Studying the effects of classic hallucinogens in the treatment of alcoholism: rationale, methodology, and current research with psilocybin.

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Bogenschutz, Michael P

2013-03-01

Recent developments in the study of classic hallucinogens, combined with a re-appraisal of the older literature, have led to a renewal of interest in possible therapeutic applications for these drugs, notably their application in the treatment of addictions. This article will first provide a brief review of the research literature providing direct and indirect support for the possible therapeutic effects of classic hallucinogens such as psilocybin and lysergic acid diethylamide (LSD) in the treatment of addictions. Having provided a rationale for clinical investigation in this area, we discuss design issues in clinical trials using classic hallucinogens, some of which are unique to this class of drug. We then discuss the current status of this field of research and design considerations in future randomized trials.

LOS ALUCINÓGENOS: SU HISTORIA, ANTROPOLOGÍA, QUÍMICA Y FARMACOLOGÍA - THE HALLUCINOGENS: THEIR HISTORY, ANTHROPOLOGY, CHEMISTRY AND PHARMACOLOGY

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MANUEL MARTÍNEZ HERRERA

2010-06-01

Full Text Available The present paperexposes hallucinogens from several points of view. These diverse lateralities indicate the basic lack of scientifici and antropological support for the psychogenic nature of a hallucinogen. This paper seeks to de-demonize that reputation and expose its history, anthropology, chemistry and pharmacology. It is possible that hallucinatory plants were amongst the first botanical specimens used by mankind in his religious ceremonies. Uses such as divination, weather prediction, contact with spirit and ancestral worlds, were among some of those shamanic functions. The study engages in chemical analysis of the different structures that appear principally responsible for hallucinatory experiences. The latter as respects LSD-25 as a special case. The pharmacology of hallucinogens is quite vast and the present paper discusses only some of the compounds. A three phase classification is also mentioned as an explanation of the hallucinatory experience itself.

Neuropharmacology of the Naturally Occurring κ-Opioid Hallucinogen Salvinorin A

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Cunningham, Christopher W.; Rothman, Richard B.; Prisinzano, Thomas E.

2011-01-01

Salvia divinorum is a perennial sage native to Oaxaca, Mexico, that has been used traditionally in divination rituals and as a treatment for the “semimagical” disease panzón de borrego. Because of the intense “out-of-body” experiences reported after inhalation of the pyrolized smoke, S. divinorum has been gaining popularity as a recreational hallucinogen, and the United States and several other countries have regulated its use. Early studies isolated the neoclerodane diterpene salvinorin A as...

Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum.

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Johnson, Matthew W; MacLean, Katherine A; Reissig, Chad J; Prisinzano, Thomas E; Griffiths, Roland R

2011-05-01

Salvinorin A is a potent, selective nonnitrogenous kappa opioid agonist and the known psychoactive constituent of Salvia divinorum, a member of the mint family that has been used for centuries by Mazatec shamans of Mexico for divination and spiritual healing. S. divinorum has over the last several years gained increased popularity as a recreational drug. This is a double-blind, placebo controlled study of salvinorin A in 4 psychologically and physically healthy hallucinogen-using adults. Across sessions, participants inhaled 16 ascending doses of salvinorin A and 4 intermixed placebo doses under comfortable and supportive conditions. Doses ranged from 0.375 μg/kg to 21 μg/kg. Subject-rated drug strength was assessed every 2 min for 60 min after inhalation. Orderly time- and dose-related effects were observed. Drug strength ratings peaked at 2 min (first time point) and definite subjective effects were no longer present at approximately 20 min after inhalation. Dose-related increases were observed on questionnaire measures of mystical-type experience (Mysticism Scale) and subjective effects associated with classic serotonergic (5-HT2(A)) hallucinogens (Hallucinogen Rating Scale). Salvinorin A did not significantly increase heart rate or blood pressure. Participant narratives indicated intense experiences characterized by disruptions in vestibular and interoceptive signals (e.g., change in spatial orientation, pressure on the body) and unusual and sometimes recurring themes across sessions such as revisiting childhood memories, cartoon-like imagery, and contact with entities. Under these prepared and supportive conditions, salvinorin A occasioned a unique profile of subjective effects having similarities to classic hallucinogens, including mystical-type effects. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

DNA internal standard for the quantitative determination of hallucinogenic plants in plant mixtures.

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Luciano, Pino; Bertea, Cinzia M; Temporale, Giovanni; Maffei, Massimo E

2007-12-01

Here, we show a new, simple, and rapid SYBR Green-based Real-Time PCR assay for the quantification of hallucinogenic plants in plant mixtures. As a test plant, Salvia divinorum Epling & Játiva-M., a perennial herb belonging to the Lamiaceae family able to induce hallucinations, changes in perception, or other psychologically induced changes with similar potency as LSD, was used. The method was tested on seven mixtures 100/0%, 80/20%, 60/40%, 40/60%, 20/80%, 10/90%, 0/100% (w/w) S. divinorum versus a non-hallucinogenic plant, Salvia officinalis. Total DNA was extracted from samples and quantified by Real-Time PCR. Arabidopsis thaliana genomic DNA was added, as internal standard, at the beginning of each extraction. A new formula for the interpretation of Real-Time PCR data, based on the relative quantification of DNA extracted from mixture versus a reference DNA extracted from a known amount of pure S. divinorum, was developed. The results of this work show an almost perfect correspondence between Real-Time PCR-calculated weight and the weight estimated by an analytical weighted method, proving the effectiveness of this method for the quantitative analysis of a given species in a plant mixture.

Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences.

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Carbonaro, Theresa M; Johnson, Matthew W; Hurwitz, Ethan; Griffiths, Roland R

2018-02-01

Although psilocybin and dextromethorphan (DXM) are hallucinogens, they have different receptor mechanisms of action and have not been directly compared. This study compared subjective, behavioral, and physiological effects of psilocybin and dextromethorphan under conditions that minimized expectancy effects. Single, acute oral doses of psilocybin (10, 20, 30 mg/70 kg), DXM (400 mg/70 kg), and placebo were administered under double-blind conditions to 20 healthy participants with histories of hallucinogen use. Instructions to participants and staff minimized expectancy effects. Various subjective, behavioral, and physiological effects were assessed after drug administration. High doses of both drugs produced similar increases in participant ratings of peak overall drug effect strength, with similar times to maximal effect and time-course. Psilocybin produced orderly dose-related increases on most participant-rated subjective measures previously shown sensitive to hallucinogens. DXM produced increases on most of these same measures. However, the high dose of psilocybin produced significantly greater and more diverse visual effects than DXM including greater movement and more frequent, brighter, distinctive, and complex (including textured and kaleidoscopic) images and visions. Compared to DXM, psilocybin also produced significantly greater mystical-type and psychologically insightful experiences and greater absorption in music. In contrast, DXM produced larger effects than psilocybin on measures of disembodiment, nausea/emesis, and light-headedness. Both drugs increased systolic blood pressure, heart rate, and pupil dilation and decreased psychomotor performance and balance. Psilocybin and DXM produced similar profiles of subjective experiences, with psilocybin producing relatively greater visual, mystical-type, insightful, and musical experiences, and DXM producing greater disembodiment.

Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness.

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MacLean, Katherine A; Johnson, Matthew W; Griffiths, Roland R

2011-11-01

A large body of evidence, including longitudinal analyses of personality change, suggests that core personality traits are predominantly stable after age 30. To our knowledge, no study has demonstrated changes in personality in healthy adults after an experimentally manipulated discrete event. Intriguingly, double-blind controlled studies have shown that the classic hallucinogen psilocybin occasions personally and spiritually significant mystical experiences that predict long-term changes in behaviors, attitudes and values. In the present report we assessed the effect of psilocybin on changes in the five broad domains of personality - Neuroticism, Extroversion, Openness, Agreeableness, and Conscientiousness. Consistent with participant claims of hallucinogen-occasioned increases in aesthetic appreciation, imagination, and creativity, we found significant increases in Openness following a high-dose psilocybin session. In participants who had mystical experiences during their psilocybin session, Openness remained significantly higher than baseline more than 1 year after the session. The findings suggest a specific role for psilocybin and mystical-type experiences in adult personality change.

Dimensionality of hallucinogen and inhalant/solvent abuse and dependence criteria: implications for the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition.

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Kerridge, Bradley T; Saha, Tulshi D; Smith, Sharon; Chou, Patricia S; Pickering, Roger P; Huang, Boji; Ruan, June W; Pulay, Attila J

2011-09-01

Prior research has demonstrated the dimensionality of Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) alcohol, nicotine, cannabis, cocaine and amphetamine abuse and dependence criteria. The purpose of this study was to examine the dimensionality of hallucinogen and inhalant/solvent abuse and dependence criteria. In addition, we assessed the impact of elimination of the legal problems abuse criterion on the information value of the aggregate abuse and dependence criteria, another proposed change for DSM-IV currently lacking empirical justification. Factor analyses and item response theory (IRT) analyses were used to explore the unidimisionality and psychometric properties of hallucinogen and inhalant/solvent abuse and dependence criteria using a large representative sample of the United States (U.S.) general population. Hallucinogen and inhalant/solvent abuse and dependence criteria formed unidimensional latent traits. For both substances, IRT models without the legal problems abuse criterion demonstrated better fit than the corresponding model with the legal problem abuse criterion. Further, there were no differences in the information value of the IRT models with and without the legal problems abuse criterion, supporting the elimination of that criterion. No bias in the new diagnoses was observed by sex, age and race-ethnicity. Consistent with findings for alcohol, nicotine, cannabis, cocaine and amphetamine abuse and dependence criteria, hallucinogen and inhalant/solvent criteria reflect underlying dimensions of severity. The legal problems criterion associated with each of these substance use disorders can be eliminated with no loss in informational value and an advantage of parsimony. Taken together, these findings support the changes to substance use disorder diagnoses recommended by the DSM-V Substance and Related Disorders Workgroup, that is, combining DSM-IV abuse and dependence criteria and eliminating the legal problems abuse

Hallucinogens and Dissociative Drugs, Including LSD, PCP, Ketamine, Dextromethorphan. National Institute on Drug Abuse Research Report Series.

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National Inst. on Drug Abuse (DHHS/PHS), Rockville, MD.

Research is developing a clearer picture of the dangers of mind-altering drugs. The goal of this report is to present the latest information to providers to help them strengthen their prevention and treatment efforts. A description is presented of dissociative drugs, and consideration is given as to why people take hallucinogens. The physical…

The NBOMe hallucinogenic drug series: Patterns of use, characteristics of users and self-reported effects in a large international sample.

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Lawn, Will; Barratt, Monica; Williams, Martin; Horne, Abi; Winstock, Adam

2014-08-01

The NBOMe compounds are a novel series of hallucinogenic drugs that are potent agonists of the 5-HT2A receptor, have a short history of human consumption and are available to buy online, in most countries. In this study, we sought to investigate the patterns of use, characteristics of users and self-reported effects. A cross-sectional anonymous online survey exploring the patterns of drug use was conducted in 2012 (n = 22,289), including questions about the use of 25B-NBOMe, 25C-NBOMe, and 25I-NBOMe and comparison drugs. We found that 2.6% of respondents (n = 582) reported having ever tried one of the three NBOMe drugs and that at 2.0%, 25I-NBOMe was the most popular (n = 442). Almost all (93.5%) respondents whose last new drug tried was a NBOMe drug, tried it in 2012, and 81.2% of this group administered the drug orally or sublingually/buccally. Subjective effects were similar to comparison serotonergic hallucinogens, though higher 'negative effects while high' and greater 'value for money' were reported. The most common (41.7%) drug source was via a website. The NBOMe drugs have emerged recently, are frequently bought using the internet and have similar effects to other hallucinogenic drugs; however, they may pose larger risks, due to the limited knowledge about them, their relatively low price and availability via the internet. © The Author(s) 2014.

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

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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.

The determination of psilocin and psilocybin in hallucinogenic mushrooms by HPLC utilizing a dual reagent acidic potassium permanganate and tris(2,2'-bipyridyl)ruthenium(II) chemiluminescence detection system.

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Anastos, Nicole; Lewis, Simon W; Barnett, Neil W; Sims, D Noel

2006-01-01

This paper describes a procedure for the determination of psilocin and psilocybin in mushroom extracts using high-performance liquid chromatography with postcolumn chemiluminescence detection. A number of extraction methods for psilocin and psilocybin in hallucinogenic mushrooms were investigated, with a simple methanolic extraction being found to be most effective. Psilocin and psilocybin were extracted from a variety of hallucinogenic mushrooms using methanol. The analytes were separated on a C12 column using a (95:5% v/v) methanol:10 mM ammonium formate, pH 3.5 mobile phase with a run time of 5 min. Detection was realized through a dual reagent chemiluminescence detection system of acidic potassium permanganate and tris(2,2'-bipyridyl)ruthenium(II). The chemiluminescence detection system gave improved detectability when compared with UV absorption at 269 nm, with detection limits of 1.2 x 10(-8) and 3.5 x 10(-9) mol/L being obtained for psilocin and psilocybin, respectively. The procedure was applied to the determination of psilocin and psilocybin in three Australian species of hallucinogenic mushroom.

β2-Adrenergic Receptor Activation Suppresses the Rat Phenethylamine Hallucinogen-Induced Head Twitch Response: Hallucinogen-Induced Excitatory Post-synaptic Potentials as a Potential Substrate

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Marek, Gerard J.; Ramos, Brian P.

2018-01-01

5-Hydroxytryptamine2A (5-HT2A) receptors are enriched in layers I and Va of the rat prefrontal cortex and neocortex and their activation increases the frequency of glutamatergic excitatory post-synaptic potentials/currents (EPSP/Cs) onto layer V pyramidal cells. A number of other G-protein coupled receptors (GPCRs) are also enriched in cortical layers I and Va and either induce (α1-adrenergic and orexin2) or suppress (metabotropic glutamate2 [mGlu2], adenosine A1, μ-opioid) both 5-HT-induced EPSCs and head twitches or head shakes induced by the phenethylamine hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI). Another neurotransmitter receptor also localized to apparent thalamocortical afferents to layers I and Va of the rat prefrontal cortex and neocortex is the β2-adrenergic receptor. Therefore, we conducted preliminary electrophysiological experiments with rat brain slices examining the effects of epinephrine on electrically-evoked EPSPs following bath application of DOI (3 μM). Epinephrine (0.3–10 μM) suppressed the late EPSPs produced by electrical stimulation and DOI. The selective β2-adrenergic receptor antagonist ICI-118,551 (300 nM) resulted in a rightward shift of the epinephrine concentration-response relationship. We also tested the selective β2-adrenergic receptor agonist clenbuterol and the antagonist ICI-118,551 on DOI-induced head twitches. Clenbuterol (0.3–3 mg/kg, i.p.) suppressed DOI (1.25 mg/kg, i.p.)-induced head twitches. This clenbuterol effect appeared to be at least partially reversed by the selective β2-adrenergic receptor antagonist ICI-118,553 (0.01–1 mg/kg, i.p.), with significant reversal at doses of 0.1 and 1 mg/kg. Thus, β2-adrenergic receptor activation reverses the effects of phenethylamine hallucinogens in the rat prefrontal cortex. While Gi/Go-coupled GPCRs have previously been shown to suppress both the electrophysiological and behavioral effects of 5-HT2A receptor activation in the mPFC, the present work appears

The persistence of the subjective in neuropsychopharmacology: observations of contemporary hallucinogen research.

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Langlitz, Nicolas

2010-01-01

The elimination of subjectivity through brain research and the replacement of so-called "folk psychology" by a neuroscientifically enlightened worldview and self-conception has been both hoped for and feared. But this cultural revolution is still pending. Based on nine months of fieldwork on the revival of hallucinogen research since the "Decade of the Brain," this paper examines how subjective experience appears as epistemic object and practical problem in a psychopharmacological laboratory. In the quest for neural correlates of (drug-induced altered states of) consciousness, introspective accounts of test subjects play a crucial role in neuroimaging studies. Firsthand knowledge of the drugs' flamboyant effects provides researchers with a personal knowledge not communicated in scientific publications, but key to the conduct of their experiments. In many cases, the "psychedelic experience" draws scientists into the field and continues to inspire their self-image and way of life. By exploring these domains the paper points to a persistence of the subjective in contemporary neuropsychopharmacology.

The “Endless Trip” among the NPS Users: Psychopathology and Psychopharmacology in the Hallucinogen-Persisting Perception Disorder. A Systematic Review

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Laura Orsolini

2017-11-01

Full Text Available Hallucinogen-persisting perception disorder (HPPD is a syndrome characterized by prolonged or reoccurring perceptual symptoms, reminiscent of acute hallucinogen effects. HPPD was associated with a broader range of LSD (lysergic acid diethylamide-like substances, cannabis, methylenedioxymethamphetamine (MDMA, psilocybin, mescaline, and psychostimulants. The recent emergence of novel psychoactive substances (NPS posed a critical concern regarding the new onset of psychiatric symptoms/syndromes, including cases of HPPD. Symptomatology mainly comprises visual disorders (i.e., geometric pseudo-hallucinations, haloes, flashes of colors/lights, motion-perception deficits, afterimages, micropsia, more acute awareness of floaters, etc., even though depressive symptoms and thought disorders may be comorbidly present. Although HPPD was first described in 1954, it was just established as a fully syndrome in 2000, with the revised fourth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR. HPPD neural substrates, risk factors, and aetiopathogenesys still largely remain unknown and under investigation, and many questions about its pharmacological targets remain unanswered too. A critical mini review on psychopathological bases, etiological hypothesis, and psychopharmacological approaches toward HPPD, including the association with some novel substances, are provided here, by means of a literature search on PubMed/Medline, Google Scholar, and Scopus databases without time restrictions, by using a specific set of keywords. Pharmacological and clinical issues are considered, and practical psychopharmacological recommendations and clinical guidelines are suggested.

Use, indications and distribution in different countries of the stimulant and hallucinogenic amphetamine derivatives under consideration by WHO.

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Keup, W

1986-06-01

Information is presented on legal manufacture, distribution, medical uses and in various countries of the stimulants and hallucinogens under consideration by the World Health Organization (WHO). Data are reported from the Substance Abuse Warning System (SAWS) in the F.R.G. and other surveillance systems regarding illicit manufacture, trafficking and abuse of these compounds internationally. In addition, it is pointed out that assessment of the liability of these compounds for abuse must consider not only the substance itself but also its potential metabolic products. These data, collectively, indicate that the substances currently of most concern with respect to abuse are fenetylline and norpseudoephedrine.

Salvia divinorum: an hallucinogenic mint which might become a new recreational drug in Switzerland.

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Giroud, C; Felber, F; Augsburger, M; Horisberger, B; Rivier, L; Mangin, P

2000-08-14

Salvia divinorum Epling & Jativa is an hallucinogenic mint traditionally used for curing and divination by the Mazatec Indians of Oaxaca, Mexico. Young people from Mexican cities were reported to smoke dried leaves of S. divinorum as a marijuana substitute. Recently, two S. divinorum specimens were seized in a large-scale illicit in-door and out-door hemp plantation. Salvinorin A also called divinorin A, a trans-neoclerodane diterpene, was identified in several organic solvent extracts by gas chromatography-mass spectrometry. The botanical identity of the plant was confirmed by comparing it to an authentic herbarium specimen. More plants were then discovered in Swiss horticulturists greenhouses. All these data taken together suggest that many attempts exist in Switzerland to use S. divinorum as a recreational drug. This phenomenon may be enhanced because neither the magic mint, nor its active compound are banned substances listed in the Swiss narcotic law.

The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: reversal by antipsychotic drugs.

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Riga, Maurizio S; Soria, Guadalupe; Tudela, Raúl; Artigas, Francesc; Celada, Pau

2014-08-01

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen component of Ayahuasca, an Amazonian beverage traditionally used for ritual, religious and healing purposes that is being increasingly used for recreational purposes in US and Europe. 5MeO-DMT is of potential interest for schizophrenia research owing to its hallucinogenic properties. Two other psychotomimetic agents, phencyclidine and 2,5-dimethoxy-4-iodo-phenylisopropylamine (DOI), markedly disrupt neuronal activity and reduce the power of low frequency cortical oscillations (<4 Hz, LFCO) in rodent medial prefrontal cortex (mPFC). Here we examined the effect of 5-MeO-DMT on cortical function and its potential reversal by antipsychotic drugs. Moreover, regional brain activity was assessed by blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). 5-MeO-DMT disrupted mPFC activity, increasing and decreasing the discharge of 51 and 35% of the recorded pyramidal neurons, and reducing (-31%) the power of LFCO. The latter effect depended on 5-HT1A and 5-HT2A receptor activation and was reversed by haloperidol, clozapine, risperidone, and the mGlu2/3 agonist LY379268. Likewise, 5-MeO-DMT decreased BOLD responses in visual cortex (V1) and mPFC. The disruption of cortical activity induced by 5-MeO-DMT resembles that produced by phencyclidine and DOI. This, together with the reversal by antipsychotic drugs, suggests that the observed cortical alterations are related to the psychotomimetic action of 5-MeO-DMT. Overall, the present model may help to understand the neurobiological basis of hallucinations and to identify new targets in antipsychotic drug development.

New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca.

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McKenna, Dennis; Riba, Jordi

2018-01-01

New World indigenous peoples are noted for their sophisticated use of psychedelic plants in shamanic and ethnomedical practices. The use of psychedelic plant preparations among New World tribes is far more prevalent than in the Old World. Yet, although these preparations are botanically diverse, almost all are chemically similar in that their active principles are tryptamine derivatives, either DMT or related constituents. Part 1 of this paper provides an ethnopharmacological overview of the major tryptamine-containing New World hallucinogens. Part 2 focuses on ayahuasca and its effects on the human brain. Using complementary neurophysiological and neuroimaging techniques, we have identified brain areas involved in the cognitive effects induced by this complex botanical preparation. Initial SPECT data showed that ayahuasca modulated activity in higher order association areas of the brain. Increased blood perfusion was observed mainly in anterior brain regions encompassing the frontomedial and anterior cingulate cortices of the frontal lobes, and in the medial regions of the temporal lobes. On the other hand, applying spectral analysis and source location techniques to cortical electrical signals, we found changes in neuronal activity that predominated in more posterior sensory-selective areas of the brain. Now, using functional connectivity analysis of brain oscillations we have been able to reconcile these seemingly contradictory findings. By measuring transfer entropy, a metric based on information theory, we have shown that ayahuasca temporarily modifies the ordinary flow of information within the brain. We propose a model in which ayahuasca reduces top-down constraints and facilitates bottom-up information transfer. By simultaneously enhancing endogenous cortical excitability and reducing higher-order cognitive control, ayahuasca temporarily disrupts neural hierarchies allowing inner exploration and a new outlook on reality.

The Experience Elicited by Hallucinogens Presents the Highest Similarity to Dreaming within a Large Database of Psychoactive Substance Reports

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Sanz, Camila; Zamberlan, Federico; Erowid, Earth; Erowid, Fire; Tagliazucchi, Enzo

2018-01-01

Ever since the modern rediscovery of psychedelic substances by Western society, several authors have independently proposed that their effects bear a high resemblance to the dreams and dreamlike experiences occurring naturally during the sleep-wake cycle. Recent studies in humans have provided neurophysiological evidence supporting this hypothesis. However, a rigorous comparative analysis of the phenomenology (“what it feels like” to experience these states) is currently lacking. We investigated the semantic similarity between a large number of subjective reports of psychoactive substances and reports of high/low lucidity dreams, and found that the highest-ranking substance in terms of the similarity to high lucidity dreams was the serotonergic psychedelic lysergic acid diethylamide (LSD), whereas the highest-ranking in terms of the similarity to dreams of low lucidity were plants of the Datura genus, rich in deliriant tropane alkaloids. Conversely, sedatives, stimulants, antipsychotics, and antidepressants comprised most of the lowest-ranking substances. An analysis of the most frequent words in the subjective reports of dreams and hallucinogens revealed that terms associated with perception (“see,” “visual,” “face,” “reality,” “color”), emotion (“fear”), setting (“outside,” “inside,” “street,” “front,” “behind”) and relatives (“mom,” “dad,” “brother,” “parent,” “family”) were the most prevalent across both experiences. In summary, we applied novel quantitative analyses to a large volume of empirical data to confirm the hypothesis that, among all psychoactive substances, hallucinogen drugs elicit experiences with the highest semantic similarity to those of dreams. Our results and the associated methodological developments open the way to study the comparative phenomenology of different altered states of consciousness and its relationship with non-invasive measurements of brain physiology. PMID

The Experience Elicited by Hallucinogens Presents the Highest Similarity to Dreaming within a Large Database of Psychoactive Substance Reports

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Camila Sanz

2018-01-01

Full Text Available Ever since the modern rediscovery of psychedelic substances by Western society, several authors have independently proposed that their effects bear a high resemblance to the dreams and dreamlike experiences occurring naturally during the sleep-wake cycle. Recent studies in humans have provided neurophysiological evidence supporting this hypothesis. However, a rigorous comparative analysis of the phenomenology (“what it feels like” to experience these states is currently lacking. We investigated the semantic similarity between a large number of subjective reports of psychoactive substances and reports of high/low lucidity dreams, and found that the highest-ranking substance in terms of the similarity to high lucidity dreams was the serotonergic psychedelic lysergic acid diethylamide (LSD, whereas the highest-ranking in terms of the similarity to dreams of low lucidity were plants of the Datura genus, rich in deliriant tropane alkaloids. Conversely, sedatives, stimulants, antipsychotics, and antidepressants comprised most of the lowest-ranking substances. An analysis of the most frequent words in the subjective reports of dreams and hallucinogens revealed that terms associated with perception (“see,” “visual,” “face,” “reality,” “color”, emotion (“fear”, setting (“outside,” “inside,” “street,” “front,” “behind” and relatives (“mom,” “dad,” “brother,” “parent,” “family” were the most prevalent across both experiences. In summary, we applied novel quantitative analyses to a large volume of empirical data to confirm the hypothesis that, among all psychoactive substances, hallucinogen drugs elicit experiences with the highest semantic similarity to those of dreams. Our results and the associated methodological developments open the way to study the comparative phenomenology of different altered states of consciousness and its relationship with non-invasive measurements of brain

Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes.

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Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Narvaez, Manuel; Oflijan, Julia; Agnati, Luigi F; Fuxe, Kjell

2014-01-03

Dopamine D2LR-serotonin 5-HT2AR heteromers were demonstrated in HEK293 cells after cotransfection of the two receptors and shown to have bidirectional receptor-receptor interactions. In the current study the existence of D2L-5-HT2A heteroreceptor complexes was demonstrated also in discrete regions of the ventral and dorsal striatum with in situ proximity ligation assays (PLA). The hallucinogenic 5-HT2AR agonists LSD and DOI but not the standard 5-HT2AR agonist TCB2 and 5-HT significantly increased the density of D2like antagonist (3)H-raclopride binding sites and significantly reduced the pKiH values of the high affinity D2R agonist binding sites in (3)H-raclopride/DA competition experiments. Similar results were obtained in HEK293 cells and in ventral striatum. The effects of the hallucinogenic 5-HT2AR agonists on D2R density and affinity were blocked by the 5-HT2A antagonist ketanserin. In a forskolin-induced CRE-luciferase reporter gene assay using cotransfected but not D2R singly transfected HEK293 cells DOI and LSD but not TCB2 significantly enhanced the D2LR agonist quinpirole induced inhibition of CRE-luciferase activity. Haloperidol blocked the effects of both quinpirole alone and the enhancing actions of DOI and LSD while ketanserin only blocked the enhancing actions of DOI and LSD. The mechanism for the allosteric enhancement of the D2R protomer recognition and signalling observed is likely mediated by a biased agonist action of the hallucinogenic 5-HT2AR agonists at the orthosteric site of the 5-HT2AR protomer. This mechanism may contribute to the psychotic actions of LSD and DOI and the D2-5-HT2A heteroreceptor complex may thus be a target for the psychotic actions of hallunicogenic 5-HT2A agonists. Copyright © 2013 Elsevier Inc. All rights reserved.

25C-NBOMe--new potent hallucinogenic substance identified on the drug market.

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Zuba, Dariusz; Sekuła, Karolina; Buczek, Agnieszka

2013-04-10

This publication reports analytical properties of a new hallucinogenic substance identified in blotter papers seized from the drug market, namely 25C-NBOMe [2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine]. The identification was based on results of comprehensive study including several analytical methods, i.e., GC-EI-MS (without derivatization and after derivatization with TFAA), LC-ESI-QTOF-MS, FTIR and NMR. The GC-MS spectrum of 25C-NBOMe was similar to those obtained for other representatives of the 25-NBOMe series, with dominant ions observed at m/z=150, 121 and 91. Fragment ions analogic to those in 2C-C (4-chloro-2,5-dimethoxy-β-phenylethanamine) were also observed, but their intensities were low. Derivatization allowed the determination of molecular mass of the investigated substance. The exact molecular mass and chemical formula were confirmed by LC-QTOF-MS experiments and fragmentation pattern under electrospray ionization was determined. The MS/MS experiments confirmed that the investigated substance was N-(2-methoxy)benzyl derivative of 2C-C. The substance was also characterized by FTIR spectroscopy to corroborate its identity. Final elucidation of the structure was performed by NMR spectroscopy. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability.

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Carhart-Harris, Robin L; Williams, Tim M; Sessa, Ben; Tyacke, Robin J; Rich, Ann S; Feilding, Amanda; Nutt, David J

2011-11-01

This study sought to assess the tolerability of intravenously administered psilocybin in healthy, hallucinogen-experienced volunteers in a mock-magnetic resonance imaging environment as a preliminary stage to a controlled investigation using functional magnetic resonance imaging to explore the effects of psilocybin on cerebral blood flow and activity. The present pilot study demonstrated that up to 2 mg of psilocybin delivered as a slow intravenous injection produces short-lived but typical drug effects that are psychologically and physiologically well tolerated. With appropriate care, this study supports the viability of functional magnetic resonance imaging work with psilocybin.

Salvia divinorum: from Mazatec medicinal and hallucinogenic plant to emerging recreational drug.

Science.gov (United States)

Zawilska, Jolanta B; Wojcieszak, Jakub

2013-09-01

Salvia divinorum is a sage endemic to a small region of Mexico and has been traditionally used by the Mazatec Indians for divination and spiritual healing. Recently, it has gained increased popularity as a recreational drug, used by adolescents and young adults as an alternative to marijuana and LSD. Salvinorin A, the major active ingredient of the plant, is considered to be the most potent known hallucinogen of natural origin. This review surveys the current state of knowledge on the neurochemical, pharmacokinetic, and pharmacological properties of salvinorin A, the trends and motivation behind S. divinorum use, and the health problems among users of the plant's products. S. divinorum induces intense, but short-lived, psychedelic-like changes in mood and perception, with concomitant hallucinations and disorientation. Many websites have misinterpreted the limited existing research-based information on the side effects of salvia as evidence for its safety. However, data accumulated over the last few years indicate that potential health risks are associated with the use of S. divinorum, especially by teenagers, users of other substances of abuse, and individuals with underlying psychotic disturbances. Taken together, the data presented in this review point to the need for further basic and clinical studies to create a basis for the development of well-addressed prevention and treatment strategies. Copyright © 2013 John Wiley & Sons, Ltd.

Hunting and hallucinogens: The use psychoactive and other plants to improve the hunting ability of dogs.

Science.gov (United States)

Bennett, Bradley C; Alarcón, Rocío

2015-08-02

Cultures throughout the world give plants to their dogs in order to improve hunting success. These practices are best developed in lowland Ecuador and Peru. There is no experimental evidence for the efficacy of these practices nor critical reviews that consider possible pharmacological effects on dogs based on the chemistry of the ethnoverterinary plants. This review has three specific aims: (1) determine what plants the Ecuadorian Shuar and Quichua give to dogs to improve their hunting abilities, (2) determine what plants other cultures give to dogs for the same purpose, and (3) assess the possible pharmacological basis for the use of these plants, particularly the psychoactive ones. We gathered Shuar (Province of Morona-Santiago) and Quichua (Napo and Orellano Provinces) data from our previous publications and field notes. All specimens were vouchered and deposited in QCNE with duplicates sent to NY and MO. Data presented from other cultures derived from published studies on ethnoveterinary medicine. Species names were updated, when necessary, and family assignments follow APG III (Angiosperm Phylogeny Group, 2009. An update of the Angiosperm Phylogeny Group classification for the orders and families of flowering plants: APG III. Bot. J. Linn. Soc. 161, 105-121). Chemical data were found using PubMed and SciFinder. The Shuar and Quichua of Ecuador use at least 22 species for ethnoveterinary purposes, including all but one of their principal hallucinogens. Literature surveys identified 43 species used in other cultures to improve hunting ability. No published studies have examined the pharmacological active of these plant species in dogs. We, thus, combined phytochemical data with the ethnobotanical reports of each plant and then classified each species into a likely pharmacological category: depuratives/deodorant, olfactory sensitizer, ophthalmic, or psychoactive. The use of psychoactive substances to improve a dog׳s hunting ability seems counterintuitive, yet

Quantitative determination of salvinorin A, a natural hallucinogen with abuse liability, in Internet-available Salvia divinorum and endemic species of Salvia in Taiwan

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Po-Xiang Lin

2014-09-01

Full Text Available In recent years, recreational use of Salvia divinorum (Lamiaceae, a herbal drug that contains a hallucinogenic ingredient, salvinorin A, has become a new phenomenon among young drug users. In Taiwan, as in many other countries, dry leaves of S. divinorum and its related concentrated extract products are available via the Internet. Besides S. divinorum, there are many endemic Salvia species whose salvinorin A content is yet unknown. To understand the abuse liability of these products, the aim of this study was to assess the concentration of salvinorin A in endemic Salvia species and Internet-available salvinorin A-related products. Samples of S. divinorum were purchased via the Internet and samples of eight endemic species of Salvia were collected in Taiwan, including S. arisanensis Hayata, S. coccinea Juss. ex Murr, S. hayatana Makino ex Hayata, S. japonica Thumb. ex Murr, S. nipponica Miq. Var. formosana (Hayata Kudo, S. scapiformis Hance, S. tashiroi Hayata. Icon. PI. Formosan, and S. keitaoensis Hayata. The content of salvinorin A was determined by high performance liquid chromatography (HPLC. Salvinorin A was extracted from the dry leaves of S. divinorum and endemic species of Salvia with methanol and analyzed on a C-18 column by isocratic elution with a mobile phase of acetonitrile–water. Salvinorin A was detected in S. divinorum, but not in the endemic Salvia species of Taiwan. Therefore, endemic species of Salvia in Taiwan may not possess hallucinogenic potential. However, the potential harm from S. divinorum available via the Internet should be thoroughly assessed in Taiwan, and control measures similar to those implemented in many other countries should be considered.

The hallucinogen d-lysergic acid diethylamide (d-LSD) induces the immediate-early gene c-Fos in rat forebrain.

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Frankel, Paul S; Cunningham, Kathryn A

2002-12-27

The hallucinogen d-lysergic acid diethylamide (d-LSD) evokes dramatic somatic and psychological effects. In order to analyze the neural activation induced by this unique psychoactive drug, we tested the hypothesis that expression of the immediate-early gene product c-Fos is induced in specific regions of the rat forebrain by a relatively low, behaviorally active, dose of d-LSD (0.16 mg/kg, i.p.); c-Fos protein expression was assessed at 30 min, and 1, 2 and 4 h following d-LSD injection. A time- and region-dependent expression of c-Fos was observed with a significant increase (PLSD administration. These data demonstrate a unique pattern of c-Fos expression in the rat forebrain following a relatively low dose of d-LSD and suggest that activation of these forebrain regions contributes to the unique behavioral effects of d-LSD. Copyright 2002 Elsevier Science B.V.

Comparative neuropharmacology of N-(2-methoxybenzyl)-2,5-dimethoxyphenethylamine (NBOMe) hallucinogens and their 2C counterparts in male rats.

Science.gov (United States)

Elmore, Joshua S; Decker, Ann M; Sulima, Agnieszka; Rice, Kenner C; Partilla, John S; Blough, Bruce E; Baumann, Michael H

2018-03-01

2,5-Dimethoxyphenethylamines (2C compounds) are 5-HT 2A/2C receptor agonists that induce hallucinogenic effects. N-methoxybenzylation of 2C compounds markedly increases their affinity for 5-HT 2A receptors, and two such analogs, 2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25C-NBOMe) and 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOMe), have emerged in recreational drug markets. Here, we investigated the neuropharmacology of 25C-NBOMe and 25I-NBOMe in rats, as compared to their 2C analogs and the prototypical 5-HT 2A/2C agonist 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine (DOI). Compounds were tested in vitro using 5-HT 2A receptor binding and calcium mobilization assays. For in vivo experiments, 25C-NBOMe (0.01-0.3 mg/kg), 25I-NBOMe (0.01-0.3 mg/kg), 2-(4-chloro-2,5-dimethoxyphenyl)ethanamine (2C-C) (0.1-3.0 mg/kg), 2-(4-iodo-2,5-dimethoxyphenyl)ethanamine (2C-I) (0.1-3.0 mg/kg) and DOI (0.03-1.0 mg/kg) were administered subcutaneously (sc) to male rats, and 5-HT 2A -mediated behaviors were assessed. NBOMes displayed higher affinity for 5-HT 2A receptors than their 2C counterparts but were substantially weaker in functional assays. 25C-NBOMe and 25I-NBOMe were much more potent at inducing wet dog shakes (WDS) and back muscle contractions (BMC) when compared to 2C-C and 2C-I. Pretreatment with the selective 5-HT 2A antagonist (R)-(2,3-dimethoxyphenyl){1-[2-(4-fluorophenyl)ethyl]-4-piperidinyl}methanol (M100907) reversed behaviors produced by all agonists. Interestingly, binding affinities at the 5-HT 2A receptor were significantly correlated with potencies to induce BMC but not WDS. Our findings show that NBOMes are highly potent 5-HT 2A agonists in rats, similar to effects in mice, and consistent with the reported hallucinogenic effects in human users. Copyright © 2018. Published by Elsevier Ltd.

A novel hemagglutinin with antiproliferative activity against tumor cells from the hallucinogenic mushroom Boletus speciosus.

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Sun, Jian; Ng, Tzi-Bun; Wang, Hexiang; Zhang, Guoqing

2014-01-01

Little was known about bioactive compounds from the hallucinogenic mushroom Boletus speciosus. In the present study, a hemagglutinin (BSH, B. speciosus hemagglutinin) was isolated from its fruiting bodies and enzymatic properties were also tested. The chromatographic procedure utilized comprised anion exchange chromatography on Q-Sepharose, cation exchange chromatography on CM-Cellulose, cation exchange chromatography on SP-Sepharose, and gel filtration by FPLC on Superdex 75. The hemagglutinin was a homodimer which was estimated to be approximately 31 kDa in size. The activity of BSH was stable up to 60°C, while there was a precipitous drop in activity when the temperature was elevated to 70°C. BSH retained 25% hemagglutinating activity when exposed to 100 mM NaOH and 25 mM HCl. The activity was potently inhibited by 1.25 mM Hg(2+) and slightly inhibited by Fe(2+), Ca(2+), and Pb(2+). None of the sugars tested showed inhibition towards BSH. Its hemagglutinating activity towards human erythrocytes type A, type B, and type AB was higher than type O. The hemagglutinin showed antiproliferative activity towards hepatoma Hep G2 cells and mouse lymphocytic leukemia cells (L1210) in vitro, with IC50 of 4.7 μ M and 7.0 μ M, respectively. It also exhibited HIV-1 reverse transcriptase inhibitory activity with an IC50 of 7.1 μ M.

A Novel Hemagglutinin with Antiproliferative Activity against Tumor Cells from the Hallucinogenic Mushroom Boletus speciosus

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Jian Sun

2014-01-01

Full Text Available Little was known about bioactive compounds from the hallucinogenic mushroom Boletus speciosus. In the present study, a hemagglutinin (BSH, B. speciosus hemagglutinin was isolated from its fruiting bodies and enzymatic properties were also tested. The chromatographic procedure utilized comprised anion exchange chromatography on Q-Sepharose, cation exchange chromatography on CM-Cellulose, cation exchange chromatography on SP-Sepharose, and gel filtration by FPLC on Superdex 75. The hemagglutinin was a homodimer which was estimated to be approximately 31 kDa in size. The activity of BSH was stable up to 60°C, while there was a precipitous drop in activity when the temperature was elevated to 70°C. BSH retained 25% hemagglutinating activity when exposed to 100 mM NaOH and 25 mM HCl. The activity was potently inhibited by 1.25 mM Hg2+ and slightly inhibited by Fe2+, Ca2+, and Pb2+. None of the sugars tested showed inhibition towards BSH. Its hemagglutinating activity towards human erythrocytes type A, type B, and type AB was higher than type O. The hemagglutinin showed antiproliferative activity towards hepatoma Hep G2 cells and mouse lymphocytic leukemia cells (L1210 in vitro, with IC50 of 4.7 μM and 7.0 μM, respectively. It also exhibited HIV-1 reverse transcriptase inhibitory activity with an IC50 of 7.1 μM.

Alcaloides e o chá de ayahuasca: uma correlação dos "estados alterados da consciência" induzido por alucinógenos Alkaloids and ayahuasca tea: a correlation of hallucinogen-induced "altered states of consciousness"

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P.A. De Souza

2011-01-01

Full Text Available Dentre as inúmeras plantas alucinógenas utilizadas por populações indígenas da bacia amazônica, talvez nenhuma delas seja mais interessante ou complexa em termos botânicos, químicos ou etnográficos, como a bebida alucinógena conhecida como ayahuasca, hoasca, medicina, vegetal ou daime. Ayahuasca é bebida psicotrópica da América do Sul de destacado uso no xamanismo de muitas tribos indígenas da Amazônia, obtida pela fervura da casca do cipó de Banisteriopis caapi com a mistura de folhas de Psycotria, principalmente P. viridis. No Brasil, ocupa posição de destaque na etnomedicina. A natureza química dos compostos ativos, bem como, a maneira de utilização faz com que essa bebida ocupe posição de destaque nos atuais estudos da neurofarmacologia, neurofisiologia e psiquiatria. Alucinógenos e substâncias relacionadas constituem poderosa base experimental para investigar a correlação biológica dos estados alterados de consciência. O estudo de alucinógenos em humanos é de suma importância porque as substâncias com essas propriedades afetam certas funções cerebrais que tipicamente caracterizam a mente humana, incluindo a cognição, volição, ego e auto-percepção. As várias manifestações dos "desequilíbrios do ego" são especialmente características psicodélicas proeminentes, que acabam naturalmente criando psicoses. Sumarizamos nessa revisão alguns aspectos importantes no estudo do chá de ayahuasca em humanos, as indicações e contra-indicações para fins terapêuticos e religiosos.Among the numerous hallucinogenic plants utilized by indigenous populations of the Amazon Basin, perhaps none is as interesting or complex in terms of botany, chemistry or ethnography as the hallucinogenic beverage known as ayahuasca, hoasca, medicine, vegetable or daime. Ayahuasca is a South American psychotropic beverage that is prominent in the shamanism of many indigenous Amazonian tribes and is obtained by boiling the bark

DNA-based taxonomic identification of basidiospores in hallucinogenic mushrooms cultivated in "grow-kits" seized by the police: LC-UV quali-quantitative determination of psilocybin and psilocin.

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Gambaro, Veniero; Roda, Gabriella; Visconti, Giacomo Luca; Arnoldi, Sebastiano; Casagni, Eleonora; Dell'Acqua, Lucia; Farè, Fiorenza; Paladino, Eleonora; Rusconi, Chiara; Arioli, Stefania; Mora, Diego

2016-06-05

The taxonomic identification of the biological material contained in the hallucinogenic mushrooms culture media, was carried out using a DNA-based approach, thus highlighting the usefulness of this approach in the forensic identification of illegal samples also when they are present as basidiospores mixed in culture media and spore-bearing fruiting body are not present. This approach is very useful as it allows the unequivocal identification of potentially illicit material before the cultivation and it enables to stop the material to the Customs and to destroy it due to its dangerousness without cultivating the "grow-kits" and without instructing a criminal case. In fact, even if psilocin and psilocybin and the whole mushrooms are illegal in many countries, there is no specific indication in the law about the so called "grow-kits", containing the spores. To confirm the data obtained by the taxonomic identification, a simple, reliable, efficient LC-UV method, using tryptamine as internal standard, suitable for the forensic quali-quantitative determination of psilocin and psilocybin in hallucinogenic mushroom was optimized, validated and applied to the mushrooms grown after the cultivation of the grow-kits seized by the judicial authority, with the authorization of the Ministry of Health. A cation exchange column was used in a gradient elution mode (Phase A: 50mMK2HPO4; 100mM NaCl pH=3 Phase B: methanol). The developed method was linear over the calibration range with a R(2)>0.9992 for both the analytes. The detection and quantification limits were respectively 0.01 and 0.1μg/mL for psilocybin and 0.05μg/mL and 0.1μg/mL for psilocin and the intra- and inter-day precision was satisfactory (coefficients of variation psilocybin in the mushrooms grown from the seized "grow-kits" ranged from 1.02 to 7.60mg/g of dry vegetable material, while the content of psilocin from 0.415 to 8.36mg/g. Copyright © 2016 Elsevier B.V. All rights reserved.

Hallucinogen-like effects of 2-([2-(4-cyano-2,5-dimethoxyphenyl) ethylamino]methyl)phenol (25CN-NBOH), a novel N-benzylphenethylamine with 100-fold selectivity for 5-HT2A receptors, in mice

DEFF Research Database (Denmark)

Fantegrossi, William E; Gray, Bradley W; Bailey, Jessica M

2015-01-01

RATIONALE: 2-([2-(4-cyano-2,5-dimethoxyphenyl)ethylamino]methyl)phenol (25CN-NBOH) is structurally similar to N-benzyl substituted phenethylamine hallucinogens currently emerging as drugs of abuse. 25CN-NBOH exhibits dramatic selectivity for 5-HT2A receptors in vitro, but has not been behaviorally...... an intermediate degree of generalization (55 %) for the DOI training dose, and these interoceptive effects were attenuated by M100907. Finally, 25CN-NBOH did not generalize to M100907 at any dose, but ketanserin fully substituted in these animals. CONCLUSIONS: 25CN-NBOH was behaviorally active, but less effective...

