patients, as measured by CD62P expression, is not altered with reported cocaine use. Furthermore, cocaine and HIV do not activate platelets in whole blood when treated ex vivo. Finally, HIV-induced platelet activation does not involve the NF-κB signaling intermediate, IKKβ. Platelet activation in HIV patients is not altered with cocaine abuse. These results support the notion that non-IKK targeting approaches will be better suited for the treatment of HIV-associated inflammatory disorders.

  15. Characterization of a recombinant humanized anti-cocaine monoclonal antibody and its Fab fragment.

    Science.gov (United States)

    Kirley, Terence L; Norman, Andrew B

    2015-01-01

    Variations of post-translational modifications are important for stability and in vivo behavior of therapeutic antibodies. A recombinant humanized anti-cocaine monoclonal antibody (h2E2) was characterized for heterogeneity of N-linked glycosylation and disulfide bonds. In addition, charge heterogeneity, which is partially due to the presence or absence of C-terminal lysine on the heavy chains, was examined. For cocaine overdose therapy, Fab fragments may be therapeutic, and thus, a simplified method of generation, purification, and characterization of the Fab fragment generated by Endoproteinase Lys-C digestion was devised. Both the intact h2E2 antibody and purified Fab fragments were analyzed for their affinities for cocaine and 2 of its metabolites, benzoylecgonine and cocaethylene, by fluorescence quenching of intrinsic antibody tyrosine and tryptophan fluorescence resulting from binding of these drugs. Binding constants obtained from fluorescence quenching measurements are in agreement with recently published radioligand and ELISA binding assays. The dissociation constants determined for the h2E2 monoclonal and its Fab fragment are approximately 1, 5, and 20 nM for cocaethylene, cocaine, and benzoylecgonine, respectively. Tryptophan fluorescence quenching (emission at 330 nm) was measured after either excitation of tyrosine and tryptophan (280 nm) or selective excitation of tryptophan alone (295 nm). More accurate binding constants are obtained using tryptophan selective excitation at 295 nm, likely due to interfering absorption of cocaine and metabolites at 280 nm. These quenching results are consistent with multiple tryptophan and tyrosine residues in or near the predicted binding location of cocaine in a previously published 3-D model of this antibody's variable region.

  16. Effect of cannabis on glutamate signalling in the brain: A systematic review of human and animal evidence.

    Science.gov (United States)

    Colizzi, Marco; McGuire, Philip; Pertwee, Roger G; Bhattacharyya, Sagnik

    2016-05-01

    Use of cannabis or delta-9-tetrahydrocannabinol (Δ9-THC), its main psychoactive ingredient, is associated with psychotic symptoms or disorder. However, the neurochemical mechanism that may underlie this psychotomimetic effect is poorly understood. Although dopaminergic dysfunction is generally recognized as the final common pathway in psychosis, evidence of the effects of Δ9-THC or cannabis use on dopaminergic measures in the brain is equivocal. In fact, it is thought that cannabis or Δ9-THC may not act on dopamine firing directly but indirectly by altering glutamate neurotransmission. Here we systematically review all studies examining acute and chronic effects of cannabis or Δ9-THC on glutamate signalling in both animals and man. Limited research carried out in humans tends to support the evidence that chronic cannabis use reduces levels of glutamate-derived metabolites in both cortical and subcortical brain areas. Research in animals tends to consistently suggest that Δ9-THC depresses glutamate synaptic transmission via CB1 receptor activation, affecting glutamate release, inhibiting receptors and transporters function, reducing enzyme activity, and disrupting glutamate synaptic plasticity after prolonged exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Cannabis Smoking in 2015

    Science.gov (United States)

    Biehl, Jason R.

    2015-01-01

    Recent legislative successes allowing expanded access to recreational and medicinal cannabis have been associated with its increased use by the public, despite continued debates regarding its safety within the medical and scientific communities. Despite legislative changes, cannabis is most commonly used by smoking, although alternatives to inhalation have also emerged. Moreover, the composition of commercially available cannabis has dramatically changed in recent years. Therefore, developing sound scientific information regarding its impact on lung health is imperative, particularly because published data conducted prior to widespread legalization are conflicting and inconclusive. In this commentary, we delineate major observations of epidemiologic investigations examining cannabis use and the potential associated development of airways disease and lung cancer to highlight gaps in pulmonary knowledge. Additionally, we review major histopathologic alterations related to smoked cannabis and define specific areas in animal models and human clinical translational investigations that could benefit from additional development. Given that cannabis has an ongoing classification as a schedule I medication, federal funding to support investigations of modern cannabis use in terms of medicinal efficacy and safety profile on lung health have been elusive. It is clear, however, that the effects of inhaled cannabis on lung health remain uncertain and given increasing use patterns, are worthy of further investigation. PMID:25996274

  18. Acute and Non-acute Effects of Cannabis on Human Memory Function: A Critical Review of Neuroimaging Studies

    NARCIS (Netherlands)

    Bossong, M.G.; Jager, G.; Bhattacharyya, S.; Allen, P.

    2014-01-01

    Smoking cannabis produces a diverse range of effects, including impairments in learning and memory. These effects are exerted through action on the endocannabinoid system, which suggests involvement of this system in human cognition. Learning and memory deficits are core symptoms of psychiatric and

  19. Acute and Non-acute Effects of Cannabis on Human Memory Function: A Critical Review of Neuroimaging Studies

    NARCIS (Netherlands)

    Bossong, M.G.; Jager, G.; Bhattacharyya, S.; Allen, P.

    2014-01-01

    Smoking cannabis produces a diverse range of effects, including impairments in learning and memory. These effects are exerted through action on the endocannabinoid system, which suggests involvement of this system in human cognition. Learning and memory deficits are core symptoms of psychiatric and

  20. Cocaine Self-Administration Produces Long-Lasting Alterations in Dopamine Transporter Responses to Cocaine

    OpenAIRE

    Siciliano, Cody A.; Fordahl, Steve C.; Jones, Sara R.

    2016-01-01

    Cocaine addiction is a debilitating neuropsychiatric disorder characterized by uncontrolled cocaine intake, which is thought to be driven, at least in part, by cocaine-induced deficits in dopamine system function. A decreased ability of cocaine to elevate dopamine levels has been repeatedly observed as a consequence of cocaine use in humans, and preclinical work has highlighted tolerance to cocaine's effects as a primary determinant in the development of aberrant cocaine taking behaviors. Her...

  1. Cannabis: evolution and ethnobotany

    National Research Council Canada - National Science Library

    Clarke, Robert Connell; Merlin, Mark David

    2013-01-01

    "Cannabis: Evolution and Ethnobotany is a comprehensive, interdisciplinary exploration of the natural origins and early evolution of this famous plant, highlighting its historic role in the development of human societies...

  2. Cannabis induced asystole.

    Science.gov (United States)

    Brancheau, Daniel; Blanco, Jessica; Gholkar, Gunjan; Patel, Brijesh; Machado, Christian

    2016-01-01

    Cannabis or marijuana is the most used recreational, and until recently illegal, drug in the United States. Although cannabis has medicinal use, its consumption has been linked to motor vehicle accidents in dose dependent fashion. Marijuana and other cannabinoids produce a multitude of effects on the human body that may result in these motor vehicle accidents. Some of the effects that marijuana has been known to cause include altered sensorium, diminished reflexes, and increased vagal tone. We present a case of cannabis induced asystole from hypervagotonia. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. The Relationship between Cocaine Use and Human Papillomavirus Infections in HIV-Seropositive and HIV-Seronegative Women

    Directory of Open Access Journals (Sweden)

    Howard Minkoff

    2008-01-01

    Full Text Available Objective. Animal data suggest that cocaine has an immunosuppressive effect, but no human studies have been conducted to assess the relation of cocaine use with human papillomavirus (HPV infection, the viral cause of cervical cancer. Since both cocaine use and HPV infection are common among HIV-positive women, we sought to determine whether use of cocaine and/or crack influences the natural history of HPV among women with or at high risk of HIV. Methods. Women enrolled in the Women's Interagency HIV Study (2278 HIV-seropositive and 826 high-risk seronegative women were examined every six months for up to 9.5 years with Pap smear, collection of cervicovaginal lavage (CVL samples, and detailed questionnaires regarding health and behavior, including use of crack and cocaine (crack/cocaine. CVLs were tested for HPV DNA by PCR, with genotyping for over forty HPV types. Results. In multivariate logistic regression models, censoring women treated for cervical neoplasia, crack/cocaine use within the last six months was associated with prevalent detection of oncogenic HPV DNA (odds ratio [OR] = 1.30 (1.09–1.55, and with oncogenic HPV-positive squamous intraepithelial lesions (SIL (OR = 1.70 (1.27–2.27, following adjustment for age, race, HIV-serostatus, and CD4+ T-cell count, the number of sexual partners in the past six months, and smoking. In multivariate Cox models crack/cocaine use was also associated with a trend that approached significance in regard to incident detection of oncogenic HPV-positive SIL (HR = 1.51, 95% CI 0.99–2.30, and while the rate of oncogenic HPV clearance was not related to cocaine use, the clearance of any SIL was significantly lower in those with versus those without recent crack/cocaine use (HR = 0.57, 95% CI 0.34–0.97. Conclusions. Cocaine use is associated with an increased risk of detection of both prevalent and incident oncogenic HPV infection, as well as an increased risk of HPV-positive SIL over time.

  4. The disposition of cocaine and opiate analytes in hair and fingernails of humans following cocaine and codeine administration.

    Science.gov (United States)

    Ropero-Miller, J D; Goldberger, B A; Cone, E J; Joseph, R E

    2000-10-01

    This study investigated the disposition patterns of cocaine and opiates into hair and fingernail specimens collected from 8 volunteers enrolled in a 10-week inpatient clinical study. All subjects were African-American males with a confirmed drug use history. Scalp hair and fingernail scrapings were collected weekly throughout the course of the study. Head hair was collected from the posterior vertex region, and fingernail scrapings were collected along the entire ventral surface of the nail plate. The specimens were introduced to successive decontamination washes including an isopropanol wash and three phosphate buffer washes. All decontamination washes were collected and analyzed. All specimens were enzymatically digested prior to being subjected to solid-phase extraction and derivatization. Analyses were performed using electron impact gas chromatography-mass spectrometry. Analytes investigated included eight cocaine analytes and five codeine analytes. The limit of quantitation for all analytes ranged from 0.1 to 0.5 ng/mg for both matrices. Cocaine was present at the highest concentrations of any analyte in both hair and nail. Benzoylecgonine and ecgonine methyl ester were the primary metabolites in both matrices and were typically less than 15% of cocaine concentrations. Codeine was the only opiate analyte identified in either hair or nail. Observed drug disposition profiles were different for hair and nails. A significant dose-response relationship was observed for hair specimens. The mean peak concentrations in hair after low dosing were half the concentration observed after high-dose administration. Generally, no clear relationship was evident between nail drug concentrations and dose. Decontamination washes removed less than 20% of the total drug present in hair, but removed most of the drug concentrations (60-100%) in nail. This investigation demonstrated that higher concentrations of drug were found in the subjects' hair than in their fingernails and that

  5. Non-fatal cocaine overdose among injecting and non-injecting cocaine users in Sydney, Australia.

    Science.gov (United States)

    Kaye, Sharlene; Darke, Shane

    2004-10-01

    To investigate the frequency of non-fatal cocaine overdose, and responses to overdoses, among injecting and non-injecting cocaine users. Cross-sectional study. Sydney, Australia. Two hundred current cocaine users. Structured interview. Thirteen per cent of the sample had overdosed on cocaine, 7% in the preceding 12 months. Cocaine injectors were more likely to have overdosed, both ever (17 v 6%) and in the preceding 12 months (9 v 3%). The most common symptoms of overdose were palpitations (68%), intense sweating (44%) and seizures (40%). The use of other drugs in combination with cocaine prior to the most recent overdose was prevalent (64%), most commonly opioids (40%), alcohol (24%) and cannabis (24%). Those who had overdosed were more likely to be female, had longer cocaine use careers, had used more cocaine in the preceding month and preceding 6 months, had higher levels of cocaine dependence and more extensive polydrug use. Twenty-four per cent had witnessed a cocaine overdose, 13% in the preceding 12 months. Injectors were more likely to have witnessed overdoses, both ever (35% v 8%) and in the preceding 12 months (20% v 3%). Experience of, and exposure to, overdose were not rare events. Cocaine users need to be aware of the possibility and nature of overdose, and that cocaine overdose can occur irrespective of method of use. There is a need to emphasise the potential danger of combining cocaine with other drugs.

  6. Synthetic cannabis and respiratory depression.

    Science.gov (United States)

    Jinwala, Felecia N; Gupta, Mayank

    2012-12-01

    In recent years, synthetic cannabis use has been increasing in appeal among adolescents, and its use is now at a 30 year peak among high school seniors. The constituents of synthetic cannabis are difficult to monitor, given the drug's easy accessibility. Currently, 40 U.S. states have banned the distribution and use of some known synthetic cannabinoids, and have included these drugs in the Schedule I category. The depressive respiratory effect in humans caused by synthetic cannabis inhalation has not been thoroughly investigated in the medical literature. We are the first to report, to our knowledge, two cases of self-reported synthetic cannabis use leading to respiratory depression and necessary intubation.

  7. [Medicinal cannabis].

    Science.gov (United States)

    Van der Meersch, H; Verschuere, A P; Bottriaux, F

    2006-01-01

    Pharmaceutical grade cannabis is available to Dutch patients from public pharmacies in the Netherlands. The first part of this paper reviews the pharmaceutical and pharmacological properties of medicinal cannabis. Detailed information about its composition and quality, potential applications, methods of administration, adverse reactions, drug interactions and safety during pregnancy or breastfeeding are given. The second part deals with the legal aspects of dispensing medicinal cannabis through pharmacies in view of the Belgian and Dutch legislation. The last part discusses the present Belgian regulation about the possession of cannabis.

  8. Reduced attentional scope in cocaine polydrug users.

    Directory of Open Access Journals (Sweden)

    Lorenza S Colzato

    Full Text Available Cocaine is Europe's second preferred recreational drug after cannabis but very little is known about possible cognitive impairments in the upcoming type of recreational cocaine user (monthly consumption. We asked whether recreational use of cocaine impacts early attentional selection processes. Cocaine-free polydrug controls (n = 18 and cocaine polydrug users (n = 18 were matched on sex, age, alcohol consumption, and IQ (using the Raven's progressive matrices, and were tested by using the Global-Local task to measure the scope of attention. Cocaine polydrug users attended significantly more to local aspects of attended events, which fits with the idea that a reduced scope of attention may be associated with the perpetuation of the use of the drug.

  9. [Cannabis and mood].

    Science.gov (United States)

    Sanches, Rafael Faria; Marques, João Mazzoncini de Azevedo

    2010-06-01

    Evaluate the relationship between acute and chronic use of cannabis and mood changes. Articles were selected by electronic search in PubMed. Chapters in books and reference lists of selected articles were also reviewed. As the research did not involve humans, there was no evaluation by a Research Ethics Committee. High rates of comorbidity between use/abuse/dependence of cannabis and affective disorders in longitudinal studies and in clinical samples were observed. Longitudinal studies indicate that, in long-term, the higher use of cannabis is associated with an increased risk of developing bipolar disorder, and probably, major depression in subjects initially without affective disorder, but was not found increased risk of cannabis use among those initially only with mania or depression. Another important observation is that substance abuse in bipolar patients may be associated with a number of negative characteristics, such as difficulty in recovering the affective symptoms, more hospitalizations, poor compliance with treatment, increased risk of suicide, aggression and a poor response to lithium. Psychosocial and pharmacological treatments are indicated for the management of comorbidity between cannabis and affective disorders. The relationship between cannabis use and mood changes are observed both in the epidemiological research and in the clinical settings.

  10. Cannabis e humor Cannabis and mood

    Directory of Open Access Journals (Sweden)

    Rafael Faria Sanches

    2010-06-01

    Full Text Available OBJETIVO: Avaliar as relações entre o uso agudo e crônico de cannabis e alterações do humor. MÉTODO: Os artigos foram selecionados por meio de busca eletrônica no indexador PubMed. Capítulos de livros e as listas de referências dos artigos selecionados também foram revisados. RESULTADOS: Observam-se elevados índices de comorbidade entre abuso/dependência de cannabis e transtornos afetivos em estudos transversais e em amostras clínicas. Estudos longitudinais indicam que, em longo prazo, o uso mais intenso de cannabis está relacionado com um risco maior de desenvolvimento de doença bipolar e, talvez, depressão maior em indivíduos inicialmente sem quadros afetivos; porém, os mesmos não encontraram maior risco de uso de cannabis entre aqueles com mania ou depressão sem esta comorbidade. Outra importante observação é que o uso de substâncias psicoativas em bipolares pode estar associado a uma série de características negativas, como dificuldade na recuperação dos sintomas afetivos, maior número de internações, piora na adesão ao tratamento, risco aumentado de suicídio, agressividade e a uma pobre resposta ao lítio. Tratamentos psicossociais e farmacológicos são indicados para o manejo da comorbidade entre cannabis e transtornos afetivos. CONCLUSÃO: As relações entre o uso de cannabis e alterações do humor são observadas tanto epidemiologicamente quanto nos contextos clínicos.OBJECTIVE: Evaluate the relationship between acute and chronic use of cannabis and mood changes. METHOD: Articles were selected by electronic search in PubMed. Chapters in books and reference lists of selected articles were also reviewed. As the research did not involve humans, there was no evaluation by a Research Ethics Committee. RESULTS: High rates of comorbidity between use/abuse/dependence of cannabis and affective disorders in longitudinal studies and in clinical samples were observed. Longitudinal studies indicate that, in long

  11. An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain from Spinal Cord Injury and Disease

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Zhao, Holly; Prasad, Hannah; Phan, Amy

    2016-01-01

    Using eight hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, the majority of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta-9-tetrahydrocannabinol on three separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was utilized to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model demonstrated a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (e.g., good drug effect, feeling high, etc.) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all p<0.0004). Psychoactive and subjective effects were dose dependent. Measurement of neuropsychological performance proved challenging because of various disabilities in the population studied. As the two active doses did not significantly differ from each other in terms of analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord. PMID:27286745

  12. Cannabis and Cannabinoids (PDQ)

    Science.gov (United States)

    ... Professionals Questions to Ask about Your Treatment Research Cannabis and Cannabinoids (PDQ®)–Patient Version Overview Go to ... treatment (see Question 9 ). Questions and Answers About Cannabis What is Cannabis ? Cannabis , also known as marijuana , ...

  13. [Cannabis smoking and lung cancer].

    Science.gov (United States)

    Underner, M; Urban, T; Perriot, J; de Chazeron, I; Meurice, J-C

    2014-06-01

    Cannabis is the most commonly smoked illicit substance in the world. It can be smoked alone in plant form (marijuana) but it is mainly smoked mixed with tobacco. The combined smoking of cannabis and tobacco is a common-place phenomenon in our society. However, its use is responsible for severe pulmonary consequences. The specific impact of smoking cannabis is difficult to assess precisely and to distinguish from the effect of tobacco. Marijuana smoke contains polycyclic aromatic hydrocarbons and carcinogens at higher concentration than tobacco smoke. Cellular, tissue, animal and human studies, and also epidemiological studies, show that marijuana smoke is a risk factor for lung cancer. Cannabis exposure doubles the risk of developing lung cancer. This should encourage clinicians to identify cannabis use and to offer patients support in quitting. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  14. Cannabis Use and Support for Cannabis Legalization

    OpenAIRE

    Palali, A.; Ours, J. C. van

    2014-01-01

    textabstractWe investigate the determinants of the support for cannabis legalization finding a causal effect of personal experience with cannabis use. Current and past cannabis users are more in favor of legalization. We relate this finding to self-interest and inside information about potential dangers of cannabis. While the self-interest effect is not very surprising, the effect of inside information suggests that cannabis use is not as harmful as cannabis users originally thought it was be...

  15. Cannabis use and support for cannabis legalization

    OpenAIRE

    Palali, A.; van Ours, J.C.

    2016-01-01

    textabstractWe investigate the determinants of the support for cannabis legalization finding a causal effect of personal experience with cannabis use. Current and past cannabis users are more in favor of legalization. We relate this finding to self-interest and inside information about potential dangers of cannabis. While the self-interest effect is not very surprising, the effect of inside information suggests that cannabis use is not as harmful as cannabis users originally thought it was be...

  16. Genotoxic and Cytotoxic Potential of Smoke Crack Cocaine on the Epithelium of the Human Oral Mucosa

    Directory of Open Access Journals (Sweden)

    Raphaela Cássia de Lima

    2016-09-01

    Full Text Available Crack cocaine is an illicit drug derived from cocaine. It can produce some damages to the lungs and oral cavity. Objective: The aim of this study was to analyze the frequency of micronuclei and some nuclear alterations in epithelial cells of crack cocaine users. Methods: Oral smears were collected from clinically normal-appearing buccal mucosa exfoliative cytology of 30 individuals (15 crack cocaine users and 15 controls. Results: Crack cocaine users consumed about 3.8 grams per day and the time consumption of the drug was of 6.4 (+3.3 years. The prevalence of micronuclei, binucleated cells, broken egg cells, budding cells, picnosis, karyolysis, and karyorrhexis was determined. The frequencies of micronuclei for case and control groups were, respectively, 2.87 + 3.46 and 0.57 + 1.6 (p=0.018. No statistical difference was observed for binucleated cells, broken egg cells, budding cells, picnosis, and karyolysis. The frequency of karyorrhexis was significantly increased on crack cocaine users than controls (54.07 + 38.58 and 24.87 + 23.97, p=0.001. Conclusion: Smoke crack might have a cytotoxic and genotoxic effects to the oral mucosa due to increased frequency of micronuclei and karyorrhexis. Thus, individuals who used crack cocaine in the long term need to be frequently examined in order to prevent neoplastic transformation.Keywords: Crack Cocaine; Micronucleus Tests; Mouth Mucosa; Cytological Techniques; Carcinogens.

  17. [Pathological gambling and addiction to cannabis: common psychosocial profile?].

    Science.gov (United States)

    Parolaa, Nathalie; Boyer, Laurent; Simon, Nicolas; Aghababian, Valérie; Lançon, Christophe

    2014-01-01

    Addiction can involve substances (heroin, cannabis, cocaine) or be characterised by behaviour (pathological gambling, addiction to sport, etc.). The question is to establish whether or not there is a specific personality profile (character, temperament) and emotional functioning (anxiety, depression, alexithymia) in subjects presenting addictive behaviour with and without substance use. To find some answers, a team from Sainte-Marguerite General Hospital in Marseille carried out a study comparing a group of cannabis addicts and a group of pathological gamblers.

  18. An in vitro model of human neocortical development using pluripotent stem cells: cocaine-induced cytoarchitectural alterations.

    Science.gov (United States)

    Kindberg, Abigail A; Bendriem, Raphael M; Spivak, Charles E; Chen, Jia; Handreck, Annelie; Lupica, Carl R; Liu, Jinny; Freed, William J; Lee, Chun-Ting

    2014-12-01

    Neocortical development involves ordered specification of forebrain cortical progenitors to various neuronal subtypes, ultimately forming the layered cortical structure. Modeling of this process using human pluripotent stem cells (hPSCs) would enable mechanistic studies of human neocortical development, while providing new avenues for exploration of developmental neocortical abnormalities. Here, we show that preserving hPSCs aggregates - allowing embryoid body formation - while adding basic fibroblast growth factor (bFGF) during neuroepithelial development generates neural rosettes showing dorsal forebrain identity, including Mash1(+) dorsal telencephalic GABAergic progenitors. Structures that mirrored the organization of the cerebral cortex formed after rosettes were seeded and cultured for 3 weeks in the presence of FGF18, BDNF and NT3. Neurons migrated along radial glia scaffolding, with deep-layer CTIP2(+) cortical neurons appearing after 1 week and upper-layer SATB2(+) cortical neurons forming during the second and third weeks. At the end of differentiation, these structures contained both glutamatergic and GABAergic neurons, with glutamatergic neurons being most abundant. Thus, this differentiation protocol generated an hPSC-based model that exhibits temporal patterning and a neuronal subtype ratio similar to that of the developing human neocortex. This model was used to examine the effects of cocaine during neocorticogenesis. Cocaine caused premature neuronal differentiation and enhanced neurogenesis of various cortical neuronal subtypes. These cocaine-induced changes were inhibited by the cytochrome P450 inhibitor cimetidine. This in vitro model enables mechanistic studies of neocorticogenesis, and can be used to examine the mechanisms through which cocaine alters the development of the human neocortex.

  19. Cannabis Use and Support for Cannabis Legalization

    NARCIS (Netherlands)

    Palali, A.; van Ours, J.C.

    2014-01-01

    We investigate the determinants of the support for cannabis legalizationfinding a causal effect of personal experience with cannabis use. Current and past cannabis users are more in favor of legalization. We relate this to self-interest and inside information about potential dangers of cannabis use.

  20. Cannabis Use and Support for Cannabis Legalization

    NARCIS (Netherlands)

    Palali, A.; van Ours, J.C.

    2014-01-01

    We investigate the determinants of the support for cannabis legalizationfinding a causal effect of personal experience with cannabis use. Current and past cannabis users are more in favor of legalization. We relate this to self-interest and inside information about potential dangers of cannabis use.

  1. Two cases of "cannabis acute psychosis" following the administration of oral cannabis

    Directory of Open Access Journals (Sweden)

    Pin Marie

    2005-04-01

    Full Text Available Abstract Background Cannabis is the most commonly used illegal drug and its therapeutic aspects have a growing interest. Short-term psychotic reactions have been described but not clearly with synthetic oral THC, especially in occasional users. Case presentations We report two cases of healthy subjects who were occasional but regular cannabis users without psychiatric history who developed transient psychotic symptoms (depersonalization, paranoid feelings and derealisation following oral administration of cannabis. In contrast to most other case reports where circumstances and blood concentrations are unknown, the two cases reported here happened under experimental conditions with all subjects negative for cannabis, opiates, amphetamines, cocaine, benzodiazepines and alcohol, and therefore the ingested dose, the time-events of effects on behavior and performance as well as the cannabinoid blood levels were documented. Conclusion While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur.

  2. Prenatal and postnatal cocaine exposure predict teen cocaine use.

    Science.gov (United States)

    Delaney-Black, Virginia; Chiodo, Lisa M; Hannigan, John H; Greenwald, Mark K; Janisse, James; Patterson, Grace; Huestis, Marilyn A; Partridge, Robert T; Ager, Joel; Sokol, Robert J

    2011-01-01

    Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n=316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Sex differences in self-reported and physiological response to oral cocaine and placebo in humans.

    Science.gov (United States)

    Singha, A K; McCance-Katz, E F; Petrakis, I; Kosten, T R; Oliveto, A

    2000-11-01

    Self-report and physiological data from 27 male and 8 female cocaine-abusing volunteers exposed to cocaine (80 mg/70 kg p.o.) and placebo were examined for sex differences in their responses. Females reported significantly greater baseline ratings on the Pentobarbital-Chlorpromazine-Alcohol Group (PCAG) (sedation) and Lysergic Acid Diethylamide (LSD) (dysphoria) subscales of the Addiction Research Center Inventory-Short Form (ARCI) relative to males. In addition, females reported significantly greater ratings on the Visual Analogs Scales (VAS) Bad Drug Effects and Anxious/Nervous scales relative to males, regardless of drug. Cocaine produced greater increase in systolic blood pressure in males following cocaine, whereas females showed greater increases following placebo. These results suggest that a placebo control is necessary to determine sex differences in response to an active drug.

  4. Cannabis and psychiatric disorders.

    Science.gov (United States)

    Loga, Slobodan; Loga-Zec, Svjetlana; Spremo, Mira

    2010-06-01

    There are connection between use of cannabis and many psychiatric disturbances in adolescents, especially "cannabis psychosis", depression, panic attacks and suicide. Negative effects could occur either as a result of a specific pharmacological effect of cannabis, or as the result of stressful experiences during the intoxication of cannabis in young people. Potentially is very dangerous high frequency suicidal ideation among cannabis users.

  5. The effect of crack cocaine addiction on the microstructure and morphology of the human striatum and thalamus using novel shape analysis and fast diffusion kurtosis imaging

    DEFF Research Database (Denmark)

    Garza-Villarreal, Eduardo A.; Mallar, Chakravarty; Hansen, Brian

    2016-01-01

    The striatum and thalamus are subcortical structures intimately involved in addiction, and the morphology and microstructure of these has been studied in murine models of cocaine addiction. However, human studies using non-invasive MRI has shown inconsistencies in morphology using volumetric...... analysis. In our study, we used MRI-based volumetric and novel shape analysis, as well as a novel fast diffusion kurtosis imaging sequence to study the morphology and microstructure of striatum and thalamus in crack cocaine addiction (CA) compared to matched healthy controls (HC). We did not find....... Our findings suggest that the use of finer methods and sequences is needed to characterize morphological and microstructural changes in cocaine addiction, and that brain changes in cocaine addiction are related to age....

  6. Pain, Cannabis Species, and Cannabis Use Disorders.

    Science.gov (United States)

    Cohen, Nicole L; Heinz, Adrienne J; Ilgen, Mark; Bonn-Miller, Marcel O

    2016-05-01

    The purpose of this study was to examine whether individuals who used medical cannabis for chronic pain were at increased risk for cannabis use problems compared with individuals who used medical cannabis for other reasons (e.g., anxiety, insomnia, and muscle spasms). An additional aim was to determine whether individuals who used cannabis for chronic pain, as well as those who reported greater within-group pain levels, demonstrated a species preference (i.e., sativa, indica, hybrids) and the extent to which species preference was associated with cannabis use problems. Participants were 163 medical cannabis users (77% male), recruited from a medical marijuana dispensary in California, who completed assessments of medical cannabis use motives, history, preferences (species type), and problems, as well as current pain level. Individuals who used cannabis to manage chronic pain experienced fewer cannabis use problems than those who did not use it for pain; among those who used it for pain, the average pain level in the past week was not associated with cannabis use problems. Furthermore, individuals who used cannabis for chronic pain were more likely to use indica over sativa. Preference for indica was associated with fewer cannabis use problems than preference for hybrid species. Individuals who use cannabis to manage chronic pain may be at a lower risk for cannabis use problems, relative to individuals who use it for other indications, potentially as a function of their species preference.

  7. Cannabis Prices and Dynamics of Cannabis Use

    OpenAIRE

    J. C. VAN OURS; Williams, J

    2005-01-01

    This paper uses duration models and self-reported cannabis histories from young Australians to study the dynamics of cannabis use. We find that low cannabis prices are associated with early initiation into cannabis use. While the decision to quit does not appear to be directly influenced by price, we find that the younger an individual is when they start using cannabis the less likely they are to quit. Therefore, low cannabis prices lead to early use and because of that they lead to a low qui...

  8. Sex Differences in Cannabis Use and Effects: A Cross-Sectional Survey of Cannabis Users

    Science.gov (United States)

    Cuttler, Carrie; Mischley, Laurie K.; Sexton, Michelle

    2016-01-01

    Abstract Introduction: Despite known sex differences in the endocannabinoid system of animals, little attention has been paid to sex differences in human's cannabis use patterns and effects. The purpose of the present study was to examine sex differences in cannabis use patterns and effects in a large sample of recreational and medical cannabis users. Methods: A large sample (n=2374) of cannabis users completed an anonymous, online survey that assessed their cannabis use practices and experiences, including the short-term acute effects of cannabis and withdrawal effects. A subsample of 1418 medical cannabis users further indicated the medical conditions for which they use cannabis and its perceived efficacy. Results: The results indicated that men reported using cannabis more frequently and in higher quantities than did women. Men were more likely to report using joints/blunts, vaporizers, and concentrates, while women were more likely to report using pipes and oral administration. Men were more likely than women to report increased appetite, improved memory, enthusiasm, altered time perception, and increased musicality when high, while women were more likely than men to report loss of appetite and desire to clean when high. Men were more likely than women to report insomnia and vivid dreams during periods of withdrawal, while women were more likely than men to report nausea and anxiety as withdrawal symptoms. Sex differences in the conditions for which medical cannabis is used, and its efficacy, were trivial. Conclusions: These results may be used to focus research on biological and psychosocial mechanisms underlying cannabis-related sex differences, to inform clinicians treating individuals with cannabis use disorders, and to inform cannabis consumers, clinicians, and policymakers about the risks and benefits of cannabis for both sexes. PMID:28861492

  9. Medicinal cannabis.

    Science.gov (United States)

    Murnion, Bridin

    2015-12-01

    A number of therapeutic uses of cannabis and its derivatives have been postulated from preclinical investigations. Possible clinical indications include spasticity and pain in multiple sclerosis, cancer-associated nausea and vomiting, cancer pain and HIV neuropathy. However, evidence is limited, may reflect subjective rather than objective outcomes, and is not conclusive. Controversies lie in how to produce, supply and administer cannabinoid products. Introduction of cannabinoids therapeutically should be supported by a regulatory and educational framework that minimises the risk of harm to patients and the community. The Regulator of Medicinal Cannabis Bill 2014 is under consideration in Australia to address this. Nabiximols is the only cannabinoid on the Australian Register of Therapeutic Goods at present, although cannabidiol has been recommended for inclusion in Schedule 4.

  10. Treatment seeking in cannabis dependence: The role of social cognition.

    Science.gov (United States)

    Papinczak, Zoe E; Connor, Jason P; Feeney, Gerald F X; Young, Ross McD; Gullo, Matthew J

    2017-01-01

    Relatively few cannabis dependent individuals seek treatment and little is known about the determinants of treatment seeking. Social Cognitive Theory (SCT) provides a useful framework for examining human behaviour and motivation which may be helpful in explaining treatment seeking. This study examined the differences in cannabis outcome expectancies and cannabis refusal self-efficacy between treatment seekers and non-treatment seekers with cannabis dependence. Non-treatment seekers were referred to an illicit drug diversion program. Treatment seekers commenced an outpatient cannabis treatment program and completed a comprehensive assessment that included measures of cannabis outcome expectancies and refusal self-efficacy. A public hospital alcohol and drug outpatient clinic. 269 non-treatment seekers and 195 individuals commencing cannabis dependence treatment. The Cannabis Expectancy Questionnaire (CEQ), Cannabis Refusal Self-Efficacy Questionnaire (CRSEQ), Severity of Dependence Scale - Cannabis (SDS-C), General Health Questionnaire (GHQ-28) and Readiness to Change Questionnaire (RTC) were completed. Treatment seekers had significantly higher levels of negative cannabis outcome expectancies and significantly lower levels of emotional relief refusal self-efficacy (belief in ability to resist using cannabis when experiencing negative affect) (pspsychological distress and self-perceived cannabis dependence compared to non-treatment seekers (pscannabis outcome expectancies and low emotional relief refusal self-efficacy may play a key role in motivation to seek treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Cannabis use and support for cannabis legalization

    NARCIS (Netherlands)

    Palali, A. (Ali); van Ours, J.C. (Jan C.)

    2016-01-01

    textabstractWe investigate the determinants of the support for cannabis legalization finding a causal effect of personal experience with cannabis use. Current and past cannabis users are more in favor of legalization. We relate this finding to self-interest and inside information about potential dan

  12. Cannabis use and support for cannabis legalization

    NARCIS (Netherlands)

    Palali, A. (Ali); J.C. van Ours (Jan)

    2016-01-01

    textabstractWe investigate the determinants of the support for cannabis legalization finding a causal effect of personal experience with cannabis use. Current and past cannabis users are more in favor of legalization. We relate this finding to self-interest and inside information about potential dan

  13. Cannabis use and support for cannabis legalization

    NARCIS (Netherlands)

    Palali, A. (Ali); J.C. van Ours (Jan)

    2016-01-01

    textabstractWe investigate the determinants of the support for cannabis legalization finding a causal effect of personal experience with cannabis use. Current and past cannabis users are more in favor of legalization. We relate this finding to self-interest and inside information about potential

  14. Cannabis use and support for cannabis legalization

    NARCIS (Netherlands)

    Palali, Ali; van Ours, Jan

    We investigate the determinants of the support for cannabis legalization finding a causal effect of personal experience with cannabis use. Current and past cannabis users are more in favor of legalization. We relate this finding to self-interest and inside information about potential dangers of

  15. Cannabis use and support for cannabis legalization

    NARCIS (Netherlands)

    Palali, Ali; van Ours, Jan

    2016-01-01

    We investigate the determinants of the support for cannabis legalization finding a causal effect of personal experience with cannabis use. Current and past cannabis users are more in favor of legalization. We relate this finding to self-interest and inside information about potential dangers of cann

  16. Cocaine withdrawal

    Science.gov (United States)

    ... feeling of discomfort Increased appetite Vivid and unpleasant dreams Slowing of activity The craving and depression can ... powerful. Exams and Tests A physical examination and history of cocaine use are often all that is ...

  17. Cocaine intoxication

    Science.gov (United States)

    ... with other substances, which can cause additional symptoms. Exams and Tests Tests may include: Blood chemistries and ... ECG) References Perrone J, Hoffman RS. Cocaine, amphetamines, caffeine, and nicotine. In: Tintinalli JE, Kelen GD, Stapczynski ...

  18. Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers.

    Science.gov (United States)

    Haney, Margaret; Ramesh, Divya; Glass, Andrew; Pavlicova, Martina; Bedi, Gillinder; Cooper, Ziva D

    2015-10-01

    Given that cannabis use is increasing in the United States, pharmacological treatment options to treat cannabis use disorder are needed. Opioid antagonists modulate cannabinoid effects and may offer a potential approach to reducing cannabis use. In this double-blind, placebo-controlled human laboratory study, we assessed the effects of naltrexone maintenance on the reinforcing, subjective, psychomotor, and cardiovascular effects of active and inactive cannabis. Nontreatment-seeking, daily cannabis smokers were randomized to receive naltrexone (50 mg: n=18 M and 5 F) or placebo (0 mg; n=26 M and 2 F) capsules for 16 days. Before, during, and after medication maintenance, participants completed 10 laboratory sessions over 4-6 weeks, assessing cannabis' behavioral and cardiovascular effects. Medication compliance was verified by observed capsule administration, plasma naltrexone, and urinary riboflavin. Relative to placebo, maintenance on naltrexone significantly reduced both active cannabis self-administration and its positive subjective effects ('good effect'). Participants in the placebo group had 7.6 times (95% CI: 1.1-51.8) the odds of self-administering active cannabis compared with the naltrexone group. This attenuation of reinforcing and positive subjective effects also influenced cannabis use in the natural ecology. Naltrexone had intrinsic effects: decreasing ratings of friendliness, food intake, and systolic blood pressure, and increasing spontaneous reports of stomach upset and headache, yet dropout rates were comparable between groups. In summary, we show for the first time that maintenance on naltrexone decreased cannabis self-administration and ratings of 'good effect' in nontreatment-seeking daily cannabis smokers. Clinical studies in patients motivated to reduce their cannabis use are warranted to evaluate naltrexone's efficacy as a treatment for cannabis use disorder.

  19. Cannabis use and bone mineral density: NHANES 2007-2010.

    Science.gov (United States)

    Bourne, Donald; Plinke, Wesley; Hooker, Elizabeth R; Nielson, Carrie M

    2017-12-01

    Cannabis use is rising in the USA. Its relationship to cannabinoid signaling in bone cells implies its use could affect bone mineral density (BMD) in the population. In a national survey of people ages 20-59, we found no association between self-reported cannabis use and BMD of the hip or spine. Cannabis is the most widely used illegal drug in the USA, and its recreational use has recently been approved in several US states. Cannabinoids play a role in bone homeostasis. We aimed to determine the association between cannabis use and BMD in US adults. In the National Health and Nutrition Examination Survey 2007-2010, 4743 participants between 20 and 59 years old, history of cannabis use was categorized into never, former (previous use, but not in last 30 days), light (1-4 days of use in last 30 days), and heavy (≥5 days of use in last 30 days). Multivariable linear regression was used to test the association between cannabis use and DXA BMD of the proximal femur and lumbar spine with adjustment for age, sex, BMI, and race/ethnicity among other BMD determinants. Sixty percent of the population reported ever using cannabis; 47% were former users, 5% were light users, and 7% were heavy users. Heavy cannabis users were more likely to be male, have a lower BMI, increased daily alcohol intake, increased tobacco pack-years, and were more likely to have used other illegal drugs (cocaine, heroin, or methamphetamines). No association between cannabis and BMD was observed for any level of use (p ≥ 0.28). A history of cannabis use, although highly prevalent and related to other risk factors for low BMD, was not independently associated with BMD in this cross-sectional study of American men and women.

  20. The intersection between cannabis and cancer in the United States.

    Science.gov (United States)

    Bowles, Daniel W; O'Bryant, Cindy L; Camidge, D Ross; Jimeno, Antonio

    2012-07-01

    In the last 15 years there has been a major shift in the laws governing medical use of cannabis in the United States. Corresponding with this change there has been escalating interest in the role that cannabis, commonly referred to as marijuana, and cannabinoids play in the care of patients with cancer. This review will examine cannabis' and cannabinoids' current and potential roles in cancer care. Specifically, we will examine five areas of cannabis medicine: (1) pharmacologic properties of cannabis; (2) its potential role in the development of human cancers, particularly smoking-related malignancies; (3) cannabinoids' potential as anti-cancer therapies; (4) cannabis and cannabinoids in the palliation of common cancer-associated symptoms; (5) current legal status of cannabis for medical purposes in the United States. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. La cannabis.

    Directory of Open Access Journals (Sweden)

    José Vicente Stalrich Canet

    1981-01-01

    Full Text Available En los últimos 20 ó 30 años hemos visto nuevos tipos de drogas que anteriormente no existían en nuestro mundo occidental o bien tenían una difusión bastante localizada y estable; me refiero, sobre todo, a los psicofármacos, los opiáceos y la cannabis corno las más importantes sin olvidar, no obstante, otras también actuales: los alucinógenos (sintéticos y naturales, inhalantes, etc. Estas nuevas r drogas conviven en nuestra sociedad con las otras más clásicas y generadoras de multitud de problemas como son el alcohol y el tabaco

  2. La cannabis.

    OpenAIRE

    José Vicente Stalrich Canet

    1981-01-01

    En los últimos 20 ó 30 años hemos visto nuevos tipos de drogas que anteriormente no existían en nuestro mundo occidental o bien tenían una difusión bastante localizada y estable; me refiero, sobre todo, a los psicofármacos, los opiáceos y la cannabis corno las más importantes sin olvidar, no obstante, otras también actuales: los alucinógenos (sintéticos y naturales), inhalantes, etc. Estas nuevas r drogas conviven en nuestra sociedad con las otras más clásicas y generadoras de multitud de pro...

  3. CANNABIS MEDICINAL

    Directory of Open Access Journals (Sweden)

    Alfredo Jácome Roca

    2014-12-01

    Full Text Available Los estupefacientes han estado presentes en la historia de la medicina desde la antigüedad. La materia médica china (Pen-ts’ao-Ching atribuida al emperador rojo Shen-nung, incluye a la Cannabis indica para reducir el dolor del reumatismo y por sus beneficios en desórdenes digestivos. El láudano (tintura alcohólica de opio, la esponja anestésica (mandrágora con opio, o la teriaca (polifármaco que contenía opio fueron pilar de la lucha contra el dolor y otros males. El opio proviene del jugo de la corteza verde de la adormidera –variedad de amapola- o Papaver somniferum y ha sido reemplazado como potente analgésico de acción central por su alcaloide morfina o por análogos como la meperidina (1. Desde sus orígenes, el ser humano ha buscado alivio en diversas plantas medicinales, la analgesia, la sedación pero también la euforia. El efecto pasajero y la taquifilaxia generada por el uso continuo impulsan un aumento en la frecuencia y en la cantidad de las dosis, perdiéndose sus beneficios y aumentando su toxicidad. En estos casos, disminuye el número y la sensibilidad de los diferentes receptores, fenómeno conocido como down-regulation. Al ser adictivos, el manejo de estos narcóticos debe ser estrictamente médico y fuertemente regulado, cosa de la que se han librado el alcohol y el tabaco. La prohibición del licor solo llevó al enriquecimiento de los contrabandistas. Hay alucinógenos menos villanos como los obtenidos de la Cannabis sativa, aunque no son demasiado benignos.

  4. A double blind, placebo-controlled study of the effects of post-retrieval propranolol on reconsolidation of memory for craving and cue reactivity in cocaine dependent humans.

    Science.gov (United States)

    Saladin, Michael E; Gray, Kevin M; McRae-Clark, Aimee L; Larowe, Steven D; Yeatts, Sharon D; Baker, Nathaniel L; Hartwell, Karen J; Brady, Kathleen T

    2013-04-01

    This study examined the effects of propranolol vs. placebo, administered immediately after a "retrieval" session of cocaine cue exposure (CCE), on craving and physiological responses occurring 24 h later during a subsequent "test" session of CCE. It was hypothesized that compared to placebo-treated cocaine-dependent (CD) individuals, propranolol-treated CD individuals would evidence attenuated craving and physiological reactivity during the test session. Secondarily, it was expected that group differences identified in the test session would be evident at a 1-week follow-up CCE session. Exploratory analyses of treatment effects on cocaine use were also performed at follow-up. CD participants received either 40 mg propranolol or placebo immediately following a "retrieval" CCE session. The next day, participants received a "test" session of CCE that was identical to the "retrieval" session except no medication was administered. Participants underwent a "follow-up" CCE session 1 week later. Craving and other reactivity measures were obtained at multiple time points during the CCE sessions. Propranolol- vs. placebo-treated participants evidenced significantly greater attenuation of craving and cardiovascular reactivity during the test session. Analysis of the follow-up CCE session data did not reveal any group differences. Although there was no evidence of treatment effects on cocaine use during follow-up, this study was insufficiently powered to rigorously evaluate differential cocaine use. This double-blind, placebo-controlled laboratory study provides the first evidence that propranolol administration following CCE may modulate memories for learning processes that subserve cocaine craving/cue reactivity in CD humans. Alternative interpretations of the findings were considered, and implications of the results for treatment were noted.

  5. An antidote for acute cocaine toxicity.

    Science.gov (United States)

    Treweek, Jennifer B; Janda, Kim D

    2012-04-02

    Not only has immunopharmacotherapy grown into a field that addresses the abuse of numerous illicit substances, but also the treatment methodologies within immunopharmacotherapy have expanded from traditional active vaccination to passive immunization with anti-drug monoclonal antibodies, optimized mAb formats, and catalytic drug-degrading antibodies. Many laboratories have focused on transitioning distinct immunopharmacotherapeutics to clinical evaluation, but with respect to the indication of cocaine abuse, only the active vaccine TA-CD, which is modeled after our original cocaine hapten GNC, has been carried through to human clinical trials. The successful application of murine mAb GNC92H2 to the reversal of cocaine overdose in a mouse model prompted investigations of human immunoglobulins with the clinical potential to serve as cocaine antidotes. We now report the therapeutic utility of a superior clone, human mAb GNCgzk (K(d) = 0.18 nM), which offers a 10-fold improvement in cocaine binding affinity. The GNCgzk manifold was engineered for rapid cocaine clearance, and administration of the F(ab')₂ and Fab formats even after the appearance of acute behavioral signs of cocaine toxicity granted nearly complete prevention of lethality. Thus, contrary to the immunopharmacotherapeutic treatment of drug self-administration, minimal antibody doses were shown to counteract the lethality of a molar excess of circulating cocaine. Passive vaccination with drug-specific antibodies represents a viable treatment strategy for the human condition of cocaine overdose.

  6. Mind Over Matter: Cocaine

    Science.gov (United States)

    ... Term(s): Teachers / NIDA Teaching Guide / Mind Over Matter Teaching Guide and Series / Cocaine Print Mind Over Matter: Cocaine Order Free Publication in: English Spanish Download PDF 806.08 KB Cocaine is ...

  7. Assessing Topographical Orientation Skills in Cannabis Users

    Science.gov (United States)

    Palermo, Liana; Bianchini, Filippo; Iaria, Giuseppe; Tanzilli, Antonio; Guariglia, Cecilia

    2012-01-01

    The long-term effects of cannabis on human cognition are still unclear, but, considering that cannabis is a widely used substance and, overall, its potential use in therapeutic interventions, it is important to evaluate them. We hypothesize that the discrepancies among studies could be attributed to the specific cognitive function investigated and that skills subserved by the hippocampus, such as the spatial orientation abilities and, specifically, the ability to form and use cognitive maps, should be more compromised than others. Indeed it has been showed that cannabis users have a reduced hippocampus and that the hippocampus is the brain region in which cannabis has the greatest effect since it contains the highest concentration of cannabinoid receptors. To test this hypothesis we asked 15 heavy cannabis users and 19 nonusers to perform a virtual navigational test, the CMT, that assesses the ability to form and use cognitive maps. We found that using cannabis has no effect on these hippocampus-dependent orientation skills. We discuss the implications of our findings and how they relate to evidence reported in the literature that the intervention of functional reorganization mechanisms in cannabis user allows them to cope with the cognitive demands of navigational tasks. PMID:22272167

  8. Assessing Topographical Orientation Skills in Cannabis Users

    Directory of Open Access Journals (Sweden)

    Liana Palermo

    2012-01-01

    Full Text Available The long-term effects of cannabis on human cognition are still unclear, but, considering that cannabis is a widely used substance and, overall, its potential use in therapeutic interventions, it is important to evaluate them. We hypothesize that the discrepancies among studies could be attributed to the specific cognitive function investigated and that skills subserved by the hippocampus, such as the spatial orientation abilities and, specifically, the ability to form and use cognitive maps, should be more compromised than others. Indeed it has been showed that cannabis users have a reduced hippocampus and that the hippocampus is the brain region in which cannabis has the greatest effect since it contains the highest concentration of cannabinoid receptors. To test this hypothesis we asked 15 heavy cannabis users and 19 nonusers to perform a virtual navigational test, the CMT, that assesses the ability to form and use cognitive maps. We found that using cannabis has no effect on these hippocampus-dependent orientation skills. We discuss the implications of our findings and how they relate to evidence reported in the literature that the intervention of functional reorganization mechanisms in cannabis user allows them to cope with the cognitive demands of navigational tasks.

  9. Integrating cannabis into clinical cancer care.

    Science.gov (United States)

    Abrams, D I

    2016-03-01

    Cannabis species have been used as medicine for thousands of years; only since the 1940s has the plant not been widely available for medical use. However, an increasing number of jurisdictions are making it possible for patients to obtain the botanical for medicinal use. For the cancer patient, cannabis has a number of potential benefits, especially in the management of symptoms. Cannabis is useful in combatting anorexia, chemotherapy-induced nausea and vomiting, pain, insomnia, and depression. Cannabis might be less potent than other available antiemetics, but for some patients, it is the only agent that works, and it is the only antiemetic that also increases appetite. Inhaled cannabis is more effective than placebo in ameliorating peripheral neuropathy in a number of conditions, and it could prove useful in chemotherapy-induced neuropathy. A pharmacokinetic interaction study of vaporized cannabis in patients with chronic pain on stable doses of sustained-release opioids demonstrated no clinically significant change in plasma opiates, while suggesting the possibility of synergistic analgesia. Aside from symptom management, an increasing body of in vitro and animal-model studies supports a possible direct anticancer effect of cannabinoids by way of a number of different mechanisms involving apoptosis, angiogenesis, and inhibition of metastasis. Despite an absence of clinical trials, abundant anecdotal reports that describe patients having remarkable responses to cannabis as an anticancer agent, especially when taken as a high-potency orally ingested concentrate, are circulating. Human studies should be conducted to address critical questions related to the foregoing effects.

  10. Metabolic Enzymes of Cocaine Metabolite Benzoylecgonine.

    Science.gov (United States)

    Chen, Xiabin; Zheng, Xirong; Zhan, Max; Zhou, Ziyuan; Zhan, Chang-Guo; Zheng, Fang

    2016-08-19

    Cocaine is one of the most addictive drugs without a U.S. Food and Drug Administration (FDA)-approved medication. Enzyme therapy using an efficient cocaine-metabolizing enzyme is recognized as the most promising approach to cocaine overdose treatment. The actual enzyme, known as RBP-8000, under current clinical development for cocaine overdose treatment is our previously designed T172R/G173Q mutant of bacterial cocaine esterase (CocE). The T172R/G173Q mutant is effective in hydrolyzing cocaine but inactive against benzoylecgonine (a major, biologically active metabolite of cocaine). Unlike cocaine itself, benzoylecgonine has an unusually stable zwitterion structure resistant to further hydrolysis in the body and environment. In fact, benzoylecgonine can last in the body for a very long time (a few days) and, thus, is responsible for the long-term toxicity of cocaine and a commonly used marker for drug addiction diagnosis in pre-employment drug tests. Because CocE and its mutants are all active against cocaine and inactive against benzoylecgonine, one might simply assume that other enzymes that are active against cocaine are also inactive against benzoylecgonine. Here, through combined computational modeling and experimental studies, we demonstrate for the first time that human butyrylcholinesterase (BChE) is actually active against benzoylecgonine, and that a rationally designed BChE mutant can not only more efficiently accelerate cocaine hydrolysis but also significantly hydrolyze benzoylecgonine in vitro and in vivo. This sets the stage for advanced studies to design more efficient mutant enzymes valuable for the development of an ideal cocaine overdose enzyme therapy and for benzoylecgonine detoxification in the environment.

  11. Teenage cardiac arrest following abuse of synthetic cannabis.

    Science.gov (United States)

    Davis, C; Boddington, D

    2015-10-01

    The cardiac effects of many illegal substances (cocaine, methadone) have previously been well described [1,2]. However the association between synthetic cannabis and cardiac arrest is less well documented. Here we describe an out-of-hospital cardiac arrest in a previously healthy 16-year-old female associated with the use of inhaled synthetic cannabis. An electronic systematic search of online databases PubMed and Embase was performed using keywords, "synthetic cannabis death" and "cardiac arrest". In this case study a previously healthy 16-year-old had a cardiac arrest after synthetic cannabis use. Despite extensive investigations no other cause for her arrest was found. To the best of our knowledge there has been one previous case report of cardiac arrest following synthetic cannabis use in a 56-year-old man [3]. This case report augments the relationship between synthetic cannabis and cardiac arrest in the medical community. More awareness surrounding the risk of synthetic cannabinoids is warranted. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  12. Cannabis and adolescent brain development.

    Science.gov (United States)

    Lubman, Dan I; Cheetham, Ali; Yücel, Murat

    2015-04-01

    Heavy cannabis use has been frequently associated with increased rates of mental illness and cognitive impairment, particularly amongst adolescent users. However, the neurobiological processes that underlie these associations are still not well understood. In this review, we discuss the findings of studies examining the acute and chronic effects of cannabis use on the brain, with a particular focus on the impact of commencing use during adolescence. Accumulating evidence from both animal and human studies suggests that regular heavy use during this period is associated with more severe and persistent negative outcomes than use during adulthood, suggesting that the adolescent brain may be particularly vulnerable to the effects of cannabis exposure. As the endocannabinoid system plays an important role in brain development, it is plausible that prolonged use during adolescence results in a disruption in the normative neuromaturational processes that occur during this period. We identify synaptic pruning and white matter development as two processes that may be adversely impacted by cannabis exposure during adolescence. Potentially, alterations in these processes may underlie the cognitive and emotional deficits that have been associated with regular use commencing during adolescence.

  13. Treatment of Crohn's disease with cannabis: an observational study.

    Science.gov (United States)

    Naftali, Timna; Lev, Lihi Bar; Yablecovitch, Doron; Yablekovitz, Doron; Half, Elisabeth; Konikoff, Fred M

    2011-08-01

    The marijuana plant cannabis is known to have therapeutic effects, including improvement of inflammatory processes. However, no report of patients using cannabis for Crohn's disease (CD) was ever published. To describe the effects of cannabis use in patients suffering from CD. In this retrospective observational study we examined disease activity, use of medication, need for surgery, and hospitalization before and after cannabis use in 30 patients (26 males) with CD. Disease activity was assessed by the Harvey Bradshaw index for Crohn's disease. Of the 30 patients 21 improved significantly after treatment with cannabis. The average Harvey Bradshaw index improved from 14 +/- 6.7 to 7 +/- 4.7 (P < 0.001). The need for other medication was significantly reduced. Fifteen of the patients had 19 surgeries during an average period of 9 years before cannabis use, but only 2 required surgery during an average period of 3 years of cannabis use. This is the first report of cannabis use in Crohn's disease in humans. The results indicate that cannabis may have a positive effect on disease activity, as reflected by reduction in disease activity index and in the need for other drugs and surgery. Prospective placebo-controlled studies are warranted to fully evaluate the efficacy and side effects of cannabis in CD.

  14. Psychomotor performance in relation to acute oral administration of Delta9-tetrahydrocannabinol and standardized cannabis extract in healthy human subjects.

    Science.gov (United States)

    Roser, Patrik; Gallinat, Jürgen; Weinberg, Gordon; Juckel, Georg; Gorynia, Inge; Stadelmann, Andreas M

    2009-08-01

    Abnormalities in psychomotor performance are a consistent finding in schizophrenic patients as well as in chronic cannabis users. The high levels of central cannabinoid (CB(1)) receptors in the basal ganglia, the cerebral cortex and the cerebellum indicate their implication in the regulation of motor activity. Based on the close relationship between cannabis use, the endogenous cannabinoid system and motor disturbances found in schizophrenia, we expected that administration of cannabinoids may change pattern of psychomotor activity like in schizophrenic patients. This prospective, double-blind, placebo-controlled cross-over study investigated the acute effects of cannabinoids on psychomotor performance in 24 healthy right-handed volunteers (age 27.9 +/- 2.9 years, 12 male) by comparing Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and standardized cannabis extract containing Delta(9)-THC and cannabidiol. Psychomotor performance was assessed by using a finger tapping test series. Cannabis extract, but not Delta(9)-THC, revealed a significant reduction of right-hand tapping frequencies that was also found in schizophrenia. As to the pure Delta(9)-THC condition, left-hand tapping frequencies were correlated with the plasma concentrations of the Delta(9)-THC metabolite 11-OH-THC. These effects are thought to be related to cannabinoid actions on CB(1) receptors in the basal ganglia, the cerebral cortex and the cerebellum. Our data further demonstrate that acute CB(1) receptor activation under the cannabis extract condition may also affect intermanual coordination (IMC) as an index of interhemispheric transfer. AIR-Scale scores as a measure of subjective perception of intoxication were dose-dependently related to IMC which was shown by an inverted U-curve. This result may be due to functional changes involving GABAergic and glutamatergic neurotransmission within the corpus callosum.

  15. New insights into cannabis consumption; abuses and possible therapeutic effects

    Directory of Open Access Journals (Sweden)

    Daniela Luiza Baconi

    2014-10-01

    Full Text Available Cannabis is one of the oldest psychotropic drugs known to humanity. The paper assesses the current knowledge on the cannabis, including the mechanisms of action and the therapeutic potential of cannabinoids. Three varieties of Cannabis plant are recognised: Cannabis sativa, Cannabis indica, and Cannabis ruderalis. The variety indica is used predominantly to obtain the drugs. Cannabis herb is usually named marijuana, while the cannabis oleoresin secreted by the glandular hairs found mainly on the flowering or fruiting tops of the plant is known as hashish. More than 400 known chemicals are present in cannabis, at least 70 of which are called cannabinoids. The major psychoactive constituent in cannabis is delta-9-tetrahydrocannabinol (Δ9-THC. It is now recognized that there are three types of cannabinoids: natural (phytocannabinoids, endogenous cannabinoids, and synthetic cannabioids. Cannabinoids exert their actions by binding to specific membrane protein, the cannabinoid receptor. To date, two subtypes of cannabinoid receptors, named cannabinoid-1 (CB1, most abundantly expressed in the central nervous system and cannabinoid-2 (CB2 receptors, found predominantly in peripheral tissues with immune functions have been cloned. Therefore, the concept of endogenous cannabinoid system (endocannabinoid system, SEC has been developed. Based on the current scientific evidence, there are several effects of cannabinoids with potential therapeutic use: antiemetic, analgesic in cancerous pains, and chronic neuropathic pain, in multiple sclerosis or spinal cord injuries. Cannabis consume can result in a state of drug dependency and cannabis withdrawal has been included in DSM-V. Cannabis plant remains controversial in the twenty-first century and the potential therapeutic of specific cannabinoid compounds and medical marijuana remains under active medical research.

  16. The effect of cannabis use on memory function: an update

    Directory of Open Access Journals (Sweden)

    Schoeler T

    2013-01-01

    Full Text Available Tabea Schoeler, Sagnik BhattacharyyaDepartment of Psychosis Studies, King's College London, Institute of Psychiatry, London, UKAbstract: Investigating the effects of cannabis use on memory function appears challenging. While early observational investigations aimed to elucidate the longer-term effects of cannabis use on memory function in humans, findings remained equivocal and pointed to a pattern of interacting factors impacting on the relationship between cannabis use and memory function, rather than a simple direct effect of cannabis. Only recently, a clearer picture of the chronic and acute effects of cannabis use on memory function has emerged once studies have controlled for potential confounding factors and started to investigate the acute effects of delta-9-tetrahydrocannabinol (Δ9-THC and cannabidiol (CBD, the main ingredients in the extract of the cannabis plant in pharmacological challenge experiments. Relatively consistent findings have been reported regarding the acute impairments induced by a single dose of Δ9-THC on verbal and working memory. It is unclear whether they may persist beyond the intoxication state. In the long-term, these impairments seem particularly likely to manifest and may also persist following abstinence if regular and heavy use of cannabis strains high in Δ9-THC is started at an early age. Although still at an early stage, studies that employed advanced neuroimaging techniques have started to model the neural underpinnings of the effects of cannabis use and implicate a network of functional and morphological alterations that may moderate the effects of cannabis on memory function. Future experimental and epidemiological studies that take into consideration individual differences, particularly previous cannabis history and demographic characteristics, but also the precise mixture of the ingredients of the consumed cannabis are necessary to clarify the magnitude and the mechanisms by which cannabis

  17. [{sup 11}]Cocaine: PET studies of cocaine pharmacokinetics, dopamine transporter availability and dopamine transporter occupancy

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, Joanna S. E-mail: fowler@bnl.gov; Volkow, Nora D.; Wang, Gene-Jack; Gatley, S. John; Logan, Jean

    2001-07-01

    Cocaine was initially labeled with carbon-11 in order to track the distribution and pharmacokinetics of this powerful stimulant and drug of abuse in the human brain and body. It was soon discovered that [{sup 11}C]cocaine was not only useful for measuring cocaine pharmacokinetics and its relationship to behavior but that it is also a sensitive radiotracer for dopamine transporter (DAT) availability. Measures of DAT availability were facilitated by the development of a graphical analysis method (Logan Plot) for reversible systems which streamlined kinetic analysis. This expanded the applications of [{sup 11}C]cocaine to studies of DAT availability in the human brain and allowed the first comparative measures of the degree of DAT occupancy by cocaine and another stimulant drug methylphenidate. This article will summarize preclinical and clinical research with [{sup 11}C]cocaine.