Salvinorin A, a kappa-opioid receptor (KOP-r agonist hallucinogen: Pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders

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Eduardo eButelman

2015-09-01

Full Text Available Salvinorin A is a potent hallucinogen, isolated from the ethnomedical plant Salvia divinorum. Salvinorin A is a selective high efficacy kappa-opioid receptor (KOPr agonist, and thus implicates the KOPr system and its endogenous agonist ligands (the dynorphins in higher functions, including cognition, and perceptual effects. Salvinorin A is the only selective KOPr ligand to be widely available outside research or medical settings, and salvinorin A- containing products have undergone frequent non-medical use. KOPr/dynorphin systems in the brain are known to be powerful counter-modulatory mechanisms to dopaminergic function, which is important in mood and reward engendered by natural and drug reinforcers (including drugs of abuse. KOPr activation (including by salvinorin A can thus cause aversion and anhedonia in preclinical models. Salvinorin A is also a completely new scaffold for medicinal chemistry approaches, since it is a non-nitrogenous neoclerodane, unlike all other known opioid ligands. Ongoing efforts have the goal of discovering novel semi-synthetic salvinorin analogs with potential KOPr-mediated pharmacotherapeutic effects (including partial agonist or biased agonist effects, with a reduced burden of undesirable effects associated with salvinorin A.

Síndrome alucinógeno, indoles alucinógenos

OpenAIRE

Serés García, L.

2016-01-01

Hallucinogenic syndrome and hallucinogenic indoles This work summarizes the information about the hallucinogenic mushrooms: history, active components, toxicity, clinical studies, diagnosis, treatment and legal aspects.

Dysregulated corticostriatal activity in open-field behavior and the head-twitch response induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine.

Science.gov (United States)

Rangel-Barajas, Claudia; Estrada-Sánchez, Ana María; Barton, Scott J; Luedtke, Robert R; Rebec, George V

2017-02-01

The substituted amphetamine, 2,5-dimethoxy-4-iodoamphetamine (DOI), is a hallucinogen that has been used to model a variety of psychiatric conditions. Here, we studied the effect of DOI on neural activity recorded simultaneously in the primary motor cortex (M1) and dorsal striatum of freely behaving FvB/N mice. DOI significantly decreased the firing rate of individually isolated neurons in M1 and dorsal striatum relative to pre-drug baseline. It also induced a bursting pattern of activity by increasing both the number of spikes within a burst and burst duration. In addition, DOI increased coincident firing between simultaneously recorded neuron pairs within the striatum and between M1 and dorsal striatum. Local field potential (LFP) activity also increased in coherence between M1 and dorsal striatum after DOI in the low frequency gamma band (30-50 Hz), while corticostriatal coherence in delta, theta, alpha, and beta activity decreased. We also assessed corticostriatal LFP activity in relation to the DOI-induced head-twitch response (HTR), a readily identifiable behavior used to assess potential treatments for the conditions it models. The HTR was associated with increased delta and decreased theta power in both M1 and dorsal striatum. Together, our results suggest that DOI dysregulates corticostriatal communication and that the HTR is associated with this dysregulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

High-Performance Liquid Chromatography with Tandem Mass Spectrometry for the Determination of Nine Hallucinogenic 25-NBOMe Designer Drugs in Urine Specimens

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Poklis, Justin L.; Clay, Deborah J.; Poklis, Alphonse

2014-01-01

We present a high-performance liquid chromatography triple quadrupole mass spectrometry (HPLC–MS-MS) method for the identification and quantification of nine serotonin 5-HT2A receptor agonist hallucinogenic substances from a new class of N-methoxybenzyl derivatives of methoxyphenylethylamine (NBOMe) designer drugs in human urine: 25H-NBOMe, 2CC-NBOMe, 25I-NBF, 25D-NBOMe, 25B-NBOMe, 2CT-NBOMe, 25I-NBMD, 25G-NBOMe and 25I-NBOMe. This assay was developed for the Virginia Commonwealth University Clinical and Forensic Toxicology laboratory to screen emergency department specimens in response to an outbreak of N-benzyl-phenethylamine derivative abuse and overdose cases in Virginia. The NBOMe derivatives were rapidly extracted from the urine specimens by use of FASt™ solid-phase extraction columns. Assay performance was determined as recommended for validation by the Scientific Working Group for Forensic Toxicology (SWGTOX) for linearity, lower limit of quantification, lower limit of detection, accuracy/bias, precision, dilution integrity, carryover, selectivity, absolute recovery, ion suppression and stability. Linearity was verified to be from 1 to 100 ng/mL for each of the nine analytes. The bias determined for the NBOMe derivatives was 86–116% with a <14% coefficient of variation over the linear range of the assay. Four different NBOMe derivatives were detected using the presented method in patient urine specimens. PMID:24535338

Hallucinogen Rating Scale (HRS - Versão brasileira: tradução e adaptação transcultural

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Suely Mizumoto

2011-01-01

Full Text Available CONTEXTO: Existe um crescente interesse científico pelos efeitos de alucinógenos em geral e, particularmente, pelo uso religioso da bebida psicoativa ayahuasca no Brasil. Todavia, não há no Brasil um instrumento padronizado para avaliar os efeitos de alucinógenos. A Hallucinogen Rating Scale (HRS é um questionário amplamente usado nos Estados Unidos e na Europa para avaliar os efeitos de diversas substâncias psicoativas, incluindo as alucinógenas. OBJETIVO: Traduzir e adaptar a HRS para o português brasileiro. MÉTODO: A adaptação foi realizada em três etapas: 1 os autores do artigo traduziram a HRS para o português, visando à elaboração de uma versão-síntese inicial; 2 foi feita retrotradução dessa versão para o inglês por dois tradutores independentes; 3 foi elaborada uma versão final em português brasileiro por um comitê de revisão. Esta versão final foi desenvolvida pela comparação entre as traduções iniciais e as retrotraduções, por um processo dialógico com o autor do instrumento. RESULTADOS: Produção da versão final da HRS em português. Observaram-se as diretrizes para equivalência semântica e conceitual entre o português e inglês na descrição de estados subjetivos induzidos por alucinógenos. CONCLUSÃO: Uma versão brasileira da HRS - instrumento largamente empregado em todo o mundo para quantificar os efeitos de psicoativos - fornece um instrumento sensível para a avaliação de efeitos de substâncias alucinógenas no Brasil.

Hallucinogenic mushrooms

OpenAIRE

Reingardienė, Dagmara; Vilčinskaitė, Jolita; Lažauskas, Robertas

2005-01-01

Haliucinogeninių grybų grupė (kiškiabudės, karteklės, mėšlinuko, skydabudės, glotniagalvės, gleiviabudės rūšys) yra psilocibino turintys grybai. Šie magiški psichoaktyvūs grybai turi serotonerginio haliucinogeno psilocibino. Psilocibinas ir jo aktyvus metabolitas psilocinas yra panašūs į lizerginės rūgšties dietilamidą (LSD). Jie greitai sukelia centrinės nervų sistemos pokyčių: ataksiją, hiperkinezę ir haliucinacijas. Šiame apžvalginiame straipsnyje analizuojama haliucinogeninių grybų vartoj...

The hallucinogen d-lysergic diethylamide (LSD) decreases dopamine firing activity through 5-HT1A, D2 and TAAR1 receptors.

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De Gregorio, Danilo; Posa, Luca; Ochoa-Sanchez, Rafael; McLaughlin, Ryan; Maione, Sabatino; Comai, Stefano; Gobbi, Gabriella

2016-11-01

d-lysergic diethylamide (LSD) is a hallucinogenic drug that interacts with the serotonin (5-HT) system binding to 5-HT 1 and 5-HT 2 receptors. Little is known about its potential interactions with the dopamine (DA) neurons of the ventral tegmental area (VTA). Using in-vivo electrophysiology in male adult rats, we evaluated the effects of cumulative doses of LSD on VTA DA neuronal activity, compared these effects to those produced on 5-HT neurons in the dorsal raphe nucleus (DRN), and attempted to identify the mechanism of action mediating the effects of LSD on VTA DA neurons. LSD, at low doses (5-20μg/kg, i.v.) induced a significant decrease of DRN 5-HT firing activity through 5-HT 2A and D 2 receptors. At these low doses, LSD did not alter VTA DA neuronal activity. On the contrary, at higher doses (30-120μg/kg, i.v.), LSD dose-dependently decreased VTA DA firing activity. The depletion of 5-HT with p-chlorophenylalanine did not modulate the effects of LSD on DA firing activity. The inhibitory effects of LSD on VTA DA firing activity were prevented by the D 2 receptor antagonist haloperidol (50μg/kg, i.v.) and by the 5-HT 1A receptor antagonist WAY-100,635 (500μg/kg, i.v.). Notably, pretreatment with the trace amine-associate receptor 1 (TAAR 1 ) antagonist EPPTB (5mg/kg, i.v.) blocked the inhibitory effect of LSD on VTA DA neurons. These results suggest that LSD at high doses strongly affects DA mesolimbic neuronal activity in a 5-HT independent manner and with a pleiotropic mechanism of action involving 5-HT 1A, D 2 and TAAR 1 receptors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Candyflipping and Other Combinations: Identifying Drug–Drug Combinations from an Online Forum

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Michael Chary

2018-04-01

Full Text Available Novel psychoactive substances (NPS refer to synthetic compounds or derivatives of more widely known substances of abuse that have emerged over the last two decades. Case reports suggest that users combine substances to achieve desired psychotropic experiences while reducing dysphoria and unpleasant somatic effects. However, the pattern of combining NPS has not been studied on a large scale. Here, we show that posts discussing NPS describe combining nootropics with sedative-hypnotics and stimulants with plant hallucinogens or psychiatric medications. Discussions that mention sedative-hypnotics most commonly also mention hallucinogens and stimulants. We analyzed 20 years of publicly available posts from Lycaeum, an Internet forum dedicated to sharing information about psychoactive substance use. We used techniques from natural language processing and machine learning to identify NPS and correlate patterns of co-mentions of substances across posts. We found that conversations mentioning synthetic hallucinogens tended to divide into those mentioning hallucinogens derived from amphetamine and those derived from ergot. Conversations that mentioned synthetic hallucinogens tended not to mention plant hallucinogens. Conversations that mention bath salts commonly mention sedative-hypnotics or nootropics while more canonical stimulants are discussed with plant hallucinogens and psychiatric medications. All types of substances are frequently compared to MDMA, DMT, cocaine, or atropine when trying to describe their effects. Our results provide the largest analysis to date of online descriptions of patterns of polysubstance use and further demonstrate the utility of social media in learning about trends in substance use. We anticipate this work to lead to a more detailed analysis of the knowledge contained online about the patterns of usage and effects of novel psychoactive substances.

41 CFR Appendix to Part 102 - 74-Rules and Regulations Governing Conduct on Federal Property

Science.gov (United States)

2010-07-01

... from— (a) Being under the influence, using or possessing any narcotic drugs, hallucinogens, marijuana... alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines. Alcoholic... the GSA Regional Administrator, which will have the same force and effect as these regulations; (e...

Ethnopharmacological survey of medicinal plants with hallucinogenic effect and plants used against pain, inflammatory diseases, diabetes and urinary lithiasis in Zagora “Morocco”.

Directory of Open Access Journals (Sweden)

Hicham Boufous

2017-12-01

Full Text Available Aim: The aim of this study was to identify different plants used in folk medicine for treating pain, inflammatory diseases, diabetes and kidney stones by the population of Zagora province, in southern east of Morocco. This investigation was undertaken during more than 2 years started in 2013 and ended in 2015. Methods: A total of 1400 person with different ages between 20 and 80 years, in twelve areas, was included in this survey; 348 were diabetes, 292 were suffering from kidney stones and 760 are healthy. Data collected was separated in two parts. The first part concerned interviewee information’s (age, sex and level of education and a second part was designed for plants uses (vernacular names, uses, parts used and mode of preparation.Use value (UV, fidelity level (FL and family use value (FUV were calculated. Results: We inventoried 83 plants species belonging to 40 families that were used, Ranunculaceae family family showed the highest significance (FUV= 0.36. Six species with the highest UV were Zygophyllum gaetulum L. (0.44, Nigella sativa (0.36, Rosmarinus officinalis L (0.36, Trigonella foenum-graecum L (0.35 and Thymus satureioides L (0.35. We identified 50 species used for treating or managing pain, 45 for diabetes, 19 for kidney stone, 7 for treating inflammatory diseases and only 3 species that were recognized with hallucinogenic effects. Conclusions: This study shows that folk medicine in Zagora still occupies a high level in primary health care. Data collected may help to preserve knowledge about different plants used and their mode of preparation. [J Complement Med Res 2017; 6(4.000: 342-350

The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms.

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Barrett, Frederick S; Bradstreet, Matthew P; Leoutsakos, Jeannie-Marie S; Johnson, Matthew W; Griffiths, Roland R

2016-12-01

Acute adverse psychological reactions to classic hallucinogens ("bad trips" or "challenging experiences"), while usually benign with proper screening, preparation, and support in controlled settings, remain a safety concern in uncontrolled settings (such as illicit use contexts). Anecdotal and case reports suggest potential adverse acute symptoms including affective (panic, depressed mood), cognitive (confusion, feelings of losing sanity), and somatic (nausea, heart palpitation) symptoms. Responses to items from several hallucinogen-sensitive questionnaires (Hallucinogen Rating Scale, the States of Consciousness Questionnaire, and the Five-Dimensional Altered States of Consciousness questionnaire) in an Internet survey of challenging experiences with the classic hallucinogen psilocybin were used to construct and validate a Challenging Experience Questionnaire. The stand-alone Challenging Experience Questionnaire was then validated in a separate sample. Seven Challenging Experience Questionnaire factors (grief, fear, death, insanity, isolation, physical distress, and paranoia) provide a phenomenological profile of challenging aspects of experiences with psilocybin. Factor scores were associated with difficulty, meaningfulness, spiritual significance, and change in well-being attributed to the challenging experiences. The factor structure did not differ based on gender or prior struggle with anxiety or depression. The Challenging Experience Questionnaire provides a basis for future investigation of predictors and outcomes of challenging experiences with classic hallucinogens. © The Author(s) 2016.

The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms

Science.gov (United States)

Barrett, Frederick S.; Bradstreet, Matthew P.; Leoutsakos, Jeannie-Marie S.; Johnson, Matthew W.; Griffiths, Roland R.

2017-01-01

Acute adverse psychological reactions to classic hallucinogens (“bad trips”, or “challenging experiences”), while usually benign with proper screening, preparation, and support in controlled settings, remain a safety concern in uncontrolled settings (such as illicit use contexts). Anecdotal and case reports suggest potential adverse acute symptoms including affective (panic, depressed mood), cognitive (confusion, feelings of losing sanity), and somatic (nausea, heart palpitation) symptoms. Responses to items from several hallucinogen-sensitive questionnaires (Hallucinogen Rating Scale, the States of Consciousness Questionnaire, and the 5-Dimensional Altered States of Consciousness questionnaire) in an internet survey of challenging experiences with the classic hallucinogen psilocybin were used to construct and validate a Challenging Experience Questionnaire (CEQ). The stand-alone CEQ was then validated in a separate sample. Seven CEQ factors (grief, fear, death, insanity, isolation, physical distress, and paranoia) provide a phenomenological profile of challenging aspects of experiences with psilocybin. Factor scores were associated with the difficulty, meaningfulness, spiritual significance, and change in well-being attributed to the challenging experiences. The factor structure did not differ based on gender or prior struggle with anxiety or depression. The CEQ provides a basis for future investigation of predictors and outcomes of challenging experiences with psilocybin, and should be explored as a measure of challenging experiences with the broad class of classic hallucinogens. PMID:27856683

A fatal poisoning involving Bromo-Dragonfly

DEFF Research Database (Denmark)

Andreasen, Mette Findal

hallucinogen, only slightly less potent than LSD. In the present case from Denmark an 18-year-old woman was found dead one morning in October 2007. The previous evening she and her boyfriend had both ingested a hallucinogen LSD-like liquid. A medico-legal autopsy was performed on the deceased. Liver, blood...

Phospholipase C mediates (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-, but not lysergic acid diethylamide (LSD)-elicited head bobs in rabbit medial prefrontal cortex.

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Schindler, Emmanuelle A D; Harvey, John A; Aloyo, Vincent J

2013-01-23

The phenethylamine and indoleamine classes of hallucinogens demonstrate distinct pharmacological properties, although they share a serotonin(2A) (5-HT(2A)) receptor mechanism of action (MOA). The 5-HT(2A) receptor signals through phosphatidylinositol (PI) hydrolysis, which is initiated upon activation of phospholipase C (PLC). The role of PI hydrolysis in the effects of hallucinogens remains unclear. In order to better understand the role of PI hydrolysis in the MOA of hallucinogens, the PLC inhibitor, 1-[6-((17β-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione (U73122), was used to study the effects of two hallucinogens, the phenethylamine, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and the indoleamine, lysergic acid diethylamide (LSD). PI hydrolysis was quantified through release of [3H]inositol-4-phosphate from living rabbit frontocortical tissue prisms. Head bobs were counted after hallucinogens were infused into the medial prefrontal cortex (mPFC) of rabbits. Both DOI and LSD stimulated PI hydrolysis in frontocortical tissue through activation of PLC. DOI-stimulated PI hydrolysis was blocked by 5-HT(2A/2C) receptor antagonist, ketanserin, whereas the LSD signal was blocked by 5-HT(2B/2C) receptor antagonist, SB206553. When infused into the mPFC, both DOI- and LSD-elicited head bobs. Pretreatment with U73122 blocked DOI-, but not LSD-elicited head bobs. The two hallucinogens investigated were distinct in their activation of the PI hydrolysis signaling pathway. The serotonergic receptors involved with DOI and LSD signals in frontocortical tissue were different. Furthermore, PLC activation in mPFC was necessary for DOI-elicited head bobs, whereas LSD-elicited head bobs were independent of this pathway. These novel findings urge closer investigation into the intracellular mechanism of action of these unique compounds. Published by Elsevier B.V.

Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience.

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Pokorny, Thomas; Preller, Katrin H; Kraehenmann, Rainer; Vollenweider, Franz X

2016-04-01

The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups (n=19, n=17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) (ppsilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Increased thalamic resting-state connectivity as a core driver of LSD-induced hallucinations.

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Müller, F; Lenz, C; Dolder, P; Lang, U; Schmidt, A; Liechti, M; Borgwardt, S

2017-12-01

It has been proposed that the thalamocortical system is an important site of action of hallucinogenic drugs and an essential component of the neural correlates of consciousness. Hallucinogenic drugs such as LSD can be used to induce profoundly altered states of consciousness, and it is thus of interest to test the effects of these drugs on this system. 100 μg LSD was administrated orally to 20 healthy participants prior to fMRI assessment. Whole brain thalamic functional connectivity was measured using ROI-to-ROI and ROI-to-voxel approaches. Correlation analyses were used to explore relationships between thalamic connectivity to regions involved in auditory and visual hallucinations and subjective ratings on auditory and visual drug effects. LSD caused significant alterations in all dimensions of the 5D-ASC scale and significantly increased thalamic functional connectivity to various cortical regions. Furthermore, LSD-induced functional connectivity measures between the thalamus and the right fusiform gyrus and insula correlated significantly with subjective auditory and visual drug effects. Hallucinogenic drug effects might be provoked by facilitations of cortical excitability via thalamocortical interactions. Our findings have implications for the understanding of the mechanism of action of hallucinogenic drugs and provide further insight into the role of the 5-HT 2A -receptor in altered states of consciousness. © 2017 The Authors Acta Psychiatrica Scandinavica Published by John Wiley & Sons Ltd.

Structure activity correlations in the inhibition of brain synaptosomal 3H-norepinephrine uptake by phenethylamine analogs. The role of α-alkyl side chain and methoxyl ring substitutions

International Nuclear Information System (INIS)

Makriyannis, A.; Bowerman, D.; Sze, P.Y.; Fournier, D.; Jong, A.P. de

1982-01-01

α-Ethylphenethylamine proved to be a weaker inhibitor of rat brain synaptosomal [ 3 H]norepinephrine ([ 3 H]NE) uptake than amphetamine, while 2-amino-tetralin and 2-amino-1,2-dihydronaphtalene, compounds in which the α-side chain ethyl group is tied to the aromatic ring have a similar inhibiting potency as amphetamine. Hallucinogenic polymethoxy substituted phenethylamine analogs have very low inhibitory potencies indicating that inhibition of NE-reuptake in brain noradrenergic neurons is not associated with the drug-induced hallucinogenic syndrome. (Auth.)

A single dose of lysergic acid diethylamide influences gene expression patterns within the mammalian brain.

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Nichols, Charles D; Sanders-Bush, Elaine

2002-05-01

Hallucinogenic drugs such as lysergic acid diethylamide (LSD) have profound effects on humans including hallucinations and detachment from reality. These remarkable behavioral effects have many similarities to the debilitating symptoms of neuropsychiatric disorders such as schizophrenia. The effects of hallucinogens are thought to be mediated by serotonin receptor activation; however, how these drugs elicit the unusual behavioral effects remains largely a mystery, despite much research. We have undertaken the first comprehensive analysis of gene expression influenced by acute LSD administration in the mammalian brain. These studies represent a novel approach to elucidate the mechanism of action of this class of drugs. We have identified a number of genes that are predicted to be involved in the processes of synaptic plasticity, glutamatergic signaling and cytoskeletal architecture. Understanding these molecular events will lead to new insights into the etiology of disorders whose behavioral symptoms resemble the temporary effects of hallucinogenic drugs, and also may ultimately result in new therapies.

Pharmacological activity of salvinorin A, the major component of Salvia divinorum.

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Listos, Joanna; Merska, Alicja; Fidecka, Sylwia

2011-01-01

The hallucinogenic plant Salvia divinorum (i.e., "magic mint") is a member of the Sage family that has been historically used for divination and shamanism by the Mazatecs. Today, S. divinorum has become increasingly popular as a recreational drug for its hallucinogenic effects. The non-nitrogenous diterpene, salvinorin A, the major active component of S. divinorum, is responsible for the hallucinogenic effect of this plant. Here, we described the behavioral effects of salvinorin A in animals including the addictive, antinociception and antidepressant properties of the drug. The present paper also demonstrates the not well recognized (or unclear) mechanisms of action of salvinorin A. The last part of the paper presents information about the legal status of S. divinorum and its derivatives. Taking into account the increasing popularity and consumption of salvinorin A and S. divinorum today, it is important to collect all data on the pharmacological profile of this plant and its products.

Clinical toxicology of newer recreational drugs.

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Hill, Simon L; Thomas, Simon H L

2011-10-01

Novel synthetic 'designer' drugs with stimulant, ecstasy-like (entactogenic) and/or hallucinogenic properties have become increasingly popular among recreational drug users in recent years. The substances used change frequently in response to market trends and legislative controls and it is an important challenge for poisons centres and clinical toxicologists to remain updated on the pharmacological and toxicological effects of these emerging agents. To review the available information on newer synthetic stimulant, entactogenic and hallucinogenic drugs, provide a framework for classification of these drugs based on chemical structure and describe their pharmacology and clinical toxicology. A comprehensive review of the published literature was performed using PUBMED and Medline databases, together with additional non-peer reviewed information sources, including books, media reports, government publications and internet resources, including drug user web forums. Novel synthetic stimulant, entactogenic or hallucinogenic designer drugs are increasingly available to users as demonstrated by user surveys, poisons centre calls, activity on internet drug forums, hospital attendance data and mortality data. Some population sub groups such as younger adults who attend dance music clubs are more likely to use these substances. The internet plays an important role in determining the awareness of and availability of these newer drugs of abuse. Most novel synthetic stimulant, entactogenic or hallucinogenic drugs of abuse can be classified according to chemical structure as piperazines (e.g. benzylpiperazine (BZP), trifluoromethylphenylpiperazine), phenethylamines (e.g. 2C or D-series of ring-substituted amfetamines, benzodifurans, cathinones, aminoindans), tryptamines (e.g. dimethyltryptamine, alpha-methyltryptamine, ethyltryptamine, 5-methoxy-alphamethyltryptamine) or piperidines and related substances (e.g. desoxypipradrol, diphenylprolinol). Alternatively classification may

The endogenous hallucinogen and trace amine N,N-dimethyltryptamine (DMT displays potent protective effects against hypoxia via sigma-1 receptor activation in human primary iPSC-derived cortical neurons and microglia-like immune cells

Directory of Open Access Journals (Sweden)

Attila Szabo

2016-09-01

Full Text Available N,N-dimethyltryptamine (DMT is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R, an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins. Due to this function, the activation of Sig-1R can mitigate the outcome of hypoxia or oxidative stress. In this paper we aimed to test the hypothesis that DMT plays a neuroprotective role in the brain by activating the Sig-1R. We tested whether DMT can mitigate hypoxic stress in in vitro cultured human cortical neurons (derived from induced pluripotent stem cells, and in monocyte-derived macrophages and dendritic cells. Here we report that DMT robustly increases the survival of these cell types in severe hypoxia (0.5% O2 through the Sig-1R. Furthermore, this phenomenon is associated with the decreased expression and function of the alpha subunit of the hypoxia-inducible factor 1 (HIF-1 suggesting that DMT-mediated Sig-1R activation may alleviate hypoxia-induced cellular stress and increase survival in a HIF-1-independent manner. Our results reveal a novel and important role of DMT in human cellular physiology. We postulate that this compound may be endogenously generated in situations of stress, ameliorating the adverse effects of hypoxic/ischemic insult to the brain.

The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells.

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Szabo, Attila; Kovacs, Attila; Riba, Jordi; Djurovic, Srdjan; Rajnavolgyi, Eva; Frecska, Ede

2016-01-01

N,N-dimethyltryptamine (DMT) is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R), an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER) and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins. Due to this function, the activation of Sig-1R can mitigate the outcome of hypoxia or oxidative stress. In this paper, we aimed to test the hypothesis that DMT plays a neuroprotective role in the brain by activating the Sig-1R. We tested whether DMT can mitigate hypoxic stress in in vitro cultured human cortical neurons (derived from induced pluripotent stem cells, iPSCs), monocyte-derived macrophages (moMACs), and dendritic cells (moDCs). Results showed that DMT robustly increases the survival of these cell types in severe hypoxia (0.5% O2) through the Sig-1R. Furthermore, this phenomenon is associated with the decreased expression and function of the alpha subunit of the hypoxia-inducible factor 1 (HIF-1) suggesting that DMT-mediated Sig-1R activation may alleviate hypoxia-induced cellular stress and increase survival in a HIF-1-independent manner. Our results reveal a novel and important role of DMT in human cellular physiology. We postulate that this compound may be endogenously generated in situations of stress, ameliorating the adverse effects of hypoxic/ischemic insult to the brain.

Altered consciousness states and endogenous psychoses: a common molecular pathway?

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Ciprian-Ollivier, J; Cetkovich-Bakmas, M G

1997-12-19

Interest in the role of indolamines in the pathogenesis of psychoses has been renewed in recent years by the development of atypical antipsychotic drugs such as clozapine, olanzapine, and risperidone, which act on serotonin receptors. Discovery of the hallucinogenic compounds called methylated indolealkyalamines (MIAs) (e.g. N,N-dimethylserotonin, or bufotenin, and N,N-dimethyltryptamine, or DMT) led proponents of the transmethylation hypothesis of schizophrenia to theorize that through some inborn error of metabolism, serotonin or tryptamine might undergo the addition of extra methyl radicals, thereby forming MIAs with hallucinogenic properties. Various studies have attempted to detect the excretion of MIAs, especially DMT, in the body fluids of psychotic patients and normal controls. Some of these studies have demonstrated elevated MIA concentrations in psychotic patients, including those with schizophrenia, compared with normal persons, and others have not. A number of variables may account for these contradictory findings. The mechanism whereby the beverage ayahuasca, which is used in certain cure and divination rituals in the Amazon Basin, exerts its hallucinogenic effects may serve as a model to explain the mechanism underlying hallucinogenic symptoms in schizophrenia and may lend support to the transmethylation hypothesis. Certain studies suggest that specific perceptual disturbances manifested by schizophrenic patients could contribute to progressive deterioration and negative symptomatology. All these findings point to the need for further study of the neurophysiology of MIAs and their pathogenetic role in endogenous psychoses.

Metabolic fate of hallucinogenic NBOMes

DEFF Research Database (Denmark)

Leth-Petersen, Sebastian; Gabel-Jensen, Charlotte; Gillings, Nic

2016-01-01

2,5-dimethoxy-N-benzylphenethylamines (NBOMes) are very potent 5-HT2AR agonists. Illicit use of these psychedelic compounds has emerged in recent years, and several fatalities have been linked to their recreational use. In its [11C]-labelled form, one NBOMe (25B-NBOMe) was recently developed...

Measurement of 3,4-MDMA and related amines in diagnostic and forensic laboratories.

Science.gov (United States)

Skrinska, Victor A; Gock, Susan B

2005-01-01

The phenylalkylamine derivatives, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy, XTC, Adam), 3,4-methylenedioxyethamphetamine (MDEA, MDE, Eve), and 3,4-methylenedioxyamphetamine (MDA), are psychostimulants with hallucinogenic properties. MDA is also a metabolite of both MDMA and MDEA. These drugs are ring-substituted amphetamine derivatives that produce hallucinogenic, entactogenic ('love drug'), and stimulating effects. MDMA was initially developed as an appetite suppressant, however, its use as a therapeutic drug has been very limited. Because of its effects as a hallucinogenic psychostimulant with relatively low toxicity, it has emerged over the last two decades as a common recreational psychostimulant or 'club drug' at 'raves'. MDMA, MDEA, and MDA are often referred to as 'rave' or 'designer' drugs. They are produced in clandestine laboratories and have an increasing presence on the illicit drug market worldwide. Significant adverse health effects have been reported that include: serotonin neurotoxicity, severe psychiatric disorders, renal failure, malignant hyperthermia, hepatitis, rhabdomyolysis, and disseminated intravascular coagulation. A number of fatal outcomes associated with severe MDMA intoxication have been reported.

Stereoselective effects of MDMA on inhibition of monoamine uptake

International Nuclear Information System (INIS)

Steele, T.D.; Nichols, D.E.; Yim, G.K.W.

1986-01-01

The R(-)-isomers of hallucinogenic phenylisopropylamines are most active, whereas the S(+)-enantiomers of amphetamine (AMPH) and methylenedioxymethamphetamine (MDMA) are more potent centrally. To determine if MDMA exhibits stereoselective effects at the biochemical level that resemble either those of amphetamine or the potent hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM), the ability of the isomers of MDMA, AMPH and DOM to inhibit uptake of radiolabelled monoamines into synaptosomes was measured. AMPH was more potent than MDMA in inhibiting uptake of 3 H-norepinephrine (NE) into hypothalamic synaptosomes and 3 H-dopamine (DA) into striatal synaptosomes. The S(+)-isomer was more active in each case. MDMA was more potent than AMPH in inhibiting uptake of 3 H-serotonin (5-HT) into hippocampal synaptosomes and exhibited a high degree of stereoselectivity, in favor of the S(+)-isomer. DOM showed only minimal activity in inhibiting uptake of any monoamine (IC 50 > 10 -5 M). These results suggest that MDMA exhibits stereoselective effects similar to those of amphetamine on monoamine uptake inhibition, a parameter that is unrelated to the mechanism of action of the hallucinogen DOM

Reasons for recent marijuana use in relation to use of other illicit drugs among high school seniors in the United States.

Science.gov (United States)

Palamar, Joseph J; Griffin-Tomas, Marybec; Kamboukos, Dimitra

2015-01-01

Studies show that illicit cannabis (marijuana) use is related to use of other illicit drugs and that reasons for use are related to frequency of marijuana use. However, research is needed to examine whether specific reasons for marijuana use are associated with use of other illicit drugs. Data from recent marijuana-using high school seniors were examined from 12 cohorts of Monitoring the Future (Weighted n = 6481) to examine whether reasons for recent marijuana use are associated with use of eight other illicit drugs. Using "to experiment" decreased odds of reporting use of each drug and using to decrease effects of other drugs increased odds of reporting use of each drug. In multivariable models, using marijuana "to experiment" decreased the odds for reporting use of hallucinogens other than LSD and narcotics other than heroin. Using marijuana for "insight" increased the odds for use of hallucinogens other than LSD, and use due to "boredom" increased the odds for reporting use of powder cocaine and hallucinogens other than LSD. Using marijuana to increase effects of other drugs increased odds of reporting use of each of the eight drugs, and using it to decrease other drug effects increased odds of reporting use of crack, hallucinogens other than LSD, and amphetamine/stimulants. This study helped identify illicit marijuana users who are more likely to report use of other illicit drugs. Prevention efforts need to focus on students who report certain reasons for marijuana use as they may be at risk for use of other illicit drugs.

Ayahuasca, dimethyltryptamine, and psychosis: a systematic review of human studies.

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Dos Santos, Rafael G; Bouso, José Carlos; Hallak, Jaime E C

2017-04-01

Ayahuasca is a hallucinogen brew traditionally used for ritual and therapeutic purposes in Northwestern Amazon. It is rich in the tryptamine hallucinogens dimethyltryptamine (DMT), which acts as a serotonin 5-HT 2A agonist. This mechanism of action is similar to other compounds such as lysergic acid diethylamide (LSD) and psilocybin. The controlled use of LSD and psilocybin in experimental settings is associated with a low incidence of psychotic episodes, and population studies corroborate these findings. Both the controlled use of DMT in experimental settings and the use of ayahuasca in experimental and ritual settings are not usually associated with psychotic episodes, but little is known regarding ayahuasca or DMT use outside these controlled contexts. Thus, we performed a systematic review of the published case reports describing psychotic episodes associated with ayahuasca and DMT intake. We found three case series and two case reports describing psychotic episodes associated with ayahuasca intake, and three case reports describing psychotic episodes associated with DMT. Several reports describe subjects with a personal and possibly a family history of psychosis (including schizophrenia, schizophreniform disorders, psychotic mania, psychotic depression), nonpsychotic mania, or concomitant use of other drugs. However, some cases also described psychotic episodes in subjects without these previous characteristics. Overall, the incidence of such episodes appears to be rare in both the ritual and the recreational/noncontrolled settings. Performance of a psychiatric screening before administration of these drugs, and other hallucinogens, in controlled settings seems to significantly reduce the possibility of adverse reactions with psychotic symptomatology. Individuals with a personal or family history of any psychotic illness or nonpsychotic mania should avoid hallucinogen intake.

Developments in harmine pharmacology--implications for ayahuasca use and drug-dependence treatment.

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Brierley, Daniel I; Davidson, Colin

2012-12-03

Ayahuasca is a hallucinogenic botanical mixture originating in the Amazon area where it is used ritually, but is now being taken globally. The 2 main constituents of ayahuasca are N,N-dimethyltryptamine (DMT), a hallucinogen, and harmine, a monoamine oxidase inhibitor (MAOI) which attenuates the breakdown of DMT, which would otherwise be broken down very quickly after oral consumption. Recent developments in ayahuasca use include the sale of these compounds on the internet and the substitution of related botanical (anahuasca) or synthetic (pharmahuasca) compounds to achieve the same desired hallucinogenic effects. One intriguing result of ayahuasca use appears to be improved mental health and a reduction in recidivism to alternate (alcohol, cocaine) drug use. In this review we discuss the pharmacology of ayahuasca, with a focus on harmine, and suggest pharmacological mechanisms for the putative reduction in recidivism to alcohol and cocaine misuse. These pharmacological mechanisms include MAOI, effects at 5-HT(2A) and imidazoline receptors and inhibition of dual-specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A) and the dopamine transporter. We also speculate on the therapeutic potential of harmine in other CNS conditions. Copyright © 2012 Elsevier Inc. All rights reserved.

Acute Intoxication following Dimethyltryptamine Ingestion

Science.gov (United States)

Higgs, Kristan V.; Wiegand, Timothy J.; Gorodetsky, Rachel M.

2018-01-01

Ayahuasca is a hallucinogenic tea that is most commonly comprised of the vine Banisteriopsis caapi alone or in combination with other plants such as Psychotria viridis. This concoction results in an orally active form of dimethyltryptamine (DMT), a hallucinogenic amine. Despite use in South America as a medicinal agent and component in religious ceremonies, interest in its recreational use and spiritual effects has led to increased use in the United States. We describe a unique case following ingestion of ayahuasca tea in a patient with history of schizophrenia resulting in personal injury and property damage. A review of ayahuasca toxicity and evaluation of serious adverse effects is also presented. PMID:29682363

Serotonergic and dopaminergic distinctions in the behavioral pharmacology of (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD).

Science.gov (United States)

Schindler, Emmanuelle A D; Dave, Kuldip D; Smolock, Elaine M; Aloyo, Vincent J; Harvey, John A

2012-03-01

After decades of social stigma, hallucinogens have reappeared in the clinical literature demonstrating unique benefits in medicine. The precise behavioral pharmacology of these compounds remains unclear, however. Two commonly studied hallucinogens, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD), were investigated both in vivo and in vitro to determine the pharmacology of their behavioral effects in an animal model. Rabbits were administered DOI or LSD and observed for head bob behavior after chronic drug treatment or after pretreatment with antagonist ligands. The receptor binding characteristics of DOI and LSD were studied in vitro in frontocortical homogenates from naïve rabbits or ex vivo in animals receiving an acute drug injection. Both DOI- and LSD-elicited head bobs required serotonin(2A) (5-HT(2A)) and dopamine(1) (D(1)) receptor activation. Serotonin(2B/2C) receptors were not implicated in these behaviors. In vitro studies demonstrated that LSD and the 5-HT(2A/2C) receptor antagonist, ritanserin, bound frontocortical 5-HT(2A) receptors in a pseudo-irreversible manner. In contrast, DOI and the 5-HT(2A/2C) receptor antagonist, ketanserin, bound reversibly. These binding properties were reflected in ex vivo binding studies. The two hallucinogens also differed in that LSD showed modest D(1) receptor binding affinity whereas DOI had negligible binding affinity at this receptor. Although DOI and LSD differed in their receptor binding properties, activation of 5-HT(2A) and D(1) receptors was a common mechanism for eliciting head bob behavior. These findings implicate these two receptors in the mechanism of action of hallucinogens. Copyright © 2011 Elsevier Inc. All rights reserved.

75 FR 37463 - Dispensing of Controlled Substances to Residents at Long Term Care Facilities

Science.gov (United States)

2010-06-29

... psychological and physical dependence; these include opioids, stimulants, depressants, hallucinogens, anabolic... Secretary delegated this responsibility to the Food and Drug Administration, which set forth the definition...

14 CFR 67.207 - Mental.

Science.gov (United States)

2010-01-01

... sympathomimetics; hallucinogens; phencyclidine or similarly acting arylcyclohexylamines; cannabis; inhalants; and... person is dependent on a substance, other than tobacco or ordinary xanthine-containing (e.g., caffeine...

14 CFR 67.107 - Mental.

Science.gov (United States)

2010-01-01

... sympathomimetics; hallucinogens; phencyclidine or similarly acting arylcyclohexylamines; cannabis; inhalants; and... person is dependent on a substance, other than tobacco or ordinary xanthine-containing (e.g., caffeine...

14 CFR 67.307 - Mental.

Science.gov (United States)

2010-01-01

... sympathomimetics; hallucinogens; phencyclidine or similarly acting arylcyclohexylamines; cannabis; inhalants; and... person is dependent on a substance, other than tobacco or ordinary xanthine-containing (e.g., caffeine...

Psilocybin--summary of knowledge and new perspectives.

Science.gov (United States)

Tylš, Filip; Páleníček, Tomáš; Horáček, Jiří

2014-03-01

Psilocybin, a psychoactive alkaloid contained in hallucinogenic mushrooms, is nowadays given a lot of attention in the scientific community as a research tool for modeling psychosis as well as due to its potential therapeutic effects. However, it is also a very popular and frequently abused natural hallucinogen. This review summarizes all the past and recent knowledge on psilocybin. It briefly deals with its history, discusses the pharmacokinetics and pharmacodynamics, and compares its action in humans and animals. It attempts to describe the mechanism of psychedelic effects and objectify its action using modern imaging and psychometric methods. Finally, it describes its therapeutic and abuse potential. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Acute Intoxication following Dimethyltryptamine Ingestion

Directory of Open Access Journals (Sweden)

Matthew H. Bilhimer

2018-01-01

Full Text Available Ayahuasca is a hallucinogenic tea that is most commonly comprised of the vine Banisteriopsis caapi alone or in combination with other plants such as Psychotria viridis. This concoction results in an orally active form of dimethyltryptamine (DMT, a hallucinogenic amine. Despite use in South America as a medicinal agent and component in religious ceremonies, interest in its recreational use and spiritual effects has led to increased use in the United States. We describe a unique case following ingestion of ayahuasca tea in a patient with history of schizophrenia resulting in personal injury and property damage. A review of ayahuasca toxicity and evaluation of serious adverse effects is also presented.

Drugs + HIV, Learn the Link

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Full Text Available ... RSS Menu Home Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/ ...

Agitation

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... Certain forms of heart, lung, liver, or kidney disease Intoxication or withdrawal from drugs of abuse (such as cocaine, marijuana, hallucinogens, PCP, or opiates) Hospitalization (older adults often ...

National Institute on Drug Abuse

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Epidemiologie užívání halucinogenních drog v České republice

Czech Academy of Sciences Publication Activity Database

Miovský, Michal; Miovská, L.

2005-01-01

Roč. 5, č. 2 (2005), s. 165-175 ISSN 1213-3841 Institutional research plan: CEZ:AV0Z70250504 Keywords : hallucinogenic substances * epidemiological indicators * drug use Subject RIV: AN - Psychology

Receptor May Underlie Gender Differences in Response to Smoking Cessation Therapy

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Benzodiazepines and Opioid

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Marijuana: Facts Parents Need to Know

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DrugFacts: Electronic Cigarettes (e-Cigarettes)

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Which Classes of Prescription Drugs Are Commonly Misused?

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Opioid Summaries by State

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DrugFacts: Heroin

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Drug and Alcohol Use -- A Significant Risk Factor for HIV

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Seeking Drug Abuse Treatment: Know What to Ask

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NIDA Notes

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Drugs, Brains, and Behavior: The Science of Addiction

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Dramatic Increases in Maternal Opioid Use and Neonatal Abstinence Syndrome

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Opioid Overdose Reversal with Naloxone (Narcan, Evzio)

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Substance Use in Women and Men

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Buprenorphine During Pregnancy Reduces Neonate Distress

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Treat Jail Detainees' Drug Abuse to Lower HIV Transmission

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Stress-Induced Enzyme Compounds Methamphetamine Neurotoxicity

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Treatment Approaches for Drug Addiction

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Regular Marijuana Users May Have Impaired Brain Reward Centers

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Marijuana

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Fentanyl

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Teens and E-cigarettes

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Cocaine

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Cigarettes and Other Tobacco Products

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Although Relatively Few, "Doctor Shoppers" Skew Opioid Prescribing

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Inhalants

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An Ambitious Research Plan to Help Solve the Opioid Crisis: HEAL Initiative

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Heroin: Statistics and Trends

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NIH HEAL Initiative

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Opioid Overdose Crisis

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Nationwide Trends

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Gene Variants Reduce Opioid Risks

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Drugged Driving

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Drug Use and Viral Infections (HIV, Hepatitis)

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Methamphetamine

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Club Drugs

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Prenatal Methamphetamine Exposure Linked with Problems

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Abuse of Prescription (Rx) Drugs Affects Young Adults Most

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What to Do If Your Adult Friend or Loved One Has a Problem with Drugs

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Fentanyl and Other Synthetic Opioids Drug Overdose Deaths

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Comorbidity

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Marijuana: Facts for Teens

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College-Age & Young Adults

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Drug Facts: Anabolic Steroids

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What to Do If You Have a Problem with Drugs: For Teens and Young Adults

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Substance Use in Women

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Expanded HIV Screening Projected to Decrease Spread of the Virus

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Among High School Seniors, Driving After Marijuana Use Surpasses Drunk Driving

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Methamphetamine Alters Brain Structures, Impairs Mental Flexibility

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Synthetic Cathinones ("Bath Salts")

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Health Consequences of Drug Misuse

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Is Marijuana Medicine?

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Understanding Drug Use and Addiction

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HIV Infection Accelerates Hepatitis C-Related Liver Fibrosis

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Teens Mix Prescription Opioids with Other Substances

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Family Checkup: Positive Parenting Prevents Drug Abuse

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75 FR 61613 - Role of Authorized Agents in Communicating Controlled Substance Prescriptions to Pharmacies

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2010-10-06

... dependence; these include substances classified as opioids, stimulants, depressants, hallucinogens, anabolic... substances in an emergency. 21 U.S.C. 829(a). An emergency for this purpose is defined by the Food and Drug...

[Non-delirious toxic psychoses in children (author's transl)].

Science.gov (United States)

Eggers, C

1975-01-01

There is an increasing occurrence of drug-intoxications in infancy, thus psychopathological changes due to intoxication also occur more frequently in children. 6 children were described with cases of acute and reversible toxic psychoses whose--mainly visual--hallucinations together with conditions of excitation and hyperactivity were the most striking features of the psychopathological picture; in contrast to the more frequent delirious confusion (delirium) disturbances of consciousness and orientation were missing. The phenomenological characteristics of halucinosis in children-a condition so far not specified in the case of infants and children-have been elaborated with regard to other psychotic phenomena during infancy and adult age. Relevant neurophysiological and psychodevelopmental findings lead to the following four theorems: 1. Drugs with hallucinotic effects facilitate the occurrence of "internal" pictures independent of external perceptions which are described phenomenologically as hallucinations. This theory is based on the fact that hallucinogenic drugs intensify the electrical potentials which are evoked by optic stimulation in the visual area, while an intracortical impulse propagation is inhibited. 2. A change in emotion either caused by situation or by exogenous or endogenous factors facilitates the development of hallucinations, especially if emotions dominate to such a degree that rational control of reality is being suppressed. Since hallucinogenic drugs exert their effects not only on the sensory system but also on brain structures which influence directly or indirectly emotional functions, hallucinations might also be evoked via this mechanism. 3. Brain stem has-apart from its importance in emotional processes-a filter effect and a controlling function of sensoric stimuli originating in the periphery. Hallucinogenic drugs can influence this screening function and have a disinhibitory effect which cause an inundation of the brain cortex by

Substance use disorder

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... Problem or risky use. The user loses any motivation; does not care about school and work; has ... through shared needles Loss of job Problems with memory and concentration, for example, hallucinogen use, including marijuana ( ...

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Full Text Available ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

Fluorescent Random Amplified Microsatellites (F-RAMS) analysis of mushrooms as a forensic investigative tool

Czech Academy of Sciences Publication Activity Database

Kallifatidis, B.; Borovička, Jan; Stránská, J.; Drábek, J.; Mills, D. K.

2014-01-01

Roč. 9, MAR (2014), s. 25-32 ISSN 1872-4973 Institutional support: RVO:61389005 Keywords : random amplified microsatellites * hallucinogenic mashrooms * DNA profiling Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.604, year: 2014

Drug abuse first aid

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... use of these drugs is a form of drug abuse. Medicines that are for treating a health problem ... about local resources. Alternative Names Overdose from drugs; Drug abuse first aid References Myck MB. Hallucinogens and drugs ...

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Full Text Available ... Drugs of Abuse Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens ... Substance Use and SUDs in LGBT Populations Treatment Trends & Statistics Women and Drugs Publications Search Publications Orderable ...

High School and Youth Trends

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... illicit drugs showed five-year declines, such as synthetic marijuana, hallucinogens other than LSD, and over-the-counter ... 8th graders who think that occasional use of synthetic marijuana or over-the-counter cough and cold medications ...

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Full Text Available ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... AIDS (acquired immune deficiency syndrome). AIDS is a disease of the immune system for which there is ...

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Full Text Available ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... is partly due to the addictive and intoxicating effects of many drugs, which can alter judgment and ...

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Full Text Available ... Commonly Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana ... person at risk for getting HIV. Drug and alcohol intoxication affect judgment and can lead to unsafe ...

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Full Text Available ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... Opioid Overdose Reversal with Naloxone (Narcan, Evzio) Pain Prevention Recovery Substance Use and SUDs in LGBT Populations ...

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Full Text Available ... Abused Drugs Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA ( ... materials include print PSAs, Web banner PSAs, promo cards, and posters. Videos The campaign includes the "After ...

Phylogenetic and chemical studies in the potential psychotropic species complex of .i.Psilocybe atrobrunnea ./i. with taxonomic and nomenclatural notes

Czech Academy of Sciences Publication Activity Database

Borovička, Jan; Oborník, Miroslav; Stříbrný, J.; Noordeloos, M. E.; Parra Sánchez, L. A.; Gryndler, Milan

2015-01-01

Roč. 34, June (2015), s. 1-9 ISSN 0031-5850 Institutional support: RVO:67985831 ; RVO:60077344 ; RVO:61388971 Keywords : Hallucinogenic fungi * Leratiomyces * phylogeny * psilocin * psilocybin * Strophariaceae Subject RIV: EF - Botanics Impact factor: 5.725, year: 2015

Drugs + HIV, Learn the Link

Medline Plus

Full Text Available ... Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) ... transmitted between users. Other infections, such as hepatitis C, can also be spread this way. Hepatitis C ...

Psilocybin for treating substance use disorders?

NARCIS (Netherlands)

Veen, B.T. de; Schellekens, A.F.A.; Verheij, M.M.M.; Homberg, J.R.

2017-01-01

INTRODUCTION: Evidence based treatment for Substance use disorders (SUD) includes psychotherapy and pharmacotherapy. However, these are only partially effective. Hallucinogens, such as psilocybin, may represent potential new treatment options for SUD. This review provides a summary of (human)

Drugs + HIV, Learn the Link

Medline Plus

Full Text Available ... Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) ... University Print Media: People en Español LATeen Viva La Fiesta! Trace Washington Times USA Today Companies: Washington ...

Advantages of analyzing postmortem brain samples in routine forensic drug screening—case series of three non-natural deaths tested positive for lysergic acid diethylamide (LSD)

DEFF Research Database (Denmark)

Mardal, Marie; Johansen, Sys Stybe; Thomsen, Ragnar

2017-01-01

Three case reports are presented, including autopsy findings and toxicological screening results, which were tested positive for the potent hallucinogenic drug lysergic acid diethylamide (LSD). LSD and its main metabolites were quantified in brain tissue and femoral blood, and furthermore hematoma...

Medical Readings on Drug Abuse.

Science.gov (United States)

Byrd, Oliver E.

Summaries are presented of over 150 articles in the recent medical and psychiatric literature. Topics covered are: effects of drugs, tobacco, alcohol, drugs used in medicine, vapor sniffing, marijuana, barbiturates, tranquilizers, amphetamines, methamphetamine, lysergic acid diethylamide, other hallucinogens, heroin and the opiates, psychiatric…

Effects of ayahuasca on the development of ethanol-induced behavioral sensitization and on a post-sensitization treatment in mice.

Science.gov (United States)

Oliveira-Lima, A J; Santos, R; Hollais, A W; Gerardi-Junior, C A; Baldaia, M A; Wuo-Silva, R; Yokoyama, T S; Costa, J L; Malpezzi-Marinho, E L A; Ribeiro-Barbosa, P C; Berro, L F; Frussa-Filho, R; Marinho, E A V

2015-04-01

Hallucinogenic drugs were used to treat alcoholic patients in the past, and recent developments in the study of hallucinogens led to a renewal of interest regarding the application of these drugs in the treatment of addiction. In this scenario, accumulating evidence suggests that the hallucinogenic brew ayahuasca (Aya) may have therapeutic effects on substance abuse problems. We investigated the effects of Aya on spontaneous locomotor activity and ethanol(Eth)-induced hyperlocomotion and subsequent locomotor sensitization by a two-injection protocol. Additionally, we tested the effect of Aya on an 8-day counter-sensitization protocol to modify sensitized responses induced by a repeated treatment with Eth (1.8g/kg) for 8 alternate days. Aya showed high sensitivity in preventing the development of Eth-induced behavioral sensitization, attenuating it at all doses (30, 100, 200, 300 or 500 mg/kg) without modifying spontaneous locomotor activity. At the highest doses (300 and 500 mg/kg), Aya also showed selectivity to both acute and sensitized Eth responses. Finally, a counter-sensitization strategy with 100 or 300 mg/kg of Aya for 8 consecutive days after the establishment of Eth-induced behavioral sensitization was effective in blocking its subsequent expression on an Eth challenge. We demonstrated that Aya not only inhibits early behaviors associated with the initiation and development of Eth addiction, but also showed effectiveness in reversing long-term drug effects expression, inhibiting the reinstatement of Eth-induced behavioral sensitization when administered in the Eth-associated environment. Copyright © 2015 Elsevier Inc. All rights reserved.

75 FR 10671 - Changes to and Consolidation of DEA Mailing Addresses

Science.gov (United States)

2010-03-09

... include substances classified as opioids, stimulants, depressants, hallucinogens, anabolic steroids, and... specified in the request. The Administration shall review the letter and forward it to the Food and Drug Administration together with the Administration comments. The Food and Drug Administration shall approve or deny...

Development of Computer-Supported Assessment and Treatment Consultation for Emotional Crises (CATCEC) for a Submarine Environment.

Science.gov (United States)

1986-03-01

SCHIZOPHRENIC DISORDER Amphetamine Delusional Disorder PARANOID DISORDER Cannabis Delusional Disorder Hallucinogen Delusional Disorder BRIEF REACTIVE...Intoxication Borderline Personality Disorder Cocaine Intoxication Histrionic Personality Disorder Caffeine Intoxication Narcissistic Personality Disorder... Cannabis Intoxication Dependent Personality Disorder ON, Inhalant Intoxication Schizoid Personality Disorder Minor Tranquilizer Intoxication Compulsive

48 CFR 245.7310-5 - Controlled substances.

Science.gov (United States)

2010-10-01

... (Bureau of Narcotics and Dangerous Drugs) to buy controlled substances as a medical practitioner, dealer... hallucinogenic drugs, shall be subject to the following special conditions: (a) Controlled Substances. Bids will... represents and warrants that it is registered under The Comprehensive Drug Abuse Prevention and Control Act...

Drug Enforcement Administration.

Science.gov (United States)

Department of Justice, Washington, DC.

This fact sheet contains information relating to drug abuse and abusers; drug traffic legislation; law enforcement; and descriptions of commonly used narcotics, stimulants, depressants, and hallucinogens. Also included is a short but explicit listing of audiovisual aids, an annotated bibliography, and drug identification pictures. The booklet…

Attributions for Abstinence from Illicit Drugs by University Students

Science.gov (United States)

Rosenberg, Harold; Baylen, Chelsea; Murray, Shanna; Phillips, Kristina; Tisak, Marie S.; Versland, Amelia; Pristas, Erica

2008-01-01

Aim: To assess college students' attributions for abstinence from alcohol and illicit drugs. Method: We recruited 125 undergraduates to rate the degree to which each of 41 listed reasons influenced their abstention from six specific substances (alcohol, MDMA/ecstasy, inhalants, cocaine, marijuana, and hallucinogens). Findings: Internal consistency…

Ayahuasca in adolescence: Qaualitative results.

Science.gov (United States)

de Rios, Marlene Dobkin; Grob, Charles S; Lopez, Enrique; da Silviera, Dartiu Xavier; Alonso, Luisa K; Doering-Silveira, Evelyn

2005-06-01

Qualitative research was conducted in Brazil among 28 ayahuasca-consuming adolescents members of the União do Vegetal Church, and 28 adolescents who never used ayahuasca. They were compared on a number of qualitative variables, including vignettes measuring moral and ethical concerns. Psychocultural studies utilizing co-occurences of variables in the realm of qualitative studies are useful in understanding and complementing quantitative studies also conducted among this population. Qualitative data show that the teens in the União do Vegetal religion appear to be healthy, thoughtful, considerate and bonded to their families and religious peers. This study examines the modern use of a powerful hallucinogenic compound within a legal religious context, and the youth who participated in these ayahuasca religious ceremonies (usually with parents and other family members) appeared not to differ from their nonayahuasca-using peers. This study helps to elucidate the full range of effects of plant hallucinogenic use within a socially-sanctioned, elder-facilitated and structured religious context.

Treatment of heroin dependence with ibogaine

NARCIS (Netherlands)

Schellekens, A.F.A.; Oosteren, A.A. van; Knuijver, T.; Verkes, R.J.; Belgers, M.

2016-01-01

Background: The use of the hallucinogen ibogaine as an anti-addiction agent has been described in several case reports, dating back to the eighties. The anti-addiction properties of ibogaine have been confirmed in a large body of animal work. Ibogaine has been shown to be effective in reducing

Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain.

Science.gov (United States)

Buckholtz, N S; Zhou, D F; Freedman, D X; Potter, W Z

1990-04-01

A dosage regimen of lysergic acid diethylamide (LSD) that reliably produces behavioral tolerance in rats was evaluated for effects on neurotransmitter receptor binding in rat brain using a variety of radioligands selective for amine receptor subtypes. Daily administration of LSD [130 micrograms/kg (0.27 mumol/kg) intraperitoneally (IP)] for 5 days produced a decrease in serotonin2 (5-hydroxytryptamine2, 5-HT2) binding in cortex (measured 24 hours after the last drug administration) but did not affect binding to other receptor systems (5-HT1A, 5-HT1B, beta-adrenergic, alpha 1- or alpha 2-adrenergic, D2-dopaminergic) or to a recognition site for 5-HT uptake. The decrease was evident within 3 days of LSD administration but was not demonstrable after the first LSD dose. Following 5 days of LSD administration the decrease was still present 48 hours, but not 96 hours, after the last administration. The indole hallucinogen psilocybin [1.0 mg/kg (3.5 mumol/kg) for 8 days] also produced a significant decrease in 5HT2 binding, but neither the nonhallucinogenic analog bromo-LSD [1.3 mg/kg (2.4 mumol/kg) for 5 days] nor mescaline [10 mg/kg (40.3 mumol/kg) for 5 or 10 days] affected 5-HT2 binding. These observations suggest that LSD and other indole hallucinogens may act as 5-HT2 agonists at postsynaptic 5-HT2 receptors. Decreased 5-HT2 binding strikingly parallels the development and loss of behavioral tolerance seen with repeated LSD administration, but the decreased binding per se cannot explain the gamut of behavioral tolerance and cross-tolerance phenomena among the indole and phenylethylamine hallucinogens.

The ethnobotany of psychoactive plant use: a phylogenetic perspective

Directory of Open Access Journals (Sweden)

Nashmiah Aid Alrashedy

2016-10-01

Full Text Available Psychoactive plants contain chemicals that presumably evolved as allelochemicals but target certain neuronal receptors when consumed by humans, altering perception, emotion and cognition. These plants have been used since ancient times as medicines and in the context of religious rituals for their various psychoactive effects (e.g., as hallucinogens, stimulants, sedatives. The ubiquity of psychoactive plants in various cultures motivates investigation of the commonalities among these plants, in which a phylogenetic framework may be insightful. A phylogeny of culturally diverse psychoactive plant taxa was constructed with their psychotropic effects and affected neurotransmitter systems mapped on the phylogeny. The phylogenetic distribution shows multiple evolutionary origins of psychoactive families. The plant families Myristicaceae (e.g., nutmeg, Papaveraceae (opium poppy, Cactaceae (peyote, Convolvulaceae (morning glory, Solanaceae (tobacco, Lamiaceae (mints, Apocynaceae (dogbane have a disproportionate number of psychoactive genera with various indigenous groups using geographically disparate members of these plant families for the same psychoactive effect, an example of cultural convergence. Pharmacological traits related to hallucinogenic and sedative potential are phylogenetically conserved within families. Unrelated families that exert similar psychoactive effects also modulate similar neurotransmitter systems (i.e., mechanistic convergence. However, pharmacological mechanisms for stimulant effects were varied even within families suggesting that stimulant chemicals may be more evolutionarily labile than those associated with hallucinogenic and sedative effects. Chemically similar psychoactive chemicals may also exist in phylogenetically unrelated lineages, suggesting convergent evolution or differential gene regulation of a common metabolic pathway. Our study has shown that phylogenetic analysis of traditionally used psychoactive plants

Interactions between lysergic acid diethylamide and dopamine-sensitive adenylate cyclase systems in rat brain.

Science.gov (United States)

Hungen, K V; Roberts, S; Hill, D F

1975-08-22

Investigations were carried out on the interactions of the hallucinogenic drug, D-lysergic acid diethylamide (D-LSD), and other serotonin antagonists with catecholamine-sensitive adenylate cyclase systems in cell-free preparations from different regions of rat brain. In equimolar concentration, D-LSD, 2-brono-D-lysergic acid diethylamide (BOL), or methysergide (UML) strongly blocked maximal stimulation of adenylate cyclase activity by either norepinephrine or dopamine in particulate preparations from cerebral cortices of young adult rats. D-LSD also eliminated the stimulation of adenylate cyclase activity of equimolar concentrations of norepinephrine or dopamine in particulate preparations from rat hippocampus. The effects of this hallucinogenic agent on adenylate cyclase activity were most striking in particulate preparations from corpus striatum. Thus, in 10 muM concentration, D-LSD not only completely eradicated the response to 10 muM dopamine in these preparations but also consistently stimulated adenylate cyclase activity. L-LSD (80 muM) was without effect. Significant activation of striatal adenylate cyclase was produced by 0.1 muM D-LSD. Activation of striatal adenylate cyclase of either D-LSD or dopamine was strongly blocked by the dopamine-blocking agents trifluoperazine, thioridazine, chlorpromazine, and haloperidol. The stimulatory effects of D-LSD and dopamine were also inhibited by the serotonin-blocking agents, BOL, 1-methyl-D-lysergic acid diethylamide (MLD), and cyproheptadine, but not by the beta-adrenergic-blocking agent, propranolol. However, these serotonin antagonists by themselves were incapable of stimulating adenylate cyclase activity in the striatal preparations. Several other hallucinogens, which were structurally related to serotonin, were also inactive in this regard, e.g., mescaline, N,N-dimethyltryptamine, psilocin and bufotenine. Serotonin itself produced a small stimulation of adenylate cyclase activity in striatal preparations and

Mind Over Matter: The Brain's Response to Drugs. Teacher's Guide.

Science.gov (United States)

National Inst. on Drug Abuse (DHHS/PHS), Rockville, MD.

This teacher's guide aims to develop an understanding among students grades 5 through 9 of the physical reality of drug use. Contents include: (1) "Brain Anatomy"; (2) "Nerve Cells and Neurotransmission"; (3) "Effects of Drugs on the Brain"; (4) "Marijuana"; (5) "Opiates"; (6) "Inhalants"; (7) "Hallucinogens"; (8) "Steroids"; (9) "Stimulants";…

Governor's Conference on Drug Dependence and Abuse. An Occasional Paper of the Honors College.

Science.gov (United States)

Milliken, William G.; And Others

1970-01-01

Following Governor Milliken's address, Dr. Dana Farnsworth defines the problem in terms of who's involved, to what extent, and with which drugs. His presentation focuses primarily on the motives of affluent young people who experiment with or become dependent upon hallucinogens, marihuana and amphetamines. He deals extensively with the drastically…

31 CFR 605.1 - Conduct on Bureau of Engraving and Printing property.

Science.gov (United States)

2010-07-01

... influence of intoxicating beverages, narcotics, hallucinogenic or dangerous drugs, or marijuana, or the consumption of such beverages or the use of such drugs or marijuana in or on the property is prohibited... such directives shall have the same force and effect as if made a part hereof. (m) Weapons and...

Drugs, Alcohol & Pregnancy.

Science.gov (United States)

Dye, Christina

Expectant parents are introduced to the effects of a variety of drugs on the unborn baby. Material is divided into seven sections. Section 1 deals with the most frequently used recreational drugs, including alcohol, marijuana, narcotics, depressants, stimulants, inhalants, and hallucinogens. Sections 2 and 3 focus on the effects of prescription…

LSD Now: 1973

Science.gov (United States)

Chunko, John A.

1973-01-01

LSD NOW is a nationwide, statistical survey and analysis of hallucinogenic drug use by individuals presently in formal educational surroundings. Analysis, concentrating on the extent and rationale related to the use of such drugs, now offers a deeper and more meaningful understanding of a particular facet of the drug culture. This understanding…

[Statement on Recent Research on LSD, Marihuana, and Other Dangerous Drugs.

Science.gov (United States)

Yolles, Stanley F.

The National Institute of Mental Health is continuing support of several studies designed to measure trends in the use of hallucinogens. Indications are that the evidence for persisting psychological and birth defect damage from chronic LSD use is minimal. Though they are a continuing problem, admissions to psychiatric units of persons with "bad…

Highlights from Drug Use Among American High School Students 1975-1977.

Science.gov (United States)

Johnston, Lloyd D.; And Others

The current prevalence of drug use among American high school seniors and the trends in use since 1975 are the two major topics treated. Also reported are prevailing attitudes and beliefs among seniors concerning various types of drug use. Eleven separate classes of drugs are distinguished: marihuana (including hashish), inhalants, hallucinogens,…

Illicit Drug Use in a Community-Based Sample of Heterosexually Identified Emerging Adults

Science.gov (United States)

Halkitis, Perry N.; Manasse, Ashley N.; McCready, Karen C.

2010-01-01

In this study we assess lifetime and recent drug use patterns among 261 heterosexually identified 18- to 25-year-olds through brief street intercept surveys conducted in New York City. Marijuana, hallucinogens, powder cocaine, and ecstasy were the most frequently reported drugs for both lifetime and recent use. Findings further suggest significant…

Associations between University Students' Reported Reasons for Abstinence from Illicit Substances and Type of Drug

Science.gov (United States)

Rosenberg, Harold; Bonar, Erin E.; Pavlick, Michelle; Jones, Lance D.; Hoffmann, Erica; Murray, Shanna; Faigin, Carol Ann; Cabral, Kyle; Baylen, Chelsea

2012-01-01

We recruited 211 undergraduates to rate the degree to which each of 34 listed reasons for not taking drugs had influenced their abstinence from MDMA/ecstasy, cocaine, marijuana, and hallucinogens. Participants rated reasons such as personal and family medical histories, religion, and physiological consequences of drug use as having little or no…

Research on acute toxicity and the behavioral effects of methanolic extract from psilocybin mushrooms and psilocin in mice.

Science.gov (United States)

Zhuk, Olga; Jasicka-Misiak, Izabela; Poliwoda, Anna; Kazakova, Anastasia; Godovan, Vladlena V; Halama, Marek; Wieczorek, Piotr P

2015-03-27

The pharmacological activities and acute toxicity of the psilocin (PC) and dried residues of the crude extracts of psychotropic mushrooms were investigated in mice. The hallucinogenic substances were effectively isolated, by using methanol, from the species of Psilocybe semilanceata and Pholiotina cyanopus, that were collected in the north-east region of Poland. The chemical analysis of these extracts, which was performed by liquid chromatography with mass spectrometry detection (LC-MS), indicated the presence of psilocin and other hallucinogenic substances, including indolealkylamines and their phosphorylated analogues. When the pure psilocin or fungal extracts were used, slight differences in determined LD50 values were observed. However, the application of PC evoked the highest level of toxicity (293.07 mg/kg) compared to the activity of extracts from Ph. cyanopus and P. semilanceata, where the level of LD50 was 316.87 mg/kg and 324.37 mg/kg, respectively. Furthermore, the behavioral test, which considered the head-twitching response (HTR), was used to assess the effects of the studied psychotropic factors on the serotonergic system. Both, the fungal extracts and psilocin evoked characteristic serotoninergic effects depending on the dose administered to mice, acting as an agonist/partial agonist on the serotonergic system. A dose of 200 mg/kg 5-hydroxytryptophan (5-HTP) induced spontaneous head-twitching in mice (100% effect), as a result of the formation of 5-hydroxytryptamine (5-HT) in the brain. Compared to the activity of 5-HTP, the intraperitoneal administration of 1mg/kg of psilocin or hallucinogenic extracts of studied mushrooms (Ph. cyanopus and P. semilanceata) reduced the number of head-twitch responses of about 46% and 30%, respectively. In contrast, the administration of PC exhibited a reduction of about 60% in HTR numbers.

Research on Acute Toxicity and the Behavioral Effects of Methanolic Extract from Psilocybin Mushrooms and Psilocin in Mice

Directory of Open Access Journals (Sweden)

Olga Zhuk

2015-03-01

Full Text Available The pharmacological activities and acute toxicity of the psilocin (PC and dried residues of the crude extracts of psychotropic mushrooms were investigated in mice. The hallucinogenic substances were effectively isolated, by using methanol, from the species of Psilocybe semilanceata and Pholiotina cyanopus, that were collected in the north-east region of Poland. The chemical analysis of these extracts, which was performed by liquid chromatography with mass spectrometry detection (LC-MS, indicated the presence of psilocin and other hallucinogenic substances, including indolealkylamines and their phosphorylated analogues. When the pure psilocin or fungal extracts were used, slight differences in determined LD50 values were observed. However, the application of PC evoked the highest level of toxicity (293.07 mg/kg compared to the activity of extracts from Ph. cyanopus and P. semilanceata, where the level of LD50 was 316.87 mg/kg and 324.37 mg/kg, respectively. Furthermore, the behavioral test, which considered the head-twitching response (HTR, was used to assess the effects of the studied psychotropic factors on the serotonergic system. Both, the fungal extracts and psilocin evoked characteristic serotoninergic effects depending on the dose administered to mice, acting as an agonist/partial agonist on the serotonergic system. A dose of 200 mg/kg 5-hydroxytryptophan (5-HTP induced spontaneous head-twitching in mice (100% effect, as a result of the formation of 5-hydroxytryptamine (5-HT in the brain. Compared to the activity of 5-HTP, the intraperitoneal administration of 1mg/kg of psilocin or hallucinogenic extracts of studied mushrooms (Ph. cyanopus and P. semilanceata reduced the number of head-twitch responses of about 46% and 30%, respectively. In contrast, the administration of PC exhibited a reduction of about 60% in HTR numbers.

Illegal substance use among Italian high school students: trends over 11 years (1999-2009.

Directory of Open Access Journals (Sweden)

Sabrina Molinaro

Full Text Available PURPOSE: To monitor changes in habits in drug use among Italian high school students. METHODS: Cross-sectional European School Survey Project on Alcohol and Other Drugs (ESPAD carried out in Italy annually for 11 years (1999-2009 with representative samples of youth attending high school. The sample size considered ranges from 15,752 to 41,365 students and response rate ranged from 85.5% to 98.6%. Data were analyzed to obtain measures of life-time prevalence (LT, use in the last year (LY, use in the last 30 days (LM, frequent use. Comparisons utilized difference in proportion tests. Tests for linear trends in proportion were performed using the Royston p trend test. RESULTS: When the time-averaged value was considered, cannabis (30% LT was the most, and heroin the least (2% frequently used, with cocaine (5%, hallucinogens (2% and stimulants (2% in between. A clear gender gap is evident for all drugs, more obvious for hallucinogens (average M/F LY prevalence ratio 2, range 1.7-2.4, p<0.05, less for cannabis (average M/F LY prevalence ratio 1.3, range 1.2-1.5, p<0.05. Data shows a change in trend between 2005 and 2008; in 2006 the trend for cannabis use and availability dropped and the price rose, while from 2005 cocaine and stimulant use prevalence showed a substantial increase and the price went down. After 2008 use of all substances seems to have decreased. CONCLUSIONS: Drug use is widespread among students in Italy, with cannabis being the most and heroin the least prevalent. Girls are less vulnerable than boys to illegal drug use. In recent years, a decrease in heroin use is overbalanced by a marked rise in hallucinogen and stimulant use.

The Use and Abuse of Psychoactive substances by Students of A ...

African Journals Online (AJOL)

Conclusion: It is pertinent to mention the observation of the absence of the use of Amphetamine, Cocaine, Opiodis and Hallucinogens in our study population. However, the need for immediate action to check this level of drug is highlighted and the need for health education in all schools is stressed. Key words: Drug abuse, ...

What Will Happen if . . . A Programmed Instruction Course on Drugs and Their Effects.

Science.gov (United States)

Health Services and Mental Health Administration (DHEW), Bethesda, MD.

Developed by the National Institute of Mental Health, this booklet offers a programed instruction course on drugs and their effects. The purpose of the text is to learn about specific drugs which are currently being used and abused by a large group of people in our society. Narcotics, stimulants, depressants, hallucinogens, and marihuana are…

[Ritual use of Anadenanthera seeds among South America natives].

Science.gov (United States)

Carod-Artal, F J; Vázquez Cabrera, C B

2007-01-01

Several South-American native societies snuff psychoactive seeds in magic-religious rituals since ancient times. To describe archeological, historical and ethnographical evidences regarding the ritual use of vilca or yopo (Anadenanthera sp). Anadenanthera seeds were used in South America 3,000 years ago. Archeological studies found vilca seeds in funerary tombs from 1,000 BC in the north of Chile and Argentina; ceramics and snuff tubes were found in San Pedro de Atacama archeological sites from the same data, and in Tiwanaku ceremonial center in Bolivian Altiplano. Today, Anadenanthera sp is used by several native groups in Orinoco basin, where is known as yopo, and in the Brazilian and Colombian Amazon. Hallucinogenic effect is due to the presence of methyl-tryptamine derivatives. Most snuff is prepared from the roasted and powdered seeds, vegetable ash and/or lime obtained from shells. Archeological and ethnographical data suggest that vilca was used and is still used by native shamans as a sacred seed in South America, due to its hallucinogenic effects.

The Association of Salvia divinorum and Psychotic Disorders: A Review of the Literature and Case Series.

Science.gov (United States)

El-Khoury, Joseph; Sahakian, Nayiri

2015-01-01

The association of substance abuse and psychotic disorders is of interest to clinicians, academics, and lawmakers. Commonly abused substances, such as cannabis, cocaine, amphetamines, and alcohol, have all been associated with substance-induced psychosis. Hallucinogens can induce desired psychedelic effects and undesirable psychomimetic reactions. These are usually transient and resolve once the duration of action is over. Sometimes, these effects persist, causing distress and requiring intervention. This article focuses on the hallucinogenic substance Salvia divinorum, the use of which has been observed, particularly among youth worldwide. We present background information based on a review of the literature and on our own clinical encounters, as highlighted by two original case reports. We hypothesize that consumption of Salvia divinorum could be associated with the development of psychotic disorders. We propose that clinicians routinely inquire about the use of Salvia in patients with substance use disorders or psychotic illnesses. More research is required to assess any relationship between Salvia divinorum and psychosis. Additionally, we advocate increased public and medical awareness of this substance and other emerging drugs of abuse.

78 FR 61991 - Schedules of Controlled Substances: Temporary Placement of Three Synthetic Phenethylamines Into...

Science.gov (United States)

2013-10-10

... 202 of the CSA, 21 U.S.C. 812, or if there is no exemption or approval in effect under section 505 of... the last 10 years for use in mapping and investigating the serotonin receptors in the mammalian brain..., and 25B-NBOMe are often purported to be Schedule I hallucinogens like lysergic acid diethylamide (LSD...

A Critical Review of the Drug/Performance Literature. Volume II.

Science.gov (United States)

1979-12-01

Cannabis Drug Tolerance Drugs and Stress Amphetamine Depressants Drug Users Ethanol Behavior Drug Abuse Drug Withdrawal Hallucinogens Cannabinoids Drug...Therapeutics Clin Tox Clinical Toxicology Couw Psychopharm Communications in Psychopharmacology Comp Psychiat Comprehensive Psychiatry Current Ther Res Current...European Journal of Toxicology Exp Neurol Experimental Neurology EEG Clin Neurophys EEG Clinical Neurophysiology EEG J EEG Journal Ger Med German Medicine

The International Nexus Between Drugs and Terror: Lessons in Conflict and Diplomacy

Science.gov (United States)

2010-12-01

opium, marijuana , coffee, coca, hallucinogens and many other drugs that predate history to keep themselves awake, lessen pain and increase virility...of the drugs that are mainly derived from natural plants such as cocaine, heroin and marijuana . The Convention on Psychotropic Substances of 1971...and 1972 amendment protocol of Single Convention, addressed the synthetic substances, creating provisions to regulate their trade, selling

Returning Home from Iraq and Afghanistan: Assessment of Readjustment Needs of Veterans, Service Members, and Their Families

Science.gov (United States)

2013-01-01

in the use of SPICE ( synthetic marijuana ) and bath salts ( synthetic methamphetamine). They worked with the base to get statistics on this and went...and Their Families 94 RETURNING HOME FROM IRAQ AND AFGHANISTAN marijuana and hashish, cocaine (including crack), heroin, hallucinogens, inhalants, and...personnel not on active duty. Drugs tested included amphetamines, cocaine, ecstasy, marijuana , MDA (methylenedioxyamphetamine), opioids, and

Preventing the Consequences of Alcohol Abuse: Identification of Soldiers at High Risk for Fatal and Serious Injuries

Science.gov (United States)

2007-01-01

comorbidity and head injury could have been an artifact of clinical protocols (e.g., toxicology screening when neurological damage is evident or...Drug dependence-cocaine dependence 304.3 - Drug dependence- cannabis dependence 304.4 - Drug dependence-amphetamine and other psychostimulant...unspecified drug dependence 305.2 – Nondependent abuse of drugs- cannabis abuse 305.3 – Nondependent abuse of drugs-hallucinogen abuse 305.4

CHALLENGES IN IDENTIFYING THE NEW-GENERATION PSYCHOACTIVE SUBSTANCES

OpenAIRE

SALKIM IŞLEK, Dilek; CENGIZ, Salih; RAYIMOĞLU, Gülten; ÇAVUŞ, Fatma; YÜKSELOĞLU, Emel Hülya

2018-01-01

A psychoactivesubstance is a substance that affects the central nervous system, alters brainfunctions, and leads to changes in perception, mood and behavior.Apart fromwell-known psychoactive substances, there are some substances callednew-generation psychoactive substances that have risen in recent years. Suchsubstances may be divided into 4 categories: Synthetic cannabinoids, cathinonederivatives, phenylethylamine derivatives, and others including tryptamines,piperazines, hallucinogenic mush...

Chemistry and Structure-Activity Relationships of Psychedelics.

Science.gov (United States)

Nichols, David E

2018-01-01

This chapter will summarize structure-activity relationships (SAR) that are known for the classic serotonergic hallucinogens (aka psychedelics), focusing on the three chemical types: tryptamines, ergolines, and phenethylamines. In the brain, the serotonin 5-HT 2A receptor plays a key role in regulation of cortical function and cognition, and also appears to be the principal target for hallucinogenic/psychedelic drugs such as LSD. It is one of the most extensively studied of the 14 known types of serotonin receptors. Important structural features will be identified for activity and, where possible, those that the psychedelics have in common will be discussed. Because activation of the 5-HT 2A receptor is the principal mechanism of action for psychedelics, compounds with 5-HT 2A agonist activity generally are quickly discarded by the pharmaceutical industry. Thus, most of the research on psychedelics can be related to activation of 5-HT 2A receptors. Therefore, much of the discussion will include not only clinical or anecdotal studies, but also will consider data from animal models as well as a certain amount of molecular pharmacology where it is known.

LSD Flashbacks - The Appearance of New Visual Imagery Not Experienced During Initial Intoxication: Two Case Reports.

Science.gov (United States)

G Lerner, Arturo; Goodman, Craig; Rudinski, Dmitri; Lev-Ran, Shaul

2014-01-01

A side effect associated with the use of synthetic hallucinogens such as lysergic acid diethylamide-(LSD) is the partial or total recurrence of perceptual disturbances which previously appeared during intoxication, despite absence of recent use. These are commonly referred to as "flashbacks" or Hallucinogen Persisting Perception Disorder (HPPD). Here we present two cases of patients with a prior history of LSD use who turned to psychiatric consultation following brief episodes of HPPD. Surprisingly, in both cases new visual imagery appeared during episodes of flashbacks which was not experienced during primary LSD use. Both subjects reported the ability to discern between LSD-associated visual disturbances and new visual imagery. This phenomenon did not cause functional impairment and in both cases caused gradual concern due to its persistence. Both patients refused medical treatment and continued psychiatric follow-up. At one year follow-up both patients reported almost complete spontaneous remission. To the best of our knowledge these are the first reported cases of LSD-related benign flashbacks in which new imagery is experienced. Reasons for this reversible and apparently harmless side effect are proposed. Conclusions from case reports should be taken with caution.

Psilocybin for treating substance use disorders?

OpenAIRE

Veen, B.T. de; Schellekens, A.F.A.; Verheij, M.M.M.; Homberg, J.R.

2017-01-01

INTRODUCTION: Evidence based treatment for Substance use disorders (SUD) includes psychotherapy and pharmacotherapy. However, these are only partially effective. Hallucinogens, such as psilocybin, may represent potential new treatment options for SUD. This review provides a summary of (human) studies on the putative therapeutic effects of psilocybin, and discusses the receptor systems, brain regions and cognitive and emotional processes mediating psilocybin's effects. Psilocybin's chemical st...

Synthesis of isotopically labeled ketamine

OpenAIRE

Stuchlíková, Lucie

2011-01-01

In this work were synthesized ketamine isotopomers. Ketamine is used in human medicine and veterinary sectors. It has very broad spectrum of pharmacological effects: anesthetic, analgesic, hallucinogenic, bronchodilator, cardiovascular and antidepressive, which is currently in the research. At first was synthesized precursor of ketamine, N- desmethylketamine which was subsequently labeled the deuterium, tritium and carbon- 14. For the determination of purity and identity mass spectrometry and...

Receptor binding profiles and behavioral pharmacology of ring-substituted N,N-diallyltryptamine analogs.

Science.gov (United States)

Klein, Landon M; Cozzi, Nicholas V; Daley, Paul F; Brandt, Simon D; Halberstadt, Adam L

2018-02-27

Substantial effort has been devoted toward understanding the psychopharmacological effects of tryptamine hallucinogens, which are thought to be mediated by activation of 5-HT 2A and 5-HT 1A receptors. Recently, several psychoactive tryptamines based on the N,N-diallyltryptamine (DALT) scaffold have been encountered as recreational drugs. Despite the apparent widespread use of DALT derivatives in humans, little is known about their pharmacological properties. We compared the binding affinities of DALT and its 2-phenyl-, 4-acetoxy-, 4-hydroxy-, 5-methoxy-, 5-methoxy-2-methyl-, 5-fluoro-, 5-fluoro-2-methyl-, 5-bromo-, and 7-ethyl-derivatives at 45 receptor and transporter binding sites. Additionally, studies in C57BL/6 J mice examined whether these substances induce the head twitch response (HTR), a 5-HT 2A receptor-mediated response that is widely used as a behavioral proxy for hallucinogen effects in humans. Most of the test drugs bound to serotonin receptors, σ sites, α 2 -adrenoceptors, dopaminergic D 3 receptors, histaminergic H 1 receptors, and the serotonin transporter. DALT and several of the ring-substituted derivatives were active in the HTR assay with the following rank order of potency: 4-acetoxy-DALT > 5-fluoro-DALT > 5-methoxy-DALT > 4-hydroxy-DALT > DALT > 5-bromo-DALT. 2-Phenyl-DALT, 5-methoxy-2-methyl-DALT, 5-fluoro-2-methyl-DALT, and 7-ethyl-DALT did not induce the HTR. HTR potency was not correlated with either 5-HT 1A or 5-HT 2A receptor binding affinity, but a multiple regression analysis indicated that 5-HT 2A and 5-HT 1A receptors make positive and negative contributions, respectively, to HTR potency (R 2  = 0.8729). In addition to supporting the established role of 5-HT 2A receptors in the HTR, these findings are consistent with evidence that 5-HT 1A activation by tryptamine hallucinogens buffers their effects on HTR. Published by Elsevier Ltd.

4-[125I]iodo-(2,5-dimethoxy)phenylisopropylamine and [3H]ketanserin labeling of 5-hydroxytryptamine2 (5HT2) receptors in mammalian cells transfected with a rat 5HT2 cDNA: Evidence for multiple states and not multiple 5HT2 receptor subtypes

International Nuclear Information System (INIS)

Teitler, M.; Leonhardt, S.; Weisberg, E.L.; Hoffman, B.J.

1990-01-01

Evidence has accumulated indicating that the radioactive hallucinogens 4-bromo-[3H](2,5-dimethoxy)phenylisopropylamine ([3H]DOB) and 4-[125I]iodo-(2,5-dimethoxy)phenylisopropylamine ([125I]DOI) label an agonist high affinity state of the 5-hydroxytryptamine2 (5HT2) receptor and [3H]ketanserin labels both agonist high and low affinity states. Recently, an alternative hypothesis has been put forward proposing that the radioactive hallucinogens are labeling a 5HT2 receptor subtype distinct from the receptor labeled by [3H]ketanserin. In order to provide definitive evidence as to which of these hypotheses is correct, the rat 5HT2 receptor gene was transfected into NIH-3T3 cells and COS cells. Neither nontransfected cell type expresses 5HT2 receptors; the transfected cells expressed high affinity binding sites for both [125I] DOI (KD = 0.8 nM and Bmax = 363 fmol/mg in NIH-3T3 cells; KD = 0.2 nM and Bmax = 26 fmol/mg in COS cells) and [3H]ketanserin (KD = 0.4 nM and Bmax = 5034 fmol/mg in NIH-3T3 cells; KD = 1.0 nM and Bmax = 432 fmol/mg in COS cells). The affinities of agonists and antagonists for the [125I]DOI-labeled receptor were significantly higher than for the [3H]ketanserin-labeled receptor. The affinities of agonists and antagonists for these binding sites were essentially identical to their affinities for the sites radiolabeled by these radioligands in mammalian brain homogenates. The [125I]DOI binding was guanyl nucleotide sensitive, indicating a coupling to a GTP-binding protein. These data indicate that the 5HT2 receptor gene product contains both the guanyl nucleotide-sensitive [125I]DOI binding site and the [3H]ketanserin binding site. Therefore, these data indicate that the 5HT2 receptor gene product can produce a high affinity binding site for the phenylisopropylamine hallucinogen agonists as well as for the 5HT2 receptor antagonists

Association between alcohol, cannabis, and other illicit substance abuse and risk of developing schizophrenia

DEFF Research Database (Denmark)

Nielsen, S M; Toftdahl, N G; Nordentoft, M

2017-01-01

.04, 95% confidence interval (CI) 5.84-6.26]. Cannabis (HR 5.20, 95% CI 4.86-5.57) and alcohol (HR 3.38, 95% CI 3.24-3.53) presented the strongest associations. Abuse of hallucinogens (HR 1.86, 95% CI 1.43-2.41), sedatives (HR 1.68, 95% CI 1.49-1.90), and other substances (HR 2.85, 95% CI 2.58-3.15) also...

Virtual Reality and Cellular Phones as a Complementary Intervention for Veterans with PTSD and Substance Use Disorders

Science.gov (United States)

2013-12-01

met criteria for primary alcohol dependence (9 in PE, and 10 in PE-VR), 6 (15.0%) met criteria for primary cannabis dependence (3 in each...Sedative 0% 0% Cannabis 20% 10% Stimulant 0% 0% Opioid 0% 5% Cocaine 5% 20% Hallucinogen 0% 0% Other 25...Davidson Trauma Scale. Psychological Medicine , 27, 153-160. Heatherton, T.F., Kozlowski, L.T., Frecker, R.C., & Fagerstroem, K.O. (1991). The

Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy

OpenAIRE

Wagner, Mark T; Mithoefer, Michael C; Mithoefer, Ann T; MacAulay, Rebecca K; Jerome, Lisa; Yazar-Klosinski, Berra; Doblin, Rick

2017-01-01

A growing body of research suggests that traumatic events lead to persisting personality change characterized by increased neuroticism. Relevantly, enduring improvements in Post-Traumatic Stress Disorder (PTSD) symptoms have been found in response to 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. There is evidence that lasting changes in the personality feature of ?openness? occur in response to hallucinogens, and that this may potentially act as a therapeutic mechanism of c...

Psilocybin-induced stimulus control in the rat.

Science.gov (United States)

Winter, J C; Rice, K C; Amorosi, D J; Rabin, R A

2007-10-01

Although psilocybin has been trained in the rat as a discriminative stimulus, little is known of the pharmacological receptors essential for stimulus control. In the present investigation rats were trained with psilocybin and tests were then conducted employing a series of other hallucinogens and presumed antagonists. An intermediate degree of antagonism of psilocybin was observed following treatment with the 5-HT(2A) receptor antagonist, M100907. In contrast, no significant antagonism was observed following treatment with the 5-HT(1A/7) receptor antagonist, WAY-100635, or the DA D(2) antagonist, remoxipride. Psilocybin generalized fully to DOM, LSD, psilocin, and, in the presence of WAY-100635, DMT while partial generalization was seen to 2C-T-7 and mescaline. LSD and MDMA partially generalized to psilocybin and these effects were completely blocked by M-100907; no generalization of PCP to psilocybin was seen. The present data suggest that psilocybin induces a compound stimulus in which activity at the 5-HT(2A) receptor plays a prominent but incomplete role. In addition, psilocybin differs from closely related hallucinogens such as 5-MeO-DMT in that agonism at 5-HT(1A) receptors appears to play no role in psilocybin-induced stimulus control.

Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction.

Science.gov (United States)

Johnson, Matthew W; Garcia-Romeu, Albert; Cosimano, Mary P; Griffiths, Roland R

2014-11-01

Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open-label pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a structured 15-week smoking cessation treatment protocol. Participants were 15 psychiatrically healthy nicotine-dependent smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake. Biomarkers assessing smoking status, and self-report measures of smoking behavior demonstrated that 12 of 15 participants (80%) showed seven-day point prevalence abstinence at 6-month follow-up. The observed smoking cessation rate substantially exceeds rates commonly reported for other behavioral and/or pharmacological therapies (typically psilocybin, these findings suggest psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models. The present study illustrates a framework for future research on the efficacy and mechanisms of hallucinogen-facilitated treatment of addiction. © The Author(s) 2014.

Effects of the Natural β-Carboline Alkaloid Harmine, a Main Constituent of Ayahuasca, in Memory and in the Hippocampus: A Systematic Literature Review of Preclinical Studies.

Science.gov (United States)

Dos Santos, Rafael G; Hallak, Jaime E C

2017-01-01

Harmine is a natural β-carboline alkaloid found in several botanical species, such as the Banisteriopsis caapi vine used in the preparation of the hallucinogenic beverage ayahuasca and the seeds of Syrian rue (Peganum harmala). Preclinical studies suggest that harmine may have neuroprotective and cognitive-enhancing effects, and retrospective/observational investigations of the mental health of long-term ayahuasca users suggest that prolonged use of this harmine-rich hallucinogen is associated with better neuropsychological functioning. Thus, in order to better investigate these possibilities, we performed a systematic literature review of preclinical studies analyzing the effects of harmine on hippocampal neurons and in memory-related behavioral tasks in animal models. We found two studies involving hippocampal cell cultures and nine studies using animal models. Harmine administration was associated with neuroprotective effects such as reduced excitotoxicity, inflammation, and oxidative stress, and increased brain-derived neurotrophic factor (BDNF) levels. Harmine also improved memory/learning in several animal models. These effects seem be mediated by monoamine oxidase or acetylcholinesterase inhibition, upregulation of glutamate transporters, decreases in reactive oxygen species, increases in neurotrophic factors, and anti-inflammatory effects. The neuroprotective and cognitive-enhancing effects of harmine should be further investigated in both preclinical and human studies.