  18. Adolescent Exposure to the Synthetic Cannabinoid WIN 55212-2 Modifies Cocaine Withdrawal Symptoms in Adult Mice

    Science.gov (United States)

    Aguilar, María A.; Ledesma, Juan Carlos; Rodríguez-Arias, Marta; Penalva, Carles; Manzanedo, Carmen; Miñarro, José; Arenas, M. Carmen

    2017-01-01

    Chronic cannabinoid consumption is an increasingly common behavior among teenagers and has been shown to cause long-lasting neurobehavioral alterations. Besides, it has been demonstrated that cocaine addiction in adulthood is highly correlated with cannabis abuse during adolescence. Cocaine consumption and subsequent abstinence from it can cause psychiatric symptoms, such as psychosis, cognitive impairment, anxiety, and depression. The aim of the present research was to study the consequences of adolescent exposure to cannabis on the psychiatric-like effects promoted by cocaine withdrawal in adult mice. We pre-treated juvenile mice with the cannabinoid CB1 receptor agonist WIN 55212-2 (WIN) and then subjected them to a chronic cocaine treatment during adulthood. Following these treatments, animals were tested under cocaine withdrawal in the following paradigms: pre-pulse inhibition, object recognition, elevated plus maze, and tail suspension. The long-term psychotic-like actions induced by WIN were not modified after cocaine cessation. Moreover, the memory impairments induced by cocaine withdrawal were not altered by previous adolescent WIN intake. However, WIN pre-treatment prevented the anxiogenic effects observed after cocaine abstinence, and led to greater depressive-like symptoms following cocaine removal in adulthood. This study is the first to show the long-lasting behavioral consequences of juvenile exposure to WIN on cocaine withdrawal in adult mice. PMID:28635664

  19. Adolescent Exposure to the Synthetic Cannabinoid WIN 55212-2 Modifies Cocaine Withdrawal Symptoms in Adult Mice.

    Science.gov (United States)

    Aguilar, María A; Ledesma, Juan Carlos; Rodríguez-Arias, Marta; Penalva, Carles; Manzanedo, Carmen; Miñarro, José; Arenas, M Carmen

    2017-06-21

    Chronic cannabinoid consumption is an increasingly common behavior among teenagers and has been shown to cause long-lasting neurobehavioral alterations. Besides, it has been demonstrated that cocaine addiction in adulthood is highly correlated with cannabis abuse during adolescence. Cocaine consumption and subsequent abstinence from it can cause psychiatric symptoms, such as psychosis, cognitive impairment, anxiety, and depression. The aim of the present research was to study the consequences of adolescent exposure to cannabis on the psychiatric-like effects promoted by cocaine withdrawal in adult mice. We pre-treated juvenile mice with the cannabinoid CB1 receptor agonist WIN 55212-2 (WIN) and then subjected them to a chronic cocaine treatment during adulthood. Following these treatments, animals were tested under cocaine withdrawal in the following paradigms: pre-pulse inhibition, object recognition, elevated plus maze, and tail suspension. The long-term psychotic-like actions induced by WIN were not modified after cocaine cessation. Moreover, the memory impairments induced by cocaine withdrawal were not altered by previous adolescent WIN intake. However, WIN pre-treatment prevented the anxiogenic effects observed after cocaine abstinence, and led to greater depressive-like symptoms following cocaine removal in adulthood. This study is the first to show the long-lasting behavioral consequences of juvenile exposure to WIN on cocaine withdrawal in adult mice.

  20. Cocaine. Specialized Information Service.

    Science.gov (United States)

    Do It Now Foundation, Phoenix, AZ.

    This compilation of journal articles on cocaine includes a report describing cocaine as the recreational drug of the middle class, statistics from the United States Department of Health on health consequences of cocaine use, an article on "speedballing" (use of cocaine and heroin in combination), and a discussion of the various ways…

  1. Pharmacokinetic Profile of Oral Cannabis in Humans: Blood and Oral Fluid Disposition and Relation to Pharmacodynamic Outcomes.

    Science.gov (United States)

    Vandrey, Ryan; Herrmann, Evan S; Mitchell, John M; Bigelow, George E; Flegel, Ronald; LoDico, Charles; Cone, Edward J

    2017-03-01

    Most research on cannabis pharmacokinetics has evaluated inhaled cannabis, but oral ("edible") preparations comprise an increasing segment of the cannabis market. To assess oral cannabis pharmacokinetics and pharmacodynamics, healthy adults (N = 6 per dose) were administered cannabis brownies containing 10, 25 or 50 mg 9-tetrahydrocannabinol (THC). Whole blood and oral fluid specimens were obtained at baseline and then for 9 days post-exposure; 6 days in a residential research setting and 3 days as outpatients. Measures of subjective, cardiovascular and performance effects were obtained at baseline and for 8 h post-ingestion. The mean Cmax for THC in whole blood was 1, 3.5 and 3.3 ng/mL for the 10, 25 and 50 mg THC doses, respectively. The mean maximum concentration (Cmax) and mean time to maximum concentration (Tmax) of 11-OH-THC in whole blood were similar to THC. Cmax blood concentrations of THCCOOH were generally higher than THC and had longer Tmax values. The mean Tmax for THC in oral fluid occurred immediately following oral dose administration, and appear to reflect local topical residue rather than systemic bioavailbility. Mean Cmax oral fluid concentrations of THCCOOH were lower than THC, erratic over time and mean Tmax occurred at longer times than THC. The window of THC detection ranged from 0 to 22 h for whole blood (limit of quantitation (LOQ) = 0.5 ng/mL) and 1.9 to 22 h for oral fluid (LOQ = 1.0 ng/mL). Subjective drug and cognitive performance effects were generally dose dependent, peaked at 1.5-3 h post-administration, and lasted 6-8 h. Whole blood cannabinoid concentrations were significantly correlated with subjective drug effects. Correlations between blood cannabinoids and cognitive performance measures, and between oral fluid and all pharmacodynamic outcomes were either non-significant or not orderly by dose. Quantitative levels of cannabinoids in whole blood and oral fluid were low compared with levels observed following inhalation of

  2. Low startle magnitude may be a behavioral marker of vulnerability to cocaine addiction.

    Science.gov (United States)

    Wheeler, Marina G; Duncan, Erica; Davis, Michael

    2017-01-01

    Cocaine addicted men have low startle magnitude persisting during prolonged abstinence. Low startle rats show greater cocaine self-administration than high startle rats. Low startle may be a marker of a vulnerability to heightened cocaine-related behaviors in rats and similarly may be a marker of vulnerability to cocaine addiction in humans.

  3. D-cycloserine and cocaine cue reactivity: preliminary findings.

    Science.gov (United States)

    Price, Kimber L; McRae-Clark, Aimee L; Saladin, Michael E; Maria, Megan M Moran-Santa; DeSantis, Stacia M; Back, Sudie E; Brady, Kathleen T

    2009-01-01

    D-cycloserine (DCS), a partial glutamate N-methyl-D-aspartic acid (NMDA) receptor agonist, enhances extinction of conditioned fear responding in rodents and facilitates exposure-based learning in humans with anxiety disorders. This preliminary study investigates DCS pretreatment on response to cocaine cues in cocaine-dependent subjects. Ten cocaine-dependent subjects were randomly assigned to receive either 50 mg DCS or matching placebo two hours before each of two 1-hour cocaine cue exposure sessions one day apart. HR and craving ratings were obtained before and during cue exposure sessions. There was a trend towards increased craving to cocaine cues in cocaine-dependent individuals after administration of DCS. The administration of DCS prior to cue exposure sessions may facilitate response activation. While facilitation of extinction-based learning by DCS may have therapeutic potential for cocaine dependence, this drug may exhibit a different profile in cocaine-dependent individuals as compared to those with anxiety disorders.

  4. Cannabis; extracting the medicine

    OpenAIRE

    Hazekamp, Arno

    2007-01-01

    The cannabis plant (Cannabis sativa L.) has a long history as a recreational drug, but also as part of traditional medicine in many cultures. Nowadays, it is used by a large number of patients worldwide, to ameliorate the symptoms of diseases varying from cancer and AIDS to multiple sclerosis and migraine. The discovery of cannabinoid-receptors and the endocannabinoid system have opened up a new and exciting field of research. But despite the pharmaceutical potential of cannabis, its classifi...

  5. Cannabis Use during Adolescent Development: Susceptibility to Psychiatric Illness.

    Science.gov (United States)

    Chadwick, Benjamin; Miller, Michael L; Hurd, Yasmin L

    2013-10-14

    Cannabis use is increasingly pervasive among adolescents today, even more common than cigarette smoking. The evolving policy surrounding the legalization of cannabis reaffirms the need to understand the relationship between cannabis exposure early in life and psychiatric illnesses. cannabis contains psychoactive components, notably Δ(9)-tetrahydrocannabinol (THC), that interfere with the brain's endogenous endocannabinoid system, which is critically involved in both pre- and post-natal neurodevelopment. Consequently, THC and related compounds could potentially usurp normal adolescent neurodevelopment, shifting the brain's developmental trajectory toward a disease-vulnerable state, predisposing early cannabis users to motivational, affective, and psychotic disorders. Numerous human studies, including prospective longitudinal studies, demonstrate that early cannabis use is associated with major depressive disorder and drug addiction. A strong association between schizophrenia and cannabis use is also apparent, especially when considering genetic factors that interact with this environmental exposure. These human studies set a foundation for carefully controlled animal studies which demonstrate similar patterns following early cannabinoid exposure. Given the vulnerable nature of adolescent neurodevelopment and the persistent changes that follow early cannabis exposure, the experimental findings outlined should be carefully considered by policymakers. In order to fully address the growing issues of psychiatric illnesses and to ensure a healthy future, measures should be taken to reduce cannabis use among teens.

  6. Cannabis use during adolescent development: susceptibility to psychiatric illness

    Directory of Open Access Journals (Sweden)

    Benjamin eChadwick

    2013-10-01

    Full Text Available Cannabis use is increasingly pervasive among adolescents today, even more common than cigarette smoking. The evolving policy surrounding the legalization of cannabis reaffirms the need to understand the relationship between cannabis exposure early in life and psychiatric illnesses. Cannabis contains psychoactive components, notably Δ9-tetrahydrocannbinol (THC, that interfere with the brain’s endogenous endocannabinoid system, which is critically involved in both pre- and post-natal neurodevelopment. Consequently, THC and related compounds could potentially usurp normal adolescent neurodevelopment, shifting the brain’s developmental trajectory towards a disease-vulnerable state, predisposing early cannabis-users to motivational, affective and psychotic disorders. Numerous human studies, including prospective longitudinal studies, demonstrate that early cannabis use is associated with major depressive disorder and drug addiction. A strong association between schizophrenia and cannabis use is also apparent, especially when considering genetic factors that interact with this environmental exposure. These human studies set a foundation for carefully controlled animal studies which demonstrate similar patterns following early cannabinoid exposure. Given the vulnerable nature of adolescent neurodevelopment and the persistent changes that follow early cannabis exposure, the experimental findings outlined should be carefully considered by policymakers. In order to fully address the growing issues of psychiatric illnesses and to ensure a healthy future, measures should be taken to reduce cannabis use among teens.

  7. Cannabis Use during Adolescent Development: Susceptibility to Psychiatric Illness

    Science.gov (United States)

    Chadwick, Benjamin; Miller, Michael L.; Hurd, Yasmin L.

    2013-01-01

    Cannabis use is increasingly pervasive among adolescents today, even more common than cigarette smoking. The evolving policy surrounding the legalization of cannabis reaffirms the need to understand the relationship between cannabis exposure early in life and psychiatric illnesses. cannabis contains psychoactive components, notably Δ9-tetrahydrocannabinol (THC), that interfere with the brain’s endogenous endocannabinoid system, which is critically involved in both pre- and post-natal neurodevelopment. Consequently, THC and related compounds could potentially usurp normal adolescent neurodevelopment, shifting the brain’s developmental trajectory toward a disease-vulnerable state, predisposing early cannabis users to motivational, affective, and psychotic disorders. Numerous human studies, including prospective longitudinal studies, demonstrate that early cannabis use is associated with major depressive disorder and drug addiction. A strong association between schizophrenia and cannabis use is also apparent, especially when considering genetic factors that interact with this environmental exposure. These human studies set a foundation for carefully controlled animal studies which demonstrate similar patterns following early cannabinoid exposure. Given the vulnerable nature of adolescent neurodevelopment and the persistent changes that follow early cannabis exposure, the experimental findings outlined should be carefully considered by policymakers. In order to fully address the growing issues of psychiatric illnesses and to ensure a healthy future, measures should be taken to reduce cannabis use among teens. PMID:24133461

  8. Effects of cocaine on honey bee dance behaviour.

    Science.gov (United States)

    Barron, Andrew B; Maleszka, Ryszard; Helliwell, Paul G; Robinson, Gene E

    2009-01-01

    The role of cocaine as an addictive drug of abuse in human society is hard to reconcile with its ecological role as a natural insecticide and plant-protective compound, preventing herbivory of coca plants (Erythroxylum spp.). This paradox is often explained by proposing a fundamental difference in mammalian and invertebrate responses to cocaine, but here we show effects of cocaine on honey bees (Apis mellifera L.) that parallel human responses. Forager honey bees perform symbolic dances to advertise the location and value of floral resources to their nest mates. Treatment with a low dose of cocaine increased the likelihood and rate of bees dancing after foraging but did not otherwise increase locomotor activity. This is consistent with cocaine causing forager bees to overestimate the value of the floral resources they collected. Further, cessation of chronic cocaine treatment caused a withdrawal-like response. These similarities likely occur because in both insects and mammals the biogenic amine neuromodulator systems disrupted by cocaine perform similar roles as modulators of reward and motor systems. Given these analogous responses to cocaine in insects and mammals, we propose an alternative solution to the paradox of cocaine reinforcement. Ecologically, cocaine is an effective plant defence compound via disruption of herbivore motor control but, because the neurochemical systems targeted by cocaine also modulate reward processing, the reinforcing properties of cocaine occur as a ;side effect'.

  9. Cocaine analytes in human hair: evaluation of concentration ratios in different cocaine sources, drug-user populations and surface-contaminated specimens.

    Science.gov (United States)

    Ropero-Miller, Jeri D; Huestis, Marilyn A; Stout, Peter R

    2012-07-01

    Hair specimens were analyzed for cocaine (COC), benzoylecgonine (BE), cocaethylene (CE) and norcocaine (NCOC) by liquid chromatography-tandem mass spectrometry. Drug-free hair was contaminated in vitro with COC from different sources with varied COC analyte concentrations. Results were compared to COC analyte concentrations in drug users' hair following self-reported COC use (Street) and in hair from participants in controlled COC administration studies (Clinical) on a closed clinical research unit. Mean ± standard error analyte concentrations in Street drug users' hair were COC 27,889 ± 7,846 (n = 38); BE 8,132 ± 2,523 (n = 38); CE 901 ± 320 (n = 20); NCOC 345 ± 72 pg/mg (n = 32). Mean percentages to COC concentration were BE 29%, CE 3% and NCOC 1%. Concentrations in hair were lower for Clinical participants. COC contamination with higher CE, BE or NCOC content produced significantly higher concentrations (P = 0.0001) of all analytes. CE/COC and NCOC/COC ratios did not improve differentiation of COC use from COC contamination. COC concentrations in illicit and pharmaceutical COC affect concentrations in contaminated hair. Criteria for distinguishing COC use from contamination under realistic concentrations were not significantly improved by adding CE and NCOC criteria to COC cutoff concentration and BE/COC ratio criteria. Current criteria for COC hair testing in many forensic drug-testing laboratories may not effectively discriminate between COC use and environmental COC exposure.

  10. Matrix solid phase dispersion assisted enzymatic hydrolysis as a novel approach for cocaine and opiates isolation from human hair.

    Science.gov (United States)

    Míguez-Framil, Martha; Cabarcos, Pamela; Tabernero, María Jesús; Bermejo, Ana María; Bermejo-Barrera, Pilar; Moreda-Piñeiro, Antonio

    2013-11-05

    The possibility of assisting enzymatic hydrolysis (EH) procedures by sample disruption mechanisms inherent to matrix solid phase dispersion (MSPD) has been explored in the current study. EH of hair specimens from poly-drug abusers was assisted by dispersing/blending the sample (0.05 g) with alumina (2.25 g) before loading the dissolved enzyme (6 mL of 1 mg mL(-1) Pronase E in 1.4 M/1.4 M Tris/HCl, pH 7.3) through the hair-alumina solid phase packaged inside a disposable MSPD syringe. The MSPD-EH method was developed, and it proved to offer quantitative results when isolating cocaine, benzoylecgonine (BZE), codeine, morphine and 6-monoacethylmorphine (6-MAM) from human hair samples. The procedure allows an on column clean-up/pre-concentration procedure of the isolated targets by attaching a previously conditioned Oasis HLB cartridge to the end of the MSPD syringe. The EH procedure of human hair with Pronase E can therefore be shortened to approximately 30 min. Within this time, sample blending/dispersion, MSPD syringe package, elution (EH when dissolved Pronase E is passing through the sample-dispersant bed), and extract clean-up and target pre-concentration stages are achieved. Gas chromatography-mass spectrometry (GC-MS) was used for determining each target after elution from the Oasis HLB cartridges with 2 mL of 2% (v/v) acetic acid in methanol, concentration by N2 stream evaporation, and dried extract derivatization with N-methyl-tert-butylsilyltrifluoroacetamide (BSTFA) and chlorotrimethylsilane (TMCS). The method was validated according to the guidance for bioanalytical method validation of the US Department of Health and Human Services, Food and Drug Administration. The simplicity of the proposed approach makes it a useful procedure for screening/quantifying drugs of abuse in hair specimens from poly-drug abusers.

  11. Cannabis and Psychosis: a Critical Overview of the Relationship.

    Science.gov (United States)

    Ksir, Charles; Hart, Carl L

    2016-02-01

    Interest in the relationship between cannabis use and psychosis has increased dramatically in recent years, in part because of concerns related to the growing availability of cannabis and potential risks to health and human functioning. There now exists a plethora of scientific articles addressing this issue, but few provide a clear verdict about the causal nature of the cannabis-psychosis association. Here, we review recent research reports on cannabis and psychosis, giving particular attention to how each report provides evidence relating to two hypotheses: (1) cannabis as a contributing cause and (2) shared vulnerability. Two primary kinds of data are brought to bear on this issue: studies done with schizophrenic patients and studies of first-episode psychosis. Evidence reviewed here suggests that cannabis does not in itself cause a psychosis disorder. Rather, the evidence leads us to conclude that both early use and heavy use of cannabis are more likely in individuals with a vulnerability to psychosis. The role of early and heavy cannabis use as a prodromal sign merits further examination, along with a variety of other problem behaviors (e.g., early or heavy use of cigarettes or alcohol and poor school performance). Future research studies that focus exclusively on the cannabis-psychosis association will therefore be of little value in our quest to better understand psychosis and how and why it occurs.

  12. Determination of cocaine in postmortem human liver exposed to overdose. Application of an innovative and efficient extraction/clean up procedure and gas chromatography-mass spectrometry analysis.

    Science.gov (United States)

    Magalhães, Elisângela Jaqueline; Ribeiro de Queiroz, Maria Eliana Lopes; Penido, Marcus Luiz de Oliveira; Paiva, Marco Antônio Ribeiro; Teodoro, Janaína Aparecida Reis; Augusti, Rodinei; Nascentes, Clésia Cristina

    2013-09-27

    A simple and efficient method was developed for the determination of cocaine in post-mortem samples of human liver via solid-liquid extraction with low temperature partitioning (SLE-LTP) and analysis by gas chromatography coupled to mass spectrometry (GC-MS). The extraction procedure was optimized by evaluating the influence of the following variables: pH of the extract, volume and composition of the extractor solvent, addition of a sorbent material (PSA: primary-secondary amine) and NaCl to clean up and increase the ionic strength of the extract. A bovine liver sample that was free of cocaine was used as a blank for the optimization of the SLE-LTP extraction procedure. The highest recovery was obtained when crushed bovine liver (2g) was treated with 2mL of ultrapure water plus 8mL of acetonitrile at physiological pH (7.4). The results also indicated no need for using PSA and NaCl. The complete analytical procedure was validated for the following figures of merit: selectivity, lower limit of quantification (LLOQ), calibration curve, recovery, precision and accuracy (for within-run and between-run experiments), matrix effect, dilution integrity and stability. The within-run and between-run precision (at four levels) varied from 2.1% to 9.4% and from 4.0% to 17.0%, respectively. A maximum deviation of 11.62% for the within-run and between-run accuracies in relation to the nominal concentrations was observed. Moreover, the LLOQ value for cocaine was 50.0ngg(-1) whereas no significant effects were noticed in the assays of dilution integrity and stability. To assess its overall performance, the optimized method was applied to the analysis of eight human liver samples collected from individuals who died due to the abusive consumption of cocaine. Due to the existence of a significant matrix effect, a blank human liver was used to construct a matrix-matched analytical curve. The concentrations of cocaine found in these samples ranged from 333.5 to 5969ngg(-1). Copyright

  13. Psychosis and cannabis

    Directory of Open Access Journals (Sweden)

    Heinz Häfner

    2005-01-01

    Full Text Available Alcohol and cannabis misuse is currently the most frequent co-morbidity disorder of schizophrenia. The following four issues will be dealt with: 1 the neurobiological basis of the psychosis-inducing, pathogenic effects of THC, the agent contained in cannabis products. 2 Can cannabis use - and for comparison alcohol abuse - prematurely trigger or even cause schizophrenia? 3 Are persons genetically liable to schizophrenia, psychosis-prone individuals or young persons before completion of brain development at an increased risk? 4 What consequences does cannabis use have on the symptomatology and further course of schizophrenia? Results from recent literature and the ABC Schizophrenia Study show that the risk for cannabis use in schizophrenia is about twice the size in healthy controls. In most cases cannabis use starts before first admission, in a third of cases before schizophrenia onset. There is an increased affinity to misuse already at the prodromal stage. Cannabis can prematurely trigger schizophrenia onset - on average eight years earlier than in non-use - and cause the illness partly in interaction with predisposing factors. Cannabis use in the course of schizophrenia increases positive symptoms and reduces affective flattening, thus leading to dysfunctional coping in some cases.

  14. Kwaliteitsnormen Medicinale Cannabis

    NARCIS (Netherlands)

    Slijkhuis C; Hoving R; Blok-Tip L; Kaste D de; KCF

    2004-01-01

    Medicinal Cannabis can be legally supplied by pharmacists to patients from the first of September 2003, although still only on prescription. The quality of this product is tested conform the monograph Cannabis flos. In this monograph tests and quality standards, such as characteristics, loss on dry

  15. Cannabis; extracting the medicine

    NARCIS (Netherlands)

    Hazekamp, Arno

    2007-01-01

    The cannabis plant (Cannabis sativa L.) has a long history as a recreational drug, but also as part of traditional medicine in many cultures. Nowadays, it is used by a large number of patients worldwide, to ameliorate the symptoms of diseases varying from cancer and AIDS to multiple sclerosis and mi

  16. Cannabis careers revisited

    DEFF Research Database (Denmark)

    Järvinen, Margaretha; Ravn, Signe

    2014-01-01

    A considerable part of today's sociological research on recreational drug use is (explicitly or implicitly) inspired by Howard Becker's classical model of deviant careers. The aim of the present paper is to directly apply Becker's theory to empirical data on present-day cannabis use and to suggest...... in treatment for cannabis problems in Copenhagen, Denmark. We suggest a revision of Becker's career model in relation to four aspects: initiation of cannabis use, differentiation between socially integrated and individualised, disintegrated use, social control from non-users, and the users' moral stance...... on cannabis. A central point of the paper is that social interaction may both motivate cannabis use, as Becker proposed, and serve as a protective factor against extensive, problematic use....

  17. Cannabis dependence, cognitive control and attentional bias for cannabis words.

    Science.gov (United States)

    Cousijn, J; Watson, P; Koenders, L; Vingerhoets, W A M; Goudriaan, A E; Wiers, R W

    2013-12-01

    One of the characteristics of people suffering from addictive behaviors is the tendency to be distracted by drug cues. This attentional bias for drug cues is thought to lead to increased craving and drug use, and may draw individuals into a vicious cycle of drug addiction. In the current study we developed a Dutch version of the cannabis Stroop task and measured attentional bias for cannabis words in a group of heavy cannabis users and matched controls. The classical Stroop task was used as a global measure of cognitive control and we examined the relationship between cognitive control, cannabis-related problems, cannabis craving and cannabis attentional bias. Using our version of the cannabis Stroop task, a group of heavy cannabis users showed attentional bias to cannabis words, whereas a control group of non-users did not. Furthermore, within the group of cannabis users, those who were clinically recognized as dependent showed a stronger attentional bias than the heavy, non-dependent users. Cannabis users who displayed reduced cognitive control (as measured with the classical Stroop task) showed increased session-induced craving. Contrary to expectations, however, cognitive control did not appear to modulate the relationship between attentional bias to cannabis words (cannabis Stroop task) and cannabis dependence. This study confirmed the relationship between cannabis dependence and attentional bias and extends this by highlighting a moderating role for cognitive control, which may make some more vulnerable to craving. © 2013.

  18. Reaction mechanism for cocaine esterase-catalyzed hydrolyses of (+)- and (-)-cocaine: unexpected common rate-determining step.

    Science.gov (United States)

    Liu, Junjun; Zhao, Xinyun; Yang, Wenchao; Zhan, Chang-Guo

    2011-05-05

    First-principles quantum mechanical/molecular mechanical free energy calculations have been performed to examine the catalytic mechanism for cocaine esterase (CocE)-catalyzed hydrolysis of (+)-cocaine in comparison with CocE-catalyzed hydrolysis of (-)-cocaine. It has been shown that the acylation of (+)-cocaine consists of nucleophilic attack of the hydroxyl group of Ser117 on the carbonyl carbon of (+)-cocaine benzoyl ester and the dissociation of (+)-cocaine benzoyl ester. The first reaction step of deacylation of (+)-cocaine, which is identical to that of (-)-cocaine, is rate-determining, indicating that CocE-catalyzed hydrolyses of (+)- and (-)-cocaine have a common rate-determining step. The computational results predict that the catalytic rate constant of CocE against (+)-cocaine should be the same as that of CocE against (-)-cocaine, in contrast with the remarkable difference between human butyrylcholinesterase-catalyzed hydrolyses of (+)- and (-)-cocaine. The prediction has been confirmed by experimental kinetic analysis on CocE-catalyzed hydrolysis of (+)-cocaine in comparison with CocE-catalyzed hydrolysis of (-)-cocaine. The determined common rate-determining step indicates that rational design of a high-activity mutant of CocE should be focused on the first reaction step of the deacylation. Furthermore, the obtained mechanistic insights into the detailed differences in the acylation between the (+)- and (-)-cocaine hydrolyses provide indirect clues for rational design of amino acid mutations that could more favorably stabilize the rate-determining transition state in the deacylation and, thus, improve the catalytic activity of CocE. This study provides a valuable mechanistic base for rational design of an improved esterase for therapeutic treatment of cocaine abuse.

  19. N-Acetylcysteine reduces cocaine-cue attentional bias and differentially alters cocaine self-administration based on dosing order.

    Science.gov (United States)

    Levi Bolin, B; Alcorn, Joseph L; Lile, Joshua A; Rush, Craig R; Rayapati, Abner O; Hays, Lon R; Stoops, William W

    2017-09-01

    Disrupted glutamate homeostasis is thought to contribute to cocaine-use disorder, in particular, by enhancing the incentive salience of cocaine stimuli. n-Acetylcysteine might be useful in cocaine-use disorder by normalizing glutamate function. In prior studies, n-acetylcysteine blocked the reinstatement of cocaine seeking in laboratory animals and reduced the salience of cocaine stimuli and delayed relapse in humans. The present study determined the ability of maintenance on n-acetylcysteine (0 or 2400mg/day, counterbalanced) to reduce the incentive salience of cocaine stimuli, as measured by an attentional bias task, and attenuate intranasal cocaine self-administration (0, 30, and 60mg). Fourteen individuals (N=14) who met criteria for cocaine abuse or dependence completed this within-subjects, double-blind, crossover-design study. Cocaine-cue attentional bias was greatest following administration of 0mg cocaine during placebo maintenance, and was attenuated by n-acetylcysteine. Cocaine maintained responding during placebo and n-acetylcysteine maintenance, but the reinforcing effects of cocaine were significantly attenuated across both maintenance conditions in participants maintained on n-acetylcysteine first compared to participants maintained on placebo first. These results collectively suggest that a reduction in the incentive salience of cocaine-related stimuli during n-acetylcysteine maintenance may be accompanied by reductions in cocaine self-administration. These results are in agreement with, and link, prior preclinical and clinical trial results suggesting that n-acetylcysteine might be useful for preventing cocaine relapse by attenuating the incentive salience of cocaine cues. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Cannabis Use Disorder in Adolescence.

    Science.gov (United States)

    Simpson, Annabelle K; Magid, Viktoriya

    2016-07-01

    Cannabis use in the adolescent population poses a significant threat of addiction potential resulting in altered neurodevelopment. There are multiple mechanisms of treatment of cannabis use disorder including behavioral therapy management and emerging data on treatment via pharmacotherapy. Recognizing the diagnostic criteria for cannabis use disorder, cannabis withdrawal syndrome, and mitigating factors that influence adolescent engagement in cannabis use allows for comprehensive assessment and management in the adolescent population. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Mitochondrial complex I dysfunction induced by cocaine and cocaine plus morphine in brain and liver mitochondria.

    Science.gov (United States)

    Cunha-Oliveira, Teresa; Silva, Lisbeth; Silva, Ana Maria; Moreno, António J; Oliveira, Catarina R; Santos, Maria S

    2013-06-07

    Mitochondrial function and energy metabolism are affected in brains of human cocaine abusers. Cocaine is known to induce mitochondrial dysfunction in cardiac and hepatic tissues, but its effects on brain bioenergetics are less documented. Furthermore, the combination of cocaine and opioids (speedball) was also shown to induce mitochondrial dysfunction. In this work, we compared the effects of cocaine and/or morphine on the bioenergetics of isolated brain and liver mitochondria, to understand their specific effects in each tissue. Upon energization with complex I substrates, cocaine decreased state-3 respiration in brain (but not in liver) mitochondria and decreased uncoupled respiration and mitochondrial potential in both tissues, through a direct effect on complex I. Morphine presented only slight effects on brain and liver mitochondria, and the combination cocaine+morphine had similar effects to cocaine alone, except for a greater decrease in state-3 respiration. Brain and liver mitochondrial respirations were differentially affected, and liver mitochondria were more prone to proton leak caused by the drugs or their combination. This was possibly related with a different dependence on complex I in mitochondrial populations from these tissues. In summary, cocaine and cocaine+morphine induce mitochondrial complex I dysfunction in isolated brain and liver mitochondria, with specific effects in each tissue.

  2. An overview of cocaethylene, an alcohol-derived, psychoactive, cocaine metabolite.

    Science.gov (United States)

    Landry, M J

    1992-01-01

    Cocaethylene is a psychoactive ethyl homologue of cocaine, and is formed exclusively during the coadministration of cocaine and alcohol. Not a natural alkaloid of the coca leaf, cocaethylene can be identified in the urine, blood, hair, and neurological and liver tissue samples of individuals who have consumed both cocaine and alcohol. With a pharmacologic profile similar to cocaine, it can block the dopamine transporter on dopaminergic presynaptic nerve terminals in the brain. It increases dopamine synaptic content, provoking enhanced postsynaptic receptor stimulation, resulting in euphoria, reinforcement, and self-administration. Equipotent to cocaine with regard to dopamine transporter affinity, cocaethylene appears to be far less potent than cocaine with regard to serotonin transporter binding. Lacking the serotonergic-related inhibitory mechanism, cocaethylene appears to be more euphorigenic and rewarding than cocaine. Synthesized and administered cocaethylene has a behavioral stimulation profile similar to cocaine. Cocaethylene has been shown to be less potent and equipotent to cocaine, and alcohol plus cocaine produces more stimulatory locomotor behavior in mice than either drug alone. Equipotent to cocaine with regard to primate reinforcement and self-administration, cocaethylene can substitute for cocaine in drug discrimination studies, and can produce stimulation of operant conditioning in rats. With regard to lethality, cocaethylene has been shown to be more potent than cocaine in mice and rats. The combination of cocaine and alcohol appears to exert more cardiovascular toxicity than either drug alone in humans. Alcohol appears to potentiate cocaine hepatotoxicity in both humans and mice.

  3. Effect of illicit recreational drugs upon sleep: cocaine, ecstasy and marijuana.

    Science.gov (United States)

    Schierenbeck, Thomas; Riemann, Dieter; Berger, Mathias; Hornyak, Magdolna

    2008-10-01

    The illicit recreational drugs cocaine, ecstasy and marijuana have pronounced effects upon sleep. Administration of cocaine increases wakefulness and suppresses REM sleep. Acute cocaine withdrawal is often associated with sleep disturbances and unpleasant dreams. Studies have revealed that polysomnographically assessed sleep parameters deteriorate even further during sustained abstinence, although patients report that sleep quality remains unchanged or improves. This deterioration of objective sleep measures is associated with a worsening in sleep-related cognitive performance. Like cocaine, 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") is a substance with arousing properties. Heavy MDMA consumption is often associated with persistent sleep disturbances. Polysomnography (PSG) studies have demonstrated altered sleep architecture in abstinent heavy MDMA users. Smoked marijuana and oral Delta-9-tetrahydrocannabinol (THC) reduce REM sleep. Moreover, acute administration of cannabis appears to facilitate falling asleep and to increase Stage 4 sleep. Difficulty sleeping and strange dreams are among the most consistently reported symptoms of acute and subacute cannabis withdrawal. Longer sleep onset latency, reduced slow wave sleep and a REM rebound can be observed. Prospective studies are needed in order to verify whether sleep disturbances during cocaine and cannabis withdrawal predict treatment outcome.

  4. CANNABIS RELATED PSYCHIATRIC SYNDROMES: A SELECTIVE REVIEW

    OpenAIRE

    Basu, Debasish; Malhotra, Anil; Varma, Vijoy K.

    1994-01-01

    Association between cannabis use and various psychiatric syndromes does exist, but their nature remains elusive. Cannabis intoxication, ‘cannabis psychosis’ and certain other conditions related with cannabis use like flashbacks and prolonged depersonalization are discussed in this paper. The controversial nature of the cannabis - schizophrenia link is noted, and various methodological issues in clinical cannabis research are highlighted.

  5. Cannabis Smoking in 2015: A Concern for Lung Health?

    Science.gov (United States)

    Biehl, Jason R; Burnham, Ellen L

    2015-09-01

    Recent legislative successes allowing expanded access to recreational and medicinal cannabis have been associated with its increased use by the public, despite continued debates regarding its safety within the medical and scientific communities. Despite legislative changes, cannabis is most commonly used by smoking, although alternatives to inhalation have also emerged. Moreover, the composition of commercially available cannabis has dramatically changed in recent years. Therefore, developing sound scientific information regarding its impact on lung health is imperative, particularly because published data conducted prior to widespread legalization are conflicting and inconclusive. In this commentary, we delineate major observations of epidemiologic investigations examining cannabis use and the potential associated development of airways disease and lung cancer to highlight gaps in pulmonary knowledge. Additionally, we review major histopathologic alterations related to smoked cannabis and define specific areas in animal models and human clinical translational investigations that could benefit from additional development. Given that cannabis has an ongoing classification as a schedule I medication, federal funding to support investigations of modern cannabis use in terms of medicinal efficacy and safety profile on lung health have been elusive. It is clear, however, that the effects of inhaled cannabis on lung health remain uncertain and given increasing use patterns, are worthy of further investigation.

  6. Dispersive liquid-liquid microextraction based on solidification of floating organic drop and high-performance liquid chromatography to the analysis of cocaine's major adulterants in human urine.

    Science.gov (United States)

    Sena, Laís Cristina Santana; Matos, Humberto Reis; Dórea, Haroldo Silveira; Pimentel, Maria Fernanda; de Santana, Danielle Cristine Almeida Silva; de Santana, Fernando José Malagueño

    2017-02-01

    A simple method has been proposed for the determination of cocaine's major adulterants (caffeine, levamisole, lidocaine, phenacetin, diltiazem, and hydroxyzine) in human urine by dispersive liquid-liquid microextraction based on solidification of floating organic drop (DLLME-SFO) in combination with high-performance liquid chromatography - photodiode array detector (HPLC-PDA). The reversed-phase chromatographic separation was obtained with a column C18 extended (250×4.6mm; 5μm; 80Å) in gradient elution mode using acetonitrile-trifluoroacetic acid 0.026% (v,v) (pH=2.5) at 1mLmin(-1) as mobile phase, at 25°C, and detection at 235nm. The analysis time was 25min. This condition had the best resolution factors (>1.15), retention factors (>0.68), number of plates (>2094.9), and separation factors (>1.05) for all targets, indicating a good separation. The kind of extraction and dispersive solvent were investigated for unifactorial design. The buffer pH, the volume of extraction and disperser solvent, and the amount of salt were optimized for full factorial design. Under optimum conditions, human urine samples were alkalized with 0.5M sodium phosphate buffer (pH 10) and added to sodium chloride (20%m/v). Acetonitrile (150μL) and 1-dodecanol (30μL) were used as dispersive and extraction solvent, respectively. The method presented linear range of 312.5-3125ngmL(-1) to caffeine and levamisole and 187.5-1875ngmL(-1) to lidocaine, phenacetin, diltiazem, and hydroxyzine. The limit of quantification was 187.5ngmL(-1) to lidocaine, phenacetin, diltiazem, and hydroxyzine and 312.5ngmL(-1) for caffeine and levamisole. The recovery mean values were between 6.0 and 42.6%. The method showed good precision and accuracy, with within- and between-run relative standard deviation and relative error less than 15%. The samples were stable after freeze-thaw cycle and short-term room temperature stability tests. Besides, this method was satisfactorily applied in urine of cocaine users. It

  7. [Medical cannabis: the opportunity versus the temptation].

    Science.gov (United States)

    Naftali, Timna

    2011-12-01

    The cannabis plant has been known to humanity for centuries as a remedy for pain, diarrhea, and inflammation. Current research has shown cannabis to be a useful remedy for many diseases, including multiple sclerosis, dystonia, and chronic pain. Cannabinoids are used to improve food intake in anorexia of AIDS patients and to prevent vomiting due to cancer chemotherapy. In inflammatory conditions cannabinoids improve pain in rheumatoid arthritis and pain and diarrhea in Crohn's disease. Cannabinoids reduce the size of brain infarct and cardiac reperfusion injury. However, cannabinoid treatment is not free of side effects including euphoria, psychosis, anxiety, paranoia, dependence and abuse. Since the cannabinoid system is involved in many physiological and pathological processes, the therapeutic potential is great. We must not be blind to the opportunity offered to us by medical cannabis just because it is an illicit drug, nor should we be temped by the quick response of patients to the central effect of cannabis. More research is warranted to explore the full potential of cannabis as medicine.

  8. Cannabis Use When it's Legal

    OpenAIRE

    J. C. VAN OURS

    2005-01-01

    This paper uses information about prime age individuals living in Amsterdam, to study whether the use of alcohol, or tobacco stimulates the use cannabis, i.e. whether alcohol or cannabis are stepping stones for cannabis.The special element of the study is that it concerns the use in an environment where not only alcohol and tobacco but also cannabis is a legal drug.It turns out that alcohol and cannabis are intertemporal substitutes while tobacco and cannabis are intertemporal complements.Onl...

  9. Cannabis Use When it's Legal

    OpenAIRE

    Ours, J. C. van

    2005-01-01

    This paper uses information about prime age individuals living in Amsterdam, to study whether the use of alcohol, or tobacco stimulates the use cannabis, i.e. whether alcohol or cannabis are stepping stones for cannabis.The special element of the study is that it concerns the use in an environment where not only alcohol and tobacco but also cannabis is a legal drug.It turns out that alcohol and cannabis are intertemporal substitutes while tobacco and cannabis are intertemporal complements.Onl...

  10. [Cannabis-induced disorders].

    Science.gov (United States)

    Soyka, M; Preuss, U; Hoch, E

    2017-03-01

    Use and misuse of cannabis and marihuana are frequent. About 5% of the adult population are current users but only 1.2% are dependent. The medical use of cannabis is controversial but there is some evidence for improvement of chronic pain and spasticity. The somatic toxicity of cannabis is well proven but limited and psychiatric disorders induced by cannabis are of more relevance, e.g. cognitive disorders, amotivational syndrome, psychoses and delusional disorders as well as physical and psychological dependence. The withdrawal symptoms are usually mild and do not require pharmacological interventions. To date there is no established pharmacotherapy for relapse prevention. Psychosocial interventions include psychoeducation, behavioral therapy and motivational enhancement. The CANDIS protocol is the best established German intervention among abstinence-oriented therapies.

  11. Cannabis in cancer care

    OpenAIRE

    2015-01-01

    © 2015 American Society for Clinical Pharmacology and Therapeutics. Cannabis has been used in medicine for thousands of years prior to achieving its current illicit substance status. Cannabinoids, the active components of Cannabis sativa, mimic the effects of the endogenous cannabinoids (endocannabinoids), activating specific cannabinoid receptors, particularly CB1 found predominantly in the central nervous system and CB2 found predominantly in cells involved with immune function. Delta-9-tet...

  12. Kwaliteitsnormen Medicinale Cannabis

    OpenAIRE

    Slijkhuis C; Hoving R; Blok-Tip L; Kaste D de; KCF

    2004-01-01

    Medicinal Cannabis can be legally supplied by pharmacists to patients from the first of September 2003, although still only on prescription. The quality of this product is tested conform the monograph Cannabis flos. In this monograph tests and quality standards, such as characteristics, loss on drying, content of delta 9 -trans-tetrahydrocannabinol, microbial contamination, and pesticide residues are given. In this report the monograph is described together with a short explanation.

  13. Individual and combined effects of cannabis and tobacco on drug reward processing in non-dependent users

    OpenAIRE

    Hindocha, C; Lawn, W; Freeman, T. P.; Curran, H. V.

    2017-01-01

    RATIONALE: Cannabis and tobacco are often smoked simultaneously in joints, and this practice may increase the risks of developing tobacco and/or cannabis use disorders. Currently, there is no human experimental research on how these drugs interact on addiction-related measures. OBJECTIVES: This study aimed to investigate how cannabis and tobacco, each alone and combined together in joints, affected individuals' demand for cannabis puffs and cigarettes, explicit liking of drug and non-drug-rel...

  14. Cross-national differences in clinically significant cannabis problems: epidemiologic evidence from 'cannabis-only' smokers in the United States, Mexico, and Colombia

    Directory of Open Access Journals (Sweden)

    Posada-Villa Jose

    2010-03-01

    Full Text Available Abstract Background Epidemiological studies show wide variability in the occurrence of cannabis smoking and related disorders across countries. This study aims to estimate cross-national variation in cannabis users' experience of clinically significant cannabis-related problems in three countries of the Americas, with a focus on cannabis users who may have tried alcohol or tobacco, but who have not used cocaine, heroin, LSD, or other internationally regulated drugs. Methods Data are from the World Mental Health Surveys Initiative and the National Latino and Asian American Study, with probability samples in Mexico (n = 4426, Colombia (n = 5,782 and the United States (USA; n = 8,228. The samples included 212 'cannabis only' users in Mexico, 260 in Colombia and 1,724 in the USA. Conditional GLM with GEE and 'exact' methods were used to estimate variation in the occurrence of clinically significant problems in cannabis only (CO users across these surveyed populations. Results The experience of cannabis-related problems was quite infrequent among CO users in these countries, with weighted frequencies ranging from 1% to 5% across survey populations, and with no appreciable cross-national variation in general. CO users in Colombia proved to be an exception. As compared to CO users in the USA, the Colombia smokers were more likely to have experienced cannabis-associated 'social problems' (odds ratio, OR = 3.0; 95% CI = 1.4, 6.3; p = 0.004 and 'legal problems' (OR = 9.7; 95% CI = 2.7, 35.2; p = 0.001. Conclusions This study's most remarkable finding may be the similarity in occurrence of cannabis-related problems in this cross-national comparison within the Americas. Wide cross-national variations in estimated population-level cumulative incidence of cannabis use disorders may be traced to large differences in cannabis smoking prevalence, rather than qualitative differences in cannabis experiences. More research is needed to identify conditions that

  15. Cross-national differences in clinically significant cannabis problems: epidemiologic evidence from 'cannabis-only' smokers in the United States, Mexico, and Colombia.

    Science.gov (United States)

    Fiestas, Fabian; Radovanovic, Mirjana; Martins, Silvia S; Medina-Mora, Maria E; Posada-Villa, Jose; Anthony, James C

    2010-03-23

    Epidemiological studies show wide variability in the occurrence of cannabis smoking and related disorders across countries. This study aims to estimate cross-national variation in cannabis users' experience of clinically significant cannabis-related problems in three countries of the Americas, with a focus on cannabis users who may have tried alcohol or tobacco, but who have not used cocaine, heroin, LSD, or other internationally regulated drugs. Data are from the World Mental Health Surveys Initiative and the National Latino and Asian American Study, with probability samples in Mexico (n = 4426), Colombia (n = 5,782) and the United States (USA; n = 8,228). The samples included 212 'cannabis only' users in Mexico, 260 in Colombia and 1,724 in the USA. Conditional GLM with GEE and 'exact' methods were used to estimate variation in the occurrence of clinically significant problems in cannabis only (CO) users across these surveyed populations. The experience of cannabis-related problems was quite infrequent among CO users in these countries, with weighted frequencies ranging from 1% to 5% across survey populations, and with no appreciable cross-national variation in general. CO users in Colombia proved to be an exception. As compared to CO users in the USA, the Colombia smokers were more likely to have experienced cannabis-associated 'social problems' (odds ratio, OR = 3.0; 95% CI = 1.4, 6.3; p = 0.004) and 'legal problems' (OR = 9.7; 95% CI = 2.7, 35.2; p = 0.001). This study's most remarkable finding may be the similarity in occurrence of cannabis-related problems in this cross-national comparison within the Americas. Wide cross-national variations in estimated population-level cumulative incidence of cannabis use disorders may be traced to large differences in cannabis smoking prevalence, rather than qualitative differences in cannabis experiences. More research is needed to identify conditions that might make cannabis-related social and legal problems more

  16. Levamisole-adulterated cocaine: Two fatal case reports and evaluation of possible cocaine toxicity potentiation.

    Science.gov (United States)

    Indorato, Francesca; Romano, Guido; Barbera, Nunziata

    2016-08-01

    Levamisole has been identified as a cocaine adulterant in the United States since 2002. Although there is a variation in the percentage of levamisole in cocaine samples between European countries, measurement of levamisole in human samples of cocaine users has become increasingly important. To our best knowledge, only five deaths are reported (one twice) as a result of complications secondary to levamisole-tainted cocaine and none of these cases reports the post-mortem levamisole concentration. In this article, we present the post-mortem levamisole concentrations in fluids and tissues in two young cocaine users, dead after levamisole-adulterated cocaine intake. With the dearth of levamisole reported concentrations in literature, this particular report is of interest to the forensic toxicological and pathological communities. This article aims to be a supplementary alert to aware the risk that may occur using levamisole-adulterated cocaine and an incentive to publication of toxicity reports and new researches involving the combination of levamisole and cocaine.

  17. Cannabis as a substitute for alcohol and other drugs

    Directory of Open Access Journals (Sweden)

    Reiman Amanda

    2009-12-01

    Full Text Available Abstract Background Substitution can be operationalized as the conscious choice to use one drug (legal or illicit instead of, or in conjunction with, another due to issues such as: perceived safety; level of addiction potential; effectiveness in relieving symptoms; access and level of acceptance. This practice of substitution has been observed among individuals using cannabis for medical purposes. This study examined drug and alcohol use, and the occurrence of substitution among medical cannabis patients. Methods Anonymous survey data were collected at the Berkeley Patient's Group (BPG, a medical cannabis dispensary in Berkeley, CA. (N = 350 The sample was 68% male, 54% single, 66% White, mean age was 39; 74% have health insurance (including MediCal, 41% work full time, 81% have completed at least some college, 55% make less than $40,000 a year. Seventy one percent report having a chronic medical condition, 52% use cannabis for a pain related condition, 75% use cannabis for a mental health issue. Results Fifty three percent of the sample currently drinks alcohol, 2.6 was the average number of drinking days per week, 2.9 was the average number of drinks on a drinking occasion. One quarter currently uses tobacco, 9.5 is the average number of cigarettes smoked daily. Eleven percent have used a non-prescribed, non OTC drug in the past 30 days with cocaine, MDMA and Vicodin reported most frequently. Twenty five percent reported growing up in an abusive or addictive household. Sixteen percent reported previous alcohol and/or drug treatment, and 2% are currently in a 12-step or other recovery program. Forty percent have used cannabis as a substitute for alcohol, 26% as a substitute for illicit drugs and 66% as a substitute for prescription drugs. The most common reasons given for substituting were: less adverse side effects (65%, better symptom management (57%, and less withdrawal potential (34% with cannabis. Conclusion The substitution of one

  18. The cannabis withdrawal syndrome: current insights

    Science.gov (United States)

    Bonnet, Udo; Preuss, Ulrich W

    2017-01-01

    The cannabis withdrawal syndrome (CWS) is a criterion of cannabis use disorders (CUDs) (Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition) and cannabis dependence (International Classification of Diseases [ICD]-10). Several lines of evidence from animal and human studies indicate that cessation from long-term and regular cannabis use precipitates a specific withdrawal syndrome with mainly mood and behavioral symptoms of light to moderate intensity, which can usually be treated in an outpatient setting. Regular cannabis intake is related to a desensitization and downregulation of human brain cannabinoid 1 (CB1) receptors. This starts to reverse within the first 2 days of abstinence and the receptors return to normal functioning within 4 weeks of abstinence, which could constitute a neurobiological time frame for the duration of CWS, not taking into account cellular and synaptic long-term neuroplasticity elicited by long-term cannabis use before cessation, for example, being possibly responsible for cannabis craving. The CWS severity is dependent on the amount of cannabis used pre-cessation, gender, and heritable and several environmental factors. Therefore, naturalistic severity of CWS highly varies. Women reported a stronger CWS than men including physical symptoms, such as nausea and stomach pain. Comorbidity with mental or somatic disorders, severe CUD, and low social functioning may require an inpatient treatment (preferably qualified detox) and post-acute rehabilitation. There are promising results with gabapentin and delta-9-tetrahydrocannabinol analogs in the treatment of CWS. Mirtazapine can be beneficial to treat CWS insomnia. According to small studies, venlafaxine can worsen the CWS, whereas other antidepressants, atomoxetine, lithium, buspirone, and divalproex had no relevant effect. Certainly, further research is required with respect to the impact of the CWS treatment setting on long-term CUD prognosis and with respect to

  19. Cannabis Use When it's Legal

    NARCIS (Netherlands)

    van Ours, J.C.

    2005-01-01

    This paper uses information about prime age individuals living in Amsterdam, to study whether the use of alcohol, or tobacco stimulates the use cannabis, i.e. whether alcohol or cannabis are stepping stones for cannabis.The special element of the study is that it concerns the use in an environment w

  20. Cannabis use and mental health

    NARCIS (Netherlands)

    van Gastel, W.A.

    2013-01-01

    Cannabis use has been implicated as a risk factor for mental health problems, (subclinical) psychotic symptoms in particular. If cannabis use was a cause of these problems, cessation would lead to improved public mental health. If cannabis use was a mere consequence of a predisposition for mental he

  1. A new mixed mode solid phase extraction strategy for opioids, cocaines, amphetamines and adulterants in human blood with hybrid liquid chromatography tandem mass spectrometry detection.

    Science.gov (United States)

    Dowling, Geraldine; Regan, Liam

    2011-04-05

    A rapid method has been developed to analyse morphine, codeine, 6-monoacetylmorphine, cocaine, benzoylecgonine, dihydrocodeine, cocaethylene, 3,4-methylenedioxyamphetamine, ketamine, 3,4-methylenedioxymethamphetamine, pseudoephedrine, lignocaine, benzylpiperazine, methamphetamine, amphetamine, methadone, phenethylamine and levamisole in human blood. Blood samples were cleaned up using mixed mode solid phase extraction using Evolute™ CX solid phase extraction cartridges and the sample aliquots were analysed by hybrid triple quadrupole linear ion trap (QTRAP) mass spectrometry with a runtime of 12.5 min. Multiple reaction monitoring (MRM) as survey scan and an enhanced product ion (EPI) scan as dependent scan were performed in an information-dependent acquisition (IDA) experiment. Finally, drug identification and confirmation was carried out by library search with a developed in-house MS/MS library based on EPI spectra at a collision energy spread of 35 ± 15 in positive mode and MRM ratios. The method was validated in blood, according to the criteria defined in Commission Decision 2002/657/EC. At least two MRM transitions for each substance were monitored in addition to EPI spectra. Deuterated analogues of analytes were used as internal standards for quantitation where possible. The method proved to be simple and time efficient and was implemented as an analytical strategy for the illicit drug monitoring of opioids, cocaines, amphetamines and adulterants in forensic cases of crime offenders, abusers or victims in the Republic of Ireland.

  2. Measuring cannabis consumption: Psychometric properties of the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (DFAQ-CU).

    Science.gov (United States)

    Cuttler, Carrie; Spradlin, Alexander

    2017-01-01

    We created the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (DFAQ-CU) because the current lack of psychometrically sound inventories for measuring these dimensions of cannabis use has impeded research on the effects of cannabis in humans. A sample of 2,062 cannabis users completed the DFAQ-CU and was used to assess the DFAQ-CU's factor structure and reliability. To assess validity, a subsample of 645 participants completed additional measures of cannabis dependence and problems (Marijuana Smoking History Questionnaire [MSHQ], Timeline Followback [TLFB], Cannabis Abuse Screening Test [CAST], Cannabis Use Disorders Identification Test Revised [CUDIT-R], Cannabis Use Problems Identification Test [CUPIT], and Alcohol Use Disorder Identification Test [AUDIT]). A six-factor structure was revealed, with factors measuring: daily sessions, frequency, age of onset, marijuana quantity, cannabis concentrate quantity, and edibles quantity. The factors were reliable, with Cronbach's alpha coefficients ranging from .69 (daily sessions) to .95 (frequency). Results further provided evidence for the factors' convergent (MSHQ, TLFB), predictive (CAST, CUDIT-R, CUPIT), and discriminant validity (AUDIT). The DFAQ-CU is the first psychometrically sound inventory for measuring frequency, age of onset, and quantity of cannabis use. It contains pictures of marijuana to facilitate the measurement of quantity of marijuana used, as well as questions to assess the use of different forms of cannabis (e.g., concentrates, edibles), methods of administering cannabis (e.g., joints, hand pipes, vaporizers), and typical THC levels. As such, the DFAQ-CU should help facilitate research on frequency, quantity, and age of onset of cannabis use.

  3. Anormalidades cognitivas no uso da cannabis Cognitive abnormalities and cannabis use

    Directory of Open Access Journals (Sweden)

    Nadia Solowij

    2010-05-01

    Full Text Available OBJETIVO: Evidências de que o uso de cannabis prejudica funções cognitivas em humanos têm-se acumulado nas décadas recentes. O propósito desta revisão é o de atualizar o conhecimento nesta área com novos achados a partir da literatura mais recente. MÉTODO: As buscas na literatura foram realizadas utilizando-se o banco de dados Web of Science até fevereiro de 2010. Foram buscados os termos "cannabi*" ou "marijuana" e "cogniti*" ou "memory" ou "attention" ou "executive function", e os estudos em humanos foram revisados preferencialmente em relação aos estudos em animais. DISCUSSÃO: O uso de cannabis prejudica a memória, a atenção, o controle inibitório, as funções executivas e a tomada de decisões, tanto durante como após o período de intoxicação aguda, persistindo por horas, dias, semanas ou mais após o último uso. Os estudos de desafio farmacológico em humanos estão elucidando a natureza e os substratos neurais das alterações cognitivas associadas a vários canabinoides. O uso pesado ou de longo prazo de cannabis parece resultar em anormalidades cognitivas mais duradouras e possivelmente em alterações cerebrais estruturais. Efeitos cognitivos adversos maiores estão associados ao uso de cannabis quando este começa no início da adolescência. CONCLUSÃO: O sistema canabinoide endógeno está envolvido nos mecanismos de regulação neural que modulam os processos subjacentes a uma gama de funções cognitivas que estão prejudicadas pela cannabis. Os déficits em usuários humanos muito provavelmente refletem, portanto, neuroadaptações e o funcionamento alterado do sistema canabinoide endógeno.OBJECTIVE: Evidence that cannabis use impairs cognitive function in humans has been accumulating in recent decades. The purpose of this overview is to update knowledge in this area with new findings from the most recent literature. METHOD: Literature searches were conducted using the Web of Science database up to

  4. Comparing Medical and Recreational Cannabis Users on Socio-Demographic, Substance and Medication Use, and Health and Disability Characteristics.

    Science.gov (United States)

    Goulet-Stock, Sybil; Rueda, Sergio; Vafaei, Afshin; Ialomiteanu, Anca; Manthey, Jakob; Rehm, Jürgen; Fischer, Benedikt

    2017-01-01

    While recreational cannabis use is common, medical cannabis programs have proliferated across North America, including a federal program in Canada. Few comparisons of medical and recreational cannabis users (RCUs) exist; this study compared these groups on key characteristics. Data came from a community-recruited sample of formally approved medical cannabis users (MCUs; n = 53), and a sub-sample of recreational cannabis users (RCUs; n = 169) from a representative adult survey in Ontario (Canada). Samples were telephone-surveyed on identical measures, including select socio-demographic, substance and medication use, and health and disability measures. Based on initial bivariate comparisons, multivariate logistical regression with a progressive adjustment approach was performed to assess independent predictors of group status. In bivariate analyses, older age, lower household income, lower alcohol use, higher cocaine, prescription opioid, depression and anxiety medication use, and lower health and disability status were significantly associated with medical cannabis use. In the multivariate analysis, final model, household income, alcohol use, and disability levels were associated with medical cannabis use. Conclusions/Scientific Significance: Compared to RCUs, medical users appear to be mainly characterized by factors negatively influencing their overall health status. Future studies should investigate the actual impact and net benefits of medical cannabis use on these health problems. © 2017 S. Karger AG, Basel.

  5. Studies of the biogenic amine transporters. VII. Characterization of a novel cocaine binding site identified with [125I]RTI-55 in membranes prepared from human, monkey and guinea pig caudate.

    Science.gov (United States)

    Rothman, R B; Silverthorn, M L; Glowa, J R; Matecka, D; Rice, K C; Carroll, F I; Partilla, J S; Uhl, G R; Vandenbergh, D J; Dersch, C M

    1998-04-01

    [125I]RTI-55 is a cocaine analog with high affinity for dopamine (DA) and serotonin (5-HT) transporters. Quantitative ligand binding studies revealed a novel high affinity [125I]RTI-55 binding site assayed under 5-HT transporter (SERT) conditions which has low affinity for almost all classic biogenic amine transporter ligands, including high affinity 5-HT transporter inhibitors such as paroxetine, but which retains high affinity for cocaine analogs. This site, termed SERT(site2) for its detection under 5-HT transporter conditions (not for an association with the SERT) occurs in monkey caudate, human caudate, and guinea pig caudate membranes, but not in rat caudate membranes. SERT(site2) is distinguished from the DA transporter (DAT) and SERT by several criteria, including a distinct ligand-selectivity profile, the inability to detect SERT(site2) in cells stably expressing the cloned human DAT, and insensitivity to irreversible ligands which inhibit [125I]RTI-55 binding to the DAT and SERT. Perhaps the most striking finding about SERT(site2) is that a wide range of representative antidepressant agents have very low affinity for SERT(site2). The affinity of cocaine for this site is not very different from the concentration cocaine achieves in the brain at pharmacological doses. Viewed collectively with the observation that ligands with high affinity for SERT(site2) are mostly cocaine analogs, these data lead us to speculate that actions of cocaine which differ from those of classic biogenic amine uptake inhibitors may be mediated in part via SERT(site2).

  6. High affinity binding of (/sup 3/H)cocaine to rat liver microsomes

    Energy Technology Data Exchange (ETDEWEB)

    El-Maghrabi, E.A.; Calligaro, D.O.; Eldefrawi, M.E.