Psilocybin-induced stimulus control in the rat

OpenAIRE

Winter, J.C.; Rice, K.C.; Amorosi, D.J.; Rabin, R.A.

2007-01-01

Although psilocybin has been trained in the rat as a discriminative stimulus, little is known of the pharmacological receptors essential for stimulus control. In the present investigation rats were trained with psilocybin and tests were then conducted employing a series of other hallucinogens and presumed antagonists. An intermediate degree of antagonism of psilocybin was observed following treatment with the 5-HT2A receptor antagonist, M100907. In contrast, no significant antagonism was obse...

Discriminative Stimulus Effects of 3,4-Methylenedioxymethamphetamine and Its Enantiomers in Mice: Pharmacokinetic Considerations

OpenAIRE

Fantegrossi, William E.; Murai, Naoki; Mathúna, Brian Ó.; Pizarro, Nieves; de la Torre, Rafael

2009-01-01

3,4-Methylenedioxymethamphetamine (MDMA) is a drug of abuse with mixed stimulant- and hallucinogen-like effects. The aims of the present studies were to establish discrimination of S(+)-MDMA, R(-)-MDMA, or their combination as racemic MDMA in separate groups of mice to assess cross-substitution tests among all three compounds, to determine the time courses of the training doses, to assess pharmacokinetic variables after single injections and after cumulative dosing, an...

Translations on Narcotics and Dangerous Drugs, Number 288

Science.gov (United States)

1977-03-10

activities, especially the scope of their drug sales and distribution activities. The Interpol agents also confiscated two pickup trucks, one Izuzu l...Barnett Va- lenzuela, and Eduardo Esquer Alvarado, 35-years old, resident of 79 Educacion Street of this city. Barnett Valenzuela owns the drugs and... especially of the urban lower classes, of a broad and concrete discussion on the problems of the use and abuse of alco- hol, hallucinogens and narcotics

Modern Clinical Research on LSD

OpenAIRE

Liechti, Matthias E.

2017-01-01

All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT2A receptor. LSD increased fe...

Adverse effects of sympathomimetic drugs in a group of adolescents

OpenAIRE

Jerí, F. Raúl; Carbajal, Carlos; Sánchez M., César

2014-01-01

Clinical observations of 35 youths who used hallucinogenic drugs for two to four years are mostly present . The proportion of males was three times compared to women , almost all households were from well integrated and belonged to a higher socio- economic level or medium . The drugs used were marijuana , LSD , barbiturates , mescaline , afetamina , methaqualone and alcohol, in various combinations . All of these young people showed signs of psychological disturbance , personality disorders g...

Fatal toxic leukoencephalopathy secondary to overdose of a new psychoactive designer drug 2C-E (“Europa”)

OpenAIRE

Sacks, Justin; Ray, M. Jordan; Williams, Sue; Opatowsky, Michael J.

2012-01-01

We present a case of a fatal toxic leukoencephalopathy following ingestion of a new psychoactive designer drug known as 2C-E or “Europa.” Recreational drugs, particularly hallucinogenic substances, appear to be growing in popularity, with increasing amounts of information available via the Internet to entice potential users. In addition, some newer “designer” psychoactive substances are available for purchase online without adverse legal consequences, therefore adding to their popularity. We ...

Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder.

Science.gov (United States)

Moreno, Francisco A; Wiegand, Christopher B; Taitano, E Keolani; Delgado, Pedro L

2006-11-01

Anecdotal reports suggest that psychedelic agents may relieve symptoms of obsessive-compulsive disorder (OCD). This modified double-blind study investigated the safety, tolerability, and clinical effects of psilocybin, a potent 5-HT(1A) and 5-HT(2A/2C) agonist, in patients with OCD. Nine subjects with DSM-IV-defined OCD and no other current major psychiatric disorder participated in up to 4 single-dose exposures to psilocybin in doses ranging from sub-hallucinogenic to frankly hallucinogenic. Low (100 microg/kg), medium (200 microg/kg), and high (300 microg/kg) doses were assigned in that order, and a very low dose (25 microg/kg) was inserted randomly and in double-blind fashion at any time after the first dose. Testing days were separated by at least 1 week. Each session was conducted over an 8-hour period in a controlled environment in an outpatient clinic; subjects were then transferred to a psychiatric inpatient unit for overnight observation. The Yale-Brown Obsessive Compulsive Scale (YBOCS) and a visual analog scale measuring overall obsessive-compulsive symptom severity were administered at 0, 4, 8, and 24 hours post-ingestion. The Hallucinogen Rating Scale was administered at 8 hours, and vital signs were recorded at 0, 1, 4, 8, and 24 hours after ingestion. The study was conducted from November 2001 to November 2004. Nine subjects were administered a total of 29 psilocybin doses. One subject experienced transient hypertension without relation to anxiety or somatic symptoms, but no other significant adverse effects were observed. Marked decreases in OCD symptoms of variable degrees were observed in all subjects during 1 or more of the testing sessions (23%-100% decrease in YBOCS score). Repeated-measures analysis of variance for all YBOCS values revealed a significant main effect of time on Wilks lambda (F = 9.86, df = 3,3; p = .046), but no significant effect of dose (F = 2.25, df = 3,3; p = .261) or interaction of time and dose (F = 0.923, df = 9,45; p

Cannabis and Breastfeeding

OpenAIRE

Garry, Aurélia; Rigourd, Virginie; Amirouche, Ammar; Fauroux, Valérie; Aubry, Sylvie; Serreau, Raphaël

2009-01-01

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 ...

The effects of d-lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-methylamphetamine (DOM) and d-amphetamine on operant responding in control and 6-hydroxydopamine-treated rats.

Science.gov (United States)

Commissaris, R; Lyness, W H; Cordon, J J; Moore, K E; Rech, R H

1980-11-01

The purpose of the present study was to determine the role of central catecholaminergic neuronal systems in the effects of LSD, DOM and d-amphetamine on fixed ratio (FR) operant responding in rats. Food-deprived male rats were trained to press a bar for food reinforcement on a FR-40 schedule. Control responding on this schedule is characterized by a rapid, constant rate of responding (approximately 100 responses/min) throughout a 40 min test session. LSD and DOM, as with other hallucinogens, produced dose-dependent periods of nonresponding or "pausing," followed by reinstatement of responding at or near the control rate. Administration of the non-hallucinogen, d-amphetamine, did not produce "pausing," but caused the response rate to slow and become erratic. In animals pretreated intraventricularly with 6-hydroxydopamine (6-OHDA; 200 micrograms/10 microliter X 2), the response to LSD and DOM was unchanged, while the response to d-amphetamine was significantly diminished. The neurotoxin significantly decreased brain catecholamines to less than 25 percent of control in al regions examined, without altering 5-HT concentrations in these same regions. These data demonstrate that the effects of LSD and DOM on FR-40 responding are quite different from those of d-amphetamine, and that this difference may be due to the extent of catecholamine involvement in the effects of these agents.

Characterization of behavioral and endocrine effects of LSD on zebrafish.

Science.gov (United States)

Grossman, Leah; Utterback, Eli; Stewart, Adam; Gaikwad, Siddharth; Chung, Kyung Min; Suciu, Christopher; Wong, Keith; Elegante, Marco; Elkhayat, Salem; Tan, Julia; Gilder, Thomas; Wu, Nadine; Dileo, John; Cachat, Jonathan; Kalueff, Allan V

2010-12-25

Lysergic acid diethylamide (LSD) is a potent hallucinogenic drug that strongly affects animal and human behavior. Although adult zebrafish (Danio rerio) are emerging as a promising neurobehavioral model, the effects of LSD on zebrafish have not been investigated previously. Several behavioral paradigms (the novel tank, observation cylinder, light-dark box, open field, T-maze, social preference and shoaling tests), as well as modern video-tracking tools and whole-body cortisol assay were used to characterize the effects of acute LSD in zebrafish. While lower doses (5-100 microg/L) did not affect zebrafish behavior, 250 microg/L LSD increased top dwelling and reduced freezing in the novel tank and observation cylinder tests, also affecting spatiotemporal patterns of activity (as assessed by 3D reconstruction of zebrafish traces and ethograms). LSD evoked mild thigmotaxis in the open field test, increased light behavior in the light-dark test, reduced the number of arm entries and freezing in the T-maze and social preference test, without affecting social preference. In contrast, LSD affected zebrafish shoaling (increasing the inter-fish distance in a group), and elevated whole-body cortisol levels. Overall, our findings show sensitivity of zebrafish to LSD action, and support the use of zebrafish models to study hallucinogenic drugs of abuse. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Straightforward single-calibrant quantification of seized designer drugs by liquid chromatography-chemiluminescence nitrogen detection.

Science.gov (United States)

Rasanen, Ilpo; Kyber, Marianne; Szilvay, Ilmari; Rintatalo, Janne; Ojanperä, Ilkka

2014-04-01

Sixty-one different psychoactive substances were quantified by liquid chromatography-chemiluminescence nitrogen detection (LC-CLND) in 177 samples, using a single secondary standard (caffeine), in a trial concerning the quantitative purity assessment of drug-related material seized by the police in 2011-2012 and customs in 2011-2013 in Finland. The substances found were predominantly substituted phenethylamines, cathinones, tryptamines and synthetic cannabinoids, which were identified by appropriate methods prior to submitting the samples for quantification by LC-CLND. The equimolarity and expanded uncertainty of measurement by LC-CLND were on average 95% and 13%, respectively, based on 16 different substances. The median (mean) purity of stimulant/hallucinogenic drug samples seized at the border was 92.9% (87.6%) and in the street 82.0% (64.5%). The corresponding figures for powdery synthetic cannabinoid samples seized at the border and in the street were 99.0% (96.8%) and 90.0% (92.2%), respectively. There was generally only one active drug to be quantified in each sample. Seized herbal samples contained 0.15-9.2% of between one and three components. LC-CLND was found to be suitable for quantification of the nitrogen-containing drugs encountered in the study, showing sufficient N-equimolarity for both stimulant/hallucinogenic drugs and synthetic cannabinoids. The technique possesses great potential as a standard technique in forensic laboratories. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Identification of 5-hydroxy-tryptamine (bufotenine) in takini (Brosimum acutifolium Huber subsp acutifolium CC Berg, Moraceae), a shamanic potion used in the Guiana Plateau

OpenAIRE

Moretti, Christian; Gaillard, Y.; Grenand, Pierre; Bevalot, F.; Prevosto, J.M.

2006-01-01

This paper is the first thorough analysis of takini, a hallucinogen used by the shamans of several peoples in Suriname, French Guiana, and the region east of the Para in Brazil. The drug is contained in the latex of the Brosimum acutifolium tree, and until now, its psychotropic properties appeared inconsistent with the more general medicinal uses of the tree in the surrounding region. Our chemical and botanical studies reveal that the active ingredient of takini is bufotenine; and that this c...

Psichotropiniai augalai lietuvių tradicijoje

OpenAIRE

Senvaitytė, Dalia

2006-01-01

Plants affecting the mind played an important role in the therapeutic and spiritual practice of many societies. Sorcerers in various parts of the world used special hallucinogenic materials to fall into a trance and to see “another dimensions”. In different regions, plants with special properties have been used by so-called “witches” in order to prepare various “magic potions”. Traces of analogous tradition can also be found in Lithuanian culture. It can be found in Lithuanian folklore and wr...

Ketamin genopdaget af både læger og misbrugere

DEFF Research Database (Denmark)

Sørensen, Anne; Barnung, Steen; Rasmussen, Lars Simon

2011-01-01

Ketamine is a unique anaesthetic because it has both hypnotic and analgesic effects and also potential hallucinogenic side effects. Lack of cardiopulmonary depression makes the drug a popular choice for anaesthesia in the prehospital setting. In recent years ketamine has been found to have anti......-hyperalgesic and opioid saving effects, opening to new ways of managing post-operative and chronic pain states. Recreational use of ketamine among night clubbers is increasing and makes acute and chronic symptoms of ketamine abuse a new challenge in emergency departments....

Ketamin genopdaget af både læger og misbrugere

DEFF Research Database (Denmark)

Sørensen, Anne; Barnung, Steen; Rasmussen, Lars Simon

2011-01-01

-hyperalgesic and opioid saving effects, opening to new ways of managing post-operative and chronic pain states. Recreational use of ketamine among night clubbers is increasing and makes acute and chronic symptoms of ketamine abuse a new challenge in emergency departments.......Ketamine is a unique anaesthetic because it has both hypnotic and analgesic effects and also potential hallucinogenic side effects. Lack of cardiopulmonary depression makes the drug a popular choice for anaesthesia in the prehospital setting. In recent years ketamine has been found to have anti...

Preliminary Analysis of the U.S. Army Security Screening Questionnaire

Science.gov (United States)

1990-12-01

06 .054.2 Alcohol (total times intoxicated ) .15 .08 .10 * P .05 ** p < .01 Note: V statistics are omitted for contingency tables wher. the cell sizes...week, but less than daily f. once or more daily B-2 3.4 Used amphetamines, hallucinogens, barbiturates, cocaine, opium, or heroin Alcohol Use 4.1...Frequency of alcohol use a. once a month or less b. more than once a month 4.2 Number of times intoxicated a. never b. one to 5 times c. more than 5 times

Udviklingen fra lægemiddel til rusmiddel

DEFF Research Database (Denmark)

Askaa, Bjarke; Horwitz, Henrik; Wøien, Vidar André

2014-01-01

Synthetic "designer drugs" with hallucinogenic properties have become increasingly popular among recreational drug users in recent years. Some of the designer drugs are chemically modified drugs previously used in treatment of depression and chronic fatigue. The drugs are available from a large...... number of internet distributers. There is very little knowledge of the clinical symptoms and how intoxicated people should be treated. We present a review of published literature (including 284 intoxicated patients) and experiences from the Danish poison centre concerning two chemical derivatives...

Prehistoric psychotropic consumption in Andean Chilean mummies

OpenAIRE

Juan P. Ogalde; Bernardo T. Arriaza; Elia Soto

2007-01-01

Hallucinogenic plants are often regarded as the main source of psychoactive drugs in antiquity to reach deep altered states of consciousness^1,2^. Many researchers believe this was particularly true during the Tiwanaku empire expansion, circa (500-1000 A.D.), along the Atacama Desert of Chile. Highly decorated snuffing tablets and tubes are often found as grave goods during this period^3,4,5,6,7,8^. Until now the type of drugs consumed in this paraphernalia has been unclear. From the modern c...

Ketamin genopdaget af både læger og misbrugere

DEFF Research Database (Denmark)

Sørensen, Anne; Barnung, Steen; Rasmussen, Lars Simon

2011-01-01

Ketamine is a unique anaesthetic because it has both hypnotic and analgesic effects and also potential hallucinogenic side effects. Lack of cardiopulmonary depression makes the drug a popular choice for anaesthesia in the prehospital setting. In recent years ketamine has been found to have anti-h......-hyperalgesic and opioid saving effects, opening to new ways of managing post-operative and chronic pain states. Recreational use of ketamine among night clubbers is increasing and makes acute and chronic symptoms of ketamine abuse a new challenge in emergency departments....

Psilocybin links binocular rivalry switch rate to attention and subjective arousal levels in humans.

Science.gov (United States)

Carter, Olivia L; Hasler, Felix; Pettigrew, John D; Wallis, Guy M; Liu, Guang B; Vollenweider, Franz X

2007-12-01

Binocular rivalry occurs when different images are simultaneously presented to each eye. During continual viewing of this stimulus, the observer will experience repeated switches between visual awareness of the two images. Previous studies have suggested that a slow rate of perceptual switching may be associated with clinical and drug-induced psychosis. The objective of the study was to explore the proposed relationship between binocular rivalry switch rate and subjective changes in psychological state associated with 5-HT2A receptor activation. This study used psilocybin, the hallucinogen found naturally in Psilocybe mushrooms that had previously been found to induce psychosis-like symptoms via the 5-HT2A receptor. The effects of psilocybin (215 microg/kg) were considered alone and after pretreatment with the selective 5-HT2A antagonist ketanserin (50 mg) in ten healthy human subjects. Psilocybin significantly reduced the rate of binocular rivalry switching and increased the proportion of transitional/mixed percept experience. Pretreatment with ketanserin blocked the majority of psilocybin's "positive" psychosis-like hallucinogenic symptoms. However, ketanserin had no influence on either the psilocybin-induced slowing of binocular rivalry or the drug's "negative-type symptoms" associated with reduced arousal and vigilance. Together, these findings link changes in binocular rivalry switching rate to subjective levels of arousal and attention. In addition, it suggests that psilocybin's effect on binocular rivalry is unlikely to be mediated by the 5-HT2A receptor.

The 5-HT1A Receptor and the Stimulus Effects of LSD in the Rat

Science.gov (United States)

Reissig, C.J.; Eckler, J.R.; Rabin, R.A.; Winter, J.C.

2005-01-01

Rationale It has been suggested that the 5-HT1A receptor plays a significant modulatory role in the stimulus effects of the indoleamine hallucinogen lysergic acid diethylamide (LSD). Objectives The present study sought to characterize the effects of several compounds with known affinity for the 5-HT1A receptor on the discriminative stimulus effects of LSD. Methods 12 Male F-344 rats were trained in a two-lever, fixed ratio10, food reinforced task with LSD (0.1 mg/kg; IP; 15 min pretreatment) as a discriminative stimulus. Combination and substitution tests with the 5-HT1A agonists, 8-OH-DPAT, buspirone, gepirone, and ipsapirone, with LSD-induced stimulus control were then performed. The effects of these 5-HT1A ligands were also tested in the presence of the selective 5-HT1A receptor antagonist, WAY-100,635 (0.3 mg/kg; SC; 30 min. pretreatment). Results In combination tests stimulus control by LSD was increased by all 5-HT1A receptor ligands with agonist properties. Similarly, in tests of antagonism, the increase in drug-appropriate responding caused by stimulation of the 5-HT1A receptor was abolished by administration of WAY-100,635. Conclusions These data, obtained using a drug discrimination model of the hallucinogenic effects of LSD, provide support for the hypothesis that the 5-HT1A receptor has a significant modulatory role in the stimulus effects of LSD. PMID:16025319

Opaque models: Using drugs and dreams to explore the neurobiological basis of mental phenomena.

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Langlitz, Nicolas

2017-01-01

On the basis of four historical and ethnographic case studies of modeling in neuroscience laboratories, this chapter introduces a distinction between transparent and opaque models. A transparent model is a simplified representation of a real world phenomenon. If it is not patently clear, it is at least much better comprehended than its objects of representation. An opaque model, by contrast, looks at one only partially understood phenomenon to stand in for another partially understood phenomenon. Here, the model is often just as complex as its target. Examples of such opaque models discussed in this chapter are the use of hallucinogen intoxication in humans and animals as well as the dreaming brain as models of psychosis as well as the dreaming brain as a model of consciousness in general. Several functions of opaque models are discussed, ranging from the generation of funding to the formulation of new research questions. While science studies scholars have often emphasized the epistemic fertility of failures of representation, the opacity of hallucinogen intoxications and dreams seems to have diminished the potential to produce positive knowledge from the representational relationship between the supposed models and their targets. Bidirectional comparisons between inebriation, dreaming, and psychosis, however, proved to be generative on the level of basic science. Moreover, the opaque models discussed in this chapter implicated cosmologies that steered research endeavors into certain directions rather than others. © 2017 Elsevier B.V. All rights reserved.

Metoksetamina – nowy związek psychoaktywny („dopalacz” o silnym działaniu psychodysleptycznym

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Agnieszka Wiesner

2015-06-01

Full Text Available During the last decade, numerous new psychoactive substances have appeared on the illegal recreational drug market. One of them is methoxetamine, a structural analogue of ketamine. The increasing popularity of methoxetamine as a recreational drug may be attributed to its potent hallucinogenic and dissociative effects. Methoxetamine exerts a wide range of effects on the central and peripheral nervous system, and some of which resemble the effects of ketamine while others vary greatly. The consumption of methoxetamine carries a significant health risk, and may even lead to fatal intoxication.

[Salem witches, flying brooms, and synthetic drugs].

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Castellanos Tejero, Manuel; Castellanos Tejero, M de los Angeles

2002-10-01

As supplementary material to Health Education programs about synthetic drugs, the authors present a historical summary on LSD, stramonium and khat. "Tripis", Special K and other synthetic pills contain these substances and are being widely used by youths. The history of these main hallucinogenic active ingredients has a strong tie to the mythology of witchcraft and witches: a historically interesting time period bearing a large amount of religious intolerance. The objective of this review is to end the belief today's youth have that they are taking new substances which have no risks.

The effects of benzofury (5-APB) on the dopamine transporter and 5-HT2-dependent vasoconstriction in the rat.

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Dawson, Patrick; Opacka-Juffry, Jolanta; Moffatt, James D; Daniju, Yusuf; Dutta, Neelakshi; Ramsey, John; Davidson, Colin

2014-01-03

5-APB, commonly marketed as 'benzofury' is a new psychoactive substance and erstwhile 'legal high' which has been implicated in 10 recent drug-related deaths in the UK. This drug was available on the internet and in 'head shops' and was one of the most commonly sold legal highs up until its recent UK temporary ban (UK Home Office). Despite its prominence, very little is known about its pharmacology. This study was undertaken to examine the pharmacology of 5-APB in vitro. We hypothesised that 5-APB would activate the dopamine and 5-HT systems which may underlie its putative stimulant and hallucinogenic effects. Autoradiographic studies showed that 5-APB displaced both [(125)I] RTI-121 and [(3)H] ketanserin from rat brain tissue suggesting affinity at the dopamine transporter and 5-HT2 receptor sites respectively. Voltammetric studies in rat accumbens brain slices revealed that 5-APB slowed dopamine reuptake, and at high concentrations caused reverse transport of dopamine. 5-APB also caused vasoconstriction of rat aorta, an effect antagonised by the 5-HT2A receptor antagonist ketanserin, and caused contraction of rat stomach fundus, which was reversed by the 5-HT2B receptor antagonist RS-127445. These data show that 5-APB interacts with the dopamine transporter and is an agonist at the 5-HT2A and 5-HT2B receptors in the rat. Thus 5-APB's pharmacology is consistent with it having both stimulant and hallucinogenic properties. In addition, 5-APB's activity at the 5-HT2B receptor may cause cardiotoxicity. © 2013.

Enhancing action of LSD on neuronal responsiveness to serotonin in a brain structure involved in obsessive-compulsive disorder.

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Zghoul, Tarek; Blier, Pierre

2003-03-01

Potent serotonin (5-HT) reuptake inhibitors are the only drugs that consistently exert a therapeutic action in obsessive-compulsive disorder (OCD). Given that some hallucinogens were reported to exert an anti-OCD effect outlasting their psychotomimetic action, possible modifications of neuronal responsiveness to 5-HT by LSD were examined in two rat brain structures: one associated with OCD, the orbitofrontal cortex (OFC), and another linked to depression, the hippocampus. The effects of concurrent microiontophoretic application of LSD and 5-HT were examined on neuronal firing rate in the rat OFC and hippocampus under chloral hydrate anaesthesia. In order to determine whether LSD could also exert a modification of 5-HT neuronal responsiveness upon systemic administration, after a delay when hallucinosis is presumably no longer present, it was given once daily (100 microg/kg i.p.) for 4 d and the experiments were carried out 24 h after the last dose. LSD attenuated the firing activity of OFC neurons, and enhanced the inhibitory effect of 5-HT when concomitantly ejected on the same neurons. In the hippocampus, LSD also decreased firing rate by itself but decreased the inhibitory action of 5-HT. The inhibitory action of 5-HT was significantly greater in the OFC, but smaller in the hippocampus, when examined after subacute systemic administration of LSD. It is postulated that some hallucinogens could have a beneficial action in OCD by enhancing the responsiveness to 5-HT in the OFC, and not necessarily in direct relation to hallucinosis. The latter observation may have theoretical implications for the pharmacotherapy of OCD.

Interaction of D-LSD with binding sites in brain: a study in vivo and in vitro

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Ebersole, B.L.J.

1985-01-01

The localization of [ 3 H]-d-lysergic acid diethylamide ([ 3 H]LSD) binding sites in the mouse brain was compared in vivo and in vitro. Radioautography of brain sections incubated with [ 3 H]LSD in vitro revealed substantial specific [ 3 H]LSD binding in cortical layers III-IV and areas CA1 and dentate gyrus in hippocampus. In contrast, in brain sections from animals that received [ 3 H]LSD in vivo, binding in hippocampus was scant and diffuse, although the pattern of labeling in cortex was similar to that seen in vitro. The low specific binding in hippocampus relative to cortex was confirmed by homogenate filtration studies of brain areas from mice that received injections of [ 3 H]LSD. Time-course studies established that peak specific binding at ten minutes was the same in cortex and hippocampus. At all times, binding in hippocampus was about one-third of that in cortex; in contrast, the concentration of free [ 3 H]LSD did not vary between regions. This finding was unexpected, because binding studies in vitro in membrane preparations indicated that the density and affinity of [ 3 H]LSD binding sites were similar in both brain regions. Saturation binding studies in vivo showed that the lower amount of [ 3 H]LSD binding in hippocampus was attributable to a lower density of sites labeled by [ 3 H]LSD. The pharmacological identify of [ 3 H]LSD binding sites in vivo may be relevant to the hallucinogenic properties of LSD and of other related hallucinogens

Psychoactive substances, alcohol and tobacco consumption in HIV-infected outpatients.

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Jacquet, Jean-Marc; Peyriere, Hélène; Makinson, Alain; Peries, Marianne; Nagot, Nicolas; Donnadieu-Rigole, Hélène; Reynes, Jacques

2018-06-01

To assess the alcohol consumption, tobacco addiction and psychoactive substance use (PSU) of people living with HIV (PLHIV). Cross-sectional study in an HIV outpatient unit. Autoquestionnaire systematically proposed to all patients during their usual clinical care visit during a 6-months period, for alcohol (AUDIT test), tobacco (Short Fagerstrom Test) and PSU (ASSIST V3.0 test). Of 1334 distributed questionnaires, 1018 PLHIV responded: 76.8% were men [528 patients were MSM), and the median age was 49 years (interquartile range: 42-46). A prevalence of excessive alcohol drinking was found in 22% [95% confidence interval (CI) 19.5-24.7%] and 44.6% (CI 41.5-47.7%) were current smokers, with high dependence in 29.1% (CI 24.9-33.7%). The prevalence of PSU was 37.8% (CI 34.8-41%) in the past 3 months: cannabis 27.7%, poppers 16.4%, cocaine 8.9%, psychotropic medications 7.1%, gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL) 4.7%, stimulants 3.1%, synthetic cathinones 2.7%, hallucinogens 1.5%. In the past 3 months, PSU was more prevalent in MSM than in non-MSM patients (46 versus 30%, P poppers) 31.0 versus 1.1%, GHB/GBL 7.8 versus 0.8%, stimulants 5.0 versus 1.1%, synthetic cathinones 4.9 versus 0.3%, and hallucinogens 2.3 versus 0.5%. Given the high prevalence of PSU and other addictions (alcohol and smoking) among PLHIV, and particularly among MSM, a systematic screening of PSU and other addictions should be part of routine clinical care.

Drug use in college students: a 13-year trend

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Gabriela Arantes Wagner

2012-06-01

Full Text Available OBJECTIVE: To analyze drug use trends among college students in 1996, 2001 and 2009. METHODS: A cross-sectional epidemiological study with a multistage stratified cluster sample with 9,974 college students was conducted in the city of São Paulo, southeastern Brazil. An anonymous self-administered questionnaire was used to collect information on drug use assessed in lifetime, the preceding 12 months and the preceding 30 days. The Bonferroni correction was used for multiple comparisons of drug use rates between surveys. RESULTS: There were changes in the lifetime use of tobacco and some other drugs (hallucinogens [6.1% to 8.8%], amphetamines [4.6% to 8.7%], and tranquilizers [5.7% to 8.2%] from 1996 to 2009. Differences in the use of other drugs over the 12 months preceding the survey were also seen: reduced use of inhalants [9.0% to 4.8%] and increased use of amphetamines [2.4% to 4.8%]. There was a reduction in alcohol [72.9% to 62.1%], tobacco [21.3% to 17.2%] and marijuana [15.0% to 11.5%] use and an increase in amphetamine use [1.9% to 3.3%] in the preceeding 30 days. CONCLUSIONS: Over the 13-year study period, there was an increase in lifetime use of tobacco, hallucinogens, amphetamines, and tranquilizers. There was an increase in amphetamine use and a reduction in alcohol use during the preceding 12 months. There was an increase in amphetamine use during the preceding 30 days.

The phenomenology of the psychotic break and Huxley's trip: substance use and the onset of psychosis.

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Nelson, Barnaby; Sass, Louis A

2008-01-01

While considerable research attention has been devoted to the causal relationship between substance use and psychosis, the phenomenology of the association between the two has largely been ignored. This is a significant shortcoming, because it blinds researchers to the possibility that there may be elements of the subjective experience of substance use and psychosis that contribute to their apparent relationship in empirical studies. The current paper examines the phenomenology of the onset of psychosis and the phenomenology of substance intoxication through consideration of two texts: Sass's account of the phenomenology of psychosis onset and Huxley's account of the experience of hallucinogenic intoxication. Sass's account of psychosis onset includes four components: Unreality, Fragmentation, Mere Being, and Apophany. The analysis reveals significant parallels - and also some differences - between this account and the phenomenology of substance intoxication. We discuss the implications of this for the causal relationship between psychosis and substance use and suggest several ways of understanding the overlapping phenomenologies. This includes the suggestion of a shared factor, perhaps best described as psychotic-like experience, which seems to involve a breakdown of the sign-referent relationship and relationship with the common-sense, practical world. However, in the onset of psychosis, this breakdown is primarily experienced as a sense of alienation from self and world, whereas in the hallucinogenic state a sense of mystical union and revelation seems predominant. Further research may extend this analysis by looking at experiences with other drugs, particularly cannabis, and by examining the phenomenology of psychotic disorder beyond the first episode. (c) 2008 S. Karger AG, Basel.

New Drugs of Abuse and Withdrawal Syndromes.

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Andrabi, Sara; Greene, Spencer; Moukaddam, Nidal; Moukkadam, Nidal; Li, Benjamin

2015-11-01

New drugs of abuse continue to emerge, including synthetic cannabinoids, synthetic cathinones, and hallucinogens. It is important to recognize their individual psychopharmacologic properties, symptoms of intoxication, and symptoms of withdrawal. Providers must be vigilant of acute medical or psychiatric complications that may arise from use of these substances. Treatment of the patient also includes recognition of any substance use disorders as well as comorbid psychiatric disorders. Although pharmacologic treatments for substance use disorder (of the drugs included in this article) are limited, there are a variety of psychotherapeutic modalities that may be of some benefit. Published by Elsevier Inc.

Forbidden therapies: Santo Daime, ayahuasca, and the prohibition of entheogens in Western society.

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Blainey, Marc G

2015-02-01

Santo Daime, a Brazilian religion organized around a potent psychoactive beverage called ayahuasca, is now being practiced across Europe and North America. Deeming ayahuasca a dangerous "hallucinogen," most Western governments prosecute people who participate in Santo Daime. On the contrary, members of Santo Daime (called "daimistas") consider ayahuasca a medicinal sacrament (or "entheogen"). Empirical studies corroborate daimistas' claim that entheogens are benign and can be beneficial when employed in controlled contexts. Following from anthropology's goal of rendering different cultural logics as mutually explicable, this article intercedes in a misunderstanding between policies of prohibition and an emergent subculture of entheogenic therapy.

Datura Stramonium Abuse: A Case Report

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Muhittin Yilmaz

2013-10-01

Full Text Available Datura stramonium, known as devils apple or tatula by the people of Turkey, is a plant known member of a belladonna alkaloid family contains atropine, hyoscyamine and scopolamine having hallucinogenic and anticholinergic effects. 19 years old male patient admitted to emergency department (ED by his relatives with the complaints of altered mental status, and meaningless speech. History revealed that patient consumed %u201CDatura stramonium%u201D for entertainment about 4 hours before the development of symptoms. In our study we described a case presented by delirium to our emergency department later diagnosed as Datura stramonium poisoning.

Intoxicant use in the prehistoric Caribbean with particular reference to spouted ceramic inhaling bowls.

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Quetta Kaye

1999-11-01

Full Text Available The New World is unusually rich in hallucinogenic plants (Schultes and Hofmann 1980: 22. Ethnological research has well documented the ritual use of these substances by the inhabitants of the South American tropical rainforests (Wassen 1965. While archaeological research has tended to concentrate on the great ancient American civilisations of the Incas, Aztecs and Maya, which also reveal ritual usage of mind altering substances (Furst and Coe 1977; Coe 1988: 222-235; Bruhns 1994: 73-74, 215-216, 391, no comparable study or research has been undertaken for the pre-Columbian inhabitants of the Caribbean islands.

Maternal and developmental toxicity of the hallucinogenic plant-based beverage ayahuasca in rats.

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da Motta, Luciana Gueiros; de Morais, Juliana Alves; Tavares, Ana Carolina A M; Vianna, Leonora Maciel Sousa; Mortari, Marcia Renata; Amorim, Rivadávio Fernandes Batista; Carvalho, Rosângela R; Paumgartten, Francisco José R; Pic-Taylor, Aline; Caldas, Eloisa Dutra

2018-04-01

Rats were treated orally with ayahuasca (AYA) on gestation days (GD) 6-20 at doses corresponding to one-(1X) to eight-fold (8X) the average dose taken by a human adult in a religious ritual, and the pregnancy outcome evaluated on GD21. Rats treated with 4X and 8X doses died during the treatment period (44 and 52%), and those that survived showed kidney injury. Rats surviving the 8X dose showed neuronal loss in hippocampal regions and in the raphe nuclei, and those from the 2X dose neuronal loss in CA1. Delayed intrauterine growth, induced embryo deaths and increased occurrence of foetal anomalies were observed at the 8X dose. At non-lethal doses, AYA enhanced embryolethality and the incidence of foetal soft-tissue and skeleton anomalies. This study suggested that AYA is developmentally toxic and that its daily use by pregnant women may pose risks for the conceptus. Copyright © 2018 Elsevier Inc. All rights reserved.

Amphetamines, Barbiturates and Hallucinogens; An Analysis of Use, Distribution, and Control. Final Report.

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McGlothlin, William H.

This report is the third of three monographs to provide perspectives on the use, distribution, and control of illicit drugs. The first, conducted in 1971, described the prevalence, use patterns, sources, distribution, and economics of the marihuana market. The second (1972) estimated the cost, benefits, and potential of approaches to narcotic…

Identification of 5-hydroxy-tryptamine (bufotenine) in takini (Brosimumacutifolium Huber subsp. acutifolium C.C. Berg, Moraceae), a shamanic potion used in the Guiana Plateau.

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Moretti, Christian; Gaillard, Yvan; Grenand, Pierre; Bévalot, Fabien; Prévosto, Jean-Michel

2006-06-30

This paper is the first thorough analysis of takini, a hallucinogen used by the shamans of several peoples in Suriname, French Guiana, and the region east of the Para in Brazil. The drug is contained in the latex of the Brosimum acutifolium tree, and until now, its psychotropic properties appeared inconsistent with the more general medicinal uses of the tree in the surrounding region. Our chemical and botanical studies reveal that the active ingredient of takini is bufotenine; and that this compound is only contained in the subspecies Brosimum acutifolium Huber subsp. acutifolium C.C. Berg that is found in the same area of the eastern Guianas.

Total Synthesis of (-)-Salvinorin A.

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Line, Nathan J; Burns, Aaron C; Butler, Sean C; Casbohm, Jerry; Forsyth, Craig J

2016-12-12

Salvinorin A (1) is natural hallucinogen that binds the human κ-opioid receptor. A total synthesis has been developed that parlays the stereochemistry of l-(+)-tartaric acid into that of (-)-1 via an unprecedented allylic dithiane intramolecular Diels-Alder reaction to obtain the trans-decalin scaffold. Tsuji allylation set the C9 quaternary center and a late-stage stereoselective chiral ligand-assisted addition of a 3-titanium furan upon a C12 aldehyde/C17 methyl ester established the furanyl lactone moiety. The tartrate diol was finally converted into the C1,C2 keto-acetate. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Could Hallucinogens Induce Permanent Pupillary Changes in (Abusers? A Case Report from New Zealand

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Ahmed Al-Imam

2017-01-01

Full Text Available An eighteen-year-old female patient of the Caucasian ethnicity from Australasia presented with a persistently dilated pupil causing her discomfort and occasional burning sensation when she is outdoors due to oversensitivity to sunlight. However, her pupillary reaction to light (pupillary light reflex was intact. The patient is a known user of psychedelic substances (entheogens including LSD, NBOMe, psilocybin, and DMT. The condition affects both eyes to the same extent. Thorough medical, neurological, and radiological examinations, including an EEG and an MRI of the head and neck region, were completely normal. All these tests failed to detect any pathophysiological or anatomical abnormalities. The patient is a known case of chronic endogenous depression in association with attention deficit hyperactivity disorder, for which she is taking citalopram and Ritalin, respectively. There was neither a family history nor a similar congenital condition in her family.

Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges.

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McKenna, Dennis J

2004-05-01

Ayahuasca is a hallucinogenic beverage that is prominent in the ethnomedicine and shamanism of indigenous Amazonian tribes. Its unique pharmacology depends on the oral activity of the hallucinogen, N,N-dimethyltryptamine (DMT), which results from inhibition of monoamine oxidase (MAO) by beta-carboline alkaloids. MAO is the enzyme that normally degrades DMT in the liver and gut. Ayahuasca has long been integrated into mestizo folk medicine in the northwest Amazon. In Brazil, it is used as a sacrament by several syncretic churches. Some of these organizations have incorporated in the United States. The recreational and religious use of ayahuasca in the United States, as well as "ayahuasca tourism" in the Amazon, is increasing. The current legal status of ayahuasca or its source plants in the United States is unclear, although DMT is a Schedule I controlled substance. One ayahuasca church has received favorable rulings in 2 federal courts in response to its petition to the Department of Justice for the right to use ayahuasca under the Religious Freedom Restoration Act. A biomedical study of one of the churches, the Uñiao do Vegetal (UDV), indicated that ayahuasca may have therapeutic applications for the treatment of alcoholism, substance abuse, and possibly other disorders. Clinical studies conducted in Spain have demonstrated that ayahuasca can be used safely in normal healthy adults, but have done little to clarify its potential therapeutic uses. Because of ayahuasca's ill-defined legal status and variable botanical and chemical composition, clinical investigations in the United States, ideally under an approved Investigational New Drug (IND) protocol, are complicated by both regulatory and methodological issues. This article provides an overview of ayahuasca and discusses some of the challenges that must be overcome before it can be clinically investigated in the United States.

Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer.

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Grob, Charles S; Danforth, Alicia L; Chopra, Gurpreet S; Hagerty, Marycie; McKay, Charles R; Halberstadt, Adam L; Greer, George R

2011-01-01

Researchers conducted extensive investigations of hallucinogens in the 1950s and 1960s. By the early 1970s, however, political and cultural pressures forced the cessation of all projects. This investigation reexamines a potentially promising clinical application of hallucinogens in the treatment of anxiety reactive to advanced-stage cancer. To explore the safety and efficacy of psilocybin in patients with advanced-stage cancer and reactive anxiety. A double-blind, placebo-controlled study of patients with advanced-stage cancer and anxiety, with subjects acting as their own control, using a moderate dose (0.2 mg/kg) of psilocybin. A clinical research unit within a large public sector academic medical center. Twelve adults with advanced-stage cancer and anxiety. In addition to monitoring safety and subjective experience before and during experimental treatment sessions, follow-up data including results from the Beck Depression Inventory, Profile of Mood States, and State-Trait Anxiety Inventory were collected unblinded for 6 months after treatment. Safe physiological and psychological responses were documented during treatment sessions. There were no clinically significant adverse events with psilocybin. The State-Trait Anxiety Inventory trait anxiety subscale demonstrated a significant reduction in anxiety at 1 and 3 months after treatment. The Beck Depression Inventory revealed an improvement of mood that reached significance at 6 months; the Profile of Mood States identified mood improvement after treatment with psilocybin that approached but did not reach significance. This study established the feasibility and safety of administering moderate doses of psilocybin to patients with advanced-stage cancer and anxiety. Some of the data revealed a positive trend toward improved mood and anxiety. These results support the need for more research in this long-neglected field. clinicaltrials.gov Identifier: NCT00302744.

Activation of serotonin 2A receptors underlies the psilocybin-induced effects on α oscillations, N170 visual-evoked potentials, and visual hallucinations.

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Kometer, Michael; Schmidt, André; Jäncke, Lutz; Vollenweider, Franz X

2013-06-19

Visual illusions and hallucinations are hallmarks of serotonergic hallucinogen-induced altered states of consciousness. Although the serotonergic hallucinogen psilocybin activates multiple serotonin (5-HT) receptors, recent evidence suggests that activation of 5-HT2A receptors may lead to the formation of visual hallucinations by increasing cortical excitability and altering visual-evoked cortical responses. To address this hypothesis, we assessed the effects of psilocybin (215 μg/kg vs placebo) on both α oscillations that regulate cortical excitability and early visual-evoked P1 and N170 potentials in healthy human subjects. To further disentangle the specific contributions of 5-HT2A receptors, subjects were additionally pretreated with the preferential 5-HT2A receptor antagonist ketanserin (50 mg vs placebo). We found that psilocybin strongly decreased prestimulus parieto-occipital α power values, thus precluding a subsequent stimulus-induced α power decrease. Furthermore, psilocybin strongly decreased N170 potentials associated with the appearance of visual perceptual alterations, including visual hallucinations. All of these effects were blocked by pretreatment with the 5-HT2A antagonist ketanserin, indicating that activation of 5-HT2A receptors by psilocybin profoundly modulates the neurophysiological and phenomenological indices of visual processing. Specifically, activation of 5-HT2A receptors may induce a processing mode in which stimulus-driven cortical excitation is overwhelmed by spontaneous neuronal excitation through the modulation of α oscillations. Furthermore, the observed reduction of N170 visual-evoked potentials may be a key mechanism underlying 5-HT2A receptor-mediated visual hallucinations. This change in N170 potentials may be important not only for psilocybin-induced states but also for understanding acute hallucinatory states seen in psychiatric disorders, such as schizophrenia and Parkinson's disease.

Intrahippocampal LSD accelerates learning and desensitizes the 5-HT(2A) receptor in the rabbit, Romano et al.

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Romano, Anthony G; Quinn, Jennifer L; Li, Luchuan; Dave, Kuldip D; Schindler, Emmanuelle A; Aloyo, Vincent J; Harvey, John A

2010-10-01

Parenteral injections of d-lysergic acid diethylamide (LSD), a serotonin 5-HT(2A) receptor agonist, enhance eyeblink conditioning. Another hallucinogen, (±)-1(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), was shown to elicit a 5-HT(2A)-mediated behavior (head bobs) after injection into the hippocampus, a structure known to mediate trace eyeblink conditioning. This study aims to determine if parenteral injections of the hallucinogens LSD, d,l-2,5-dimethoxy-4-methylamphetamine, and 5-methoxy-dimethyltryptamine elicit the 5-HT(2A)-mediated behavior of head bobs and whether intrahippocampal injections of LSD would produce head bobs and enhance trace eyeblink conditioning. LSD was infused into the dorsal hippocampus just prior to each of eight conditioning sessions. One day after the last infusion of LSD, DOI was infused into the hippocampus to determine whether there had been a desensitization of the 5-HT(2A) receptor as measured by a decrease in DOI-elicited head bobs. Acute parenteral or intrahippocampal LSD elicited a 5-HT(2A) but not a 5-HT(2C)-mediated behavior, and chronic administration enhanced conditioned responding relative to vehicle controls. Rabbits that had been chronically infused with 3 or 10 nmol per side of LSD during Pavlovian conditioning and then infused with DOI demonstrated a smaller increase in head bobs relative to controls. LSD produced its enhancement of Pavlovian conditioning through an effect on 5-HT(2A) receptors located in the dorsal hippocampus. The slight, short-lived enhancement of learning produced by LSD appears to be due to the development of desensitization of the 5-HT(2A) receptor within the hippocampus as a result of repeated administration of its agonist (LSD).

Complex discriminative stimulus properties of (+)lysergic acid diethylamide (LSD) in C57Bl/6J mice.

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Benneyworth, Michael A; Smith, Randy L; Barrett, Robert J; Sanders-Bush, Elaine

2005-06-01

The drug discrimination procedure is the most frequently used in vivo model of hallucinogen activity. Historically, most drug discrimination studies have been conducted in the rat. With the development of genetically modified mice, a powerful new tool has become available for investigating the mechanisms of drug-induced behavior. The current paper is part of an ongoing effort to determine the utility of the drug discrimination technique for evaluating hallucinogenic drugs in mice. To establish the training procedures and characterize the stimulus properties of (+)lysergic acid diethylamide (LSD) in mice. Using a two-lever drug discrimination procedure, C57Bl/6J mice were trained to discriminate 0.45 mg/kg LSD vs saline on a VI30 sec schedule of reinforcement, with vanilla-flavored Ensure serving as the reinforcer. As in rats, acquisition was orderly, but the training dose was nearly five-fold higher for mice than rats. LSD lever selection was dose-dependent. Time-course studies revealed a rapid loss of the LSD stimulus effects. The 5-HT(2A/2C) receptor agonist, 2,5-dimethoxy-4-bromoamphetamine [(-)DOB] (1.0 mg/kg), substituted fully for LSD and the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) (1.6 mg/kg), substituted partially for LSD. Pretreatment with the 5-HT(2A) receptor-selective antagonist, MDL 100907, or the 5-HT(1A)-selective antagonist WAY 100635, showed that each antagonist only partially blocked LSD discrimination. Substitution of 1.0 mg/kg (-)DOB for LSD was fully blocked by pretreatment with MDL 100907 but unaltered by WAY 100635 pretreatment. These data suggest that in mice the stimulus effects of LSD have both a 5-HT(2A) receptor and a 5-HT(1A) receptor component.