    1988-01-01

    )/sup 3/H)cocaine bound reversible, with high affinity and stereospecificity to rat liver microsomes. Little binding was detected in the lysosomal, mitochondrial and nuclear fractions. The binding kinetics were slow and the kinetically calculated K/sub D/ was 2 nM. Induction of mixed function oxidases by phenobarbital did not produce significant change in (/sup 3/H)cocaine binding. On the other hand, chronic administration of cocaine reduced (/sup 3/H)cocaine binding drastically. Neither treatment affected the affinity of the liver binding protein for cocaine. Microsomes from mouse and human livers had less cocaine-binding protein and lower affinity for cocaine than those from rat liver. Binding of (/sup 3/H)cocaine to rat liver microsomes was insensitive to monovalent cations and > 10 fold less sensitive to biogenic amines than the cocaine receptor in rat striatum. However, the liver protein had higher affinity for cocaine and metabolites except for norcocaine. Amine uptake inhibitors displaced (/sup 3/H)cocaine binding to liver with a different rank order of potency than their displacement of (/sup 3/H)cocaine binding to striatum. This high affinity (/sup 3/H)cocaine binding protein in liver is not likely to be monooxygenase, but may have a role in cocaine-induced hepatotoxicity

  7. Reaching out towards cannabis: approach-bias in heavy cannabis users predicts changes in cannabis use

    NARCIS (Netherlands)

    Cousijn, J.; Goudriaan, A.E.; Wiers, R.W.

    2011-01-01

    Aims Repeated drug exposure can lead to an approach-bias, i.e. the relatively automatically triggered tendencies to approach rather that avoid drug-related stimuli. Our main aim was to study this approach-bias in heavy cannabis users with the newly developed cannabis Approach Avoidance Task (cannabi

  8. Medical uses of marijuana (Cannabis sativa): fact or fallacy?

    Science.gov (United States)

    Maule, W J

    2015-01-01

    Marijuana (Cannabis sativa) has been used throughout the world medically, recreationally and spiritually for thousands of years. In South Africa, from the mid-19th century to the 1920s, practitioners prescribed it for a multitude of conditions. In 1928 it was classified as a Schedule I substance, illegal, and without medical value. Ironically, with this prohibition, cannabis became the most widely used illicit recreational drug, not only in South Africa, but worldwide. Cannabis is generally regarded as enjoyable and relaxing without the addictive risks of opioids or stimulants. In alternative medicine circles it has never lost its appeal. To date 23 States in the USA have legalised its medical use despite the federal ban. Unfortunately, little about cannabis is not without controversy. Its main active ingredient, δ-9-tetrahydrocannabinol (THC), was not isolated until 1964, and it was not until the 1990s that the far-reaching modulatory activities of the endocannabinoid system in the human body was studied. This system's elucidation raises the possibility of many promising pharmaceutical applications, even as restrictions show no sign of abating. Recreational use of cannabis continues to increase, despite growing evidence of its addictive potential, particularly in the young. Public approval drives medical cannabis legalisation efforts without the scientific data normally required to justify a new medication's introduction. This review explores these controversies and whether cannabis is a panacea, a scourge, or both.

  9. Development of a method for the determination of cocaine, cocaethylene and norcocaine in human breast milk using liquid phase microextraction and gas chromatography-mass spectrometry.

    Science.gov (United States)

    Silveira, Gabriela de Oliveira; Belitsky, Íris Tikkanen; Loddi, Silvana; Rodrigues de Oliveira, Carolina Dizioli; Zucoloto, Alexandre Dias; Fruchtengarten, Ligia Veras Gimenez; Yonamine, Mauricio

    2016-08-01

    Most licit and illicit substances consumed by the nursing mother might be excreted in breast milk, which may cause potential short and long term harmful effects for the breastfed infant. The extraction of substances from this matrix represents an analytical challenge due to its high protein and fat content as well as the fact that its composition changes during postpartum period. The aim of the present study was to develop a liquid phase microextraction (LPME) method for detection of the active substances: cocaine (COC), cocaethylene (CE) and norcocaine (NCOC) in human breast milk using gas chromatography-mass spectrometry (GC-MS). Validation was performed working on spiked human breast milk samples. The limits of detection (LOD) and quantification (LOQ) were of 6 and 12ng/mL, respectively, for all analytes. Calibration curves were linear over a concentration range of 12.0ng/mL-1000ng/mL (r(2)=0.99). No interferences were noticed at the retention times of interest. Within-run and between-run precision was always less or equal to 15 as % relative standard deviation, and bias ranged from 3 to 18%. Forty six milk samples were analyzed. Only one sample was confirmed to be COC positive (138ng/mL) and another one presented COC concentration near the LOD (6ng/mL). This method has shown to be a reliable alternative for the determination of cocaine, cocaethylene and norcocaine in human breast milk in the fields of clinical and forensic toxicology. LPME extraction procedure demonstrated to be a rather promising, low cost and environmental-friendly technique for the purpose of this study.

  10. Chronic inhibition of dopamine β-hydroxylase facilitates behavioral responses to cocaine in mice.

    Directory of Open Access Journals (Sweden)

    Meriem Gaval-Cruz

    Full Text Available The anti-alcoholism medication, disulfiram (Antabuse, decreases cocaine use in humans regardless of concurrent alcohol consumption and facilitates cocaine sensitization in rats, but the functional targets are unknown. Disulfiram inhibits dopamine β-hydroxylase (DBH, the enzyme that converts dopamine (DA to norepinephrine (NE in noradrenergic neurons. The goal of this study was to test the effects of chronic genetic or pharmacological DBH inhibition on behavioral responses to cocaine using DBH knockout (Dbh -/- mice, disulfiram, and the selective DBH inhibitor, nepicastat. Locomotor activity was measured in control (Dbh +/- and Dbh -/- mice during a 5 day regimen of saline+saline, disulfiram+saline, nepicastat+saline, saline+cocaine, disulfiram+cocaine, or nepicastat+cocaine. After a 10 day withdrawal period, all groups were administered cocaine, and locomotor activity and stereotypy were measured. Drug-naïve Dbh -/- mice were hypersensitive to cocaine-induced locomotion and resembled cocaine-sensitized Dbh +/- mice. Chronic disulfiram administration facilitated cocaine-induced locomotion in some mice and induced stereotypy in others during the development of sensitization, while cocaine-induced stereotypy was evident in all nepicastat-treated mice. Cocaine-induced stereotypy was profoundly increased in the disulfiram+cocaine, nepicastat+cocaine, and nepicastat+saline groups upon cocaine challenge after withdrawal in Dbh +/- mice. Disulfiram or nepicastat treatment had no effect on behavioral responses to cocaine in Dbh -/- mice. These results demonstrate that chronic DBH inhibition facilitates behavioral responses to cocaine, although different methods of inhibition (genetic vs. non-selective inhibitor vs. selective inhibitor enhance qualitatively different cocaine-induced behaviors.

  11. Medicinal cannabis in oncology.

    Science.gov (United States)

    Engels, Frederike K; de Jong, Floris A; Mathijssen, Ron H J; Erkens, Joëlle A; Herings, Ron M; Verweij, Jaap

    2007-12-01

    In The Netherlands, since September 2003, a legal medicinal cannabis product, constituting the whole range of cannabinoids, is available for clinical research, drug development strategies, and on prescription for patients. To date, this policy, initiated by the Dutch Government, has not yet led to the desired outcome; the amount of initiated clinical research is less than expected and only a minority of patients resorts to the legal product. This review aims to discuss the background for the introduction of legal medicinal cannabis in The Netherlands, the past years of Dutch clinical experience in oncology practice, possible reasons underlying the current outcome, and future perspectives.

  12. The draft genome and transcriptome of Cannabis sativa

    OpenAIRE

    van Bakel, Harm; Stout, Jake M.; Cote, Atina G; Tallon, Carling M; Sharpe, Andrew G; Hughes, Timothy R.; Page, Jonathan E.

    2011-01-01

    Background Cannabis sativa has been cultivated throughout human history as a source of fiber, oil and food, and for its medicinal and intoxicating properties. Selective breeding has produced cannabis plants for specific uses, including high-potency marijuana strains and hemp cultivars for fiber and seed production. The molecular biology underlying cannabinoid biosynthesis and other traits of interest is largely unexplored. Results We sequenced genomic DNA and RNA from the marijuana strain Pur...

  13. Characteristics of substance use disorder treatment patients using medical cannabis for pain.

    Science.gov (United States)

    Ashrafioun, Lisham; Bohnert, Kipling M; Jannausch, Mary; Ilgen, Mark A

    2015-03-01

    This study was designed to assess the prevalence and correlates of self-reported medical cannabis use for pain in a substance use disorder (SUD) treatment program. Participants (n=433) aged 18 years and older were recruited from February 2012 to July 2014 at a large residential SUD treatment program. They completed a battery of questionnaires to assess demographics, usual pain level in the past three months (using the 11-point Numeric Rating Scale for pain), depression (using the Beck Depression Inventory), previous types of pain treatments, and lifetime and past-year use of substances (using the Addiction Severity Index). Using both adjusted and unadjusted logistic regression models, we compared those who reported medical cannabis use for pain with those who did not report it. Overall, 15% of the sample (n=63) reported using medical cannabis for pain in the past year. After adjusting for age, medical cannabis use for pain was significantly associated with past-year use of alcohol, cocaine, heroin, other opioids, and sedatives, but was not associated with usual pain level or depression. It was also associated with past year treatment of pain using prescription pain relievers without prescriptions. These results indicate that medical cannabis use for pain is relatively common and is associated with more extensive substance use among SUD patients. Future work is needed to develop and evaluate strategies to assess and treat individuals who report medical cannabis for pain in SUD treatment settings. Published by Elsevier Ltd.

  14. Unique prediction of cannabis use severity and behaviors by delay discounting and behavioral economic demand.

    Science.gov (United States)

    Strickland, Justin C; Lile, Joshua A; Stoops, William W

    2017-07-01

    Few studies have simultaneously evaluated delay discounting and behavioral economic demand to determine their unique contribution to drug use. A recent study in cannabis users found that monetary delay discounting uniquely predicted cannabis dependence symptoms, whereas cannabis demand uniquely predicted use frequency. This study sought to replicate and extend this research by evaluating delay discounting and behavioral economic demand measures for multiple commodities and including a use quantity measure. Amazon.com's Mechanical Turk was used to sample individuals reporting recent cannabis use (n=64) and controls (n=72). Participants completed measures of monetary delay discounting as well as alcohol and cannabis delay discounting and demand. Cannabis users and controls did not differ on monetary delay discounting or alcohol delay discounting and demand. Among cannabis users, regression analyses indicated that cannabis delay discounting uniquely predicted use severity, whereas cannabis demand uniquely predicted use frequency and quantity. These effects remained significant after controlling for other delay discounting and demand measures. This research replicates previous outcomes relating delay discounting and demand with cannabis use and extends them by accounting for the contribution of multiple commodities. This research also demonstrates the ability of online crowdsourcing methods to complement traditional human laboratory techniques. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Simultaneous quantitation of cocaine, opiates, and their metabolites in human hair by positive ion chemical ionization gas chromatography-mass spectrometry.

    Science.gov (United States)

    Höld, K M; Wilkins, D G; Rollins, D E; Joseph, R E; Cone, E J

    1998-03-01

    A sensitive method is developed for the combined extraction of cocaine (COC), cocaethylene (CE), benzoylecgonine (BE), ecgonine methyl ester (EME), norcocaine (NORCOC), 6-acetylmorphine (6-MAM), codeine (COD), norcodeine (NORCOD), morphine (MOR), and normorphine (NORMOR) from human head hair using an enzyme-based digestion technique (Protease VIII/DTT/Tris-buffer pH 6.5 at 22 degrees C). After pH adjustment to 5.5, the digests are extracted with a solid-phase extraction procedure using Bond-Elut Certify columns. The extract residues are evaporated at 40 degrees C, reconstituted in 20 microL of ethyl acetate, and derivatized with the reagents N-methyl-N-trimethylsilylheptafluorobutyramide (MSHFBA), N-methyl-bis-heptafluorobutyramide (MBHFBA), and N-trimethylsilylimidazole (TMSIM). Analyses are performed by positive ion chemical ionization gas chromatography-mass spectrometry using a DB-1 capillary column. Two injections are performed on each extract to optimize sensitivity for all analytes. The assay is capable of reliably quantitating 500 pg/mg of all compounds and is linear to 50 ng/mg, except for BE, which is linear to 25.0 ng/mg. The method was used to analyze human hair samples obtained from cocaine and heroin users. COC, BE, and EME are detectable in all samples, whereas NORCOC, CE, COD, 6-MAM, and MOR are detected in only some samples. Norcodeine and normorphine are not detected. The assay is currently being used to analyze hair samples from a study investigating the mechanisms of drug disposition in hair.

  16. Intense sweetness surpasses cocaine reward.

    Directory of Open Access Journals (Sweden)

    Magalie Lenoir

    Full Text Available BACKGROUND: Refined sugars (e.g., sucrose, fructose were absent in the diet of most people until very recently in human history. Today overconsumption of diets rich in sugars contributes together with other factors to drive the current obesity epidemic. Overconsumption of sugar-dense foods or beverages is initially motivated by the pleasure of sweet taste and is often compared to drug addiction. Though there are many biological commonalities between sweetened diets and drugs of abuse, the addictive potential of the former relative to the latter is currently unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that when rats were allowed to choose mutually-exclusively between water sweetened with saccharin-an intense calorie-free sweetener-and intravenous cocaine-a highly addictive and harmful substance-the large majority of animals (94% preferred the sweet taste of saccharin. The preference for saccharin was not attributable to its unnatural ability to induce sweetness without calories because the same preference was also observed with sucrose, a natural sugar. Finally, the preference for saccharin was not surmountable by increasing doses of cocaine and was observed despite either cocaine intoxication, sensitization or intake escalation-the latter being a hallmark of drug addiction. CONCLUSIONS: Our findings clearly demonstrate that intense sweetness can surpass cocaine reward, even in drug-sensitized and -addicted individuals. We speculate that the addictive potential of intense sweetness results from an inborn hypersensitivity to sweet tastants. In most mammals, including rats and humans, sweet receptors evolved in ancestral environments poor in sugars and are thus not adapted to high concentrations of sweet tastants. The supranormal stimulation of these receptors by sugar-rich diets, such as those now widely available in modern societies, would generate a supranormal reward signal in the brain, with the potential to override self

  17. Estimating the harms and costs of cannabis-attributable collisions in the Canadian provinces.

    Science.gov (United States)

    Wettlaufer, Ashley; Florica, Roxana O; Asbridge, Mark; Beirness, Douglas; Brubacher, Jeffrey; Callaghan, Russell; Fischer, Benedikt; Gmel, Gerrit; Imtiaz, Sameer; Mann, Robert E; McKiernan, Anna; Rehm, Jürgen

    2017-04-01

    In 2012, 10% of Canadians used cannabis and just under half of those who use cannabis were estimated to have driven under the influence of cannabis. Substantial evidence has accumulated to indicate that driving after cannabis use increases collision risk significantly; however, little is known about the extent and costs associated with cannabis-related traffic collisions. This study quantifies the costs of cannabis-related traffic collisions in the Canadian provinces. Province and age specific cannabis-attributable fractions (CAFs) were calculated for traffic collisions of varying severity. The CAFs were applied to traffic collision data in order to estimate the total number of persons involved in cannabis-attributable fatal, injury and property damage only collisions. Social cost values, based on willingness-to-pay and direct costs, were applied to estimate the costs associated with cannabis-related traffic collisions. The 95% confidence intervals were calculated using Monte Carlo methodology. Cannabis-attributable traffic collisions were estimated to have caused 75 deaths (95% CI: 0-213), 4407 injuries (95% CI: 20-11,549) and 7794 people (95% CI: 3107-13,086) were involved in property damage only collisions in Canada in 2012, totalling $1,094,972,062 (95% CI: 37,069,392-2,934,108,175) with costs being highest among younger people. The cannabis-attributable driving harms and costs are substantial. The harm and cost of cannabis-related collisions is an important factor to consider as Canada looks to legalize and regulate the sale of cannabis. This analysis provides evidence to help inform Canadian policy to reduce the human and economic costs of drug-impaired driving. Copyright © 2017 Canadian Centre on Substance Abuse. Published by Elsevier B.V. All rights reserved.

  18. [Cocaine - Characteristics and addiction].

    Science.gov (United States)

    Girczys-Połedniok, Katarzyna; Pudlo, Robert; Jarząb, Magdalena; Szymlak, Agnieszka

    Cocaine use leads to health, social and legal problems. The aim of this paper is to discuss cocaine action, addicts characteristics, use patterns and consequences, as well as addiction treatment methods. A literature review was based on the Medline, PubMed, Polish Medical Bibliography databases and the Silesian Library resources. The Police and Central Statistical Office statistics, as well as the World Health Organization, the European Monitoring Centre for Drugs and Drug Addiction and the National Office for Combating Drug Addiction reports were used. Cocaine leads to mood improvement, appetite decrease, physical and intellectual activity enhancement, euphoria, inflated self-esteem, social networking ease and increased sexual desire. Cocaine hydrochloride is mainly used intranasaly, but also as intravenous and subcutaneous injections. Cocaine use and first addiction treatment fall in later age compared to other psychoactive substances. There is a high men to women ratio among addicts. There is a relationship between cocaine addiction, the presence of other disorders and genetic predisposition to addiction development. Polish reports indicate higher popularity of cocaine among people with a high economic and social status. Although Poland is a country with the low percentage of cocaine use, its popularity is growing. The consequences of cocaine use concern somatic and mental health problems, socioeconomic and legal conditions. The drug plays a role in crimes and traffic accidents. Because of the risks associated with cocaine use, it has been listed in a register of drugs attached to the Act on Counteracting Drug Addiction. Addiction treatment includes psychological, pharmacological and harm reduction strategies. Med Pr 2016;67(4):537-544.

  19. Attitudes towards cannabis legalization in Iceland

    OpenAIRE

    Sigurbjörg Lára Kristinsdóttir 1991

    2016-01-01

    The debate on whether or not cannabis should be legalized has been growing in recent years. The legality of cannabis varies from country to country. Possession of cannabis have been decriminalized or legalized in numerous countries. The main aim of the present study was to examine both what characterizes those who are in favor of cannabis legalization and the potential effect on the community and cannabis consumption if cannabis would be legalized. The participants were 1198 obtained from an ...

  20. Cocaine and the nervous system.

    Science.gov (United States)

    Prakash, A; Das, G

    1993-12-01

    Cocaine abuse today has reached greater heights than it did during the first cocaine epidemic in the late nineteenth century. It is estimated that one out of every four Americans has used cocaine and some six million people in the US use it regularly. Although cocaine affects all systems in the body, the central nervous system (CNS) is the primary target. Cocaine blocks the reuptake of neurotransmitters in the neuronal synapses. Almost all CNS effects of cocaine can be attributed to this mechanism. Euphoria, pharmacological pleasure and intense cocaine craving share basis in this system. The effects of cocaine on other organ systems, in addition to its effects on the CNS, account for the majority of the complications associated with cocaine abuse. In this paper, the CNS effects following cocaine administration and their treatment are discussed.

  1. Cannabis Decriminalization and the Age of Onset of Cannabis Use

    OpenAIRE

    Cervený, J.; van Ours, J.C.; Chomynova, Pavla; Mravcik, Viktor

    2015-01-01

    This paper examines the effect of a change in drugs policy on the age of onset of cannabis use. We use 2012 survey data from the Czech Republic where in 2010 a law was introduced decriminalizing personal possession of small quantities of several illicit drugs, including cannabis. We estimate the effect of the policy change using a mixed proportional hazards framework that models the starting rate of cannabis use, i.e. the transition to first cannabis use. We find that the decriminalization of...

  2. Dose-dependent cannabis use, depressive symptoms, and FAAH genotype predict sleep quality in emerging adults: a pilot study.

    Science.gov (United States)

    Maple, Kristin E; McDaniel, Kymberly A; Shollenbarger, Skyler G; Lisdahl, Krista M

    2016-07-01

    Cannabis has been shown to affect sleep in humans. Findings from animal studies indicate that higher endocannabinoid levels promote sleep, suggesting that chronic use of cannabis, which downregulates endocannabinoid activity, may disrupt sleep. This study sought to determine if past-year cannabis use and genes that regulate endocannabinoid signaling, FAAH rs324420 and CNR1 rs2180619, predicted sleep quality. As depression has been previously associated with both cannabis and sleep, the secondary aim was to determine if depressive symptoms moderated or mediated these relationships. Data were collected from 41 emerging adult (ages 18-25) cannabis users. Exclusion criteria included Axis I disorders (besides SUD) and medical and neurologic disorders. Relationships were tested using multiple regressions, controlling for demographic variables, past-year substance use, and length of cannabis abstinence. Greater past-year cannabis use and FAAH C/C genotype were associated with poorer sleep quality. CNR1 genotype did not significantly predict sleep quality. Depressive symptoms moderated the relationship between cannabis use and sleep at a nonsignificant trend level, such that participants with the higher cannabis use and depressive symptoms reported the more impaired sleep. Depressive symptoms mediated the relationship between FAAH genotype and sleep quality. This study demonstrates a dose-dependent relationship between chronic cannabis use and reported sleep quality, independent of abstinence length. Furthermore, it provides novel evidence that depressive symptoms mediate the relationship between FAAH genotype and sleep quality in humans. These findings suggest potential targets to impact sleep disruptions in cannabis users.

  3. Quantification by HPLC-MS/MS of atropine in human serum and clinical presentation of six mild-to-moderate intoxicated atropine-adulterated-cocaine users

    NARCIS (Netherlands)

    Boermans, PAMM; Go, HS; Wessels, AMA; Uges, DRA

    2006-01-01

    An unexpectedly high number of initially suspected cocaine-intoxicated patients was presented to a general hospital in Lelystad, The Netherlands. Based on the unusual toxidram rate of not fitting cocaine intoxication, the suspicion of co-presence of an anticholinergic agent was raised. A newly devel

  4. [Comorbidity in 207 cannabis users in a specific outpatient setting].

    Science.gov (United States)

    Guillem, E; Arbabzadeh-Bouchez, S; Vorspan, F; Bellivier, F

    2015-06-01

    Health care seeking for a problematic use of cannabis is in progress in France. The aim is to assess the addictive and psychiatric comorbidity in cannabis users seen in the specific setting at the Lariboisière hospital. Two hundred and seven cannabis users were included from January 2004 to December 2009. Twelve-month and lifetime diagnosis of abuse and dependence (cannabis, alcohol, cocaine/crack) (DSM-IV), current and lifetime mood disorders, anxiety disorders, eating disorders and psychotic disorders were assessed (Mini-International Neuropsychiatric Interview). Logistic regression analyses identified adjusted odds ratios associated with the gender and the health care seeking (P=0.01). One hundred and forty-seven men (71%) and 60 women (29%), 29.3±8.6 years (15.2-51.6 years). Most of the outpatients ask for health care themselves (59.7%), whereas 19.4% are asked to seek health care by relatives (19.4%) or because of an academic, health or justice injunction (20.4%). In total, 49.3% of the outpatients are single, 35.7% are cohabitating, 9.3% are married and 6.3% are separated/divorced. About 20.4% of the outpatients are students, 35.7% have a professional activity, 19% are jobless, 2.4% are impaired, 0.5% are retired, at home and 12.1% do not have an official income. Twelve-month and lifetime prevalence of abuse/dependence are: cannabis (10.1/82.1% and 8.7/88.4%), alcohol (9.7/8.7% and 19.3/18.8%), cocaine/crack (2.4/3.4% and 4.8/11.6%). The mean duration of cannabis dependence for the current dependent users is 8.4±5.8 years. The mean number of "joints" during the last 6 months is 6±4.3, the mean amount of cannabis per week is 12.5±11.3g. About 51.3% of the dependent users report externalized and/or internalized disorders at school during childhood and adolescence. In total, 19.4% of the dependent users have a suicide attempt history and 18.9% have a psychiatric hospitalisation history, more frequently women (Pdepressive disorder (MDD) (29.1% and 57

  5. Snow Control - An RCT protocol for a web-based self-help therapy to reduce cocaine consumption in problematic cocaine users

    Directory of Open Access Journals (Sweden)

    Sullivan Robin

    2011-09-01

    Full Text Available Abstract Background Cocaine use has increased in most European countries, including Switzerland, and many states worldwide. The international literature has described treatment models that target the general population. In addition to supplying informative measures at the level of primary and secondary prevention, the literature also offers web-based self-help tools for problematic substance users, which is in line with tertiary prevention. Such programs, however, have been primarily tested on individuals with problematic alcohol and cannabis consumption, but not on cocaine-dependent individuals. Methods/Design This paper presents the protocol of a randomised clinical trial to test the effectiveness of a web-based self-help therapy to reduce cocaine use in problematic cocaine users. The primary outcome is severity of cocaine dependence. Secondary outcome measures include cocaine craving, consumption of cocaine and other substances of abuse in the past month, and changes in depression characteristics. The therapy group will receive a 6-week self-help therapy to reduce cocaine consumption based on methods of Cognitive Behavioural Therapy, principles of Motivational Interviewing and self-control practices. The control group will be presented weekly psycho-educative information with a quiz. The predictive validity of participant characteristics on treatment retention and outcome will be explored. Discussion To the best of our knowledge, this will be the first randomised clinical trial to test the effectiveness of online self-help therapy to reduce or abstain from cocaine use. It will also investigate predictors of outcome and retention. This trial is registered at Current Controlled Trials and is traceable as NTR-ISRCTN93702927.

  6. Cannabis - from cultivar to chemovar.

    Science.gov (United States)

    Hazekamp, A; Fischedick, J T

    2012-01-01

    The medicinal use of Cannabis is increasing as countries worldwide are setting up official programs to provide patients with access to safe sources of medicinal-grade Cannabis. An important question that remains to be answered is which of the many varieties of Cannabis should be made available for medicinal use. Drug varieties of Cannabis are commonly distinguished through the use of popular names, with a major distinction being made between Indica and Sativa types. Although more than 700 different cultivars have already been described, it is unclear whether such classification reflects any relevant differences in chemical composition. Some attempts have been made to classify Cannabis varieties based on chemical composition, but they have mainly been useful for forensic applications, distinguishing drug varieties, with high THC content, from the non-drug hemp varieties. The biologically active terpenoids have not been included in these approaches. For a clearer understanding of the medicinal properties of the Cannabis plant, a better classification system, based on a range of potentially active constituents, is needed. The cannabinoids and terpenoids, present in high concentrations in Cannabis flowers, are the main candidates. In this study, we compared cultivars obtained from multiple sources. Based on the analysis of 28 major compounds present in these samples, followed by principal component analysis (PCA) of the quantitative data, we were able to identify the Cannabis constituents that defined the samples into distinct chemovar groups. The study indicates the usefulness of a PCA approach for chemotaxonomic classification of Cannabis varieties.

  7. Pretreatment with group I metabotropic glutamate receptors antagonists attenuates lethality induced by acute cocaine overdose and expression of sensitization to hyperlocomotor effect of cocaine in mice.

    Science.gov (United States)

    Kotlinska, Jolanta; Bochenski, Marcin

    2011-01-01

    Cocaine abuse and dependence is a worldwide health problem. However, there are no currently approved medications to reduce cocaine abuse/relapse and toxicity. The aim of the present study was to test, whether group I metabotropic glutamate receptors (mGluRs) antagonists (mGluR1 and mGluR5) differentially regulate toxic versus behavioral effects of cocaine, both phenomena relevant to the psychopathology of cocaine addiction in humans. In the present study, we assessed the impact of mGluR1 antagonist-EMQMCM and mGluR5 antagonist-MTEP on the cocaine-induced lethality and the expression of sensitization to hyperlocomotor effect of cocaine in mice. Our study indicated that EMQMCM and MTEP, both substances at the doses of 5 and 10 mg/kg (but not 2.5 mg/kg), decreased cocaine-induced lethality produced by 75 mg/kg of cocaine, which was given acutely. The effect of EMQMCM was dose-dependent, and this compound at the dose of 10 mg/kg almost completely abolished the lethality induced by cocaine. MTEP reduced this cocaine effect at the doses of 5 and 10 mg/kg, equally. Furthermore, EMQMCM (1.25-5 mg/kg) at the doses of 2.5 and 5.0 mg/kg, and MTEP (2.5-10 mg/kg) only at the highest dose of 10 mg/kg, significantly reduced the expression of cocaine-induced (10 mg/kg) behavioral sensitization. Our results suggest that stimulation of mGluR1 and mGluR5 is involved in lethal effect of cocaine overdose and cocaine seeking behavior evaluated in behavioral sensitization test. However, the participation of mGluR1 in these cocaine effects seems to be dominant. Therefore, antagonists showing preferences towards mGluR1 might be useful in therapy of cocaine toxicity and abuse.

  8. Attitudes of cannabis growers to regulation of cannabis cultivation under a non-prohibition cannabis model.

    Science.gov (United States)

    Lenton, Simon; Frank, Vibeke A; Barratt, Monica J; Dahl, Helle Vibeke; Potter, Gary R

    2015-03-01

    How cannabis cultivation is dealt with under various examples of cannabis legalization or regulation is an important consideration in design of such schemes. This study aimed to (i) investigate support among current or recent cannabis growers, for various potential policy options for cannabis cultivation if prohibition were repealed, and (ii) explore the support for these options across countries, scale of growing operations, demographics, drug use and cannabis supply involvement variables. This study utilized data from the online web survey of largely 'small-scale' cannabis cultivators, aged 18yrs and over, in eleven countries conducted by the Global Cannabis Cultivation Research Consortium (GCCRC). Data from 1722 current and recent cannabis growers in Australia, Denmark and the UK, who were all asked about policy, were included in the analysis. It investigated support for various frameworks for cultivation: (no regulation (free market); adult only; growing licenses; restrictions on plant numbers; licensed business-only sale; approved commercial growing; etc.). Among current growers, support for these options were compared across countries, across scale of growing operations, and by demographics, drug use and crime variables. Although there were some between country differences in support for the various policy options, what was striking was the similarity of the proportions for each of the eight most popular policy options. Among current growers, many of these positions were predicted by demographic, drug use and cannabis growing variables which were conceptually congruent with these positions. The results have relevance for the provisions regarding cannabis cultivation in the design of new non-prohibitionist models of cannabis which are increasingly under consideration. It should be of interest to policy makers, drug policy researchers, law enforcement and cannabis cultivators. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. A critique of cannabis legalization proposals in Canada.

    Science.gov (United States)

    Kalant, Harold

    2016-08-01

    An editorial in this issue describes a cannabis policy framework document issued by a major Canadian research centre, calling for legalization of non-medical use under strict controls to prevent increase in use, especially by adolescents and young adults who are most vulnerable to adverse effects of cannabis. It claims that such a system would eliminate the severe personal, social and monetary costs of prohibition, diminish the illicit market, and provide more humane management of cannabis use disorders. It claims that experience with regulation of alcohol and tobacco will enable a system based on public health principles to control access of youth to cannabis without the harm caused by prohibition. The present critique argues that the claims made against decriminalization and for legalization are unsupported, or even contradicted, by solid evidence. Early experience in other jurisdictions suggests that legalization increases use by adolescents and its attendant harms. Regulation of alcohol use does not provide a good model for cannabis controls because there is widespread alcohol use and harm among adolescents and young adults. Government monopolies of alcohol sale have been used primarily as sources of revenue rather than for guarding public health, and no reason has been offered to believe they would act differently with respect to cannabis. Good policy decisions require extensive unbiased information about the individual and social benefits and costs of both drug use and proposed control measures, and value judgments about the benefit/harm balance of each option. Important parts of the necessary knowledge about cannabis are not yet available, so that the value judgments are not yet possible. Therefore, a better case can be made for eliminating some of the harms of prohibition by decriminalization of cannabis possession and deferring decision about legalization until the necessary knowledge has been acquired.

  10. Cannabis Decriminalization and the Age of Onset of Cannabis Use

    NARCIS (Netherlands)

    Cervený, J.; van Ours, J.C.; Chomynova, Pavla; Mravcik, Viktor

    2015-01-01

    This paper examines the effect of a change in drugs policy on the age of onset of cannabis use. We use 2012 survey data from the Czech Republic where in 2010 a law was introduced decriminalizing personal possession of small quantities of several illicit drugs, including cannabis. We estimate the

  11. Cannabis Decriminalization and the Age of Onset of Cannabis Use

    NARCIS (Netherlands)

    Cervený, J.; van Ours, J.C.; Chomynova, Pavla; Mravcik, Viktor

    2015-01-01

    This paper examines the effect of a change in drugs policy on the age of onset of cannabis use. We use 2012 survey data from the Czech Republic where in 2010 a law was introduced decriminalizing personal possession of small quantities of several illicit drugs, including cannabis. We estimate the eff

  12. When cannabis is available and visible at school - A multilevel analysis of students' cannabis use

    NARCIS (Netherlands)

    Kuntsche, E.N.

    2010-01-01

    Aims - To investigate the links between the visibility of cannabis use in school (measured by teachers’ reports of students being under the influence of cannabis on school premises), the proportion of cannabis users in the class, perceived availability of cannabis, as well as adolescent cannabis use

  13. Cannabis and tolerance: acute drug impairment as a function of cannabis use history

    NARCIS (Netherlands)

    Ramaekers, J.G.; Wel, J.H. van; Spronk, D.B.; Toennes, S.W.; Kuypers, K.P.; Theunissen, E.L.; Verkes, R.J.

    2016-01-01

    Cannabis use history as predictor of neurocognitive response to cannabis intoxication remains subject to scientific and policy debates. The present study assessed the influence of cannabis on neurocognition in cannabis users whose cannabis use history ranged from infrequent to daily use. Drug users

  14. When cannabis is available and visible at school - A multilevel analysis of students' cannabis use

    NARCIS (Netherlands)

    Kuntsche, E.N.

    2010-01-01

    Aims - To investigate the links between the visibility of cannabis use in school (measured by teachers’ reports of students being under the influence of cannabis on school premises), the proportion of cannabis users in the class, perceived availability of cannabis, as well as adolescent cannabis use

  15. Distance to Cannabis-Shops and Age of Onset of Cannabis Use

    NARCIS (Netherlands)

    Palali, A.; van Ours, J.C.

    2013-01-01

    Abstract: In the Netherlands cannabis use is quasi-legalized. Small quantities of cannabis can be bought in cannabis-shops. We investigate how the distance to the nearest cannabis- shop affects the age of onset of cannabis use. We use a Mixed Proportional Hazard rate framework to take account of

  16. Distance to cannabis-shops and age of onset of cannabis use

    NARCIS (Netherlands)

    Palali, A.; van Ours, J.C.

    In the Netherlands, cannabis use is quasi-legalized. Small quantities of cannabis can be bought in cannabis shops. We investigate how the distance to the nearest cannabis shop affects the age of onset of cannabis use. We use a mixed proportional hazard rate framework to take account of observable as

  17. When cannabis is available and visible at school - A multilevel analysis of students' cannabis use

    NARCIS (Netherlands)

    Kuntsche, E.N.

    2010-01-01

    Aims - To investigate the links between the visibility of cannabis use in school (measured by teachers’ reports of students being under the influence of cannabis on school premises), the proportion of cannabis users in the class, perceived availability of cannabis, as well as adolescent cannabis

  18. Cannabis and tolerance: acute drug impairment as a function of cannabis use history

    NARCIS (Netherlands)

    Ramaekers, J.G.; Wel, J.H. van; Spronk, D.B.; Toennes, S.W.; Kuypers, K.P.; Theunissen, E.L.; Verkes, R.J.

    2016-01-01

    Cannabis use history as predictor of neurocognitive response to cannabis intoxication remains subject to scientific and policy debates. The present study assessed the influence of cannabis on neurocognition in cannabis users whose cannabis use history ranged from infrequent to daily use. Drug users

  19. When Cannabis Is Available and Visible at School--A Multilevel Analysis of Students' Cannabis Use

    Science.gov (United States)

    Kuntsche, Emmanuel

    2010-01-01

    Aims: To investigate the links between the visibility of cannabis use in school (measured by teachers' reports of students being under the influence of cannabis on school premises), the proportion of cannabis users in the class, perceived availability of cannabis, as well as adolescent cannabis use. Methods: A multilevel regression model was…

  20. Distance to cannabis-shops and age of onset of cannabis use

    NARCIS (Netherlands)

    Palali, A.; van Ours, J.C.

    2015-01-01

    In the Netherlands, cannabis use is quasi-legalized. Small quantities of cannabis can be bought in cannabis shops. We investigate how the distance to the nearest cannabis shop affects the age of onset of cannabis use. We use a mixed proportional hazard rate framework to take account of observable as

  1. Distance to Cannabis-Shops and Age of Onset of Cannabis Use

    NARCIS (Netherlands)

    Palali, A.; van Ours, J.C.

    2013-01-01

    Abstract: In the Netherlands cannabis use is quasi-legalized. Small quantities of cannabis can be bought in cannabis-shops. We investigate how the distance to the nearest cannabis- shop affects the age of onset of cannabis use. We use a Mixed Proportional Hazard rate framework to take account of obs

  2. When Cannabis Is Available and Visible at School--A Multilevel Analysis of Students' Cannabis Use

    Science.gov (United States)

    Kuntsche, Emmanuel

    2010-01-01

    Aims: To investigate the links between the visibility of cannabis use in school (measured by teachers' reports of students being under the influence of cannabis on school premises), the proportion of cannabis users in the class, perceived availability of cannabis, as well as adolescent cannabis use. Methods: A multilevel regression model was…

  3. Topiramate's effects on cocaine-induced subjective mood, craving and preference for money over drug taking.

    Science.gov (United States)

    Johnson, Bankole A; Roache, John D; Ait-Daoud, Nassima; Gunderson, Erik W; Haughey, Heather M; Wang, Xin-Qun; Liu, Lei

    2013-05-01

    Topiramate, presumably through antagonism of excitatory glutaminergic pathways and facilitation of inhibitory gamma-aminobutyric acid neurons in the cortico-mesolimbic system, might reduce cocaine's abuse liability. We tested whether topiramate (100 mg twice daily) would reduce the euphoria, subjective mood, craving and preference for cocaine over money induced by low and high doses (0.325 and 0.65 mg/kg i.v., respectively) of experimentally administered cocaine in 24 male and female, cocaine-dependent, non-treatment-seeking research volunteers in a university in-patient laboratory. We utilized a randomized, double-blind, placebo-controlled, within-subject, Latin-square cross-over design in which three experimental challenge doses of low-dose cocaine, high-dose cocaine and placebo were administered in counterbalanced order after 5 days of topiramate or matching placebo pre-treatments separated by a 1-week washout period (2006-2009). After placebo pre-treatments, cocaine produced dose-related increases in euphoria, stimulant effects, craving for more cocaine and monetary value of cocaine in a behavioral preference test of cocaine versus money choice. Topiramate pre-treatment reduced the cocaine-related craving and monetary value of high-dose cocaine while increasing the monetary value, euphoria and stimulant effects of low-dose cocaine. Validated and standardized human experimental methods evaluating the potential for topiramate to alter cocaine's abuse liability suggest that topiramate may reduce the reinforcing effects and craving induced by higher cocaine doses. Low-dose cocaine might appear to have some enhancement of its stimulant properties in the presence of topiramate's prominent sedative effects. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

  4. Cocaine and Pregnancy

    Science.gov (United States)

    ... weight. Cocaine may increase the risk for preterm delivery. Babies who are born prematurely often start life with ... Is there any way to know if my baby has been harmed before delivery? If you are worried that your baby may ...

  5. Maybe a new killer in illicit cocaine.

    Science.gov (United States)

    Fucci, Nadia

    2011-06-15

    This is the study of the author that refers about a case of a 46 years old man found dead inside his house, the death was related to cocaine intake. The police found the corpse laying in his bed with a sheet of newspaper rolled up and a few plastic coverings containing trace of cocaine on the desk. Toxicological analysis was performed and drug levels measured by means of gas chromatography/mass spectrometry technology. Based on the autopsy findings and toxicological results the cause of death was related to an acute intoxication due to cocaine "overdose". In addition to the presence of cocaine and smaller alkaloids, in the sheet made of newspaper rolled up and eluted of the nasal mucosas has been highlighted the presence of 2,6-disopropylnaphtalene (2,6-DIPN), a fungicidal pesticide very health hazard for human. A very easy, simple and selective gas chromatography mass spectrometry method was employed for the detection of 2,6-DIPN in the cocaine powder. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Novel pharmacotherapeutic treatments for cocaine addiction

    Directory of Open Access Journals (Sweden)

    Kosten Thomas R

    2011-11-01

    Full Text Available Abstract Cocaine is a stimulant that leads to the rapid accumulation of catecholamines and serotonin in the brain due to prevention of their re-uptake into the neuron that released the neurotransmitter. Cocaine dependence is a public health concern and cause of significant morbidity and mortality worldwide. At present, there are no approved medications for the treatment of this devastating illness, and behavioral interventions have proven to be of limited use. However, there have been a number of recent trials testing promising agents including dopamine agonists, GABAergic medications and the cocaine vaccine. Here we discuss the most recent human clinical trials of potential medications for treatment of cocaine dependence, as well as pre-clinical studies for another promising agent, levo tetrahydropalmatine. Examination of these recent findings shows promise for GABAergic medications and the cocaine vaccine, as well as unique medications such as disulfiram, whose mechanism remains to be determined. Future work may also confirm specific subgroups of patients for treatment response based on clinical characteristics, biomarkers and pharmacogenetics. This review highlights the need for further, bigger studies in order to determine optimal clinical usage.

  7. Pattern of intake and drug craving predict the development of cocaine addiction-like behavior in rats.

    Science.gov (United States)

    Belin, David; Balado, Eric; Piazza, Pier Vincenzo; Deroche-Gamonet, Véronique

    2009-05-15

    Clinical observations suggest that cocaine addiction often emerges with new patterns of use. Whether these changes are a cause of addiction or its consequence is unknown. We investigated whether the development of an addiction-like behavior in the rat is associated with the pattern of cocaine intake and with cocaine craving, a major feature of cocaine addiction. To determine whether changes in the pattern of cocaine use and enhanced craving precede or parallel the onset of addiction, we used a rat addiction model that incorporates core features of human addiction. For this purpose, the pattern of inter-infusion intervals (a measure of pattern of cocaine intake), sensitivity to cocaine-induced reinstatement (a measure of cocaine craving), and addiction-like behaviour were assessed over several months of intravenous cocaine self-administration. We found that, even at early stages of cocaine self-administration, both the pattern of cocaine intake and the intensity of drug-induced reinstatement predict the severity of cocaine use, measured after 75 days of self-administration. Our results identify key predictors of cocaine addiction-intensified pattern of drug use and high drug-induced craving-that may help in the identification of subjects at risk for subsequent development of severe cocaine addiction.

  8. Cannabis Use and Mental Health Problems

    NARCIS (Netherlands)

    van Ours, J.C.; Williams, J.

    2009-01-01

    This paper investigates whether cannabis use leads to worse mental health. To do so, we account for common unobserved factors affecting mental health and cannabis consumption by modeling mental health jointly with the dynamics of cannabis use. Our main finding is that using cannabis increases the li

  9. Beyond Cannabis: Plants and the Endocannabinoid System.

    Science.gov (United States)

    Russo, Ethan B

    2016-07-01

    Plants have been the predominant source of medicines throughout the vast majority of human history, and remain so today outside of industrialized societies. One of the most versatile in terms of its phytochemistry is cannabis, whose investigation has led directly to the discovery of a unique and widespread homeostatic physiological regulator, the endocannabinoid system. While it had been the conventional wisdom until recently that only cannabis harbored active agents affecting the endocannabinoid system, in recent decades the search has widened and identified numerous additional plants whose components stimulate, antagonize, or modulate different aspects of this system. These include common foodstuffs, herbs, spices, and more exotic ingredients: kava, chocolate, black pepper, and many others that are examined in this review.

  10. Cocaine in blood of coca chewers.

    Science.gov (United States)

    Homstedt, B; Lindgren, J E; Rivier, L; Plowman, T

    1979-01-01

    Coca leaves (Erythroxylum coca Lamarck) and powder (5 - 10 g) were taken orally by human subjects in the same way as South American natives do. The cocaine, as measured by mass fragmentography, was immediately detected in the blood, reached peak concentrations from 10 - 150 ng/ml plasma at 0.38 - 1.95 hours, and persisted in the plasma for more than 7 hours. Half-lives of the elimination of cocaine were calculated and ranged from 1.0 to 1.9 hours. The absorption half-lives ranged from 0.2 to 0.6 hours. The shape of the curves fits with the subjective effects reported. There is no reason to believe that the stimulating effect achieved by the use of either coca leaves or powder is not due to cocaine.

  11. Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines.

    Science.gov (United States)

    Zgair, Atheer; Wong, Jonathan Cm; Lee, Jong Bong; Mistry, Jatin; Sivak, Olena; Wasan, Kishor M; Hennig, Ivo M; Barrett, David A; Constantinescu, Cris S; Fischer, Peter M; Gershkovich, Pavel

    2016-01-01

    There has been an escalating interest in the medicinal use of Cannabis sativa in recent years. Cannabis is often administered orally with fat-containing foods, or in lipid-based pharmaceutical preparations. However, the impact of lipids on the exposure of patients to cannabis components has not been explored. Therefore, the aim of this study is to elucidate the effect of oral co-administration of lipids on the exposure to two main active cannabinoids, Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD). In this study, oral co-administration of lipids enhanced the systemic exposure of rats to THC and CBD by 2.5-fold and 3-fold, respectively, compared to lipid-free formulations. In vitro lipolysis was conducted to explore the effect of lipids on the intestinal solubilisation of cannabinoids. More than 30% of THC and CBD were distributed into micellar fraction following lipolysis, suggesting that at least one-third of the administered dose will be available for absorption following co-administration with lipids. Both cannabinoids showed very high affinity for artificial CM-like particles, as well as for rat and human CM, suggesting high potential for intestinal lymphatic transport. Moreover, comparable affinity of cannabinoids for rat and human CM suggests that similar increased exposure effects may be expected in humans. In conclusion, co-administration of dietary lipids or pharmaceutical lipid excipients has the potential to substantially increase the exposure to orally administered cannabis and cannabis-based medicines. The increase in patient exposure to cannabinoids is of high clinical importance as it could affect the therapeutic effect, but also toxicity, of orally administered cannabis or cannabis-based medicines.

  12. Molecular profiling of midbrain dopamine regions in cocaine overdose victims.

    Science.gov (United States)

    Tang, Wen-Xue; Fasulo, Wendy H; Mash, Deborah C; Hemby, Scott E

    2003-05-01

    Chronic cocaine use in humans and animal models is known to lead to pronounced alterations in neuronal function in brain regions associated with drug reinforcement. To evaluate whether the alterations in gene expression in cocaine overdose victims are associated with specific dopamine populations in the midbrain, cDNA arrays and western blotting were used to compare gene and protein expression patterns between cocaine overdose victims and age-matched controls in the ventral tegmental area (VTA) and lateral substantia nigra (l-SN). Array analysis revealed significant up-regulation of numerous transcripts in the VTA, but not in the l-SN, of cocaine overdose victims including NMDAR1, GluR2, GluR5 and KA2 receptor mRNA (p overdose victims and controls were observed for GluR1, R3 or R4 mRNA levels. Correspondingly, western blot analysis revealed VTA-selective up-regulation of CREB (p cocaine overdose victims. The present results indicate that selective alterations of CREB and certain ionotropic glutamate receptor (iGluR) subtypes appear to be associated with chronic cocaine use in humans in a region-specific manner. Moreover, as subunit composition determines the functional properties of iGluRs, the observed changes may indicate alterations in the excitability of dopamine transmission underlying long-term biochemical and behavioral effects of cocaine in humans.

  13. Reaching out towards cannabis: approach-bias in heavy cannabis users predicts changes in cannabis use

    NARCIS (Netherlands)

    Cousijn, J.; Goudriaan, A.E.; Wiers, R.W.

    2011-01-01

    Aims Repeated drug exposure can lead to an approach-bias, i.e. the relatively automatically triggered tendencies to approach rather that avoid drug-related stimuli. Our main aim was to study this approach-bias in heavy cannabis users with the newly developed cannabis Approach Avoidance Task

  14. Cannabis and creativity: highly potent cannabis impairs divergent thinking in regular cannabis users.

    Science.gov (United States)

    Kowal, Mikael A; Hazekamp, Arno; Colzato, Lorenza S; van Steenbergen, Henk; van der Wee, Nic J A; Durieux, Jeffrey; Manai, Meriem; Hommel, Bernhard

    2015-03-01

    Cannabis users often claim that cannabis has the potential to enhance their creativity. Research suggests that aspects of creative performance might be improved when intoxicated with cannabis; however, the evidence is not conclusive. The aim of this study was to investigate the acute effects of cannabis on creativity. We examined the effects of administering a low (5.5 mg delta-9-tetrahydrocannabinol [THC]) or high (22 mg THC) dose of vaporized cannabis vs. placebo on creativity tasks tapping into divergent (Alternate Uses Task) and convergent (Remote Associates Task) thinking, in a population of regular cannabis users. The study used a randomized, double-blind, between-groups design. Participants in the high-dose group (n = 18) displayed significantly worse performance on the divergent thinking task, compared to individuals in both the low-dose (n = 18) and placebo (n = 18) groups. The findings suggest that cannabis with low potency does not have any impact on creativity, while highly potent cannabis actually impairs divergent thinking.

  15. Statistics on cannabis users skew perceptions of cannabis use

    Directory of Open Access Journals (Sweden)

    Rachel Melissa Burns

    2013-11-01

    Full Text Available Collecting information about the prevalence of cannabis use is necessary but not sufficient for understanding the size, dynamics, and outcomes associated with cannabis markets. This paper uses two data sets describing cannabis consumption in the United States and Europe to highlight 1 differences in inferences about sub-populations based on the measure used to quantify cannabis-related activity; 2 how different measures of cannabis-related activity can be used to more accurately describe trends in cannabis usage over time; and 3 the correlation between frequency of use in the past month and average grams consumed per day. Key findings: Focusing on days of use instead of prevalence shows substantially greater increases in U.S. cannabis use in recent years; however, the recent increase is mostly among adults, not youth. Relatively more rapid growth in use days also occurred among the college-educated and Hispanic. Further, data from a survey conducted in several European countries show a strong positive correlation between frequency of use and quantity consumed per day of use, suggesting consumption is even more skewed toward the minority of heavy users than is suggested by days-of-use calculations.

  16. Cocaine is low on the value ladder of rats: possible evidence for resilience to addiction.

    Directory of Open Access Journals (Sweden)

    Lauriane Cantin

    Full Text Available BACKGROUND: Assessing the relative value of cocaine and how it changes with chronic drug use represents a long-standing goal in addiction research. Surprisingly, recent experiments in rats--by far the most frequently used animal model in this field--suggest that the value of cocaine is lower than previously thought. METHODOLOGY/PRINCIPAL FINDINGS: Here we report a series of choice experiments that better define the relative position of cocaine on the value ladder of rats (i.e., preference rank-ordering of different rewards. Rats were allowed to choose either taking cocaine or drinking water sweetened with saccharin--a nondrug alternative that is not biologically essential. By systematically varying the cost and concentration of sweet water, we found that cocaine is low on the value ladder of the large majority of rats, near the lowest concentrations of sweet water. In addition, a retrospective analysis of all experiments over the past 5 years revealed that no matter how heavy was past cocaine use most rats readily give up cocaine use in favor of the nondrug alternative. Only a minority, fewer than 15% at the heaviest level of past cocaine use, continued to take cocaine, even when hungry and offered a natural sugar that could relieve their need of calories. CONCLUSIONS/SIGNIFICANCE: This pattern of results (cocaine abstinence in most rats; cocaine preference in few rats maps well onto the epidemiology of human cocaine addiction and suggests that only a minority of rats would be vulnerable to cocaine addiction while the large majority would be resilient despite extensive drug use. Resilience to drug addiction has long been suspected in humans but could not be firmly established, mostly because it is difficult to control retrospectively for differences in drug self-exposure and/or availability in human drug users. This conclusion has important implications for preclinical research on the neurobiology of cocaine addiction and for future medication

  17. Preclinical Assessment of Lisdexamfetamine as an Agonist Medication Candidate for Cocaine Addiction: Effects in Rhesus Monkeys Trained to Discriminate Cocaine or to Self-Administer Cocaine in a Cocaine Versus Food Choice Procedure.

    Science.gov (United States)

    Banks, Matthew L; Hutsell, Blake A; Blough, Bruce E; Poklis, Justin L; Negus, S Stevens

    2015-01-24

    Chronic amphetamine treatment decreases cocaine consumption in preclinical and human laboratory studies and in clinical trials. Lisdexamfetamine is an amphetamine prodrug in which L-lysine is conjugated to the terminal nitrogen of d-amphetamine. Prodrugs may be advantageous relative to their active metabolites due to slower onsets and longer durations of action; however, lisdexamfetamine treatment's efficacy in decreasing cocaine consumption is unknown. This study compared lisdexamfetamine and d-amphetamine effects in rhesus monkeys using two behavioral procedures: (1) a cocaine discrimination procedure (training dose = 0.32mg/kg cocaine, i.m.); and (2) a cocaine-versus-food choice self-administration procedure. In the cocaine-discrimination procedure, lisdexamfetamine (0.32-3.2mg/kg, i.m.) substituted for cocaine with lower potency, slower onset, and longer duration of action than d-amphetamine (0.032-0.32mg/kg, i.m.). Consistent with the function of lisdexamfetamine as an inactive prodrug for amphetamine, the time course of lisdexamfetamine effects was related to d-amphetamine plasma levels by a counter-clockwise hysteresis loop. In the choice procedure, cocaine (0-0.1mg/kg/injection, i.v.) and food (1g banana-flavored pellets) were concurrently available, and cocaine maintained a dose-dependent increase in cocaine choice under baseline conditions. Treatment for 7 consecutive days with lisdexamfetamine (0.32-3.2mg/kg/day, i.m.) or d-amphetamine (0.032-0.1mg/kg/h, i.v.) produced similar dose-dependent rightward shifts in cocaine dose-effect curves and decreases in preference for 0.032mg/kg/injection cocaine. Lisdexamfetamine has a slower onset and longer duration of action than amphetamine but retains amphetamine's efficacy to reduce the choice of cocaine in rhesus monkeys. These results support further consideration of lisdexamfetamine as an agonist-based medication candidate for cocaine addiction. © The Author 2015. Published by Oxford University Press on

  18. [Ten years of emergency attendances for cocaine-users in Spain].

    Science.gov (United States)

    Galicia, Miguel; Nogué, Santiago; Burillo-Putze, Guillermo

    2014-10-07

    Cocaine is the second most consumed illegal drug in the western world, following cannabis. Since 1998, it is also the drug that more attendances generate in different emergency devices, and it is responsible for more of 60% of the emergencies directly related to drug consumption. This work reviews the main Spanish scientific articles published in the last 10 years, in which different factors related to the use of this drug have been analyzed in relation to the use of emergency by cocaine users. A total of 8,795 patients were included (interval 57-1,755), with an average age of 32.64 years (SD 3.02), and an average percentage of positives to cocaine of 54.78% (SD 47.03); there were 7 works with 100% of subjects being positive to cocaine. Males predominated with an average of 78.69% (SD 12). They presented cardiovascular symptoms in 30% cases (SD 22.7), neurological symptoms in 11.6% cases (SD 4.28) and psychiatric symptoms in 49.32% cases (SD 23.87). There was a multiple consumption in 49.02% of patients (interval 4.3-76.2), fundamentally associated with alcohol (57.78%, SD 6.18) and cannabis (21.56%, SD 10.72). Two hundred and forty-six patients (2.8%) needed admission and 8 died (0.09%). Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  19. Association Between Regular Cannabis Use and Ganglion Cell Dysfunction.

    Science.gov (United States)

    Schwitzer, Thomas; Schwan, Raymund; Albuisson, Eliane; Giersch, Anne; Lalanne, Laurence; Angioi-Duprez, Karine; Laprevote, Vincent

    2017-01-01

    Because cannabis use is a major public health concern and cannabis is known to act on central neurotransmission, studying the retinal ganglion cells in individuals who regularly use cannabis is of interest. To determine whether the regular use of cannabis could alter the function of retinal ganglion cells in humans. For this case-control study, individuals who regularly use cannabis, as well as healthy controls, were recruited, and data were collected from February 11 to October 28, 2014. Retinal function was used as a direct marker of brain neurotransmission abnormalities in complex mental phenomena. Amplitude and implicit time of the N95 wave on results of pattern electroretinography. Twenty-eight of the 52 participants were regular cannabis users (24 men and 4 women; median age, 22 years [95% CI, 21-24 years]), and the remaining 24 were controls (20 men and 4 women; median age, 24 years [95% CI, 23-27 years]). There was no difference between groups in terms of age (P = .13) or sex (P = .81). After adjustment for the number of years of education and alcohol use, there was a significant increase for cannabis users of the N95 implicit time on results of pattern electroretinography (median, 98.6 milliseconds [95% CI, 93.4-99.5]) compared with controls (median, 88.4 milliseconds [95% CI, 85.0-91.1]), with 8.4 milliseconds as the median of the differences (95% CI, 4.9-11.5; P cannabis users and controls in their corresponding group. The positive predictive value was 78.6% (95% CI, 60.5%-89.8%), and the negative predictive value was 75.0% (95% CI, 55.1%-88.0%). Our results demonstrate a delay in transmission of action potentials by the ganglion cells in regular cannabis users, which could support alterations in vision. Our findings may be important from a public health perspective since they could highlight the neurotoxic effects of cannabis use on the central nervous system as a result of how it affects retinal processing.

  20. Long term stability of cannabis resin and cannabis extracts

    DEFF Research Database (Denmark)

    Lindholst, Christian

    2010-01-01

      The aim of the present study was to investigate the stability of cannabinoids in cannabis resin slabs and cannabis extracts upon long-term storage. The levels of tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD) and cannabigerol (CBG) on both neutral and acidic form were measured...... stored in extracted form at room temperature the degradation rate of acidic THC increased significantly relative to resin material with concentration halve-lives of 35 and 91 days in daylight and darkness, respectively. Once cannabis material is extracted into organic solvents, care should be taken...

  1. Cannabis species and cannabinoid concentration preference among sleep-disturbed medicinal cannabis users.

    Science.gov (United States)

    Belendiuk, Katherine A; Babson, Kimberly A; Vandrey, Ryan; Bonn-Miller, Marcel O

    2015-11-01

    Individuals report using cannabis for the promotion of sleep, and the effects of cannabis on sleep may vary by cannabis species. Little research has documented preferences for particular cannabis types or cannabinoid concentrations as a function of use for sleep disturbances. 163 adults purchasing medical cannabis for a physical or mental health condition at a cannabis dispensary were recruited. They provided self-report of (a) whether cannabis use was intended to help with sleep problems (e.g. insomnia, nightmares), (b) sleep quality (PSQI), (c) cannabis use (including preferred type), and (d) symptoms of DSM-5 cannabis dependence. 81 participants reported using cannabis for the management of insomnia and 14 participants reported using cannabis to reduce nightmares. Individuals using cannabis to manage nightmares preferred sativa to indica strains (Fisher's exact test (2) = 6.83, p cannabis dependence compared with those who preferred indica strains (χ(2)(2) = 4.09, p cannabis with significantly higher concentrations of CBD. Individuals who reported at least weekly use of hypnotic medications used cannabis with lower THC concentrations compared to those who used sleep medications less frequently than weekly (t(17) = 2.40, p cannabis used were observed in this convenience sample of individuals using cannabis for the management of sleep disturbances. Controlled prospective studies are needed to better characterize the impact that specific components of cannabis have on sleep. Copyright © 2015. Published by Elsevier Ltd.

  2. Reactivity to laboratory stress provocation predicts relapse to cocaine.

    Science.gov (United States)

    Back, Sudie E; Hartwell, Karen; DeSantis, Stacia M; Saladin, Michael; McRae-Clark, Aimee L; Price, Kimber L; Moran-Santa Maria, Megan M; Baker, Nathaniel L; Spratt, Eve; Kreek, Mary Jeanne; Brady, Kathleen T

    2010-01-01

    Cocaine dependence is a chronic relapsing disorder characterized by periods of abstinence and high rates of return to drug using behavior. Elevated levels of stress have been associated with relapse to cocaine; however, the nature of this association is not well understood. The relationship between reactivity to three human laboratory provocations and relapse to cocaine was investigated. Participants were 53 cocaine-dependent individuals who were admitted for a 2-day inpatient stay during which a psychosocial provocation (i.e., the Trier Social Stress Task), a pharmacological provocation (i.e., administration of 1 microg/kg corticotrophin releasing hormone; CRH), and a drug cue exposure paradigm were completed. Adrenocortico-trophic hormone (ACTH), cortisol, heart rate, and subjective cocaine craving and stress were assessed at baseline and at multiple time points post-task. Participants' cocaine use was monitored for approximately 1 month following testing. The majority (72.3%) of participants relapsed to cocaine during the follow-up period. In response to the CRH and drug cue exposure, elevated subjective craving and stress were significant predictors of cocaine use during follow-up. In response to the Trier, attenuated neuroendocrine responses were significant predictors of cocaine use. The findings provide further evidence of the ability of laboratory paradigms to predict relapse. The observed associations between stress reactivity and subsequent cocaine use highlight the clinical importance of the findings. Predictors of relapse may vary based on the type of provocation utilized. Interventions aimed at normalizing stress response, as measured using laboratory paradigms, may prove useful in relapse prevention. Published by Elsevier Ireland Ltd.

  3. [Sigmund Freud and cocaine].

    Science.gov (United States)

    Lebzeltern, G

    1983-11-11

    The basic tenet proposed by J. V. Scheidt states that the narcotic drug, cocaine played a role in the development of psychoanalysis which has been underestimated up to the present day. It is a fact that Freud himself took cocaine (in small doses) for about two years, and that he began his dream interpretation approximately ten years later. Scheidt believes that a long, unconscious conflict related to the cocaine-induced states of euphoria (ten years later) suddenly led to the beginnings of dream interpretation. The question to be answered now is: Why did this happen precisely in 1895? The foundations of psychoanalysis had already been laid, the application of the new method to the treatment of nervous disorders (heart complaints, train phobias, etc.) was certainly obvious. During this self-analysis it became necessary, first of all, to come to terms with the self-reproaches-which lay on the surface and were more accessible to consciousness-related to Freud's cocaine period (Fleischl-Marxow becomes addicted to cocaine, the most terrible night ever experienced, death of this friend, Freud's warning came too late). It was only when Freud has come to terms with this phase of his life that the road to the deepest part, the discovery of the Oedipus complex in the fall of 1897, was cleared.

  4. [Consumption of cannabis in adolescents].

    Science.gov (United States)

    Phan, O; Obradovic, I; Har, A

    2017-01-01

    Over the past 10 years, the consumption of cannabis among adolescents has dramatically increased. Today, adolescent cannabis use is a major public health problem. Two forms of cannabis are commonly smoked: herb (marijuana) and resin. These forms have a high concentration of tetrahydrocannabinol, the active molecule of cannabis. Recent research has helped understand how the cannabinoid system works. This system combines specific receptors and specific molecules: the endocannabinoids. The effects of cannabis use are now well documented. Some adolescents report subjective positive effects. They use it not only on a recreational basis, but also to deal with their emotions. Over the long term, cannabis increases the risk of depression and schizophrenia for those adolescents who are at risk. Use, misuse, and dependence are frequently associated with heavy psychopathologic problems such as vulnerability and depression. Many cannabis dependence psychotherapies have shown their efficacy and efficiency. Motivational interviews, cognitive behavioral therapy, multidimensional family therapy (MDFT), and residential treatment have proved highly effective. MDFT seems very effective, especially in cases of heavy use. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Terpene synthases from Cannabis sativa.

    Science.gov (United States)

    Booth, Judith K; Page, Jonathan E; Bohlmann, Jörg

    2017-01-01

    Cannabis (Cannabis sativa) plants produce and accumulate a terpene-rich resin in glandular trichomes, which are abundant on the surface of the female inflorescence. Bouquets of different monoterpenes and sesquiterpenes are important components of cannabis resin as they define some of the unique organoleptic properties and may also influence medicinal qualities of different cannabis strains and varieties. Transcriptome analysis of trichomes of the cannabis hemp variety 'Finola' revealed sequences of all stages of terpene biosynthesis. Nine cannabis terpene synthases (CsTPS) were identified in subfamilies TPS-a and TPS-b. Functional characterization identified mono- and sesqui-TPS, whose products collectively comprise most of the terpenes of 'Finola' resin, including major compounds such as β-myrcene, (E)-β-ocimene, (-)-limonene, (+)-α-pinene, β-caryophyllene, and α-humulene. Transcripts associated with terpene biosynthesis are highly expressed in trichomes compared to non-resin producing tissues. Knowledge of the CsTPS gene family may offer opportunities for selection and improvement of terpene profiles of interest in different cannabis strains and varieties.

  6. Phytochemistry of Cannabis sativa L.

    Science.gov (United States)

    ElSohly, Mahmoud A; Radwan, Mohamed M; Gul, Waseem; Chandra, Suman; Galal, Ahmed

    Cannabis (Cannabis sativa, or hemp) and its constituents-in particular the cannabinoids-have been the focus of extensive chemical and biological research for almost half a century since the discovery of the chemical structure of its major active constituent, Δ(9)-tetrahydrocannabinol (Δ(9)-THC). The plant's behavioral and psychotropic effects are attributed to its content of this class of compounds, the cannabinoids, primarily Δ(9)-THC, which is produced mainly in the leaves and flower buds of the plant. Besides Δ(9)-THC, there are also non-psychoactive cannabinoids with several medicinal functions, such as cannabidiol (CBD), cannabichromene (CBC), and cannabigerol (CBG), along with other non-cannabinoid constituents belonging to diverse classes of natural products. Today, more than 560 constituents have been identified in cannabis. The recent discoveries of the medicinal properties of cannabis and the cannabinoids in addition to their potential applications in the treatment of a number of serious illnesses, such as glaucoma, depression, neuralgia, multiple sclerosis, Alzheimer's, and alleviation of symptoms of HIV/AIDS and cancer, have given momentum to the quest for further understanding the chemistry, biology, and medicinal properties of this plant.This contribution presents an overview of the botany, cultivation aspects, and the phytochemistry of cannabis and its chemical constituents. Particular emphasis is placed on the newly-identified/isolated compounds. In addition, techniques for isolation of cannabis constituents and analytical methods used for qualitative and quantitative analysis of cannabis and its products are also reviewed.

  7. Treatment of cannabis use among people with psychotic or depressive disorders: a systematic review.

    Science.gov (United States)

    Baker, Amanda L; Hides, Leanne; Lubman, Dan I

    2010-03-01

    This article systematically reviews the evidence from randomized controlled trials (RCTs) for pharmacologic and psychological approaches to the treatment of cannabis use among individuals with psychotic or depressive disorders. A systematic literature search was conducted using the PubMed and PsychINFO databases from inception to December 2008. Individual searches in cannabis use (search terms: marijuana, cannabis, marijuana abuse, cannabis abuse, marijuana usage, cannabis usage), mental disorders (search terms: mood disorders, affective disorders, anxiety disorders, anxiety, depressive disorder, depression, psychotic disorders, psychosis, mental disorders), and pharmacotherapy (search terms: medication, drug therapy, pharmacotherapy, psychopharmacology, clinical trials, drug trial, treatment trial) were conducted and limited to humans, adolescents and adults. A search combining the individual cannabis use, mental disorder and pharmacotherapy searches produced 1,713 articles (PubMed = 1,398; PsychINFO = 315). Combining the cannabis use and mental disorder searches while limiting them to English articles and RCTs produced a total of 286 articles (PubMed = 228; PsychINFO = 58). From this literature, there were 7 RCTs conducted among mental health clients that reported cannabis use outcomes using pharmacologic or psychological interventions. While few RCTs have been conducted, there is evidence that pharmacologic and psychological interventions are effective for reducing cannabis use in the short-term among people with psychotic disorders or depression. Although it is difficult to make evidence-based treatment recommendations due to the paucity of research in this area, available studies indicate that effectively treating the mental health disorder with standard pharmacotherapy may be associated with a reduction in cannabis use and that longer or more intensive psychological interventions rather than brief interventions may be required, particularly among heavier

  8. Cannabis Epidemiology: A Selective Review

    Science.gov (United States)

    Anthony, James C.; Lopez-Quintero, Catalina; Alshaarawy, Omayma

    2017-01-01

    Background Globally, the most widely used set of compounds among the internationally regulated drugs is cannabis. Objective To review evidence from epidemiological research on cannabis, organized in relation to this field’s five main rubrics: quantity, location, causes, mechanisms, and prevention/control. Method The review covers a selection of evidence from standardized population surveys, official statistics, and governmental reports, as well as published articles and books identified via MEDLINE, Web of Science, and Google Scholar as of July 2016. Results In relation to quantity, an estimated 3% to 5% of the world population is thought to have tried a cannabis product, with at least one fairly recent use, mainly extra-medical and outside boundaries of prescribed use. Among cannabis users in the United States, roughly one in 7–8 has engaged in medical marijuana use. In relation to location, prevalence proportions reveal important variations across countries and between subgroups within countries. Regarding causes and mechanisms of starting to use cannabis, there is no compelling integrative and replicable conceptual model or theoretical formulation. Most studies of mechanisms have focused upon a ‘gateway sequence’ and person-to-person diffusion, with some recent work on disability-adjusted life years. A brief review of cannabis use consequences, as well as prevention and control strategies is also provided. Conclusion At present, we know much about the frequency and occurrence of cannabis use, with too little replicable definitive evidence with respect to the other main rubrics. Given a changing regulatory environment for cannabis products, new institutions such as an independent International Cannabis Products Safety Commission may be required to produce evidence required to weigh benefits versus costs. It is not clear that government sponsored research will be sufficient to meet consumer demand for balanced points of view and truly definitive evidence

  9. Transplacental pharmacokinetics of cocaine and benzoylecgonine in plasma and hair of rhesus monkeys.

    Science.gov (United States)

    Bailey, B; Morris, P; McMartin, K I; Klein, J; Duhart, H M; Gillam, M P; Binienda, Z; Slikker, W; Paule, M G; Koren, G

    1998-01-01

    There is large variability in the rate and extent of fetal damage from cocaine in humans; however, the sources of such variability are not presently known. In order to study the relationship between maternal cocaine pharmacokinetics at the end of pregnancy and maternal or infant cocaine and benzoylecgonine hair concentrations at birth, ten rhesus monkeys were administered cocaine intramuscularly throughout pregnancy. Cocaine and benzoylecgonine hair concentrations were determined at birth and correlated with maternal pharmacokinetics during pregnancy. There were no correlations between either maternal cocaine Cmax or AUC0-infinity and maternal and infant hair cocaine or benzoylecgonine concentrations. There were no significant correlations between maternal hair benzoylecgonine concentrations and either maternal benzoylecgonine AUC0-120 (r = 0.60; P = 0.07) or benzoylecgonine Cmax (r = 0.60; P = 0.07). No correlations existed between infant hair benzoylecgonine concentrations and either maternal benzoylecgonine AUC0-120 (r = 0.30; P = 0.40) or benzoylecgonine Cmax (r = 0.30; P = 0.40). Also, no correlation was found between maternal cocaine dose and maternal or infant cocaine and benzoylecgonine hair concentrations. In comparison to toxicants such as nicotine and carbon monoxide for which there is a good correlation between maternal systemic exposure and neonatal concentrations, the lack of a similar relationship for cocaine is consistent with the role of the placenta in contributing to the variability in the amounts of cocaine reaching the fetus and hence, potentially to the risk of adverse fetal outcome.

  10. (Re)introducing medicinal cannabis.

    Science.gov (United States)

    Mather, Laurence E; Rauwendaal, Evert R; Moxham-Hall, Vivienne L; Wodak, Alex D

    2013-12-16

    • After considering extensive scientific and medical evidence, a New South Wales Legislative Council multiparty committee recommended that medicinal cannabis should lawfully be made available for selected-use pharmacotherapy. • The evidence indicates that cannabis has genuine medicinal utility in patients with certain neuropathic conditions, with acceptable levels of risk from mostly mild side effects. • The potential medical benefits of cannabis pharmacotherapy have largely been overlooked, with research and society's attention, in most parts of the world, being directed towards the hazards of its recreational use. • The NSW Government has since dismissed the unanimous and compassionate recommendations of their committee.

  11. Cocaine cardiomyopathy: A case report

    Directory of Open Access Journals (Sweden)

    Georgiev Antonio

    2014-12-01

    Full Text Available Cocaine is the second most common illicit drug used and the most frequent cause of drug related deaths. The use of cocaine is associated with both, acute and chronic complications, that may involve any system, but the most common system affected is cardiovascular one. Cocaine cardiomyopathy may result from the use of cocaine. This article presents a first case in Republic of Macedonia of 24-year-old male with reversible cocaine-related cardiomyopathy. Clinical presentation, laboratory, X-ray, ultrasound findings and treatment are reviewed.

  12. Kappa-opioid receptor signaling in the striatum as a potential modulator of dopamine transmission in cocaine dependence

    Directory of Open Access Journals (Sweden)

    Pierre eTrifilieff

    2013-06-01

    Full Text Available Cocaine addiction is accompanied by a decrease in striatal dopamine signaling, measured as a decrease in dopamine D2 receptor binding as well as blunted dopamine release in the striatum. These alterations in dopamine transmission have clinical relevance, and have been shown to correlate with cocaine-seeking behavior and response to treatment for cocaine dependence. However, the mechanisms contributing to the hypodopaminergic state in cocaine addiction remain unknown. Here we review the Positron Emission Tomography (PET imaging studies showing alterations in D2 receptor binding potential and dopamine transmission in cocaine abusers and their significance in cocaine-seeking behavior. Based on animal and human studies, we propose that the kappa receptor/dynorphin system, because of its impact on dopamine transmission and upregulation following cocaine exposure, could contribute to the hypodopaminergic state reported in cocaine addiction, and could thus be a relevant target for treatment development.

  13. Hypocretin-1 receptors regulate the reinforcing and reward-enhancing effects of cocaine: Pharmacological and behavioral genetics evidence

    Directory of Open Access Journals (Sweden)

    Jonathan eHollander

    2012-07-01

    Full Text Available Considerable evidence suggests that transmission at hypocretin-1 (orexin-1 receptors (Hcrt-R1 plays an important role in the reinstatement of extinguished cocaine-seeking behaviors in rodents. However, far less is known about the role for hypocretin transmission in regulating ongoing cocaine-taking behavior. Here, we investigated the effects of the selective Hcrt-R1 antagonist SB-334867 on cocaine intake, as measured by intravenous (IV cocaine self-administration in rats. The stimulatory effects of cocaine on brain reward systems contribute to the establishment and maintenance of cocaine-taking behaviors. Therefore, we also assessed the effects of SB-334867 on the reward-enhancing properties of cocaine, as measured by cocaine-induced lowering of intracranial self-stimulation (ICSS thresholds. Finally, to definitively establish a role for Hcrt-R1 in regulating cocaine intake, we assessed IV cocaine self-administration in Hcrt-R1 knockout mice. We found that SB-334867 (1-4 mg/kg dose-dependently decreased cocaine (0.5 mg/kg/infusion self-administration in rats but did not alter responding for food rewards under the same schedule of reinforcement. This suggests that SB-334867 decreased cocaine reinforcement without negatively impacting operant performance. SB-334867 (1-4 mg/kg also dose-dependently attenuated the stimulatory effects of cocaine (10 mg/kg on brain reward systems, as measured by reversal of cocaine-induced lowering of ICSS thresholds in rats. Finally, we found that Hcrt-R1 knockout mice self-administered far less cocaine than wildtype mice across the entire dose-response function. These data demonstrate that Hcrt-R1 play an important role in regulating the reinforcing and reward-enhancing properties of cocaine, and suggest that hypocretin transmission is likely essential for establishing and maintaining the cocaine habit in human addicts.

  14. Anticonvulsants for cocaine dependence.

    Science.gov (United States)

    Minozzi, Silvia; Cinquini, Michela; Amato, Laura; Davoli, Marina; Farrell, Michael F; Pani, Pier Paolo; Vecchi, Simona

    2015-04-17

    Cocaine dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Although effective pharmacotherapy is available for alcohol and heroin dependence, none is currently available for cocaine dependence, despite two decades of clinical trials primarily involving antidepressant, anticonvulsivant and dopaminergic medications. Extensive consideration has been given to optimal pharmacological approaches to the treatment of individuals with cocaine dependence, and both dopamine antagonists and agonists have been considered. Anticonvulsants have been candidates for use in the treatment of addiction based on the hypothesis that seizure kindling-like mechanisms contribute to addiction. To evaluate the efficacy and safety of anticonvulsants for individuals with cocaine dependence. We searched the Cochrane Drugs and Alcohol Group Trials Register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6), MEDLINE (1966 to June 2014), EMBASE (1988 to June 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to June 2014), Web of Science (1991 to June 2014) and the reference lists of eligible articles. All randomised controlled trials and controlled clinical trials that focus on the use of anticonvulsant medications to treat individuals with cocaine dependence. We used the standard methodological procedures expected by The Cochrane Collaboration. We included a total of 20 studies with 2068 participants. We studied the anticonvulsant drugs carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate and vigabatrin. All studies compared anticonvulsants versus placebo. Only one study had one arm by which the anticonvulsant was compared with the antidepressant desipramine. Upon comparison of anticonvulsant versus placebo, we found no significant differences for any of the efficacy and safety measures. Dropouts: risk ratio (RR) 0.95, 95

  15. Weeding Out the Truth: Adolescents and Cannabis.

    Science.gov (United States)

    Ammerman, Seth; Tau, Gregory

    2016-01-01

    The use of cannabis for both legal (similar to alcohol) and medical purposes is becoming more common. Although cannabis remains an illegal Schedule 1 drug federally, as of November 2015, 23 states and the District of Columbia have legalized "medical" cannabis, and 4 states and the District of Columbia have legalized the use of cannabis for adults aged 21 years and older. It is very likely that more and more states will sooner rather than later allow cannabis for both medical and legal purposes. This review article will focus on a variety of issues relevant to the current debate about cannabis, and will address the following.

  16. [Therapeutic potential of Cannabis sativa].

    Science.gov (United States)

    Avello L, Marcia; Pastene N, Edgar; Fernández R, Pola; Córdova M, Pia

    2017-03-01

    Cannabis sativa (marihuana) is considered an illicit drug due to its psychoactive properties. Recently, the Chilean government opened to the use cannabis in the symptomatic treatment of some patients. The biological effects of cannabis render it useful for the complementary treatment of specific clinical situations such as chronic pain. We retrieved scientific information about the analgesic properties of cannabis, using it as a safe drug. The drug may block or inhibit the transmission of nervous impulses at different levels, an effect associated with pain control. Within this context and using adequate doses, forms and administration pathways, it can be used for chronic pain management, considering its effectiveness and low cost. It could also be considered as an alternative in patients receiving prolonged analgesic therapies with multiple adverse effects.

  17. Marijuana (Cannabis) and Multiple Sclerosis

    Science.gov (United States)

    ... Related Conditions Acute Disseminated Encephalomyelitis (ADEM) Balo’s Disease HTLV-I Associated Myelopathy (HAM) Neuromyelitis Optica (NMO) Schilder's ... Studies of note On effects of cannabis on cognition / cognitive function in people with MS: 20 subjects ...

  18. Structural analysis of thermostabilizing mutations of cocaine esterase

    Energy Technology Data Exchange (ETDEWEB)

    Narasimhan, Diwahar; Nance, Mark R.; Gao, Daquan; Ko, Mei-Chuan; Macdonald, Joanne; Tamburi, Patricia; Yoon, Dan; Landry, Donald M.; Woods, James H.; Zhan, Chang-Guo; Tesmer, John J.G.; Sunahara, Roger K. (Michigan); (Columbia); (Kentucky)

    2010-09-03

    Cocaine is considered to be the most addictive of all substances of abuse and mediates its effects by inhibiting monoamine transporters, primarily the dopamine transporters. There are currently no small molecules that can be used to combat its toxic and addictive properties, in part because of the difficulty of developing compounds that inhibit cocaine binding without having intrinsic effects on dopamine transport. Most of the effective cocaine inhibitors also display addictive properties. We have recently reported the use of cocaine esterase (CocE) to accelerate the removal of systemic cocaine and to prevent cocaine-induced lethality. However, wild-type CocE is relatively unstable at physiological temperatures ({tau}{sub 1/2} {approx} 13 min at 37 C), presenting challenges for its development as a viable therapeutic agent. We applied computational approaches to predict mutations to stabilize CocE and showed that several of these have increased stability both in vitro and in vivo, with the most efficacious mutant (T172R/G173Q) extending half-life up to 370 min. Here we present novel X-ray crystallographic data on these mutants that provide a plausible model for the observed enhanced stability. We also more extensively characterize the previously reported variants and report on a new stabilizing mutant, L169K. The improved stability of these engineered CocE enzymes will have a profound influence on the use of this protein to combat cocaine-induced toxicity and addiction in humans.

  19. 21 CFR 862.3250 - Cocaine and cocaine metabolite test system.

    Science.gov (United States)

    2010-04-01

    ... treatment of cocaine use or overdose. (b) Classification. Class II. ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cocaine and cocaine metabolite test system. 862... Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a) Identification. A cocaine and...

  20. Sex differences in selecting between food and cocaine reinforcement are mediated by estrogen.

    Science.gov (United States)

    Kerstetter, Kerry A; Ballis, Maya A; Duffin-Lutgen, Stevie; Carr, Amanda E; Behrens, Alexandra M; Kippin, Tod E

    2012-11-01

    Cocaine-dependent women, relative to their male counterparts, report shorter cocaine-free periods and report transiting faster from first use to entering treatment for addiction. Similarly, preclinical studies indicate that female rats, particularly those in the estrus phase of their reproductive cycle, show increased operant responding for cocaine under a wide variety of schedules. Making maladaptive choices is a component of drug dependence, and concurrent reinforcement schedules that examine cocaine choice offers an animal model of the conditions of human drug use; therefore, the examination of sex differences in decision-making may be critical to understanding why women display a more severe profile of cocaine addiction than men. Accordingly, we assessed sex and estrous cycle differences in choice between food (45 mg grain pellets) and intravenous cocaine (0.4 or 1.0 mg/kg per infusion) reinforcement in male, female (freely cycling), and ovariectomized (OVX) females treated with either estrogen benzoate (EB; 5 μg per day) or vehicle. At both cocaine doses, intact female rats choose cocaine over food significantly more than male rats. However, the estrous cycle did not impact the level of cocaine choice in intact females. Nevertheless, OVX females treated with vehicle exhibited a substantially lower cocaine choice compared with those receiving daily EB or to intact females. These results demonstrate that intact females have a greater preference for cocaine over food compared with males. Furthermore, this higher preference is estrogen-dependent, but does not vary across the female reproductive cycle, suggesting that ovarian hormones regulate cocaine choice. The present findings indicate that there is a biological predisposition for females to forgo food reinforcement to obtain cocaine reinforcement, which may substantially contribute to women experiencing a more severe profile of cocaine addiction than men.

  1. Cocaine versus food choice procedure in rats: environmental manipulations and effects of amphetamine.

    Science.gov (United States)

    Thomsen, Morgane; Barrett, Andrew C; Negus, S Stevens; Caine, S Barak

    2013-03-01

    We have adapted a nonhuman primate model of cocaine versus food choice to the rat species. To evaluate the procedure, we tested cocaine versus food choice under a variety of environmental manipulations as well as pharmacological pretreatments. Complete cocaine-choice dose-effect curves (0-1.0 mg/kg/infusion) were obtained for each condition under concurrent fixed ratio schedules of reinforcement. Percentage of responding emitted on the cocaine-reinforced lever was not affected significantly by removal of cocaine-associated visual or auditory cues, but it was decreased after removal of response-contingent or response-independent cocaine infusions. Cocaine choice was sensitive to the magnitude and fixed ratio requirement of both the cocaine and food reinforcers. We also tested the effects of acute (0.32, 0.56, 1.0, 1.8 mg/kg) and chronic (0.1, 0.32 mg/kg/hr) d-amphetamine treatment on cocaine choice. Acute and chronic d-amphetamine had opposite effects, with acute increasing and chronic decreasing cocaine choice, similar to observations in humans and in nonhuman primates. The results suggest feasibility and utility of the choice procedure in rats and support its comparability to similar procedures used in humans and monkeys. © Society for the Experimental Analysis of Behavior.

  2. Cocaine Versus Food Choice Procedure in Rats: Environmental Manipulations and Effects of Amphetamine

    Science.gov (United States)

    Thomsen, Morgane; Barrett, Andrew C.; Negus, S. Stevens; Caine, S. Barak

    2014-01-01

    We have adapted a nonhuman primate model of cocaine versus food choice to the rat species. To evaluate the procedure, we tested cocaine versus food choice under a variety of environmental manipulations as well as pharmacological pretreatments. Complete cocaine-choice dose-effect curves (0–1.0 mg/kg/infusion) were obtained for each condition under concurrent fixed ratio schedules of reinforcement. Percentage of responding emitted on the cocaine-reinforced lever was not affected significantly by removal of cocaine-associated visual or auditory cues, but it was decreased after removal of response-contingent or response-independent cocaine infusions. Cocaine choice was sensitive to the magnitude and fixed ratio requirement of both the cocaine and food reinforcers. We also tested the effects of acute (0.32, 0.56, 1.0, 1.8 mg/kg) and chronic (0.1, 0.32 mg/kg/hr) d-amphetamine treatment on cocaine choice. Acute and chronic d-amphetamine had opposite effects, with acute increasing and chronic decreasing cocaine choice, similar to observations in humans and in nonhuman primates. The results suggest feasibility and utility of the choice procedure in rats and support its comparability to similar procedures used in humans and monkeys. PMID:23319458

  3. Toxic Effects of Cannabis and Cannabinoids: Animal Data

    Directory of Open Access Journals (Sweden)

    Pierre Beaulieu

    2005-01-01

    Full Text Available The present article reviews the main toxic effects of cannabis and cannabinoids in animals. Toxic effects can be separated into acute and chronic classifications. Acute toxicity studies show that it is virtually impossible to die from acute administration of marijuana or tetrahydrocannabinol, the main psychoactive component of cannabis. Chronic toxicity involves lesions of airway and lung tissues, as well as problems of neurotoxicity, tolerance and dependence, and dysregulations in the immune and hormonal systems. Animal toxicity data, however, are difficult to extrapolate to humans.

  4. Demand Curves for Hypothetical Cocaine in Cocaine-Dependent Individuals

    Science.gov (United States)

    Bruner, Natalie R.; Johnson, Matthew W.

    2013-01-01

    Rationale Drug purchasing tasks have been successfully used to examine demand for hypothetical consumption of abused drugs including heroin, nicotine, and alcohol. In these tasks drug users make hypothetical choices whether to buy drugs, and if so, at what quantity, at various potential prices. These tasks allow for behavioral economic assessment of that drug's intensity of demand (preferred level of consumption at extremely low prices) and demand elasticity (sensitivity of consumption to price), among other metrics. However, a purchasing task for cocaine in cocaine-dependent individuals has not been investigated. Objectives This study examined a novel Cocaine Purchasing Task and the relation between resulting demand metrics and self-reported cocaine use data. Methods Participants completed a questionnaire assessing hypothetical purchases of cocaine units at prices ranging from $0.01 to $1,000. Demand curves were generated from responses on the Cocaine Purchasing Task. Correlations compared metrics from the demand curve to measures of real-world cocaine use. Results Group and individual data were well modeled by a demand curve function. The validity of the Cocaine Purchasing Task was supported by a significant correlation between the demand curve metrics of demand intensity and Omax (determined from Cocaine Purchasing Task data) and self-reported measures of cocaine use. Partial correlations revealed that after controlling for demand intensity, demand elasticity and the related measure, Pmax, were significantly correlated with real-world cocaine use. Conclusions Results indicate that the Cocaine Purchasing Task produces orderly demand curve data, and that these data relate to real-world measures of cocaine use. PMID:24217899

  5. Demand curves for hypothetical cocaine in cocaine-dependent individuals.

    Science.gov (United States)

    Bruner, Natalie R; Johnson, Matthew W

    2014-03-01

    Drug purchasing tasks have been successfully used to examine demand for hypothetical consumption of abused drugs including heroin, nicotine, and alcohol. In these tasks, drug users make hypothetical choices whether to buy drugs, and if so, at what quantity, at various potential prices. These tasks allow for behavioral economic assessment of that drug's intensity of demand (preferred level of consumption at extremely low prices) and demand elasticity (sensitivity of consumption to price), among other metrics. However, a purchasing task for cocaine in cocaine-dependent individuals has not been investigated. This study examined a novel Cocaine Purchasing Task and the relation between resulting demand metrics and self-reported cocaine use data. Participants completed a questionnaire assessing hypothetical purchases of cocaine units at prices ranging from $0.01 to $1,000. Demand curves were generated from responses on the Cocaine Purchasing Task. Correlations compared metrics from the demand curve to measures of real-world cocaine use. Group and individual data were well modeled by a demand curve function. The validity of the Cocaine Purchasing Task was supported by a significant correlation between the demand curve metrics of demand intensity and O max (determined from Cocaine Purchasing Task data) and self-reported measures of cocaine use. Partial correlations revealed that after controlling for demand intensity, demand elasticity and the related measure, P max, were significantly correlated with real-world cocaine use. Results indicate that the Cocaine Purchasing Task produces orderly demand curve data, and that these data relate to real-world measures of cocaine use.

  6. Buying cannabis in 'coffee shops'.

    Science.gov (United States)

    Monshouwer, Karin; Van Laar, Margriet; Vollebergh, Wilma A

    2011-03-01

    The key objective of Dutch cannabis policy is to prevent and limit the risks of cannabis consumption for users, their direct environment and society ('harm reduction'). This paper will focus on the tolerated sale of cannabis in 'coffee shops'. We give a brief overview of Dutch policy on coffee shops, its history and recent developments. Furthermore, we present epidemiological data that may be indicative of the effects of the coffee shop policy on cannabis and other drug use. Dutch coffee shop policy has become more restrictive in recent years and the number of coffee shops has decreased. Cannabis prevalence rates in the adult population are somewhat below the European average; the rate is relatively high among adolescents; and age of first use appears to be low. On a European level, the use of hard drugs in both the Dutch adult and adolescent population is average to low (except for ecstasy among adults). International comparisons do not suggest a strong, upward effect of the coffee shop system on levels of cannabis use, although prevalence rates among Dutch adolescents give rise to concern. Furthermore, the coffee shop system appears to be successful in separating the hard and soft drugs markets. Nevertheless, in recent years, issues concerning the involvement of organised crime and the public nuisance related to drug tourism have given rise to several restrictive measures on the local level and have sparked a political debate on the reform of Dutch drug policy. © 2011 Trimbos Institute.

  7. Solitary cannabis use in adolescence as a correlate and predictor of cannabis problems.

    Science.gov (United States)

    Creswell, Kasey G; Chung, Tammy; Clark, Duncan B; Martin, Christopher S

    2015-11-01

    Most adolescent cannabis use occurs in social settings among peers. Solitary cannabis use during adolescence may represent an informative divergence from normative behavior with important implications for understanding risk for cannabis problems. This longitudinal study examined associations of adolescent solitary cannabis use with levels of cannabis use and problems in adolescence and in young adulthood. Cannabis using-adolescents aged 12-18 were recruited from clinical programs (n=354; 43.8% female; 83.3% Caucasian) and community sources (n=93; 52.7% female; 80.6% Caucasian). Participants reported on cannabis use patterns and diagnostic symptoms at baseline and multiple follow-ups into young adulthood. Compared to social-only users, adolescent solitary cannabis users were more likely to be male and reported more frequent cannabis use and more DSM-IV cannabis use disorder (CUD) symptoms. Regression analyses showed that solitary cannabis use in adolescence predicted CUD symptom counts in young adulthood (age 25) after controlling for demographic variables and the frequency of adolescent cannabis use. However, solitary adolescent cannabis use was no longer predictive of age 25 CUD symptoms after additionally controlling for adolescent CUD symptoms. Solitary cannabis use is associated with greater cannabis use and problems during adolescence, but evidence is mixed that it predicts young adult cannabis problems. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. The teratogenicity of cocaine.

    Science.gov (United States)

    Fantel, A G; Macphail, B J

    1982-08-01

    Pregnancy rats and mice received high doses of cocaine hydrochloride by intraperitoneal injection. Despite treatment periods which included most of organogenesis, no increase in congenital abnormalities was observed. Rats showed significant reductions in maternal and fetal weights as well as increased resorption frequencies. Fetal edema was also found. Mice showed only decreased fetal weights with no increase in malformations.

  9. Hemp (Cannabis sativa L.).

    Science.gov (United States)

    Feeney, Mistianne; Punja, Zamir K

    2015-01-01

    Hemp (Cannabis sativa L.) suspension culture cells were transformed with Agrobacterium tumefaciens strain EHA101 carrying the binary plasmid pNOV3635. The plasmid contains a phosphomannose isomerase (PMI) selectable marker gene. Cells transformed with PMI are capable of metabolizing the selective agent mannose, whereas cells not expressing the gene are incapable of using the carbon source and will stop growing. Callus masses proliferating on selection medium were screened for PMI expression using a chlorophenol red assay. Genomic DNA was extracted from putatively transformed callus lines, and the presence of the PMI gene was confirmed using PCR and Southern hybridization. Using this method, an average transformation frequency of 31.23% ± 0.14 was obtained for all transformation experiments, with a range of 15.1-55.3%.

  10. Distance to Cannabis Shops and Age of Onset of Cannabis Use.

    Science.gov (United States)

    Palali, Ali; van Ours, Jan C

    2015-11-01

    In the Netherlands, cannabis use is quasi-legalized. Small quantities of cannabis can be bought in cannabis shops. We investigate how the distance to the nearest cannabis shop affects the age of onset of cannabis use. We use a mixed proportional hazard rate framework to take account of observable as well as unobservable characteristics that influence the uptake of cannabis. We find that distance matters. Individuals who grow up within 20 km of a cannabis shop have a lower age of onset. Copyright © 2014 John Wiley & Sons, Ltd.

  11. Emotion recognition during cocaine intoxication.

    Science.gov (United States)

    Kuypers, K P C; Steenbergen, L; Theunissen, E L; Toennes, S W; Ramaekers, J G

    2015-11-01

    Chronic or repeated cocaine use has been linked to impairments in social skills. It is not clear whether cocaine is responsible for this impairment or whether other factors, like polydrug use, distort the observed relation. We aimed to investigate this relation by means of a placebo-controlled experimental study. Additionally, associations between stressor-related activity (cortisol, cardiovascular parameters) induced by the biological stressor cocaine, and potential cocaine effects on emotion recognition were studied. Twenty-four healthy recreational cocaine users participated in this placebo-controlled within-subject study. Participants were tested between 1 and 2 h after treatment with oral cocaine (300 mg) or placebo. Emotion recognition of low and high intensity expressions of basic emotions (fear, anger, disgust, sadness, and happiness) was tested. Findings show that cocaine impaired recognition of negative emotions; this was mediated by the intensity of the presented emotions. When high intensity expressions of Anger and Disgust were shown, performance under influence of cocaine 'normalized' to placebo-like levels while it made identification of Sadness more difficult. The normalization of performance was most notable for participants with the largest cortisol responses in the cocaine condition compared to placebo. It was demonstrated that cocaine impairs recognition of negative emotions, depending on the intensity of emotion expression and cortisol response.

  12. Tips for Teens: The Truth about Cocaine

    Science.gov (United States)

    ... and intense cravings.Cocaine may give users atemporary illusion of power and energy,but it often leaves ... of dollars on cocaine each week. Stay in control. Cocaine impairs your judgment, which may lead to ...

  13. Enhanced Choice for Viewing Cocaine Pictures in Cocaine Addiction

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, S.J.; Goldstein, R.; Moeller, S.J.; Maloney, T. Parvaz, M.A.; Dunning, J.P.; Alia-Klein, N.; Woicik, P.A.; Hajcak, G.; Telang, F.; Wang, G.-J.; Volkow, N.D.; Goldstein, R.Z.

    2009-02-01

    Individuals with cocaine use disorder (CUD) chose cocaine over nondrug rewards. In two newly designed laboratory tasks with pictures, we document this modified choice outside of a cocaine administration paradigm. Choice for viewing cocaine, pleasant, unpleasant, or neutral pictures-under explicit contingencies (choice made between two fully visible side-by-side images) and under more implicit contingencies (selections made between pictures hidden under flipped-over cards)-was examined in 20 CUD and 20 matched healthy control subjects. Subjects also provided self-reported ratings of each picture's pleasantness and arousal. Under both contingencies, CUD subjects chose to view more cocaine pictures than control subjects, group differences that were not fully explained by the self-reported picture ratings. Furthermore, whereas CUD subjects choice for viewing cocaine pictures exceeded choice for viewing unpleasant pictures (but did not exceed choice for viewing pleasant pictures, in contrast to their self-reported ratings), healthy control subjects avoided viewing cocaine pictures as frequently as, or even more than, unpleasant pictures. Finally, CUD subjects with the most cocaine viewing selections, even when directly compared with selections of the pleasant pictures, also reported the most frequent recent cocaine use. Enhanced drug-related choice in cocaine addiction can be demonstrated even for nonpharmacologic (pictorial) stimuli. This choice, which is modulated by alternative stimuli, partly transcends self-reports (possibly indicative of a disconnect in cocaine addiction between self-reports and objective behavior) to provide an objective marker of addiction severity. Neuroimaging studies are needed to establish the neural underpinnings of such enhanced cocaine-related choice.

  14. Therapeutic Benefits of Cannabis: A Patient Survey

    OpenAIRE

    2014-01-01

    Clinical research regarding the therapeutic benefits of cannabis (“marijuana”) has been almost non-existent in the United States since cannabis was given Schedule I status in the Controlled Substances Act of 1970. In order to discover the benefits and adverse effects perceived by medical cannabis patients, especially with regards to chronic pain, we hand-delivered surveys to one hundred consecutive patients who were returning for yearly re-certification for medical cannabis use in Hawai‘i.

  15. Cocaine affects foraging behaviour and biogenic amine modulated behavioural reflexes in honey bees.

    Science.gov (United States)

    Søvik, Eirik; Even, Naïla; Radford, Catherine W; Barron, Andrew B

    2014-01-01

    In humans and other mammals, drugs of abuse alter the function of biogenic amine pathways in the brain leading to the subjective experience of reward and euphoria. Biogenic amine pathways are involved in reward processing across diverse animal phyla, however whether cocaine acts on these neurochemical pathways to cause similar rewarding behavioural effects in animal phyla other than mammals is unclear. Previously, it has been shown that bees are more likely to dance (a signal of perceived reward) when returning from a sucrose feeder after cocaine treatment. Here we examined more broadly whether cocaine altered reward-related behaviour, and biogenic amine modulated behavioural responses in bees. Bees developed a preference for locations at which they received cocaine, and when foraging at low quality sucrose feeders increase their foraging rate in response to cocaine treatment. Cocaine also increased reflexive proboscis extension to sucrose, and sting extension to electric shock. Both of these simple reflexes are modulated by biogenic amines. This shows that systemic cocaine treatment alters behavioural responses that are modulated by biogenic amines in insects. Since insect reward responses involve both octopamine and dopamine signalling, we conclude that cocaine treatment altered diverse reward-related aspects of behaviour in bees. We discuss the implications of these results for understanding the ecology of cocaine as a plant defence compound. Our findings further validate the honey bee as a model system for understanding the behavioural impacts of cocaine, and potentially other drugs of abuse.

  16. Cocaine affects foraging behaviour and biogenic amine modulated behavioural reflexes in honey bees

    Directory of Open Access Journals (Sweden)

    Eirik Søvik

    2014-11-01

    Full Text Available In humans and other mammals, drugs of abuse alter the function of biogenic amine pathways in the brain leading to the subjective experience of reward and euphoria. Biogenic amine pathways are involved in reward processing across diverse animal phyla, however whether cocaine acts on these neurochemical pathways to cause similar rewarding behavioural effects in animal phyla other than mammals is unclear. Previously, it has been shown that bees are more likely to dance (a signal of perceived reward when returning from a sucrose feeder after cocaine treatment. Here we examined more broadly whether cocaine altered reward-related behaviour, and biogenic amine modulated behavioural responses in bees. Bees developed a preference for locations at which they received cocaine, and when foraging at low quality sucrose feeders increase their foraging rate in response to cocaine treatment. Cocaine also increased reflexive proboscis extension to sucrose, and sting extension to electric shock. Both of these simple reflexes are modulated by biogenic amines. This shows that systemic cocaine treatment alters behavioural responses that are modulated by biogenic amines in insects. Since insect reward responses involve both octopamine and dopamine signalling, we conclude that cocaine treatment altered diverse reward-related aspects of behaviour in bees. We discuss the implications of these results for understanding the ecology of cocaine as a plant defence compound. Our findings further validate the honey bee as a model system for understanding the behavioural impacts of cocaine, and potentially other drugs of abuse.

  17. Effect of cocaine dependence on brain connections: Clinical implications

    Science.gov (United States)

    Ma, Liangsuo; Steinberg, Joel L.; Moeller, F. Gerard; Johns, Sade E.; Narayana, Ponnada A.

    2015-01-01

    Cocaine dependence (CD) is associated with several cognitive deficits. Accumulating evidence, based on human and animal studies, has led to models for interpreting the neural basis of cognitive functions as interactions between functionally related brain regions. In this review, we focus on the magnetic resonance imaging (MRI) studies using brain connectivity techniques as related to CD. The majority of these brain connectivity studies indicated that cocaine use is associated with altered brain connectivity between different structures, including cortical-striatal regions and default mode network. In cocaine users, some of the altered brain connectivity measures are associated with behavioral performance, history of drug use, and treatment outcome. The implications of these brain connectivity findings to the treatment of CD and the pros and cons of the major brain connectivity techniques are discussed. Finally potential future directions in cocaine use disorder research using brain connectivity techniques are briefly described. PMID:26512421

  18. Novel C-1 Substituted Cocaine Analogs Unlike Cocaine or Benztropine

    OpenAIRE

    Reith, Maarten E. A.; Ali, Solav; Hashim, Audrey; Sheikh, Imran S.; Theddu, Naresh; Gaddiraju, Narendra V.; Mehrotra, Suneet; Schmitt, Kyle C.; Murray, Thomas F.; Sershen, Henry; Unterwald, Ellen M.; Davis, Franklin A.

    2012-01-01

    Despite a wealth of information on cocaine-like compounds, there is no information on cocaine analogs with substitutions at C-1. Here, we report on (R)-(−)-cocaine analogs with various C-1 substituents: methyl (2), ethyl (3), n-propyl (4), n-pentyl (5), and phenyl (6). Analog 2 was equipotent to cocaine as an inhibitor of the dopamine transporter (DAT), whereas 3 and 6 were 3- and 10-fold more potent, respectively. None of the analogs, however, stimulated mouse locomotor activity, in contrast...

  19. fMRI study of neural sensitization to hedonic stimuli in long-term, daily cannabis users.

    Science.gov (United States)

    Filbey, Francesca M; Dunlop, Joseph; Ketcherside, Ariel; Baine, Jessica; Rhinehardt, Tyler; Kuhn, Brittany; DeWitt, Sam; Alvi, Talha

    2016-10-01

    Although there is emergent evidence illustrating neural sensitivity to cannabis cues in cannabis users, the specificity of this effect to cannabis cues as opposed to a generalized hyper-sensitivity to hedonic stimuli has not yet been directly tested. Using fMRI, we presented 53 daily, long-term cannabis users and 68 non-using controls visual and tactile cues for cannabis, a natural reward, and, a sensory-perceptual control object to evaluate brain response to hedonic stimuli in cannabis users. The results showed an interaction between group and reward type such that the users had greater response during cannabis cues relative to natural reward cues (i.e., fruit) in the orbitofrontal cortex, striatum, anterior cingulate gyrus, and ventral tegmental area compared to non-users (cluster-threshold z = 2.3, P behavior correlations between neural response to cannabis cues in fronto-striatal-temporal regions and subjective craving, marijuana-related problems, withdrawal symptoms, and levels of THC metabolites (cluster-threshold z = 2.3, P < 0.05). These findings demonstrate hyper-responsivity, and, specificity of brain response to cannabis cues in long-term cannabis users that are above that of response to natural reward cues. These observations are concordant with incentive sensitization models suggesting sensitization of mesocorticolimbic regions and disruption of natural reward processes following drug use. Although the cross-sectional nature of this study does not provide information on causality, the positive correlations between neural response and indicators of cannabis use (i.e., THC levels) suggest that alterations in the reward system are, in part, related to cannabis use. Hum Brain Mapp 37:3431-3443, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  20. Cannabis use, cognitive functioning and behaviour problems

    NARCIS (Netherlands)

    Griffith-Lendering, Merel Frederique Heleen

    2013-01-01

    During early adolescence, there is no association between internalizing behaviour and cannabis use. There is an association between externalizing behaviour and cannabis use, where externalizing behaviour precedes cannabis use rather than the other way around. Secondly, during adolescence, there is a

  1. Long term stability of cannabis resin and cannabis extracts

    DEFF Research Database (Denmark)

    Lindholst, Christian

    2010-01-01

      The aim of the present study was to investigate the stability of cannabinoids in cannabis resin slabs and cannabis extracts upon long-term storage. The levels of tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD) and cannabigerol (CBG) on both neutral and acidic form were measured...... at room temperature, 4 °C and - 20 °C for up to 4 years. Acidic THC degrades exponentially via decarboxylation with concentration halve-lives of approximately 330 and 462 days in daylight and darkness, respectively. The degradation of neutral THC seems to occur somewhat slower. When cannabinoids were...... stored in extracted form at room temperature the degradation rate of acidic THC increased significantly relative to resin material with concentration halve-lives of 35 and 91 days in daylight and darkness, respectively. Once cannabis material is extracted into organic solvents, care should be taken...

  2. Cocaine Causes Apoptotic Death in Rat Mesencephalon and Striatum Primary Cultures.

    Science.gov (United States)

    Lepsch, Lucilia B; Planeta, Cleopatra S; Scavone, Critoforo

    2015-01-01

    To study cocaine's toxic effects in vitro, we have used primary mesencephalic and striatal cultures from rat embryonic brain. Treatment with cocaine causes a dramatic increase in DNA fragmentation in both primary cultures. The toxicity induced by cocaine was paralleled with a concomitant decrease in the microtubule associated protein 2 (MAP2) and/or neuronal nucleus protein (NeuN) staining. We also observed in both cultures that the cell death caused by cocaine was induced by an apoptotic mechanism, confirmed by TUNEL assay. Therefore, the present paper shows that cocaine causes apoptotic cell death and inhibition of the neurite prolongation in striatal and mesencephalic cell culture. These data suggest that if similar neuronal damage could be produced in the developing human brain, it could account for the qualitative or quantitative defects in neuronal pathways that cause a major handicap in brain function following prenatal exposure to cocaine.

  3. Public opinion and medical cannabis policies: examining the role of underlying beliefs and national medical cannabis policies

    OpenAIRE

    SZNITMAN, SHARON R.; Bretteville-Jensen, Anne Line

    2015-01-01

    Background Debate about medical cannabis legalization are typically informed by three beliefs: (1) cannabis has medical effects, (2) medical cannabis is addictive and (3) medical cannabis legalization leads to increased used of cannabis for recreational purposes (spillover effects). We examined how strongly these beliefs are associated with public support for medical cannabis legalization and whether this association differs across divergent medical cannabis policy regimes. Methods Robust reg...

  4. Pneumorachis after cocaine sniffing

    Directory of Open Access Journals (Sweden)

    S. Challita

    2014-01-01

    Full Text Available Air in the epidural space is called pneumorachis. The usual mechanism of pneumorachis is air diffusion from the mediastinal tissue layers through the inter-vertebral foramen. Alternatively, air can diffuse directly after spine traumas (e.g., blunt deceleration with vertebral dislocation or medical procedures. Several mechanisms could explain pneumomediastinum and pneumorachis after cocaine sniffing. Passive apnea and/or cough that occur after sniffing can cause intra alveolar hyper-pressure, which is responsible for alveolar rupture and air diffusion. Another mechanism is alveolar wall fragility and rupture induced by repeated cocaine sniffing, in turn causing air diffusion to the mediastinum, sub-cutaneous tissues and the epidural space. The diagnosis is usually made on Chest tomography scan. Management consists in close monitoring in the intensive care unit to detect aggravation of pneumomediastinum and pneumorachis, which would require surgical management. Supplemental nasal oxygen can be given to accelerate nitrogen washout. We present a case of a 28 years old male who presented to the emergency department for chest pain directly after sniffing cocaine. A computed tomography scan of the chest showed pneumomediastinum, pneumorachis and sub-cutaneous emphysema. The patient was admitted for 24 h: after that delay, surveillance chest tomodensitometry showed stability, and he could be discharged without further treatment.

  5. Finding cannabinoids in hair does not prove cannabis consumption.

    Science.gov (United States)

    Moosmann, Bjoern; Roth, Nadine; Auwärter, Volker

    2015-10-07

    Hair analysis for cannabinoids is extensively applied in workplace drug testing and in child protection cases, although valid data on incorporation of the main analytical targets, ∆9-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-THC (THC-COOH), into human hair is widely missing. Furthermore, ∆9-tetrahydrocannabinolic acid A (THCA-A), the biogenetic precursor of THC, is found in the hair of persons who solely handled cannabis material. In the light of the serious consequences of positive test results the mechanisms of drug incorporation into hair urgently need scientific evaluation. Here we show that neither THC nor THCA-A are incorporated into human hair in relevant amounts after systemic uptake. THC-COOH, which is considered an incontestable proof of THC uptake according to the current scientific doctrine, was found in hair, but was also present in older hair segments, which already grew before the oral THC intake and in sebum/sweat samples. Our studies show that all three cannabinoids can be present in hair of non-consuming individuals because of transfer through cannabis consumers, via their hands, their sebum/sweat, or cannabis smoke. This is of concern for e.g. child-custody cases as cannabinoid findings in a child's hair may be caused by close contact to cannabis consumers rather than by inhalation of side-stream smoke.

  6. Cannabis Smoking and Cardiovascular Health: It's Complicated.

    Science.gov (United States)

    Piano, M R

    2017-08-01

    Many states have legalized cannabis use for treatment of certain medical conditions or have legalized cannabis for recreational use. Consequently, cannabis use prevalence has escalated, giving rise to concerns about potential health effects. Cannabis smoking remains the most prevalent route of administration and is associated with inhalation of chemical toxicants. The aim of this article is to summarize the effects of cannabis smoking on the vasculature and occurrence of cardiovascular (CV) events such as myocardial infarction (MI) and stroke. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  7. Medicinal cannabis: moving the debate forward.

    Science.gov (United States)

    Newton-Howes, Giles; McBride, Sam

    2016-11-18

    There has been increased interest in cannabis as a medicine both nationally and internationally. Internationally, cannabis is accepted as a medication for a variety of purposes in a variety of legal guises and this, associated with anecdotes of the utility of cannabis as medication has led for calls for it to be 'medicalised' in New Zealand. This viewpoint discusses the issues associated with this approach to accessing cannabis and some of the difficulties that may be associated with it. It is important doctors are at the forefront of the debate surrounding medicalised cannabis. Recommendations as to the ongoing debate are offered.

  8. Dose-Dependent Cannabis Use, Depressive Symptoms, and FAAH Genotype Predict Sleep Quality in Emerging Adults: A Pilot Study

    Science.gov (United States)

    Maple, Kristin E.; McDaniel, Kymberly A.; Shollenbarger, Skyler G.; Lisdahl, Krista M.

    2017-01-01

    Background Cannabis has been shown to affect sleep in humans. Findings from animal studies indicate that higher endocannabinoid levels promote sleep, suggesting that chronic use of cannabis, which downregulates endocannabinoid activity, may disrupt sleep. Objectives This study sought to determine if past year cannabis use and genes that regulate endocannabinoid signaling, FAAH rs324420 and CNR1 rs2180619, predicted sleep quality. As depression has been previously associated with both cannabis and sleep, the secondary aim was to determine if depressive symptoms moderated or mediated these relationships. Methods Data were collected from 41 emerging adult (ages 18–25) cannabis users. Exclusion criteria included Axis I disorders (besides SUD) and medical and neurologic disorders. Relationships were tested using multiple regressions, controlling for demographic variables, past year substance use, and length of cannabis abstinence. Results Greater past year cannabis use and FAAH C/C genotype were associated with poorer sleep quality. CNR1 genotype did not significantly predict sleep quality. Depressive symptoms moderated the relationship between cannabis use and sleep at a non-significant trend level, such that participants with the greatest cannabis use and most depressive symptoms reported the most impaired sleep. Depressive symptoms mediated the relationship between FAAH genotype and sleep quality. Conclusions This study demonstrates a dose-dependent relationship between chronic cannabis use and reported sleep quality, independent of abstinence length. Furthermore, it provides novel evidence that depressive symptoms mediate the relationship between FAAH genotype and sleep quality in humans. These findings suggest potential targets to impact sleep disruptions in cannabis users. PMID:27074158

  9. Rational design of an enzyme mutant for anti-cocaine therapeutics

    Science.gov (United States)

    Zheng, Fang; Zhan, Chang-Guo

    2008-09-01

    (-)-Cocaine is a widely abused drug and there is no available anti-cocaine therapeutic. The disastrous medical and social consequences of cocaine addiction have made the development of an effective pharmacological treatment a high priority. An ideal anti-cocaine medication would be to accelerate (-)-cocaine metabolism producing biologically inactive metabolites. The main metabolic pathway of cocaine in body is the hydrolysis at its benzoyl ester group. Reviewed in this article is the state-of-the-art computational design of high-activity mutants of human butyrylcholinesterase (BChE) against (-)-cocaine. The computational design of BChE mutants have been based on not only the structure of the enzyme, but also the detailed catalytic mechanisms for BChE-catalyzed hydrolysis of (-)-cocaine and (+)-cocaine. Computational studies of the detailed catalytic mechanisms and the structure-and-mechanism-based computational design have been carried out through the combined use of a variety of state-of-the-art techniques of molecular modeling. By using the computational insights into the catalytic mechanisms, a recently developed unique computational design strategy based on the simulation of the rate-determining transition state has been employed to design high-activity mutants of human BChE for hydrolysis of (-)-cocaine, leading to the exciting discovery of BChE mutants with a considerably improved catalytic efficiency against (-)-cocaine. One of the discovered BChE mutants (i.e., A199S/S287G/A328W/Y332G) has a ˜456-fold improved catalytic efficiency against (-)-cocaine. The encouraging outcome of the computational design and discovery effort demonstrates that the unique computational design approach based on the transition-state simulation is promising for rational enzyme redesign and drug discovery.

  10. An aptamer folding-based sensory platform decorated with nanoparticles for simple cocaine testing.

    Science.gov (United States)

    Guler, Emine; Bozokalfa, Guliz; Demir, Bilal; Gumus, Zinar Pinar; Guler, Bahar; Aldemir, Ebru; Timur, Suna; Coskunol, Hakan

    2017-04-01

    The consumption of illicit drugs such as cannabis, cocaine, and amphetamines is still a major health and social problem, creating an abuse in adults especially. Novel techniques which estimate the drug of abuse are needed for the detection of newly revealed psychoactive drugs. Herein, we have constructed a combinatorial platform by using quantum dots (QDs) and gold nanoparticles (AuNPs) as well as a functional aptamer which selectively recognizes cocaine and its metabolite benzoylecgonine (BE). We have called it an aptamer folding-based sensory device (AFSD). For the fabrication of AFSD, QDs were initially immobilized onto the poly-L-lysine coated μ-well surfaces. Then, the AuNP-aptamer conjugates were bound to the QDs. The addition of cocaine or BE caused a change in the aptamer structure which induced the close interaction of AuNPs with the QDs. Hence, quenching of the fluorescence of QDs was observed depending on the analyte amount. The linearity of cocaine and BE was 1.0-10 nM and 1.0-25 μM, respectively. Moreover, the limits of detection for cocaine and BE were calculated as 0.138 nM and 1.66 μM. The selectivity was tested by using different interfering substances (methamphetamine, bovine serum albumin, codeine, and 3-acetamidophenol). To investigate the use of AFSD in artificial urine matrix, cocaine/BE spiked samples were applied. Also, confirmatory analyses by using high performance liquid chromatography were performed. It is shown that AFSD has a good potential for testing the cocaine abuse and can be easily adapted for detection of various addictive drugs by changing the aptamer according to desired analytes. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  11. The Importance of Family Relations for Cannabis Users: The Case of Serbian Adolescents

    Directory of Open Access Journals (Sweden)

    Zorica Terzic Supic

    2013-03-01

    Full Text Available Background: Adolescence is transitional stage of physical and mental human development occuring between childhood and adult life. Social interactions and environmental factors together are important predictors of adolescent cannabis use. This study aimed to examine the relationship between the social determinants and adolescents behavior with cannabis consumption.Methods: A cross sectional study as part of the European School Survey Project on Alcohol and other Drugs was conducted among 6.150 adolescents aged 16 years in three regions of Serbia, and three types of schools (gymnasium, vocational – professional, and vocational – handicraft during May – June 2008. A multivariate logistic regression analysis was carried out to obtain adjusted odds ratios with 95% confidence intervals in which the dependent variable was cannabis consumption non-user and user.Results: Among 6.7% of adolescents who had tried cannabis at least one in their lives, boys were more involved in cannabis use than girls, especially boys from gymnasium school. Well off family, lower education of mother, worse relations with parents were significantly associated with cannabis use (P < 0.05. Behaviors like skipping from schools, frequent evening outs, and playing on slot machines were also related to cannabis use (P < 0.05.Conclusions: The study confirmed the importance of family relationship development. Drug use preventive programmes should include building interpersonal trust in a family lifecycle and school culture.

  12. Passive inhalation of cannabis smoke

    Energy Technology Data Exchange (ETDEWEB)

    Law, B.; Mason, P.A.; Moffat, A.C.; King, L.J.; Marks, V.

    1984-09-01

    Six volunteers each smoked simultaneously, in a small unventilated room (volume 27 950 liter), a cannabis cigarette containing 17.1 mg delta 9-tetrahydrocannabinol (THC). A further four subjects - passive inhalers - remained in the room during smoking and afterwards for a total of 3 h. Blood and urine samples were taken from all ten subjects and analyzed by radioimmunoassay for THC metabolites. The blood samples from the passive subjects taken up to 3 h after the start of exposure to cannabis smoke showed a complete absence of cannabinoids. In contrast, their urine samples taken up to 6 h after exposure showed significant concentrations of cannabinoid metabolites (less than or equal to 6.8 ng ml-1). These data, taken with the results of other workers, show passive inhalation of cannabis smoke to be possible. These results have important implications for forensic toxicologists who are frequently called upon to interpret cannabinoid levels in body fluids.

  13. A hybrid liquid chromatography-mass spectrometry strategy in a forensic laboratory for opioid, cocaine and amphetamine classes in human urine using a hybrid linear ion trap-triple quadrupole mass spectrometer.

    Science.gov (United States)

    Dowling, Geraldine; Regan, Liam; Tierney, Julie; Nangle, Michael

    2010-10-29

    A rapid method has been developed to analyse morphine, codeine, morphine-3-glucuronide, 6-monoacetylmorphine, cocaine, benzoylegonine, buprenorphine, dihydrocodeine, cocaethylene, 3,4-methylenedioxyamphetamine, ketamine, 3,4-methylenedioxymethamphetamine, pseudoephedrine, lignocaine, benzylpiperazine, methamphetamine, amphetamine, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine and methadone in human urine. Urine samples were diluted with methanol:water (1:1, v/v) and sample aliquots were analysed by hybrid linear ion trap-triple quadrupole mass spectrometry with a runtime of 12.5 min. Multiple reaction monitoring (MRM) as survey scan and an enhanced product ion (EPI) scan as dependent scan were performed in an information-dependent acquisition (IDA) experiment. Finally, drug identification and confirmation was carried out by library search with a developed in-house MS/MS library based on EPI spectra at a collision energy spread of 35±15 in positive mode and MRM ratios. The method was validated in urine, according to the criteria defined in Commission Decision 2002/657/EC. At least two MRM transitions for each substance were monitored in addition to EPI spectra and deuterated analytes were used as internal standards for quantitation. The reporting level was 0.05 μg mL(-1) for the range of analytes tested. The regression coefficients (r(2)) for the calibration curves (0-4 μg mL(-1)) in the study were ≥0.98. The method proved to be simple and time efficient and was implemented as an analytical strategy for the illicit drug monitoring of opioids, cocaines and amphetamines in criminal samples from crime offenders, abusers or victims in the Republic of Ireland. To the best of our knowledge there are no hybrid LC-MS applications using MRM mode and product ion spectra in the linear ion trap mode for opioids, cocaines or amphetamines with validation data in urine.

  14. A mechanism for the inhibition of neural progenitor cell proliferation by cocaine.

    Directory of Open Access Journals (Sweden)

    Chun-Ting Lee

    2008-06-01

    Full Text Available BACKGROUND: Prenatal exposure of the developing brain to cocaine causes morphological and behavioral abnormalities. Recent studies indicate that cocaine-induced proliferation inhibition and/or apoptosis in neural progenitor cells may play a pivotal role in causing these abnormalities. To understand the molecular mechanism through which cocaine inhibits cell proliferation in neural progenitors, we sought to identify the molecules that are responsible for mediating the effect of cocaine on cell cycle regulation. METHODS AND FINDINGS: Microarray analysis followed by quantitative real-time reverse transcription PCR was used to screen cocaine-responsive and cell cycle-related genes in a neural progenitor cell line where cocaine exposure caused a robust anti-proliferative effect by interfering with the G1-to-S transition. Cyclin A2, among genes related to the G1-to-S cell cycle transition, was most strongly down-regulated by cocaine. Down-regulation of cyclin A was also found in cocaine-treated human primary neural and A2B5+ progenitor cells, as well as in rat fetal brains exposed to cocaine in utero. Reversing cyclin A down-regulation by gene transfer counteracted the proliferation inhibition caused by cocaine. Further, we found that cocaine-induced accumulation of reactive oxygen species, which involves N-oxidation of cocaine via cytochrome P450, promotes cyclin A down-regulation by causing an endoplasmic reticulum (ER stress response, as indicated by increased phosphorylation of eIF2alpha and expression of ATF4. In the developing rat brain, the P450 inhibitor cimetidine counteracted cocaine-induced inhibition of neural progenitor cell proliferation as well as down-regulation of cyclin A. CONCLUSIONS: Our results demonstrate that down-regulation of cyclin A underlies cocaine-induced proliferation inhibition in neural progenitors. The down-regulation of cyclin A is initiated by N-oxidative metabolism of cocaine and consequent ER stress. Inhibition of

  15. Dopaminergic mechanisms of cocaine use

    NARCIS (Netherlands)

    Veeneman - Rijkens, M.M.J.

    2011-01-01

    Cocaine addiction is an enormous medical problem for which there is currently no effective pharmacotherapy. In order to develop treatments for this disorder, it is essential to understand the neurobiological underpinnings of cocaine addiction. One of the behavioral characteristics of addiction is an

  16. An fMRI-Based Neural Signature of Decisions to Smoke Cannabis.

    Science.gov (United States)

    Bedi, Gillinder; Lindquist, Martin A; Haney, Margaret

    2015-11-01

    Drug dependence may be at its core a pathology of choice, defined by continued decisions to use drugs irrespective of negative consequences. Despite evidence of dysregulated decision making in addiction, little is known about the neural processes underlying the most clinically relevant decisions drug users make: decisions to use drugs. Here, we combined functional magnetic resonance imaging (fMRI), machine learning, and human laboratory drug administration to investigate neural activation underlying decisions to smoke cannabis. Nontreatment-seeking daily cannabis smokers completed an fMRI choice task, making repeated decisions to purchase or decline 1-12 placebo or active cannabis 'puffs' ($0.25-$5/puff). One randomly selected decision was implemented. If the selected choice had been bought, the cost was deducted from study earnings and the purchased cannabis smoked in the laboratory; alternatively, the participant remained in the laboratory without cannabis. Machine learning with leave-one-subject-out cross-validation identified distributed neural activation patterns discriminating decisions to buy cannabis from declined offers. A total of 21 participants were included in behavioral analyses; 17 purchased cannabis and were thus included in fMRI analyses. Purchasing varied lawfully with dose and cost. The classifier discriminated with 100% accuracy between fMRI activation patterns for purchased vs declined cannabis at the level of the individual. Dorsal striatum, insula, posterior parietal regions, anterior and posterior cingulate, and dorsolateral prefrontal cortex all contributed reliably to this neural signature of decisions to smoke cannabis. These findings provide the basis for a brain-based characterization of drug-related decision making in drug abuse, including effects of psychological and pharmacological interventions on these processes.