Return of the lysergamides. Part I: Analytical and behavioral characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD)

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Brandt, Simon D.; Kavanagh, Pierce V.; Westphal, Folker; Stratford, Alexander; Elliott, Simon P.; Hoang, Khoa; Wallach, Jason; Halberstadt, Adam L.

2015-01-01

1-Propionyl-d-lysergic acid diethylamide hemitartrate (1P-LSD) has become available as a ‘research chemical’ in form of blotters and powdered material. This non-controlled derivative of d-lysergic acid diethylamide (LSD) has previously not been described in the published literature despite being closely related to 1-acetyl-LSD (ALD-52), which was developed in the 1950s. This study describes the characterization of 1P-LSD in comparison with LSD using various chromatographic, mass spectrometric methods and nuclear magnetic resonance spectroscopy. An important feature common to LSD and other serotonergic hallucinogens is that they produce 5-HT2A-receptor activation and induce the head-twitch response (HTR) in rats and mice. In order to assess whether 1P-LSD displays LSD-like properties and activates the 5-HT2A receptor, male C57BL/6J mice were injected with vehicle (saline) or 1P-LSD (0.025–0.8 mg/kg, IP) and HTR assessed for 30 min using magnetometer coil recordings. It was found that 1P-LSD produced a dose-dependent increase in HTR counts, and that it had ~38% (ED50 = 349.6 nmol/kg) of the potency of LSD (ED50 = 132.8 nmol/kg). Furthermore, the HTR was abolished when 1P-LSD administration followed pre-treatment with the selective 5-HT2A receptor antagonist M100907 (0.1 mg/kg, SC), which confirms that the behavioral response is mediated by activation of the 5-HT2A receptor. These results indicate that 1P-LSD produces LSD-like effects in mice, consistent with its classification as a serotonergic hallucinogen. Nevertheless, the extent to which 1P-LSD might show psychoactive effects in humans similar to LSD remains to be investigated. PMID:26456305

The effect of psilocin on memory acquisition, retrieval and consolidation in rat.

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Lukas eRambousek

2014-05-01

Full Text Available The involvement of the serotonin system in the pathophysiology of schizophrenia has been elucidated by experiments with hallucinogens. Application of a hallucinogen to humans leads to changes in perception, cognition, emotions and induction of psychotic-like symptoms that resemble symptoms of schizophrenia. In rodent studies, their acute administration affects sensorimotor gating, locomotor activity, social behavior and cognition including working memory, the phenotypes are considered as an animal model of schizophrenia. The complexity and singularity of human cognition raises questions about the validity of animal models utilizing agonists of 5-HT2A receptors. The present study thus investigated the effect of psilocin on memory acquisition, reinforced retrieval and memory consolidation in rats. Psilocin is a main metabolite of psilocybin acting as an agonist at 5-HT2A receptors with a contribution of 5-HT2C and 5-HT1A receptors. First, we tested the effect of psilocin on the acquisition of a Carousel maze, a spatial task requiring navigation using distal cues, attention and cognitive coordination. Psilocin significantly impaired the acquisition of the Carousel Maze at both doses (1 and 4 mg/kg. The higher dose of psilocin blocked the learning processes even in an additional session when the rats received only saline. Next, we examined the effect of psilocin on reinforced retrieval and consolidation in the Morris water maze (MWM. The dose of 4 mg/kg disrupted reinforced retrieval in the Morris water maze. However, the application of a lower dose was without any significant effect. Finally, neither the low nor high dose of psilocin injected post-training caused a deficit in memory consolidation in the MWM. Taken together, the psilocin dose dependently impaired the acquisition of the Carousel maze and reinforced retrieval in MWM; however, it had no effect on memory consolidation.

Case series: toxicity from 25B-NBOMe--a cluster of N-bomb cases.

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Gee, Paul; Schep, Leo J; Jensen, Berit P; Moore, Grant; Barrington, Stuart

2016-01-01

Background A new class of hallucinogens called NBOMes has emerged. This class includes analogues 25I-NBOMe, 25C-NBOMe and 25B-NBOMe. Case reports and judicial seizures indicate that 25I-NBOMe and 25C-NBOMe are more prevalently abused. There have been a few confirmed reports of 25B-NBOMe use or toxicity. Report Observational case series. This report describes a series of 10 patients who suffered adverse effects from 25B-NBOMe. Hallucinations and violent agitation predominate along with serotonergic/stimulant signs such as mydriasis, tachycardia, hypertension and hyperthermia. The majority (7/10) required sedation with benzodiazepines. Analytical method 25B-NBOMe concentrations in plasma and urine were quantified in all patients using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Peak plasma levels were measured between 0.7-10.1 ng/ml. Discussion The NBOMes are desired by users because of their hallucinogenic and stimulant effects. They are often sold as LSD or synthetic LSD. Reported cases of 25B- NBOMe toxicity are reviewed and compared to our series. Seizures and one pharmacological death have been described but neither were observed in our series. Based on our experience with cases of mild to moderate toxicity, we suggest that management should be supportive and focused on preventing further (self) harm. High doses of benzodiazepines may be required to control agitation. Patients who develop significant hyperthermia need to be actively managed. Conclusions Effects from 25B-NBOMe in our series were similar to previous individual case reports. The clinical features were also similar to effects from other analogues in the class (25I-NBOMe, 25C-NBOMe). Violent agitation frequently present along with signs of serotonergic stimulation. Hyperthermia, rhabdomyolysis and kidney injury were also observed.

Novel strategies for sample preparation in forensic toxicology.

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Samanidou, Victoria; Kovatsi, Leda; Fragou, Domniki; Rentifis, Konstantinos

2011-09-01

This paper provides a review of novel strategies for sample preparation in forensic toxicology. The review initially outlines the principle of each technique, followed by sections addressing each class of abused drugs separately. The novel strategies currently reviewed focus on the preparation of various biological samples for the subsequent determination of opiates, benzodiazepines, amphetamines, cocaine, hallucinogens, tricyclic antidepressants, antipsychotics and cannabinoids. According to our experience, these analytes are the most frequently responsible for intoxications in Greece. The applications of techniques such as disposable pipette extraction, microextraction by packed sorbent, matrix solid-phase dispersion, solid-phase microextraction, polymer monolith microextraction, stir bar sorptive extraction and others, which are rapidly gaining acceptance in the field of toxicology, are currently reviewed.

Substance use among medical students in Barcelona (Spain). A comparison with previous surveys.

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Rodriguez, M E; Cami, J

1986-11-01

During the academic year 1983-1984, a survey on drug consumption was conducted among medical students in Barcelona. There was a high proportion of smokers in both sexes. Alcohol consumption was four times higher among men than women; high proof beverages were becoming the most common drinks. Coffee was the caffeine drink consumed by almost the whole population studied. Although cannabis derivatives had been tried at least once by almost all the students, regular consumers were almost non-existent. Amphetamine consumption was restricted to examination periods. The use of opiates, cocaine, hallucinogens, and solvents was rare for the sample. Results from this study are compared with those from similar surveys conducted 5 and 10 years ago.

Immunological effects of ayahuasca in humans.

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dos Santos, Rafael Guimarães

2014-01-01

Ayahuasca is a botanical hallucinogen traditionally used by indigenous groups of the northwest Amazon. In the last decade, the use of ayahuasca has spread from Brazil, Colombia, Ecuador, and Peru to the U.S., Europe, Asia, and Africa. Despite acute and long-term evidence of good tolerability and safety for ayahuasca administered in the laboratory or ritually consumed in religious contexts, little is known about the immunological impact of ayahuasca on humans. Since ayahuasca is used by an increasing number of consumers, and considering its therapeutic potential, more information is needed regarding ayahuasca potential risks. This article presents a brief overview of the available data regarding the immunological impact of ayahuasca in humans.

Determination of Tryptamines and β-Carbolines in Ayahuasca Beverage Consumed During Brazilian Religious Ceremonies.

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Santos, Mônica Cardoso; Navickiene, Sandro; Gaujac, Alain

2017-05-01

Ayahuasca is a potent hallucinogenic beverage prepared from Banisteriopsis caapi in combination with other psychoactive plants. N,N-dimethyltryptamine, tryptamine, harmine, harmaline, harmalol, and tetrahydroharmine were quantified in ayahuasca samples using a simple and low-cost method based on SPE and LC with UV diode-array detection. The experimental variables that affect the SPE method, such as type of solid phase and nature of solvent, were optimized. The method showed good linearity (r > 0.9902) and repeatability (RSD ayahuasca cooking process from a religious group located in the municipality of Fortaleza, state of Ceará, Brazil. The results showed that concentrations of the target compounds ranged from 0.3 to 36.7 g/L for these samples.

Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance.

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Dinis-Oliveira, Ricardo Jorge

2017-02-01

Psilocybin and psilocin are controlled substances in many countries. These are the two main hallucinogenic compounds of the "magic mushrooms" and both act as agonists or partial agonists at 5-hydroxytryptamine (5-HT) 2A subtype receptors. During the last few years, psilocybin and psilocin have gained therapeutic relevance but considerable physiological variability between individuals that can influence dose-response and toxicological profile has been reported. This review aims to discuss metabolism of psilocybin and psilocin, by presenting all major and minor psychoactive metabolites. Psilocybin is primarily a pro-drug that is dephosphorylated by alkaline phosphatase to active metabolite psilocin. This last is then further metabolized, psilocin-O-glucuronide being the main urinary metabolite with clinical and forensic relevance in diagnosis.

Psilocybin impairs high-level but not low-level motion perception.

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Carter, Olivia L; Pettigrew, John D; Burr, David C; Alais, David; Hasler, Felix; Vollenweider, Franz X

2004-08-26

The hallucinogenic serotonin(1A&2A) agonist psilocybin is known for its ability to induce illusions of motion in otherwise stationary objects or textured surfaces. This study investigated the effect of psilocybin on local and global motion processing in nine human volunteers. Using a forced choice direction of motion discrimination task we show that psilocybin selectively impairs coherence sensitivity for random dot patterns, likely mediated by high-level global motion detectors, but not contrast sensitivity for drifting gratings, believed to be mediated by low-level detectors. These results are in line with those observed within schizophrenic populations and are discussed in respect to the proposition that psilocybin may provide a model to investigate clinical psychosis and the pharmacological underpinnings of visual perception in normal populations.

[The substance experience, a history of LSD].

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Beck, François; Bonnet, Nicolas

2013-04-01

This article reviews the recent knowledge on LSD stemming from various disciplines among which pharmacology, sociology and epidemiology. The d-lysergic acid diethylamide (LSD) is a particularly powerful hallucinogenic substance. It produces distortions and hearing, visual and tactile hallucinations. Rarely used (only 1.7% of people aged 15-64 years old have tried it in their lifetime), this very powerful drug generates a strong apprehension within the general population, but the ethnographical studies show that its image seems rather good among illicit drug users. This representation relies both on the proper effects of this substance and also on the history of LSD very closely linked to the counterculture characteristic of the years 1960-1970. © 2013 médecine/sciences – Inserm / SRMS.

Identification of N,N-dimethyltryptamine and beta-carbolines in psychotropic ayahuasca beverage.

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Gambelunghe, Cristiana; Aroni, Kyriaki; Rossi, Riccardo; Moretti, Luca; Bacci, Mauro

2008-10-01

Recently many people have shown great interest in traditional indigenous practices and popular medicine, involving the ingestion of natural psychotropic drugs. We received a request to analyze and determine the nature of a dark green liquid with a dark brown plant sediment, which the police had seized at an airport and inside the home of a person belonging to the 'Santo Daime' religious movement. Gas chromatography/mass spectrometry analysis of the extract identified N,N-dimethyltryptamine, a potent hallucinogen, and the beta-carboline alkaloids harmine and harmaline, revealing monoamine oxidase A-inhibiting properties. These substances are typical components of Ayahuasca, a South American psychotropic beverage obtained by boiling the bark of the liana Banisteriopsis caapi together with the leaves of various admixture plants, principally Psychotria viridis.

Fatal toxic leukoencephalopathy secondary to overdose of a new psychoactive designer drug 2C-E ("Europa").

Science.gov (United States)

Sacks, Justin; Ray, M Jordan; Williams, Sue; Opatowsky, Michael J

2012-10-01

We present a case of a fatal toxic leukoencephalopathy following ingestion of a new psychoactive designer drug known as 2C-E or "Europa." Recreational drugs, particularly hallucinogenic substances, appear to be growing in popularity, with increasing amounts of information available via the Internet to entice potential users. In addition, some newer "designer" psychoactive substances are available for purchase online without adverse legal consequences, therefore adding to their popularity. We describe magnetic resonance imaging (MRI) findings to include selective diffuse toxic injury of the cerebral white matter with sparing of the cortex and most of the deep gray nuclei. To our knowledge, this is the first reported description of cerebral findings on MRI that are likely related to a lethal ingestion of 2C-E.

Use of synthetic stimulants and hallucinogens in a cohort of electronic dance music festival attendees.

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Mohr, Amanda L A; Friscia, Melissa; Yeakel, Jillian K; Logan, Barry K

2018-01-01

Novel psychoactive substances (NPS), often characterized as unregulated psychoactive compounds designed to circumvent existing legislation, have become mainstream on the illicit drug market. Because of their physical and mind-altering properties, NPS may be deliberately or inadvertently ingested at electronic dance music (EDM) festivals to enhance the attendees' appreciation of the music and overall experience. Their widespread use at EDM festivals have been well documented and several adverse events and fatalities associated with NPS ingestion have been reported in the United States. The diversity and rapid turnover in the prevalence of any particular NPS at any given point of time has created several challenges for public health officials, law enforcement, and forensic science communities. Epidemiological studies are often published long after drugs have cycled through the peak of their popularity with users and the scope of testing frequently failing to detect, identify or report the most recently available drugs. The aims of the study included discovering emerging NPS, ascertaining their overall prevalence and determining patterns of use and trends within this targeted population. Over the course of two years, biological samples were collected from 396 (126 blood samples; 227 urine samples; and 384 oral fluid samples) EDM festival attendees. Additionally, survey data regarding prescription and recreational drug use within the last week were collected with follow-up questions related to what substance(s) the person had ingested, amount taken, when the substance was last taken and perceived effects. All biological samples were screened and subsequently confirmed and/or quantified, when appropriate. In response to survey questions, 72% of the participants reported using a recreational drug or medicinal substance within the last week. Users most commonly reported using marijuana and alcohol, followed by "Molly" and cocaine. Of the 396 individuals tested, approximately 75% of the population was positive in at least one biological specimen for drugs and/or alcohol. Of those positive samples, 36% were confirmed to contain one or more NPS and/or 3,4-methylenedioxy-methamphetamine (MDMA). High rates of turnover and spikes in popularity related to NPS are supported by samples confirming positive for alpha-PVP in 2014, however, one year later not a single case was positive for alpha-PVP, and instead increasing numbers of subjects were positive for ethylone. Copyright © 2017 Elsevier B.V. All rights reserved.

Tolerance to LSD and DOB induced shaking behaviour: differential adaptations of frontocortical 5-HT(2A) and glutamate receptor binding sites.

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Buchborn, Tobias; Schröder, Helmut; Dieterich, Daniela C; Grecksch, Gisela; Höllt, Volker

2015-03-15

Serotonergic hallucinogens, such as lysergic acid diethylamide (LSD) and dimethoxy-bromoamphetamine (DOB), provoke stereotype-like shaking behaviour in rodents, which is hypothesised to engage frontocortical glutamate receptor activation secondary to serotonin2A (5-HT2A) related glutamate release. Challenging this hypothesis, we here investigate whether tolerance to LSD and DOB correlates with frontocortical adaptations of 5-HT2A and/or overall-glutamate binding sites. LSD and DOB (0.025 and 0.25 mg/kg, i.p.) induce a ketanserin-sensitive (0.5 mg/kg, i.p., 30-min pretreatment) increase in shaking behaviour (including head twitches and wet dog shakes), which with repeated application (7× in 4 ds) is undermined by tolerance. Tolerance to DOB, as indexed by DOB-sensitive [(3)H]spiroperidol and DOB induced [(35)S]GTP-gamma-S binding, is accompanied by a frontocortical decrease in 5-HT2A binding sites and 5-HT2 signalling, respectively; glutamate-sensitive [(3)H]glutamate binding sites, in contrast, remain unchanged. As to LSD, 5-HT2 signalling and 5-HT2A binding, respectively, are not or only marginally affected, yet [(3)H]glutamate binding is significantly decreased. Correlation analysis interrelates tolerance to DOB to the reduced 5-HT2A (r=.80) as well as the unchanged [(3)H]glutamate binding sites (r=.84); tolerance to LSD, as opposed, shares variance with the reduction in [(3)H]glutamate binding sites only (r=.86). Given that DOB and LSD both induce tolerance, one correlating with 5-HT2A, the other with glutamate receptor adaptations, it might be inferred that tolerance can arise at either level. That is, if a hallucinogen (like LSD in our study) fails to induce 5-HT2A (down-)regulation, glutamate receptors (activated postsynaptic to 5-HT2A related glutamate release) might instead adapt and thus prevent further overstimulation of the cortex. Copyright © 2014 Elsevier B.V. All rights reserved.

Return of the lysergamides. Part I: Analytical and behavioural characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD).

Science.gov (United States)

Brandt, Simon D; Kavanagh, Pierce V; Westphal, Folker; Stratford, Alexander; Elliott, Simon P; Hoang, Khoa; Wallach, Jason; Halberstadt, Adam L

2016-09-01

1-Propionyl-d-lysergic acid diethylamide hemitartrate (1P-LSD) has become available as a 'research chemical' in the form of blotters and powdered material. This non-controlled derivative of d-lysergic acid diethylamide (LSD) has previously not been described in the published literature despite being closely related to 1-acetyl-LSD (ALD-52), which was developed in the 1950s. This study describes the characterization of 1P-LSD in comparison with LSD using various chromatographic and mass spectrometric methods, infrared and nuclear magnetic resonance spectroscopy. An important feature common to LSD and other serotonergic hallucinogens is that they produce 5-HT2A -receptor activation and induce the head-twitch response (HTR) in rats and mice. In order to assess whether 1P-LSD displays LSD-like properties and activates the 5-HT2A receptor, male C57BL/6 J mice were injected with vehicle (saline) or 1P-LSD (0.025-0.8 mg/kg, IP) and HTR assessed for 30 min using magnetometer coil recordings. It was found that 1P-LSD produced a dose-dependent increase in HTR counts, and that it had ~38% (ED50  = 349.6 nmol/kg) of the potency of LSD (ED50  = 132.8 nmol/kg). Furthermore, HTR was abolished when 1P-LSD administration followed pretreatment with the selective 5-HT2A receptor antagonist M100907 (0.1 mg/kg, SC), which was consistent with the concept that the behavioural response was mediated by activation of the 5-HT2A receptor. These results indicate that 1P-LSD produces LSD-like effects in mice, consistent with its classification as a serotonergic hallucinogen. Nevertheless, the extent to which 1P-LSD might show psychoactive effects in humans similar to LSD remains to be investigated. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Recent Advances in Methamphetamine Neurotoxicity Mechanisms and Its Molecular Pathophysiology

Directory of Open Access Journals (Sweden)

Shaobin Yu

2015-01-01

Full Text Available Methamphetamine (METH is a sympathomimetic amine that belongs to phenethylamine and amphetamine class of psychoactive drugs, which are widely abused for their stimulant, euphoric, empathogenic, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, METH produces persistent damage to dopamine and serotonin release in nerve terminals, gliosis, and apoptosis. This review summarized the numerous interdependent mechanisms including excessive dopamine, ubiquitin-proteasome system dysfunction, protein nitration, endoplasmic reticulum stress, p53 expression, inflammatory molecular, D3 receptor, microtubule deacetylation, and HIV-1 Tat protein that have been demonstrated to contribute to this damage. In addition, the feasible therapeutic strategies according to recent studies were also summarized ranging from drug and protein to gene level.

Cannabis and Breast feeding

Energy Technology Data Exchange (ETDEWEB)

Garry, A [Department dIngenierie Biologique, Ecole Polytechnique de Universite de Nice - Sophia Antipolis, 1645 Route des Lucioles, 06410 Biot (France); Virginie Rigourd, V; Aubry, S [Lactarium d' Ile de France, Institut de Puericulture et de Perinatalogie, 26 Boulevard Brune, 75014 Paris (France); Amirouche, A; Fauroux, V [Centre de Recherche Clinique Paris Centre, 89 rue d' Assas, 75006 Paris (France); Serreau, R [Centre de Recherche Clinique Paris Centre EA 3620, 89 rue d' Assas 75006 Paris (France)

2009-07-01

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 breast feeding 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 breast feeding. Mothers who use cannabis must stop breast feeding, or ask for medical assistance to stop cannabis use in order to provide her baby with all the benefits of human milk.

Cannabis and Breast feeding

International Nuclear Information System (INIS)

Garry, A.; Virginie Rigourd, V.; Aubry, S.; Amirouche, A.; Fauroux, V.; Serreau, R.

2009-01-01

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 breast feeding 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 breast feeding. Mothers who use cannabis must stop breast feeding, or ask for medical assistance to stop cannabis use in order to provide her baby with all the benefits of human milk.

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.

Effects of varied doses of psilocybin on time interval reproduction in human subjects.

Science.gov (United States)

Wackermann, Jirí; Wittmann, Marc; Hasler, Felix; Vollenweider, Franz X

2008-04-11

Action of a hallucinogenic substance, psilocybin, on internal time representation was investigated in two double-blind, placebo-controlled studies: Experiment 1 with 12 subjects and graded doses, and Experiment 2 with 9 subjects and a very low dose. The task consisted in repeated reproductions of time intervals in the range from 1.5 to 5s. The effects were assessed by parameter kappa of the 'dual klepsydra' model of internal time representation, fitted to individual response data and intra-individually normalized with respect to initial values. The estimates kappa were in the same order of magnitude as in earlier studies. In both experiments, kappa was significantly increased by psilocybin at 90 min from the drug intake, indicating a higher loss rate of the internal duration representation. These findings are tentatively linked to qualitative alterations of subjective time in altered states of consciousness.

Synesthetic hallucinations induced by psychedelic drugs in a congenitally blind man.

Science.gov (United States)

Dell'Erba, Sara; Brown, David J; Proulx, Michael J

2018-04-01

This case report offers rare insights into crossmodal responses to psychedelic drug use in a congenitally blind (CB) individual as a form of synthetic synesthesia. BP's personal experience provides us with a unique report on the psychological and sensory alterations induced by hallucinogenic drugs, including an account of the absence of visual hallucinations, and a compelling look at the relationship between LSD induced synesthesia and crossmodal correspondences. The hallucinatory experiences reported by BP are of particular interest in light of the observation that rates of psychosis within the CB population are extremely low. The phenomenology of the induced hallucinations suggests that experiences acquired through other means, might not give rise to "visual" experiences in the phenomenological sense, but instead gives rise to novel experiences in the other functioning senses. Copyright © 2018 Elsevier Inc. All rights reserved.

Jurema-Preta (Mimosa tenuiflora [Willd.] Poir.: a review of its traditional use, phytochemistry and pharmacology

Directory of Open Access Journals (Sweden)

Rafael Sampaio Octaviano de Souza

2008-10-01

Full Text Available Numerous plant species are used throughout the world to achieve the modified states of conscientiousness. Some of them have been used for the therapeutic purposes, such as Mimosa tenuiflora (Willd Poir. (family Mimosaceae known as "jurema-preta", an hallucinogenic plant traditionally used for curing and divination by the Indians of northeastern Brazil. In this review, several aspects of the use, phytochemistry, and pharmacology of this plant are considered.Numerosas espécies de plantas são usadas para alterar estados de consciência. Algumas são utilizadas para fins terapêuticos, como Mimosa tenuiflora (Willd Poir. (Mimosaceae conhecida como "jurema-preta", uma planta alucinógena, tradicionalmente utilizada pelos índios no nordeste do Brasil. Nesta revisão, são considerados diversos aspectos do uso, fitoquímica e farmacologia desta planta.

Analysis of psilocin, bufotenine and LSD in hair.

Science.gov (United States)

Martin, Rafaela; Schürenkamp, Jennifer; Gasse, Angela; Pfeiffer, Heidi; Köhler, Helga

2015-03-01

A method for the simultaneous extraction of the hallucinogens psilocin, bufotenine, lysergic acid diethylamide (LSD) as well as iso-LSD, nor-LSD and O-H-LSD from hair with hydrochloride acid and methanol is presented. Clean-up of the hair extracts is performed with solid phase extraction using a mixed-mode cation exchanger. Extracts are measured with liquid chromatography coupled with electrospray tandem mass spectrometry. The method was successfully validated according to the guidelines of the 'Society of Toxicological and Forensic Chemistry' (GTFCh). To obtain reference material hair was soaked in a solution of the analytes in dimethyl sulfoxide/methanol to allow incorporation into the hair. These fortified hair samples were used for method development and can be employed as quality controls. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Prohibited or regulated? LSD psychotherapy and the United States Food and Drug Administration.

Science.gov (United States)

Oram, Matthew

2016-09-01

Over the 1950s and early 1960s, the use of the hallucinogenic drug lysergic acid diethylamide (LSD) to facilitate psychotherapy was a promising field of psychiatric research in the USA. However, during the 1960s, research began to decline, before coming to a complete halt in the mid-1970s. This has commonly been explained through the increase in prohibitive federal regulations during the 1960s that aimed to curb the growing recreational use of the drug. However, closely examining the Food and Drug Administration's regulation of LSD research in the 1960s will reveal that not only was LSD research never prohibited, but that the administration supported research to a greater degree than has been recognized. Instead, the decline in research reflected more complex changes in the regulation of pharmaceutical research and development. © The Author(s) 2016.

Drug Policy and Indigenous Peoples.

Science.gov (United States)

Burger, Julian; Kapron, Mary

2017-06-01

This paper identifies the principal concerns of indigenous peoples with regard to current international treaties on certain psychoactive substances and policies to control and eradicate their production, trafficking, and sale. Indigenous peoples have a specific interest in the issue since their traditional lands have become integrated over time into the large-scale production of coca, opium poppy, and cannabis crops, in response to high demand from the American and European markets, among others. As a consequence, indigenous peoples are persecuted because of their traditional use of these and other plant-based narcotics and hallucinogens. They are also victims of the drug producers who remove them from their lands or forcibly recruit them into the production process. As indigenous peoples are caught in the violent world of illicit drug production, law enforcement often targets them first, resulting in disproportionate rates of criminalization and incarceration.

Health behaviours in a Canadian community college sample: prevalence of drug use and interrelationships among behaviours.

Science.gov (United States)

Mathieson, C M; Faris, P D; Stam, H J; Egger, L A

1992-01-01

This study investigated the prevalence of drug use among a Canadian college sample and the covariation of drug taking and other health-related behaviours. A representative sample of students at a community college in Alberta were interviewed using telephone surveys, mail-in questionnaires and face-to-face interviews. Data was collected on drug, alcohol and caffeine use, cigarette smoking, eating habits, sleep habits and exercise. While use of illicit drugs did not appear to be widespread, alcohol appeared to be a primary substance abuse problem for a minority of subjects. Factor analysis indicated that the various health habits did not form one dimension of health-related behaviours. Four separate factors emerged: abusive drinking, eating habits, a drug use factor (caffeine intake, smoking, cannabis and hallucinogen use), and exercise levels. Findings are discussed in terms of their implications for future research, treatment and intervention.

Advantages of analyzing postmortem brain samples in routine forensic drug screening—case series of three non-natural deaths tested positive for lysergic acid diethylamide (LSD)

DEFF Research Database (Denmark)

Mardal, Marie; Johansen, Sys Stybe; Thomsen, Ragnar

2017-01-01

Three case reports are presented, including autopsy findings and toxicological screening results, which were tested positive for the potent hallucinogenic drug lysergic acid diethylamide (LSD). LSD and its main metabolites were quantified in brain tissue and femoral blood, and furthermore hematoma...... and urine when available. LSD, its main metabolite 2-oxo-3-hydroxy-LSD (oxo-HO-LSD), and iso-LSD were quantified in biological samples according to a previously published procedure involving liquid-liquid extraction and ultra-high performance liquid chromatography − tandem mass spectrometry (UHPLC......-MS/MS). LSD was measured in the brain tissue of all presented cases at a concentration level from 0.34 −10.8 μg/kg. The concentration level in the target organ was higher than in peripheral blood. Additional psychoactive compounds were quantified in blood and brain tissue, though all below toxic concentration...

Strategies for the capillary electrophoretic separation of indole alkaloids in Psilocybe semilanceata.

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Pedersen-Bjergaard, S; Rasmussen, K E; Sannes, E

1998-01-01

While the hallucinogenic mushrooms Psilocybe semilanceata have previously been analyzed for the indole alkaloids psilocybin and baeocystin by capillary zone electrophoresis (CZE) at pH 11.5, the present work focused on the development of an alternative and complementary capillary electrophoretic method for their identification. Owing to their structural similarity and zwitterionic nature, the compounds were difficult to resolve based on different interactions with cationic or anionic micelles. However, while the attempts with micellar electrokinetic chromatography (MEKC) were unsuccessful, rapid derivatization with propyl chloroformate and reanalysis by CZE at pH 11.5 was effective to support identification of the two indole alkaloids. Psilocin was difficult to analyze by CZE at pH 11.5 owing to comigration with the electroosmotic flow. For this compound, the pH of the running buffer was reduced to 7.2 to effectively enhance the electrophoretic mobility.

The effects of intracranial administration of hallucinogens on operant behavior in the rat. I. Lysergic acid diethylamide.

Science.gov (United States)

Mokler, D J; Stoudt, K W; Sherman, L C; Rech, R H

1986-10-01

Lysergic acid diethylamide (LSD) was infused in one microliter volumes into discrete brain regions of rats trained to press a bar for food reinforcement. The sites were chosen as major areas of the brain 5-hydroxytryptamine (5HT) system: the dorsal and median raphe nuclei, dorsal hippocampus, lateral habenular nuclei, and the prefrontal cortex. Following training in a fixed ratio-40 (FR-40) operant behavior rats were implanted for the lateral habenular nuclei, dorsal hippocampus and the prefrontal cortex. Following recovery from surgery, LSD (8.6 to 86 micrograms) or vehicle was infused immediately before a daily operant session. Infusion of vehicle was inactive. LSD produced a dose-dependent decrease in reinforcements and an increase in 10-sec periods of non-responding (pause intervals). LSD was significantly more potent when infused into the dorsal raphe nucleus than following intracerebroventricular (ICV) administration, whereas LSD was less potent when infused into the median raphe, lateral habenula or dorsal hippocampus. ED50s for increases in pause intervals were 9, 13, 23, 25, and 54 micrograms for infusion into the dorsal raphe, prefrontal cortex, dorsal hippocampus, median raphe, and lateral habenular nuclei, respectively. The ED50 for ICV administration in a previous study was 15 micrograms. The ED50 of LSD placed into the prefrontal cortex did not differ significantly from that of the ICV infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

The risk of adolescent suicide across patterns of drug use: a nationally representative study of high school students in the United States from 1999 to 2009.

Science.gov (United States)

Wong, Shane Shucheng; Zhou, Bo; Goebert, Deborah; Hishinuma, Earl S

2013-10-01

Substance use is associated with suicidal ideation, planning and attempts among adolescents, but it is unclear how this association varies across different types and number of substances. This study examined the association between patterns of substance use and suicidality among a nationally representative sample of high school students in the United States during the last decade. Data from the 2001 to 2009 Youth Risk Behavior Survey including 73,183 high school students were analyzed. Logistic regression analyses examined the association between lifetime use of ten common substances of abuse (alcohol, cocaine, ecstasy, hallucinogens, heroin, inhalants, marijuana, methamphetamines, steroids, and tobacco) and four measures of suicidality over the last year (suicidal ideation, suicide plan, suicide attempt, and severe suicide attempt requiring medical attention), controlling for potential confounders (socio-demographic variables, interpersonal violence, sexual intercourse, and symptoms of depression and eating disorder). Among the ten substances, univariate analysis demonstrates that adolescents reporting a history of heroin use have the strongest association with suicidal ideation, suicide plan, suicide attempts and severe suicide attempts in the last year (odds ratio = 5.0, 5.9, 12.0, and 23.6 compared to non-users), followed by users of methamphetamines (OR = 4.3-13.1) and steroids (OR = 3.7-11.8). Cocaine, ecstasy, hallucinogens and inhalants had a moderate association with suicidality (OR = 3.1-10.8). Users of marijuana, alcohol and tobacco also had an increased odds ratio of suicidality (OR = 1.9-5.2). The association between each of ten substances and the four measures of suicidality remained significant with multivariate analysis controlling for multiple confounders (p suicide attempts. The seven illicit substances had a stronger association with severe suicide attempts as compared to all other confounding risk factors except depression. The number of

Cine-club

CERN Multimedia

Ciné-club

2013-01-01

Thursday 4 July 2013 at 20:00 CERN Council Chamber Pi Directed by Darren Aronofsky (USA, 1998) Original version English; french subtitles; 83 minutes First work of director Darren Aronofsky, PI is an intense, hallucinogenic, and an extremely adept exploration into the world of independent science fiction. Depicting one man's obsession to construct a theoretical, numerical order out of chaos in an attempt to decipher a pattern to both the stock market and existence as a whole, he has launched a sense-numbing expedition that simultaneously complies with and defies expectations of science-fiction cinema. Without expensive special effects, Aronofsky uses innovative cinematography and perfectly conceived music to construct both the paranoid world and fanatical fascination of one man’s quest for absolute knowledge. Aronofsky has masterfully fused mathematics and theology to create an eerie sci-fi world lying somewhere between Stanley Kubrick and Rod Serling. Awarded at Sundance Film Festi...

Structure of the Nanobody-Stabilized Active State of the Kappa Opioid Receptor.

Science.gov (United States)

Che, Tao; Majumdar, Susruta; Zaidi, Saheem A; Ondachi, Pauline; McCorvy, John D; Wang, Sheng; Mosier, Philip D; Uprety, Rajendra; Vardy, Eyal; Krumm, Brian E; Han, Gye Won; Lee, Ming-Yue; Pardon, Els; Steyaert, Jan; Huang, Xi-Ping; Strachan, Ryan T; Tribo, Alexandra R; Pasternak, Gavril W; Carroll, F Ivy; Stevens, Raymond C; Cherezov, Vadim; Katritch, Vsevolod; Wacker, Daniel; Roth, Bryan L

2018-01-11

The κ-opioid receptor (KOP) mediates the actions of opioids with hallucinogenic, dysphoric, and analgesic activities. The design of KOP analgesics devoid of hallucinatory and dysphoric effects has been hindered by an incomplete structural and mechanistic understanding of KOP agonist actions. Here, we provide a crystal structure of human KOP in complex with the potent epoxymorphinan opioid agonist MP1104 and an active-state-stabilizing nanobody. Comparisons between inactive- and active-state opioid receptor structures reveal substantial conformational changes in the binding pocket and intracellular and extracellular regions. Extensive structural analysis and experimental validation illuminate key residues that propagate larger-scale structural rearrangements and transducer binding that, collectively, elucidate the structural determinants of KOP pharmacology, function, and biased signaling. These molecular insights promise to accelerate the structure-guided design of safer and more effective κ-opioid receptor therapeutics. Copyright © 2017 Elsevier Inc. All rights reserved.

LSD in pubic hair in a fatality.

Science.gov (United States)

Gaulier, Jean-michel; Maublanc, Julie; Lamballais, Florence; Bargel, Sophie; Lachâtre, Gérard

2012-05-10

Lysergic acid diethylamide (LSD) is a potent hallucinogen, active at very low dosage and its determination in body fluids in a forensic context may present some difficulties, even more so in hair. A dedicated liquid chromatography-electrospray-tandem mass spectrometry (LC-ES-MS/MS) assay in hair was used to document the case of a 24-year-old man found dead after a party. Briefly, after a decontamination step, a 50mg sample of the victim's pubic hair was cut into small pieces (LSD. A LSD concentration of 0.66pg/mg of pubic hair was observed. However, this result remains difficult to interpret owing to the concomitant LSD presence in the victim's post mortem blood and urine, the lack of previously reported LSD concentrations in hair, and the absence of data about LSD incorporation and stability in pubic hair. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

2012 David W. Robertson Award for Excellence in Medicinal Chemistry: Neoclerodanes as Atypical Opioid Receptor Ligands⊥

Science.gov (United States)

Prisinzano, Thomas E.

2013-01-01

The neoclerodane diterpene salvinorin A is the major active component of the hallucinogenic mint plant Salvia divinorum Epling & Játiva (Lamiaceae). Since the finding that salvinorin A exerts its potent psychotropic actions through the activation of opioid receptors, the site of action of morphine and related analogues, there has been much interest in elucidating the underlying mechanisms behind its effects. These effects are particularly remarkable, because (1) salvinorin A is the first reported non-nitrogenous opioid receptor agonist, and (2) its effects are not mediated through the previously investigated targets of psychotomimetics. This perspective outlines our research program, illustrating a new direction to the development of tools to further elucidate the biological mechanisms of drug tolerance and dependence. The information gained from these efforts is expected to facilitate the design of novel agents to treat pain, drug abuse, and other CNS disorders. PMID:23548164

Ayahuasca in adolescence: a preliminary psychiatric assessment.

Science.gov (United States)

Da Silveira, Dartiu Xavier; Grob, Charles S; de Rios, Marlene Dobkin; Lopez, Enrique; Alonso, Luisa K; Tacla, Cristiane; Doering-Silveira, Evelyn

2005-06-01

Ayahuasca is believed to be harmless for those (including adolescents) drinking it within a religious setting. Nevertheless controlled studies on the mental/ psychiatric status of ritual hallucinogenic ayahuasca concoction consumers are still lacking. In this study, 40 adolescents from a Brazilian ayahuasca sect were compared with 40 controls matched on sex, age, and educational background for psychiatric symptomatology. Screening scales for depression, anxiety, alcohol consumption patterns (abuse), attentional problems, and body dysmorphic disorders were used. It was found that, compared to controls, considerable lower frequencies of positive scoring for anxiety, body dismorphism, and attentional problems were detected among ayahuasca-using adolescents despite overall similar psychopathological profiles displayed by both study groups. Low frequencies of psychiatric symptoms detected among adolescents consuming ayahuasca within a religious context may reflect a protective effect due to their religious affiliation. However further studies on the possible interference of other variables in the outcome are necessary.

Quantification of 25C-NBOMe in a fatal poisoning case

DEFF Research Database (Denmark)

Andreasen, Mette Findal; Telving, Rasmus; Rosendal, Ingrid

2015-01-01

, Aarhus University (Denmark) Introduction Recently, a new class of hallucinogenic drugs termed NBOMe has appeared on the drug market and has gained prominence. They have no recognized therapeutic use, and adverse negative health effects have been reported. NBOMe drugs are analogs of the 2C series...... of psychedelic phenethylamine drugs that contain an N-o-methoxybenzyl (“NBOMe”) substituent, which significantly affects their pharmacological activities. The three most frequently reported drugs in this series are 25I-NBOMe, 25B-NBOMe and 25C-NBOMe. Prior to 2010, essentially no history of the human use...... of drugs of the NBOMe class had been reported on the internet. Since then, reports of intoxication and deaths associated with the intake of these drugs have increased. 25I-NBOMe seems to be the most widely abused drug of the NBOMe derivatives, and signs and symptoms of 25I-NBOMe intoxication have been...

Neurotoxicity of methamphetamine and 3,4-methylenedioxymethamphetamine.

Science.gov (United States)

Halpin, Laura E; Collins, Stuart A; Yamamoto, Bryan K

2014-02-27

Amphetamines are a class of psychostimulant drugs that are widely abused for their stimulant, euphoric, empathogenic and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, methamphetamine and 3,4 methylenedioxymethamphetamine (MDMA) produce persistent damage to dopamine and serotonin nerve terminals. This review summarizes the numerous interdependent mechanisms including excitotoxicity, mitochondrial damage and oxidative stress that have been demonstrated to contribute to this damage. Emerging non-neuronal mechanisms by which the drugs may contribute to monoaminergic terminal damage, as well as the neuropsychiatric consequences of this terminal damage are also presented. Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) have similar chemical structures and pharmacologic properties compared to other abused substances including cathinone (khat), as well as a relatively new class of novel synthetic amphetamines known as 'bath salts' that have gained popularity among drug abusers. © 2013.

[The impact of psilocybin on visual perception and spatial orientation--neuropsychological approach].

Science.gov (United States)

Jastrzebski, Mikolaj; Bala, Aleksandra

2013-01-01

Psilocybin is a substance of natural origin, occurring in hallucinogenic mushrooms (most common in the Psilocybe family). After its synthesis in 1958 research began on its psychoactive properties, particularly strong effects on visual perception and spatial orientation. Due to the very broad spectrum of psilocybin effects research began on the different ranges of its actions--including the effect on physiological processes (such as eye saccada movements). Neuro-imaging and neurophysiological research (positron emission tomography-PET and electroencephalography-EEG), indicate a change in the rate of metabolism of the brain and desync cerebral hemispheres. Experimental studies show the changes in visual perception and distortion from psilocybin in the handwriting style of patients examined. There are widely described subjective experiences reported by the subjects. There are also efforts to apply testing via questionnaire on people under the influence of psilocybin, in the context of the similarity of psilocybin-induced state to the initial stages of schizophrenia, as well as research aimed at creating an 'artificial' model of the disease.

[Acute dextromethorphan poisoning based on the records of the Department of Toxicology and Internal Diseases in Poznan].

Science.gov (United States)

Łukasik-Głebocka, Magdalena; Sommerfeld, Karina

2009-01-01

The recreational usage of dextrometorphan, the popular antitussive medicine, has become alarming in Poland. The euphoric and hallucinogenic activity of this drug manifests after high doses, usually ranging from 225 to 1500 mg that may lead to acute poisoning. Currently, dextrometh-orphan is considered as addictive substance. In this article we describe the symptoms of acute dextrometorphan poisoning that have been observed in 11 patients, aged between 16 and 31 years that have been treated in the Department of Toxicology and Internal Diseases Raszeja Hospital in Poznan. In the course of intoxication the most frequent symptom was balance disturbation (12.50%), impaired motoric coordination (11.36%), confusion (11.36%) and papillary dilation (11.36%). Agitation (9.09%), tachycardia (7.95%), hallucinations (6.82%), disartria (5.68%) and hypertension (4.55%) were less common. The doses of dextromethorphan ranged from 4.28 to 16.67 mg/kg. All the patients were treated symptomatically. They recovered without sequelae and were discharged after 1-3 days of hospitalization.

Synthesis of Neoclerodane Diterpenes and Their Pharmacological Effects

Science.gov (United States)

Lovell, Kimberly M.; Prevatt-Smith, Katherine M.; Lozama, Anthony; Prisinzano, Thomas E.

Salvinorin A is a neoclerodane diterpene that has been shown to be an agonist at kappa opioid receptors. Its unique structure makes it an attractive target for synthetic organic chemists due to its seven chiral centers and diterpene scaffold. This molecule is also interesting to pharmacologists because it is a non-serotonergic hallucinogen, and the first opioid ligand discovered that lacks a basic nitrogen. There have been several total synthesis approaches to salvinorin A, and these will be detailed within this chapter. Additionally, research efforts have concentrated on structure modification of the salvinorin A scaffold through semi-synthetic methods. Most modifications have focused on the manipulation of the acetate at C-2 and the furan ring. However, chemistry has also been developed to generate analogs at the C-1 ketone, the C-4 methyl ester, and the C-17 lactone. The synthetic methodologies developed for the salvinorin A scaffold will be described, as well as specific analogs with interesting biological activities.

Crystal Structure of an LSD-Bound Human Serotonin Receptor

Energy Technology Data Exchange (ETDEWEB)

Wacker, Daniel; Wang, Sheng; McCorvy, John D.; Betz, Robin M.; Venkatakrishnan, A.J.; Levit, Anat; Lansu, Katherine; Schools, Zachary L.; Che, Tao; Nichols, David E.; Shoichet, Brian K.; Dror, Ron O.; Roth, Bryan L. (UNCSM); (UNC); (Stanford); (Stanford-MED); (UCSF)

2017-01-01

The prototypical hallucinogen LSD acts via serotonin receptors, and here we describe the crystal structure of LSD in complex with the human serotonin receptor 5-HT2B. The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD’s key diethylamide moiety. LSD dissociates exceptionally slow from both 5-HT2BR and 5-HT2AR—a major target for its psychoactivity. Molecular dynamics (MD) simulations suggest that LSD’s slow binding kinetics may be due to a “lid” formed by extracellular loop 2 (EL2) at the entrance to the binding pocket. A mutation predicted to increase the mobility of this lid greatly accelerates LSD’s binding kinetics and selectively dampens LSD-mediated β-arrestin2 recruitment. This study thus reveals an unexpected binding mode of LSD; illuminates key features of its kinetics, stereochemistry, and signaling; and provides a molecular explanation for LSD’s actions at human serotonin receptors.

LSD, 5-HT (serotonin), and the evolution of a behavioral assay.