  17. Cannabis use expectancies mediate the relation between depressive symptoms and cannabis use among cannabis-dependent veterans.

    Science.gov (United States)

    Farris, Samantha G; Zvolensky, Michael J; Boden, Matthew Tyler; Bonn-Miller, Marcel O

    2014-01-01

    The current study examined the cross-sectional associations between depressive symptoms and cannabis use, and the mediating role of positive and negative expectancies of cannabis use. Participants (n = 100) were cannabis-dependent veterans recruited as part of a larger self-guided cannabis quit study. Baseline (prequit) data were used. Depressive symptoms were assessed using the General Depression subscale of the Inventory of Depression and Anxiety Symptoms (IDAS), and cannabis use expectancies were assessed using the Marijuana Effect Expectancies Questionnaire. Quantity of cannabis use in the past 90 days was assessed with the Timeline Follow-Back. A parallel multiple mediation path analysis was conducted to simultaneously examine the effects of positive and negative expectancies as mediators of the relation between IDAS-Depression and prequit cannabis use. Results indicated that depressive symptoms were indirectly related to cannabis use through positive, but not negative, expectancies. This effect was unique to IDAS-Dysphoria symptoms. Depressive symptoms, particularly cognitive-affective symptom features, may be important to consider in better understanding positive cannabis effect expectancies among veterans in regard to cannabis use.

  18. Posttraumatic stress disorder and cannabis use characteristics among military veterans with cannabis dependence.

    Science.gov (United States)

    Boden, Matthew Tyler; Babson, Kimberly A; Vujanovic, Anka A; Short, Nicole A; Bonn-Miller, Marcel O

    2013-01-01

    The present study is the first to explore links between PTSD and cannabis use characteristics immediately prior to a cannabis quit attempt, including motives, use problems, withdrawal, and craving. Measures of PTSD diagnosis, symptom severity, and cannabis use characteristics were administered to a sample of cannabis dependent military veterans (n = 94). Hypotheses were tested with a series of analyses of variance and covariance and hierarchical multiple regressions with Bonferroni corrections. Analyses were conducted with and without adjusting for variance shared with substance use (cannabis, alcohol, tobacco) in the previous 90 days, and co-occurring mood, anxiety, and substance use diagnoses. Compared to participants without PTSD, participants with PTSD reported significantly increased: (a) use of cannabis to cope, (b) severity of cannabis withdrawal, and (c) experiences of craving related to compulsivity, emotionality, and anticipation, with findings regarding coping and craving remaining significant after adjusting for covariates. Among the total sample, PTSD symptom severity was positively associated with (a) use of cannabis to cope, (b) cannabis use problems, (c) severity of cannabis withdrawal, and (d) experiences of craving related to compulsivity and emotionality, with findings regarding withdrawal and emotion-related craving remaining significant after adjusting for covariates. Thus, links between PTSD and using cannabis to cope, severity of cannabis withdrawal, and especially craving appear robust across measures of PTSD and analytical method. The results of this study provide support for models that posit a pernicious feedback loop between PTSD symptomatology and cannabis use. Copyright © American Academy of Addiction Psychiatry.

  19. Longitudinal Effects of Embryonic Exposure to Cocaine on Morphology, Cardiovascular Physiology, and Behavior in Zebrafish

    Directory of Open Access Journals (Sweden)

    Eric J. Mersereau

    2016-05-01

    Full Text Available A sizeable portion of the societal drain from cocaine abuse results from the complications of in utero drug exposure. Because of challenges in using humans and mammalian model organisms as test subjects, much debate remains about the impact of in utero cocaine exposure. Zebrafish offer a number of advantages as a model in longitudinal toxicology studies and are quite sensitive physiologically and behaviorally to cocaine. In this study, we have used zebrafish to model the effects of embryonic pre-exposure to cocaine on development and on subsequent cardiovascular physiology and cocaine-induced conditioned place preference (CPP in longitudinal adults. Larval fish showed a progressive decrease in telencephalic size with increased doses of cocaine. These treated larvae also showed a dose dependent response in heart rate that persisted 24 h after drug cessation. Embryonic cocaine exposure had little effect on overall health of longitudinal adults, but subtle changes in cardiovascular physiology were seen including decreased sensitivity to isoproterenol and increased sensitivity to cocaine. These longitudinal adult fish also showed an embryonic dose-dependent change in CPP behavior, suggesting an increased sensitivity. These studies clearly show that pre-exposure during embryonic development affects subsequent cocaine sensitivity in longitudinal adults.

  20. Longitudinal Effects of Embryonic Exposure to Cocaine on Morphology, Cardiovascular Physiology, and Behavior in Zebrafish.

    Science.gov (United States)

    Mersereau, Eric J; Boyle, Cody A; Poitra, Shelby; Espinoza, Ana; Seiler, Joclyn; Longie, Robert; Delvo, Lisa; Szarkowski, Megan; Maliske, Joshua; Chalmers, Sarah; Darland, Diane C; Darland, Tristan

    2016-05-31

    A sizeable portion of the societal drain from cocaine abuse results from the complications of in utero drug exposure. Because of challenges in using humans and mammalian model organisms as test subjects, much debate remains about the impact of in utero cocaine exposure. Zebrafish offer a number of advantages as a model in longitudinal toxicology studies and are quite sensitive physiologically and behaviorally to cocaine. In this study, we have used zebrafish to model the effects of embryonic pre-exposure to cocaine on development and on subsequent cardiovascular physiology and cocaine-induced conditioned place preference (CPP) in longitudinal adults. Larval fish showed a progressive decrease in telencephalic size with increased doses of cocaine. These treated larvae also showed a dose dependent response in heart rate that persisted 24 h after drug cessation. Embryonic cocaine exposure had little effect on overall health of longitudinal adults, but subtle changes in cardiovascular physiology were seen including decreased sensitivity to isoproterenol and increased sensitivity to cocaine. These longitudinal adult fish also showed an embryonic dose-dependent change in CPP behavior, suggesting an increased sensitivity. These studies clearly show that pre-exposure during embryonic development affects subsequent cocaine sensitivity in longitudinal adults.

  1. Molecular Mechanisms of Cannabis Signaling in the Brain.

    Science.gov (United States)

    Ronan, Patrick J; Wongngamnit, Narin; Beresford, Thomas P

    2016-01-01

    Cannabis has been cultivated and used by humans for thousands of years. Research for decades was focused on understanding the mechanisms of an illegal/addictive drug. This led to the discovery of the vast endocannabinoid system. Research has now shifted to understanding fundamental biological questions related to one of the most widespread signaling systems in both the brain and the body. Our understanding of cannabinoid signaling has advanced significantly in the last two decades. In this review, we discuss the state of knowledge on mechanisms of Cannabis signaling in the brain and the modulation of key brain neurotransmitter systems involved in both brain reward/addiction and psychiatric disorders. It is highly probable that various cannabinoids will be found to be efficacious in the treatment of a number of psychiatric disorders. However, while there is clearly much potential, marijuana has not been properly vetted by the medical-scientific evaluation process and there are clearly a range of potentially adverse side-effects-including addiction. We are at crossroads for research on endocannabinoid function and therapeutics (including the use of exogenous treatments such as Cannabis). With over 100 cannabinoid constituents, the majority of which have not been studied, there is much Cannabis research yet to be done. With more states legalizing both the medicinal and recreational use of marijuana the rigorous scientific investigation into cannabinoid signaling is imperative. Copyright © 2016. Published by Elsevier Inc.

  2. Cocaine – Characteristics and addiction

    Directory of Open Access Journals (Sweden)

    Katarzyna Girczys-Połedniok

    2016-08-01

    Full Text Available Cocaine use leads to health, social and legal problems. The aim of this paper is to discuss cocaine action, addicts characteristics, use patterns and consequences, as well as addiction treatment methods. A literature review was based on the Medline, PubMed, Polish Medical Bibliography databases and the Silesian Library resources. The Police and Central Statistical Office statistics, as well as the World Health Organization, the European Monitoring Centre for Drugs and Drug Addiction and the National Office for Combating Drug Addiction reports were used. Cocaine leads to mood improvement, appetite decrease, physical and intellectual activity enhancement, euphoria, inflated self-esteem, social networking ease and increased sexual desire. Cocaine hydrochloride is mainly used intranasaly, but also as intravenous and subcutaneous injections. Cocaine use and first addiction treatment fall in later age compared to other psychoactive substances. There is a high men to women ratio among addicts. There is a relationship between cocaine addiction, the presence of other disorders and genetic predisposition to addiction development. Polish reports indicate higher popularity of cocaine among people with a high economic and social status. Although Poland is a country with the low percentage of cocaine use, its popularity is growing. The consequences of cocaine use concern somatic and mental health problems, socioeconomic and legal conditions. The drug plays a role in crimes and traffic accidents. Because of the risks associated with cocaine use, it has been listed in a register of drugs attached to the Act on Counteracting Drug Addiction. Addiction treatment includes psychological, pharmacological and harm reduction strategies. Med Pr 2016;67(4:537–544

  3. Cannabis for Pain and Headaches: Primer.

    Science.gov (United States)

    Kim, Philip S; Fishman, Michael A

    2017-04-01

    Marijuana has been used both medicinally and recreationally since ancient times and interest in its compounds for pain relief has increased in recent years. The identification of our own intrinsic, endocannabinoid system has laid the foundation for further research. Synthetic cannabinoids are being developed and synthesized from the marijuana plant such as dronabinol and nabilone. The US Food and Drug Administration approved the use of dronabinol and nabilone for chemotherapy-associated nausea and vomiting and HIV (Human Immunodeficiency Virus) wasting. Nabiximols is a cannabis extract that is approved for the treatment of spasticity and intractable pain in Canada and the UK. Further clinical trials are studying the effect of marijuana extracts for seizure disorders. Phytocannabinoids have been identified as key compounds involved in analgesia and anti-inflammatory effects. Other compounds found in cannabis such as flavonoids and terpenes are also being investigated as to their individual or synergistic effects. This article will review relevant literature regarding medical use of marijuana and cannabinoid pharmaceuticals with an emphasis on pain and headaches.

  4. Cannabis Mobile Apps: A Content Analysis.

    Science.gov (United States)

    Ramo, Danielle E; Popova, Lucy; Grana, Rachel; Zhao, Shirley; Chavez, Kathryn

    2015-08-12

    Mobile technology is pervasive and widely used to obtain information about drugs such as cannabis, especially in a climate of rapidly changing cannabis policy; yet the content of available cannabis apps is largely unknown. Understanding the resources available to those searching for cannabis apps will clarify how this technology is being used to reflect and influence cannabis use behavior. We investigated the content of 59 cannabis-related mobile apps for Apple and Android devices as of November 26, 2014. The Apple and Google Play app stores were searched using the terms "cannabis" and "marijuana." Three trained coders classified the top 20 apps for each term and each store, using a coding guide. Apps were examined for the presence of 20 content codes derived by the researchers. Total apps available for each search term were 124 for cannabis and 218 for marijuana in the Apple App Store, and 250 each for cannabis and marijuana on Google Play. The top 20 apps in each category in each store were coded for 59 independent apps (30 Apple, 29 Google Play). The three most common content areas were cannabis strain classification (33.9%), facts about cannabis (20.3%), and games (20.3%). In the Apple App Store, most apps were free (77%), all were rated "17+" years, and the average user rating was 3.9/5 stars. The most popular apps provided cannabis strain classifications (50%), dispensary information (27%), or general facts about cannabis (27%). Only one app (3%) provided information or resources related to cannabis abuse, addiction, or treatment. On Google Play, most apps were free (93%), rated "high maturity" (79%), and the average user rating was 4.1/5. The most popular app types offered games (28%), phone utilities (eg, wallpaper, clock; 21%) and cannabis food recipes (21%); no apps addressed abuse, addiction, or treatment. Cannabis apps are generally free and highly rated. Apps were most often informational (facts, strain classification), or recreational (games), likely

  5. Study Parses Comorbidity of Cannabis Use and Social Anxiety

    Science.gov (United States)

    ... Use and Social Anxiety Study Parses Comorbidity of Cannabis Use and Social Anxiety Email Facebook Twitter October ... difficulties and other cannabis-related problems. SAD and Cannabis Use Severity Further analysis suggested that people with ...

  6. Pharmacology of Marihuana (Cannabis sativa)

    Science.gov (United States)

    Maickel, Roger P.

    1973-01-01

    A detailed discussion of marihuana (Cannabis sativa) providing the modes of use, history, chemistry, and physiologic properties of the drug. Cites research results relating to the pharmacologic effects of marihuana. These effects are categorized into five areas: behavioral, cardiovascular-respiratory, central nervous system, toxicity-toxicology,…

  7. Pharmacology of Marihuana (Cannabis sativa)

    Science.gov (United States)

    Maickel, Roger P.

    1973-01-01

    A detailed discussion of marihuana (Cannabis sativa) providing the modes of use, history, chemistry, and physiologic properties of the drug. Cites research results relating to the pharmacologic effects of marihuana. These effects are categorized into five areas: behavioral, cardiovascular-respiratory, central nervous system, toxicity-toxicology,…

  8. Medical cannabis - the Canadian perspective.

    Science.gov (United States)

    Ko, Gordon D; Bober, Sara L; Mindra, Sean; Moreau, Jason M

    2016-01-01

    Cannabis has been widely used as a medicinal agent in Eastern medicine with earliest evidence in ancient Chinese practice dating back to 2700 BC. Over time, the use of medical cannabis has been increasingly adopted by Western medicine and is thus a rapidly emerging field that all pain physicians need to be aware of. Several randomized controlled trials have shown a significant and dose-dependent relationship between neuropathic pain relief and tetrahydrocannabinol - the principal psychoactive component of cannabis. Despite this, barriers exist to use from both the patient perspective (cost, addiction, social stigma, lack of understanding regarding safe administration) and the physician perspective (credibility, criminality, clinical evidence, patient addiction, and policy from the governing medical colleges). This review addresses these barriers and draws attention to key concerns in the Canadian medical system, providing updated treatment approaches to help clinicians work with their patients in achieving adequate pain control, reduced narcotic medication use, and enhanced quality of life. This review also includes case studies demonstrating the use of medical marijuana by patients with neuropathic low-back pain, neuropathic pain in fibromyalgia, and neuropathic pain in multiple sclerosis. While significant preclinical data have demonstrated the potential therapeutic benefits of cannabis for treating pain in osteoarthritis, rheumatoid arthritis, fibromyalgia, and cancer, further studies are needed with randomized controlled trials and larger study populations to identify the specific strains and concentrations that will work best with selected cohorts.

  9. Transient Retinal Dysfunctions after Acute Cannabis Use.

    Science.gov (United States)

    Schwitzer, Thomas; Robert, Matthieu P; Giersch, Anne; Angioi-Duprez, Karine; Ingster-Moati, Isabelle; Pon-Monnier, Amandine; Schwan, Raymund; Laprevote, Vincent

    2016-01-01

    Although cannabis is very widespread worldwide, the impact of cannabis on visual function remains poorly understood. This is partly due to numerous difficulties met in developing clinical studies in cannabis users. Here, we report the first documented case of neuroretinal dysfunction after acute cannabis smoking. This observation was favored by the need of an annual ophthalmic evaluation in the context of a chloroquine intake for a systemic lupus erythematosus in a 47-year-old heavy cannabis user. A complete ophthalmic evaluation including visual acuity tests, intraocular pressure, fundoscopic examination, automated 10° central visual field, full-field electroretinogram (ERG) and multifocal ERG was performed twice - 30 min and 5 h after cannabis smoking. A strong decrease (up to 48%) in the a-wave amplitude of the full-field ERG was measured 30 min after cannabis smoking for all scotopic responses compared with the responses 5 h after smoking. Other tests showed reproducible results between the 2 series of measurements. This clinical case suggests that acute inhalation of cannabis affects the photoreceptors functioning. This rare situation suggests further investigations are required on the impact of cannabis on retinal processing, especially since cannabis has been incriminated in car injuries. © 2016 S. Karger AG, Basel.

  10. Investigating the Potential Influence of Cause of Death and Cocaine Levels on the Differential Expression of Genes Associated with Cocaine Abuse

    Science.gov (United States)

    Bannon, Michael J.; Savonen, Candace L.; Hartley, Zachary J.; Johnson, Magen M.; Schmidt, Carl J.

    2015-01-01

    The development of new therapeutic strategies for the treatment of complex brain disorders such as drug addiction is likely to be advanced by a more complete understanding of the underlying molecular pathophysiology. Although the study of postmortem human brain represents a unique resource in this regard, it can be challenging to disentangle the relative contribution of chronic pathological processes versus perimortem events to the observed changes in gene expression. To begin to unravel this issue, we analyzed by quantitative PCR the midbrain expression of numerous candidate genes previously associated with cocaine abuse. Data obtained from chronic cocaine abusers (and matched control subjects) dying of gunshot wounds were compared with a prior study of subjects with deaths directly attributable to cocaine abuse. Most of the genes studied (i.e., tyrosine hydroxylase, dopamine transporter, forkhead box A2, histone variant H3 family 3B, nuclear factor kappa B inhibitor alpha, growth arrest and DNA damage-inducible beta) were found to be differentially expressed in chronic cocaine abusers irrespective of immediate cause of death or perimortem levels of cocaine, suggesting that these may represent core pathophysiological changes arising with chronic drug abuse. On the other hand, chemokine C-C motif ligand 2 and jun proto-oncogene expression were unaffected in cocaine-abusing subjects dying of gunshot wounds, in contrast to the differential expression previously reported in cocaine-related fatalities. The possible influence of cause of death and other factors on the cocaine-responsiveness of these genes is discussed. PMID:25658879

  11. Quantifying the Clinical Significance of Cannabis Withdrawal

    Science.gov (United States)

    Allsop, David J.; Copeland, Jan; Norberg, Melissa M.; Fu, Shanlin; Molnar, Anna; Lewis, John; Budney, Alan J.

    2012-01-01

    Background and Aims Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. Methods and Results A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001). Conclusions Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes. PMID:23049760

  12. COCAINE CARDIOMYOPATHY—A CASE REPORT

    OpenAIRE

    Georgiev Antonio; Zhivadinovik Julija

    2014-01-01

    Abstract: Cocaine is the second most common illicit drug used and the most frequent cause of drug related deaths. The use of cocaine is associated with both, acute and chronic complications, that may involve any system, but the most common system affected is cardiovascular one. Cocaine cardiomyopathy may result from the use of cocaine. This article presents a first case in Republic of Macedonia of 24-year-old male with reversible cocaine- related cardiomyopathy. Clinical presentation...

  13. Prospective Assessment of Cannabis Withdrawal in Adolescents with Cannabis Dependence: A Pilot Study

    Science.gov (United States)

    Milin, Robert; Manion, Ian; Dare, Glenda; Walker, Selena

    2008-01-01

    A study to identify and assess the withdrawal symptoms in adolescents afflicted with cannabis dependence is conducted. Results conclude that withdrawal symptoms of cannabis were present in adolescents seeking treatment for this substance abuse.

  14. Cannabis use vulnerability among socially anxious users: cannabis craving during a social interaction.

    Science.gov (United States)

    Buckner, Julia D; Ecker, Anthony H; Vinci, Christine

    2013-03-01

    Socially anxious individuals appear especially vulnerable to cannabis-related problems. However, the nature of the social anxiety-cannabis relation remains unclear. The present study examined the timing and specificity of cannabis craving in response to a social anxiety induction task among 82 (71% female) cannabis users randomly assigned to either a social interaction or reading task. Participants completed ratings of substance (cannabis, alcohol, cigarette) craving at baseline (prior to being informed of task assignment), before, during, and after task. The Time × Condition interaction was significant such that cannabis craving increased from before to during the task among participants in the social interaction condition, but not among those in the reading condition. This effect was specific to cannabis craving and was not observed for craving for alcohol or cigarettes. Data suggest that increases in state social anxiety may play a role in cannabis use behaviors. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  15. Prospective Assessment of Cannabis Withdrawal in Adolescents with Cannabis Dependence: A Pilot Study

    Science.gov (United States)

    Milin, Robert; Manion, Ian; Dare, Glenda; Walker, Selena

    2008-01-01

    A study to identify and assess the withdrawal symptoms in adolescents afflicted with cannabis dependence is conducted. Results conclude that withdrawal symptoms of cannabis were present in adolescents seeking treatment for this substance abuse.

  16. Baclofen in the management of cannabis dependence syndrome

    OpenAIRE

    Imbert, Bruce; Labrune, Nathalie; Lancon, Christophe; Simon, Nicolas

    2014-01-01

    Cannabis is the most commonly used illicit drug in the world. However, only few studies have shown the efficacy of pharmacologic agents in targeting cannabis withdrawal symptoms or reducing the reinforcing effects of cannabis. Baclofen has been shown to reduce cannabis withdrawal symptoms and the subjective effects of cannabis. We think that the clinical utility of baclofen for cannabis dependence is a reasonable approach. A case report using baclofen is presented and provides preliminary sup...

  17. Unintentional Cannabis Intoxication in Toddlers.

    Science.gov (United States)

    Claudet, Isabelle; Mouvier, Sébastien; Labadie, Magali; Manin, Cécile; Michard-Lenoir, Anne-Pascale; Eyer, Didier; Dufour, Damien

    2017-09-01

    In France, cannabis consumption is illegal. The health impact of its increasing use and higher tetrahydrocannabinol (THC) concentrations is still poorly documented, particularly that of unintentional pediatric intoxications. We sought to evaluate the French national trend of admissions for unintentional cannabis intoxication in children over an 11-year period (2004-2014). A retrospective, national, multicenter, observational study of a pediatric cohort. All children aged cannabis intoxication (compatible symptoms and positive toxicological screening results) during the reference period were included. Twenty-four PEDs participated in our study; 235 children were included, and 71% of the patients were 18 months old or younger. Annual admissions increased by a factor of 13. Hashish resin was the main form ingested (72%). During the study period, the evolution was characterized by a national increase in intoxications, younger intoxicated children (1.28 ± 0.4 vs 1.7 ± 0.7 years, P = .005), and more comas (n = 38) (P = .05, odds ratio 3.5 [1.02-11.8]). Compared with other intoxications, other PED admissions, and the same age population, cannabis-related admissions were greater. There was a potential link between the increased incidence of comas and increased THC concentration in resin seized in France over the period. Children are collateral victims of changing trends in cannabis use and a prevailing THC concentration. Intoxicated children are more frequent, are younger, and have intoxications that are more severe. This raises a real issue of public health. Copyright © 2017 by the American Academy of Pediatrics.

  18. Cocrystallization studies of full-length recombinant butyrylcholinesterase (BChE) with cocaine

    Energy Technology Data Exchange (ETDEWEB)

    Asojo, Oluwatoyin Ajibola; Asojo, Oluyomi Adebola; Ngamelue, Michelle N.; Homma, Kohei; Lockridge, Oksana (Nebraska-Med)

    2011-09-16

    Human butyrylcholinesterase (BChE; EC 3.1.1.8) is a 340 kDa tetrameric glycoprotein that is present in human serum at about 5 mg l{sup -1} and has well documented therapeutic effects on cocaine toxicity. BChE holds promise as a therapeutic that reduces and finally eliminates the rewarding effects of cocaine, thus weaning an addict from the drug. There have been extensive computational studies of cocaine hydrolysis by BChE. Since there are no reported structures of BChE with cocaine or any of the hydrolysis products, full-length monomeric recombinant wild-type BChE was cocrystallized with cocaine. The refined 3 {angstrom} resolution structure appears to retain the hydrolysis product benzoic acid in sufficient proximity to form a hydrogen bond to the active-site Ser198.

  19. Fatty Acid Amide Hydrolase Binding in Brain of Cannabis Users: Imaging With the Novel Radiotracer [(11)C]CURB.

    Science.gov (United States)

    Boileau, Isabelle; Mansouri, Esmaeil; Williams, Belinda; Le Foll, Bernard; Rusjan, Pablo; Mizrahi, Romina; Tyndale, Rachel F; Huestis, Marilyn A; Payer, Doris E; Wilson, Alan A; Houle, Sylvain; Kish, Stephen J; Tong, Junchao

    2016-11-01

    One of the major mechanisms for terminating the actions of the endocannabinoid anandamide is hydrolysis by fatty acid amide hydrolase (FAAH), and inhibitors of the enzyme were suggested as potential treatment for human cannabis dependence. However, the status of brain FAAH in cannabis use disorder is unknown. Brain FAAH binding was measured with positron emission tomography and [(11)C]CURB in 22 healthy control subjects and ten chronic cannabis users during early abstinence. The FAAH genetic polymorphism (rs324420) and blood, urine, and hair levels of cannabinoids and metabolites were determined. In cannabis users, FAAH binding was significantly lower by 14%-20% across the brain regions examined than in matched control subjects (overall Cohen's d = 0.96). Lower binding was negatively correlated with cannabinoid concentrations in blood and urine and was associated with higher trait impulsiveness. Lower FAAH binding levels in the brain may be a consequence of chronic and recent cannabis exposure and could contribute to cannabis withdrawal. This effect should be considered in the development of novel treatment strategies for cannabis use disorder that target FAAH and endocannabinoids. Further studies are needed to examine possible changes in FAAH binding during prolonged cannabis abstinence and whether lower FAAH binding predates drug use. Copyright © 2016 Society of Biological Psychiatry. All rights reserved.

  20. Clinical potential of methylphenidate in the treatment of cocaine addiction: a review of the current evidence

    Directory of Open Access Journals (Sweden)

    Dürsteler KM

    2015-06-01

    Full Text Available Kenneth M Dürsteler,1,2 Eva-Maria Berger,1 Johannes Strasser,1 Carlo Caflisch,2 Jochen Mutschler,2 Marcus Herdener,2 Marc Vogel1 1Center for Addictive Disorders, Psychiatric University Clinics Basel, Basel, Switzerland; 2Center for Addictive Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland Background: Cocaine use continues to be a public health problem, yet there is no proven effective pharmacotherapy for cocaine dependence. A promising approach to treating cocaine dependence may be agonist-replacement therapy, which is already used effectively in the treatment of opioid and tobacco dependence. The replacement approach for cocaine dependence posits that administration of a long-acting stimulant medication should normalize the neurochemical and behavioral perturbations resulting from chronic cocaine use. One potential medication to be substituted for cocaine is methylphenidate (MPH, as this stimulant possesses pharmacobehavioral properties similar to those of cocaine. Aim: To provide a qualitative review addressing the rationale for the use of MPH as a cocaine substitute and its clinical potential in the treatment of cocaine dependence. Methods: We searched MEDLINE for clinical studies using MPH in patients with cocaine abuse/dependence and screened the bibliographies of the articles found for pertinent literature. Results: MPH, like cocaine, increases synaptic dopamine by inhibiting dopamine reuptake. The discriminative properties, reinforcing potential, and subjective effects of MPH and cocaine are almost identical and, importantly, MPH has been found to substitute for cocaine in animals and human volunteers under laboratory conditions. When taken orally in therapeutic doses, its abuse liability, however, appears low, which is especially true for extended-release MPH preparations. Though there are promising data in the literature, mainly from case reports and

  1. Cannabis Mobile Apps: A Content Analysis

    Science.gov (United States)

    Popova, Lucy; Grana, Rachel; Zhao, Shirley; Chavez, Kathryn

    2015-01-01

    Background Mobile technology is pervasive and widely used to obtain information about drugs such as cannabis, especially in a climate of rapidly changing cannabis policy; yet the content of available cannabis apps is largely unknown. Understanding the resources available to those searching for cannabis apps will clarify how this technology is being used to reflect and influence cannabis use behavior. Objective We investigated the content of 59 cannabis-related mobile apps for Apple and Android devices as of November 26, 2014. Methods The Apple and Google Play app stores were searched using the terms “cannabis” and “marijuana.” Three trained coders classified the top 20 apps for each term and each store, using a coding guide. Apps were examined for the presence of 20 content codes derived by the researchers. Results Total apps available for each search term were 124 for cannabis and 218 for marijuana in the Apple App Store, and 250 each for cannabis and marijuana on Google Play. The top 20 apps in each category in each store were coded for 59 independent apps (30 Apple, 29 Google Play). The three most common content areas were cannabis strain classification (33.9%), facts about cannabis (20.3%), and games (20.3%). In the Apple App Store, most apps were free (77%), all were rated “17+” years, and the average user rating was 3.9/5 stars. The most popular apps provided cannabis strain classifications (50%), dispensary information (27%), or general facts about cannabis (27%). Only one app (3%) provided information or resources related to cannabis abuse, addiction, or treatment. On Google Play, most apps were free (93%), rated “high maturity” (79%), and the average user rating was 4.1/5. The most popular app types offered games (28%), phone utilities (eg, wallpaper, clock; 21%) and cannabis food recipes (21%); no apps addressed abuse, addiction, or treatment. Conclusions Cannabis apps are generally free and highly rated. Apps were most often informational

  2. Cocaine tolerance in honey bees.

    Directory of Open Access Journals (Sweden)

    Eirik Søvik

    Full Text Available Increasingly invertebrates are being used to investigate the molecular and cellular effects of drugs of abuse to explore basic mechanisms of addiction. However, in mammals the principle factors contributing to addiction are long-term adaptive responses to repeated drug use. Here we examined whether adaptive responses to cocaine are also seen in invertebrates using the honey bee model system. Repeated topical treatment with a low dose of cocaine rendered bees resistant to the deleterious motor effects of a higher cocaine dose, indicating the development of physiological tolerance to cocaine in bees. Cocaine inhibits biogenic amine reuptake transporters, but neither acute nor repeated cocaine treatments caused measurable changes in levels of biogenic amines measured in whole bee brains. Our data show clear short and long-term behavioural responses of bees to cocaine administration, but caution that, despite the small size of the bee brain, measures of biogenic amines conducted at the whole-brain level may not reveal neurochemical effects of the drug.

  3. PET imaging predicts future body weight and cocaine preference

    Energy Technology Data Exchange (ETDEWEB)

    Michaelides M.; Wang G.; Michaelides M.; Thanos P.K. Kim R.; Cho J.; Ananth M.; Wang G.-J.; Volkow N.D.

    2011-08-28

    Deficits in dopamine D2/D3 receptor (D2R/D3R) binding availability using PET imaging have been reported in obese humans and rodents. Similar deficits have been reported in cocaine-addicts and cocaine-exposed primates. We found that D2R/D3R binding availability negatively correlated with measures of body weight at the time of scan (ventral striatum), at 1 (ventral striatum) and 2 months (dorsal and ventral striatum) post scan in rats. Cocaine preference was negatively correlated with D2R/D3R binding availability 2 months (ventral striatum) post scan. Our findings suggest that inherent deficits in striatal D2R/D3R signaling are related to obesity and drug addiction susceptibility and that ventral and dorsal striatum serve dissociable roles in maintaining weight gain and cocaine preference. Measuring D2R/D3R binding availability provides a way for assessing susceptibility to weight gain and cocaine abuse in rodents and given the translational nature of PET imaging, potentially primates and humans.

  4. The Social Context of Cannabis Use: Relationship to Cannabis Use Disorders and Depressive Symptoms among College Students

    OpenAIRE

    Beck, Kenneth H.; Caldeira, Kimberly M.; Vincent, Kathryn B.; O'Grady, Kevin E.; Wish, Eric D.; Arria, Amelia M.

    2009-01-01

    Few studies have investigated the association between the social context of cannabis use and cannabis use disorder (CUD). This longitudinal study of college students aimed to: develop a social context measure of cannabis use; examine the degree to which social context is associated with the transition from non-problematic cannabis use to CUD; and, examine the association between social context of cannabis use and depressive symptoms. The analytic sample consisted of 322 past-year cannabis use...

  5. Är cannabis den nya folkölen? : Unga cannabisanvändares tal om cannabis

    OpenAIRE

    Jansson, Mari; Tally, Molly

    2015-01-01

    The aim of this study was to examine young adult cannabis users’ attitudes towards cannabis and their perception of the normalization of cannabis. The purpose was also to explore how their views of cannabis correspond with norms regarding cannabis. This study is based on interviews with five young adult cannabis users. The theoretical framework is based on Parker’s normalization thesis, Goffman’s notion of stigma, Becker’s definition of outsiders and the definition of social identity develope...

  6. Är cannabis den nya folkölen? : Unga cannabisanvändares tal om cannabis

    OpenAIRE

    Jansson, Mari; Tally, Molly

    2015-01-01

    The aim of this study was to examine young adult cannabis users’ attitudes towards cannabis and their perception of the normalization of cannabis. The purpose was also to explore how their views of cannabis correspond with norms regarding cannabis. This study is based on interviews with five young adult cannabis users. The theoretical framework is based on Parker’s normalization thesis, Goffman’s notion of stigma, Becker’s definition of outsiders and the definition of social identity develope...

  7. Inhaled medicinal cannabis and the immunocompromised patient.

    Science.gov (United States)

    Ruchlemer, Rosa; Amit-Kohn, Michal; Raveh, David; Hanuš, Lumír

    2015-03-01

    Medicinal cannabis is an invaluable adjunct therapy for pain relief, nausea, anorexia, and mood modification in cancer patients and is available as cookies or cakes, as sublingual drops, as a vaporized mist, or for smoking. However, as with every herb, various microorganisms are carried on its leaves and flowers which when inhaled could expose the user, in particular immunocompromised patients, to the risk of opportunistic lung infections, primarily from inhaled molds. The objective of this study was to identify the safest way of using medicinal cannabis in immunosuppressed patients by finding the optimal method of sterilization with minimal loss of activity of cannabis. We describe the results of culturing the cannabis herb, three methods of sterilization, and the measured loss of a main cannabinoid compound activity. Systematic sterilization of medicinal cannabis can eliminate the risk of fatal opportunistic infections associated with cannabis among patients at risk.

  8. Pathways to psychosis in cannabis abuse.

    Science.gov (United States)

    Shrivastava, Amresh; Johnston, Megan; Terpstra, Kristen; Bureau, Yves

    2015-04-01

    Cannabis has been implicated as a risk factor for the development of schizophrenia, but the exact biological mechanisms remain unclear. In this review, we attempt to understand the neurobiological pathways that link cannabis use to schizophrenia. This has been an area of great debate; despite similarities between cannabis users and schizophrenia patients, the evidence is not sufficient to establish cause-and-effect. There have been advances in the understanding of the mechanisms of cannabis dependence as well as the role of the cannabinoid system in the development of psychosis and schizophrenia. The neurobiological mechanisms associated with the development of psychosis and effects from cannabis use may be similar but remain elusive. In order to better understand these associations, this paper will show common neurobiological and neuroanatomical changes as well as common cognitive dysfunction in cannabis users and patients of schizophrenia. We conclude that epidemiologic evidence highlights potential causal links; however, neurobiological evidence for causality remains weak.

  9. Molecular mechanism for a gateway drug: epigenetic changes initiated by nicotine prime gene expression by cocaine.

    Science.gov (United States)

    Levine, Amir; Huang, Yanyou; Drisaldi, Bettina; Griffin, Edmund A; Pollak, Daniela D; Xu, Shiqin; Yin, Deqi; Schaffran, Christine; Kandel, Denise B; Kandel, Eric R

    2011-11-02

    In human populations, cigarettes and alcohol generally serve as gateway drugs, which people use first before progressing to marijuana, cocaine, or other illicit substances. To understand the biological basis of the gateway sequence of drug use, we developed an animal model in mice and used it to study the effects of nicotine on subsequent responses to cocaine. We found that pretreatment of mice with nicotine increased the response to cocaine, as assessed by addiction-related behaviors and synaptic plasticity in the striatum, a brain region critical for addiction-related reward. Locomotor sensitization was increased by 98%, conditioned place preference was increased by 78%, and cocaine-induced reduction in long-term potentiation (LTP) was enhanced by 24%. The responses to cocaine were altered only when nicotine was administered first, and nicotine and cocaine were then administered concurrently. Reversing the order of drug administration was ineffective; cocaine had no effect on nicotine-induced behaviors and synaptic plasticity. Nicotine primed the response to cocaine by enhancing its ability to induce transcriptional activation of the FosB gene through inhibition of histone deacetylase, which caused global histone acetylation in the striatum. We tested this conclusion further and found that a histone deacetylase inhibitor simulated the actions of nicotine by priming the response to cocaine and enhancing FosB gene expression and LTP depression in the nucleus accumbens. Conversely, in a genetic mouse model characterized by reduced histone acetylation, the effects of cocaine on LTP were diminished. We achieved a similar effect by infusing a low dose of theophylline, an activator of histone deacetylase, into the nucleus accumbens. These results from mice prompted an analysis of epidemiological data, which indicated that most cocaine users initiate cocaine use after the onset of smoking and while actively still smoking, and that initiating cocaine use after smoking

  10. Cannabis use and first manic episode.

    Science.gov (United States)

    Bally, Nathalie; Zullino, Daniele; Aubry, Jean-Michel

    2014-08-01

    Cannabis is the most commonly abused drug among patients with bipolar disorder. Available data has shown that the risk of psychotic disorders increases with the frequency and intensity of cannabis abuse. The present purpose was to review relevant studies to investigate whether cannabis use can be linked to the onset of mania in bipolar disorder. Articles published between 1972 and December 2013 were searched on Medline and PsychInfo using the following keywords: first manic episode, or onset mania, or bipolar disorder and cannabis. Relevant papers cited in the references of selected articles were further considered for inclusion into the review. Lifetime use of cannabis among bipolar patients appears to be around 70% and approximately 30% of patients with a bipolar disorder present a comorbidity of cannabis abuse or dependence. Cannabis use is associated with younger age at onset of first mania and with more frequent depressive or manic episodes, although the evidence is somewhat inconsistent. Likewise cannabis consumption is related to poorer outcome and an increased risk of rapid cycling or mixed episodes. In contrast, neuro-cognitive functioning seems to be positively affected in patients with psychiatric comorbidity. While cannabis use often precedes first manic episodes, the causal direction remains to be determined. Variations in definition of cannabis use/dependence. Lack of controlled studies limiting definite conclusions about a putative causal relationship between cannabis and onset of mania. Further investigations are needed to clarify the relationships between cannabis use and first manic episode. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Cannabis use and cognition in schizophrenia

    Directory of Open Access Journals (Sweden)

    Else-Marie Løberg

    2009-11-01

    Full Text Available People with schizophrenia frequently report cannabis use, and cannabis may be a risk factor for schizophrenia, mediated through effects on brain function and biochemistry. Thus, it is conceivable that cannabis may also influence cognitive functioning in this patients group. We report data from our own laboratory on the use of cannabis by schizophrenia patients, and review the existing literature on the effects of cannabis on cognition in schizophrenia and related psychosis. Of the 23 studies that were found, 14 reported that the cannabis users had better cognitive performance than the schizophrenia non-users. Eight studies reported no or minimal differences in cognitive performance in the two groups, but only one study reported better cognitive performance in the schizophrenia non-user group. Our own results confirm the overall impression from the literature review of better cognitive performance in the cannabis user group. These paradoxical findings may have several explanations, which are discussed. We suggest that cannabis causes a transient cognitive breakdown enabling the development of psychosis, imitating the typical cognitive vulnerability seen in schizophrenia. This is further supported by an earlier age of onset and fewer neurological soft signs in the cannabis-related schizophrenia group, suggesting an alternative pathway to psychosis.

  12. Effects of quitting cannabis on respiratory symptoms

    Science.gov (United States)

    Hancox, Robert J.; Shin, Hayden H.; Gray, Andrew R.; Poulton, Richie; Sears, Malcolm R.

    2016-01-01

    Smoking cannabis is associated with symptoms of bronchitis. Little is known about the persistence of symptoms after stopping cannabis use. We assessed associations between changes in cannabis use and respiratory symptoms in a population-based cohort of 1037 young adults. Participants were asked about cannabis and tobacco use at ages 18, 21, 26, 32 and 38 years. Symptoms of morning cough, sputum production, wheeze, dyspnoea on exertion and asthma diagnoses were ascertained at the same ages. Frequent cannabis use was defined as ≥52 occasions over the previous year. Associations between frequent cannabis use and respiratory symptoms were analysed using generalised estimating equations with adjustments for tobacco smoking, asthma, sex and age. Frequent cannabis use was associated with morning cough (OR 1.97, pcannabis use was associated with reductions in the prevalence of cough, sputum and wheeze to levels similar to nonusers. Frequent cannabis use is associated with symptoms of bronchitis in young adults. Reducing cannabis use often leads to a resolution of these symptoms. PMID:25837035

  13. [Cannabis use and impairment of respiratory function].

    Science.gov (United States)

    Underner, M; Urban, T; Perriot, J; Peiffer, G; Meurice, J-C

    2013-04-01

    Cannabis is the most commonly smoked illicit substance in many countries including France. It can be smoked alone in plant form (marijuana) but in our country it is mainly smoked in the form of cannabis resin mixed with tobacco. The technique of inhaling cannabis differs from that of tobacco, increasing the time that the smoke spends in contact with the bronchial mucosal and its impact on respiratory function. One cigarette composed of cannabis and tobacco is much more harmful than a cigarette containing only tobacco. In cannabis smokers there is an increased incidence of respiratory symptoms and episodes of acute bronchitis. Cannabis produces a rapid bronchodilator effect; chronic use provokes a reduction in specific conductance and increase in airways resistance. Studies on the decline of Forced Expiratory Volume are discordant. Cannabis smoke and tetrahydrocannabinol irritate the bronchial tree. They bring about histological signs of airways inflammation and alter the fungicidal and antibacterial activity of alveolar macrophages. Inhalation of cannabis smoke is a risk factor for lung cancer. Stopping smoking cannabis will bring about important benefits for lung function. This should encourage clinicians to offer patients support in quitting smoking.

  14. Therapeutic benefits of cannabis: a patient survey.

    Science.gov (United States)

    Webb, Charles W; Webb, Sandra M

    2014-04-01

    Clinical research regarding the therapeutic benefits of cannabis ("marijuana") has been almost non-existent in the United States since cannabis was given Schedule I status in the Controlled Substances Act of 1970. In order to discover the benefits and adverse effects perceived by medical cannabis patients, especially with regards to chronic pain, we hand-delivered surveys to one hundred consecutive patients who were returning for yearly re-certification for medical cannabis use in Hawai'i. The response rate was 94%. Mean and median ages were 49.3 and 51 years respectively. Ninety-seven per cent of respondents used cannabis primarily for chronic pain. Average pain improvement on a 0-10 pain scale was 5.0 (from 7.8 to 2.8), which translates to a 64% relative decrease in average pain. Half of all respondents also noted relief from stress/anxiety, and nearly half (45%) reported relief from insomnia. Most patients (71%) reported no adverse effects, while 6% reported a cough or throat irritation and 5% feared arrest even though medical cannabis is legal in Hawai'i. No serious adverse effects were reported. These results suggest that Cannabis is an extremely safe and effective medication for many chronic pain patients. Cannabis appears to alleviate pain, insomnia, and may be helpful in relieving anxiety. Cannabis has shown extreme promise in the treatment of numerous medical problems and deserves to be released from the current Schedule I federal prohibition against research and prescription.

  15. Therapeutic potential of cannabis-related drugs.

    Science.gov (United States)

    Alexander, Stephen P H

    2016-01-04

    In this review, I will consider the dual nature of Cannabis and cannabinoids. The duality arises from the potential and actuality of cannabinoids in the laboratory and clinic and the 'abuse' of Cannabis outside the clinic. The therapeutic areas currently best associated with exploitation of Cannabis-related medicines include pain, epilepsy, feeding disorders, multiple sclerosis and glaucoma. As with every other medicinal drug of course, the 'trick' will be to maximise the benefit and minimise the cost. After millennia of proximity and exploitation of the Cannabis plant, we are still playing catch up with an understanding of its potential influence for medicinal benefit.

  16. Medicinal cannabis: rational guidelines for dosing.

    Science.gov (United States)

    Carter, Gregory T; Weydt, Patrick; Kyashna-Tocha, Muraco; Abrams, Donald I

    2004-05-01

    The medicinal value of cannabis (marijuana) is well documented in the medical literature. Cannabinoids, the active ingredients in cannabis, have many distinct pharmacological properties. These include analgesic, anti-emetic, anti-oxidative, neuroprotective and anti-inflammatory activity, as well as modulation of glial cells and tumor growth regulation. Concurrent with all these advances in the understanding of the physiological and pharmacological mechanisms of cannabis, there is a strong need for developing rational guidelines for dosing. This paper will review the known chemistry and pharmacology of cannabis and, on that basis, discuss rational guidelines for dosing.

  17. Medical cannabis and chronic opioid therapy.

    Science.gov (United States)

    Reisfield, Gary M

    2010-12-01

    Fourteen states and the District of Columbia have legalized the use of cannabis for medical purposes. A small, high-quality literature supports the efficacy of medical cannabis for the treatment of neuropathic pain. The smoked botanical product, however, is associated with a number of adverse medical and psychiatric consequences. Furthermore, experimental data indicate that acute use of cannabis results in impairment of every important metric related to the safe operation of a motor vehicle. Epidemiological data show associations between recent cannabis use and both psychomotor impairment and motor vehicle crashes, associations that are strengthened by the concomitant use of alcohol and other central nervous system depressants. Finally, data from pain clinics reveals an unusually high prevalence of cannabis use in nearly all age groups and an association between cannabis use and opioid and other substance misuse. Based on available data and expert opinion, concomitant use of cannabis and opioids is an absolute contraindication to the operation of a motor vehicle. In patients who use cannabis and are prescribed opioids, heightened vigilance for opioid- and other substance-related problems is warranted. It is appropriate to refrain from prescribing opioids to individuals using medical cannabis if there is reasonable suspicion that the combination will pose a risk to the patient or others.

  18. Quantification of Cannabinoid Content in Cannabis

    Science.gov (United States)

    Tian, Y.; Zhang, F.; Jia, K.; Wen, M.; Yuan, Ch.

    2015-09-01

    Cannabis is an economically important plant that is used in many fields, in addition to being the most commonly consumed illicit drug worldwide. Monitoring the spatial distribution of cannabis cultivation and judging whether it is drug- or fiber-type cannabis is critical for governments and international communities to understand the scale of the illegal drug trade. The aim of this study was to investigate whether the cannabinoids content in cannabis could be spectrally quantified using a spectrometer and to identify the optimal wavebands for quantifying the cannabinoid content. Spectral reflectance data of dried cannabis leaf samples and the cannabis canopy were measured in the laboratory and in the field, respectively. Correlation analysis and the stepwise multivariate regression method were used to select the optimal wavebands for cannabinoid content quantification based on the laboratory-measured spectral data. The results indicated that the delta-9-tetrahydrocannabinol (THC) content in cannabis leaves could be quantified using laboratory-measured spectral reflectance data and that the 695 nm band is the optimal band for THC content quantification. This study provides prerequisite information for designing spectral equipment to enable immediate quantification of THC content in cannabis and to discriminate drug- from fiber-type cannabis based on THC content quantification in the field.

  19. Cocaine depresses GABAA current of hippocampal neurons.

    Science.gov (United States)

    Ye, J H; Liu, P L; Wu, W H; McArdle, J J

    1997-10-01

    Although blockade of dopamine re-uptake and the resulting elevation of excitatory agonists is commonly thought the primary mechanism of cocaine-induced seizures, it is possible that other neurotransmitters such as gamma-aminobutyric acid (GABA) are involved. To examine this possibility, the effects of cocaine on the whole cell GABA current (IGABA) of freshly isolated rat hippocampal neurons were investigated with the patch-clamp technique. Preincubation or acute application of cocaine reversibly suppressed IGABA. The IC50 was 127 microM when cocaine was applied before the application of GABA. The concentration-response relations of cocaine in various GABA concentrations revealed that cocaine inhibited IGABA non-competitively. This effect of cocaine appeared to be independent of voltage. The present study suggests that the GABA receptor/channel complex is also a target for cocaine's action. The suppression of IGABA may contribute to cocaine-induced seizures.

  20. Finding cannabinoids in hair does not prove cannabis consumption

    OpenAIRE

    Bjoern Moosmann; Nadine Roth; Volker Auwärter

    2015-01-01

    Hair analysis for cannabinoids is extensively applied in workplace drug testing and in child protection cases, although valid data on incorporation of the main analytical targets, ∆9-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-THC (THC-COOH), into human hair is widely missing. Furthermore, ∆9-tetrahydrocannabinolic acid A (THCA-A), the biogenetic precursor of THC, is found in the hair of persons who solely handled cannabis material. In the light of the serious consequences of positive tes...

  1. Symptoms of obsessive-compulsive disorder predict cannabis misuse.

    Science.gov (United States)

    Spradlin, Alexander; Mauzay, Dakota; Cuttler, Carrie

    2017-09-01

    Cannabis use has been linked to many psychological disorders. There is, however, a paucity of research investigating the link between cannabis use and obsessive-compulsive disorder (OCD). The present study sought to examine this link by exploring associations between severity of OCD symptoms, cannabis use, and cannabis misuse; determining whether these associations exist above and beyond symptoms of anxiety, depression, and stress; and testing the mediating role of cannabis coping motives (i.e., using cannabis to cope with negative affect and other problems). A large sample of young adult cannabis users (n=430) completed an online survey containing measures of OCD symptoms, cannabis use, cannabis misuse, and cannabis use motives. Severity of OCD (as indexed by higher scores on the Obsessive-Compulsive Inventory-Revised) was unrelated to frequency and quantity of cannabis use, but it was significantly, positively related to increased cannabis misuse. These effects persisted after controlling for anxiety, depression, and stress. The specific feature of obsessing was found to consistently predict cannabis misuse. Finally, an indirect effect of severity of OCD on cannabis misuse via coping motives was discovered. Together, these findings indicate that there may be an association between OCD and cannabis misuse that is independent of anxiety, depression, and stress, and that is mediated by coping motives. Based on these findings, we recommend that individuals with OCD symptoms avoid using cannabis because they may be more vulnerable to the development of problematic use and cannabis use disorder. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Role of Sigma Receptor in Cocaine-Mediated Induction of Glial Fibrillary Acidic Protein: Implications for HAND.

    Science.gov (United States)

    Yang, Lu; Yao, Honghong; Chen, Xufeng; Cai, Yu; Callen, Shannon; Buch, Shilpa

    2016-03-01

    Cocaine abuse has been shown to accelerate the progression of human immunodeficiency virus (HIV)-1-associated neurological disorders (HANDs) partially through increasing neuroinflammatory response mediated by activated astrocytes; however, the detailed molecular mechanism of cocaine-mediated astrocyte activation is unclear. In the current study, we demonstrated increased astrogliosis in the cortical regions of brains from HIV(+) cocaine abusers compared with the HIV(+) group without cocaine abuse. We next sought to explore whether cocaine exposure could result in increased expression of glial fibrillary acidic protein (GFAP), a filament protein critical for astrocyte activation. Exposure of cocaine to astrocytes resulted in rapid translocation of sigma receptor to the plasma membrane with subsequent activation of downstream signaling pathways. Using a pharmacological approach, we provide evidence that cocaine-mediated upregulation of GFAP expression involved activation of mitogen-activated protein kinase (MAPK) signaling with subsequent downstream activation of the early growth response gene 1 (Egr-1). Egr-1 activation, in turn, caused transcriptional regulation of GFAP. Corroboration of these findings in vivo demonstrated increased expression of GFAP in the cortical region of mice treated with cocaine compared with the saline injected controls. A thorough understanding of how cocaine mediates astrogliosis could have implications for the development of therapeutic interventions aimed at HIV-infected cocaine abusers.

  3. Prenatal cocaine exposure decreases parvalbumin-immunoreactive neurons and GABA-to-projection neuron ratio in the medial prefrontal cortex.

    Science.gov (United States)

    McCarthy, Deirdre M; Bhide, Pradeep G

    2012-01-01

    Cocaine abuse during pregnancy produces harmful effects not only on the mother but also on the unborn child. The neurotransmitters dopamine and serotonin are known as the principal targets of the action of cocaine in the fetal and postnatal brain. However, recent evidence suggests that cocaine can impair cerebral cortical GABA neuron development and function. We sought to analyze the effects of prenatal cocaine exposure on the number and distribution of GABA and projection neurons (inhibitory interneurons and excitatory output neurons, respectively) in the mouse cerebral cortex. We found that the prenatal cocaine exposure decreased GABA neuron numbers and GABA-to-projection neuron ratio in the medial prefrontal cortex of 60-day-old mice. The neighboring prefrontal cortex did not show significant changes in either of these measures. However, there was a significant increase in projection neuron numbers in the prefrontal cortex but not in the medial prefrontal cortex. Thus, the effects of cocaine on GABA and projection neurons appear to be cortical region specific. The population of parvalbumin-immunoreactive GABA neurons was decreased in the medial prefrontal cortex following the prenatal cocaine exposure. The cocaine exposure also delayed the developmental decline in the volume of the medial prefrontal cortex. Thus, prenatal cocaine exposure produced persisting and region-specific effects on cortical cytoarchitecture and impaired the physiological balance between excitatory and inhibitory neurotransmission. These structural changes may underlie the electrophysiological and behavioral effects of prenatal cocaine exposure observed in animal models and human subjects.

  4. Intracellular mechanisms of cocaine-memory reconsolidation in the basolateral amygdala and dorsal hippocampus

    Science.gov (United States)

    Wells, Audrey Marie

    The ability of cocaine-associated environmental contexts to promote relapse in abstinent humans and reinstatement of cocaine-seeking behavior in laboratory animals depends on the formation and maintenance of maladaptive context-response-cocaine associative memories, the latter of which can be disrupted by manipulations that interfere with memory reconsolidation. Memory reconsolidation refers to a protein synthesis-dependent phenomenon whereby memory traces are reincorporated back into long-term memory storage following their retrieval and subsequent destabilization. To elucidate the distinctive roles of the basolateral amygdala (BLA) and dorsal hippocampus (DH) in the reconsolidation of context-response-cocaine memories, Experiments 1-3 evaluated novel molecular mechanisms within each structure that control this phenomenon. Experiment 1 tested the hypothesis that activation of the extracellular signal-regulated kinase (ERK) in the BLA and nucleus accumbens core (NACc - a substrate for Pavlovian cocaine-memory reconsolidation) would critically control instrumental cocaine-memory reconsolidation. To determine this, rats were re-exposed to a context that had previously been used for cocaine self-administration (i.e., cocaine memory-reactivation) and immediately thereafter received bilateral intra-BLA or intra-NACc microinfusions of the ERK inhibitor U0126 or vehicle (VEH) and were subsequently tested for drug context-induced cocaine-seeking behavior (non-reinforced lever responding) ~72 h later. Re-exposure to the cocaine-paired context at test fully reinstated cocaine-seeking behavior, relative to responding in an alternate, extinction context, and post-reactivation U0126 treatment in the BLA, but not the NACc, impaired cocaine-seeking behavior, relative to VEH. This effect was associated with a temporary increase in ERK2, but not ERK1, phosphorylation in the BLA and required explicit reactivation of the target memory trace (i.e., did not similarly manifest when U

  5. Ultrasound-assisted extraction of volatile compounds from industrial Cannabis sativa L. inflorescences

    Directory of Open Access Journals (Sweden)

    C. Da Porto

    2014-02-01

    Full Text Available Summary. This study investigated the use of ultrasound-assisted extraction (UAE to recovery  volatile compounds from the inflorescences of a fiber type Cannabis sativa L. cultivar. The results show that ultrasonic treatment not longer than 5 min allows to obtain an enhanced concentration of terpenes in comparison with maceration. Instead, an ultrasonic treatment longer than 5 min increased  the concentration of δ-9-tetraidrocannabinol (THC. A preliminary screening of cannabis inflorescences scent was performed by headspace solid-phase microextraction (HS-SPME with gas chromatography-mass spectrometry (GC-MS avoiding the chemical modification and artifact formation that can occur in conventional methods . Industrial relevance. Inflorescences of fiber type Cannabis sativa cultivars are generally considered waste parts for fiber industry, although the inflorescences’ volatiles are pleasant to the human sensory system. Cannabis scent originate from volatile monoterpenes and sesquiterpenes . Traditionally, the recovery of floral fragrances from plants is by water distillation (hydro-distillation or steam distillation to produce essential oils. However, these techniques take at least several hours and require the application of heating, which can produce the degradation of thermo labile compounds present in the starting plant material. Ultrasound-assisted extraction can be use as alternative method to extract aroma compounds from inflorescences of fiber type  Cannabis sativa. The extracts so obtained could be used as ingredients for perfumes (cosmetic industry or flavorings for beverages (food industry.Keywords. Ultrasound; Extraction; Cannabis sativa L.; terpenes; THC; HS-SPME

  6. Cocaine Causes Apoptotic Death in Rat Mesencephalon and Striatum Primary Cultures

    Directory of Open Access Journals (Sweden)

    Lucilia B. Lepsch

    2015-01-01

    Full Text Available To study cocaine’s toxic effects in vitro, we have used primary mesencephalic and striatal cultures from rat embryonic brain. Treatment with cocaine causes a dramatic increase in DNA fragmentation in both primary cultures. The toxicity induced by cocaine was paralleled with a concomitant decrease in the microtubule associated protein 2 (MAP2 and/or neuronal nucleus protein (NeuN staining. We also observed in both cultures that the cell death caused by cocaine was induced by an apoptotic mechanism, confirmed by TUNEL assay. Therefore, the present paper shows that cocaine causes apoptotic cell death and inhibition of the neurite prolongation in striatal and mesencephalic cell culture. These data suggest that if similar neuronal damage could be produced in the developing human brain, it could account for the qualitative or quantitative defects in neuronal pathways that cause a major handicap in brain function following prenatal exposure to cocaine.

  7. Metabolomics of cocaine: implications in toxicity.

    Science.gov (United States)

    Dinis-Oliveira, Ricardo Jorge

    2015-01-01

    Cocaine is the most commonly used illicit drug among those seeking care in Emergency Departments or drug detoxification centers. Cocaine, chemically known as benzoylmethylecgonine, is a naturally occurring substance found in the leaves of the Erythroxylum coca plant. The pharmacokinetics of cocaine is dependent on multiple factors, such as physical/chemical form, route of administration, genetics and concurrent consumption of alcohol. This review aims to discuss metabolomics of cocaine, namely by presenting all known metabolites of cocaine and their roles in the cocaine-mediated toxic effects.

  8. Medical Cannabis in Arizona: Patient Characteristics, Perceptions, and Impressions of Medical Cannabis Legalization.

    Science.gov (United States)

    Troutt, William D; DiDonato, Matthew D

    2015-01-01

    Many advances have been made toward understanding the benefits of medical cannabis. However, less is known about medical cannabis patients themselves. Prior research has uncovered many important patient characteristics, but most of that work has been conducted with participants in California, who may not represent medical cannabis patients throughout the United States. Furthermore, it is unknown if medical cannabis legalization, which typically imposes strict regulations on cannabis cultivation and sale, impacts patients' experiences acquiring and using cannabis. The goal of this study was to address these limitations by (1) examining the characteristics, perceptions, and behaviors of medical cannabis patients in Arizona; and (2) questioning participants with a history of cannabis use regarding their experiences with cannabis before and after legalization. Patients in Arizona share many characteristics with those in California, but also key differences, such as average age and degree of cannabis consumption. Participants also had positive perceptions of the effect of medical cannabis legalization, reporting that feelings of safety and awareness were higher after legalization compared to before. The results are discussed in relation to evidence from patients in other states and in terms of their potential policy implications.

  9. Cannabis consumption by female psychology students: the influence of perceived stress, coping and consumption of drugs in their social environment [Consumo de cannabis en alumnas de Psicología: influencia del estrés percibido, afrontamiento y consumo de drogas en su entorno

    Directory of Open Access Journals (Sweden)

    Cristina Vargas

    2012-03-01

    Full Text Available The consumption of cannabis has increased in the female population. The risk and protection factors associated with an increase or decrease in its consumption may differ as a function of gender, age and substance consumed. The objectives of the present study were to examine the relevance to cannabis consumption by female students of legal drugs consumed by the university students and family members, the consumption of legal and illicit drugs by friends, sociodemographic factors and, psychological variables (perceived stress and different coping strategies. Three questionnaires were administered to 465 female students studying for Psychology degrees. The prevalence of cannabis consumption was 36.3%. The variables predicting its consumption were: a consumption of illicit drugs and cocaine by friends; b consumption of tobacco by the students; c emotion-oriented coping.

  10. Cannabis and Related Impairment: The Unique Roles of Cannabis Use to Cope with Social Anxiety and Social Avoidance

    Science.gov (United States)

    Buckner, Julia D.; Zvolensky, Michael J.

    2017-01-01

    Background and Objectives Social anxiety appears to be a risk factor for cannabis-related problems. Socially anxious individuals are vulnerable to using cannabis to cope in social situations and to avoiding social situations if marijuana is unavailable. Yet, the relative impact of cannabis use to cope with social anxiety relative to use to cope with negative affect more broadly has yet to be examined. Methods The present study used the Marijuana to Cope with Social Anxiety Scale (MCSAS) to examine the incremental validity of using cannabis use to cope in social situations (MCSAS-Cope) and avoidance of social situations if cannabis is unavailable (MCSAS-Avoid) in a community-recruited sample of 123 (34.1% female) current cannabis users. Results After controlling for age of first cannabis use, gender, alcohol and tobacco use, other cannabis use motives, and cannabis expectancies, MCSAS-Cope remained significantly positively related to cannabis use frequency and cannabis-related problems. After controlling for age of first cannabis use, gender, alcohol and tobacco use, and experiential avoidance, MCSAS-Avoid remained significantly related to cannabis problems but not frequency. Discussion and Conclusions The present findings suggest that cannabis use to manage social forms of anxiety may be important to understanding cannabis use behaviors. Scientific Significance The current findings identify cognitive/motivational factors implicated in more frequent cannabis use and in cannabis-related impairment, which may be essential to inform efforts to further refine prevention and treatment efforts. PMID:25196146

  11. Cardiac Fas-dependent and mitochondria-dependent apoptosis after chronic cocaine abuse.

    Science.gov (United States)

    Liou, Cher-Ming; Tsai, Shiow-Chwen; Kuo, Chia-Hua; Ting, Hua; Lee, Shin-Da

    2014-04-09

    To evaluate whether chronic cocaine abuse will increase cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, thirty-two male Wistar rats at 3-4 months of age were randomly divided into a vehicle-treated group (phosphate-buffered saline, PBS, 0.5 mL, SQ per day) and a cocaine-treated group (Cocaine, 10 mg/kg, SQ per day). After 3 months of treatment, the excised left ventricles were measured by H&E staining, Western blotting, DAPI staining and TUNEL assays. More cardiac TUNEL-positive apoptotic cells were observed in the Cocaine group than the PBS group. Protein levels of TNF-alpha, Fas ligand, Fas death receptor, FADD, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts in the Cocaine group were significantly increased, compared to the PBS group. Protein levels of cardiac Bax, cytosolic cytochrome c, t-Bid-to-Bid, Bak-to-Bcl-xL, Bax-to-Bcl-2 ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the Cocaine group, compared to the PBS group. Chronic cocaine exposure appeared to activate the cardiac Fas-dependent and mitochondria-dependent apoptosis, which may indicate a possible mechanism for the development of cardiac abnormalities in humans with chronic cocaine abuse.

  12. Cardiac Fas-Dependent and Mitochondria-Dependent Apoptosis after Chronic Cocaine Abuse

    Directory of Open Access Journals (Sweden)

    Cher-Ming Liou

    2014-04-01

    Full Text Available To evaluate whether chronic cocaine abuse will increase cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, thirty-two male Wistar rats at 3–4 months of age were randomly divided into a vehicle-treated group (phosphate-buffered saline, PBS, 0.5 mL, SQ per day and a cocaine-treated group (Cocaine, 10 mg/kg, SQ per day. After 3 months of treatment, the excised left ventricles were measured by H&E staining, Western blotting, DAPI staining and TUNEL assays. More cardiac TUNEL-positive apoptotic cells were observed in the Cocaine group than the PBS group. Protein levels of TNF-alpha, Fas ligand, Fas death receptor, FADD, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis extracted from excised hearts in the Cocaine group were significantly increased, compared to the PBS group. Protein levels of cardiac Bax, cytosolic cytochrome c, t-Bid-to-Bid, Bak-to-Bcl-xL, Bax-to-Bcl-2 ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis were significantly increased in the Cocaine group, compared to the PBS group. Chronic cocaine exposure appeared to activate the cardiac Fas-dependent and mitochondria-dependent apoptosis, which may indicate a possible mechanism for the development of cardiac abnormalities in humans with chronic cocaine abuse.

  13. Effects of Repeated Cocaine Exposure on Habit Learning and Reversal by N-Acetylcysteine

    Science.gov (United States)

    Corbit, Laura H; Chieng, Billy C; Balleine, Bernard W

    2014-01-01

    Exposure to drugs of abuse can result in a loss of control over both drug- and nondrug-related actions by accelerating the transition from goal-directed to habitual control, an effect argued to reflect changes in glutamate homeostasis. Here we examined whether exposure to cocaine accelerates habit learning and used in vitro electrophysiology to investigate its effects on measures of synaptic plasticity in the dorsomedial (DMS) and dorsolateral (DLS) striatum, areas critical for actions and habits, respectively. We then administered N-acetylcysteine (NAC) in an attempt to normalize glutamate homeostasis and hence reverse the cellular and behavioral effects of cocaine exposure. Rats received daily injections of cocaine (30 mg/kg) for 6 days and were then trained to lever press for a food reward. We used outcome devaluation and whole-cell patch-clamp electrophysiology to assess the behavioral and cellular effects of cocaine exposure. We then examined the ability of NAC to reverse the effects of cocaine exposure on these measures. Cocaine treatment produced a deficit in goal-directed action, as assessed by outcome devaluation, and increased the frequency of spontaneous and miniature excitatory postsynaptic currents (EPSCs) in the DMS but not in the DLS. Importantly, NAC treatment both normalized EPSC frequency and promoted goal-directed control in cocaine-treated rats. The promotion of goal-directed control has the potential to improve treatment outcomes in human cocaine addicts. PMID:24531561

  14. Nutritional effects of marijuana, heroin, cocaine, and nicotine.

    Science.gov (United States)

    Mohs, M E; Watson, R R; Leonard-Green, T

    1990-09-01

    Use of addictive drugs, such as cocaine, marijuana, and nicotine, affects food and liquid intake behavior, taste preference, and body weight. Changes in specific nutrient status and metabolism can also develop; heroin addiction can cause hyperkalemia and morphine use can result in calcium inhibition. Nutrition-related physiological aspects, such as impaired gastrin release, hypercholesterolemia, hypothermia, and hyperthermia, are also seen with morphine use. Nutrition-related conditions can affect sensitivity to and dependence on drugs and their effects. Diabetes decreases sensitivity to and dependence on morphine, protein deprivation produces preferential fat utilization with low cocaine use, and vitamin D deficiency decelerates morphine dependency. During use and/or withdrawal from nicotine, heroin, marijuana, and cocaine, major changes in food selection and intake occur, which result in weight gain or loss. Detailed human studies are needed to investigate the effects of drug use on the broad spectrum of nutrients and to determine the role of nutrition during drug withdrawal.

  15. Examining the profile of high-potency cannabis and its association with severity of cannabis dependence.

    Science.gov (United States)

    Freeman, T P; Winstock, A R

    2015-11-01

    Cannabis use is decreasing in England and Wales, while demand for cannabis treatment in addiction services continues to rise. This could be partly due to an increased availability of high-potency cannabis. Adults residing in the UK were questioned about their drug use, including three types of cannabis (high potency: skunk; low potency: other grass, resin). Cannabis types were profiled and examined for possible associations between frequency of use and (i) cannabis dependence, (ii) cannabis-related concerns. Frequent use of high-potency cannabis predicted a greater severity of dependence [days of skunk use per month: b = 0.254, 95% confidence interval (CI) 0.161-0.357, p cannabis was not associated with dependence (days of other grass use per month: b = 0.020, 95% CI -0.029 to 0.070, p = 0.436; days of resin use per month: b = 0.025, 95% CI -0.019 to 0.067, p = 0.245). Frequency of cannabis use (all types) did not predict severity of cannabis-related concerns. High-potency cannabis was clearly distinct from low-potency varieties by its marked effects on memory and paranoia. It also produced the best high, was preferred, and most available. High-potency cannabis use is associated with an increased severity of dependence, especially in young people. Its profile is strongly defined by negative effects (memory, paranoia), but also positive characteristics (best high, preferred type), which may be important when considering clinical or public health interventions focusing on cannabis potency.

  16. Quality of Web-Based Information on Cannabis Addiction

    Science.gov (United States)

    Khazaal, Yasser; Chatton, Anne; Cochand, Sophie; Zullino, Daniele

    2008-01-01

    This study evaluated the quality of Web-based information on cannabis use and addiction and investigated particular content quality indicators. Three keywords ("cannabis addiction," "cannabis dependence," and "cannabis abuse") were entered into two popular World Wide Web search engines. Websites were assessed with a standardized proforma designed…

  17. Cannabis in Europe: Dynamics in perception, policy and markets

    NARCIS (Netherlands)

    Korf, D.J.

    2008-01-01

    After its re-introduction in the 1960s, cannabis has become the most widely used illicit drug in Europe. Along with the spread of cannabis use, its social meaning has changed over time. Today old paradigms are having renewed appeal, in particular on the subject of cannabis and schizophrenia. Cannabi

  18. Quality of Web-Based Information on Cannabis Addiction

    Science.gov (United States)

    Khazaal, Yasser; Chatton, Anne; Cochand, Sophie; Zullino, Daniele

    2008-01-01

    This study evaluated the quality of Web-based information on cannabis use and addiction and investigated particular content quality indicators. Three keywords ("cannabis addiction," "cannabis dependence," and "cannabis abuse") were entered into two popular World Wide Web search engines. Websites were assessed with a standardized proforma designed…

  19. Cannabis (marijuana) contamination of United States and foreign paper currency.

    Science.gov (United States)

    Lavins, Eric S; Lavins, Bethany D; Jenkins, Amanda J

    2004-09-01

    It is well known that United States paper currency in general circulation is contaminated with trace amounts of illicit substances such as cocaine, heroin and marijuana. As is the case with cocaine, differentiating "background levels" of the various cannabinoid constituents of Cannabis sativa L., namely, Delta(9)-tetrahydrocannabinol (THC), cannabinol (CBN), and cannabidiol (CBD) contaminating currency found in the general circulation from currency associated with illegal drug activity is imperative if a legal nexus is to be established with the latter. We analyzed 165 randomly collected paper currency notes from 12 U.S. cities (N = 125) and 4 foreign countries (N = 40) for THC, CBD, CBN, 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol, and 11-hydroxy-Delta(9)-tetrahydrocannabinol. Uncirculated US 1 dollar notes were added as negative controls. Drug residues were washed from individual bills, extracted using a liquid-liquid extraction protocol, derivatized, and quantitated by gas chromatography-mass spectrometry by selected ion monitoring. For the US 1 dollar currency, THC was present in 1.6% (2 notes), CBN 10.31% (13 notes), CBD 1.6% (2 notes). The following concentrations were determined: 0.085 microg/bill and 0.146 microg/bill for THC; 0.014-0.774 microg/bill (mean 0.166 microg/bill) for CBN; and 0.032 microg/bill and 0.086 microg/bill for CBD. For the foreign currency (Colombia, Qatar, India, and New Zealand), THC and CBN were present in 22.5% (9 notes). The following concentration ranges were determined: THC 0.026-0.065 microg/bill (mean 0.049 microg/bill), CBN 0.061-0.197 microg/bill (mean 0.115 microg/bill). All of the positive THC and CBN were found in the New Zealand polypropylene notes. This study demonstrated that marijuana (cannabinoids) may contaminate both paper and plastic currency.

  20. Behaviour of hygrine and cuscohygrine in illicit cocaine production establishes their use as markers for chewing coca leaves in contrast with cocaine abuse.

    Science.gov (United States)

    Rubio, Nelida Cristina; Thurmann, Denise; Krumbiegel, Franziska; Pragst, Fritz

    2017-02-01

    Hygrine (HYG) and cuscohygrine (CUS) are natural alkaloids of coca leaves but are not found in illicit cocaine seizures. Therefore, they were proposed as markers for coca chewing in contrast to cocaine abuse in urine and hair testing. In order to examine at which step of the illegal cocaine production these compounds are lost, coca leaves were processed according to an authentic procedure by extraction with lime and kerosene, re-extraction with sulphuric acid, and precipitation of coca paste with ammonia. Non-extracted and extracted coca leaves, acidic extract and coca paste were analyzed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for cocaine, ecgonine methyl ester (EME), cinnamoylcocaine (CIN), HYG, and CUS. It follows from the results that under these conditions, HYG and CUS are extracted only to a minor extent by kerosene and are not precipitated from the acidic re-extract in the coca paste. Due to this behaviour in illegal cocaine production, they fulfil the conditions as markers for coca chewing in an optimal way. However, for unambiguous discrimination between coca chewing and cocaine abuse in human samples, additional markers of manufactured cocaine are required. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Cannabis use disorders and brain morphology

    NARCIS (Netherlands)

    Lorenzetti, V.; Cousijn, J.; Preedy, V.R.

    2016-01-01

    Cannabis use disorders (CUDs) affect 13.1. million individuals worldwide and represent the most vulnerable portion of regular cannabis users. Neuroanatomical alterations in the brain may mediate the adverse outcomes of CUDs. We reviewed findings from 16 structural neuroimaging studies of gray matter

  2. Cannabis og cannabinoidreceptorer--misbrug og psykose

    DEFF Research Database (Denmark)

    Hjorthøj, Carsten; Nordentoft, Merete; Fink-Jensen, Anders

    2008-01-01

    Abuse of alcohol and drugs often co-occur with psychotic disorders. In this article, we introduce to the reader a number of receptors and neurotransmitter-systems involved in cannabis-abuse. Subsequently, we introduce the connection between abuse - particularly cannabis-abuse - and psychotic...

  3. The dynamics of cannabis use and dependence

    NARCIS (Netherlands)

    van der Pol, P.M.

    2014-01-01

    Young adults who often smoke cannabis are at higher risk of dependence, but most do not become dependent. This thesis examined the question: Which frequent cannabis users are/become/stay dependent, and seek treatment, and which do not? It was answered with a three-year prospective cohort of 600 youn

  4. Cannabis og cannabinoidreceptorer misbrug og psykose

    DEFF Research Database (Denmark)

    Hjorthoj, C.; Nordentoft, M.; Fink-Jensen, A.

    2008-01-01

    Abuse of alcohol and drugs often co-occur with psychotic disorders. In this article, we introduce to the reader a number of receptors and neurotransmitter-systems involved in cannabis-abuse. Subsequently, we introduce the connection between abuse - particularly cannabis-abuse - and psychotic...

  5. The dynamics of cannabis use and dependence

    NARCIS (Netherlands)

    van der Pol, P.M.

    2014-01-01

    Young adults who often smoke cannabis are at higher risk of dependence, but most do not become dependent. This thesis examined the question: Which frequent cannabis users are/become/stay dependent, and seek treatment, and which do not? It was answered with a three-year prospective cohort of 600 youn

  6. Cannabis og cannabinoidreceptorer misbrug og psykose

    DEFF Research Database (Denmark)

    Hjorthoj, C.; Nordentoft, M.; Fink-Jensen, A.

    2008-01-01

    Abuse of alcohol and drugs often co-occur with psychotic disorders. In this article, we introduce to the reader a number of receptors and neurotransmitter-systems involved in cannabis-abuse. Subsequently, we introduce the connection between abuse - particularly cannabis-abuse - and psychotic...

  7. Cannabis og cannabinoidreceptorer--misbrug og psykose

    DEFF Research Database (Denmark)

    Hjorthøj, Carsten; Nordentoft, Merete; Fink-Jensen, Anders

    2008-01-01

    Abuse of alcohol and drugs often co-occur with psychotic disorders. In this article, we introduce to the reader a number of receptors and neurotransmitter-systems involved in cannabis-abuse. Subsequently, we introduce the connection between abuse - particularly cannabis-abuse - and psychotic...

  8. Therapeutic Use of Cannabis in Inflammatory Bowel Disease

    Science.gov (United States)

    Katz, Seymour

    2016-01-01

    The marijuana plant Cannabis sativa and its derivatives, cannabinoids, have grown increasingly popular as a potential therapy for inflammatory bowel disease (IBD). Studies have shown that modulation of the endocannabinoid system, which regulates various functions in the body and has been shown to play a key role in the pathogenesis of IBD, has a therapeutic effect in mouse colitis. Epidemiologic data and human therapy studies reveal a possible role for cannabinoids in the symptomatic treatment of IBD, although it has yet to be determined in human populations whether cannabinoids have therapeutic anti-inflammatory effects in IBD or are simply masking its many debilitating symptoms. Large, double-blind, randomized, placebo-controlled trials using serial inflammatory markers, biopsy findings, and endoscopic disease severity to demonstrate objective improvement in IBD are necessary before cannabis can be empirically accepted and recommended as an IBD treatment option. Questions concerning its safety profile and adverse effects prompt the need for further research, particularly in regard to dosing and route of administration to maximize benefits and limit potential harms. Cannabis use should be reserved for symptomatic control in patients with severe IBD refractory to the currently available standard-of-care and complementary and alternative medicines. PMID:28035196

  9. Cannabis arteritis: ever more important to consider.

    Science.gov (United States)

    Santos, Rui Pedro; Resende, Cristina Isabel Pinho; Vieira, Ana Paula; Brito, Celeste

    2017-03-13

    Cannabis arteritis (CA) is a major and underdiagnosed cause of peripheral arterial disease in young patients. A 34-year-old man, daily smoker of 20 cigarettes and two cannabis cigarettes for 14 years, presented with a necrotic plaque of left hallux for 3 weeks. The Doppler ultrasound and angiography were compatible with severe Buerger's disease. Submitted to a revascularisation procedure and hypocoagulation with rivaroxaban. He had ceased smoking but maintained consumption of cannabis. Owing to the persistence of distal necrosis, amputation of the hallux was performed with good evolution. CA is a subtype of Buerger's disease. It is poorly known but increasingly prevalent and manifests in cannabis users regardless of tobacco use. The drug is considered at least a cofactor of the arteriopathy. The most effective treatment is cessation of consumption. Being cannabis one of the most consumed drugs, its mandatory to ask about its use in all young patients with arteriopathy.

  10. Association Between Cannabis and Psychosis: Epidemiologic Evidence.

    Science.gov (United States)

    Gage, Suzanne H; Hickman, Matthew; Zammit, Stanley

    2016-04-01

    Associations between cannabis use and psychotic outcomes are consistently reported, but establishing causality from observational designs can be problematic. We review the evidence from longitudinal studies that have examined this relationship and discuss the epidemiologic evidence for and against interpreting the findings as causal. We also review the evidence identifying groups at particularly high risk of developing psychosis from using cannabis. Overall, evidence from epidemiologic studies provides strong enough evidence to warrant a public health message that cannabis use can increase the risk of psychotic disorders. However, further studies are required to determine the magnitude of this effect, to determine the effect of different strains of cannabis on risk, and to identify high-risk groups particularly susceptible to the effects of cannabis on psychosis. We also discuss complementary epidemiologic methods that can help address these questions. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. The draft genome and transcriptome of Cannabis sativa.

    Science.gov (United States)

    van Bakel, Harm; Stout, Jake M; Cote, Atina G; Tallon, Carling M; Sharpe, Andrew G; Hughes, Timothy R; Page, Jonathan E

    2011-10-20

    Cannabis sativa has been cultivated throughout human history as a source of fiber, oil and food, and for its medicinal and intoxicating properties. Selective breeding has produced cannabis plants for specific uses, including high-potency marijuana strains and hemp cultivars for fiber and seed production. The molecular biology underlying cannabinoid biosynthesis and other traits of interest is largely unexplored. We sequenced genomic DNA and RNA from the marijuana strain Purple Kush using shortread approaches. We report a draft haploid genome sequence of 534 Mb and a transcriptome of 30,000 genes. Comparison of the transcriptome of Purple Kush with that of the hemp cultivar 'Finola' revealed that many genes encoding proteins involved in cannabinoid and precursor pathways are more highly expressed in Purple Kush than in 'Finola'. The exclusive occurrence of Δ9-tetrahydrocannabinolic acid synthase in the Purple Kush transcriptome, and its replacement by cannabidiolic acid synthase in 'Finola', may explain why the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) is produced in marijuana but not in hemp. Resequencing the hemp cultivars 'Finola' and 'USO-31' showed little difference in gene copy numbers of cannabinoid pathway enzymes. However, single nucleotide variant analysis uncovered a relatively high level of variation among four cannabis types, and supported a separation of marijuana and hemp. The availability of the Cannabis sativa genome enables the study of a multifunctional plant that occupies a unique role in human culture. Its availability will aid the development of therapeutic marijuana strains with tailored cannabinoid profiles and provide a basis for the breeding of hemp with improved agronomic characteristics.

  12. Cannabis and neuropsychiatry, 1: benefits and risks.

    Science.gov (United States)

    Andrade, Chittaranjan

    2016-05-01

    Cannabis is popularly believed to be a relatively benign substance. Cannabis is also considered to have potential medical benefits, and medical marijuana has been legislated in many parts of the world. However, a recent meta-analysis found that cannabinoids were associated with only modest benefits for chemotherapy-related nausea and vomiting, small and inconsistent benefits for pain and spasticity, and inconclusive benefits for other indications such as improvement of appetite and weight, reduction in tic severity, and improvement of mood or sleep. On the flip side, cannabinoids and cannabis have acute and long-term adverse effects. In randomized controlled trials, cannabinoids increase the risk of total adverse events, serious adverse events, and dropout due to adverse events. Cannabis impairs cognition, and driving after cannabis use is associated with an increased risk of traffic accidents, including fatal accidents. Long-term cannabis use may lead to dependence, respiratory conditions, psychosis, and possibly cancer, as well. Cannabis use during pregnancy may compromise certain pregnancy outcomes such as fetal growth, and use during adolescence may compromise neurodevelopment, social adjustment, and vocational success. The composition and bioavailability of cannabis vary across preparations of the substance and routes of administration; this limits the ability to generalize the findings of studies. The findings of older research may no longer apply to current strains of cannabis that are higher in psychotogenic content. It is important for medical professionals and the lay public to understand the limitations of the efficacy data and the seriousness of the risks associated with cannabis use in medical and recreational contexts.

  13. Cocaine and "pharmacological kindling" in the rat.

    Science.gov (United States)

    Stripling, J S

    1983-11-01

    The concept of "pharmacological kindling" has been used to explain the behavioral sensitization to cocaine produced by repeated administration of subconvulsive doses. This idea was tested by the repeated administration of cocaine to rats followed by electrical kindling of the olfactory bulb (a site at which cocaine has prominent electrophysiologic effects). No significant effect of cocaine on kindling was found. The relationship of this finding to studies using other drugs is discussed.

  14. Citalopram enhances cocaine's subjective effects in rats

    OpenAIRE

    Soto, Paul L.; Hiranita, Takato; Katz, Jonathan L.

    2009-01-01

    Serotonin-selective reuptake inhibitors (SSRIs) have been shown to enhance the locomotor stimulatory, discriminative-stimulus, and convulsive effects of cocaine in rodents. A pharmacokinetic mechanism for the interaction is supported by increases in the brain levels of cocaine by fluoxetine treatment. Furthermore, the locomotor-stimulant effects of cocaine in rodents are enhanced by fluoxetine and fluvoxamine, SSRIs known to inhibit cocaine-metabolizing cytochrome P450 enzymes, whereas citalo...

  15. Cannabis Withdrawal Symptoms in Non-Treatment-Seeking Adult Cannabis Smokers

    Science.gov (United States)

    Levin, Kenneth H.; Copersino, Marc L.; Heishman, Stephen J.; Liu, Fang; Kelly, Deanna L.; Boggs, Douglas L.; Gorelick, David A.

    2010-01-01

    Background Cannabis withdrawal is not recognized in DSM-IV because of doubts about its clinical significance. Objectives Assess the phenomenon of cannabis withdrawal and its relationship to relapse in non-treatment-seeking adults. Subjects Convenience sample of 469 adult cannabis smokers who had made a quit attempt while not in a controlled environment. Methods Subjects completed a 176-item Marijuana Quit Questionnaire collecting information on sociodemographic characteristics, cannabis use history, and their “most difficult” cannabis quit attempt. Results 42.4% of subjects had experienced a lifetime withdrawal syndrome, of whom 70.4% reported using cannabis in response to withdrawal. During the index quit attempt, 95.5% of subjects reported ≥1 individual withdrawal symptom (mean [SD] 9.5 [6.1], median 9.0); 43.1% reported ≥10. Number of withdrawal symptoms was significantly associated with greater frequency and amount of cannabis use, but symptoms occurred even in those using less than weekly. Symptoms were usually of ≥ moderate intensity and often prompted actions to relieve them. Alcohol (41.5 %) and tobacco (48.2%) were used more often than cannabis (33.3%) for this purpose. There was little change during withdrawal in use of other legal or illegal substances. Conclusions Cannabis withdrawal is a common syndrome among adults not seeking treatment. The intention to relieve withdrawal symptoms can drive relapse during quit attempts, giving cannabis withdrawal clinical significance as a target of treatment. PMID:20510550

  16. Immunohistochemical distribution of cocaine- and amphetamine-regulated transcript peptide - like immunoreactive (CART-LI) nerve fibers and various degree of co-localization with other neuronal factors in the circular muscle layer of human descending colon.

    Science.gov (United States)

    Gonkowski, Sławomir; Kamińska, Barbara; Landowski, Piotr; Całka, Jarosław

    2013-07-01

    Cocaine- and amphetamine-regulated transcript peptide (CART) is a neuromediator and/or neuromodulator in nerve structures within the gastrointestinal tract, but knowledge about its distribution, functions and co-localisation with other neuronal factors, especially in humans, is very scarce. During the present investigation the distribution and immunohistochemical reaction (IR) of CART - like immunoreactive (CART-LI) nerve fibers in the circular muscle layer of human descending colon were studied. Fragments of human colon were processed for double labelling immunofluorescence using a mixture of anti-CART antibodies with antibodies against vesicular acetylocholine transporter (VAChT), vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase - activating peptide (PACAP), substance P (SP), galanin (GAL) and nitric oxide synthase (NOS). Thick CART-LI nerve fibers formed a very dense meshwork within the colonic circular muscle layer in all patients studied. The highest number of CART - positive nerves also contained VAChT and/or VIP. A slightly lower level of co-localisation was observed in the case of CART and PACAP or CART and NOS. Only single nerve fibers were concurrently immunoreactive to CART and SP or CART and GAL. The present study reports for the first time a detailed description of the IR of CART-LI nerve fibers in the circular muscle layer within adult human descending colon.

  17. Using cannabis to help you sleep: heightened frequency of medical cannabis use among those with PTSD.

    Science.gov (United States)

    Bonn-Miller, Marcel O; Babson, Kimberly A; Vandrey, Ryan

    2014-03-01

    The use of cannabis for medical purposes is proliferating in the U.S., and PTSD is an explicitly approved condition for accessing medical cannabis in 5 states. Prior research suggests that people with PTSD often use cannabis to help cope with their condition, and that doing so results in more frequent and problematic cannabis use patterns. Specific coping motivations, such as sleep improvement, among medical cannabis users, have not been examined. The present study evaluated specific coping use motivations, frequency of cannabis and alcohol use, and mental health among a convenience sample of patients (N=170) at a medical cannabis dispensary in California. Those with high PTSD scores were more likely to use cannabis to improve sleep, and for coping reasons more generally, compared with those with low PTSD scores. Cannabis use frequency was greater among those with high PTSD scores who used for sleep promoting purposes compared with those with low PTSD scores or those who did not use for sleep promoting purposes. Consistent with prior research, this study found increased rates of coping-oriented use of cannabis and greater frequency of cannabis use among medical users with high PTSD scores compared with low PTSD scores. In addition, sleep improvement appears to be a primary motivator for coping-oriented use. Additional research is needed to examine the health consequences of this pattern of cannabis use and whether alternative sleep promoting interventions (e.g. CBT-I) could reduce the reliance on cannabis for adequate sleep among those with PTSD. Published by Elsevier Ireland Ltd.

  18. Vaping cannabis (marijuana): parallel concerns to e-cigs?

    OpenAIRE

    Budney, Alan J.; Sargent, James D.; Lee, Dustin C.

    2015-01-01

    The proliferation of vaporization (‘vaping’) as a method for administering cannabis raises many of the same public health issues being debated and investigated in relation to e-cigarettes (e-cigs). Good epidemiological data on the prevalence of vaping cannabis are not yet available, but with current trends towards societal approval of medicinal and recreational use of cannabis, the pros and cons of vaping cannabis warrant study. As with e-cigs, vaping cannabis portends putative health benefit...

  19. Legalising medical use of cannabis in South Africa: Is the empirical evidence sufficient to support policy shifts in this direction?

    Science.gov (United States)

    Parry, Charles D H; Myers, Bronwyn J

    2014-03-12

    Inkatha Freedom Party MP Mario Oriani-Ambrosini's impassioned plea to legalise the medical use of cannabis must be understood in the context of his own condition as well as legislative changes in at least ten countries. This article argues that any decisions to shift policy must be based on a consideration of the evidence on the risks and benefits associated with the medical use of cannabis for the individual and broader society. It concludes that there are important gaps in the evidence base, particularly in human trials supporting the efficacy of cannabis use for treating and preventing medical conditions and alleviating negative symptoms associated with these conditions. South African researchers should be enabled actively to support development of the necessary evidence base actively by conducting preclinical and clinical research in this area. Human trials to establish the efficacy of the use of cannabis/cannabinoids in addressing AIDS wasting syndrome and other negative sequelae of HIV and AIDS are especially needed.

  20. Prenatal and acute cocaine exposure affects neural responses and habituation to visual stimuli

    Directory of Open Access Journals (Sweden)

    Elizabeth Brooke Riley

    2015-08-01

    Full Text Available Psychostimulants have many effects on visual function, from adverse, following acute and prenatal exposure to therapeutic, on attention deficit. To determine the impact of prenatal and acute cocaine exposure on visual processing, we studied neuronal responses to visual stimuli in two brain regions of a transgenic larval zebrafish expressing the calcium indicator GCaMP-HS. We found that both red light (LF and dark (DF flashes elicited similar responses in the optic tectum neuropil (TOn, while the dorsal telencephalon (dTe responded only to LF. Acute cocaine (0.5 μM reduced neuronal responses to LF in both brain regions but did not affect responses to DF. Repeated stimulus presentation led to habituation of dTe neurons to LF. Acute cocaine prevented habituation. TOn habituated to DF, but not LF, and DF habituation was not modified by cocaine. Remarkably, prenatal cocaine exposure prevented the effects of acute cocaine on LF response amplitude and habituation later in development in both brain regions, but did not affect DF responses. We discovered that, in spite of similar neural responses to LF and DF in the TO (superior colliculus in mammals, responses to LF are more complex, involving dTe (homologous to the cerebral cortex, and are more vulnerable to cocaine. Our results demonstrate that acute cocaine exposure affects visual processing differentially by brain region, and that prenatal cocaine exposure modifies zebrafish visual processing in multiple structures in a stimulus-dependent manner. These findings are in accordance with the major role that the optic tectum and cerebral cortex play in sustaining visual attention, and support the hypothesis that modification of these areas by prenatal cocaine exposure may be responsible for visual deficits noted in humans. This model offers new methodological approaches for studying the adverse and therapeutic effects of psychostimulants on attention, and for the development of new pharmacological

  1. The emergency care of cocaine intoxications.

    NARCIS (Netherlands)

    Vroegop, M.P.; Franssen, E.J.; Voort, P.H. van der; Berg, T.N. van den; Langeweg, R.J.; Kramers, C.

    2009-01-01

    Cocaine is frequently used, especially among adolescents and by men between the age of 25 and 44. Many of them are able to use cocaine in normal day-to-day life, without any problems. Reduced prices of cocaine and other recreational drugs such as MDMA (ecstasy) and gamma hydroxybutyrate (GHB) has le

  2. Current Therapeutic Cannabis Controversies and Clinical Trial Design Issues

    Science.gov (United States)

    Russo, Ethan B.

    2016-01-01

    This overview covers a wide range of cannabis topics, initially examining issues in dispensaries and self-administration, plus regulatory requirements for production of cannabis-based medicines, particularly the Food and Drug Administration “Botanical Guidance.” The remainder pertains to various cannabis controversies that certainly require closer examination if the scientific, consumer, and governmental stakeholders are ever to reach consensus on safety issues, specifically: whether botanical cannabis displays herbal synergy of its components, pharmacokinetics of cannabis and dose titration, whether cannabis medicines produce cyclo-oxygenase inhibition, cannabis-drug interactions, and cytochrome P450 issues, whether cannabis randomized clinical trials are properly blinded, combatting the placebo effect in those trials via new approaches, the drug abuse liability (DAL) of cannabis-based medicines and their regulatory scheduling, their effects on cognitive function and psychiatric sequelae, immunological effects, cannabis and driving safety, youth usage, issues related to cannabis smoking and vaporization, cannabis concentrates and vape-pens, and laboratory analysis for contamination with bacteria and heavy metals. Finally, the issue of pesticide usage on cannabis crops is addressed. New and disturbing data on pesticide residues in legal cannabis products in Washington State are presented with the observation of an 84.6% contamination rate including potentially neurotoxic and carcinogenic agents. With ongoing developments in legalization of cannabis in medical and recreational settings, numerous scientific, safety, and public health issues remain. PMID:27683558

  3. Evaluating the efficacy of a web-based self-help intervention with and without chat counseling in reducing the cocaine use of problematic cocaine users: the study protocol of a pragmatic three-arm randomized controlled trial.

    Science.gov (United States)

    Schaub, Michael P; Maier, Larissa J; Wenger, Andreas; Stark, Lars; Berg, Oliver; Beck, Thilo; Quednow, Boris B; Haug, Severin

    2015-07-10

    Web-based self-help interventions that aim to reduce problematic substance use are able to reach "hidden" consumer groups in the general population who often fear stigmatization and thus avoid institutional addiction treatment. In Western European countries, including Switzerland, cocaine is the most widely used psychoactive substance after alcohol, tobacco, and cannabis. Although approximately one in six users develop serious problems of dependency, only a minority seeks help from psychiatrists or in outpatient counseling centers or psychiatric hospitals. Offering web-based therapy treatment may potentially reach users who hesitate to approach institutional treatment services and help them reduce their cocaine use before they get into more serious trouble. The study will use a three-arm randomized controlled trial (RCT) design to test the efficacy of a web-based self-help intervention with or without guided chat counseling compared with that of a waiting list control condition in reducing or stopping cocaine use. The primary outcome measure will be the weekly quantity of cocaine used. Secondary outcome measures will include the number of cocaine use days in the past 30 days, the severity of cocaine dependence, the use of alcohol, tobacco, and/or other illicit drugs, changes in mental health symptoms, and treatment retention. The self-help intervention will consist of eight modules that are designed to reduce cocaine use and depression symptoms. These modules are based on the principles of Motivational Enhancement Therapy and Cognitive Behavioral Therapy, such as Behavioral Self-Management. The three individual chat therapy sessions will be based on the same therapy approaches and will be tailored to participants' self-help data and aim to assist the reinstatement of social rewards and the improvement of social support and relationships. This study will be the first RCT to test the effectiveness of a web-based self-help intervention in combination with or without

  4. Health aspects of cannabis: revisited.

    Science.gov (United States)

    Hollister, Leo E.

    1998-07-01

    Literature pertaining to the effects of cannabis use and health which has been published during the past 11 years has been reviewed. Many older concerns about adverse effects on health (chromosomal damage, 'cannabinol psychosis', endocrine abnormalities, cardiac events, impaired immunity) no longer seem to elicit much interest. Continuing concerns about the adverse cognitive effects of chronic use indicate that these can be demonstrated by proper testing; some studies suggest that they may be long-lasting. Although cannabis does not produce a specific psychosis, the possibility exists that it may exacerbate schizophrenia in persons predisposed to that disorder. However, evidence from retrospective surveys must always be questioned. Tolerance and dependence have occurred in man, confirming previous findings in many other species. Addiction tends to be mild and is probably less severe than with other social drugs. Driving under the influence of cannabis is impaired acutely; how long such impairments last is still unknown. More exacting tasks, such as flying an airplane, may be impaired for as long as 24 hours. While there is no doubt that marijuana smoke contains carcinogens, an increase in cancer among users has thus far been anecdotal. Because of the long latent period between cancer induction and initiation of cigarette smoking, the full story is yet to be told. Marijuana use during pregnancy is not advised although the consequences are usually not greater than those of smoking cigarettes, and far less than those from alcohol use. Whether smoked marijuana should become a therapeutic agent requires a cost-benefit analysis of the potential benefits versus the adverse effects of such use as we now know them.

  5. Studies towards the improvement of an anti-cocaine monoclonal antibody for treatment of acute overdose.

    Science.gov (United States)

    Zhou, Bin; Eubanks, Lisa M; Jacob, Nicholas T; Ellis, Beverly; Roberts, Amanda J; Janda, Kim D

    2016-10-15

    There is currently no clinically-approved antidote for cocaine overdose. Efforts to develop a therapy via passive immunization have resulted in a human monoclonal antibody, GNCgzk, with a high affinity for cocaine (Kd=0.18nM). Efforts to improve the production of antibody manifolds based on this antibody are disclosed. The engineering of an HRV 3C protease cleavage site into the GNCgzk IgG has allowed for increased production of a F(ab')2 with a 20% superior capacity to reduce mortality for cocaine overdose in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Old drug new trick: levamisole-adulterated cocaine causing acute kidney injury.

    Science.gov (United States)

    Ammar, Abeer T; Livak, Mark; Witsil, Joanne C

    2015-02-01

    Levamisole is an agent previously used in humans and later withdrawn from the US drug market due to concerns of agranulocytosis.It is currently used as an adulterating agent in cocaine, bringing to light toxicities typically manifested by vasculitis and skin necrosis.We report a case of a 36-year-old crack cocaine user who presented with a purpuric rash on her face and limbs. Levamisole-induced vasculitis was suspected, and she therefore underwent an extensive work-up. In addition to these findings, she also presented with acute kidney injury of unknown etiology, which was later attributed to levamisoleadulterated cocaine.

  7. [Neurologic complications of cocaine abuse].

    Science.gov (United States)

    Van Viet, H; Chevalier, P; Sereni, C; Bornet, P; Bautier, P; Degos, C F; Rullière, R

    1990-06-02

    Cocaine is increasingly used by drug addicts. It is considered harmless, but numerous, varied and often serious complications due to its abuse have been published. Among these, neurological complications are in the forefront. They include generalized or partial epileptic seizures, ischaemic or haemorrhagic cerebral vascular accidents, visual loss caused by optic neuropathy or by retinal artery occlusion, headaches and exacerbation of tics. Infections of the central nervous system are possible via endocarditis or septicaemia of venous or nasal origin. Neurological disorders may also occur as a consequence of a major cardiovascular complication induced by cocaine (myocardial infarction and/or dysrhythmia, aortic dissection). These neurological complications are unpredictable, and they weigh heavily on the functional and sometimes vital prognosis in habitual or occasional cocaine abusers.

  8. Cannabis Use Frequency and Use-Related Impairment among African American and White Users: The Impact of Cannabis Use Motives

    Science.gov (United States)

    Shah, Sonia M.; Dean, Kimberlye E.; Zvolensky, Michael J.

    2015-01-01

    Objectives Cannabis use motives are differentially related to cannabis-related impairment and coping motives appear to have the strongest relation to use-related impairment. However, it is currently unknown whether African American individuals differ from White persons in reasons for using cannabis. It is also unknown whether motives’ relations to cannabis use and related impairment vary as a function of race. The present study examined the role of race on cannabis use motives and tested whether motives’ relations with cannabis use and related impairment differed by race. Design The sample consisted of 111 (67.6% non-Hispanic White, 32.4% African American) current cannabis-using adults. Results African American participants did not significantly differ from White participants on cannabis use frequency or use-related impairment. African American participants endorsed more social motives than White participants. Race interacted with social, coping, and conformity motives to predict cannabis-related impairment such that these motives were positively related to cannabis impairment among African American, but not White, participants. Conclusion Although African American and White participants do not differ in their cannabis use frequency or cannabis-related impairment, they appear to use cannabis for different reasons. Further, conformity, coping, and social motives were differentially associated with cannabis-related impairment as a function of race. Findings suggest motives for cannabis use should be contexualized in the context of race. PMID:26264291

  9. Brugada Pattern Electrocardiogram Unmasked with Cocaine Ingestion

    Directory of Open Access Journals (Sweden)

    M. Chadi Alraies

    2013-01-01

    Full Text Available Cocaine is considered a leading cause of drug-related deaths. This is usually sudden, unwitnessed, and without prodromal features. It has been reported that in-hospital mortality is close to 2%. Cocaine has powerful central nervous system effects1 and acute cocaine overdose has been associated with hyperthermia, agitation, paranoid ideation, status epilepticus, ventricular fibrillation, ventricular tachycardia, and myocardial infarction (MI. The mechanisms of cocaine-related death remain poorly understood. We report a patient who survived massive cocaine ingestion with psychomotor agitation and generalized seizures followed by asystolic cardiac arrest and transient Brugada pattern on electrocardiogram (ECG.

  10. Cocaine distribution in wild Erythroxylum species.

    Science.gov (United States)

    Bieri, Stefan; Brachet, Anne; Veuthey, Jean-Luc; Christen, Philippe

    2006-02-20

    Cocaine distribution was studied in leaves of wild Erythroxylum species originating from Bolivia, Brazil, Ecuador, Paraguay, Peru, Mexico, USA, Venezuela and Mauritius. Among 51 species, 28 had never been phytochemically investigated before. Cocaine was efficiently and rapidly extracted with methanol, using focused microwaves at atmospheric pressure, and analysed without any further purification by capillary gas chromatography coupled to mass spectrometry. Cocaine was reported for the first time in 14 species. Erythroxylum laetevirens was the wild species with the highest cocaine content. Its qualitative chromatographic profile also revealed other characteristic tropane alkaloids. Finally, its cocaine content was compared to those of two cultivated coca plants as well as with a coca tea bag sample.

  11. Multiple Gastrointestinal Complications of Crack Cocaine Abuse

    Directory of Open Access Journals (Sweden)

    Neal Carlin

    2014-01-01

    Full Text Available Cocaine and its alkaloid free base “crack-cocaine” have long since been substances of abuse. Drug abuse of cocaine via oral, inhalation, intravenous, and intranasal intake has famously been associated with a number of medical complications. Intestinal ischemia and perforation remain the most common manifestations of cocaine associated gastrointestinal disease and have historically been associated with oral intake of cocaine. Here we find a rare case of two relatively uncommon gastrointestinal complications of hemorrhage and pancreatitis presenting within a single admission in a chronic crack cocaine abuser.

  12. Cannabis Cue Reactivity and Craving Among Never, Infrequent and Heavy Cannabis Users

    OpenAIRE

    Henry, Erika A.; Kaye, Jesse. T.; Bryan, Angela D.; Hutchison, Kent E.; Ito, Tiffany A.

    2013-01-01

    Substance cue reactivity is theorized as having a significant role in addiction processes, promoting compulsive patterns of drug-seeking and drug-taking behavior. However, research extending this phenomenon to cannabis has been limited. To that end, the goal of the current work was to examine the relationship between cannabis cue reactivity and craving in a sample of 353 participants varying in self-reported cannabis use. Participants completed a visual oddball task whereby neutral, exercise,...

  13. Analysis of Cannabis Seizures in NSW, Australia: Cannabis Potency and Cannabinoid Profile

    OpenAIRE

    Wendy Swift; Alex Wong; Li, Kong M.; Arnold, Jonathon C.; McGregor, Iain S.

    2013-01-01

    Recent analysis of the cannabinoid content of cannabis plants suggests a shift towards use of high potency plant material with high levels of Δ(9)-tetrahydrocannabinol (THC) and low levels of other phytocannabinoids, particularly cannabidiol (CBD). Use of this type of cannabis is thought by some to predispose to greater adverse outcomes on mental health and fewer therapeutic benefits. Australia has one of the highest per capita rates of cannabis use in the world yet there has been no previous...

  14. Cannabis Liberalization and Adolescent Cannabis Use: A Cross-National Study in 38 Countries

    Science.gov (United States)

    Shi, Yuyan; Lenzi, Michela; An, Ruopeng

    2015-01-01

    Aims To assess the associations between types of cannabis control policies at country level and prevalence of adolescent cannabis use. Setting, Participants and Design Multilevel logistic regressions were performed on 172,894 adolescents 15 year of age who participated in the 2001/2002, 2005/2006, or 2009/2010 cross-sectional Health Behaviour in School-Aged Children (HBSC) survey in 38 European and North American countries. Measures Self-reported cannabis use status was classified into ever use in life time, use in past year, and regular use. Country-level cannabis control policies were categorized into a dichotomous measure (whether or not liberalized) as well as 4 detailed types (full prohibition, depenalization, decriminalization, and partial prohibition). Control variables included individual-level sociodemographic characteristics and country-level economic characteristics. Findings Considerable intra-class correlations (.15-.19) were found at country level. With respect to the dichotomized cannabis control policy, adolescents were more likely to ever use cannabis (odds ratio (OR) = 1.10, p = .001), use in past year (OR = 1.09, p = .007), and use regularly (OR = 1.26, p = .004). Although boys were substantially more likely to use cannabis, the correlation between cannabis liberalization and cannabis use was smaller in boys than in girls. With respect to detailed types of policies, depenalization was associated with higher odds of past-year use (OR = 1.14, p = .013) and regular use (OR = 1.23, p = .038), and partial prohibition was associated with higher odds of regular use (OR = 2.39, p = .016). The correlation between cannabis liberalization and regular use was only significant after the policy had been introduced for more than 5 years. Conclusions Cannabis liberalization with depenalization and partial prohibition policies was associated with higher levels of regular cannabis use among adolescents. The correlations were heterogeneous between genders and

  15. Prenatal IV Cocaine: Alterations in Auditory Information Processing

    Directory of Open Access Journals (Sweden)

    Charles F. Mactutus

    2011-06-01

    Full Text Available One clue regarding the basis of cocaine-induced deficits in attentional processing is provided by the clinical findings of changes in the infants’ startle response; observations buttressed by neurophysiological evidence of alterations in brainstem transmission time. Using the IV route of administration and doses that mimic the peak arterial levels of cocaine use in humans, the present study examined the effects of prenatal cocaine on auditory information processing via tests of the acoustic startle response (ASR, habituation, and prepulse inhibition (PPI in the offspring. Nulliparous Long-Evans female rats, implanted with an IV access port prior to breeding, were administered saline, 0.5, 1.0, or 3.0 mg/kg/injection of cocaine HCL (COC from gestation day (GD8-20 (1x/day-GD8-14, 2x/day-GD15-20. COC had no significant effects on maternal/litter parameters or growth of the offspring. At 18-20 days of age, one male and one female, randomly selected from each litter displayed an increased ASR (>30% for males at 1.0 mg/kg and >30% for females at 3.0 mg/kg. When reassessed in adulthood (D90-100, a linear dose-response increase was noted on response amplitude. At both test ages, within-session habituation was retarded by prenatal cocaine treatment. Testing the females in diestrus vs. estrus did not alter the results. Prenatal cocaine altered the PPI response function across interstimulus interval (ISI and induced significant sex-dependent changes in response latency. Idazoxan, an alpha2-adrenergic receptor antagonist, significantly enhanced the ASR, but less enhancement was noted with increasing doses of prenatal cocaine. Thus, in utero exposure to cocaine, when delivered via a protocol designed to capture prominent features of recreational usage, causes persistent, if not permanent, alterations in auditory information processing, and suggests dysfunction of the central noradrenergic circuitry modulating, if not mediating, these responses.

  16. [Abuse of cannabis preparations].

    Science.gov (United States)

    Dukanović, B

    1991-01-01

    The author reviews the basic features, nature of action and the effects of the canabis drugs (hashish and marijuana) on human organism. The review starts with the well known fact that these kinds of drugs are the oldest ones and the most widely known to the civilization. It reviews in details very wide effects of the canabis drugs on the mental functions as well as the clinical expression of that action, where the basic mechanisms dominate: euphorogenic, sedative and psychodelic. With a detailed description of all psychopathological phenomena that appear in the chronic hashish and marijuana addicts, where the amotivation syndrome and flash back are particularly pointed out.

  17. Cannabis Users' Recommended Warnings for Packages of Legally Sold Cannabis: An Australia-Centered Study.

    Science.gov (United States)

    Malouff, John M; Johnson, Caitlin E; Rooke, Sally E

    2016-01-01

    Introduction: Although cannabis use creates health risks, governments have recently been legalizing either medical use or leisure use. These governments can mandate health warnings on cannabis packages. Prior research examined recommended warnings of cannabis experts. The aim of this study was to obtain suggested cannabis health and safety warnings from cannabis users. Methods: We used a media release, Facebook postings, and announcements in university classes to seek individuals who had used cannabis at least once according to their own report. Using online data collection software that keeps participants anonymous, we asked the individuals to suggest a warning that governments could mandate on cannabis packages. Results: In total, 288 users suggested warnings. Categorizing the warnings into content categories led to six warning topics: (1) risk of harm to mental health and psychological functioning; (2) risk of operating machinery while under the influence; (3) short-term physical side effects; (4) responsible use; (5) long-term negative physical effects; and (6) dependence, addiction, or abuse. The user-suggested warnings overlapped with six expert-recommended warnings identified in prior survey research and included two content areas that did not feature in expert-recommended warnings: short-term physical side effects and the importance of responsible use. Conclusions: The results are consistent with prior findings that some youths perceive cannabis use as potentially harmful. The current findings provide possible new content for warnings on cannabis packages.

  18. Sleep quality moderates the relation between depression symptoms and problematic cannabis use among medical cannabis users.

    Science.gov (United States)

    Babson, Kimberly A; Boden, Matthew Tyler; Bonn-Miller, Marcel O

    2013-05-01

    This study sought to extend research on the relation between depression symptoms and problematic cannabis use by evaluating the potential moderating role of perceived sleep quality among medical cannabis users. This employed a cross-sectional design. The sample consisted of 162 adults (mean age = 42.05 years, SD = 14.8; 22% female), with current recommendations from a doctor for medical cannabis, recruited from a medical cannabis dispensary. Consistent with previous research, individuals with heightened depression symptoms had greater problematic cannabis use. In addition, perceived sleep quality moderated this relation, such that depression symptoms differentially related to problematic cannabis use as a function of perceived quality of sleep (ΔR(2) = .03, p = .02). Participants with higher levels of depression and good perceived sleep quality had the greatest rates of problematic cannabis use. These results suggest that individuals with heightened depression may have higher rates of problematic cannabis use, in part, because of the beneficial effects of cannabis in terms of perceived sleep quality.

  19. Quality and Yield of Cannabis Products

    DEFF Research Database (Denmark)

    Kastorp, Grith; Lindholst, Christian

    2011-01-01

    Abstract. 180 seizures containing 667 different samples of cannabis products from 5 police districts in Jutland were examined from 2008 to the present. The samples were divided into the groups: hashish, marihuana (leaves and buds) and whole plants (indoors and outdoors). Cannabis seized from indoor...... cultivation was examined in order to determine THC content and yield. The results are used by the Danish Police Attorney to estimate expected yields in cases with unripe cannabis plants. The results indicate that the THC content found in locally grown marihuana is slightly higher than in hashish. However...

  20. Cocaine use and the breastfeeding mother.

    Science.gov (United States)

    Jones, Wendy

    2015-01-01

    Cocaine is the second most commonly used illicit drug. Use in pregnancy and breastfeeding may have severe consequences for the baby due to its pharmacokinetic properties. Midwives need to be aware of the prolonged action of cocaine and be alert to the possibility of cocaine toxicity if a baby is excessively irritable and tachycardic. Euphoric highs are brief but breast milk and urine remain positive for long periods. Infant urine following exposure to cocaine via breast milk may remain positive for up to 60 hours. Mothers who snort cocaine should pump and dump breast milk for 24-48 hours. Passive inhalation of crack cocaine smoke may also result in infants with positive toxicology screens. Cocaine powder should never be applied to the nipples of breastfeeding mothers.

  1. Dependent cannabis users at a music festival - prevalence and correlates

    DEFF Research Database (Denmark)

    Hesse, Morten; Tutenges, Sébastien

    2011-01-01

    Background In most western countries, the most prevalent type of illicit substance-use dependence in most is cannabis dependence. Historically, cannabis has been associated with several music genres, and the drug is widely used at music festivals. Methods Based on a survey of 380 music festival...... guests, we estimated the prevalence of cannabis dependence, as defined by a score of 3 or more on the Severity of Dependence Scale, as well as festival goers' use of cannabis during the past year. Results 143 (38%) reported having used cannabis within the past year (past year cannabis users......), and of these respondents, 21 (15%) screened positive for cannabis dependence. Compared to non-dependent cannabis users, the cannabis dependent respondents were more likely to be daily smokers, they reported having attended fewer music festivals during their lifetime, and they scored higher on self-reported sensation...

  2. Cocaine Hoppers : The Nigerian Involvement in the Global Cocaine Trade

    NARCIS (Netherlands)

    Oboh, Jude Roys

    2016-01-01

    In recent decades, Nigerian criminal drug ‘barons’ and ‘gangs’ have come to dominate international cocaine trafficking via West Africa to destination countries globally, a trend that presents a serious security threat to Africa and the world. This work provides empirical evidence to define and

  3. Cocaine Hoppers : The Nigerian Involvement in the Global Cocaine Trade

    NARCIS (Netherlands)

    Oboh, Jude Roys

    2016-01-01

    In recent decades, Nigerian criminal drug ‘barons’ and ‘gangs’ have come to dominate international cocaine trafficking via West Africa to destination countries globally, a trend that presents a serious security threat to Africa and the world. This work provides empirical evidence to define and expla

  4. [Cannabis in France, new insights].

    Science.gov (United States)

    Costentin, Jean

    2014-03-01

    France holds the record for cannabis use in Europe, especially among adolescents. This drug of abuse is thus mainly used during a very sensitive period of brain development, education, vehicle driving and development of life projects. In addition, synthetic derivatives of tetrahydrocannabinol (THC), which are more noxious than cannabis itself are now appearing on the market. Traficking and cultivation for personnal use have intensified; products proposed for sale are richer in THC; and some methods of consumption (e-cigarettes, vaporizers, water pipes) increase the supply of THC to the lungs and thence to the body and brain. It is in this context that attempts are being made to legalize this drug of abuse. Other attempts are made to disguise it as a medication. Meanwhile, the list of its psychic as well as physical damages grows longer, with some very severe cases of major injuries. This evolution takes place in spite of numerous warnings expressed by the French Academy of Medicine. Subsequently, it is prompted to carefully and vigorously denounce these events. This will be the aim of this thematic session.

  5. The α1 Antagonist Doxazosin Alters the Behavioral Effects of Cocaine in Rats

    Directory of Open Access Journals (Sweden)

    Colin N. Haile

    2012-11-01

    Full Text Available Medications that target norepinephrine (NE neurotransmission alter the behavioral effects of cocaine and may be beneficial for stimulant-use disorders. We showed previously that the short-acting, α1-adrenergic antagonist, prazosin, blocked drug-induced reinstatement of cocaine-seeking in rats and doxazosin (DOX, a longer-acting α1 antagonist blocked cocaine’s subjective effects in cocaine-dependent volunteers. To further characterize DOX as a possible pharmacotherapy for cocaine dependence, we assessed its impact on the development and expression of cocaine-induced locomotor sensitization in rats. Rats (n = 6–8 were administered saline, cocaine (COC, 10 mg/kg or DOX (0.3 or 1.0 mg/kg alone or in combination for 5 consecutive days (development. Following 10-days of drug withdrawal, all rats were administered COC and locomotor activity was again assessed (expression. COC increased locomotor activity across days indicative of sensitization. The high dose (1.0 mg/kg, but not the low dose (0.3 mg/kg of DOX significantly decreased the development and expression of COC sensitization. DOX alone did not differ from saline. These results are consistent with studies showing that α1 receptors are essential for the development and expression of cocaine’s behavioral effects. Results also suggest that blockade of both the development and expression of locomotor sensitization may be important characteristics of possible pharmacotherapies for cocaine dependence in humans.

  6. Abnormal regulation for progesterone production in placenta with prenatal cocaine exposure in rats.

    Science.gov (United States)

    Wu, L; Yan, J; Qu, S C; Feng, Y Q; Jiang, X L

    2012-12-01

    Cocaine abuse in pregnant women is currently a significant public hygiene problem and is tightly associated with elevated risk for preterm delivery. Placental steroidogenesis especially progesterone production was essential for success and maintenance of pregnancy in humans and rodents. In the present study, we determined the impact of prenatal cocaine exposure on pathways of placental progesterone synthesis in rats. Pregnant rats were treated cocaine twice daily (15 mg/kg/day) during the third trimester, and the maternal and fetal plasma progesterone and pregnenolone concentrations were detected. We also examined both the protein and mRNA expression of some key enzymes and regulators for progesterone production in placenta. Results showed that, after maternal cocaine use during pregnancy, progesterone and pregnenolone concentrations in both maternal and fetal rats were significantly decreased. Although prenatal cocaine exposure had no effects on placental 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1) expression, protein and mRNA expression of the cholesterol side-chain cleavage enzyme (P450scc/CYP11a) in placenta was significantly inhibited. Moreover, protein and mRNA expressions of MLN64 that regulating cholesterol transport and activating protein 2γ (AP2γ/Tfap2c) that controlling P450scc/CYP11a gene expression in placenta were both decreased following maternal cocaine use in pregnancy. Collectively, this study suggested that prenatal cocaine exposure could insult the placental progesterone production in rats possibly associated with the high risk for preterm delivery.

  7. Immunohistochemical distribution of cocaine and amphetamine regulatory peptide-like immunoreactive (CART-LI) nerve fibers in the circular muscle layer and their relationship to other peptides in the human caecum.

    Science.gov (United States)

    Bulc, Michał; Gonkowski, Sławomir; Landowski, Piotr; Kamińska, Barbara; Całka, Jarosław

    2014-07-01

    Motor activity of the gastrointestinal tract is extensively controlled by the enteric nervous system (ENS). Numerous neurotransmitters and neuromodulators are responsible for this regulation. One of them is cocaine- and amphetamine-regulated transcript peptide (CART). So far, there are few reports available concerning the distribution, functions, and co-localization of CART in the human gastrointestinal tract. The aim of the present investigation was to study the distribution and degree of co-localization of CART with substances taking part in conducting sensory stimuli, such as: substance P (SP), neurokinin A (NKA), calcitonin gene related peptide (CGRP) and Leu 5 enkephalin (L-ENK) in the circular muscle layer of the human caecum. CART-like immunoreactive (CART-LI) nerve fibers formed a very dense meshwork in the circular muscle layer of the caecum in all patients studied. Moreover, all neuronal substances tested during the present investigation were observed in CART-LI processes, but the degree of co-localization depended on the type of substance. The highest number of CART-positive nerves also contained L-ENK. A slightly lower level of co-localization was observed in the case of CART and SP or NKA, while only single nerve fibers were simultaneously CART- and CGRP-positive.

  8. Cannabis in movement disorders.

    Science.gov (United States)

    Müller-Vahl, K R; Kolbe, H; Schneider, U; Emrich, H M

    1999-10-01

    Central cannabinoid receptors are densely located in the output nuclei of the basal ganglia (globus pallidus, substantia nigra pars reticulata), suggesting their involvement in the regulation of motor activity. Furthermore, there is evidence that endogenous cannabinoid transmission plays a role in the manipulation of other transmitter systems within the basal ganglia by increasing GABAergic transmission, inhibiting glutamate release and affecting dopaminergic uptake. Most hyperkinetic and hypokinetic movement disorders are caused by a dysfunction of basal ganglia-thalamo-cortical loops. It has been suggested that an endogenous cannabinoid tone participates in the control of movements and, therefore, the central cannabinoid system might play a role in the pathophysiology of these diseases. During the last years in humans a limited number of clinical trials demonstrated that cannabinoids might be useful in the treatment of movement disorders. Despite the lack of controlled studies there is evidence that cannabinoids are of therapeutic value in the treatment of tics in Tourette syndrome, the reduction of levodopa-induced dyskinesia in Parkinson s disease and some forms of tremor and dystonia. It can be speculated that cannabinoid antagonists might be useful in the treatment of chorea in Huntington s disease and hypokinetic parkinsonian syndromes.

  9. Pulmonary alterations in cocaine users

    Directory of Open Access Journals (Sweden)

    Mário Terra Filho

    Full Text Available CONTEXT: Brazilian researchers have recently recognized a marked increase in the number of people using abusable drugs and the consequences of this habit. It has become a major public health problem in a potentially productive segment of the general population. In the last few years, several medical articles have given special emphasis to pulmonary complications related to cocaine use. This review is based on this information and experience acquired with groups of cocaine users. OBJECTIVE: To present to physicians the pulmonary aspects of cocaine use and warn about the various effects this drug has on the respiratory system, stressing those related to long-term use. DESIGN: Narrative review. METHOD: Pulmonary complications are described. These may include infections (Staphylococcus aureus, pulmonary tuberculosis, acquired immunodeficiency syndrome/aids, etc., aspiration pneumonia, lung abscess, empyema, septic embolism, non-cardiogenic pulmonary edema, barotrauma, pulmonary granulomatosis, bronchiolitis obliterans and organizing pneumonia, pneumonitis and interstitial fibrosis, pneumonitis hypersensitivity, lung infiltrates and eosinophilia in individuals with bronchial hyperreactivity, diffuse alveolar hemorrhage, vasculitis, pulmonary infarction, pulmonary hypertension and alterations in gas exchange. It is concluded that physicians should give special attention to the various pulmonary and clinical manifestations related to cocaine use, particularly in young patients.

  10. Suicidal Ideation Induced by Episodic Cannabis Use

    Directory of Open Access Journals (Sweden)

    Michele Raja

    2009-01-01

    Full Text Available The report describes a patient who presented suicidal ideation only in two different occasions, immediately after acute cannabis intoxication. He used cannabis only in these two circumstances. Although a definite association between cannabis use and suicidal ideation or behavior has been already reported in the literature, the described case presents two original clinical aspects that deserve consideration. First, episodic assumption of cannabis induced suicidal ideation abruptly. Second, suicidal ideation appeared independent of mood depression, stressors, or life events, suggesting that suicidality may be not a direct consequence of depression and appears to be a relatively independent psychopathological dimension. There seems to be no linear relation between the severity of depression and the risk of suicide.

  11. [Alveolar haemorrhage following a cannabis water pipe].