Science.gov (United States)

Appel, James B; West, William B; Buggy, James

2004-01-01

Research in our laboratory, supported by NIDA and facilitated by Roger Brown, has indicated that serotonergic neuronal systems are involved in the discriminative stimulus effects of LSD. However, the only compounds that fully antagonize the LSD cue act at both serotonin (5-HT) and dopamine (DA) receptors. In addition, substitution for LSD in standard drug vs. no-drug (DND) discriminations does not necessarily predict either similar mechanisms of action or hallucinogenic potency because 'false positives' occur when animals are given drugs such as lisuride (LHM), quipazine, or, possibly, yohimbine. These effects can be greatly reduced by using drug vs. drug (D-D), drug vs. drug vs. no drug (D-ND), or drug vs. ' other' drug (saline, cocaine, pentobarbital) training procedures. Additional studies, in which drugs were administered directly into the cerebral ventricles or specific brain areas, suggest that structures containing terminal fields of serotonergic neurons might be involved in the stimulus effects of LSD.

Crystal Structure of an LSD-Bound Human Serotonin Receptor.

Science.gov (United States)

Wacker, Daniel; Wang, Sheng; McCorvy, John D; Betz, Robin M; Venkatakrishnan, A J; Levit, Anat; Lansu, Katherine; Schools, Zachary L; Che, Tao; Nichols, David E; Shoichet, Brian K; Dror, Ron O; Roth, Bryan L

2017-01-26

The prototypical hallucinogen LSD acts via serotonin receptors, and here we describe the crystal structure of LSD in complex with the human serotonin receptor 5-HT 2B . The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD's key diethylamide moiety. LSD dissociates exceptionally slow from both 5-HT 2B R and 5-HT 2A R-a major target for its psychoactivity. Molecular dynamics (MD) simulations suggest that LSD's slow binding kinetics may be due to a "lid" formed by extracellular loop 2 (EL2) at the entrance to the binding pocket. A mutation predicted to increase the mobility of this lid greatly accelerates LSD's binding kinetics and selectively dampens LSD-mediated β-arrestin2 recruitment. This study thus reveals an unexpected binding mode of LSD; illuminates key features of its kinetics, stereochemistry, and signaling; and provides a molecular explanation for LSD's actions at human serotonin receptors. PAPERCLIP. Copyright © 2017 Elsevier Inc. All rights reserved.

The 2014 Philip S. Portoghese Medicinal Chemistry Lectureship: The "Phenylalkylaminome" with a Focus on Selected Drugs of Abuse.

Science.gov (United States)

Glennon, Richard A

2017-04-13

The phenylalkylamine, particularly the phenylethylamine, moiety is a common structural feature found embedded in many clinically approved agents. Greater still is its occurrence in drugs of abuse. The simplest phenylethylamine, 2-phenylethylamine itself, is without significant central action when administered at moderate doses, but fairly simple structural modifications profoundly impact its pharmacology and result in large numbers of useful pharmacological tools, agents with therapeutic potential, and in drugs of abuse (e.g., hallucinogens, central stimulants, empathogens), the latter of which are the primary focus here. In vivo drug discrimination techniques and in vitro receptor/transporter methods have been applied to understand the actions of these phenylalkylamines and their mechanisms of action. Thus far, depending upon pendent substituents, certain receptors (e.g., serotonin receptors) and monoamine transporters (i.e., serotonin, dopamine, and norepinephrine transporters) have been implicated as playing major roles in the actions of these abused agents in a complex and, at times, interwoven manner.

[Use of psychoactive drugs by health sciences undergraduate students at the Federal University in Amazonas, Brazil].

Science.gov (United States)

Lucas, Ana Cyra dos Santos; Parente, Rosana Cristina Pereira; Picanço, Neila Soares; Conceição, Denis Alvaci; Costa, Karen Regina Carim da; Magalhães, Igor Rafael dos Santos; Siqueira, João Cladirson Alves

2006-03-01

A survey was conducted with 521 undergraduate health sciences students from the Federal University in Amazonas, Manaus, Brazil. Lifetime alcohol consumption was reported by 87.7% students, as compared to 30.7% for tobacco, with the latter reported more frequently by males (39.7%). The most common illicit drugs were solvents (11.9%), marijuana (9.4%), amphetamines and anxiolytics (9.2% each), cocaine (2.1%), and hallucinogens (1.2%). The main reason for illicit drug use was curiosity. Lifetime use of anabolic steroids was reported by 2.1% of the students. Alcohol abuse in the previous 30 days was reported by 12.4% of the students. Events following drinking included: fights (4.7%), accidents (2.4%), classroom absenteeism (33.7%), and job absenteeism (11.8%). Another important finding was that 47.3% of students drove after drinking. Opinions on drug abuse and patterns agree with those from similar studies in other regions of Brazil.

Chronic non-fatal Datura abuse in a patient of paranoid schizophrenia: a case report.

Science.gov (United States)

Khanra, Sourav; Khess, C R J; Srivastava, Naveen

2015-04-01

A range of psychoactive substances used by patients suffering from schizophrenia varies and may include those which are fatal and may cause serious toxicity leading to death. We here present a case report of a patient suffering from paranoid schizophrenia, who was abusing Datura stramonium over a prolonged period. A 32 year old male presented with aggressive behaviour, irritability for 6 years and regular intake of Datura seeds for 3 years. After taking detailed history and mental status examination (MSE), diagnoses of paranoid schizophrenia and mental and behavioral disorder due to use of hallucinogen were made. He had shown improvement on standard treatment with antipsychotics. D. stramonium is recognized among emerging new psychoactive substances being used across the world. Among various theories we discuss self-medication hypothesis as a mediating factor for this case. Though D. stramonium is notorious for its life threatening sequelae, clinicians should be aware of its chronic abuse as self-medication. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ayahuasca Alters Structural Parameters of the Rat Aorta.

Science.gov (United States)

Pitol, Dimitrius L; Siéssere, Selma; Dos Santos, Rafael G; Rosa, Maria L N M; Hallak, Jaime E C; Scalize, Priscilla H; Pereira, Bruno F; Iyomasa, Melina M; Semprini, Marisa; Riba, Jordi; Regalo, Simone C H

2015-07-01

Ayahuasca is a hallucinogenic brew traditionally used by Northwestern Amazonian indigenous groups for therapeutic purposes. It is prepared by the decoction of Banisteriopsis caapi with the leaves of Psychotria viridis. Banisteriopsis caapi contains β-carbolines that are inhibitors of monoamine oxidase and P. viris is rich in dimethyltryptamine, a 5-HT(1A/2A/2C) agonist. Acute ayahuasca administration produces moderate cardiovascular effects in healthy volunteers, but information regarding long-term use is lacking. This study investigated the effects of ayahuasca (2-4 mL/kg) in the rat aorta after acute and chronic (14 days) administration. Ayahuasca caused flattening and stretching of vascular smooth muscle cells and changes in the arrangement and distribution of collagen and elastic fibers. Chronic treatment with the higher dose significantly increased media thickness and the ratio of media thickness to lumen diameter. More research is needed on the cardiovascular function of long-term ayahuasca consumers.

A critical evaluation of reports associating ayahuasca with life-threatening adverse reactions.

Science.gov (United States)

dos Santos, Rafael Guimarāes

2013-01-01

Ayahuasca is a botanical hallucinogenic preparation traditionally consumed by Northwestern Amazonian indigenous groups. Scientific evidence suggests good tolerability after acute administration of ayahuasca and also after years or even decades of its ritual consumption. Nevertheless, some scientific and media reports associate ayahuasca or some of its alkaloids with severe intoxications. The purpose of the present text is to do a critical evaluation of these reports. The evaluation of the cases highlights the fact that some lack accurate forensic/toxicological information, while others are not directly relevant to traditional ayahuasca preparations. These limitations reduce the possibility of an accurate risk assessment, which could indicate potential contraindications and susceptibilities for ayahuasca consumption. Nevertheless, even with these limitations, the cases suggest that previous cardiac and hepatic pathologies and current use of serotonergic drugs/medications are contraindications to ayahuasca use, and that caution should be taken when using different botanical species and extracted/synthetic alkaloids to prepare ayahuasca analogues.

The epistemic innocence of psychedelic states.

Science.gov (United States)

Letheby, Chris

2016-01-01

One recent development in epistemology, the philosophical study of knowledge, is the notion of 'epistemic innocence' introduced by Bortolotti and colleagues. This concept expresses the idea that certain suboptimal cognitive processes may nonetheless have epistemic (knowledge-related) benefits. The idea that delusion or confabulation may have psychological benefits is familiar enough. What is novel and interesting is the idea that such conditions may also yield significant and otherwise unavailable epistemic benefits. I apply the notion of epistemic innocence to research on the transformative potential of psychedelic drugs. The popular epithet 'hallucinogen' exemplifies a view of these substances as fundamentally epistemically detrimental. I argue that the picture is more complicated and that some psychedelic states can be epistemically innocent. This conclusion is highly relevant to policy debates about psychedelic therapy. Moreover, analysing the case of psychedelics can shed further light on the concept of epistemic innocence itself. Copyright © 2015 Elsevier Inc. All rights reserved.

The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro.

Science.gov (United States)

Morales-García, Jose A; de la Fuente Revenga, Mario; Alonso-Gil, Sandra; Rodríguez-Franco, María Isabel; Feilding, Amanda; Perez-Castillo, Ana; Riba, Jordi

2017-07-13

Banisteriopsis caapi is the basic ingredient of ayahuasca, a psychotropic plant tea used in the Amazon for ritual and medicinal purposes, and by interested individuals worldwide. Animal studies and recent clinical research suggests that B. caapi preparations show antidepressant activity, a therapeutic effect that has been linked to hippocampal neurogenesis. Here we report that harmine, tetrahydroharmine and harmaline, the three main alkaloids present in B. caapi, and the harmine metabolite harmol, stimulate adult neurogenesis in vitro. In neurospheres prepared from progenitor cells obtained from the subventricular and the subgranular zones of adult mice brains, all compounds stimulated neural stem cell proliferation, migration, and differentiation into adult neurons. These findings suggest that modulation of brain plasticity could be a major contribution to the antidepressant effects of ayahuasca. They also expand the potential application of B. caapi alkaloids to other brain disorders that may benefit from stimulation of endogenous neural precursor niches.

Use and Accidental Exposure to Hallucinogenic Agents Reported to the Czech Toxicological Information Centre From 1995 to 2008

Czech Academy of Sciences Publication Activity Database

Mrázová, K.; Navrátil, Tomáš; Pelclová, D.

2011-01-01

Roč. 46, č. 4 (2011), s. 460-465 ISSN 1082-6084 R&D Projects: GA AV ČR IAA400400806 Institutional research plan: CEZ:AV0Z40400503 Keywords : substance use * drug use * marijuana Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.104, year: 2011

Prevalência do uso de drogas entre escolares do ensino médio do Município de São José do Rio Preto, São Paulo, Brasil Drug abuse prevalence among secondary school students in São José do Rio Preto, São Paulo State, Brazil

Directory of Open Access Journals (Sweden)

Elissandro de Freitas Silva

2006-06-01

Full Text Available Este estudo dispõe-se a estudar as taxas de prevalência de consumo de substâncias psicoativas entre escolares do ensino médio no Município de São José do Rio Preto, São Paulo, Brasil, e sua distribuição por sexo e período escolar. Utilizou-se um estudo de corte transversal em escolas públicas do ensino médio do município com uma amostragem de conglomerados. Aplicaram-se 1.041 questionários autopreenchíveis de maneira coletiva nas classes, mantidos sem identificação. As prevalências do consumo na vida foram: álcool 77%, tabaco 28,7%, solventes 18,1%, maconha 12,1%, anfetamínicos 3,7%, cocaína 3,3%, alucinógenos 3,1%, e crack 1,4%. O uso na semana de maconha foi o maior (2,8%, seguido dos solventes (1,3%. O sexo masculino consumiu mais álcool, maconha, cocaína e crack que o feminino. O período noturno teve prevalência significantemente superior para o tabaco, maconha, cocaína e alucinógeno. No presente estudo, verificou-se uma caracterização da prevalência do consumo de substâncias psicoativas em São José do Rio Preto semelhante à encontrada em outros estudos brasileiros.This study investigates the prevalence of drug consumption among secondary school students in São José do Rio Preto, São Paulo State, Southeast Brazil, and its distribution in relation to gender and grade in school. A cross-sectional survey was carried out in São José do Rio Preto. A self-applied questionnaire was answered by a proportional sample of 1,041 teenagers enrolled in 9th, 10th, and 11th grades in public schools. Lifetime consumption of psychoactive substances was: alcohol 77%, tobacco 28.7%, solvents 18.1%, marijuana 12.1%, amphetamines 3.7%, cocaine 3.3%, hallucinogens 3.1%, and crack 1.4%. Weekly use of marijuana was the highest (2.8%, followed by solvents (1.3%. Males consumed more alcohol, marijuana, cocaine, and crack than females. Nighttime use of tobacco, marijuana, cocaine, and hallucinogens was observed. In the present

Perceived ease of access to alcohol, tobacco and other substances in rural and urban US students.

Science.gov (United States)

Warren, Jacob C; Smalley, K Bryant; Barefoot, K Nikki

2015-01-01

Ease of access to substances has been shown to have a direct and significant relationship with substance use for school-aged children. Previous research involving rural samples of middle and high school students reveals that perceived ease of access to substances is a significant predictor of recent use among rural adolescents; however, it is unclear if perceived access to substances varies between rural and urban areas. The purpose of the present study was to examine rural-urban differences in perceived ease of access to alcohol, smoking and chewing tobacco, marijuana, and seven other substances in the US state of Georgia in order to better inform and promote future substance use prevention and programming efforts in rural areas. Data were analyzed from the 2013 Georgia Student Health Survey II, administered in all public and interested private/charter schools in the state of Georgia. A total of 513 909 students (18.2% rural) indicated their perceived ease of access to 11 substances on a four-point Likert-type scale. Rural-urban differences were investigated using χ2 analysis. In general, it appeared the rural-urban differences fell along legal/illicit lines. For middle school students, a significant difference in perceived ease of access was found for each substance, with rural students reporting greater access to smoking tobacco, chewing tobacco, and steroids, and urban students reporting greater access to alcohol, marijuana, cocaine, inhalants, ecstasy, methamphetamine, hallucinogens, and prescription drugs. Rural high school students reported higher access to alcohol, smoking tobacco, chewing tobacco, and steroids, with urban students reporting higher access to marijuana, cocaine, inhalants, ecstasy, and hallucinogens. Perceptions of ease of access more than doubled for each substance in both geographies between middle and high school. The present study found multiple and fairly consistent differences between rural and urban students' perceived ease of access

25C-NBOMe: Preliminary Data on Pharmacology, Psychoactive Effects, and Toxicity of a New Potent and Dangerous Hallucinogenic Drug

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Francesco Saverio Bersani

2014-01-01

Full Text Available Introduction. The use of novel psychoactive substances (NPSs has rapidly increased as well as their online availability. The aim of this paper is to provide a comprehensive review of the nature and the risks associated with 25C-NBOMe, which has recently appeared in the drug market. Methods. A systematic analysis of the scientific literature and a qualitative assessment of online and media resources (e.g., e-newsgroups, chat-rooms, and e-newsletters in 10 languages were carried out. Results. 25C-NBOMe is sold online as legal LSD or as research chemical with different designations such as “Boom,” “Pandora,” “Holland film,” or “N-bomb.” It is a partial agonist of 5-HT2A receptors. It is usually ingested orally/sublingually and, less commonly, nasally, through injection, vaginally, rectally, and smoked. Its effects include sublingual numbing, stimulation, “body high,” hallucinations, dissociation, and anxiety. 25C-NBOMe presents high risk of overdoses; acute toxicity and fatalities have been reported. Conclusions. 25C-NBOMe consumption represents an emerging phenomenon with potential harmful effects. Its use is increased by its online availability at low costs. Health and other professionals should be informed about this new trend of substance use.

Acute toxicity of Psilocybe cubensis (Ear. Sing., Strophariaceae, aqueous extract in mice

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Thiago Berti Kirsten

Full Text Available Psilocybe cubensis (Ear. Sing., Strophariaceae, is a hallucinogen mushroom that has been used since the old times by humans, causing several psychotic effects. P. cubensis contains two tryptamine derivates: psilocybin and psilocin, agonists of the 5-HT2 receptor (serotonin. The main objective of this study was to investigate the acute toxicity effects of P. cubensis aqueous extract (PCAE administration in mice. Male and female adult Swiss mice received PCAE 0.1 mL/10 g i.p., and were observed individually, directly in a glass box and in an open-field. In relation to the data of the control group, PCAE-treated animals presented: an increased gnawing, appearance of wet-dog shakes and a decreased locomotion and rearing frequencies after 29-38 min. Also a clear gender difference was detected, being female mice more sensible to the PCAE than males. It was suggested that PCAE administration produced specific effects on mice behaviors, characteristic of drugs which interfere on central serotonergic and dopaminergic systems. Finally, the observational methods here employed were efficient to evaluate the toxic effects of the extract.

GMP-compliant radiosynthesis of [18F]altanserin and human plasma metabolite studies

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Hasler, F.; Kuznetsova, O.F.; Krasikova, R.N.; Cservenyak, T.; Quednow, B.B.; Vollenweider, F.X.; Ametamey, S.M.; Westera, G.

2009-01-01

[ 18 F]altanserin is the preferred radiotracer for in-vivo labeling of serotonin 2A receptors by positron emission tomography (PET). We report a modified synthesis procedure suited for reliable production of multi-GBq amounts of [ 18 F]altanserin useful for application in humans. We introduced thermal heating for drying of [ 18 F]fluoride as well as for the reaction instead of microwave heating. We furthermore describe solid phase extraction and HPLC procedures for quantitative determination of [ 18 F]altanserin and metabolites in plasma. The time course of arterial plasma activity with and without metabolite correction was determined. 90 min after bolus injection, 38.4% of total plasma activity derived from unchanged [ 18 F]altanserin. Statistical comparison of kinetic profiles of [ 18 F]altanserin metabolism in plasma samples collected in the course of two ongoing studies employing placebo, the serotonin releaser dexfenfluramine and the hallucinogen psilocybin, revealed the same tracer metabolism. We conclude that metabolite analysis for correction of individual plasma input functions used in tracer modeling is not necessary for [ 18 F]altanserin studies involving psilocybin or dexfenfluramine treatment

Availability of websites offering to sell psilocybin spores and psilocybin.

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Lott, Jason P; Marlowe, Douglas B; Forman, Robert F

2009-09-01

This study assesses the availability of websites offering to sell psilocybin spores and psilocybin, a powerful hallucinogen contained in Psilocybe mushrooms. Over a 25-month period beginning in March 2003, eight searches were conducted in Google using the term "psilocybin spores." In each search the first 100 nonsponsored links obtained were scored by two independent raters according to standardized criteria to determine whether they offered to sell psilocybin or psilocybin spores. No attempts were made to procure the products offered for sale in order to ascertain whether the marketed psilocybin was in fact "genuine" or "counterfeit." Of the 800 links examined, 58% led to websites offering to sell psilocybin spores. Additionally, evidence that whole Psilocybe mushrooms are offered for sale online was obtained. Psilocybin and psilocybin spores were found to be widely available for sale over the Internet. Online purchase of psilocybin may facilitate illicit use of this potent psychoactive substance. Additional studies are needed to assess whether websites offering to sell psilocybin and psilocybin spores actually deliver their products as advertised.

Using psilocybin to investigate the relationship between attention, working memory, and the serotonin 1A and 2A receptors.

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Carter, Olivia L; Burr, David C; Pettigrew, John D; Wallis, Guy M; Hasler, Felix; Vollenweider, Franz X

2005-10-01

Increasing evidence suggests a link between attention, working memory, serotonin (5-HT), and prefrontal cortex activity. In an attempt to tease out the relationship between these elements, this study tested the effects of the hallucinogenic mixed 5-HT1A/2A receptor agonist psilocybin alone and after pretreatment with the 5-HT2A antagonist ketanserin. Eight healthy human volunteers were tested on a multiple-object tracking task and spatial working memory task under the four conditions: placebo, psilocybin (215 microg/kg), ketanserin (50 mg), and psilocybin and ketanserin. Psilocybin significantly reduced attentional tracking ability, but had no significant effect on spatial working memory, suggesting a functional dissociation between the two tasks. Pretreatment with ketanserin did not attenuate the effect of psilocybin on attentional performance, suggesting a primary involvement of the 5-HT1A receptor in the observed deficit. Based on physiological and pharmacological data, we speculate that this impaired attentional performance may reflect a reduced ability to suppress or ignore distracting stimuli rather than reduced attentional capacity. The clinical relevance of these results is also discussed.

Innovative recruitment using online networks: lessons learned from an online study of alcohol and other drug use utilizing a web-based, respondent-driven sampling (webRDS) strategy.

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Bauermeister, José A; Zimmerman, Marc A; Johns, Michelle M; Glowacki, Pietreck; Stoddard, Sarah; Volz, Erik

2012-09-01

We used a web version of Respondent-Driven Sampling (webRDS) to recruit a sample of young adults (ages 18-24) and examined whether this strategy would result in alcohol and other drug (AOD) prevalence estimates comparable to national estimates (National Survey on Drug Use and Health [NSDUH]). We recruited 22 initial participants (seeds) via Facebook to complete a web survey examining AOD risk correlates. Sequential, incentivized recruitment continued until our desired sample size was achieved. After correcting for webRDS clustering effects, we contrasted our AOD prevalence estimates (past 30 days) to NSDUH estimates by comparing the 95% confidence intervals of prevalence estimates. We found comparable AOD prevalence estimates between our sample and NSDUH for the past 30 days for alcohol, marijuana, cocaine, Ecstasy (3,4-methylenedioxymethamphetamine, or MDMA), and hallucinogens. Cigarette use was lower than NSDUH estimates. WebRDS may be a suitable strategy to recruit young adults online. We discuss the unique strengths and challenges that may be encountered by public health researchers using webRDS methods.

Human platelet ( sup 125 I)R-DOI binding sites. Characterization by in vitro autoradiography

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Himeno, A.; Saavedra, J.M. (National Institute of Mental Health, Bethesda, MD (USA))

1990-02-01

We quantified binding sites for 2,5-dimethoxy-4-iodo-phenylisopropylamine (DOI), a 5-HT2 agonist and hallucinogen, in human platelets. We incubated sections from human platelet pellets with ({sup 125}I)R-DOI with or without 1 mumol/L ketanserin, followed by autoradiography and computerized microdensitometry. We corrected the values of binding density by the protein content of each section with a densitometric protein assay. The present method revealed a single class of high affinity binding sites for ({sup 125}I)R-DOI, with a Kd of 6.4 +/- 0.7 nmol/L and a Bmax of 100 +/- 10 fmol/mg protein. Kd and Bmax for ({sup 125}I)R-DOI determined by the classical membrane binding assay, were 2.7 +/- 0.4 nmol/L and 100 +/- 10 fmol/mg protein, respectively. The present method is precise, very sensitive, and allows the characterization of ({sup 125}I)R-DOI binding in sections obtained from as little as 3 ml of blood. Standardization is possible after correction by the protein content of each individual section.

Black henbane and its toxicity – a descriptive review

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Anahita Alizadeh

2014-09-01

Full Text Available Black henbane (BH or Hyoscyamus niger, has been used as a medicine since last centuries and has been described in all traditional medicines. It applies as a herbal medicine, but may induce intoxication accidentally or intentionally. All part of BH including leaves, seeds and roots contain some alkaloids such as Hyoscyamine, Atropine, Tropane and Scopolamine. BH has pharmacological effects like bronchodilating, antisecretory, urinary bladder relaxant, spasmolytic, hypnotic, hallucinogenic, pupil dilating, sedative and anti-diarrheal properties. Clinical manifestations of acute BH poisoning are very wide which include mydriasis, tachycardia, arrhythmia, agitation, convulsion and coma, dry mouth, thirst, slurred speech, difficulty speaking, dysphagia, warm flushed skin, pyrexia, nausea, vomiting, headache, blurred vision and photophobia, urinary retention, distension of the bladder, drowsiness, hyper reflexia, auditory, visual or tactile hallucinations, confusion, disorientation, delirium, aggressiveness, and combative behavior. The main treatment of BH intoxicated patients is supportive therapies including gastric emptying (not by Ipecac, administration of activated charcoal and benzodiazepines. Health care providers and physicians particularly emergency physicians and clinical toxicologists should know the nature, medical uses, clinical features, diagnosis and management of BH poisoning.

Acquired auditory-visual synesthesia: A window to early cross-modal sensory interactions

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Pegah Afra

2009-01-01

Full Text Available Pegah Afra, Michael Funke, Fumisuke MatsuoDepartment of Neurology, University of Utah, Salt Lake City, UT, USAAbstract: Synesthesia is experienced when sensory stimulation of one sensory modality elicits an involuntary sensation in another sensory modality. Auditory-visual synesthesia occurs when auditory stimuli elicit visual sensations. It has developmental, induced and acquired varieties. The acquired variety has been reported in association with deafferentation of the visual system as well as temporal lobe pathology with intact visual pathways. The induced variety has been reported in experimental and post-surgical blindfolding, as well as intake of hallucinogenic or psychedelics. Although in humans there is no known anatomical pathway connecting auditory areas to primary and/or early visual association areas, there is imaging and neurophysiologic evidence to the presence of early cross modal interactions between the auditory and visual sensory pathways. Synesthesia may be a window of opportunity to study these cross modal interactions. Here we review the existing literature in the acquired and induced auditory-visual synesthesias and discuss the possible neural mechanisms.Keywords: synesthesia, auditory-visual, cross modal

The neuropsychology of cannabis and other substance use in schizophrenia: review of the literature and critical evaluation of methodological issues.

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Coulston, Carissa M; Perdices, Michael; Tennant, Christopher C

2007-11-01

Research on the neuropsychology of substance use in schizophrenia has been steadily growing over the past decade. However, significant gaps remain in the knowledge of individual substances and their relationship to cognition in the schizophrenia spectrum disorders. Approximately 65 studies to date have directly examined this relationship. Of these, approximately 20 have focused on nicotine, 15 on alcohol, 10 on cocaine, three on stimulants/hallucinogens, one on benzodiazepines, 10 on polydrug abuse, and seven on cannabis. Research on cannabis is especially lacking, given that worldwide it is the most commonly used illicit drug in schizophrenia, is used at higher rates in schizophrenia than in the general population, and makes its own unique contribution to the onset and prognosis of schizophrenia. In the present paper an overview of the neuropsychology literature on substance use in schizophrenia is presented, with special emphasis on cannabis. This incorporates a discussion of the methodological limitations inherent in these studies, and range of potential confounding variables that were not considered or controlled, providing directions for future research into the cognitive correlates of cannabis and other substance use in schizophrenia.

D-serine deficiency attenuates the behavioral and cellular effects induced by the hallucinogenic 5-HT(2A) receptor agonist DOI

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Santini, Martin A; Balu, Darrick T; Puhl, Matthew D

2014-01-01

Both the serotonin and glutamate systems have been implicated in the pathophysiology of schizophrenia, as well as in the mechanism of action of antipsychotic drugs. Psychedelic drugs act through the serotonin 2A receptor (5-HT2AR), and elicit a head-twitch response (HTR) in mice, which directly...... correlates to 5-HT2AR activation and is absent in 5-HT2AR knockout mice. The precise mechanism of this response remains unclear, but both an intrinsic cortico-cortical pathway and a thalamo-cortical pathway involving glutamate release have been proposed. Here, we used a genetic model of NMDAR hypofunction......RNA. These altered functional responses in SRKO mice were not associated with changes in cortical or hippocampal 5-HT levels or in 5-HT2AR and metabotropic glutamate-2 receptor (mGluR2) mRNA and protein expression. Together, these findings suggest that D-serine-dependent NMDAR activity is involved in mediating...

To use or not to use: an update on licit and illicit ketamine use

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Yuet-wah Cheung

2011-03-01

Full Text Available Jih-Heng Li1, Balasingam Vicknasingam2, Yuet-wah Cheung3, Wang Zhou4, Adhi Wibowo Nurhidayat5, Don C Des Jarlais6, Richard Schottenfeld71College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 2National Centre for Drug Research, Universiti Sains Malaysia, Malaysia; 3Department of Sociology, The Chinese University of Hong Kong, Hong Kong, China; 4Wuhan Center for Disease Control and Prevention, Wuhan, China; 5Drug Dependence Hospital RSKO, Jakarta, Indonesia; 6Beth Israel Medical Center, New York, NY; 7School of Psychiatry, Yale University, CT, USAAbstract: Ketamine, a derivative of phencyclidine that was developed in the 1960s, is an anesthetic and analgesic with hallucinogenic effects. In this paper, the pharmacological and toxicological effects of ketamine are briefly reviewed. Ketamine possesses a wide safety margin but such a therapeutic benefit is somewhat offset by its emergence phenomenon (mind-body dissociation and delirium and hallucinogenic effects. The increasing abuse of ketamine, initially predominantly in recreational scenes to experience a “k-hole” and other hallucinatory effects but more recently also as a drug abused during the workday or at home, has further pushed governments to confine its usage in many countries. Recently, urinary tract dysfunction has been associated with long-term ketamine use. In some long-term ketamine users, such damage can be irreversible and could result in renal failure and dialysis. Although ketamine has not yet been scheduled in the United Nations Conventions, previous studies using different assessment parameters to score the overall harms of drugs indicated that ketamine may cause more harm than some of the United Nations scheduled drugs. Some countries in Southeast and East Asia have reported an escalating situation of ketamine abuse. Dependence, lower urinary tract dysfunction, and sexual impulse or violence were the most notable among the ketamine-associated symptoms in these

Ayahuasca Exposure: Descriptive Analysis of Calls to US Poison Control Centers from 2005 to 2015.

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Heise, C William; Brooks, Daniel E

2017-09-01

Ayahuasca is a hallucinogenic plant preparation which usually contains the vine Banisteriopsis caapi and the shrub Psychotria viridis. This tea originates from the Amazon Basin where it is used in religious ceremonies. Because interest in these religious groups spreading as well as awareness of use of ayahuasca for therapeutic and recreational purposes, its use is increasing. Banisteriopsis caapi is rich in β-carbolines, especially harmine, tetrahydroharmine and harmaline, which have monoamine oxidase inhibiting (MAOI) activity. Psychotria viridis contains the 5HT2A/2C/1A receptor agonist hallucinogen N,N-dimethyltryptamine (DMT). Usual desired effects include hallucination, dissociation, mood alteration and perception change. Undesired findings previously reported are nausea, vomiting, hypertension, and tachycardia. All human exposure calls reported to the American Association of Poison Controls Centers' (AAPCC) National Poison Data System (NPDS) between September 1, 2005 and September 1, 2015 were reviewed. Cases were filtered for specific plant derived ayahuasca-related product codes. Abstracted data included the following: case age and gender, exposure reason, exposure route, clinical manifestations, treatments given, medical outcomes and fatality. Five hundred and thirty-eight exposures to ayahuasca botanical products were reported. The majority of the calls to poison control centers came from healthcare facilities (83%). The most common route of exposure was ingestion. Most cases were men (437, 81%, 95% CI 77.7% - 84.3%). The median age was 21 (IQR 18-29). Most exposures were acute. Three hundred thirty-seven (63%) were reported to have a major or moderate clinical effect. The most common clinical manifestations reported were hallucinations (35%), tachycardia (34%), agitation (34%), hypertension (16%), mydriasis (13%) and vomiting (6%). Benzodiazepines were commonly given (30%). There were 28 cases in the series who required endotracheal intubation (5

GMP-compliant radiosynthesis of [{sup 18}F]altanserin and human plasma metabolite studies

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Hasler, F. [University Hospital of Psychiatry, Heffter Research Center, Zurich (Switzerland)], E-mail: fehasler@bli.uzh.ch; Kuznetsova, O.F.; Krasikova, R.N. [Institute of the Human Brain, Russian Academy of Science, St. Petersburg (Russian Federation); Cservenyak, T. [Center for Radiopharmaceutical Sciences of ETH, PSI and University Hospital Zurich (Switzerland); Quednow, B.B.; Vollenweider, F.X. [University Hospital of Psychiatry, Heffter Research Center, Zurich (Switzerland); Ametamey, S.M.; Westera, G. [Center for Radiopharmaceutical Sciences of ETH, PSI and University Hospital Zurich (Switzerland)

2009-04-15

[{sup 18}F]altanserin is the preferred radiotracer for in-vivo labeling of serotonin 2A receptors by positron emission tomography (PET). We report a modified synthesis procedure suited for reliable production of multi-GBq amounts of [{sup 18}F]altanserin useful for application in humans. We introduced thermal heating for drying of [{sup 18}F]fluoride as well as for the reaction instead of microwave heating. We furthermore describe solid phase extraction and HPLC procedures for quantitative determination of [{sup 18}F]altanserin and metabolites in plasma. The time course of arterial plasma activity with and without metabolite correction was determined. 90 min after bolus injection, 38.4% of total plasma activity derived from unchanged [{sup 18}F]altanserin. Statistical comparison of kinetic profiles of [{sup 18}F]altanserin metabolism in plasma samples collected in the course of two ongoing studies employing placebo, the serotonin releaser dexfenfluramine and the hallucinogen psilocybin, revealed the same tracer metabolism. We conclude that metabolite analysis for correction of individual plasma input functions used in tracer modeling is not necessary for [{sup 18}F]altanserin studies involving psilocybin or dexfenfluramine treatment.

Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers.

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Johnson, Matthew W; Sewell, R Andrew; Griffiths, Roland R

2012-06-01

Psilocybin is a well-characterized classic hallucinogen (psychedelic) with a long history of religious use by indigenous cultures, and nonmedical use in modern societies. Although psilocybin is structurally related to migraine medications, and case studies suggest that psilocybin may be efficacious in treatment of cluster headache, little is known about the relationship between psilocybin and headache. This double-blind study examined a broad range of psilocybin doses (0, 5, 10, 20, and 30 mg/70 kg) on headache in 18 healthy participants. Psilocybin frequently caused headache, the incidence, duration, and severity of which increased in a dose-dependent manner. All headaches had delayed onset, were transient, and lasted no more than a day after psilocybin administration. Possible mechanisms for these observations are discussed, and include induction of delayed headache through nitric oxide release. These data suggest that headache is an adverse event to be expected with the nonmedical use of psilocybin-containing mushrooms as well as the administration of psilocybin in human research. Headaches were neither severe nor disabling, and should not present a barrier to future psilocybin research. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Illicit drug use and treatment in South Africa: a review.

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Peltzer, Karl; Ramlagan, Shandir; Johnson, Bruce D; Phaswana-Mafuya, Nancy

2010-11-01

This review synthesizes available epidemiological data on current drug use and substance user treatment admissions in South Africa since 1994, and how changes in the political, economic, and social structures within South Africa, both before and after Apartheid, has made the country more vulnerable to drug use. Based on national surveys, current use of cannabis ranged among adolescents from 2% to 9% and among adults it was 2%, cocaine/crack (0.3%), mandrax/sedatives (0.3%), club drugs/amphetamine-type stimulants (0.2%), opiates (0.1%), and hallucinogens (0.1%). The use of primary illicit substance at admission to South African drug user treatment centers was cannabis 16.9%, methamphetamine (tik) 12.8%, crack/cocaine 9.6%, cannabis and mandrax 3.4%, heroin/opiates 9.2%, and prescription and OTC drugs 2.6%. An increase in substance user treatment admissions has increased. While the prevalence of illicit drug use in South Africa is relatively low compared to the United States and Australia, prevention and intervention policies need to be designed to reduce these levels by targeting the more risky subpopulations identified from this review.

Revisiting Wasson's Soma: exploring the effects of preparation on the chemistry of Amanita muscaria.

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Feeney, Kevin

2010-12-01

In 1968 R. Gordon Wasson first proposed his groundbreaking theory identifying Soma, the hallucinogenic sacrament of the Vedas, as the Amanita muscaria mushroom. While Wasson's theory has garnered acclaim, it is not without its faults. One omission in Wasson's theory is his failure to explain how pressing and filtering Soma, as described in the Rig Veda, supports his theory of Soma's identity. Several critics have reasoned that such preparation should be unnecessary if equivalent results can be obtained by consuming the raw plant, as is done with other psychoactive mushrooms. In order to address these specific criticisms over 600 anecdotal accounts of Amanita muscaria inebriation were collected and analyzed to determine the impact of preparation on Amanita muscaria's effects. The findings of this study demonstrated that the effects of Amanita muscaria were related to the type of preparation employed, and that its toxic effects were considerably reduced by preparations that paralleled those described for Soma in the Rig Veda. While unlikely to end debate over the identity of Soma, this study's findings help to solidify the foundation of Wasson's theory, and also to demonstrate the importance of preparation in understanding and uncovering the true identity of Soma.

The claustrum’s proposed role in consciousness is supported by the effect and target localization of Salvia Divinorum

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Klaus M Stiefel

2014-02-01

Full Text Available This article brings together three findings and ideas relevant for the understanding of human consciousness: (I Crick's and Koch's theory that the claustrum is a conductor of consciousness center crucial for subjective conscious experience. (II Subjective reports of the consciousness-altering effects the plant Salvia divinorum, whose primary active ingredient is salvinorin A, a -opioid receptor agonist. (III The high density of -opioid receptors in the claustrum. Fact III suggests that the consciousness-altering effects of salvinorin A are due to a κ-opioid receptor mediated inhibition of primarily the claustrum and, additionally, the deep layers of the cortex, mainly in prefrontal areas. Consistent with Crick & Koch’s theory that the claustrum plays a key role in consciousness, our analysis of the subjective effects of Salvia divinorum finds that salvia disrupts certain facets of consciousness much more than the largely-serotonergic hallucinogen LSD. Based on this data and on the relevant literature, we suggest that the claustrum does indeed serve as a conductor for certain aspects of higher-order integration of brain activity, while integration of auditory and visual signals mostly relies on coordination by other areas including parietal cortex and the pulvinar.

Lysergic acid diethylamide causes photoreceptor cell damage through inducing inflammatory response and oxidative stress.

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Hu, Qi-Di; Xu, Ling-Li; Gong, Yan; Wu, Guo-Hai; Wang, Yu-Wen; Wu, Shan-Jun; Zhang, Zhe; Mao, Wei; Zhou, Yu-Sheng; Li, Qin-Bo; Yuan, Jian-Shu

2018-01-19

Lysergic acid diethylamide (LSD), a classical hallucinogen, was used as a popular and notorious substance of abuse in various parts of the world. Its abuse could result in long-lasting abnormalities in retina and little is known about the exact mechanism. This study was to investigate the effect of LSD on macrophage activation state at non-toxic concentration and its resultant toxicity to photoreceptor cells. Results showed that cytotoxicity was caused by LSD on 661 W cells after co-culturing with RAW264.7 cells. Treatment with LSD-induced RAW264.7 cells to the M1 phenotype, releasing more pro-inflammatory cytokines, and increasing the M1-related gene expression. Moreover, after co-culturing with RAW264.7 cells, significant oxidative stress in 661 W cells treated with LSD was observed, by increasing the level of malondialdehyde (MDA) and reactive oxygen species (ROS), and decreasing the level of glutathione (GSH) and the activity of superoxide dismutase (SOD). Our study demonstrated that LSD caused photoreceptor cell damage by inducing inflammatory response and resultant oxidative stress, providing the scientific rationale for the toxicity of LSD to retina.

The Students\\' Knowledge, Attitude and Performance about Prevention of Using of Ecstasy

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Mitra Zolfaghari

2009-08-01

Full Text Available Introduction: In recent decades because of stimulant and hallucinogenic properties of ecstasy, it has been found so many users among adolescent and youth people. The aim of present study was the study of students' knowledge, attitude and performance related to prevention of using of ecstasy. Method: This descriptive – analytic study has done in 400 female students of government schools of zone no. 17. The sample selected by clustering random sampling and their knowledge, attitude, and performance measured by using of researchers developed questionnaire which shown sufficient level of validity and reliability. Results: The results showed that the majority of students (41% had low knowledge, 56% had positive attitude, and 55.1% had good performance related to prevention of using of ecstasy. Also, there was positive relationship between students' knowledge and attitude also attitude and performance. There was also positive relationship between some of the demographic characteristics and the students' knowledge, attitude and performance related to prevention of using of ecstasy. Conclusion: Finding of the research showed that the students' knowledge related to use of ecstasy is low, therefore appropriate instructional intervention in order to promote the students' knowledge is necessary.

Ayahuasca Tourism: Participants in Shamanic Rituals and their Personality Styles, Motivation, Benefits and Risks.

Science.gov (United States)

Kavenská, Veronika; Simonová, Hana

2015-01-01

Ayahuasca continues to attract tourists to South America, where there has been a growth in the number of centers offering hallucinogenic ayahuasca experiences. The aims of this study were to (1) discover the reasons foreigners seek this type of experience; (2) define what an ayahuasca experience entails; (3) discover subjective perceptions of ayahuasca's benefits and risks; and (4) describe personality styles of participants using the personality questionnaire (PSSI). Participants (N=77) were persons who had travelled to South America to use ayahuasca. Among the most frequent motivations were curiosity, desire to treat mental health problems, need for self-knowledge, interest in psychedelic medicine, spiritual development, and finding direction in life. Frequently mentioned benefits included self-knowledge, change in the way one relates to oneself, spiritual development, improved interpersonal relations, overcoming mental and physical problems, and gaining a new perspective on life. Stated potential risks included lack of trust in the shaman or organizer, inaccurate information provided by the shaman or organizer, and exposure to dangerous situations. PSSI results showed that people using ayahuasca scored significantly above the norm on the scales of intuition, optimism, ambition, charm, and helpfulness and significantly lower on the scales of distrust and quietness.

Establishment of Radiolabelling Method for the Development of Neurodegenerative Disease Imaging Agent Using 5-HT{sub 1A} Subtype of Receptor Anatagonist

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Choi, Sun Ju; Choi, Sang Mu; Kim, On Hee; Hong, Young Don; Park, Kyung Bae [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2005-07-01

The 5-HT1A subtype of receptors for the neurotransmitter serotonin is predominantly located in the limbic forebrain. And it is involved in the modulation of emotion and the function of the hypothalamus. Since 5-HT1A receptors are implicated in the pathogenesis of anxiety, depression, hallucinogenic behaviour, motion sickness and eating disorders, they are an important target for drug therapy and diagnosis of diseases. Serotonin is synthesized from the amino acid L-tryptophan by sequential hydroxylation and decarboxylation. It is stored in presynaptic vesicles and released from nerve terminals during neuronal firing. One of the best-characterised binding sites for serotonin is the 5-HT1A receptor. This is mainly due to the relatively early discovery of a selective ligand, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) for this subpopulation. Thus, many researchers have tried to develop a radioligand capable of assessing in vivo changes in 5-HT1A receptors in depressed subjects, people with anxiety disorders, patients with Alzheimer's disease and schizophrenics. In present study, we studied the radioligands which would play a role in visualization and quantification of this important neuroreceptor for single-photon emission tomography (SPET)

Establishment of Radiolabelling Method for the Development of Neurodegenerative Disease Imaging Agent Using 5-HT1A Subtype of Receptor Anatagonist

International Nuclear Information System (INIS)

Choi, Sun Ju; Choi, Sang Mu; Kim, On Hee; Hong, Young Don; Park, Kyung Bae

2005-01-01

The 5-HT1A subtype of receptors for the neurotransmitter serotonin is predominantly located in the limbic forebrain. And it is involved in the modulation of emotion and the function of the hypothalamus. Since 5-HT1A receptors are implicated in the pathogenesis of anxiety, depression, hallucinogenic behaviour, motion sickness and eating disorders, they are an important target for drug therapy and diagnosis of diseases. Serotonin is synthesized from the amino acid L-tryptophan by sequential hydroxylation and decarboxylation. It is stored in presynaptic vesicles and released from nerve terminals during neuronal firing. One of the best-characterised binding sites for serotonin is the 5-HT1A receptor. This is mainly due to the relatively early discovery of a selective ligand, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) for this subpopulation. Thus, many researchers have tried to develop a radioligand capable of assessing in vivo changes in 5-HT1A receptors in depressed subjects, people with anxiety disorders, patients with Alzheimer's disease and schizophrenics. In present study, we studied the radioligands which would play a role in visualization and quantification of this important neuroreceptor for single-photon emission tomography (SPET)

Effects of Ayahuasca and its Alkaloids on Drug Dependence: A Systematic Literature Review of Quantitative Studies in Animals and Humans.

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Nunes, Amanda A; Dos Santos, Rafael G; Osório, Flávia L; Sanches, Rafael F; Crippa, José Alexandre S; Hallak, Jaime E C

2016-01-01

Recently, the anti-addictive potential of ayahuasca, a dimethyltryptamine(DMT)- and β-carboline-rich hallucinogenic beverage traditionally used by indigenous groups of the Northwest Amazon and currently by syncretic churches worldwide, has received increased attention. To better evaluate this topic, we performed a systematic literature review using the PubMed database to find quantitative studies (using statistical analysis) that assessed the effects of ayahuasca or its components in drug-related symptoms or disorders. We found five animal studies (using harmaline, harmine, or ayahuasca) and five observational studies of regular ayahuasca consumers. All animal studies showed improvement of biochemical or behavioral parameters related to drug-induced disorders. Of the five human studies, four reported significant reductions of dependence symptoms or substance use, while one did not report significant results. The mechanisms responsible for the anti-addictive properties of ayahuasca and its alkaloids are not clarified, apparently involving both peripheral MAO-A inhibition by the β-carbolines and central agonism of DMT at 5-HT2A receptors expressed in brain regions related to the regulation of mood and emotions. Although results are promising, controlled studies are needed to replicate these preliminary findings.

Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members.