    Science.gov (United States)

    Moatemri, Z; Zaibi, H; Dabboussi, S; Mhamedi, S; Aichaouia, C; Khadhraoui, M; Cheikh, R

    2016-10-01

    Respiratory toxicity of cannabis is well-known today particularly with the new consumption patterns. We report the case of a 25-year-old man admitted for haemoptysis, with unfavourable outcome and acute respiratory failure. Various explorations concluded to acute respiratory distress syndrome secondary to diffuse alveolar haemorrhage. Etiological assessment was initially negative. Outcome was favourable during hospitalization, authorizing the discharge of our patient. Two days later, alveolar haemorrhage recur, with positive toxicological tests for cannabis and the patient admits smoking cannabis by plastic "bang". We illustrate, through this case, the severity of respiratory complications caused by new methods of using cannabis, particularly with plastic 'bang', hence the need to insist of the importance of supported withdrawal and to inform young people how these techniques are serious.ssss. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. Serotonin2C receptors and drug addiction: focus on cocaine.

    Science.gov (United States)

    Devroye, Céline; Filip, Malgorzata; Przegaliński, Edmund; McCreary, Andrew C; Spampinato, Umberto

    2013-10-01

    This review provides an overview of the role of central serotonin2C (5-HT2C) receptors in drug addiction, specifically focusing on their impact on the neurochemical and behavioral effects of cocaine, one of the most worldwide abused drug. First, we described the neurochemical and electrophysiological mechanisms underlying the interaction between 5-HT2C receptors and the mesocorticolimbic dopaminergic network, in keeping with the key role of this system in drug abuse and dependence. Thereafter, we focused on the role of 5-HT2C receptors in the effects of cocaine in various preclinical behavioral models used in drug addiction research, such as locomotor hyperactivity, locomotor sensitization, drug discrimination, and self-administration, to end with an overview of the neurochemical mechanisms underlying the interactions between 5-HT2C receptors, mesocorticolimbic dopamine system, and cocaine. On their whole, the presented data provide compelling preclinical evidence that 5-HT2C receptor agonists may have efficacy in the treatment of cocaine abuse and dependence, thereby underlying the need for additional clinical studies to ascertain whether preclinical data translate to the human.

  13. Acute brain metabolic effects of cocaine in rhesus monkeys with a history of cocaine use.

    Science.gov (United States)

    Henry, Porche' Kirkland; Murnane, Kevin S; Votaw, John R; Howell, Leonard L

    2010-12-01

    Cocaine addiction involves an escalation in drug intake which alters many brain functions. The present study documented cocaine-induced changes in brain metabolic activity as a function of cocaine self-administration history. Experimentally naive rhesus monkeys (N = 6) were given increasing access to cocaine under a fixed-ratio schedule of intravenous (i.v.) drug self-administration. PET imaging with F-18 labeled fluorodeoxyglucose (FDG) was used to measure acute intramuscular (i.m.) cocaine-induced changes in brain metabolism in the cocaine-naïve state, following 60 sessions under limited-access conditions (1 h/day), following 60 sessions under extended-access conditions (4 h/day), and following 4 weeks of drug withdrawal. In the cocaine-naïve state, cocaine-induced increases in brain metabolism were restricted to the prefrontal cortex. As cocaine exposure increased from limited to extended access, metabolic effects expanded throughout the frontal cortex and were induced within the striatum. Conversely, cocaine-induced activation was far less robust following withdrawal. The results highlight a progressive expansion of the metabolic effects of cocaine to include previously unaffected dopamine innervated brain regions as a consequence of cocaine self-administration history. The identification of brain regions progressively influenced by drug exposure may be highly relevant toward efforts to develop treatments for cocaine addiction.

  14. Decreased striatal and enhanced thalamic dopaminergic responsivity in detoxified cocaine abusers

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.J.; Fowler, J.S. [Brookhaven National Lab., Stony Brook, NY (United States)] [and others

    1997-05-01

    It has been hypothesized that cocaine addiction could result from decreased brain dopamine (DA) function. However, little is known about changes in (DA) neurotransmission in human cocaine addiction. We used PET and [C-11]raclopride, a DA D2 receptor ligand sensitive to competition with endogenous DA, to measure relative changes in extracellular DA induced by methylphenidate (MP) in 20 cocaine abusers (3-6 weeks after cocaine discontinuation) and 23 controls. MP did not affect the transport of [C-11]raclopride from blood to brain (K1); however it induced a significant reduction in DA D2 receptor availability (Bmax/Kd) in striatum. The magnitude of ND-induced changes in striatal [C-11]raclopride binding were significantly larger in controls (21 + 13% change from baseline) than in cocaine abusers (9 {+-} 13 %) (ANOVA p < 0.005). In cocaine abusers, but not in controls, MP also decreased Bmax/Kd values in thalamus (29 {+-} 35 %) (ANOVA p < 0.005). There were no differences in plasma MP concentration between the groups. In striatum MP-induced changes in Bmax/Kd were significantly correlated with MP-induced changes in self reports of restlessness (r = 0.49, df 42, p < 0.002). In thalamus MP-induced changes in Bmax/Kd were significantly correlated with ND-induced changes in self reports of cocaine craving (r = 0.57, df 42, p < 0.0001). These results are compatible with a decrease in striatal DA brain function in cocaine abusers. They also suggest a participation of thalamic DA pathways in cocaine addiction.

  15. Significance of cannabis use to dental practice.

    Science.gov (United States)

    Maloney, William James

    2011-04-01

    The illicit use of the three main forms of cannabis-marijuana, hash, hash oil-pose certain obstacles and challenges to the dental professional. There are a number of systemic, as well as oral/head and neck manifestations, associated with cannabis use. Dentists need to be aware of these manifestations in order to take whatever precautions and/or modifications to the proposed treatment that might be necessary.

  16. 20. Integrating Cannabis Into Clinical Care

    OpenAIRE

    Abrams, Donald

    2013-01-01

    Focus Areas: Integrative Approaches to Care, Mental Health, Alleviating Pain Cannabis is now available to patients as a medicine in 18 states and the District of Columbia. Unfortunately, due to the long-standing prohibition, most providers have little information regarding the medicinal use of this versatile botanical. The history of cannabis as medicine will be reviewed. This presentation will summarize the main components of the plant and their pharmacologic effects, highlighting the entour...

  17. Medical cannabis – the Canadian perspective

    OpenAIRE

    Ko, Gordon D.; Bober, Sara L; Mindra, Sean; Moreau, Jason M

    2016-01-01

    Cannabis has been widely used as a medicinal agent in Eastern medicine with earliest evidence in ancient Chinese practice dating back to 2700 BC. Over time, the use of medical cannabis has been increasingly adopted by Western medicine and is thus a rapidly emerging field that all pain physicians need to be aware of. Several randomized controlled trials have shown a significant and dose-dependent relationship between neuropathic pain relief and tetrahydrocannabinol – the principal psychoactive...

  18. Advice of the Italian CCTN on the toxicity of Cannabis sativa

    Energy Technology Data Exchange (ETDEWEB)

    Camoni, I. [ed.] [Istituto Superiore di Sanita`, Rome (Italy). Lab. di Tossicologia Applicata; Mucci, N. [ed.] [ISPESL, Monteporzio Catone, Roma (Italy). Dip. di Medicina del Lavoro; Paroli, E. [ed.] [Rome, Univ. `La Sapienza` (Italy). Fac. di Medicina, Ist. di Farmacologia

    1998-06-01

    This recommendation of the Italian National Toxicological Committee (CCTN) regards the possible toxic effects of some products derived from Cannabis sativa, indica variety. The CCTN has especially evaluated genotoxic, immunological and toxic to reproduction effects of these substances, on the basis of the results from both experimental studies and observations on humans. [Italiano] Il documento contiene il parere della CCTN sui potenziali effetti tossici di alcuni derivati della Cannabis sativa, varieta` indica. Il parere e` stato elaborato sulla base dei risultati sia di studi sperimentali sia dei limitati studi sull`uomo, prendendo in particolare considerazione gli effetti genotossici, tossico-riproduttivi ed immunologici.

  19. The impact of cannabis use on age of onset and clinical characteristics in first-episode psychotic patients. Data from the Psychosis Incident Cohort Outcome Study (PICOS).

    Science.gov (United States)

    Tosato, Sarah; Lasalvia, Antonio; Bonetto, Chiara; Mazzoncini, Rodolfo; Cristofalo, Doriana; De Santi, Katia; Bertani, Mariaelena; Bissoli, Sarah; Lazzarotto, Lorenza; Marrella, Giovanna; Lamonaca, Dario; Riolo, Rosanna; Gardellin, Francesco; Urbani, Anna; Tansella, Michele; Ruggeri, Mirella

    2013-04-01

    Cannabis use is frequent among first-episode psychosis (FEP) patients and has been associated with several clinical features. This study aimed in an FEP sample to determine whether cannabis use is associated with (1) a higher level of positive symptoms, a lower level of depression and a better premorbid adjustment, (2) an earlier age of onset, and a better premorbid IQ. The study was conducted within the framework of the Psychosis Incident Cohort Outcome Study (PICOS), a multisite collaborative research on FEP patients who attended the psychiatric services in Veneto Region, Italy. Standardized instruments were used to collect sociodemographic, clinical, and drug use data. A total of 555 FEP patients met the inclusion criteria, 517 of whom received an ICD-10 diagnosis of psychosis; 397 (55% males; mean age: 32 yrs ± 9.5) were assessed. Out of these, 311 patients agreed to be interviewed on drug and alcohol misuse; 20.3% was positive for drug misuse: cannabis (19.0%), cocaine (3.9%), and hallucinogens (3.9%). Cannabis use was not associated with a higher level of positive symptoms, but correlated with less severe depressive symptoms. No relationship was observed between premorbid adjustment or IQ and cannabis use. FEP patients who used cannabis had an earlier age of onset than abstinent patients, even after adjusting for gender and diagnosis. Our results suggest a possible causal role of cannabis in triggering psychosis in certain vulnerable subjects. Particular attention must be paid to this behaviour, because reducing cannabis use can delay or prevent some cases of psychosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Biological aspects of cannabis consumption in schizophrenia

    Directory of Open Access Journals (Sweden)

    Serban Ionela Lacramioara

    2015-01-01

    Full Text Available Schizophrenia and psychotic disorders are major health issues with particular implications for both the individual and the medical system. Epidemiological data show a more frequent consumption of drugs in schizophrenic patients when compared to the general population. Studies have shown that the abuse of substances is the most common comorbidity associated with schizophrenia. Among illicit substances, cannabis is the most commonly encountered among patients with schizophrenia. Similar clinical features of schizophrenia and cannabis consumption could be explained by some common neurobiological implications. N-methyl-D-aspartate (NMDA receptor stimulation is associated with psychotic-type phenomena and schizophrenia and NMDA receptors are involved in the clinical effects of cannabis consumption. Thus, the CB1 receptors that are spread mainly at the level of the NMDA secretory neurons are activated by tetrahydrocannabinol, the psychoactive component of cannabis. Moreover, cannabis abuse in association with other factors may contribute in triggering schizophrenia. Therefore, patients diagnosed with schizophrenia that abuse substances such as cannabis could represent a special category of patients that require a complex therapeutic approach, especially considering the multiple problems implicated, such as reduced compliance with treatment, unfavorable evolution and prognosis with multiple relapses and frequent hospitalizations.

  1. Role of cannabis in psychiatric disturbance.

    Science.gov (United States)

    Knight, F

    1976-01-01

    Clinical observation suggests that cannabis is implicated in some types of psychiatric disturbance. A record of admissions to two urban and four rural hospitals in Jamaica is examined along with details of individual cases. One-third of male admissions to the psychiatric hospital have used cannabis. Of 74 males admitted to another psychiatric service over a 12-month period, 29 had used cannabis. Ten of these patients were diagnosed as "ganja psychosis," and four others were classified as "marijuana-modified mania." At another psychiatric service, 54 of 223 admissions (24.2%) for functional psychosis presented with cannabis usage as a comtributory factor. These 54 patients included 14 and seven cases of hypomanic and depressive reactions, respectively. At three other rural general hospitals, psychiatric admissions for psychosis showed 11 of 51, seven of 18, and 39 of 75 patients, respectively, in whom cannabis was considered directly responsible. These findings lend support to the idea of causation of illness or modification of existing illness. The negative findings of controlled studies in the same country are not inconsistent. A suggested classification for adverse reactions to cannabis offered by one author is recommended, because it is in accord with common local clinical experience.

  2. Negative consequences associated with dependence in daily cannabis users

    Directory of Open Access Journals (Sweden)

    Earleywine Mitch

    2007-01-01

    Full Text Available Abstract Background Cannabis is the most widely consumed illicit substance in America, with increasing rates of use. Some theorists tend to link frequency of use with cannabis dependence. Nevertheless, fewer than half of daily cannabis users meet DSM-IV-TR criteria for cannabis dependence. This study seeks to determine whether the negative aspects associated with cannabis use can be explained by a proxy measure of dependence instead of by frequency of use. Results Over 2500 adult daily cannabis users completed an Internet survey consisting of measures of cannabis and other drug use, in addition to measures of commonly reported negative problems resulting from cannabis use. We compared those who met a proxy measure of DSM-IV-TR criteria for cannabis dependence (N = 1111 to those who did not meet the criteria (N = 1770. Cannabis dependent subjects consumed greater amounts of cannabis, alcohol, and a variety of other drugs. They also had lower levels of motivation, happiness, and satisfaction with life, with higher levels of depression and respiratory symptoms. Conclusion Although all of our subjects reported daily use, only those meeting proxy criteria for cannabis dependence reported significant associated problems. Our data suggest that dependence need not arise from daily use, but consuming larger amounts of cannabis and other drugs undoubtedly increases problems.

  3. Negative consequences associated with dependence in daily cannabis users.

    Science.gov (United States)

    Looby, Alison; Earleywine, Mitch

    2007-01-10

    Cannabis is the most widely consumed illicit substance in America, with increasing rates of use. Some theorists tend to link frequency of use with cannabis dependence. Nevertheless, fewer than half of daily cannabis users meet DSM-IV-TR criteria for cannabis dependence. This study seeks to determine whether the negative aspects associated with cannabis use can be explained by a proxy measure of dependence instead of by frequency of use. Over 2500 adult daily cannabis users completed an Internet survey consisting of measures of cannabis and other drug use, in addition to measures of commonly reported negative problems resulting from cannabis use. We compared those who met a proxy measure of DSM-IV-TR criteria for cannabis dependence (N = 1111) to those who did not meet the criteria (N = 1770). Cannabis dependent subjects consumed greater amounts of cannabis, alcohol, and a variety of other drugs. They also had lower levels of motivation, happiness, and satisfaction with life, with higher levels of depression and respiratory symptoms. Although all of our subjects reported daily use, only those meeting proxy criteria for cannabis dependence reported significant associated problems. Our data suggest that dependence need not arise from daily use, but consuming larger amounts of cannabis and other drugs undoubtedly increases problems.

  4. c-Fos expression associated with reinstatement of cocaine-seeking behavior by response-contingent conditioned cues.

    Science.gov (United States)

    Kufahl, Peter R; Zavala, Arturo R; Singh, Akanksha; Thiel, Kenneth J; Dickey, Erin D; Joyce, Jeffrey N; Neisewander, Janet L

    2009-10-01

    The capability of cocaine cues to generate craving in cocaine-dependent humans, even after extended abstinence, is modeled in rats using cue reinstatement of extinguished cocaine-seeking behavior. We investigated neural activity associated with incentive motivational effects of cocaine cues using c-fos mRNA and Fos protein expression as markers. Unlike preceding studies, we used response-contingent presentation of discrete cues to elicit cocaine seeking. Rats were first trained to press a lever, resulting in cocaine reinforcement and light and tone cues. Rats then underwent extinction training, during which lever presses decreased. On the test day, rats either received response-contingent cocaine cues or received no cues. The cues reinstated extinguished cocaine-seeking behavior on the test day. In general, cue-elicited c-fos mRNA and protein expression were similar and both were enhanced in the prefrontal cortex, ventral tegmental area (VTA), dorsal striatum, and nucleus accumbens. Cues elicited more widespread Fos protein expression relative to our previous research in which cues were presented noncontingently without prior extinction training, including increases in the VTA, substantia nigra, ventral subiculum, and lateral entorhinal cortex. We also observed a correlation between cocaine-seeking behavior and Fos in the agranular insula (AgI) and basolateral amygdala (BLA). The findings suggest that connections between BLA and AgI play a role in cue-elicited incentive motivation for cocaine and that reinstatement of cocaine seeking by response-contingent cues activates a similar corticolimbic circuit as that observed with other modes of cue presentation; however, activation of midbrain and ventral hippocampal regions may be unique to reinstatement by response-contingent cues.

  5. Effects of 14-day treatment with the schedule III anorectic phendimetrazine on choice between cocaine and food in rhesus monkeys.

    Science.gov (United States)

    Banks, Matthew L; Blough, Bruce E; Negus, S Stevens

    2013-08-01

    The clinical utility of monoamine releasers such as phenmetrazine or d-amphetamine as candidate agonist medications for cocaine dependence is hindered by their high abuse liability. Phendimetrazine is a clinically available schedule III anorectic that functions as a prodrug for phenmetrazine and thus may have lower abuse liability. This study determined the effects of continuous 14-day treatment with phendimetrazine on cocaine vs. food choice in rhesus monkeys (N=4). Responding was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and cocaine injections (0-0.1mg/kg/injection, fixed-ratio 10 schedule). Cocaine choice dose-effect curves were determined daily before and during 14-day periods of continuous intravenous treatment with saline or (+)-phendimetrazine (0.32-1.0mg/kg/h). Effects of 14-day treatment with (+)-phenmetrazine (0.1-0.32 mg/kg/h; N=5) and d-amphetamine (0.032-0.1mg/kg/h; N=6) were also examined for comparison. During saline treatment, food was primarily chosen during availability of low cocaine doses (0, 0.0032, and 0.01 mg/kg/injection), and cocaine was primarily chosen during availability of higher cocaine doses (0.032 and 0.1mg/kg/injection). Phendimetrazine initially decreased overall responding without significantly altering cocaine choice. Over the course of 14 days, tolerance developed to rate decreasing effects, and phendimetrazine dose-dependently decreased cocaine choice (significant at 0.032 mg/kg/injection cocaine). Phenmetrazine and d-amphetamine produced qualitatively similar effects. These results demonstrate that phendimetrazine can produce significant, though modest, reductions in cocaine choice in rhesus monkeys. Phendimetrazine may be especially suitable as a candidate medication for human studies because of its schedule III clinical availability. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Predicting the transition from frequent cannabis use to cannabis dependence: a three-year prospective study.

    NARCIS (Netherlands)

    van der Pol, P.; Liebregts, N.; de Graaf, R.; Korf, D.J.; van den Brink, W.; van Laar, M.

    2013-01-01

    Background Frequent cannabis users are at high risk of dependence, still most (near) daily users are not dependent. It is unknown why some frequent users develop dependence, whereas others do not. This study aims to identify predictors of first-incidence DSM-IV cannabis dependence in frequent cannab

  7. Predicting the transition from frequent cannabis use to cannabis dependence: a three-year prospective study.

    NARCIS (Netherlands)

    van der Pol, P.; Liebregts, N.; de Graaf, R.; Korf, D.J.; van den Brink, W.; van Laar, M.

    2013-01-01

    Background Frequent cannabis users are at high risk of dependence, still most (near) daily users are not dependent. It is unknown why some frequent users develop dependence, whereas others do not. This study aims to identify predictors of first-incidence DSM-IV cannabis dependence in frequent cannab

  8. Predicting the transition from frequent cannabis use to cannabis dependence: a three-year prospective study.

    NARCIS (Netherlands)

    van der Pol, P.; Liebregts, N.; de Graaf, R.; Korf, D.J.; van den Brink, W.; van Laar, M.

    2013-01-01

    Background Frequent cannabis users are at high risk of dependence, still most (near) daily users are not dependent. It is unknown why some frequent users develop dependence, whereas others do not. This study aims to identify predictors of first-incidence DSM-IV cannabis dependence in frequent

  9. Cannabis Reclassification: What Is the Message to the Next Generation of Cannabis Users?

    Science.gov (United States)

    McCrystal, Patrick; Winning, Kerry

    2009-01-01

    At the beginning of 2004 the UK government downgraded the legal status of cannabis from a Class B to a Class C drug. Following a review of this decision two years later, cannabis remained a Class C substance--which for some contrasted with the potential harmful social and health effects associated with its use, particularly for young people. These…

  10. Reasons for Cannabis Use and Effects of Cannabis Use as Reported by Patients with Psychotic Disorders

    NARCIS (Netherlands)

    N. Dekker; D.H. Linszen; L. de Haan

    2009-01-01

    Background: Cannabis is one of the most commonly used substances in patients with a psychotic disorder and is associated with a higher risk of psychotic relapses. Identifying reasons for cannabis use and subjective effects in patients with psychotic disorders can provide insight into the functions o

  11. Early Versus Late Onset of Cannabis Use: Differences in Striatal Response to Cannabis Cues

    Science.gov (United States)

    Wetherill, Reagan R.; Hager, Nathan; Jagannathan, Kanchana; Mashhoon, Yasmin; Pater, Heather; Childress, Anna Rose; Franklin, Teresa R.

    2017-01-01

    Addiction theories posit that addiction is the result of a progressive transition from voluntary to habitual, compulsive drug use—changes that have been linked, in animals, to a shift from ventral to dorsal striatal control over drug-seeking behavior. Thus, we hypothesized that early-onset (EOs) cannabis users versus late-onset (LOs) cannabis users might exhibit, respectively, greater dorsal versus ventral striatal response to drug cues. We used functional magnetic resonance imaging and an event-related blood oxygen level-dependent backward-masking task to evaluate striatal responses to backward-masked cannabis cues (vs. neutral cues) in EOs (cannabis use patterns. Direct comparisons revealed that EOs showed greater response to cannabis cues in the dorsal striatum than LOs (p 50 voxels). Within-group analyses revealed that EOs showed greater neural response to cannabis cues in the dorsal striatum, whereas LOs exhibited greater neural response to cannabis cues in the ventral striatum. Although cross-sectional, these findings are consistent with recent addiction theories suggesting a progressive shift from ventral to dorsal striatal control over drug-seeking behavior and highlight the importance of age of onset of cannabis use on the brain and cognition.

  12. Cannabis Reclassification: What Is the Message to the Next Generation of Cannabis Users?

    Science.gov (United States)

    McCrystal, Patrick; Winning, Kerry

    2009-01-01

    At the beginning of 2004 the UK government downgraded the legal status of cannabis from a Class B to a Class C drug. Following a review of this decision two years later, cannabis remained a Class C substance--which for some contrasted with the potential harmful social and health effects associated with its use, particularly for young people. These…

  13. Cannabis, Collaterals, and Coronary Occlusion

    Directory of Open Access Journals (Sweden)

    Kalpa De Silva

    2011-01-01

    Full Text Available A 51-year-old gentleman, who regularly smoked cannabis, presented with chest pain and diaphoresis. He was haemodynamically stable. ECG showed ST depression, inferiorly, and 1 mm ST elevation in lead aVR. Emergent coronary angiography showed thrombotic occlusion of the left main coronary artery (LMCA, the dominant RCA provided Rentrop grade II collaterals to the LAD. The LMCA was successfully reopened by deployment of a bare-metal stent. Animal heart models suggest that endogenous cannibinoids may cause ischaemic preconditioning. This case suggests that the severity of ischaemia, and hence ECG changes and haemodynamic consequences following an acute occlusion of the LMCA, can be ameliorated by coronary collateralisation and possibly by preconditioning of the myocardium.

  14. Levamisole-Contaminated Cocaine: An Emergent Cause of Vasculitis and Skin Necrosis

    Directory of Open Access Journals (Sweden)

    Osama Souied

    2014-01-01

    Full Text Available The prevalence of cocaine adulterated with levamisole-induced vasculitis is increasing and physicians should be aware of this unique entity. There have been many reports of cutaneous vasculitis syndrome caused by cocaine which is contaminated with levamisole. Levamisole was used as an antihelminth drug and later was rescinded from use in humans due to adverse effects. Through this paper, we will report a 39-year-old crack cocaine user who presented with purpuric rash and skin necrosis of his ear lobes. Levamisole-induced vasculitis syndrome was suspected. A urine toxicology screen was positive for cocaine, opiates, and marijuana. Blood work revealed positive titres of ANA and p-ANCA, as well as anti-cardiolipin antibody. Biopsy taken from the left ear showed focal acute inflammation, chronic inflammation with thrombus formation, and extravasated blood cells. Treatment was primarily supportive with wound care.

  15. Levamisole-Contaminated Cocaine: An Emergent Cause of Vasculitis and Skin Necrosis

    Science.gov (United States)

    Mobarakai, Neville

    2014-01-01

    The prevalence of cocaine adulterated with levamisole-induced vasculitis is increasing and physicians should be aware of this unique entity. There have been many reports of cutaneous vasculitis syndrome caused by cocaine which is contaminated with levamisole. Levamisole was used as an antihelminth drug and later was rescinded from use in humans due to adverse effects. Through this paper, we will report a 39-year-old crack cocaine user who presented with purpuric rash and skin necrosis of his ear lobes. Levamisole-induced vasculitis syndrome was suspected. A urine toxicology screen was positive for cocaine, opiates, and marijuana. Blood work revealed positive titres of ANA and p-ANCA, as well as anti-cardiolipin antibody. Biopsy taken from the left ear showed focal acute inflammation, chronic inflammation with thrombus formation, and extravasated blood cells. Treatment was primarily supportive with wound care. PMID:24778656

  16. Atypical Dopamine Uptake Inhibitors that Provide Clues About Cocaine's Mechanism at the Dopamine Transporter

    Science.gov (United States)

    Hauck Newman, Amy; Katz, Jonathan L.

    The dopamine transporter (DAT) has been a primary target for cocaine abuse/addiction medication discovery. However predicted addiction liability and limited clinical evaluation has provided a formidable challenge for development of these agents for human use. The unique and atypical pharmacological profile of the benztropine (BZT) class of dopamine uptake inhibitors, in preclinical models of cocaine effects and abuse, has encouraged further development of these agents. Moreover, in vivo studies have challenged the original DAT hypothesis and demonstrated that DAT occupancy and subsequent increases in dopamine produced by BZT analogues are significantly delayed and long lasting, as compared to cocaine. These important and distinctive elements are critical to the lack of abuse liability among BZT analogues, and improve their potential for development as treatments for cocaine abuse and possibly other neuropsychiatric disorders.

  17. Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine's action in vivo

    OpenAIRE

    Tallarida, Christopher S.; Egan, Erin; Alejo, Gissel D.; Raffa, Robert; Tallarida, Ronald J.; Rawls, Scott M.

    2014-01-01

    Levamisole is estimated by the Drug Enforcement Agency (DEA) to be present in about 80% of cocaine seized in the United States and linked to debilitating, and sometimes fatal, immunologic effects in cocaine abusers. One explanation for the addition of levamisole to cocaine is that it increases the amount of product and enhances profits. An alternative possibility, and one investigated here, is that levamisole alters cocaine's action in vivo. We specifically investigated effects of levamisole ...

  18. Cannabis use patterns and motives: A comparison of younger, middle-aged, and older medical cannabis dispensary patients.

    Science.gov (United States)

    Haug, Nancy A; Padula, Claudia B; Sottile, James E; Vandrey, Ryan; Heinz, Adrienne J; Bonn-Miller, Marcel O

    2017-09-01

    Medical cannabis is increasingly being used for a variety of health conditions as more states implement legislation permitting medical use of cannabis. Little is known about medical cannabis use patterns and motives among adults across the lifespan. The present study examined data collected at a medical cannabis dispensary in San Francisco, California. Participants included 217 medical cannabis patients who were grouped into age-defined cohorts (younger: 18-30, middle-aged: 31-50, and older: 51-72). The age groups were compared on several measures of cannabis use, motives and medical conditions using one-way ANOVAs, chi-square tests and linear regression analyses. All three age groups had similar frequency of cannabis use over the past month; however, the quantity of cannabis used and rates of problematic cannabis use were higher among younger users relative to middle-aged and older adults. The association between age and problematic cannabis use was moderated by age of regular use initiation such that earlier age of regular cannabis use onset was associated with more problematic use in the younger users, but not among older users. Middle-aged adults were more likely to report using medical cannabis for insomnia, while older adults were more likely to use medical cannabis for chronic medical problems such as cancer, glaucoma and HIV/AIDS. Younger participants reported cannabis use when bored at a greater rate than middle-aged and older adults. Findings suggest that there is an age-related risk for problematic cannabis use among medical cannabis users, such that younger users should be monitored for cannabis use patterns that may lead to deleterious consequences. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Cannabis Use Patterns and Motives: A Comparison of Younger, Middle-Aged, and Older Medical Cannabis Dispensary Patients

    Science.gov (United States)

    Haug, Nancy A.; Padula, Claudia B.; Sottile, James E.; Vandrey, Ryan; Heinz, Adrienne J.; Bonn-Miller, Marcel O.

    2017-01-01

    Introduction Medical cannabis is increasingly being used for a variety of health conditions as more states implement legislation permitting medical use of cannabis. Little is known about medical cannabis use patterns and motives among adults across the lifespan. Methods The present study examined data collected at a medical cannabis dispensary in San Francisco, California. Participants included 217 medical cannabis patients who were grouped into age-defined cohorts (younger: 18–30, middle-aged: 31–50, and older: 51–72). The age groups were compared on several measures of cannabis use, motives and medical conditions using one-way ANOVAs, chi-square tests and linear regression analyses. Results All three age groups had similar frequency of cannabis use over the past month; however, the quantity of cannabis used and rates of problematic cannabis use were higher among younger users relative to middle-aged and older adults. The association between age and problematic cannabis use was moderated by age of regular use initiation such that earlier age of regular cannabis use onset was associated with more problematic use in the younger users, but not among older users. Middle-aged adults were more likely to report using medical cannabis for insomnia, while older adults were more likely to use medical cannabis for chronic medical problems such as cancer, glaucoma and HIV/AIDS. Younger participants reported cannabis use when bored at a greater rate than middle-aged and older adults. Conclusions Findings suggest that there is an age-related risk for problematic cannabis use among medical cannabis users, such that younger users should be monitored for cannabis use patterns that may lead to deleterious consequences. PMID:28340421

  20. Major depressive disorder, suicidal ideation, and suicide attempt in twins discordant for cannabis dependence and early-onset cannabis use.

    Science.gov (United States)

    Lynskey, Michael T; Glowinski, Anne L; Todorov, Alexandre A; Bucholz, Kathleen K; Madden, Pamela A F; Nelson, Elliot C; Statham, Dixie J; Martin, Nicholas G; Heath, Andrew C

    2004-10-01

    Previous research has reported both a moderate degree of comorbidity between cannabis dependence and major depressive disorder (MDD) and that early-onset cannabis use is associated with increased risks for MDD. To examine whether associations between both lifetime cannabis dependence and early cannabis use and measures of MDD, suicidal ideation, and suicide attempt persist after controlling for genetic and/or shared environmental influences. Cross-sectional survey of twin pairs discordant for lifetime cannabis dependence and those discordant for early cannabis use. General population sample of twins (median age, 30 years). Two hundred seventy-seven same-sex twin pairs discordant for cannabis dependence and 311 pairs discordant for early-onset cannabis use (before age 17 years). Self-report measures of DSM-IV-defined lifetime MDD, suicidal ideation, and suicide attempt. Individuals who were cannabis dependent had odds of suicidal ideation and suicide attempt that were 2.5 to 2.9 times higher than those of their non-cannabis-dependent co-twin. Additionally, cannabis dependence was associated with elevated risks of MDD in dizygotic but not in monozygotic twins. Those who initiated cannabis use before age 17 years had elevated rates of subsequent suicide attempt (odds ratio, 3.5 [95% confidence interval, 1.4-8.6]) but not of MDD or suicidal ideation. Early MDD and suicidal ideation were significantly associated with subsequent risks of cannabis dependence in discordant dizygotic pairs but not in discordant monozygotic pairs. Comorbidity between cannabis dependence and MDD likely arises through shared genetic and environmental vulnerabilities predisposing to both outcomes. In contrast, associations between cannabis dependence and suicidal behaviors cannot be entirely explained by common predisposing genetic and/or shared environmental predispositions. Previously reported associations between early-onset cannabis use and subsequent MDD likely reflect shared genetic and

  1. Medicinal Use of Cannabis: History and Current Status

    Directory of Open Access Journals (Sweden)

    Harold Kalant

    2001-01-01

    Full Text Available OBJECTIVE: To provide an overview of the history and pharmacology of cannabis in relation to current scientific knowledge concerning actual and potential therapeutic uses of cannabis preparations and pure cannabinoids.

  2. Limitations to the Dutch cannabis toleration policy: Assumptions underlying the reclassification of cannabis above 15% THC.

    Science.gov (United States)

    Van Laar, Margriet; Van Der Pol, Peggy; Niesink, Raymond

    2016-08-01

    The Netherlands has seen an increase in Δ9-tetrahydrocannabinol (THC) concentrations from approximately 8% in the 1990s up to 20% in 2004. Increased cannabis potency may lead to higher THC-exposure and cannabis related harm. The Dutch government officially condones the sale of cannabis from so called 'coffee shops', and the Opium Act distinguishes cannabis as a Schedule II drug with 'acceptable risk' from other drugs with 'unacceptable risk' (Schedule I). Even in 1976, however, cannabis potency was taken into account by distinguishing hemp oil as a Schedule I drug. In 2011, an advisory committee recommended tightening up legislation, leading to a 2013 bill proposing the reclassification of high potency cannabis products with a THC content of 15% or more as a Schedule I drug. The purpose of this measure was twofold: to reduce public health risks and to reduce illegal cultivation and export of cannabis by increasing punishment. This paper focuses on the public health aspects and describes the (explicit and implicit) assumptions underlying this '15% THC measure', as well as to what extent these are supported by scientific research. Based on scientific literature and other sources of information, we conclude that the 15% measure can provide in theory a slight health benefit for specific groups of cannabis users (i.e., frequent users preferring strong cannabis, purchasing from coffee shops, using 'steady quantities' and not changing their smoking behaviour), but certainly not for all cannabis users. These gains should be weighed against the investment in enforcement and the risk of unintended (adverse) effects. Given the many assumptions and uncertainty about the nature and extent of the expected buying and smoking behaviour changes, the measure is a political choice and based on thin evidence.

  3. Impaired insight in cocaine addiction: laboratory evidence and effects on cocaine-seeking behaviour

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, S.J.; Moeller, S.J.; Maloney, T.; Parvaz, M.A.; Alia-Klein, N.; Woicik, P.A.; Telang, F.; Wang, G.-J.; Volkow, N.D.; Goldstein, R.Z.

    2010-04-15

    Neuropsychiatric disorders are often characterized by impaired insight into behaviour. Such an insight deficit has been suggested, but never directly tested, in drug addiction. Here we tested for the first time this impaired insight hypothesis in drug addiction, and examined its potential association with drug-seeking behaviour. We also tested potential modulation of these effects by cocaine urine status, an individual difference known to impact underlying cognitive functions and prognosis. Sixteen cocaine addicted individuals testing positive for cocaine in urine, 26 cocaine addicted individuals testing negative for cocaine in urine, and 23 healthy controls completed a probabilistic choice task that assessed objective preference for viewing four types of pictures (pleasant, unpleasant, neutral and cocaine). This choice task concluded by asking subjects to report their most selected picture type; correspondence between subjects self-reports with their objective choice behaviour provided our index of behavioural insight. Results showed that the urine positive cocaine subjects exhibited impaired insight into their own choice behaviour compared with healthy controls; this same study group also selected the most cocaine pictures (and fewest pleasant pictures) for viewing. Importantly, however, it was the urine negative cocaine subjects whose behaviour was most influenced by insight, such that impaired insight in this subgroup only was associated with higher cocaine-related choice on the task and more severe actual cocaine use. These findings suggest that interventions to enhance insight may decrease drug-seeking behaviour, especially in urine negative cocaine subjects, potentially to improve their longer-term clinical outcomes.

  4. Cocaine self-administration disrupts mesolimbic dopamine circuit function and attenuates dopaminergic responsiveness to cocaine.

    Science.gov (United States)

    Siciliano, Cody A; Ferris, Mark J; Jones, Sara R

    2015-08-01

    Dopaminergic projections from the ventral midbrain to the nucleus accumbens (NAc) have long been implicated in encoding associations between reward availability and environmental stimuli. As such, this circuit is instrumental in guiding behaviors towards obtaining maximal rewards based on previous experience. Cocaine acts on the dopamine system to exert its reinforcing effects and it is thought that cocaine-induced dysregulation of dopamine neurotransmission contributes to the difficulty that cocaine addicts exhibit in selecting environmentally appropriate behaviors. Here we used cocaine self-administration combined with in vivo fast scan cyclic voltammetry in anesthetised rats to examine the function of the ventral tegmental area to NAc projection neurons. Over 5 days of cocaine self-administration (fixed-ratio 1; 1.5 mg/kg/injection; 40 injections/day), animals increased their rate of intake. Following cocaine self-administration, there was a marked reduction in ventral tegmental area-stimulated NAc dopamine release. Additionally, there was a decreased augmentation of stimulated dopamine overflow in response to a cocaine challenge. These findings demonstrate that cocaine induces a hypodopaminergic state, which may contribute to the inflexible drug-taking and drug-seeking behaviors observed in cocaine abusers. Additionally, tolerance to the ability of cocaine to elevate dopamine may lead to increased cocaine intake in order to overcome decreased effects, another hallmark of cocaine abuse. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  5. Short-term declines in CD4 levels associated with cocaine use in HIV-1 seropositive, minority injecting drug users.

    Science.gov (United States)

    Siddiqui, N. S.; Brown, L. S.; Makuch, R. W.

    1993-01-01

    This study evaluates the association of cocaine use with short-term change in CD4 counts among human immunodeficiency virus type 1 (HIV-1) seropositive, minority injecting drug users prior to the introduction of zidovudine (AZT). Ninety-eight HIV-1 seropositive subjects were recruited from six inner-city, methadone maintenance clinics. A baseline assessment included a short questionnaire regarding drug behavior and quantitation of CD4 cell counts. These measures were repeated on all subjects 3 to 4 months later. Thirty-eight subjects reported using cocaine between baseline and 4-month follow-up evaluations. Males and African Americans were more likely to be cocaine users (P < .01). Cocaine users were more likely to engage in heroin and needle use (P < .001). Cocaine users experienced a significant decline in CD4 cells compared with nonusers (P = .013); no marked difference in CD4 decline was noted between heroin users and nonusers (P = .19). Multivariate analysis showed that a decline in CD4 counts was 2.82 times more likely to occur in cocaine users than in cocaine nonusers (90% two-sided confidence interval of 1.08, 7.37). These findings support the hypothesis of a possible link between cocaine use and short-term CD4 decline in HIV-1 seropositive injecting drug users. PMID:8478971

  6. Survey of Australians using cannabis for medical purposes

    OpenAIRE

    Dillon Paul; Gates Peter; Swift Wendy

    2005-01-01

    Abstract Background The New South Wales State Government recently proposed a trial of the medical use of cannabis. Australians who currently use cannabis medicinally do so illegally and without assurances of quality control. Given the dearth of local information on this issue, this study explored the experiences of medical cannabis users. Methods Australian adults who had used cannabis for medical purposes were recruited using media stories. A total of 147 respondents were screened by phone a...

  7. Application of medical cannabis in patients with the neurodegeneration disorders

    OpenAIRE

    Lidia Kotuła; Paulina Sobstyl; Jan Sobstyl; Paulina Chwil; Karol Terlecki; Jolanta Karwat; Paulina Gil-Kulik; Alicja Niedojadło; Janusz Kocki

    2014-01-01

    Medical cannabis is the dried flowers of the female Cannabis sativa L. plant. Cannabis contains a number of active elements, including dronabinol (THC) and cannabidiol (CBD). Dronabinol is usually the main ingredient. The body’s own cannabinoid system has been identified. The discovery of this system, which comprises endocannabinoids and receptors, confirmed that cannabis has a positive effect on certain illnesses and conditions. Two types of cannabinoid receptors have been identified: CB1 an...

  8. Reaction Mechanism for Cocaine Esterase-Catalyzed Hydrolyses of (+)- and (−)-Cocaine: Unexpected Common Rate-Determining Step

    OpenAIRE

    Liu, Junjun; Zhao, Xinyun; Yang, Wenchao; Zhan, Chang-Guo

    2011-01-01

    First-principles quantum mechanical/molecular mechanical (QM/MM)-free energy (FE) calculations have been performed to examine catalytic mechanism for cocaine esterase (CocE)-catalyzed hydrolysis of (+)-cocaine in comparison with CocE-catalyzed hydrolysis of (−)-cocaine. It has been shown that the acylation of (+)-cocaine consists of nucleophilic attack of hydroxyl group of Ser117 on carbonyl carbon of (+)-cocaine benzoyl ester and the dissociation of (+)-cocaine benzoyl ester. The first react...

  9. Cocaine challenge enhances release of neuroprotective amino acid taurine in the striatum of chronic cocaine treated rats: a microdialysis study

    OpenAIRE

    Yablonsky-Alter, Elena; Agovic, Mervan S.; Gashi, Eleonora; Lidsky, Theodore I.; Friedman, Eitan; Banerjee, Shailesh P.

    2009-01-01

    Drug addiction is a serious public health problem. There is increasing evidence on the involvement of augmented glutamatergic transmission in cocaine-induced addiction and neurotoxicity. We investigated effects of acute or chronic cocaine administration and cocaine challenge following chronic cocaine exposure on the release of excitotoxic glutamate and neuroprotective taurine in the rat striatum by microdialysis. Cocaine challenge, following withdrawal after repeated cocaine exposure markedly...

  10. Training and Practices of Cannabis Dispensary Staff.

    Science.gov (United States)

    Haug, Nancy A; Kieschnick, Dustin; Sottile, James E; Babson, Kimberly A; Vandrey, Ryan; Bonn-Miller, Marcel O

    2016-01-01

    Introduction: The proliferation of cannabis dispensaries within the United States has emerged from patient demand for the legalization of cannabis as an alternative treatment for a number of conditions and symptoms. Unfortunately, nothing is known about the practices of dispensary staff with respect to recommendation of cannabis strains/concentrations for specific patient ailments. To address this limitation, the present study assessed the training and practices of cannabis dispensary staff. Materials and Methods: Medical and nonmedical dispensary staff (n=55) were recruited via e-mail and social media to complete an online survey assessing their demographic characteristics, dispensary features, patient characteristics, formal training, and cannabis recommendation practices. Results: Fifty-five percent of dispensary staff reported some formal training for their position, with 20% reporting medical/scientific training. A majority (94%) indicated that they provide specific cannabis advice to patients. In terms of strains, dispensary staff trended toward recommendations of Indica for anxiety, chronic pain, insomnia, nightmares, and Tourette's syndrome. They were more likely to recommend Indica and hybrid plants for post-traumatic stress disorder (PTSD)/trauma and muscle spasms. In contrast, staff were less likely to recommend Indica for depression; hybrid strains were most often recommended for amyotrophic lateral sclerosis (ALS). In terms of cannabinoid concentrations, dispensary staff were most likely to recommend a 1:1 ratio of delta-9-tetrahydrocannabinol (THC):cannabidiol (CBD) for patients suffering from anxiety, Crohn's disease, hepatitis C, and PTSD/trauma, while patients seeking appetite stimulation were most likely to be recommended THC. Staff recommended high CBD for arthritis and Alzheimer's disease and a high CBD or 1:1 ratio for ALS, epilepsy, and muscle spasms. Conclusions: Although many dispensary staff are making recommendations consistent with

  11. Cannabis: A Treasure Trove or Pandora's Box?

    Science.gov (United States)

    Solymosi, Katalin; Köfalvi, Attila

    2017-01-01

    Cannabis is one of the earliest cultivated plants. Cannabis of industrial utility and culinary value is generally termed as hemp. Conversely, cannabis that is bred for medical, spiritual and recreational purposes is called marijuana. The female marijuana plant produces a significant quantity of bio- and psychoactive phytocannabinoids, which regained the spotlight with the discovery of the endocannabinoid system of the animals in the early 90's. Nevertheless, marijuana is surrounded by controversies, debates and misconceptions related to its taxonomic classification, forensic identification, medical potential, legalization and its long-term health consequences. In the first part, we provide an in-depth review of the botany and taxonomy of Cannabis. We then overview the biosynthesis of phytocannabinoids within the glandular trichomes with emphasis on the role of peculiar plastids in the production of the secreted material. We also compile the analytical methods used to determine the phytocannabinoid composition of glandular trichomes. In the second part, we revisit the psychobiology and molecular medicine of marijuana. We summarize our current knowledge on the recreational use of cannabis with respect to the modes of consumption, short-term effects, chronic health consequences and cannabis use disorder. Next, we overview the molecular targets of a dozen major and minor bioactive cannabinoids in the body. This helps us introduce the endocannabinoid system in an unprecedented detail: its up-todate molecular biology, pharmacology, physiology and medical significance, and beyond. In conclusion, we offer an unbiased survey about cannabis to help better weigh its medical value versus the associated risks. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Molecular approaches to treatments for cocaine abuse

    Science.gov (United States)

    Flippen-Anderson, Judith L.; George, Clifford; Deschamps, Jeffrey R.

    2003-02-01

    Cocaine is a potent stimulant of the central nervous system with severe addiction potential. Its abuse is a major problem worldwide. The exact mechanism of action of cocaine is still uncertain but it is known that its reinforcing and stimulant effects are related to its ability to inhibit the membrane bound dopamine transporter (DAT). This paper discusses efforts that are underway to identify ligands for possible use in the treatment of cocaine abuse. Much of this effort has been focussed on understanding cocaine interactions at DAT receptor sites.

  13. Cannabis in Europe: Dynamics in perception, policy and markets

    NARCIS (Netherlands)

    Korf, D.J.

    2008-01-01

    After its re-introduction in the 1960s, cannabis has become the most widely used illicit drug in Europe. Along with the spread of cannabis use, its social meaning has changed over time. Today old paradigms are having renewed appeal, in particular on the subject of cannabis and schizophrenia.

  14. The Long and Winding Road to Cannabis Legalization

    NARCIS (Netherlands)

    van Ours, J.C.

    2011-01-01

    In almost all countries supply, distribution and use of cannabis is prohibited. Nevertheless, cannabis is the most popular illicit drug. Prohibition does not seem to work. The debate on legalization of cannabis is often emotional with strong views of both proponents and opponents but ignorance preva

  15. The Long and Winding Road to Cannabis Legalization

    NARCIS (Netherlands)

    van Ours, J.C.

    2011-01-01

    In almost all countries supply, distribution and use of cannabis is prohibited. Nevertheless, cannabis is the most popular illicit drug. Prohibition does not seem to work. The debate on legalization of cannabis is often emotional with strong views of both proponents and opponents but ignorance preva

  16. Infant with Altered Consciousness after Cannabis Passive Inhalation

    Science.gov (United States)

    Zarfin, Yehoshua; Yefet, Enav; Abozaid, Said; Nasser, Wael; Mor, Tamer; Finkelstein, Yoram

    2012-01-01

    We report on an infant who was admitted to hospital with severe neurological symptoms following passive inhalation of cannabis. To date, cannabis abuse has been described almost entirely in adolescents and adults. In early childhood, however, cannabis effects were almost exclusively discussed in the context of maternal prenatal exposure, and the…

  17. Mull it over: cannabis vaporizers and harm reduction.

    Science.gov (United States)

    Gartner, Coral E

    2015-11-01

    Legalization of cannabis is likely to lead to greater use. Balanced regulation of potentially less harmful modes of administration, such as vaporizers, is needed. Further research is warranted not only on the direct health effects of vaping cannabis, but also on its potential to decrease co-administration of tobacco with cannabis.

  18. Infant with Altered Consciousness after Cannabis Passive Inhalation

    Science.gov (United States)

    Zarfin, Yehoshua; Yefet, Enav; Abozaid, Said; Nasser, Wael; Mor, Tamer; Finkelstein, Yoram

    2012-01-01

    We report on an infant who was admitted to hospital with severe neurological symptoms following passive inhalation of cannabis. To date, cannabis abuse has been described almost entirely in adolescents and adults. In early childhood, however, cannabis effects were almost exclusively discussed in the context of maternal prenatal exposure, and the…

  19. [Cocaine-related gastric perforation].

    Science.gov (United States)

    Ring, A; Stein, E; Stern, J

    2010-06-01

    Since the 1980s the abuse of cocaine has been -associated with gastroduodenal perforations in the United States. Here, we report the case of a 28-year-old man who came to our hospital with severe abdominal pain after smoking cocaine. Physical examination revealed generalised abdominal guarding. His X-ray did not show any free intraperitoneal air. However, there was a slightly elevated white blood cell count. Upon laparoscopic exploration of the abdomen, the -patient was found to have a generalised peritonitis secondary to a perforation of the prepyloric anterior wall. The operative procedure consisted of ulcer excision and primary closure with a pyloroplasty as well as an extensive abdominal irrigation after laparotomy.

  20. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32330 subjects from the International Cannabis Consortium

    NARCIS (Netherlands)

    Stringer, S.; Minica, C. C.; Verweij, K. J. H.; Mbarek, H.; Bernard, M.; Derringer, J.; van Eijk, K. R.; Isen, J. D.; Loukola, A.; Maciejewski, D. F.; Mihailov, E.; van der Most, P. J.; Sanchez-Mora, C.; Roos, L.; Sherva, R.; Walters, R.; Ware, J. J.; Abdellaoui, A.; Bigdeli, T. B.; Branje, S. J. T.; Brown, S. A.; Bruinenberg, M.; Casas, M.; Esko, T.; Garcia-Martinez, I.; Gordon, S. D.; Harris, J. M.; Hartman, C. A.; Henders, A. K.; Heath, A. C.; Hickie, I. B.; Hickman, M.; Hopfer, C. J.; Hottenga, J. J.; Huizink, A. C.; Irons, D. E.; Kahn, R. S.; Korhonen, T.; Kranzler, H. R.; Krauter, K.; van Lier, P. A. C.; Lubke, G. H.; Madden, P. A. F.; Magi, R.; McGue, M. K.; Medland, S. E.; Meeus, W. H. J.; Miller, M. B.; Montgomery, G. W.; Nivard, M. G.; Nolte, I. M.; Oldehinkel, A. J.; Pausova, Z.; Qaiser, B.; Quaye, L.; Ramos-Quiroga, J. A.; Richarte, V.; Rose, R. J.; Shin, J.; Stallings, M. C.; Stiby, A. I.; Wall, T. L.; Wright, M. J.; Koot, H. M.; Paus, T.; Hewitt, J. K.; Ribases, M.; Kaprio, J.; Boks, M. P.; Snieder, H.; Spector, T.; Munafo, M. R.; Metspalu, A.; Gelernter, J.; Boomsma, D. I.; Iacono, W. G.; Martin, N. G.; Gillespie, N. A.; Derks, E. M.; Vink, J. M.

    2016-01-01

    Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable

  1. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium

    NARCIS (Netherlands)

    Stringer, S; Minică, C C; Verweij, K J H; Mbarek, H; Bernard, M; Derringer, J; van Eijk, K R; Isen, J D; Loukola, A; Maciejewski, Dominique F.; Mihailov, E; van der Most, P J; Sánchez-Mora, C; Roos, L; Sherva, R; Walters, R; Ware, J J; Abdellaoui, A; Bigdeli, T B; Branje, S J T; Brown, S A; Bruinenberg, M; Casas, M; Esko, T; Garcia-Martinez, I; Gordon, S D; Harris, J M; Hartman, C A; Henders, A K; Heath, A C; Hickie, I B; Hickman, M; Hopfer, C J; Hottenga, J J; Huizink, A C; Irons, D E; Kahn, R S; Korhonen, T; Kranzler, H R; Krauter, K; van Lier, P A C; Lubke, G H; Madden, P A F; Mägi, R; McGue, M K; Medland, S E; Meeus, W H J; Miller, M B; Montgomery, G W; Nivard, M G; Nolte, I M; Oldehinkel, A J; Pausova, Z; Qaiser, B; Quaye, L; Ramos-Quiroga, J A; Richarte, V; Rose, R J; Shin, J; Stallings, M C; Stiby, A I; Wall, T L; Wright, M J; Koot, H M; Paus, T; Hewitt, J K; Ribasés, M; Kaprio, J; Boks, M P; Snieder, H; Spector, T; Munafò, M R; Metspalu, A; Gelernter, J; Boomsma, D I; Iacono, W G; Martin, N G; Gillespie, N A; Derks, E M; Vink, J M

    2016-01-01

    Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (

  2. The relationship between cannabis use and measures of anxiety and depression in a sample of college campus cannabis users and non-users post state legalization in Colorado

    National Research Council Canada - National Science Library

    Troup, Lucy J; Andrzejewski, Jeremy A; Braunwalder, Jacob T; Torrence, Robert D

    2016-01-01

    As part of an ongoing research program into the relationship between cannabis use and emotion processing, participants were assessed on their level of cannabis exposure using the Recreational Cannabis...

  3. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32330 subjects from the International Cannabis Consortium

    NARCIS (Netherlands)

    Stringer, S.; Minica, C. C.; Verweij, K. J. H.; Mbarek, H.; Bernard, M.; Derringer, J.; van Eijk, K. R.; Isen, J. D.; Loukola, A.; Maciejewski, D. F.; Mihailov, E.; van der Most, P. J.; Sanchez-Mora, C.; Roos, L.; Sherva, R.; Walters, R.; Ware, J. J.; Abdellaoui, A.; Bigdeli, T. B.; Branje, S. J. T.; Brown, S. A.; Bruinenberg, M.; Casas, M.; Esko, T.; Garcia-Martinez, I.; Gordon, S. D.; Harris, J. M.; Hartman, C. A.; Henders, A. K.; Heath, A. C.; Hickie, I. B.; Hickman, M.; Hopfer, C. J.; Hottenga, J. J.; Huizink, A. C.; Irons, D. E.; Kahn, R. S.; Korhonen, T.; Kranzler, H. R.; Krauter, K.; van Lier, P. A. C.; Lubke, G. H.; Madden, P. A. F.; Magi, R.; McGue, M. K.; Medland, S. E.; Meeus, W. H. J.; Miller, M. B.; Montgomery, G. W.; Nivard, M. G.; Nolte, I. M.; Oldehinkel, A. J.; Pausova, Z.; Qaiser, B.; Quaye, L.; Ramos-Quiroga, J. A.; Richarte, V.; Rose, R. J.; Shin, J.; Stallings, M. C.; Stiby, A. I.; Wall, T. L.; Wright, M. J.; Koot, H. M.; Paus, T.; Hewitt, J. K.; Ribases, M.; Kaprio, J.; Boks, M. P.; Snieder, H.; Spector, T.; Munafo, M. R.; Metspalu, A.; Gelernter, J.; Boomsma, D. I.; Iacono, W. G.; Martin, N. G.; Gillespie, N. A.; Derks, E. M.; Vink, J. M.

    2016-01-01

    Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (

  4. Approach-Bias Predicts Development of Cannabis Problem Severity in Heavy Cannabis Users: Results from a Prospective FMRI Study

    Science.gov (United States)

    Cousijn, Janna; Goudriaan, Anna E.; Ridderinkhof, K. Richard; van den Brink, Wim; Veltman, Dick J.; Wiers, Reinout W.

    2012-01-01

    A potentially powerful predictor for the course of drug (ab)use is the approach-bias, that is, the pre-reflective tendency to approach rather than avoid drug-related stimuli. Here we investigated the neural underpinnings of cannabis approach and avoidance tendencies. By elucidating the predictive power of neural approach-bias activations for future cannabis use and problem severity, we aimed at identifying new intervention targets. Using functional Magnetic Resonance Imaging (fMRI), neural approach-bias activations were measured with a Stimulus Response Compatibility task (SRC) and compared between 33 heavy cannabis users and 36 matched controls. In addition, associations were examined between approach-bias activations and cannabis use and problem severity at baseline and at six-month follow-up. Approach-bias activations did not differ between heavy cannabis users and controls. However, within the group of heavy cannabis users, a positive relation was observed between total lifetime cannabis use and approach-bias activations in various fronto-limbic areas. Moreover, approach-bias activations in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) independently predicted cannabis problem severity after six months over and beyond session-induced subjective measures of craving. Higher DLPFC/ACC activity during cannabis approach trials, but lower activity during cannabis avoidance trials were associated with decreases in cannabis problem severity. These findings suggest that cannabis users with deficient control over cannabis action tendencies are more likely to develop cannabis related problems. Moreover, the balance between cannabis approach and avoidance responses in the DLPFC and ACC may help identify individuals at-risk for cannabis use disorders and may be new targets for prevention and treatment. PMID:22957019

  5. Approach-bias predicts development of cannabis problem severity in heavy cannabis users: results from a prospective FMRI study.

    Directory of Open Access Journals (Sweden)

    Janna Cousijn

    Full Text Available A potentially powerful predictor for the course of drug (abuse is the approach-bias, that is, the pre-reflective tendency to approach rather than avoid drug-related stimuli. Here we investigated the neural underpinnings of cannabis approach and avoidance tendencies. By elucidating the predictive power of neural approach-bias activations for future cannabis use and problem severity, we aimed at identifying new intervention targets. Using functional Magnetic Resonance Imaging (fMRI, neural approach-bias activations were measured with a Stimulus Response Compatibility task (SRC and compared between 33 heavy cannabis users and 36 matched controls. In addition, associations were examined between approach-bias activations and cannabis use and problem severity at baseline and at six-month follow-up. Approach-bias activations did not differ between heavy cannabis users and controls. However, within the group of heavy cannabis users, a positive relation was observed between total lifetime cannabis use and approach-bias activations in various fronto-limbic areas. Moreover, approach-bias activations in the dorsolateral prefrontal cortex (DLPFC and anterior cingulate cortex (ACC independently predicted cannabis problem severity after six months over and beyond session-induced subjective measures of craving. Higher DLPFC/ACC activity during cannabis approach trials, but lower activity during cannabis avoidance trials were associated with decreases in cannabis problem severity. These findings suggest that cannabis users with deficient control over cannabis action tendencies are more likely to develop cannabis related problems. Moreover, the balance between cannabis approach and avoidance responses in the DLPFC and ACC may help identify individuals at-risk for cannabis use disorders and may be new targets for prevention and treatment.

  6. Polysubstance use in cannabis users referred for treatment: Drug use profiles, psychiatric comorbidity and cannabis-related beliefs

    Directory of Open Access Journals (Sweden)

    Jason Paul Connor

    2013-08-01

    Full Text Available Background: Population-based surveys demonstrate cannabis users are more likely to use both illicit and licit substances, compared with non-cannabis users. Few studies have examined the substance use profiles of cannabis users referred for treatment. Coexisting mental health symptoms and underlying cannabis-related beliefs associated with these profiles remains unexplored.Methods: Comprehensive drug use and dependence severity (Severity of Dependence Scale- Cannabis [SDS-C] data were collected on a sample of 826 cannabis users referred for treatment. Patients completed the General Health Questionnaire (GHQ-28, Cannabis Expectancy Questionnaire (CEQ, and Cannabis Refusal Self-Efficacy Questionnaire (CRSEQ and Positive Symptoms and Manic-Excitement subscales of the Brief Psychiatric Rating Scale (BPRS. Latent class analysis (LCA was performed on last month use of drugs to identify patterns of multiple drug use. Mental health comorbidity and cannabis beliefs were examined by identified drug use pattern.Results: A three-class solution provided the best fit to the data- (1 Cannabis and tobacco users (n = 176, (2 Cannabis, tobacco, and alcohol users (n = 498, and (3 wide-ranging substance users (n = 132. Wide-ranging substance users (3 reported higher levels of cannabis dependence severity, negative cannabis expectancies, lower opportunistic and emotional relief self-efficacy, higher levels of depression and anxiety, and higher manic-excitement and positive psychotic symptoms.Conclusion: In a sample of cannabis users referred for treatment, wide-ranging substance use was associated with elevated risk on measures of cannabis dependence, comorbid psychopathology and dysfunctional cannabis cognitions. These findings have implications for cognitive-behavioural assessment and treatment.

  7. Stimulation of 5-HT(1B) receptors enhances cocaine reinforcement yet reduces cocaine-seeking behavior.

    Science.gov (United States)

    Pentkowski, Nathan S; Acosta, Jazmin I; Browning, Jenny R; Hamilton, Elizabeth C; Neisewander, Janet L

    2009-09-01

    Paradoxically, stimulation of 5-HT(1B) receptors (5-HT(1B)Rs) enhances sensitivity to the reinforcing effects of cocaine but attenuates incentive motivation for cocaine as measured using the extinction/reinstatement model. We revisited this issue by examining the effects of a 5-HT(1B)R agonist, CP94253, on cocaine reinforcement and cocaine-primed reinstatement, predicting that CP94253 would enhance cocaine-seeking behavior reinstated by a low priming dose, similar to its effect on cocaine reinforcement. Rats were trained to self-administer cocaine (0.75 mg/kg, i.v.) paired with light and tone cues. For reinstatement experiments, they then underwent daily extinction training to reduce cocaine-seeking behavior (operant responses without cocaine reinforcement). Next, they were pre-treated with CP94253 (3-10 mg/kg, s.c.) and either tested for cocaine-primed (10 or 2.5 mg/kg, i.p.) or cue-elicited reinstatement of extinguished cocaine-seeking behavior. For reinforcement, effects of CP94253 (5.6 mg/kg) across a range of self-administered cocaine doses (0-1.5 mg/kg, i.v.) were examined. Cocaine dose-dependently reinstated cocaine-seeking behavior, but contrary to our prediction, CP94253 reduced reinstatement with both priming doses. Similarly, CP94253 reduced cue-elicited reinstatement. In contrast, CP94253 shifted the self-administration dose-effect curve leftward, consistent with enhanced cocaine reinforcement. When saline was substituted for cocaine, CP94253 reduced response rates (i.e. cocaine-seeking behavior). In subsequent control experiments, CP94253 decreased open-arm exploration in an elevated plus-maze suggesting an anxiogenic effect, but had no effect on locomotion or sucrose reinforcement. These results provide strong evidence that stimulation of 5-HT(1B)Rs produces opposite effects on cocaine reinforcement and cocaine-seeking behavior, and further suggest that 5-HT(1B)Rs may be a novel target for developing medications for cocaine dependence.

  8. Diazepam alters cocaine self-administration, but not cocaine-stimulated locomotion or nucleus accumbens dopamine

    OpenAIRE

    2008-01-01

    Cocaine is known to enhance nucleus accumbens dopamine (NAcc DA), serve as a positive reinforcer and produce negative effects, such as anxiety. The influence of diazepam on cocaine intake, cocaine-stimulated behavioral activity and NAcc DA was investigated using self-administration and experimenter-administered intravenous (i.v.) cocaine. In Experiment 1, rats were pretreated with diazepam (0.25 mg/kg) or saline (0.1 ml) 30 minutes prior to 20 daily 1-hr cocaine (0.75 mg/kg/inj) self-administ...

  9. Cannabis tea revisited: a systematic evaluation of the cannabinoid composition of cannabis tea.

    Science.gov (United States)

    Hazekamp, Arno; Bastola, Krishna; Rashidi, Hassan; Bender, Johan; Verpoorte, Rob

    2007-08-15

    Cannabis is one of the oldest known medicinal plants, and a large variety of biological activities have been described. The main constituents, the cannabinoids, are thought to be most important for these activities. Although smoking of cannabis is by far the most common way of consumption, a significant part of medicinal users consume it in the form of a tea. However, not much is known about the composition of cannabis tea, or the effect of different parameters during preparation, handling or storage. In this study we used the high-grade cannabis available in Dutch pharmacies to study the cannabinoid composition of tea under standardized and quantitative conditions. Experimental conditions were systematically varied in order to mimic the possible variations made by medicinal users. During analysis there was a specific focus on the cannabinoid tetrahydrocannabinol and its acidic precursor, tetrahydrocannabinolic acid. Also the role of non-psychoactive cannabinoids as components of cannabis tea are discussed. The results obtained in this study provide a clear quantitative insight in the phytochemistry of cannabis tea preparation and can contribute to a better appreciation of this mode of cannabis administration.

  10. Cannabis Beyond Good and Evil. How genetic and epidemiological factors shape the relationship between cannabis and psychosis

    NARCIS (Netherlands)

    Schubart, C.D.

    2013-01-01

    The studies presented in this thesis aimed to identify genetic and non-genetic (epidemiological) factors that shape the association between cannabis use and psychosis. We showed that the age of first use of cannabis is a determinant for the strength of the association between cannabis use and psycho

  11. Maternal age and trajectories of cannabis use.

    Science.gov (United States)

    De Genna, Natacha M; Cornelius, Marie D; Goldschmidt, Lidush; Day, Nancy L

    2015-11-01

    Becoming a mother is a developmental transition that has been linked to desistance from substance use. However, timing of motherhood may be a key determinant of cannabis use in women, based on preliminary evidence from teenage mothers. The goal of this study was to identify trajectories of maternal cannabis use, and to determine if maternal age was associated with different trajectories of use. This prospective study examined 456 pregnant women recruited at a prenatal clinic, ranging in age from 13 to 42 years. The women were interviewed about their cannabis use 1 year prior to pregnancy and during each trimester of pregnancy, and at 6, 10, 14, and 16 years post-partum. A growth mixture model of cannabis use reported at each time point clearly delineated four groups: non/unlikely to use, decreasing likelihood of use, late desistance, and increasing likelihood/chronic use (Lo-Mendell-Rubin adjusted LRT test statistic=35.7, pcannabis across 17 years, including later desistance post-partum and increasing/chronic use. Other substance use and chronic depressive symptoms were also associated with more frequent use. These findings have implications for both prevention and treatment of cannabis use in mothers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. A fatal overdose of cocaine associated with coingestion of marijuana, buprenorphine, and fluoxetine. Body fluid and tissue distribution of cocaine and its metabolites determined by hydrophilic interaction chromatography-mass spectrometry(HILIC-MS).

    Science.gov (United States)

    Giroud, Christian; Michaud, Katarzyna; Sporkert, Frank; Eap, Chin; Augsburger, Marc; Cardinal, Pascal; Mangin, Patrice

    2004-09-01

    (about 1 mg/L) were measured in bile and urine. Very high levels of cocaine were determined in hair (160 ng/mg), indicating chronic cocaine use. A low concentration of anhydroecgonine methylester was also found in urine (0.65 mg/L) suggesting recent cocaine inhalation. Therapeutic blood concentrations of fluoxetine (0.15 mg/L) and buprenorphine (0.1 microg/L) were also discovered. A relatively high concentration of Delta(9)-THC was measured both in peripheral blood (8.2 microg/L) and brain cortex (13.5 microg/kg), suggesting that the victim was under the influence of cannabis at the time of death. In addition, fluoxetine might have enhanced the toxic effects of cocaine because of its weak pro-arrhythmogenic properties. Likewise, combination of cannabinoids and cocaine might have increase detrimental cardiovascular effects. Altogether, these results indicate a lethal cocaine overdose with a minor contribution of fluoxetine and cannabinoids.

  13. Analysis of cannabis seizures in NSW, Australia: cannabis potency and cannabinoid profile.

    Directory of Open Access Journals (Sweden)

    Wendy Swift

    Full Text Available Recent analysis of the cannabinoid content of cannabis plants suggests a shift towards use of high potency plant material with high levels of Δ(9-tetrahydrocannabinol (THC and low levels of other phytocannabinoids, particularly cannabidiol (CBD. Use of this type of cannabis is thought by some to predispose to greater adverse outcomes on mental health and fewer therapeutic benefits. Australia has one of the highest per capita rates of cannabis use in the world yet there has been no previous systematic analysis of the cannabis being used. In the present study we examined the cannabinoid content of 206 cannabis samples that had been confiscated by police from recreational users holding 15 g of cannabis or less, under the New South Wales "Cannabis Cautioning" scheme. A further 26 "Known Provenance" samples were analysed that had been seized by police from larger indoor or outdoor cultivation sites rather than from street level users. An HPLC method was used to determine the content of 9 cannabinoids: THC, CBD, cannabigerol (CBG, and their plant-based carboxylic acid precursors THC-A, CBD-A and CBG-A, as well as cannabichromene (CBC, cannabinol (CBN and tetrahydrocannabivarin (THC-V. The "Cannabis Cautioning" samples showed high mean THC content (THC+THC-A = 14.88% and low mean CBD content (CBD+CBD-A = 0.14%. A modest level of CBG was detected (CBG+CBG-A = 1.18% and very low levels of CBC, CBN and THC-V (<0.1%. "Known Provenance" samples showed no significant differences in THC content between those seized from indoor versus outdoor cultivation sites. The present analysis echoes trends reported in other countries towards the use of high potency cannabis with very low CBD content. The implications for public health outcomes and harm reduction strategies are discussed.

  14. Analysis of Cannabis Seizures in NSW, Australia: Cannabis Potency and Cannabinoid Profile

    Science.gov (United States)

    Li, Kong M.; Arnold, Jonathon C.; McGregor, Iain S.

    2013-01-01

    Recent analysis of the cannabinoid content of cannabis plants suggests a shift towards use of high potency plant material with high levels of Δ9-tetrahydrocannabinol (THC) and low levels of other phytocannabinoids, particularly cannabidiol (CBD). Use of this type of cannabis is thought by some to predispose to greater adverse outcomes on mental health and fewer therapeutic benefits. Australia has one of the highest per capita rates of cannabis use in the world yet there has been no previous systematic analysis of the cannabis being used. In the present study we examined the cannabinoid content of 206 cannabis samples that had been confiscated by police from recreational users holding 15 g of cannabis or less, under the New South Wales “Cannabis Cautioning” scheme. A further 26 “Known Provenance” samples were analysed that had been seized by police from larger indoor or outdoor cultivation sites rather than from street level users. An HPLC method was used to determine the content of 9 cannabinoids: THC, CBD, cannabigerol (CBG), and their plant-based carboxylic acid precursors THC-A, CBD-A and CBG-A, as well as cannabichromene (CBC), cannabinol (CBN) and tetrahydrocannabivarin (THC-V). The “Cannabis Cautioning” samples showed high mean THC content (THC+THC-A = 14.88%) and low mean CBD content (CBD+CBD-A = 0.14%). A modest level of CBG was detected (CBG+CBG-A = 1.18%) and very low levels of CBC, CBN and THC-V (cannabis with very low CBD content. The implications for public health outcomes and harm reduction strategies are discussed. PMID:23894589

  15. Manipulating a "cocaine engram" in mice.

    Science.gov (United States)

    Hsiang, Hwa-Lin Liz; Epp, Jonathan R; van den Oever, Michel C; Yan, Chen; Rashid, Asim J; Insel, Nathan; Ye, Li; Niibori, Yosuke; Deisseroth, Karl; Frankland, Paul W; Josselyn, Sheena A

    2014-10-15

    Experience with drugs of abuse (such as cocaine) produces powerful, long-lasting memories that may be important in the development and persistence of drug addiction. The neural mechanisms that mediate how and where these cocaine memories are encoded, consolidated and stored are unknown. Here we used conditioned place preference in mice to examine the precise neural circuits that support the memory of a cocaine-cue association (the "cocaine memory trace" or "cocaine engram"). We found that a small population of neurons (∼10%) in the lateral nucleus of amygdala (LA) were recruited at the time of cocaine-conditioning to become part of this cocaine engram. Neurons with increased levels of the transcription factor CREB were preferentially recruited or allocated to the cocaine engram. Ablating or silencing neurons overexpressing CREB (but not a similar number of random LA neurons) before testing disrupted the expression of a previously acquired cocaine memory, suggesting that neurons overexpressing CREB become a critical hub in what is likely a larger cocaine memory engram. Consistent with theories that coordinated postencoding reactivation of neurons within an engram or cell assembly is crucial for memory consolidation (Marr, 1971; Buzsáki, 1989; Wilson and McNaughton, 1994; McClelland et al., 1995; Girardeau et al., 2009; Dupret et al., 2010; Carr et al., 2011), we also found that post-training suppression, or nondiscriminate activation, of CREB overexpressing neurons impaired consolidation of the cocaine memory. These findings reveal mechanisms underlying how and where drug memories are encoded and stored in the brain and may also inform the development of treatments for drug addiction.

  16. A thermostable bacterial cocaine esterase rapidly eliminates cocaine from brain in nonhuman primates.

    Science.gov (United States)

    Howell, L L; Nye, J A; Stehouwer, J S; Voll, R J; Mun, J; Narasimhan, D; Nichols, J; Sunahara, R; Goodman, M M; Carroll, F I; Woods, J H

    2014-07-01

    A long-acting, thermostable bacterial cocaine esterase (CocE) has been identified that rapidly degrades cocaine with a K(M) of 1.33+0.085 μM. In vivo evaluation of CocE has shown protection against convulsant and lethal effects of cocaine in rodents, confirming the therapeutic potential of CocE against cocaine overdose. However, the current study is the first to evaluate the effects of CocE on cocaine brain levels. Positron emission tomogrpahy neuroimaging of [(11)C]cocaine was used to evaluate the time course of cocaine elimination from brain in the presence and absence of CocE in nonhuman primates. Systemic administration of CocE eliminated cocaine from the rhesus-monkey brain approximately three times faster than control conditions via peripheral actions through attenuating the input function from blood plasma. The efficiency of this process is sufficient to alleviate or prevent adverse central nervous system effects induced by cocaine. Although the present study used tracer doses of cocaine to access brain clearance, these findings further support the development of CocE for the treatment of acute cocaine toxicity.

  17. Bacterial cocaine esterase: a protein-based therapy for cocaine overdose and addiction.

    Science.gov (United States)

    Narasimhan, Diwahar; Woods, James H; Sunahara, Roger K

    2012-02-01

    Cocaine is highly addictive and there are no pharmacotherapeutic drugs available to treat acute cocaine toxicity or chronic abuse. Antagonizing an inhibitor such as cocaine using a small molecule has proven difficult. The alternative approach is to modify cocaine's pharmacokinetic properties by sequestering or hydrolyzing it in serum and limiting access to its sites of action. We took advantage of a bacterial esterase (CocE) that has evolved to hydrolyze cocaine and have developed it as a therapeutic that rapidly and specifically clears cocaine from the subject. Native enzyme was unstable at 37°C, thus limiting CocE's potential. Innovative computational methods based on the protein's structure helped elucidate its mechanism of destabilization. Novel protein engineering methodologies were applied to substantially improve its stability in vitro and in vivo. These improvements rendered CocE as a powerful and efficacious therapeutic to treat cocaine intoxication and lead the way towards developing a therapy for addiction.

  18. Levamisole-Contaminated Cocaine Use in HIV-Infected and Uninfected Unstably Housed Women.

    Science.gov (United States)

    Riley, Elise D; Kral, Alex H; Cohen, Jennifer; Dilworth, Samantha E; Shumway, Martha; Lynch, Kara L

    2016-09-01

    A growing number of case reports cite serious health complications linked to the cocaine adulterant, levamisole and women are disproportionately affected; however, the clinical effects are not well established. Between April and October of 2010, we conducted a cross-sectional study among 222 homeless and unstably housed women (116 human immunodeficiency virus [HIV]-infected and 106 HIV-uninfected). Immune markers and behavioral factors were compared in separate models by cocaine and levamisole exposure. Overall, 63% of participants were toxicology positive for cocaine/benzoylecgonine, 85% of whom also tested positive for levamisole. Differences in immune markers did not reach levels of significance among HIV-uninfected persons. Compared to HIV-infected persons who were negative for both cocaine and levamisole, the adjusted odds of low white blood cell count were significantly higher among HIV-infected persons positive for both (p = 0.03), but not for those positive for cocaine only. Neutrophil count and HIV viral load did not differ by cocaine and levamisole status among HIV-infected persons. In a separate model, the adjusted odds of testing positive for levamisole were higher among African American women compared to Caucasian and Asian women (p = 0.02). In the context of high levamisole prevalence, results suggest that decreased immune function as a result of levamisole exposure occurs mainly in individuals who are already immune compromised (e.g., HIV-positive), and race/ethnicity appears to be an important factor in understanding levamisole exposure among cocaine-using women. While larger and geographically diverse studies are needed to elucidate these initial findings, results suggest that levamisole may be one mechanism of immune dysfunction in HIV-infected cocaine-using women.

  19. Prenatal and acute cocaine exposure affects neural responses and habituation to visual stimuli.

    Science.gov (United States)

    Riley, Elizabeth; Kopotiyenko, Konstantin; Zhdanova, Irina

    2015-01-01

    Psychostimulants have many effects on visual function, from adverse following acute and prenatal exposure to therapeutic on attention deficit. To determine the impact of prenatal and acute cocaine exposure on visual processing, we studied neuronal responses to visual stimuli in two brain regions of a transgenic larval zebrafish expressing the calcium indicator GCaMP-HS. We found that both red light (LF) and dark (DF) flashes elicited similar responses in the optic tectum neuropil (TOn), while the dorsal telencephalon (dTe) responded only to LF. Acute cocaine (0.5 μM) reduced neuronal responses to LF in both brain regions but did not affect responses to DF. Repeated stimulus presentation (RSP) led to habituation of dTe neurons to LF. Acute cocaine prevented habituation. TOn habituated to DF, but not LF, and DF habituation was not modified by cocaine. Remarkably, prenatal cocaine exposure (PCE) prevented the effects of acute cocaine on LF response amplitude and habituation later in development in both brain regions, but did not affect DF responses. We discovered that, in spite of similar neural responses to LF and DF in the TO (superior colliculus in mammals), responses to LF are more complex, involving dTe (homologous to the cerebral cortex), and are more vulnerable to cocaine. Our results demonstrate that acute cocaine exposure affects visual processing differentially by brain region, and that PCE modifies zebrafish visual processing in multiple structures in a stimulus-dependent manner. These findings are in accordance with the major role that the optic tectum and cerebral cortex play in sustaining visual attention, and support the hypothesis that modification of these areas by PCE may be responsible for visual deficits noted in humans. This model offers new methodological approaches for studying the adverse and therapeutic effects of psychostimulants on attention, and for the development of new pharmacological interventions.

  20. Growth, development, and behavior in early childhood following prenatal cocaine exposure: a systematic review.

    Science.gov (United States)

    Frank, D A; Augustyn, M; Knight, W G; Pell, T; Zuckerman, B

    2001-03-28

    Despite recent studies that failed to show catastrophic effects of prenatal cocaine exposure, popular attitudes and public policies still reflect the belief that cocaine is a uniquely dangerous teratogen. To critically review outcomes in early childhood after prenatal cocaine exposure in 5 domains: physical growth; cognition; language skills; motor skills; and behavior, attention, affect, and neurophysiology. Search of MEDLINE and Psychological Abstracts from 1984 to October 2000. Studies selected for detailed review (1) were published in a peer-reviewed English-language journal; (2) included a comparison group; (3) recruited samples prospectively in the perinatal period; (4) used masked assessment; and (5) did not include a substantial proportion of subjects exposed in utero to opiates, amphetamines, phencyclidine, or maternal human immunodeficiency virus infection. Thirty-six of 74 articles met criteria and were reviewed by 3 authors. Disagreements were resolved by consensus. After controlling for confounders, there was no consistent negative association between prenatal cocaine exposure and physical growth, developmental test scores, or receptive or expressive language. Less optimal motor scores have been found up to age 7 months but not thereafter, and may reflect heavy tobacco exposure. No independent cocaine effects have been shown on standardized parent and teacher reports of child behavior scored by accepted criteria. Experimental paradigms and novel statistical manipulations of standard instruments suggest an association between prenatal cocaine exposure and decreased attentiveness and emotional expressivity, as well as differences on neurophysiologic and attentional/affective findings. Among children aged 6 years or younger, there is no convincing evidence that prenatal cocaine exposure is associated with developmental toxic effects that are different in severity, scope, or kind from the sequelae of multiple other risk factors. Many findings once thought

  1. Cannabis depenalisation, drug consumption and crime - evidence from the 2004 cannabis declassification in the UK.

    Science.gov (United States)

    Braakmann, Nils; Jones, Simon

    2014-08-01

    This paper investigates the link between cannabis depenalisation and crime using individual-level panel data for England and Wales from 2003 to 2006. We exploit the declassification of cannabis in the UK in 2004 as a natural experiment. Specifically, we use the fact that the declassification changed expected punishments differently in various age groups due to thresholds in British criminal law and employ a difference-in-differences type design using data from the longitudinal version of the Offending, Crime and Justice Survey. Our findings suggest essentially no increases in either cannabis consumption, consumption of other drugs, crime and other forms of risky behaviour.

  2. Decriminalization of cannabis--potential risks for children?

    Science.gov (United States)

    Amirav, Israel; Luder, Anthony; Viner, Yuri; Finkel, Martin

    2011-04-01

    The legalization of cannabis for medicinal purposes is becoming increasingly widespread worldwide. The anticipated growing ease of access to cannabis may create an increased risk for passive and/or active ingestion by children. We report a case of a 1.5-year-old infant who presented with unexplained coma that was later proved to be associated with the ingestion of cannabis. This case highlights the importance of considering cannabis ingestion in the differential diagnosis of infantile and toddler coma and the need for public education regarding the risks of childhood exposure in the light of the legalization of cannabis for medical purposes and its greater availability.

  3. Prevalence of levamisole and aminorex in patients tested positive for cocaine in a French University Hospital.

    Science.gov (United States)

    Eiden, Céline; Peyrière, Hélène; Diot, Caroline; Mathieu, Olivier

    2015-01-01

    The prevalence of levamisole in urine samples of subjects positive for cocaine in the US was estimated at 78% (95%confidence interval or CI: 73%-83%). However, levamisole was not quantified, and at the time of this report, aminorex was not known to be a possible metabolite of levamisole in human. Moreover no data are available in Europe. The aim of this study was to determine the prevalence and concentration of levamisole and aminorex in positive cocaine urine toxicology tests, and in serum samples of cocaine-positive subjects driving under the influence of drugs or forensic autopsies. Consecutive urine toxicology samples tested positive for cocaine by immunoassay (EMIT, Siemens) from April to May 2014 at the toxicology laboratory of a French University Hospital, and blood samples of cocaine-positive subjects driving under the influence of drugs or forensic autopsies from April to December 2014 were analyzed by liquid chromatography-tandem mass spectrometry or LC-MS/MS (3200 QTrap, AB Sciex) to detect and quantify the presence of levamisole and aminorex. Forty-two urine samples tested positive for cocaine in 39 patients (79.5% males) with a median age of 43 [range: 20-51] years. Toxicological analyses were mainly required by addictions care centers (n = 17; 40%) in the context of the routine management of addict patients. Cocaine concentrations were above the limit of quantification for 33 patients, with a median value of 228 [0-645,000] ng/ml. Levamisole was detected in 32 urine samples (76%) (median concentration: 1,430 ng/ml, range: 30-258,000). Aminorex was never detected. During the study period, levamisole was detected in 87.5% of cocaine-positive blood samples of the subjects driving under the influence of drugs or forensic autopsies. In this prospective study, the prevalence of levamisole in cocaine-positive samples was 76%. Over this period, although clinical complications related to cocaine use were reported (agitation, road accident, and cardiac arrest

  4. Dorsal medial prefrontal cortex (MPFC) circuitry in rodent models of cocaine use: implications for drug addiction therapies.

    Science.gov (United States)

    Jasinska, Agnes J; Chen, Billy T; Bonci, Antonello; Stein, Elliot A

    2015-03-01

    Although the importance of the medial prefrontal cortex (MPFC) in cocaine addiction is well established, its precise contribution to cocaine seeking, taking and relapse remains incompletely understood. In particular, across two different models of cocaine self-administration, pharmacological or optogenetic activation of the dorsal MPFC has been reported to sometimes promote and sometimes inhibit cocaine seeking. We highlight important methodological differences between the two experimental paradigms and propose a framework to potentially reconcile the apparent discrepancy. We also draw parallels between these pre-clinical models of cocaine self-administration and human neuro-imaging studies in cocaine users, and argue that both lines of evidence point to dynamic interactions between cue-reactivity processes and control processes within the dorsal MPFC circuitry. From a translational perspective, these findings underscore the importance of interventions and therapeutics targeting not just a brain region, but a specific computational process within that brain region, and may have implications for the design and implementation of more effective treatments for human cocaine addiction. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  5. The Use of Cannabis for Headache Disorders

    Science.gov (United States)

    Lochte, Bryson C.; Beletsky, Alexander; Samuel, Nebiyou K.; Grant, Igor

    2017-01-01

    Abstract Headache disorders are common, debilitating, and, in many cases, inadequately managed by existing treatments. Although clinical trials of cannabis for neuropathic pain have shown promising results, there has been limited research on its use, specifically for headache disorders. This review considers historical prescription practices, summarizes the existing reports on the use of cannabis for headache, and examines the preclinical literature exploring the role of exogenous and endogenous cannabinoids to alter headache pathophysiology. Currently, there is not enough evidence from well-designed clinical trials to support the use of cannabis for headache, but there are sufficient anecdotal and preliminary results, as well as plausible neurobiological mechanisms, to warrant properly designed clinical trials. Such trials are needed to determine short- and long-term efficacy for specific headache types, compatibility with existing treatments, optimal administration practices, as well as potential risks. PMID:28861505

  6. Opiate and Cocaine Exposed Newborns: Growth Outcomes.

    Science.gov (United States)

    Butz, Arlene M.; Kaufmann, Walter E.; Royall, Richard; Kolodner, Ken; Pulsifer, Margaret B.; Lears, Mary Kathleen; Henderson, Robin; Belcher, Harolyn; Sellers, Sherri; Wilson, Modena

    1999-01-01

    Examines growth parameters at birth in 204 infants born to mothers who used cocaine and/or opiates during pregnancy. Outcome measures included birth weight, length, and head circumference. Study provides support that in utero cocaine exposure may confer more risk for somatic growth retardation at birth than opiate exposure. (Author/GCP)

  7. Levamisole-contaminated cocaine : a hairy affair

    NARCIS (Netherlands)

    van der Veer, Tjeerd; Pennings, Ed; Tervaert, J W Cohen; Korswagen, Lindy-Anne

    2015-01-01

    Levamisole-contaminated cocaine can induce severe systemic vasculitis. The diagnosis can be challenging, especially when substance abuse is uncertain. We present the case of a 42-year-old woman suffering from vasculitis due to levamisole-contaminated cocaine, who persistently denied substance abuse.

  8. Cilioretinal artery occlusion following intranasal cocaine insufflations

    Directory of Open Access Journals (Sweden)

    Balaji Kannan

    2011-01-01

    Full Text Available Cocaine is used to produce a euphoric effect by abusers, who may be unaware of the devastating systemic and ocular side effects of this drug. We describe the first known case of cilioretinal artery occlusion after intranasal cocaine abuse.

  9. Osteonecrosis following alcohol, cocaine, and steroid use.

    LENUS (Irish Health Repository)

    Ziraldo, Laura

    2012-02-01

    Alcohol, steroids and cocaine have all been shown to be independent risk factors for osteonecrosis when taken in excess. Here we present a case of a young girl who developed debilitating osteonecrosis secondary to low doses of alcohol, steroids and cocaine. We feel it is important to highlight to those caring for such patients of the potential devastating complication of these three agents.

  10. A Simple Economic Model of Cocaine Production

    Science.gov (United States)

    1994-01-01

    the production dhain that are vulnerable to itr o as well as providing a clearer picture of the path that cocaine takes before reading retail markts in...In fact, given the volatility of cocaine product prices in PBC, it is probably not uncommon for segments of production to be unprofitable at times

  11. Signs of Cocaine Abuse and Addiction

    Science.gov (United States)

    ... Use and Addiction Signs of Cocaine Use and Addiction Listen ©istock.com/ AntonioGuillern After the "high" of the cocaine wears off, you can "crash" and feel tired and sad for days. You also get a strong craving to take the drug again to try to ...

  12. Pathways from cannabis to psychosis: a review of the evidence

    Directory of Open Access Journals (Sweden)

    Jonathan K Burns

    2013-10-01

    Full Text Available The nature of the relationship between cannabis use and psychosis is complex and remains unclear. Researchers and clinicians remain divided regarding key issues such as whether or not cannabis is an independent cause of psychosis and schizophrenia. This paper reviews the field in detail, examining questions of causality, the neurobiological basis for such causality and for differential inter-individual risk, the clinical and cognitive features of psychosis in cannabis users, and patterns of course and outcome of psychosis in the context of cannabis use. The author proposes two major pathways from cannabis to psychosis based on a differentiation between early-initiated lifelong cannabis use and a scenario where vulnerable individuals without a lifelong pattern of use consume cannabis over a relatively brief period of time just prior to psychosis onset. Additional key factors determining the clinical and neurobiological manifestation of psychosis as well as course and outcome in cannabis users include: underlying genetic and developmental vulnerability to schizophrenia-spectrum disorders; and whether or not cannabis use ceases or continues after the onset of psychosis. Finally, methodological guidelines are presented for future research aimed at both elucidating the pathways that lead from cannabis to psychosis and clarifying the long-term outcome of the disorder in those who have a history of using cannabis.

  13. Cannabis and development of dual diagnoses: A literature review.

    Science.gov (United States)

    Hanna, Rebecca C; Perez, Jessica M; Ghose, Subroto

    2017-07-01

    The use of cannabis has garnered more attention recently with ongoing efforts at marijuana legalization. The consequences of cannabis use are not clearly understood and remain a concern. To review the acute and persistent effects of cannabis use and associations with psychiatric disorders. Using Pubmed and PsychInfo, we conducted a narrative review of the literature on cannabis and psychiatric comorbidity using the keywords cannab*, marijuana, schizo*, psychosis, mood, depression, mania, bipolar, and anxiety. There is substantial evidence of cannabis use leading to other illicit drug use and of an association between cannabis use and psychosis. A few reports suggest an association with bipolar disorder while the association with depression and anxiety disorders is mixed. Whenever an association is observed between cannabis use and psychiatric disorders, the relationship is generally an adverse one. Age at the time of cannabis use appears to be an important factor with stronger associations observed between adolescent onset cannabis use and later onset of psychiatric disorders. Additional studies taking into account potential confounds (such as withdrawal symptoms, periods of abstinence, and other substance use) and moderators (such as age of initiation of cannabis use, the amount and frequency of drug use, prior history of childhood maltreatment, and gender) are needed to better understand the psychiatric consequences of cannabis use.

  14. Cocaine and other illicit drugs in airborne particulates in urban environments: A reflection of social conduct and population size

    Energy Technology Data Exchange (ETDEWEB)

    Viana, M., E-mail: mar.viana@idaea.csic.es [Institute for Environmental Assessment and Water Research (IDAEA-CSIC), C/Jordi Girona 18, 08034 Barcelona (Spain); Postigo, C., E-mail: cprqam@cid.csic.es [Institute for Environmental Assessment and Water Research (IDAEA-CSIC), C/Jordi Girona 18, 08034 Barcelona (Spain); Querol, X., E-mail: xavier.querol@idaea.csic.es [Institute for Environmental Assessment and Water Research (IDAEA-CSIC), C/Jordi Girona 18, 08034 Barcelona (Spain); Alastuey, A., E-mail: andres.alastuey@idaea.csic.es [Institute for Environmental Assessment and Water Research (IDAEA-CSIC), C/Jordi Girona 18, 08034 Barcelona (Spain); Lopez de Alda, M.J., E-mail: mlaqam@cid.csic.es [Institute for Environmental Assessment and Water Research (IDAEA-CSIC), C/Jordi Girona 18, 08034 Barcelona (Spain); Barcelo, D., E-mail: dbcqam@cid.csic.es [Institute for Environmental Assessment and Water Research (IDAEA-CSIC), C/Jordi Girona 18, 08034 Barcelona (Spain); King Saud University, Box 2454, Riyadh 11451 (Saudi Arabia); Artinano, B., E-mail: b.artinano@ciemat.es [Centre for Energy, Environment and Technology Research (CIEMAT), Av. Complutense 22, 28040 Madrid (Spain); Lopez-Mahia, P., E-mail: purmahia@udc.es [Department of Analytical Chemistry, University of A Coruna, Campus A Zapateira, 15071 A Coruna (Spain); Garcia Gacio, D., E-mail: dgarcia@udc.es [Department of Analytical Chemistry, University of A Coruna, Campus A Zapateira, 15071 A Coruna (Spain); Cots, N., E-mail: nuria.cots@gencat.ca [Department of the Environment, Catalonia Regional Government, Av. Diagonal 525, 08193 Barcelona (Spain)

    2011-05-15

    Levels of cocaine and other psychoactive substances in atmospheric particulate matter (PM) were determined in urban environments representing distinct social behaviours with regard to drug abuse: night-life, university and residential areas. Three cities (with population >1 million and <0.3 million inhabitants) were selected. Mean daily levels of drugs in PM were 11-336 pg/m{sup 3} for cocaine, 23-34 pg/m{sup 3} for cannabinoids, and 5-90 pg/m{sup 3} for heroin. The highest levels were recorded on weekends, with factors with respect to weekdays of 1-3 for cocaine, 1-2 for cannabinoids and 1.1-1.7 for heroin. Higher levels were detected in the night-life areas, pointing towards consumption and trafficking as major emission sources, and possibly ruling out drug manufacture. The similarities in temporal trends at all sites suggested a city-scale transport of psychoactive substances. Correlations were detected between cocaine and amphetamine consumption (r{sup 2} = 0.98), and between heroin and cannabinoids (r{sup 2}>0.82). - Highlights: > Cocaine, heroin, cannabis and related illicit drugs are found in detectable amounts in urban air. > Illicit drug consumption and small-scale trafficking are the major emission sources. > Illicit drugs remain in atmospheric particles and are transported across cities during at least 5 days. > Levels of illicit drugs increase from residential to night-life areas, and maximise on weekends. > Correlations between illicit drugs were detected, suggesting differences in consumer groups. - The presence of illicit drugs in atmospheric particles can be used to track illicit drug abuse.

  15. Comparing adults who use cannabis medically with those who use recreationally: Results from a national sample.

    Science.gov (United States)

    Lin, Lewei A; Ilgen, Mark A; Jannausch, Mary; Bohnert, Kipling M

    2016-10-01

    Cannabis has been legalized for medical use in almost half of the states in the U.S. Although laws in these states make the distinction between medical and recreational use of cannabis, the prevalence of people using medical cannabis and how distinct this group is from individuals using cannabis recreationally is unknown at a national level. Data came from the 2013 National Survey on Drug Use and Health (NSDUH). All adults endorsing past year cannabis use who reported living in a state that had legalized medical cannabis were divided into recreational cannabis use only and medical cannabis use. Demographic and clinical characteristics were compared across these two groups. 17% of adults who used cannabis in the past year used cannabis medically. There were no significant differences between those who used medically versus recreationally in race, education, past year depression and prevalence of cannabis use disorders. In adjusted analyses, those with medical cannabis use were more likely to have poorer health and lower levels of alcohol use disorders and non-cannabis drug use. A third of those who reported medical cannabis use endorsed daily cannabis use compared to 11% in those who reported recreational use exclusively. Adults who use medical and recreational cannabis shared some characteristics, but those who used medical cannabis had higher prevalence of poor health and daily cannabis use. As more states legalize cannabis for medical use, it is important to better understand similarities and differences between people who use cannabis medically and recreationally. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Keep off the grass? Cannabis, cognition and addiction.

    Science.gov (United States)

    Curran, H Valerie; Freeman, Tom P; Mokrysz, Claire; Lewis, David A; Morgan, Celia J A; Parsons, Loren H

    2016-05-01

    In an increasing number of states and countries, cannabis now stands poised to join alcohol and tobacco as a legal drug. Quantifying the relative adverse and beneficial effects of cannabis and its constituent cannabinoids should therefore be prioritized. Whereas newspaper headlines have focused on links between cannabis and psychosis, less attention has been paid to the much more common problem of cannabis addiction. Certain cognitive changes have also been attributed to cannabis use, although their causality and longevity are fiercely debated. Identifying why some individuals are more vulnerable than others to the adverse effects of cannabis is now of paramount importance to public health. Here, we review the current state of knowledge about such vulnerability factors, the variations in types of cannabis, and the relationship between these and cognition and addiction.

  17. Counselling young cannabis users by text message

    DEFF Research Database (Denmark)

    Laursen, Ditte

    2010-01-01

    This article presents the results of a study of two SMS services aimed at providing young people with information on cannabis and helping them to reduce their consumption of the drug. The attitude of the 12 participants in the study towards the SMS services is generally positive, but they prefer...... factual information to advice and counselling. The messages prompt reflection and awareness among the recipients, and their repetitive, serial nature plays a significant part in the process of change. This is especially true of the young people whose use of cannabis is recreational. For them, the SMS...

  18. Cannabis: challenges between legislation and cognitive competence

    OpenAIRE

    Cuartas Arias, Jorge Mauricio; Faculty of Psychology, Universidad San Buenaventura, Medellín, Colombia.

    2015-01-01

    Marihuana (Cannabis) is the most consumed illicit drug worldwide. By 2013, 180,6 million people, that is 3.9 % of the world population consumed the substance, within a wide range of age (15 to 64 years old). In Colombia, it has been estimated that 1 of every 3 students has tried marihuana in their life. Additionally, the reported data by 2012 informed that the prevail of 15,2% placed the country in the highest position of cannabis consumption among Peru, Ecuador and Bolivia, let along the eas...

  19. A Single Amphetamine Infusion Reverses Deficits in Dopamine Nerve-Terminal Function Caused by a History of Cocaine Self-Administration.

    Science.gov (United States)

    Ferris, Mark J; Calipari, Erin S; Rose, Jamie H; Siciliano, Cody A; Sun, Haiguo; Chen, Rong; Jones, Sara R

    2015-07-01

    There are ∼ 1.6 million people who meet the criteria for cocaine addiction in the United States, and there are currently no FDA-approved pharmacotherapies. Amphetamine-based dopamine-releasing drugs have shown efficacy in reducing the motivation to self-administer cocaine and reducing intake in animals and humans. It is hypothesized that amphetamine acts as a replacement therapy for cocaine through elevation of extracellular dopamine levels. Using voltammetry in brain slices, we tested the ability of a single amphetamine infusion in vivo to modulate dopamine release, uptake kinetics, and cocaine potency in cocaine-naive animals and after a history of cocaine self-administration (1.5 mg/kg/infusion, fixed-ratio 1, 40 injections/day × 5 days). Dopamine kinetics were measured 1 and 24 h after amphetamine infusion (0.56 mg/kg, i.v.). Following cocaine self-administration, dopamine release, maximal rate of uptake (Vmax), and membrane-associated dopamine transporter (DAT) levels were reduced, and the DAT was less sensitive to cocaine. A single amphetamine infusion reduced Vmax and membrane DAT levels in cocaine-naive animals, but fully restored all aspects of dopamine terminal function in cocaine self-administering animals. Here, for the first time, we demonstrate pharmacologically induced, immediate rescue of deficits in dopamine nerve-terminal function in animals with a history of high-dose cocaine self-administration. This observation supports the notion that the DAT expression and function can be modulated on a rapid timescale and also suggests that the pharmacotherapeutic actions of amphetamine for cocaine addiction go beyond that of replacement therapy.

  20. Mechanisms underlying the link between cannabis use and prospective memory.

    Directory of Open Access Journals (Sweden)

    Carrie Cuttler

    Full Text Available While the effects of cannabis use on retrospective memory have been extensively examined, only a limited number of studies have focused on the links between cannabis use and prospective memory. We conducted two studies to examine the links between cannabis use and both time-based and event-based prospective memory as well as potential mechanisms underlying these links. For the first study, 805 students completed an online survey designed to assess cannabis consumption, problems with cannabis use indicative of a disorder, and frequency of experiencing prospective memory failures. The results showed small to moderate sized correlations between cannabis consumption, problems with cannabis use, and prospective memory. However, a series of mediation analyses revealed that correlations between problems with cannabis use and prospective memory were driven by self-reported problems with retrospective memory. For the second study, 48 non-users (who had never used cannabis, 48 experimenters (who had used cannabis five or fewer times in their lives, and 48 chronic users (who had used cannabis at least three times a week for one year were administered three objective prospective memory tests and three self-report measures of prospective memory. The results revealed no objective deficits in prospective memory associated with chronic cannabis use. In contrast, chronic cannabis users reported experiencing more internally-cued prospective memory failures. Subsequent analyses revealed that this effect was driven by self-reported problems with retrospective memory as well as by use of alcohol and other drugs. Although our samples were not fully characterized with respect to variables such as neurological disorders and family history of substance use disorders, leaving open the possibility that these variables may play a role in the detected relationships, the present findings indicate that cannabis use has a modest effect on self-reported problems with

  1. Responsible and controlled use: Older cannabis users and harm reduction.

    Science.gov (United States)

    Lau, Nicholas; Sales, Paloma; Averill, Sheigla; Murphy, Fiona; Sato, Sye-Ok; Murphy, Sheigla

    2015-08-01

    Cannabis use is becoming more accepted in mainstream society. In this paper, we use Zinberg's classic theoretical framework of drug, set, and setting to elucidate how older adult cannabis users managed health, social and legal risks in a context of normalized cannabis use. We present selected findings from our qualitative study of Baby Boomer (born 1946-1964) cannabis users in the San Francisco Bay Area. Data collection consisted of a recorded, in-depth life history interview followed by a questionnaire and health survey. Qualitative interviews were analyzed to discover the factors of cannabis harm reduction from the users' perspectives. Interviewees made harm reduction choices based on preferred cannabis derivatives and routes of administration, as well as why, when, where, and with whom to use. Most interviewees minimized cannabis-related harms so they could maintain social functioning in their everyday lives. Responsible and controlled use was described as moderation of quantity and frequency of cannabis used, using in appropriate settings, and respect for non-users. Users contributed to the normalization of cannabis use through normification. Participants followed rituals or cultural practices, characterized by sanctions that helped define "normal" or "acceptable" cannabis use. Users contributed to cannabis normalization through their harm reduction methods. These cultural practices may prove to be more effective than formal legal prohibitions in reducing cannabis-related harms. Findings also suggest that users with access to a regulated market (medical cannabis dispensaries) were better equipped to practice harm reduction. More research is needed on both cannabis culture and alternative routes of administration as harm reduction methods. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Cocaine treatment admissions at three sentinel sites in South Africa (1997-2006): findings and implications for policy, practice and research.

    Science.gov (United States)

    Parry, Charles D H; Plüddemann, Andreas; Myers, Bronwyn J

    2007-12-28

    Accurate prevalence data on cocaine use, that points to where problems exist and the extent of these problems, is necessary to guide the formulation of effective substance abuse policy and practice. The purpose of this study was to provide surveillance information about the nature and extent of problematic cocaine use in South Africa. Data were collected between January 1997 and December 2006 on admissions for drug abuse treatment through a regular monitoring system involving 56 drug treatment centres and programmes in Cape Town, Gauteng Province (Johannesburg and Pretoria) and the Eastern Cape every six months as part of the South African Community Epidemiology Network on Drug Use (SACENDU). A one-page form was completed by treatment centre personnel to obtain demographic data, the patients' primary and secondary substances of abuse, the mode, frequency and age of first use of substance, and information on prior treatment. Treatment indicators point to a significant increase in cocaine related admissions over time in all sites, but with substantial inter-site variation, particularly in recent years. The data indicate high levels of crack cocaine use and high levels of daily usage among patients, most of whom were first time admissions. Patients with cocaine related problems continue to be predominantly male, with a mean age of around 30 years. Substantial changes in the racial profile of patients have occurred over time. Poly drug use is high with cocaine often used with alcohol, cannabis and other drugs. These trends point to the possibility of cocaine use becoming a serious health and social issue in South Africa and demonstrate the utility of continued monitoring of cocaine treatment admissions in the future. They also highlight the need to address cocaine use in national and provincial policy planning and intervention efforts. In terms of treatment, the findings highlight the need to ensure that treatment practitioners are adequately trained to address

  3. Cocaine treatment admissions at three sentinel sites in South Africa (1997–2006: findings and implications for policy, practice and research

    Directory of Open Access Journals (Sweden)

    Plüddemann Andreas

    2007-12-01

    Full Text Available Abstract Background Accurate prevalence data on cocaine use, that points to where problems exist and the extent of these problems, is necessary to guide the formulation of effective substance abuse policy and practice. The purpose of this study was to provide surveillance information about the nature and extent of problematic cocaine use in South Africa. Methods Data were collected between January 1997 and December 2006 on admissions for drug abuse treatment through a regular monitoring system involving 56 drug treatment centres and programmes in Cape Town, Gauteng Province (Johannesburg and Pretoria and the Eastern Cape every six months as part of the South African Community Epidemiology Network on Drug Use (SACENDU. A one-page form was completed by treatment centre personnel to obtain demographic data, the patients' primary and secondary substances of abuse, the mode, frequency and age of first use of substance, and information on prior treatment. Results Treatment indicators point to a significant increase in cocaine related admissions over time in all sites, but with substantial inter-site variation, particularly in recent years. The data indicate high levels of crack cocaine use and high levels of daily usage among patients, most of whom were first time admissions. Patients with cocaine related problems continue to be predominantly male, with a mean age of around 30 years. Substantial changes in the racial profile of patients have occurred over time. Poly drug use is high with cocaine often used with alcohol, cannabis and other drugs. Conclusion These trends point to the possibility of cocaine use becoming a serious health and social issue in South Africa and demonstrate the utility of continued monitoring of cocaine treatment admissions in the future. They also highlight the need to address cocaine use in national and provincial policy planning and intervention efforts. In terms of treatment, the findings highlight the need to ensure that

  4. Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine's action in vivo.

    Science.gov (United States)

    Tallarida, Christopher S; Egan, Erin; Alejo, Gissel D; Raffa, Robert; Tallarida, Ronald J; Rawls, Scott M

    2014-04-01

    Levamisole is estimated by the Drug Enforcement Agency (DEA) to be present in about 80% of cocaine seized in the United States and linked to debilitating, and sometimes fatal, immunologic effects in cocaine abusers. One explanation for the addition of levamisole to cocaine is that it increases the amount of product and enhances profits. An alternative possibility, and one investigated here, is that levamisole alters cocaine's action in vivo. We specifically investigated effects of levamisole on cocaine's stereotypical and place-conditioning effects in an established invertebrate (planarian) assay. Acute exposure to levamisole or cocaine produced concentration-dependent increases in stereotyped movements. For combined administration of the two agents, isobolographic analysis revealed that the observed stereotypical response was enhanced relative to the predicted effect, indicating synergism for the interaction. In conditioned place preference (CPP) experiments, cocaine produced a significant preference shift; in contrast, levamisole was ineffective at all concentrations tested. For combination experiments, a submaximal concentration of cocaine produced CPP that was enhanced by inactive concentrations of levamisole, indicating synergism. The present results provide the first experimental evidence that levamisole enhances cocaine's action in vivo. Most important is the identification of synergism for the levamisole/cocaine interaction, which now requires further study in mammals.

  5. Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine's action in vivo

    Science.gov (United States)

    Tallarida, Christopher S.; Egan, Erin; Alejo, Gissel D.; Raffa, Robert; Tallarida, Ronald J.; Rawls, Scott M.

    2014-01-01

    Levamisole is estimated by the Drug Enforcement Agency (DEA) to be present in about 80% of cocaine seized in the United States and linked to debilitating, and sometimes fatal, immunologic effects in cocaine abusers. One explanation for the addition of levamisole to cocaine is that it increases the amount of product and enhances profits. An alternative possibility, and one investigated here, is that levamisole alters cocaine's action in vivo. We specifically investigated effects of levamisole on cocaine's stereotypical and place-conditioning effects in an established invertebrate (planarian) assay. Acute exposure to levamisole or cocaine produced concentration-dependent increases in stereotyped movements. For combined administration of the two agents, isobolographic analysis revealed that the observed stereotypical response was enhanced relative to the predicted effect, indicating synergism for the interaction. In conditioned place preference (CPP) experiments, cocaine produced a significant preference shift; in contrast, levamisole was ineffective at all concentrations tested. For combination experiments, a submaximal concentration of cocaine produced CPP that was enhanced by inactive concentrations of levamisole, indicating synergism. The present results provide the first experimental evidence that levamisole enhances cocaine's action in vivo. Most important is the identification of synergism for the levamisole/cocaine interaction, which now requires further study in mammals. PMID:24440755

  6. Anorexic activity of cocaine and coca extract in naive and cocaine tolerant rats.

    Science.gov (United States)

    Vee, G L; Fink, G B; Constantine, G H

    1983-04-01

    Dose response curves for reducing limited access food consumption were determined for cocaine HCl IP, cocaine HCl PO, and whole Erythroxylum coca extract PO. The ED50's for cocaine HCl in drug naive rats were 19.6 mg/kg (IP) and 34.6 mg/kg (PO). When the dose of E. coca extract was expressed in terms of cocaine HCl content, the ED50 was 52.6 mg/kg (PO). When dose response curves were determined in rats that had received cocaine (45 mg/kg, PO) for 30 days, a shift to the right in the cocaine HCl curve (an ED50 of 98.4 mg/kg PO) indicated tolerance. However, the shift to the right was less for E. coca extract than for cocaine HCl. Although the anorexic activity of E. coca extract was less than that of an equivalent amount of cocaine in naive rats it was often more than that of equivalent doses of cocaine HCl in tolerant rats. Interaction with other constituents of E. coca extract appears to alter the potency of the cocaine content of the extract in different directions in naive and tolerant rats.

  7. Personality traits of cocaine-dependent patients associated with cocaine-positive baseline urine at hospitalization.

    Science.gov (United States)

    de Los Cobos, José Pérez; Siñol, Núria; Bañulus, Enrique; Batlle, Francisca; Tejero, Antoni; Trujols, Joan

    2010-01-01

    Cocaine abstinence at treatment entry is considered a predictor of good response in cocaine dependence treatment. Therefore, identification of factors facilitating pretreatment cocaine abstinence could be useful for developing new therapeutic strategies. This retrospective chart review study examines the association between personality traits and cocaine-positive baseline urinalysis (CPB) in cocaine-dependent inpatients. All 107 participants met DSM-IV criteria for cocaine dependence, and were admitted consecutively to a closed addiction unit for detoxification treatment. Personality was assessed with the Temperament and Character Inventory and the Millon Clinical Multiaxial Inventory (MCMI-II). CPB was detected in 80 patients (74.8%). The logistic regression model solely based on personality dimensions showed that only the MCMI-II avoidant traits were significantly associated with a decreased probability of cocaine-dependent patients presenting CPB. The logistic regression model based on both personality dimensions and substance use-related variables alike retained the number of days of cocaine use during the last 30 days as a risk factor, and alcohol dependence and the MCMI-II schizoid dimension as protective factors in predicting CPB results. Avoidant and schizoid traits are personality dimensions of cocaine-dependent patients that are associated with cocaine abstinence prior to inpatient admission. These findings suggest an inverse relationship between social isolation and CPB. Notwithstanding, more research is needed, not only to assess the generalizability of these findings, but also to enrich the personality and substance use model with variables related to readiness to change.

  8. Cannabis-dependence risk relates to synergism between neuroticism and proenkephalin SNPs associated with amygdala gene expression: case-control study.

    Directory of Open Access Journals (Sweden)

    Didier Jutras-Aswad

    Full Text Available Many young people experiment with cannabis, yet only a subgroup progress to dependence suggesting individual differences that could relate to factors such as genetics and behavioral traits. Dopamine receptor D2 (DRD2 and proenkephalin (PENK genes have been implicated in animal studies with cannabis exposure. Whether polymorphisms of these genes are associated with cannabis dependence and related behavioral traits is unknown.Healthy young adults (18-27 years with cannabis dependence and without a dependence diagnosis were studied (N = 50/group in relation to a priori-determined single nucleotide polymorphisms (SNPs of the DRD2 and PENK genes. Negative affect, Impulsive Risk Taking and Neuroticism-Anxiety temperamental traits, positive and negative reward-learning performance and stop-signal reaction times were examined. The findings replicated the known association between the rs6277 DRD2 SNP and decisions associated with negative reinforcement outcomes. Moreover, PENK variants (rs2576573 and rs2609997 significantly related to Neuroticism and cannabis dependence. Cigarette smoking is common in cannabis users, but it was not associated to PENK SNPs as also validated in another cohort (N = 247 smokers, N = 312 non-smokers. Neuroticism mediated (15.3%-19.5% the genetic risk to cannabis dependence and interacted with risk SNPs, resulting in a 9-fold increase risk for cannabis dependence. Molecular characterization of the postmortem human brain in a different population revealed an association between PENK SNPs and PENK mRNA expression in the central amygdala nucleus emphasizing the functional relevance of the SNPs in a brain region strongly linked to negative affect.Overall, the findings suggest an important role for Neuroticism as an endophenotype linking PENK polymorphisms to cannabis-dependence vulnerability synergistically amplifying the apparent genetic risk.

  9. Neurophysiology of motor function following cannabis discontinuation in chronic cannabis smokers: an fMRI study.

    Science.gov (United States)

    Pillay, Srinivasan S; Rogowska, Jadwiga; Kanayama, Gen; Jon, Duk-In; Gruber, Staci; Simpson, Norah; Cherayil, Monisha; Pope, Harrison G; Yurgelun-Todd, Deborah A

    2004-12-07

    The objective of this study was to identify the differences in cerebral activation between chronic cannabis smokers and controls in response to finger sequencing. We hypothesized that attentional areas related to motor function as well as primary and supplementary motor cortices would show diminished activation in chronic cannabis smokers. Nine cannabis smokers and 16 controls were included in these analyses. Scanning was performed on a GE 1.5T scanner. Echo planar images and high-resolution MR images were acquired. The challenge paradigm included left and right finger sequencing. Group differences in cerebral activation were examined for Brodmann areas (BA) 4, 6, 24, and 32 using ROI analyses in SPM. Cannabis users, tested within 4-36 h of discontinuation, exhibited significantly less activation than controls in BA 24 and 32 bilaterally during right- and left-sided sequencing and for BA 6 in all tasks except for left-sided sequencing in the left hemisphere. There were no statistically significant differences for BA 4. None of these regional activations correlated with urinary cannabis concentration and verbal IQ for smokers. These results suggest that recently abstinent chronic cannabis smokers produce reduced activation in motor cortical areas in response to finger sequencing compared to controls.

  10. Sex differences in cannabis withdrawal symptoms among treatment-seeking cannabis users

    Science.gov (United States)

    Herrmann, Evan S.; Weerts, Elise M.; Vandrey, Ryan

    2015-01-01

    Over 300,000 individuals enter treatment for cannabis use disorders (CUDs) in the U.S. annually. Cannabis withdrawal is associated with poor CUD treatment outcomes, but no prior studies have examined sex differences in withdrawal among treatment-seeking cannabis users. Treatment-seeking cannabis users (45 women and 91 men) completed a Marijuana Withdrawal Checklist (MWC) at treatment intake to retrospectively characterize withdrawal symptoms experienced during their most recent quit attempt. Composite Withdrawal Discomfort Scale (WDS) scores were calculated using the 14 items on the MWC that correspond to valid cannabis withdrawal symptoms described in DSM-5. Demographic and substance use characteristics, overall WDS scores, and scores on individual WDS symptoms were compared between women and men. Women had higher overall WDS scores than men, and women had higher scores than men on six individual symptoms in two domains, mood symptoms (irritability, restlessness, increased anger, violent outbursts) and gastrointestinal symptoms (nausea, stomach pain). Follow-up analyses isolating the incidence and severity of WDS symptoms demonstrated that women generally reported a higher number of individual withdrawal symptoms than men, and that they reported experiencing some symptoms as more severe. This is the first report to demonstrate that women seeking treatment for CUDs may experience more withdrawal then men during quit attempts. Prospective studies of sex differences in cannabis withdrawal are warranted. PMID:26461168

  11. Dopamine transporter inhibition is required for cocaine-induced stereotypy

    OpenAIRE

    Tilley, Michael R.; Gu, Howard H.

    2008-01-01

    The primary mechanism by which cocaine induces stereotypy has been difficult to discern because cocaine has three high affinity targets, the reuptake transporters for dopamine (DAT), norepinephrine, and serotonin. To dissect out the role of DAT in cocaine effects, we generated a knock-in mouse line with a cocaine insensitive DAT (DAT-CI mice). DAT-CI mice provide a powerful tool that can directly test whether DAT inhibition is important for cocaine-induced stereotypy. We found that acute coca...

  12. Variations and origin of the atmospheric pollen of Cannabis detected in the province of Tetouan (NW Morocco): 2008-2010.

    Science.gov (United States)

    Aboulaich, Nadia; Trigo, M Mar; Bouziane, Hassan; Cabezudo, Baltasar; Recio, Marta; El Kadiri, Mohamed; Ater, Mohammed

    2013-01-15

    Cannabis, also called marihuana or hemp, is a wind-pollinated plant that produces hundreds of flowers on large inflorescences. It is also one of the oldest psychoactive plants known to humanity. Morocco has become one of the main producers of Cannabis resin (hashish), primarily supplying the European market. The aim of this paper is to ascertain whether the atmospheric monitoring of Cannabis pollen can play a role, from a criminological point of view, in the surveillance of Cannabis cultivation in the area of Tetouan (NW Morocco) as well as to estimate pollen emission so that the sensitive population can be warned about the allergic diseases that its pollen can cause. Aerobiological samplings were made with the aid of a Hirst type volumetric trap (Hirst, 1952), which worked uninterruptedly during a 3-year period (2008-2010) according to the methodology proposed by the Spanish Aerobiology Network, the REA. Cannabis pollen was present in the atmosphere of Tetouan mainly from early April to late August, a period in which about 95% of the annual counts were registered. The highest levels were detected in June and July, with concentrations more or less evenly distributed throughout the day with slight increases of 5% between 12:00 and 16:00 h. The strong association between skin test reactivity, respiratory symptoms, and pollination period found by other authors, together with the levels registered, suggests that Cannabis pollen could be a clinically important aeroallergen for sensitive patients. On the other hand, the data obtained could serve as an indicator of the cultivation activity of this species and should be taken into account by the state authorities since they provide strong evidence of the existence of Cannabis crops in the region of Tetouan.

  13. Structural and Functional Imaging Studies in Chronic Cannabis Users: A Systematic Review of Adolescent and Adult Findings

    Science.gov (United States)

    Batalla, Albert; Bhattacharyya, Sagnik; Yücel, Murat; Fusar-Poli, Paolo; Crippa, Jose Alexandre; Nogué, Santiago; Torrens, Marta; Pujol, Jesús; Farré, Magí; Martin-Santos, Rocio

    2013-01-01

    Background The growing concern about cannabis use, the most commonly used illicit drug worldwide, has led to a significant increase in the number of human studies using neuroimaging techniques to determine the effect of cannabis on brain structure and function. We conducted a systematic review to assess the evidence of the impact of chronic cannabis use on brain structure and function in adults and adolescents. Methods Papers published until August 2012 were included from EMBASE, Medline, PubMed and LILACS databases following a comprehensive search strategy and pre-determined set of criteria for article selection. Only neuroimaging studies involving chronic cannabis users with a matched control group were considered. Results One hundred and forty-two studies were identified, of which 43 met the established criteria. Eight studies were in adolescent population. Neuroimaging studies provide evidence of morphological brain alterations in both population groups, particularly in the medial temporal and frontal cortices, as well as the cerebellum. These effects may be related to the amount of cannabis exposure. Functional neuroimaging studies suggest different patterns of resting global and brain activity during the performance of several cognitive tasks both in adolescents and adults, which may indicate compensatory effects in response to chronic cannabis exposure. Limitations However, the results pointed out methodological limitations of the work conducted to date and considerable heterogeneity in the findings. Conclusion Chronic cannabis use may alter brain structure and function in adult and adolescent population. Further studies should consider the use of convergent methodology, prospective large samples involving adolescent to adulthood subjects, and data-sharing initiatives. PMID:23390554

  14. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.

    Science.gov (United States)

    Russo, Ethan B

    2011-08-01

    Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, α-pinene, linalool, β-caryophyllene, caryophyllene oxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrance components common to human diets that have been designated Generally Recognized as Safe by the US Food and Drug Administration and other regulatory agencies. Terpenoids are quite potent, and affect animal and even human behaviour when inhaled from ambient air at serum levels in the single digits ng·mL(-1) . They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Particular focus will be placed on phytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcus aureus). Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC that could increase its therapeutic index. Methods for investigating entourage effects in future experiments will be proposed. Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of new therapeutic products is possible from this venerable plant. http

  15. Screening for illicit drugs in pooled human urine and urinated soil samples and studies on the stability of urinary excretion products of cocaine, MDMA, and MDEA in wastewater by hyphenated mass spectrometry techniques

    DEFF Research Database (Denmark)

    Mardal, Marie; Kinyua, Juliet; Ramin, Pedram

    2017-01-01

    chromatography – mass spectrometry / mass spectrometry (HILIC-MS/MS) method of quantifying urinary targets of identified drugs in wastewater; and (3) to conduct a 24 h stability study, using PU and US to better reflect the chemical environment for targets in wastewater. Cocaine (COC) and ecstasy-like compounds...

  16. d-Cycloserine combined with cue exposure therapy fails to attenuate subjective and physiological craving in cocaine dependence

    Science.gov (United States)

    Santa Ana, Elizabeth J.; Prisciandaro, James J.; Saladin, Michael E.; McRae-Clark, Aimee L.; Shaftman, Stephanie R.; Nietert, Paul J.; Brady, Kathleen T.

    2014-01-01

    Background Based on preclinical studies showing that the partial N-methyl-d-aspartate (NMDA) agonist d-cycloserine (DCS) facilitates extinction of cocaine self-administration and cocaine-induced conditioned place preference, we evaluated whether 50 mg of DCS would reduce craving to cocaine cues when combined with cue exposure (CE) in cocaine dependent humans. Methods In this double-blind placebo-controlled pilot study, 47 cocaine dependent participants were randomized to DCS or placebo (PBO), plus CE. Participants received DCS or PBO 30 minutes prior to two CE sessions, conducted one day apart. Craving and heart rate was assessed prior to CE sessions, during CE trials, and after CE trials. These measures were assessed again at a 1-week follow-up (session 3) after the second CE session. Results DCS failed to significantly attenuate cocaine cue reactivity based on subjective craving and physiological reactivity (heart rate) compared to PBO. The CE protocol, consisting of repeated exposure to drug cues combined with skills training, resulted in extinction to cocaine cues as suggested by decreased craving within and between sessions in both treatment conditions. All participants exhibited elevated heart rate with repeated exposures, demonstrating a potentiation in heart rate between sessions. PMID:25808169

  17. Early-Onset, Regular Cannabis Use Is Linked to IQ Decline

    Science.gov (United States)

    ... Is Linked to IQ Decline Early-Onset, Regular Cannabis Use Is Linked to IQ Decline Email Facebook ... that cannabis use may harm the developing brain. Cannabis Use Correlates With Cognitive Decline The study participants ...

  18. Counselling young cannabis users by text message

    DEFF Research Database (Denmark)

    Laursen, Ditte

    2010-01-01

    This article presents the results of a study of two SMS services aimed at providing young people with information on cannabis and helping them to reduce their consumption of the drug. The attitude of the 12 participants in the study towards the SMS services is generally positive, but they prefer ...

  19. Residual effects of prolonged heavy cannabis use

    NARCIS (Netherlands)

    van Amsterdam JGC; van der Laan JW; Slangen JL; LGM

    1996-01-01

    Recente literatuur werd geraadpleegd om na te gaan of langdurig gebruik van van grote hoeveelheden cannabis (dagelijks gebruik gedurende minimaal 6 maanden) leidt tot aanhoudende cognitieve effecten en effecten op het immuunsysteem. Het resultaat van deze studie is weergegeven in het huidige rappor

  20. Quality and Yield of Cannabis Products

    DEFF Research Database (Denmark)

    Kastorp, Grith; Lindholst, Christian

    2011-01-01

    cultivation was examined in order to determine THC content and yield. The results are used by the Danish Police Attorney to estimate expected yields in cases with unripe cannabis plants. The results indicate that the THC content found in locally grown marihuana is slightly higher than in hashish. However...