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Santos, R G; Landeira-Fernandez, J; Strassman, R J; Motta, V; Cruz, A P M

2007-07-25

The use of the hallucinogenic brew ayahuasca, obtained from infusing the shredded stalk of the malpighiaceous plant Banisteriopsis caapi with the leaves of other plants such as Psychotria viridis, is growing in urban centers of Europe, South and North America in the last several decades. Despite this diffusion, little is known about its effects on emotional states. The present study investigated the effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in members of the Santo Daime, an ayahuasca-using religion. Standard questionnaires were used to evaluate state-anxiety (STAI-state), trait-anxiety (STAI-trait), panic-like (ASI-R) and hopelessness (BHS) in participants that ingested ayahuasca for at least 10 consecutive years. The study was done in the Santo Daime church, where the questionnaires were administered 1h after the ingestion of the brew, in a double-blind, placebo-controlled procedure. While under the acute effects of ayahuasca, participants scored lower on the scales for panic and hopelessness related states. Ayahuasca ingestion did not modify state- or trait-anxiety. The results are discussed in terms of the possible use of ayahuasca in alleviating signs of hopelessness and panic-like related symptoms.

Long-term effects of ayahuasca in patients with recurrent depression: a 5-year qualitative follow-up

Directory of Open Access Journals (Sweden)

Rafael G. Dos Santos

Full Text Available Abstract Background Ayahuasca is a botanical hallucinogenic preparation traditionally used by indigenous populations of Northwestern Amazonian countries for ritual and therapeutic purposes. It is rich in β-carboline alkaloids and N,N-dimethyltryptamine (DMT. Preclinical, observational, and experimental studies suggest that ayahuasca and its alkaloids have anxiolytic and antidepressive effects. We recently reported in an open-label trial that ayahuasca administration was associated with significant decreases in depression symptoms for 2-3 weeks after the experimental session in 17 patients with treatment-resistant major depressive disorder. Objectives To investigate if the experiment had any long-lasting effects on patients Methods Eight patients were interviewed 4 to 7 years after ayahuasca intake. Results Our results suggest that ayahuasca was well tolerated and that symptom reductions were limited to a few weeks. Importantly, most patients believed that the experience was among the most important of their lives, even 4-7 years later. Discussion To the best of our knowledge, this is the first long-term follow-up of a clinical sample that participated in an ayahuasca trial. Further studies with different and repeated dosing should be designed to further explore the antidepressive and anxiolytic effects of ayahuasca.

Psychedelic Fauna for Psychonaut Hunters: A Mini-Review.

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Orsolini, Laura; Ciccarese, Michela; Papanti, Duccio; De Berardis, Domenico; Guirguis, Amira; Corkery, John M; Schifano, Fabrizio

2018-01-01

Currently different classes of psychoactive substances are easily available for abuse, including several hundred novel psychoactive substances (NPS). Some of these drugs occur naturally in plants and animals or are chemically modified from plant or animal compounds and have been abused by humans over millennia. Recently, the occurrence of a new "drug culture" (e.g., psychonauts) who consume a great variety of NPS with hallucinogenic/psychedelic properties, facilitated the development of a new "psychedelic trend" toward the consumption of substances contained in some species of animals ("psychedelic fauna"). The present review aims at providing an overview of the most commonly abused "psychedelic animals," by combining a dual search strategy coming from online psychonauts' experiences and English literature searches on the PubMed/Medline Google Scholar databases. A multilingual qualitative assessment on a range of websites and online resources was performed in order to identify a list of animals who possess some psychoactive properties and could be abused by humans for recreational purposes. Several species are implicated (i.e., ants, amphibians, fish). Routes of administration depend on the animal, substance included, metabolism, toxicity and individual, social and cultural variability. Online purchase and access are easy through tourism-related search strategies (" frog trip ," " help of charmer snake," " religious trip ").

Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies.

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Studerus, Erich; Kometer, Michael; Hasler, Felix; Vollenweider, Franz X

2011-11-01

Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.

Psilocybin for treating substance use disorders?

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de Veen, Bas T H; Schellekens, Arnt F A; Verheij, Michel M M; Homberg, Judith R

2017-02-01

Evidence based treatment for Substance use disorders (SUD) includes psychotherapy and pharmacotherapy. However, these are only partially effective. Hallucinogens, such as psilocybin, may represent potential new treatment options for SUD. This review provides a summary of (human) studies on the putative therapeutic effects of psilocybin, and discusses the receptor systems, brain regions and cognitive and emotional processes mediating psilocybin's effects. Psilocybin's chemical structure is similar to that of serotonin. Dysregulations in the serotonin system are associated with alterations in stress hormones, such as cortisol, and mood disorders. After psilocybin administration cortisol levels spike and activate the executive control network, with subsequent increased control over emotional processes, and relief of negative thinking and persistent negative emotions. Preliminary data of ongoing alcohol and smoking addiction studies in humans shows promising effects of psilocybin administration on substance use. Importantly, psilocybin has a low risk of toxicity and dependence and can be used safely under controlled clinical conditions. Areas covered: This paper is a narrative review based on the search terms: psilocybin, substance use disorder, addiction, depression, serotonin. Literature on potential efficacy and mechanisms of action of psilocybin in SUD is discussed. Expert commentary: Recent positive findings with psilocybin need confirmation in well-designed placebo controlled randomized trials employing a large sample size.

Assessing the extent and nature of wildlife trade on the dark web.

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Harrison, Joseph R; Roberts, David L; Hernandez-Castro, Julio

2016-08-01

Use of the internet as a trade platform has resulted in a shift in the illegal wildlife trade. Increased scrutiny of illegal wildlife trade has led to concerns that online trade of wildlife will move onto the dark web. To provide a baseline of illegal wildlife trade on the dark web, we downloaded and archived 9852 items (individual posts) from the dark web, then searched these based on a list of 121 keywords associated with illegal online wildlife trade, including 30 keywords associated with illegally traded elephant ivory on the surface web. Results were compared with items known to be illegally traded on the dark web, specifically cannabis, cocaine, and heroin, to compare the extent of the trade. Of these 121 keywords, 4 resulted in hits, of which only one was potentially linked to illegal wildlife trade. This sole case was the sale and discussion of Echinopsis pachanoi (San Pedro cactus), which has hallucinogenic properties. This negligible level of activity related to the illegal trade of wildlife on the dark web relative to the open and increasing trade on the surface web may indicate a lack of successful enforcement against illegal wildlife trade on the surface web. © 2016 Society for Conservation Biology.

Associations between attention deficit hyperactivity disorder symptom domains and DSM-IV lifetime substance dependence.

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Ameringer, Katherine J; Leventhal, Adam M

2013-01-01

Most studies of attention deficit hyperactivity disorder (ADHD) in the substance dependence literature have assessed ADHD as a single, categorical entity. This approach limits characterization across the spectrum of ADHD symptomatology and may mask differences across the two core domains of ADHD symptoms-hyperactive-impulsive (HI) and inattention (IN). Further, it is unclear whether relations of HI and IN symptoms to substance dependence extend across drug classes and to the general population. This cross-sectional study investigated associations of lifetime ADHD HI and IN symptom levels to individual classes of lifetime substance dependence (alcohol, nicotine, depressants, opioids, stimulants, cannabis, hallucinogens, polysubstance) in a population-based sample of 34,653 American adults. HI and IN were associated with the majority of dependence diagnoses in a linear pattern, such that each additional symptom was associated with a proportional increase in odds of dependence. After adjusting for the overlap between symptom domains, both HI and IN uniquely associated with alcohol, nicotine, and polysubstance dependence, but only HI uniquely associated with dependence on illicit substances. These findings suggest that individuals in the general population with elevated levels of ADHD (particularly HI) symptoms are at risk for various forms of substance dependence and could benefit from preventive interventions. Copyright © American Academy of Addiction Psychiatry.

Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy.

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Wagner, Mark T; Mithoefer, Michael C; Mithoefer, Ann T; MacAulay, Rebecca K; Jerome, Lisa; Yazar-Klosinski, Berra; Doblin, Rick

2017-08-01

A growing body of research suggests that traumatic events lead to persisting personality change characterized by increased neuroticism. Relevantly, enduring improvements in Post-Traumatic Stress Disorder (PTSD) symptoms have been found in response to 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. There is evidence that lasting changes in the personality feature of "openness" occur in response to hallucinogens, and that this may potentially act as a therapeutic mechanism of change. The present study investigated whether heightened Openness and decreased Neuroticism served as a mechanism of change within a randomized trial of MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD. The Clinician-Administered PTSD Scale (CAPS) Global Scores and NEO PI-R Personality Inventory (NEO) Openness and Neuroticism Scales served as outcome measures. Results indicated that changes in Openness but not Neuroticism played a moderating role in the relationship between reduced PTSD symptoms and MDMA treatment. Following MDMA-assisted psychotherapy, increased Openness and decreased Neuroticism when comparing baseline personality traits with long-term follow-up traits also were found. These preliminary findings suggest that the effect of MDMA-assisted psychotherapy extends beyond specific PTSD symptomatology and fundamentally alters personality structure, resulting in long-term persisting personality change. Results are discussed in terms of possible mechanisms of psychotherapeutic change.

Pathological findings in 2 cases of fatal 25I-NBOMe toxicity.

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Walterscheid, Jeffrey P; Phillips, Garrett T; Lopez, Ana E; Gonsoulin, Morna L; Chen, Hsin-Hung; Sanchez, Luis A

2014-03-01

The research compound 25I-NBOMe, also known as CIMBI-5 or INBMeO, was created in academic laboratories as a potent serotonin 2A receptor agonist. Because of its high affinity and ambiguous legal status, recreational drug enthusiasts have used this compound as a powerful alternative to other hallucinogenic drugs such as lysergic acid diethylamide. We report 2 deaths after 25I-NBOMe ingestion by decedents who attended separate "rave" parties. The first case involved a 21-year-old male who admitted taking "acid" to his friend. A sudden violent rage caused him to flail about, and he subsequently became unresponsive. The postmortem examination revealed numerous external injuries that were consistent with physical aggression. The second case involved a 15-year-old female who was socializing outside a rave party, became ill, and rapidly deteriorated as her friend transported her to the hospital. The postmortem assessment was similar to the first case in that external contusions featured prominently. Comprehensive toxicology screens in both cases revealed only evidence of marijuana use. A deeper analysis using time-of-flight mass spectrometry revealed the presence of 25I-NBOMe, which was further confirmed by tandem-mass spectrometry. The behavior and injuries in these cases reveal a consistent pattern preceding fatal 25I-NBOMe toxicity.

Trends in Substance Use Across the Nation and South Dakota.

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Daniel, Jeremy; Owen, Amanda

2016-01-01

With the discovery of morphine in the early 1800s, substance abuse quickly followed. Next came the production of heroin and other synthetic opioids, along with increases in nonmedical use of prescription medications. In the 21st century, drug abuse and addiction continues to rise nationwide with the three most common drugs abused in adolescents being marijuana, synthetic marijuana, and hallucinogens. Among adolescents and adults nationwide, rates of alcohol, opioids, and amphetamine use have increased over the last decade. In South Dakota, the most prevalent drugs consist of alcohol, methamphetamine, heroin, and prescription opioids. Through the implementation and use of the Prescription Drug Monitoring Program (PDMP) by the South Dakota Board of Pharmacy (SDBOP), hydrocodone/acetaminophen has been identified as the most dispensed controlled substance in the state with roughly 21,000 prescriptions dispensed last November alone. While the PDMP does not necessarily encompass all controlled substances used by the patient (e.g., those purchased from illicit sources), the generation of PDMP reports by physicians and pharmacists is still beneficial. With increased use of the PDMP along with urine drug screens and patient interviews, health care professionals can continue to work collaboratively to help curb the growing epidemic of substance use. Copyright© South Dakota State Medical Association.

Phytochemical investigation of natural and in vitro raised Vṛddhadāruka plants.

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Bharati, Asha Jyoti; Bansal, Yogendra Kumar

2014-01-01

Argyreia nervosa commonly known as elephant creeper (English) and Vṛddhadāruka (Sanskrit) is a woody climber that belongs to the family Convolvulaceae. Seeds of this plant contain hallucinogens including ergot alkaloids and a naturally occurring lysergic acid amide. Traditionally the plant is used in the treatment of gonorrhea, strangury, chronic ulcers, diabetes, anemia and cerebral disorders. The plant is also used as appetitiser, brain tonic, cardiotonic, aphrodisiac. It possesses anti-inflammatory, immunomodulatory, antibacterial, antiviral and antifungal activities. To give an account of information on in vitro regeneration and phytochemical analysis of the plant. Nodal explants were selected for in vitro regeneration. Different aerial parts viz., seeds, natural and in vitro leaf, stem and callus were dried and extracted with different solvents and were subjected to various phytochemical analyses. Different concentrations of 6-benzylaminopurine showed shoot and root initiation. The study of phytochemical screening of different extracts showed the presence of bioactive substances like flavonoids, alkaloids, terpenoids, etc. The study will provide an efficient in vitro protocol for micropropagation as an alternative method to conserve the plant and shows the presence of some important secondary metabolites in the nature grown and in vitro raised plants which can be useful for treatment of various diseases.

Disrupted integration of sensory stimuli with information about the movement of the body as a mechanism explaining LSD-induced experience.

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Juszczak, Grzegorz R

2017-03-01

LSD (lysergic acid diethylamide) is a model psychedelic drug used to study mechanism underlying the effects induced by hallucinogens. However, despite advanced knowledge about molecular mechanism responsible for the effects induced by LSD and other related substances acting at serotonergic 5-HT 2a receptors, we still do not understand how these drugs trigger specific sensory experiences. LSD-induced experience is characterised by perception of movement in the environment and by presence of various bodily sensations such as floating in space, merging into surroundings and movement out of the physical body (the out-of-body experience). It means that a large part of the experience induced by the LSD can be simplified to the illusory movement that can be attributed to the self or to external objects. The phenomenology of the LSD-induced experience has been combined with the fact that serotonergic neurons provide all major parts of the brain with information about the level of tonic motor activity, occurrence of external stimuli and the execution of orienting responses. Therefore, it has been proposed that LSD-induced stimulation of 5-HT 2a receptors disrupts the integration of the sensory stimuli with information about the movement of the body leading to perception of illusory movement. Copyright © 2017 Elsevier Ltd. All rights reserved.

Forensic analysis of Salvia divinorum using multivariate statistical procedures. Part I: discrimination from related Salvia species.

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Willard, Melissa A Bodnar; McGuffin, Victoria L; Smith, Ruth Waddell

2012-01-01

Salvia divinorum is a hallucinogenic herb that is internationally regulated. In this study, salvinorin A, the active compound in S. divinorum, was extracted from S. divinorum plant leaves using a 5-min extraction with dichloromethane. Four additional Salvia species (Salvia officinalis, Salvia guaranitica, Salvia splendens, and Salvia nemorosa) were extracted using this procedure, and all extracts were analyzed by gas chromatography-mass spectrometry. Differentiation of S. divinorum from other Salvia species was successful based on visual assessment of the resulting chromatograms. To provide a more objective comparison, the total ion chromatograms (TICs) were subjected to principal components analysis (PCA). Prior to PCA, the TICs were subjected to a series of data pretreatment procedures to minimize non-chemical sources of variance in the data set. Successful discrimination of S. divinorum from the other four Salvia species was possible based on visual assessment of the PCA scores plot. To provide a numerical assessment of the discrimination, a series of statistical procedures such as Euclidean distance measurement, hierarchical cluster analysis, Student's t tests, Wilcoxon rank-sum tests, and Pearson product moment correlation were also applied to the PCA scores. The statistical procedures were then compared to determine the advantages and disadvantages for forensic applications.

d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology.

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De Gregorio, Danilo; Comai, Stefano; Posa, Luca; Gobbi, Gabriella

2016-11-23

d-Lysergic Acid Diethylamide (LSD) is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles' reference lists for preclinical studies regarding the mechanism of action involved in the psychotic-like effects induced by LSD. LSD's mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT 2A receptor as a partial agonist and 5-HT 1A as an agonist. LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating dopamine D₂, Trace Amine Associate receptor 1 (TAAR₁) and 5-HT 2A . More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. LSD's effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA) mechanism or acting on TAAR₁ receptors.

LSD Acutely Impairs Fear Recognition and Enhances Emotional Empathy and Sociality.

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Dolder, Patrick C; Schmid, Yasmin; Müller, Felix; Borgwardt, Stefan; Liechti, Matthias E

2016-10-01

Lysergic acid diethylamide (LSD) is used recreationally and has been evaluated as an adjunct to psychotherapy to treat anxiety in patients with life-threatening illness. LSD is well-known to induce perceptual alterations, but unknown is whether LSD alters emotional processing in ways that can support psychotherapy. We investigated the acute effects of LSD on emotional processing using the Face Emotion Recognition Task (FERT) and Multifaceted Empathy Test (MET). The effects of LSD on social behavior were tested using the Social Value Orientation (SVO) test. Two similar placebo-controlled, double-blind, random-order, crossover studies were conducted using 100 μg LSD in 24 subjects and 200 μg LSD in 16 subjects. All of the subjects were healthy and mostly hallucinogen-naive 25- to 65-year-old volunteers (20 men, 20 women). LSD produced feelings of happiness, trust, closeness to others, enhanced explicit and implicit emotional empathy on the MET, and impaired the recognition of sad and fearful faces on the FERT. LSD enhanced the participants' desire to be with other people and increased their prosocial behavior on the SVO test. These effects of LSD on emotion processing and sociality may be useful for LSD-assisted psychotherapy.

Comparing three cohorts of MSM sampled via sex parties, bars/clubs, and Craigslist.org: implications for researchers and providers.

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Grov, Christian; Rendina, H Jonathon; Parsons, Jeffrey T

2014-08-01

With limited exceptions, few studies have systematically reported on psychosocial and demographic characteristic differences in samples of men who have sex with men (MSM) based on where they were recruited. This study compared three sexually active cohorts of MSM recruited via Craigslist.org (recruited via modified time-space sampling), gay bars and clubs (recruited via time-space sampling), and private sex parties (identified via passive recruitment and listserves), finding mixed results with regard to differences in demographic characteristics, STI history, and psychosocial measures. Men recruited from sex parties were significantly older, reported more symptoms of sexual compulsivity, more likely to be HIV-positive, more likely to report a history of STIs, and more likely to self-identify as a barebacker, than men recruited from the other two venues. In contrast, men from Craigslist.org reported the lowest levels of attachment to the gay and bisexual community and were the least likely to self-identify as gay. Men from bars and clubs were significantly younger, and were more likely to report use of hallucinogens and crack or cocaine. Our findings highlight that the venues in which MSM are recruited have meaningful consequences in terms of the types of individuals who are reached.

Firearm carrying and concurrent substance use behaviours in a community-based sample of emerging adults.

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Buschmann, Robert N; Prochaska, John D; Baillargeon, Jacques G; Temple, Jeff R

2017-12-01

This paper examines associations between high-risk gun carrying and substance use in emerging adults (ages 18-22). The coexistence of these high-risk behaviours in a general population of emerging adults can have disastrous consequences. Dating it Safe is an ongoing longitudinal (2010-2016) survey of emerging adults recruited from seven high schools in five south-east Texas-area school districts (current sample n=684). Multiple logistic regression modelling was used to examine the association between past-year use of legal and illegal substances and past-year firearm carrying for a reason other than sport or hunting. 6% of emerging adults carried firearms in the past year, with most (68%) carrying for protection. Use of cocaine, hallucinogens, methamphetamine, ecstasy and prescription medications in the past year, as well as episodic heavy drinking in the past month, was associated with increased risk of carrying a firearm (ppast-year substance use behaviours. These findings extend previous research and suggest directions for further exploration of the clustering of high-risk behaviours in emerging adults. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Global Scientific Production on Illicit Drug Addiction: A Two-Decade Analysis.

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Khalili, Malahat; Rahimi-Movaghar, Afarin; Shadloo, Behrang; Mojtabai, Ramin; Mann, Karl; Amin-Esmaeili, Masoumeh

2018-04-06

Addiction science has made great progress in the past decades. We conducted a scientometric study in order to quantify the number of publications and the growth rate globally, regionally, and at country levels. In October 2015, we searched the Scopus database using the general keywords of addiction or drug-use disorders combined with specific terms regarding 4 groups of illicit drugs - cannabis, opioids, cocaine, and other stimulants or hallucinogens. All documents published during the 20-year period from 1995 to 2014 were included. A total of 95,398 documents were retrieved. The highest number of documents were on opioids, both globally (60.1%) and in each of 5 continents. However, studies on cannabis showed a higher growth rate in the last 5-year period of the study (2010-2014). The United States, the United Kingdom, Germany, Canada, Australia, France, Spain, Italy, China, and Japan - almost all studies were from high-income countries - occupied the top 10 positions and produced 81.4% of the global science on drug addiction. As there are important socio-cultural differences in the epidemiology and optimal clinical care of addictive disorders, it is suggested that low- and more affected middle-income countries increase their capacity to conduct research and disseminate the knowledge in this field. © 2018 S. Karger AG, Basel.

Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor.

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Bunzow, J R; Sonders, M S; Arttamangkul, S; Harrison, L M; Zhang, G; Quigley, D I; Darland, T; Suchland, K L; Pasumamula, S; Kennedy, J L; Olson, S B; Magenis, R E; Amara, S G; Grandy, D K

2001-12-01

The trace amine para-tyramine is structurally and functionally related to the amphetamines and the biogenic amine neurotransmitters. It is currently thought that the biological activities elicited by trace amines such as p-tyramine and the psychostimulant amphetamines are manifestations of their ability to inhibit the clearance of extracellular transmitter and/or stimulate the efflux of transmitter from intracellular stores. Here we report the discovery and pharmacological characterization of a rat G protein-coupled receptor that stimulates the production of cAMP when exposed to the trace amines p-tyramine, beta-phenethylamine, tryptamine, and octopamine. An extensive pharmacological survey revealed that psychostimulant and hallucinogenic amphetamines, numerous ergoline derivatives, adrenergic ligands, and 3-methylated metabolites of the catecholamine neurotransmitters are also good agonists at the rat trace amine receptor 1 (rTAR1). These results suggest that the trace amines and catecholamine metabolites may serve as the endogenous ligands of a novel intercellular signaling system found widely throughout the vertebrate brain and periphery. Furthermore, the discovery that amphetamines, including 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy"), are potent rTAR1 agonists suggests that the effects of these widely used drugs may be mediated in part by this receptor as well as their previously characterized targets, the neurotransmitter transporter proteins.

[Psychotherapy with Adjuvant use of Serotonergic Psychoactive Substances: Possibilities and Challenges].

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Majić, Tomislav; Jungaberle, Henrik; Schmidt, Timo T; Zeuch, Andrea; Hermle, Leo; Gallinat, Jürgen

2017-07-01

Background  Recently, scientific interest in the therapeutic potential of serotonergic and psilocybin hallucinogens (psychedelics) such as lysergic acid diethylamide (LSD) and entactogens like 3,4-methylendioxymethamphetamine (MDMA) within the framework of psychotherapy has resumed. The present article provides an overview on the current evidence on substance-assisted psychotherapy with these substances. Method  A selective search was carried out in the PubMed and Cochrane Library including studies investigating the clinical use of serotonergic psychoactive substances since 2000. Results  Studies were found investigating the following indications: alcohol (LSD and psilocybin) and tobacco addiction (psilocybin), anxiety and depression in patients suffering from life-threatening somatic illness (LSD and psilocybin), obsessive-compulsive disorder (OCD) (psilocybin), treatment-resistant major depression (psilocybin), and posttraumatic stress disorder (PTSD) (MDMA). Discussion  Substance use disorders, PTSD and anxiety and depression in patients suffering from life-threatening somatic illness belong to the indications with the best evidence for substance-assisted psychotherapy with serotonergic psychoactive agents. To date, studies indicate efficacy and relatively good tolerability. Further studies are needed to determine whether these substances may represent suitable and effective treatment options for some treatment-resistant psychiatric disorders in the future. © Georg Thieme Verlag KG Stuttgart · New York.

Changes in spirituality among ayahuasca ceremony novice participants.

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Trichter, Stephen; Klimo, Jon; Krippner, Stanley

2009-06-01

Ayahuasca, a hallucinogenic plant brew from the Amazon basin used as part of healing ceremonies by the local indigenous people of the region for centuries, is now being consumed by growing numbers of people throughout the world. Anecdotal evidence and previous research suggest that there are spiritual effects experienced among participants who take part in ayahuasca ceremonies. The current study examined whether novice participants' spirituality was affected through participation in an ayahuasca ceremony, and if so, how. A mixed-design method was used, comparing those participating in an ayahuasca ceremony to those who did not participate. This investigation used the Peak Experience Profile, the Spiritual Well-being Scale, and the Mysticism Scale as quantitative measures. Participant interviews and written accounts of ceremony experiences were analyzed. Results showed that neither the SWB score nor the M-Scale score increased significantly after participating in an ayahuasca ceremony. However, it was found that the higher the PEP score, the greater the positive change in SWB and M-Scale scores. Qualitative data revealed common spiritual themes in many of the participants' interviews and written accounts. Experiential differences were displayed within the ayahuasca ceremony group, warranting continued investigation into, and identification of, various confounding variables that prompt reported changes in spirituality within some participants while not in others.

Safety and side effects of ayahuasca in humans--an overview focusing on developmental toxicology.

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dos Santos, Rafael Guimarães

2013-01-01

Despite being relatively well studied from a botanical, chemical, and (acute) pharmacological perspective, little is known about the possible toxic effects of ayahuasca (an hallucinogenic brew used for magico-ritual purposes) in pregnant women and in their children, and the potential toxicity of long-term ayahuasca consumption. It is the main objective of the present text to do an overview of the risks and possible toxic effects of ayahuasca in humans, reviewing studies on the acute ayahuasca administration to humans, on the possible risks associated with long-term consumption by adults and adolescents, and on the possible toxic effects on pregnant animals and in their offspring. Acute ayahuasca administration, as well as long-term consumption of this beverage, does not seem to be seriously toxic to humans. Although some nonhuman developmental studies suggested possible toxic effects of ayahuasca or of some of its alkaloids, the limited human literature on adolescents exposed to ayahuasca as early as in the uterus reports no serious toxic effects of the ritual consumption of the brew. Researchers must take caution when extrapolating nonhuman data to humans and more data are needed in basic and human research before a definite opinion can be made regarding the possible toxic effects of ayahuasca in pregnant women and in their children.

Report on psychoactive drug use among adolescents using ayahuasca within a religious context.

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Doering-Silveira, Evelyn; Grob, Charles S; de Rios, Marlene Dobkin; Lopez, Enrique; Alonso, Luisa K; Tacla, Cristiane; Da Silveira, Dartiu Xavier

2005-06-01

Ritual use of ayahuasca within the context of the Brazilian ayahuasca churches often starts during late childhood or early adolescence. Premature access to psychoactive drugs may represent a risk factor for drug misuse. Conversely, religious affiliation seems to play a protective role in terms of substance abuse. The objective of this study was to describe patterns of drug use in a sample of adolescents using ayahuasca within a religious setting. Forty-one adolescents from a Brazilian ayahuasca sect were compared with 43 adolescents who never drank ayahuasca. No significant differences were identified in terms of lifetime substance consumption. Throughout the previous year period, ayahuasca adolescents used less alcohol (46.31%) than the comparison group (74.4%). Recent use of alcohol was also more frequent among the latter group (65.1%) than among ayahuasca drinkers (32.5%). Although not statistically significant, slight differences in terms of patterns of drug use were definitely observed among groups. Despite their early exposure to a hallucinogenic substance, adolescents using ayahuasca in a controlled setting were mostly comparable to controls except for a considerably smaller proportion of alcohol users. Religious affiliation may have played a central role as a possible protective factor for alcohol use. Thus, ayahuasca seems to be a relatively safe substance as far as drug misuse is concerned.

Altered states of consciousness and short-term psychological after-effects induced by the first time ritual use of ayahuasca in an urban context in Brazil.

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Barbosa, Paulo Cesar Ribeiro; Giglio, Joel Sales; Dalgalarrondo, Paulo

2005-06-01

This report describes psychological assessments of the first time ritual use of ayahuasca in the religious groups União do Vegetal and Santo Daime. Nineteen subjects who tried the beverage in Santo Daime rituals and nine subjects who tried it in União do Vegetal rituals were evaluated one to four days before their first ayahuasca experience in life and one to two weeks after this experience. Semistructured interviews and a structured psychiatric scale were used in the first evaluation to elicit set variables concerning attitudes towards the ayahuasca experience and to elicit mental health status. Mental health status was reassessed in the second evaluation, which also included a semistructured interview concerning the phenomenology of altered states of consciousness (ASCs). Predominantly positive expectancies concerning the ayahuasca experience were the most prominent findings concerning set variables. Visual phenomena, numinousness, peacefulness, insights and a distressing reaction were the most salient ASC experiences. A significant reduction of the intensity of minor psychiatric symptoms occurred in the Santo Daime group after the hallucinogen experience. Subjects in both groups reported behavioral changes towards assertiveness, serenity and vivacity/joy. The set and setting hypothesis, suggestibility processes, as well as the supposed unique effects of ayahuasca are used in discussing these findings.

Societal risk as seen by the French public

International Nuclear Information System (INIS)

Karpowicz-Lazreg, C.; Mullet, E.

1993-01-01

Mean risk magnitude judgments expressed by French students on 90 hazardous activities are reported and compared with findings on American, Hungarian, and Norwegian samples. In many respects, rating of perceived risk in the French sample is highly comparable to rating in American subjects. American and French people tend to share the same preoccupations to the same extent. The only major differences concern hallucinatory drugs and oral contraceptives. The Norwegians and French ratings differ much more. Norwegians and French people generally have the same preoccupations (which make Norwegian ratings the best predictor of French ratings) but not to the same extent. The French are much more concerned with a whole series of activities connected to violence, the implementation of high technology or agricultural technology. However, like the Norwegians, the French are extremely concerned about the spread of hallucinogenic drugs. The Hungarian and French ratings differ on practically all instances, except on basic activities or substances in all industrialized nations (caffeine, motorcycles, ...). Differences were observed within the French sample itself. Women more than men consider that home appliances in general and large-scale public transportation are potentially dangerous. Science students more than art students tend to fear a certain number of medical techniques and a certain number of toxic substances (e.g., smoking). 7 refs., 1 tab

Phytochemical investigation of natural and in vitro raised Vṛddhadāruka plants

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Asha Jyoti Bharati

2014-01-01

Full Text Available Background: Argyreia nervosa commonly known as elephant creeper (English and Vṛddhadāruka (Sanskrit is a woody climber that belongs to the family Convolvulaceae. Seeds of this plant contain hallucinogens including ergot alkaloids and a naturally occurring lysergic acid amide. Traditionally the plant is used in the treatment of gonorrhea, strangury, chronic ulcers, diabetes, anemia and cerebral disorders. The plant is also used as appetitiser, brain tonic, cardiotonic, aphrodisiac. It possesses anti-inflammatory, immunomodulatory, antibacterial, antiviral and antifungal activities. Objective: To give an account of information on in vitro regeneration and phytochemical analysis of the plant. Materials and Methods: Nodal explants were selected for in vitro regeneration. Different aerial parts viz., seeds, natural and in vitro leaf, stem and callus were dried and extracted with different solvents and were subjected to various phytochemical analyses. Results: Different concentrations of 6-benzylaminopurine showed shoot and root initiation. The study of phytochemical screening of different extracts showed the presence of bioactive substances like flavonoids, alkaloids, terpenoids, etc. Conclusion: The study will provide an efficient in vitro protocol for micropropagation as an alternative method to conserve the plant and shows the presence of some important secondary metabolites in the nature grown and in vitro raised plants which can be useful for treatment of various diseases.

Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study.

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Bogenschutz, Michael P; Forcehimes, Alyssa A; Pommy, Jessica A; Wilcox, Claire E; Barbosa, P C R; Strassman, Rick J

2015-03-01

Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants' responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p psilocybin session (at week 4) strongly predicted change in drinking during weeks 5-8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms. NCT02061293. © The Author(s) 2015.

Prediction of psilocybin response in healthy volunteers.

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Studerus, Erich; Gamma, Alex; Kometer, Michael; Vollenweider, Franz X

2012-01-01

Responses to hallucinogenic drugs, such as psilocybin, are believed to be critically dependent on the user's personality, current mood state, drug pre-experiences, expectancies, and social and environmental variables. However, little is known about the order of importance of these variables and their effect sizes in comparison to drug dose. Hence, this study investigated the effects of 24 predictor variables, including age, sex, education, personality traits, drug pre-experience, mental state before drug intake, experimental setting, and drug dose on the acute response to psilocybin. The analysis was based on the pooled data of 23 controlled experimental studies involving 409 psilocybin administrations to 261 healthy volunteers. Multiple linear mixed effects models were fitted for each of 15 response variables. Although drug dose was clearly the most important predictor for all measured response variables, several non-pharmacological variables significantly contributed to the effects of psilocybin. Specifically, having a high score in the personality trait of Absorption, being in an emotionally excitable and active state immediately before drug intake, and having experienced few psychological problems in past weeks were most strongly associated with pleasant and mystical-type experiences, whereas high Emotional Excitability, low age, and an experimental setting involving positron emission tomography most strongly predicted unpleasant and/or anxious reactions to psilocybin. The results confirm that non-pharmacological variables play an important role in the effects of psilocybin.

Prediction of psilocybin response in healthy volunteers.

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Erich Studerus

Full Text Available Responses to hallucinogenic drugs, such as psilocybin, are believed to be critically dependent on the user's personality, current mood state, drug pre-experiences, expectancies, and social and environmental variables. However, little is known about the order of importance of these variables and their effect sizes in comparison to drug dose. Hence, this study investigated the effects of 24 predictor variables, including age, sex, education, personality traits, drug pre-experience, mental state before drug intake, experimental setting, and drug dose on the acute response to psilocybin. The analysis was based on the pooled data of 23 controlled experimental studies involving 409 psilocybin administrations to 261 healthy volunteers. Multiple linear mixed effects models were fitted for each of 15 response variables. Although drug dose was clearly the most important predictor for all measured response variables, several non-pharmacological variables significantly contributed to the effects of psilocybin. Specifically, having a high score in the personality trait of Absorption, being in an emotionally excitable and active state immediately before drug intake, and having experienced few psychological problems in past weeks were most strongly associated with pleasant and mystical-type experiences, whereas high Emotional Excitability, low age, and an experimental setting involving positron emission tomography most strongly predicted unpleasant and/or anxious reactions to psilocybin. The results confirm that non-pharmacological variables play an important role in the effects of psilocybin.

Relationships Between Using Other Substances and Socio-Demographic Characteristics in Opiate Dependents

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Melike Nebioglu,Hacer Yalniz

2013-02-01

Full Text Available Objective: We aimed to determine the variables that can be a risk factor for addiction like age, gender, education level, school cession, first using age, substance use period, frequency and using other addictive substances among people who have a diagnosis of opiate addiction. Methods: This is a descriptive and cross-sectional study in AMBAUM ( Akdeniz University Alcohol and Substance Dependence Research and Practice Center between February 1,2010- April30, 2010. 84 inpatient and outpatient patients (60 men, 24 women between age 14-37, who have a diagnosis of opiate addiction according to DSM IV-TR diagnostic criteria recruited in this study. All participating patients completed a standard questionaire and sociodemographic data form face to face. The results were analyzed with chi-squared test by using SPSS 16 statistics program. Results: In our patients nicotin addiction prevalance is 100%, alcohol using prevalance is 91.7%, cannabis using prevalance 86.9%, ecstasy using prevalance 54.8%, cocain using prevalance 48.8%, polysubstance using prevalance 47.6%, hallucinogen using prevalance 27.4%, addictive medical drug using prevalance 17.9%. Conclusions: This epidemiological study guide us in the monitoring and evalution of the opiate use and prevalance of other substance use with opiate addiction. Keywords: Prevalence, heroin, polysubstance dependence. [TAF Prev Med Bull 2013; 12(1.000: 35-42

Effects of LSD on grooming behavior in serotonin transporter heterozygous (Sert⁺/⁻) mice.

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Kyzar, Evan J; Stewart, Adam Michael; Kalueff, Allan V

2016-01-01

Serotonin (5-HT) plays a crucial role in the brain, modulating mood, cognition and reward. The serotonin transporter (SERT) is responsible for the reuptake of 5-HT from the synaptic cleft and regulates serotonin signaling in the brain. In humans, SERT genetic variance is linked to the pathogenesis of various psychiatric disorders, including anxiety, autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD). Rodent self-grooming is a complex, evolutionarily conserved patterned behavior relevant to stress, ASD and OCD. Genetic ablation of mouse Sert causes various behavioral deficits, including increased anxiety and grooming behavior. The hallucinogenic drug lysergic acid diethylamide (LSD) is a potent serotonergic agonist known to modulate human and animal behavior. Here, we examined heterozygous Sert(+/-) mouse behavior following acute administration of LSD (0.32 mg/kg). Overall, Sert(+/-) mice displayed a longer duration of self-grooming behavior regardless of LSD treatment. In contrast, LSD increased serotonin-sensitive behaviors, such as head twitching, tremors and backwards gait behaviors in both Sert(+/+) and Sert(+/-) mice. There were no significant interactions between LSD treatment and Sert gene dosage in any of the behavioral domains measured. These results suggest that Sert(+/-) mice may respond to the behavioral effects of LSD in a similar manner to wild-type mice. Copyright © 2015 Elsevier B.V. All rights reserved.

Acute neurotoxicity after yohimbine ingestion by a body builder.

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Giampreti, Andrea; Lonati, Davide; Locatelli, Carlo; Rocchi, Loretta; Campailla, Maria Teresa

2009-09-01

Yohimbine is an alkaloid obtained from the Corynanthe yohimbe tree and other biological sources. Yohimbine is currently approved in the United States for erectile dysfunction and has undergone resurgence in street use as an aphrodisiac and mild hallucinogen. In recent years yohimbine use has become common in body-building communities for its presumed lipolytic and sympathomimetic effects. We describe a 37-year-old bodybuilder in which severe acute neurotoxic effects occurred in 2 h after yohimbine ingestion. The patient presented with malaise, vomiting, loss of consciousness, and repeated seizures after ingestion of 5 g of yohimbine during a body-building competition in a gymnasium. His Glasgow Coma Score was 3, requiring orotracheal intubation. Two hours after admission, vital signs were blood pressure 259/107 mmHg and heart rate 140 beats/min. Treatment with furosemide, labetalol, clonidine, and urapidil and gastrointestinal decontamination were performed. Twelve hours later the patient was extubated with normal hemodynamic parameters and neurological examination. The yohimbine blood levels at 3, 6, 14, and 22 h after ingestion were 5,240; 2,250; 1,530; and 865 ng/mL, respectively, with a mean half-life of 2 h. Few data are available about yohimbine toxicity and the related blood levels. This is a case of a large ingestion of yohimbine in which severe hemodynamic and neurological manifestations occurred and elevated blood levels of yohimbine were detected.

d-Lysergic Acid Diethylamide (LSD as a Model of Psychosis: Mechanism of Action and Pharmacology

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Danilo De Gregorio

2016-11-01

Full Text Available d-Lysergic Acid Diethylamide (LSD is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles’ reference lists for preclinical studies regarding the mechanism of action involved in the psychotic-like effects induced by LSD. LSD’s mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT2A receptor as a partial agonist and 5-HT1A as an agonist. LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating dopamine D2, Trace Amine Associate receptor 1 (TAAR1 and 5-HT2A. More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. LSD’s effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA mechanism or acting on TAAR1 receptors.

Cross-generational effects on gender differences in psychoactive drug abuse and dependence.

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Holdcraft, Laura C; Iacono, William G

2004-05-10

Studies of patients with cocaine and heroin use disorders have shown gender differences in prevalence, course, and outcome. These differences may be decreasing in successive generations. Less is known about gender differences in course and symptomatology for other illicit drug use disorders, especially in community samples. Participants (1323 men and 1384 women) who were biological or step-parents of twins and born in the 1940-1960s, from the Minnesota Twin-Family Study (MTFS) were divided into two cohorts based on the median birth year. A structured interview was used to assess DSM-III-R cannabis, amphetamine, cocaine and hallucinogen use disorders. There was a higher prevalence of each of these drug disorders and earlier onset of cannabis and amphetamine use disorders in later-born participants. For most drug use disorder categories, men and women were similar with respect to age of onset and severity of disorder but women had a shorter course of drug use disorders. Women with amphetamine disorders were atypical with respect to having a higher frequency of use but similar number of lifetime uses compared to men, and more emotional effects of amphetamine intoxication than men. In addition, women with amphetamine disorders were more likely to have anorexia nervosa than those without amphetamine disorders. These results have several implications for prevention, etiology and treatment.

Metabolites identification of harmane in vitro/in vivo in rats by ultra-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry.

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Li, Shuping; Liu, Wei; Teng, Liang; Cheng, Xuemei; Wang, Zhengtao; Wang, Changhong

2014-04-01

Harmane, a β-carboline alkaloid with a wide spectrum of pharmacological activities, is naturally present in the human diet, in numerous foodstuffs and in hallucinogenic plants such as Peganum harmala, Banisteriopsis caapi and Tribulus terrestris. However, the precise metabolic fate of harmane remains unknown. In order to know whether harmane is extensively metabolized, a rapid and sensitive method using ultra-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC/ESI-QTOF-MS) was used to analyze the metabolic profile of harmane in vitro and in vivo in rats. A total of 21 metabolites were identified from the rat liver microsomes and rat liver S9 (9), rat urine (11), feces (16), bile (16), and plasma (10) after a single oral administration of harmane using MetaboLynx™ and MassFragment ™ software tools. It indicated that the biliary and faecal clearance were the major excretion routes for harmane as well as its metabolites. The specific CLogP values combined with different acidic and alkaline mobile phase were helpful and useful for distinguishing N-oxidation and monohydroxylation metabolites. The metabolic transformation pathways of harmane included monohydroxylation, dihydroxylation, N-oxidation, O-glucuronide conjugation, O-sulphate conjugation, and glutathione conjugation. In conclusion, this study showed an insight into the metabolism of harmane. Copyright © 2014 Elsevier B.V. All rights reserved.

Are patients with panic disorder respiratory subtype more vulnerable to tobacco, alcohol or illicit drug use?

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Rafael C. Freire

2013-01-01

Full Text Available BACKGROUND: Studies have documented high use of tobacco, alcohol and illicit drugs in patients with panic disorder (PD. The comorbid substance use disorders worsen the prognosis of mood and anxiety disorders. The respiratory subtype (RS of PD seems to represent a more severe and distinct form of this disorder associated with higher familial history of PD and more comorbidity with other anxiety disorders. OBJECTIVES: Describe the patterns of tobacco, alcohol or illicit drug use in PD patients, and also to ascertain if patients with the RS use these substances more than those of the non-respiratory subtype. METHODS: This is a cross-sectional study with 71 PD patients. The Alcohol Use Disorders Identification Test and Fagerstrom Tobacco Questionnaire were used in the evaluation. Patients with four or five respiratory symptoms were classified in the RS, the remaining patients were classified as non-respiratory subtype. RESULTS: In our sample 31.0% were smokers, 11.3% were hazardous alcohol users and none of them was using illicit drugs. There were no differences between the respiratory and non-respiratory subtypes regarding the use of tobacco, alcohol, cannabis, cocaine, stimulants and hallucinogens. DISCUSSION: The RS was not correlated to the use of tobacco, alcohol and illicit drugs. Additional epidemiological and clinical studies focusing the relationship between PD and substance use are warranted.

Concurrent and simultaneous polydrug use: latent class analysis of an Australian nationally representative sample of young adults.

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Lake-Hui eQuek

2013-11-01

Full Text Available Background: Alcohol use and illicit drug use peak during young adulthood (around 18-29 years of age, but comparatively little is known about polydrug use in nationally representative samples of young adults. Drawing on a nationally representative cross-sectional survey (Australian National Drug Strategy Household Survey, this study examines polydrug use patterns and associated psychosocial risk factors among young adults (n = 3,333; age 19-29. Method: The use of a broad range of licit and illicit drugs were examined, including alcohol, tobacco, cannabis, cocaine, hallucinogens, ecstasy, ketamine, GHB, inhalants, steroids, barbiturates, meth/amphetamines, heroin, methadone/buprenorphine, other opiates, painkillers and tranquillizers/sleeping pills. Latent class analysis was employed to identify patterns of polydrug use. Results: Polydrug use in this sample was best described using a 5-class solution. The majority of young adults predominantly used alcohol only (52.3%, alcohol and tobacco (34.18%. The other classes were cannabis, ecstasy, and licit drug use (9.4%, cannabis, amphetamine derivative, and licit drug use (2.8%, and sedative and alcohol use (1.3%. Young adult males with low education and/or high income were most at risk of polydrug use. Conclusion: Almost half of young adults reported polydrug use, highlighting the importance of post-high school screening for key risk factors and polydrug use profiles, and the delivery of early intervention strategies targeting illicit drugs.

Acute Datura Stramonium poisoning in East of Iran - a case series.

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Amini, Mahnaz; Khosrojerdi, Hamid; Afshari, Reza

2012-01-01

Datura Stramonium (DS) is a common weed along roadsides, in cornfields and pastures and in waste areas. It belongs to the family Solanaceae and its toxic components are tropane belladonna alkaloids. It has been used voluntarily by teenagers for its hallucinogenic effect. The plant is named in Iran as Tatoore. Symptoms and signs of acute D. Stramonium poisoning usually are similar to anticholinergic syndrome. This study is done in order to clarify the status of this poisoning in our region. This study is a case series on all patients admitted to Imam Reza Hospital, Mashhad, Iran, with acute D. Stramonium poisoning between 2008 and 2011. We observed their symptoms, signs, routine laboratory test results and treatment used to control their symptoms. There were 19 patients included in our study. Children were poisoned more commonly than teenagers and poisoning in adults was rare. All of the children ingested the plant accidentally. The most presenting symptom was irritability and the most common sign was sinus tachycardia. There was not any presentation of seizure or coma. Most of the symptoms were controlled by parenteral benzodiazepines and there were no need to use of cholinergic agents such as physostigmine. Our study showed most of D. Stramonium poisoned population in our region are children. We suggest decreasing accessibility to the plant in order to decrease the incidence of its poisoning.

Is Project Towards No Drug Abuse (Project TND) an evidence-based drug and violence prevention program? A review and reappraisal of the evaluation studies.

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Gorman, Dennis M

2014-08-01

This paper critically reviews the published evidence pertaining to Project Towards No Drug Abuse (Project TND). Publications from seven evaluation studies of Project TND are reviewed, and the results from these are discussed as related to the following outcomes: main effects on the use of cigarettes, alcohol and marijuana; main effects on the use of "hard drugs," defined in the evaluations as cocaine, hallucinogens, stimulants, inhalants, ecstasy and other drugs (e.g., depressants, PCP, steroids and heroin); subgroup and interaction analyses of drug use; and violence-related behaviors. Very few main effects have been found for cigarette, alcohol and marijuana use in the Project TND evaluations. While studies do report main effects for hard drug use, these findings are subject to numerous threats to validity and may be attributable to the data analyses employed. Similarly, while isolated subgroup and interaction effects were found for alcohol use among baseline nonusers and some violence-related behaviors in the early Project TND evaluations, these findings have not been replicated in more recent studies and may result from multiple comparisons between study conditions. In conclusion, there is little evidence to support the assertion that Project TND is an effective drug or violence prevention program. The broader implications of these findings for prevention science are discussed and suggestions are made as to how the quality of research in the field might be improved.

Ritualistic Use of Ayahuasca versus Street Use of Similar Substances Seized by the Police: A Key Factor Involved in the Potential for Intoxications and Overdose?

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Lanaro, Rafael; Calemi, Débora Bressanim de Aquino; Togni, Loraine Rezende; Costa, José Luiz; Yonamine, Maurício; Cazenave, Silvia de Oliveira Santos; Linardi, Alessandra

2015-01-01

The ritualistic use of ayahuasca is becoming a global phenomenon. This beverage contains a combination of monoamine oxidase inhibitors (harmine, harmaline, and tetrahydroharmine) and N,N-dimethyltryptamine, the main substance responsible for its visionary effect. The recreational use of similar alkaloids and N,N-dimethyltryptamine has increased in recent years, mainly because of their hallucinogenic effects. In the present study, the concentrations of psychoactive alkaloids in three powder samples seized by the São Paulo State Police and nine ayahuasca aqueous extracts were analyzed by HPLC-DAD in an attempt to distinguish between illicit drugs and the religious beverage. The alkaloids detected (μg/mL) in the ayahuasca aqueous extracts were N,N-dimethyltryptamine (402-2070.3), harmaline (27.5-181.3), harmine (294.5-2893.8), and tetrahydroharmine (849.5-2052.5), whereas, of the three powder samples, one contained only N,N-dimethyltryptamine (82% and 2% w/w, respectively) while the other contained only harmaline (16%, w/w) and harmine (12%, w/w). The ritualistic use of ayahuasca involves oral intake and the probability of overdose is minimized by serotonergic stimulation of vagal pathways, leading to vomiting and diarrhea. In contrast, the recreational use of N,N-dimethyltryptamine involves consumption mainly by smoking or inhalation, both of which markedly increase its bioavailability and the potential for intoxications.

"Not for human consumption": a review of emerging designer drugs.

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Musselman, Megan E; Hampton, Jeremy P

2014-07-01

Synthetic, or "designer" drugs, are created by manipulating the chemical structures of other psychoactive drugs so that the resulting product is structurally similar but not identical to illegal psychoactive drugs. Originally developed in the 1960s as a way to evade existing drug laws, the use of designer drugs has increased dramatically over the past few years. These drugs are deceptively packaged as "research chemicals," "incense," "bath salts," or "plant food," among other names, with labels that may contain warnings such as "not for human consumption" or "not for sale to minors." The clinical effects of most new designer drugs can be described as either hallucinogenic, stimulant, or opioid-like. They may also have a combination of these effects due to designer side-chain substitutions. The easy accessibility and rapid emergence of new designer drugs have created challenges for health care providers when treating patients presenting with acute toxicity from these substances, many of which can produce significant and/or life-threatening adverse effects. Moreover, the health care provider has no way to verify the contents and/or potency of the agent ingested because it can vary between packages and distributors. Therefore, a thorough knowledge of the available designer drugs, common signs and symptoms of toxicity associated with these agents, and potential effective treatment modalities are essential to appropriately manage these patients. © 2014 Pharmacotherapy Publications, Inc.

"Legal Highs"--An Emerging Epidemic of Novel Psychoactive Substances.

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Zawilska, Jolanta B

2015-01-01

During the last decade, there has been an increase in the availability and use of novel psychoactive substances (NPS), also known as "legal highs," across the world. They include a wide range of products, from natural plant-originated substances to synthetic compounds, that can be purchased both online and from high street retailers. "Legal highs" mimic psychoactive effects of illicit drugs of abuse. However, they are claimed to consist of compounds that are legal to sell, possess, and use, often labeled as "not for human consumption" to circumvent drug abuse legislation. Based on the spectrum of their actions on cognitive processes, mood, and behavior, "legal highs" can be classified into four basis categories: amphetamine- and ecstasy-like stimulants, synthetic cannabinoids (SCs), hallucinogenic/dissociative, and opioid-like compounds. NPS may, however, exhibit a combination of these actions due to their designed chemical structure. Although the prevalence and pattern of NPS use differ between various countries, the most popular groups are SCs and psychostimulants, described in this chapter. Currently, there is limited information available on the potential acute toxicity (harms) associated with the use of these substances. However, the number of intoxicated people presenting with emergencies is constantly increasing, providing evidence that negative health and social consequences may indeed seriously affect recreational and chronic users. © 2015 Elsevier Inc. All rights reserved.

Consumption of new psychoactive substances in a Spanish sample of research chemical users.

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González, Débora; Ventura, Mireia; Caudevilla, Fernando; Torrens, Marta; Farre, Magi

2013-07-01

To know the pattern of use of new psychoactive substances (NPSs) in a Spanish sample of research chemical (RC) users and to deepen the RC user profile and risk reduction strategies employed. This study is a cross-sectional survey by means of a specific questionnaire. Recruitment was carried out at music festivals, at non-governmental organizations (NGOs), and through announcements on an online forum. Two RC user profiles were defined, according to whether they search information through online forums. A total of 230 users participated. The most frequent RCs were hallucinogenic phenethylamines (2C-B 80.0%, 2C-I 39.6%) and cathinones (methylone 40.1%, mephedrone 35.2%). The most frequent combination of RC with other illegal drugs was with cannabis (68.6%) and 2C-B with MDMA (28.3%). Subjects who are consulting drug forums (group 1) use more RC, obtain RC by Internet, and use more frequently risk prevention strategies. Regarding the risk-reduction strategies in this group, users sought information concerning RC before consuming them (100%), used precision scales to calculate dosage (72.3%), and analyzed the contents before consumption (68.8%). There is a specific RC user profile with extensive knowledge and consumption of substances, using different strategies to reduce risks associated to its consumption. Copyright © 2013 John Wiley & Sons, Ltd.

The detection and quantitative analysis of the psychoactive component of Salvia divinorum, salvinorin A, in human biological fluids using liquid chromatography-mass spectrometry.

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McDonough, Pamela C; Holler, Justin M; Vorce, Shawn P; Bosy, Thomas Z; Magluilo, Joseph; Past, Marilyn R

2008-01-01

Salvia divinorum, a member of the mint plant family, has hallucinogenic properties that have become increasingly sought after by recreational drug users. The main psychoactive component, salvinorin A, has potency comparable to lysergic acid diethylamide. Though still legal to possess in most of the United States and much of Europe, little is known regarding the compound's long-term health effects, addiction liability, and pharmacokinetics. Limited data are available in the scientific literature, and few analytical methods are published for the detection in human biological fluids. These factors contribute to the unfamiliarity of the compound and complicate the method development process necessary to accommodate special requested testing for salvinorin A. A sensitive analytical method for the detection and quantitation of salvinorin A in human biological fluids was developed and validated to resolve analytical shortcomings. The method utilizes a solid-phase extraction technique coupled with liquid chromatography-electrospray ionization mass spectrometry operated in selected ion monitoring mode. The assay has a linear range of 5.0-100 ng/mL with a correlation coefficient of 0.997. The limit of detection and limit of quantitation were experimentally determined as 2.5 and 5.0 ng/mL, respectively. The method has been applied to blood and urine samples successfully and can be used to detect the presence of salvinorin A in forensic testing.

Evidence of Syndemics and Sexuality-Related Discrimination Among Young Sexual-Minority Women.

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Coulter, Robert W S; Kinsky, Suzanne M; Herrick, Amy L; Stall, Ron D; Bauermeister, José A

2015-09-01

Syndemics, or the co-occurrence and interaction of health problems, have been examined extensively among young men who have sex with men, but their existence remain unexamined, to our knowledge, among sexual-minority (i.e., lesbian, gay, and bisexual) women. Thus, we investigated if syndemics were present among young sexual-minority women, and if sexual-orientation discrimination was an independent variable of syndemic production. A total of 467 sexual-minority women between the ages of 18 and 24 completed a cross-sectional online survey regarding their substance use, mental health, sexual behaviors, height, weight, and experiences of discrimination. We used structural equation modeling to investigate the presence of syndemics and their relationship to sexual-orientation discrimination. Heavy episodic drinking, marijuana use, ecstasy use, hallucinogen use, depressive symptoms, multiple sexual partners, and history of sexually transmitted infections (STIs) comprised syndemics in this population (chi-square=24.989, P=.201; comparative fit index [CFI]=0.946; root mean square error of approximation [RMSEA]=0.023). Sexual-orientation discrimination is significantly and positively associated with the latent syndemic variable (unstandardized coefficient=0.095, Pdiscrimination (unstandardized coefficient=0.602, P>.05). Syndemics appear to be present and associated with sexual-orientation discrimination among young sexual-minority women. Interventions aimed at reducing discrimination or increasing healthy coping may help reduce substance use, depressive symptoms, and sexual risk behaviors in this population.

Health Disparities in Drug- and Alcohol-Use Disorders: A 12-Year Longitudinal Study of Youths After Detention.

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Welty, Leah J; Harrison, Anna J; Abram, Karen M; Olson, Nichole D; Aaby, David A; McCoy, Kathleen P; Washburn, Jason J; Teplin, Linda A

2016-05-01

To examine sex and racial/ethnic differences in the prevalence of 9 substance-use disorders (SUDs)--alcohol, marijuana, cocaine, hallucinogen or PCP, opiate, amphetamine, inhalant, sedative, and unspecified drug--in youths during the 12 years after detention. We used data from the Northwestern Juvenile Project, a prospective longitudinal study of 1829 youths randomly sampled from detention in Chicago, Illinois, starting in 1995 and reinterviewed up to 9 times in the community or correctional facilities through 2011. Independent interviewers assessed SUDs with Diagnostic Interview Schedule for Children 2.3 (baseline) and Diagnostic Interview Schedule version IV (follow-ups). By median age 28 years, 91.3% of males and 78.5% of females had ever had an SUD. At most follow-ups, males had greater odds of alcohol- and marijuana-use disorders. Drug-use disorders were most prevalent among non-Hispanic Whites, followed by Hispanics, then African Americans (e.g., compared with African Americans, non-Hispanic Whites had 32.1 times the odds of cocaine-use disorder [95% confidence interval = 13.8, 74.7]). After detention, SUDs differed markedly by sex, race/ethnicity, and substance abused, and, contrary to stereotypes, did not disproportionately affect African Americans. Services to treat substance abuse--during incarceration and after release--would reach many people in need, and address health disparities in a highly vulnerable population.

Neurobehavioral, reflexological and physical development of Wistar rat offspring exposed to ayahuasca during pregnancy and lactation

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Carolina Dizioli Rodrigues de Oliveira

2011-09-01

Full Text Available Ayahuasca is a hallucinogenic beverage prepared by the decoction of plants native to the Amazon Basin region. The beverage has been used throughout the world by members of some syncretic religious movements. Despite the recent legalization of ayahuasca in Brazil for religious purposes, there is little pre-clinical and clinical information attesting to its safety, particularly in relation to the use during pregnancy. The aim of the current work was to determine the effects of perinatal exposure to ayahuasca (from the 6th day of pregnancy to the 10th day of lactation on physical, reflexology and neurobehavioral parameters of the Wistar rat offspring. The offspring showed no statistically significant changes in the physical and reflexology parameters evaluated. However, in adult rats, perinatally exposed to ayahuasca, an increase in frequency of entries in open arms in elevated plus-maze test, a decrease in total time of interaction in social interaction test, a decrease in time of latency for the animal to start swimming and a decrease of the minimum convulsant dose induced by pentylenetetrazol were observed. In conclusion, our results showed that the use of ayahuasca by mothers during pregnancy and lactation reduced the general anxiety and social motivation of the rat offspring. Besides, it promoted a higher sensitivity for initiation and spread of seizure activity.

Neurobehavioral, reflexological and physical development of Wistar rat offspring exposed to ayahuasca during pregnancy and lactation

Directory of Open Access Journals (Sweden)

Carolina Dizioli Rodrigues de Oliveira

2011-12-01

Full Text Available Ayahuasca is a hallucinogenic beverage prepared by the decoction of plants native to the Amazon Basin region. The beverage has been used throughout the world by members of some syncretic religious movements. Despite the recent legalization of ayahuasca in Brazil for religious purposes, there is little pre-clinical and clinical information attesting to its safety, particularly in relation to the use during pregnancy. The aim of the current work was to determine the effects of perinatal exposure to ayahuasca (from the 6th day of pregnancy to the 10th day of lactation on physical, reflexology and neurobehavioral parameters of the Wistar rat offspring. The offspring showed no statistically significant changes in the physical and reflexology parameters evaluated. However, in adult rats, perinatally exposed to ayahuasca, an increase in frequency of entries in open arms in elevated plus-maze test, a decrease in total time of interaction in social interaction test, a decrease in time of latency for the animal to start swimming and a decrease of the minimum convulsant dose induced by pentylenetetrazol were observed. In conclusion, our results showed that the use of ayahuasca by mothers during pregnancy and lactation reduced the general anxiety and social motivation of the rat offspring. Besides, it promoted a higher sensitivity for initiation and spread of seizure activity.

MDMA-assisted therapy: A new treatment model for social anxiety in autistic adults.

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Danforth, Alicia L; Struble, Christopher M; Yazar-Klosinski, Berra; Grob, Charles S

2016-01-04

The first study of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of social anxiety in autistic adults commenced in the spring of 2014. The search for psychotherapeutic options for autistic individuals is imperative considering the lack of effective conventional treatments for mental health diagnoses that are common in this population. Serious Adverse Events (SAEs) involving the administration of MDMA in clinical trials have been rare and non-life threatening. To date, MDMA has been administered to over 1133 individuals for research purposes without the occurrence of unexpected drug-related SAEs that require expedited reporting per FDA regulations. Now that safety parameters for limited use of MDMA in clinical settings have been established, a case can be made to further develop MDMA-assisted therapeutic interventions that could support autistic adults in increasing social adaptability among the typically developing population. As in the case with classic hallucinogens and other psychedelic drugs, MDMA catalyzes shifts toward openness and introspection that do not require ongoing administration to achieve lasting benefits. This infrequent dosing mitigates adverse event frequency and improves the risk/benefit ratio of MDMA, which may provide a significant advantage over medications that require daily dosing. Consequently, clinicians could employ new treatment models for social anxiety or similar types of distress administering MDMA on one to several occasions within the context of a supportive and integrative psychotherapy protocol. Copyright © 2015 Elsevier Inc. All rights reserved.

Indole compounds in some culinary-medicinal higher basidiomycetes from Poland.

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Muszynska, Bozena; Sutkowska-Ziaja, Katarzyna; Ekiert, Halina

2011-01-01

Methanolic extracts of two species collected from natural habitats in Poland, Boletus edulis and Suillus luteus, and one species from a commercial source, Pleurotus ostreatus, were analyzed for the presence of non-hallucinogenic indole compounds. The contents of indole compounds in these species were both qualitatively and quantitatively diverse, ranging from 0.01 to 34.11 mg/100 g d.w. Two of 11 tested indole compounds, 5-hydroxytryptophan (0.18, 2.08, 1.63 mg/100 g d.w.) and serotonin (6.52, 10.14, 34.11 mg/100 g d.w.), were present in all three species under study. B. edulis and S. luteus were found to contain L-tryptophan (0.39 and 2.61 mg/100g d.w.) and melatonin (0.68 and 0.71 mg/100 g d.w.). Tryptamine was present in two species, i.e., B. edulis (1.17 mg/100 g d.w.) and in P. ostreatus (0.91 mg/100 g d.w.), in which slight amounts of indole acetonitrile (0.04 and 0.01 mg/100 g d.w., respectively) were also identified. Indoleacetic acid was a common metabolite for P. ostreatus and S. luteus and its contents amounted to 0.21 and 0.04 mg/100 g d.w., respectively. Indole compounds degradation products kynurenic acid (2.63 mg/100 g d.w.) and kynurenine sulfate were (19.57 mg/100 g d.w.) were observed only in S. luteus.

Evaluation of methamphetamine-associated socioeconomic status and addictive behaviors, and their impact on oral health.

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Rommel, Niklas; Rohleder, Nils H; Wagenpfeil, Stefan; Haertel-Petri, Roland; Kesting, Marco R

2015-11-01

Chronic methamphetamine abuse can lead to multiple health hazards. In particular, the substance is associated with devastating effects on oral health including symptoms such as rampant caries, gingiva inflammation, and xerostomia, whereby the term "Meth Mouth" occurs in the current literature. However, "Meth Mouth" pathology is primarily described on the basis of individual cases or has been evaluated without consideration of the mass of potential influencing factors. Therefore, we have conducted a systematic study to investigate the effects of accompanying factors and circumstances on oral health in cases of chronic methamphetamine abuse. In cooperation with two centers for addiction medicine, we assessed the data of 100 chronic methamphetamine users and 100 matched-pair controls between March 2012 and November 2013. We investigated their socioeconomic status, details of methamphetamine consumption behavior, collateral consumption of sugar beverages, nicotine alcohol, and other addictive substances including cannabis, opioids, other stimulants, and hallucinogens, and dental care. We found considerably greater unstable social circumstances, a high collateral consumption of substances with pathogenic potential for the stomatognathic system, and significantly poorer dental care in the methamphetamine-user group. Various factors have to be considered with regard to methamphetamine use and its influence on oral health. These factors can trigger potential damage by the drug methamphetamine possibly leading to the symptoms of "Meth Mouth", and should be considered in prevention and therapy strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Altered network hub connectivity after acute LSD administration

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Felix Müller

Full Text Available LSD is an ambiguous substance, said to mimic psychosis and to improve mental health in people suffering from anxiety and depression. Little is known about the neuronal correlates of altered states of consciousness induced by this substance. Limited previous studies indicated profound changes in functional connectivity of resting state networks after the administration of LSD. The current investigation attempts to replicate and extend those findings in an independent sample. In a double-blind, randomized, cross-over study, 100 μg LSD and placebo were orally administered to 20 healthy participants. Resting state brain activity was assessed by functional magnetic resonance imaging. Within-network and between-network connectivity measures of ten established resting state networks were compared between drug conditions. Complementary analysis were conducted using resting state networks as sources in seed-to-voxel analyses. Acute LSD administration significantly decreased functional connectivity within visual, sensorimotor and auditory networks and the default mode network. While between-network connectivity was widely increased and all investigated networks were affected to some extent, seed-to-voxel analyses consistently indicated increased connectivity between networks and subcortical (thalamus, striatum and cortical (precuneus, anterior cingulate cortex hub structures. These latter observations are consistent with findings on the importance of hubs in psychopathological states, especially in psychosis, and could underlay therapeutic effects of hallucinogens as proposed by a recent model. Keywords: LSD, fMRI, Functional connectivity, Networks, Hubs

Desomorphine (Krokodil): An overview of its chemistry, pharmacology, metabolism, toxicology and analysis.

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Florez, Diego Hernando Ângulo; Dos Santos Moreira, Ana Maria; da Silva, Pedro Rafael; Brandão, Ricardo; Borges, Marcella Matos Cordeiro; de Santana, Fernando José Malagueño; Borges, Keyller Bastos

2017-04-01

"Krokodil" or "Crocodile" is an illegal homemade desomorphine drug obtained from chemical reactions of commercial codeine drugs with several other powerful and highly toxic chemical agents increasing its addiction and hallucinogenic effects when compared with other morphine analogues. This paper summarizes a complete review about an old drug called desomorphine (Krokodil), presenting its chemistry, pharmacology, metabolism, toxicology and analysis. It is of particular interest and concern because this cheaper injectable semisynthetic opioid drug has been largely used in recent years for recreational purposes in several Eastern European as well as North and South American countries, despite known damage to health that continuous use might induce. These injuries are much stronger and more aggressive than morphine's, infecting and rotting skin and soft tissue to the bone of addicts at the point of injection in less than three years, which, in most cases, evolves to death. On this basis, it is imperative that literature reviews focus on the chemistry, pharmacology, toxicology and analysis of dangerous Krokodil to find strategies for rapid and effective determination to mitigate its adverse effects on addicts and prevent consumption. It is crucial to know the symptoms and consequences of the use of Krokodil, as well as METHODS: for identification and quantification of desomorphine, contaminants and metabolites, which can help the forensic work of diagnosis and propose actions to control and eradicate this great danger to public health around the world. Copyright © 2017 Elsevier B.V. All rights reserved.

Advantages of analyzing postmortem brain samples in routine forensic drug screening-Case series of three non-natural deaths tested positive for lysergic acid diethylamide (LSD).

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Mardal, Marie; Johansen, Sys Stybe; Thomsen, Ragnar; Linnet, Kristian

2017-09-01

Three case reports are presented, including autopsy findings and toxicological screening results, which were tested positive for the potent hallucinogenic drug lysergic acid diethylamide (LSD). LSD and its main metabolites were quantified in brain tissue and femoral blood, and furthermore hematoma and urine when available. LSD, its main metabolite 2-oxo-3-hydroxy-LSD (oxo-HO-LSD), and iso-LSD were quantified in biological samples according to a previously published procedure involving liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). LSD was measured in the brain tissue of all presented cases at a concentration level from 0.34-10.8μg/kg. The concentration level in the target organ was higher than in peripheral blood. Additional psychoactive compounds were quantified in blood and brain tissue, though all below toxic concentration levels. The cause of death in case 1 was collision-induced brain injury, while it was drowning in case 2 and 3 and thus not drug intoxication. However, the toxicological findings could help explain the decedent's inability to cope with brain injury or drowning incidents. The presented findings could help establish reference concentrations in brain samples and assist in interpretation of results from forensic drug screening in brain tissue. This is to the author's knowledge the first report of LSD, iso-LSD, and oxo-HO-LSD measured in brain tissue samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Ophthalmological assessment of cannabis-induced persisting perception disorder: is there a direct retinal effect?

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Zobor, Ditta; Strasser, Torsten; Zobor, Gergely; Schober, Franziska; Messias, Andre; Strauss, Olaf; Batra, Anil; Zrenner, Eberhart

2015-04-01

Cannabis is a psychotomimetic agent that induces impairment of sensory perception. We present detailed clinical and electrophysiological data of patients with hallucinogen persisting perception disorder (HPPD) after marijuana consumption. A HPPD patient and four heavy cannabis smokers with no visual disturbances (controls) underwent complete ophthalmological examination including psychophysical tests (visual acuity, color vision, visual field, and dark adaptation) and detailed electrophysiological examinations, including extended Ganzfeld ERG, multifocal ERG, and electrooculography (EOG). Furthermore, electrically evoked phosphene thresholds (EPTs) were measured to further evaluate retinal function. Ophthalmological and most electrophysiological examinations were within normal limits for the HPPD patient and for all control subjects. Interestingly, EOG results of the HPPD patient showed a slightly reduced fast oscillation ratio, diminished standing potentials of the slow oscillations, and a light peak within normal range resulting in higher Arden ratios. The EPTs of the patient were reduced, in particular for pulses with long durations (50 ms) causing visual sensations even at lowest possible currents of the neurostimulator. The control subjects did not reveal such alterations. Our findings suggest a direct effect of cannabinoids on the retina and retinal pigment epithelium function, which may be involved in disturbances of the visual function experienced after drug consumption. The observations presented here may contribute to the elucidation of the detailed mechanism. Furthermore, EOG and EPT measurements may be useful tools to demonstrate long-term retinal alterations in cannabis-induced HPPD in patients.

New Challenges in the Narcotics World

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Nicoleta-Elena Buzatu

2011-05-01

Full Text Available The consumption of narcotics is one of the problems the international world is confronted withnowadays; its direct or indirect effects lead to the conclusion that it represents a worrying phenomenon meantto be taken into account by the international programs of co-operation. In contrast with the mature population,the younger population is much more receptive to the new, much more attracted by new experiments and,consequently, by risks. The narcotics flagellum is one of the most complex, profound and dramaticphenomena met with in the contemporary world. Narcotization is the morbid habit of repeatedly taking andusing ever higher doses of more or less toxic substances able to generate a psychological and physicaladdiction to them. Unhappily due to the lack of information, people think that the illegal substances only –heroine, marijuana, cocaine, etc. – are considered drugs. Not long ago there appeared the so-called “mixes ofethno-botanical plants” that are perfectly legal, and many consumers have replaced narcotics - as marijuana,for example - with plant mixes. According to explanations given by the Ethno-botanical ExplanatoryDictionary, ethno-biology is a branch that studies the mutual relationship between man and plant. InRomania, ethno-botanical plants are sold under the generic names of “aroma therapeutic” or “ethnobotanical”plants. The numerous researches meant to decode the molecular and biochemical structure of theseherbs, the researchers found that consumers are described as facing hallucinogenic effects caused by somesynthetic substances - cannabinoids - added by manufacturers.

Autroadiographic characterization of 125I-labeled 2,5-dimethoxy-4-iodophenylisopropylamine (DOI): A phenylisopropylamine derivative labeling both 5HT2 and 5HT1c receptors

International Nuclear Information System (INIS)

Appel, N.M.; Mitchell, W.M.; Garlick, R.K.; Glennon, R.A.; Titeler, M.; De Souza, E.B.

1990-01-01

The best-characterized 5HT 2 radioligands, such as [ 3 H]ketanserin and [ 3 H]spiperone, are antagonists that label both high- and low-affinity states of this receptor. Recently, the radiolabeled phenylisopropylamine hallucinogens DOB and DOI, which are agonists at 5HT 2 receptors, have been demonstrated to label selectively the high-affinity state of brain 5HT 2 receptors. In the present study, the authors determined optimum conditions for autoradiographic visualization of [ 125 I]DOI binding and characterized its pharmacology and guanine nucleotide sensitivity under those conditions. In slide-mounted tissue sections (rat forebrain; two 10 μm sections/slide), (±)[ 125 I]DOI binding was saturable, of high affinity (K D ∼4nM) and displayed a pharmacological profile [R(-)DOI > spiperone > DOB > (±)DOI > ketanserin > S(+)DOI > 5HT > DOM] comparable to that seen in homogenate assays. Consistent with coupling of 5HT 2 receptors to a guanine nucleotide regulatory protein, [ 125 I]DOI binding was inhibited by guanine nucleotides but not by ATP. In autoradiograms, high densities of [ 125 I]DOI binding sites were present in frontal cortex, olfactory tubercle, claustrum, caudate/putamen and mamillary nuclei with lower densities in trigeminal and solitary nuclei. The highest density of [ 125 l]DOI binding was observed in choroid plexus; these binding sites displayed a pharmacological profile characteristic of 5HT 1C receptors. These data suggest that [ 125 I]DOI labels both 5HT 2 and 5HT 1C receptors

Inhaled Loxapine for Agitation in Intoxicated Patients: A Case Series.

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Roncero, Carlos; Ros-Cucurull, Elena; Palma-Álvarez, Raúl Felipe; Abad, Alfonso Carlos; Fadeuilhe, Christian; Casas, Miquel; Grau-López, Lara

Episodes of agitation are frequent in intoxicated patients who have a substance use disorder, a psychiatric disorder or both (dual diagnosis). For managing the agitation, it is necessary to act promptly in a safe environment and addressing any underlying etiology. Inhaled loxapine improves symptoms of agitation in adults with psychiatric disorders (eg, schizophrenia) within 10 minutes of administration. Recently, some reports have documented the usefulness of loxapine in dual diagnoses patients with agitation. However, the efficacy of loxapine in intoxicated patients has not been deeply addressed. This report describes a case series of 12 patients (with addiction or dual disorder) who received inhaled loxapine for symptoms of psychomotor agitation during intoxication with different substances (eg, alcohol, cannabis, or cocaine) at 1 center in Spain. Data from 12 patients were reviewed, 5 patients were attended at the emergency room, 4 at the addiction and dual diagnosis unit, and 3 were treated during hospitalization for detoxification. All patients were under effects of substances. They had substance use disorder (including cannabis, cocaine, alcohol, hypnotics, and hallucinogens), and almost all (90%) presented 1 or more psychiatric disorders. One dose of inhaled loxapine was effective in 9 patients (75%), and in 3 patients, a second dose was required. Only mild dizziness was reported in 1 patient after the second dose. The acute agitation was effectively and quickly managed with inhaled loxapine in all intoxicated patients and enabled the appropriate clinical evaluation of the agitated state and the patient's management.

Seeing with the eyes shut: neural basis of enhanced imagery following Ayahuasca ingestion.

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de Araujo, Draulio B; Ribeiro, Sidarta; Cecchi, Guillermo A; Carvalho, Fabiana M; Sanchez, Tiago A; Pinto, Joel P; de Martinis, Bruno S; Crippa, Jose A; Hallak, Jaime E C; Santos, Antonio C

2012-11-01

The hallucinogenic brew Ayahuasca, a rich source of serotonergic agonists and reuptake inhibitors, has been used for ages by Amazonian populations during religious ceremonies. Among all perceptual changes induced by Ayahuasca, the most remarkable are vivid "seeings." During such seeings, users report potent imagery. Using functional magnetic resonance imaging during a closed-eyes imagery task, we found that Ayahuasca produces a robust increase in the activation of several occipital, temporal, and frontal areas. In the primary visual area, the effect was comparable in magnitude to the activation levels of natural image with the eyes open. Importantly, this effect was specifically correlated with the occurrence of individual perceptual changes measured by psychiatric scales. The activity of cortical areas BA30 and BA37, known to be involved with episodic memory and the processing of contextual associations, was also potentiated by Ayahuasca intake during imagery. Finally, we detected a positive modulation by Ayahuasca of BA 10, a frontal area involved with intentional prospective imagination, working memory and the processing of information from internal sources. Therefore, our results indicate that Ayahuasca seeings stem from the activation of an extensive network generally involved with vision, memory, and intention. By boosting the intensity of recalled images to the same level of natural image, Ayahuasca lends a status of reality to inner experiences. It is therefore understandable why Ayahuasca was culturally selected over many centuries by rain forest shamans to facilitate mystical revelations of visual nature. Copyright © 2011 Wiley Periodicals, Inc.

Recreational Use, Analysis and Toxicity of Tryptamines

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Tittarelli, Roberta; Mannocchi, Giulio; Pantano, Flaminia; Romolo, Francesco Saverio

2015-01-01

The definition New psychoactive substances (NPS) refers to emerging drugs whose chemical structures are similar to other psychoactive compounds but not identical, representing a “legal” alternative to internationally controlled drugs. There are many categories of NPS, such as synthetic cannabinoids, synthetic cathinones, phenylethylamines, piperazines, ketamine derivatives and tryptamines. Tryptamines are naturally occurring compounds, which can derive from the amino acid tryptophan by several biosynthetic pathways: their structure is a combination of a benzene ring and a pyrrole ring, with the addition of a 2-carbon side chain. Tryptamines include serotonin and melatonin as well as other compounds known for their hallucinogenic properties, such as psilocybin in ‘Magic mushrooms’ and dimethyltryptamine (DMT) in Ayahuasca brews. Aim: To review the scientific literature regarding tryptamines and their derivatives, providing a summary of all the available information about the structure of these compounds, their effects in relationship with the routes of administration, their pharmacology and toxicity, including articles reporting cases of death related to intake of these substances. Methods: A comprehensive review of the published scientific literature was performed, using also non peer-reviewed information sources, such as books, government publications and drug user web fora. Conclusions: Information from Internet and from published scientific literature, organized in the way we proposed in this review, provides an effective tool for specialists facing the emerging NPS threat to public health and public security, including the personnel working in Emergency Department. PMID:26074742

Novel Psychoactive Substances-Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs.

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Hassan, Zurina; Bosch, Oliver G; Singh, Darshan; Narayanan, Suresh; Kasinather, B Vicknasingam; Seifritz, Erich; Kornhuber, Johannes; Quednow, Boris B; Müller, Christian P

2017-01-01

A feature of human culture is that we can learn to consume chemical compounds, derived from natural plants or synthetic fabrication, for their psychoactive effects. These drugs change the mental state and/or the behavioral performance of an individual and can be instrumentalized for various purposes. After the emergence of a novel psychoactive substance (NPS) and a period of experimental consumption, personal and medical benefits and harm potential of the NPS can be estimated on evidence base. This may lead to a legal classification of the NPS, which may range from limited medical use, controlled availability up to a complete ban of the drug form publically accepted use. With these measures, however, a drug does not disappear, but frequently continues to be used, which eventually allows an even better estimate of the drug's properties. Thus, only in rare cases, there is a final verdict that is no more questioned. Instead, the view on a drug can change from tolerable to harmful but may also involve the new establishment of a desired medical application to a previously harmful drug. Here, we provide a summary review on a number of NPS for which the neuropharmacological evaluation has made important progress in recent years. They include mitragynine ("Kratom"), synthetic cannabinoids (e.g., "Spice"), dimethyltryptamine and novel serotonergic hallucinogens, the cathinones mephedrone and methylone, ketamine and novel dissociative drugs, γ-hydroxybutyrate, γ-butyrolactone, and 1,4-butanediol. This review shows not only emerging harm potentials but also some potential medical applications.

Effects and risks associated with novel psychoactive substances: mislabeling and sale as bath salts, spice, and research chemicals.

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Hohmann, Nicolas; Mikus, Gerd; Czock, David

2014-02-28

The number of newly reported psychoactive substances in Europe is now higher than ever. In order to evade legal restrictions, old and novel psychoactive substances from medical research and their derivatives are commonly mislabeled as "not for human consumption" and offered for sale on the Internet and elsewhere. Such substances are widely taken by young people as "club drugs." Their consumption must be considered in the differential diagnosis of psychiatric, neurological, cardiovascular, or metabolic disturbances of unclear origin in a young patient. Selective review of pertinent literature retrieved by a PubMed search, including publications by government-sponsored organizations. From 2010 to 2012, 163 substances were reported to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), mostly either synthetic cannabinoids (39.3%) or synthetic cathinones (16.6%). Synthetic cannabinoids alter mood and perception; intoxications cause agitation, tachy cardia, and arterial hypertension. Synthetic cathinones are hallucinogenic stimulants with predominantly cardiovascular and psychiatric side effects. Severe intoxications cause serotonin syndrome and potentially fatal rhabdomyolysis. Substances in either of these classes often escape detection in screening tests. Young persons who present with agitation and cardiovascular and/or psychiatric manifestations of unclear origin and whose drug screening tests are negative may be suffering from an intoxication with a novel psychoactive substance. Physicians should know the classes of such substances and their effects. Targeted toxicological analysis can be carried out in a toxicology laboratory or a facility for forensic medicine.

The Mechanistic Basis for Noncompetitive Ibogaine Inhibition of Serotonin and Dopamine Transporters*

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Bulling, Simon; Schicker, Klaus; Zhang, Yuan-Wei; Steinkellner, Thomas; Stockner, Thomas; Gruber, Christian W.; Boehm, Stefan; Freissmuth, Michael; Rudnick, Gary; Sitte, Harald H.; Sandtner, Walter

2012-01-01

Ibogaine, a hallucinogenic alkaloid proposed as a treatment for opiate withdrawal, has been shown to inhibit serotonin transporter (SERT) noncompetitively, in contrast to all other known inhibitors, which are competitive with substrate. Ibogaine binding to SERT increases accessibility in the permeation pathway connecting the substrate-binding site with the cytoplasm. Because of the structural similarity between ibogaine and serotonin, it had been suggested that ibogaine binds to the substrate site of SERT. The results presented here show that ibogaine binds to a distinct site, accessible from the cell exterior, to inhibit both serotonin transport and serotonin-induced ionic currents. Ibogaine noncompetitively inhibited transport by both SERT and the homologous dopamine transporter (DAT). Ibogaine blocked substrate-induced currents also in DAT and increased accessibility of the DAT cytoplasmic permeation pathway. When present on the cell exterior, ibogaine inhibited SERT substrate-induced currents, but not when it was introduced into the cytoplasm through the patch electrode. Similar to noncompetitive transport inhibition, the current block was not reversed by increasing substrate concentration. The kinetics of inhibitor binding and dissociation, as determined by their effect on SERT currents, indicated that ibogaine does not inhibit by forming a long-lived complex with SERT, but rather binds directly to the transporter in an inward-open conformation. A kinetic model for transport describing the noncompetitive action of ibogaine and the competitive action of cocaine accounts well for the results of the present study. PMID:22451652

The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters.

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Bulling, Simon; Schicker, Klaus; Zhang, Yuan-Wei; Steinkellner, Thomas; Stockner, Thomas; Gruber, Christian W; Boehm, Stefan; Freissmuth, Michael; Rudnick, Gary; Sitte, Harald H; Sandtner, Walter

2012-05-25

Ibogaine, a hallucinogenic alkaloid proposed as a treatment for opiate withdrawal, has been shown to inhibit serotonin transporter (SERT) noncompetitively, in contrast to all other known inhibitors, which are competitive with substrate. Ibogaine binding to SERT increases accessibility in the permeation pathway connecting the substrate-binding site with the cytoplasm. Because of the structural similarity between ibogaine and serotonin, it had been suggested that ibogaine binds to the substrate site of SERT. The results presented here show that ibogaine binds to a distinct site, accessible from the cell exterior, to inhibit both serotonin transport and serotonin-induced ionic currents. Ibogaine noncompetitively inhibited transport by both SERT and the homologous dopamine transporter (DAT). Ibogaine blocked substrate-induced currents also in DAT and increased accessibility of the DAT cytoplasmic permeation pathway. When present on the cell exterior, ibogaine inhibited SERT substrate-induced currents, but not when it was introduced into the cytoplasm through the patch electrode. Similar to noncompetitive transport inhibition, the current block was not reversed by increasing substrate concentration. The kinetics of inhibitor binding and dissociation, as determined by their effect on SERT currents, indicated that ibogaine does not inhibit by forming a long-lived complex with SERT, but rather binds directly to the transporter in an inward-open conformation. A kinetic model for transport describing the noncompetitive action of ibogaine and the competitive action of cocaine accounts well for the results of the present study.

Using selected scenes from Brazilian films to teach about substance use disorders, within medical education.

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Castaldelli-Maia, João Mauricio; Oliveira, Hercílio Pereira; Andrade, Arthur Guerra; Lotufo-Neto, Francisco; Bhugra, Dinesh

2012-01-01

Themes like alcohol and drug abuse, relationship difficulties, psychoses, autism and personality dissociation disorders have been widely used in films. Psychiatry and psychiatric conditions in various cultural settings are increasingly taught using films. Many articles on cinema and psychiatry have been published but none have presented any methodology on how to select material. Here, the authors look at the portrayal of abusive use of alcohol and drugs during the Brazilian cinema revival period (1994 to 2008). Qualitative study at two universities in the state of São Paulo. Scenes were selected from films available at rental stores and were analyzed using a specifically designed protocol. We assessed how realistic these scenes were and their applicability for teaching. One author selected 70 scenes from 50 films (graded for realism and teaching applicability > 8). These were then rated by another two judges. Rating differences among the three judges were assessed using nonparametric tests (P 8) were defined as "quality scenes". Thirty-nine scenes from 27 films were identified as "quality scenes". Alcohol, cannabis, cocaine, hallucinogens and inhalants were included in these. Signs and symptoms of intoxication, abusive/harmful use and dependence were shown. We have produced rich teaching material for discussing psychopathology relating to alcohol and drug use that can be used both at undergraduate and at postgraduate level. Moreover, it could be seen that certain drug use behavioral patterns are deeply rooted in some Brazilian films and groups.

A typology of drug selling among young adults in the United States.

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Vaughn, Michael G; Salas-Wright, Christopher P; DeLisi, Matt; Shook, Jeffrey J; Terzis, Lauren

2015-02-01

Although studies have found that young adults who sell drugs are more likely to be involved in risky behaviors than those who do not sell drugs, there has been relatively little research that has explored heterogeneity among young adults who sell drugs. Using a pooled sample of 18 to 25 year olds from the National Survey on Drug Use and Health (2006-2010) who report past-year drug selling (N = 5,373), this study employs latent profile analysis to specify latent groups and assess the correlates of group membership. Findings indicate substantial differences among young adults who sell drugs. In particular, the analysis found four groups of drug sellers: normative (49.6%), club drug users (23.6%), polysubstance users (16.0%), and criminal offenders (10.8%). Club drug users were characterized by high levels of ecstasy and hallucinogen use, polysubstance users were more likely to be depressed and anxious, White and female than the other groups. Criminal offenders were overwhelmingly male and more likely to be comprised of African-Americans and Hispanics. RESULTS indicate that drug selling in early adulthood varies substantially. Contrary to media and popular notions most drug sellers are not involved in crime and polysubstance using drug sellers are in clear need of mental health services. Further, most drug sellers in this age range are White. Findings suggest that policy efforts that operate under the assumption of homogeneity of drug selling may be misguided.

Multiple DSM-5 substance use disorders: A national study of US adults.

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McCabe, Sean Esteban; West, Brady T; Jutkiewicz, Emily M; Boyd, Carol J

2017-09-01

Our aim is to determine the lifetime and past-year prevalence estimates of multiple Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) substance use disorders (SUDs) among U.S. adults. The 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions featured in-person interviews with a nationally representative sample of adults aged 18 and older. The majority of past-year nonalcohol DSM-5 SUDs had at least 1 other co-occurring past-year SUD, ranging from 56.8% (SE = 3.4) for past-year prescription opioid use disorder to 97.5% (SE = 2.7) for past-year hallucinogen use disorder. In contrast, only 15.0% (SE = 0.6) of past-year alcohol use disorders had a co-occurring past-year SUD. The odds of past-year multiple SUDs were greater among males, younger adults, African-Americans, and those with mood, personality, posttraumatic stress, or multiple psychiatric disorders. Assessment, diagnosis, and treatment often focus on individual substance-specific SUDs rather than multiple SUDs, despite evidence for substantial rates of polysubstance use in clinical and epidemiological studies. There are notable differences in the prevalence of multiple SUDs between alcohol use disorders and other nonalcohol SUDs that have important clinical implications; for example, multiple SUDs are more persistent than individual SUDs. These findings suggest that clinical assessment and diagnosis should screen for multiple SUDs, especially among adults with nonalcohol DSM-5 SUDs. Copyright © 2017 John Wiley & Sons, Ltd.

El Dioscórides de Andrés Laguna en los textos de Cervantes: de la materia medicinal al universo literario

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Francisco López-Muñoz

2007-12-01

Full Text Available The literary works of Miguel de Cervantes have been widely studied from numerous points of view, including the medical one. In the present work, we defend the hypothesis that the Andrés Laguna version of Dioscorides was the source used by Cervantes in his literary passages related to therapeutic aspects, especially in relation to plants with medicinal properties. This book, a copy of which was in Cervantes’ private library, is the only medical treatise cited by the novelist in any of his writings (Don Quixote. Apart from the medicinal plants mentioned in his works, of which we have identified chicory, oleander, henbane, opium poppy, rosemary, rhubarb, tobacco, tamarisk, seeds of spurge, and vervain, Cervantes also seemed familiar with the effects of different pharmaceutical preparations produced from plants (white ointment, Aparicio’s Oil, narcotic powders, etc.. Our hypothesis is backed up by Cervantes’ use of descriptions similar to those of Laguna in his Dioscorides (the hallucinogenic effects of witches’ ointments in The Colloquy of the Dogs, the therapeutic properties of rosemary in the treatment of wounds and traumatisms in Don Quixote, the narcotic effects of opium in The Jealous Extremaduran, the psychodysleptic effects of some love potions in The Licentiate of Glass, or the toxic effects of some poisons in The Spanish-English Lady, and even, in some cases, by use of Laguna’s similar quotations (as in his reference to the purging of excessive bile in Don Quixote.

Smart drugs and synthetic androgens for cognitive and physical enhancement: revolving doors of cosmetic neurology.

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Frati, Paola; Kyriakou, Chrystalla; Del Rio, Alessandro; Marinelli, Enrico; Vergallo, Gianluca Montanari; Zaami, Simona; Busardò, Francesco P

2015-01-01

Cognitive enhancement can be defined as the use of drugs and/or other means with the aim to improve the cognitive functions of healthy subjects in particular memory, attention, creativity and intelligence in the absence of any medical indication. Currently, it represents one of the most debated topics in the neuroscience community. Human beings always wanted to use substances to improve their cognitive functions, from the use of hallucinogens in ancient civilizations in an attempt to allow them to better communicate with their gods, to the widespread use of caffeine under various forms (energy drinks, tablets, etc.), to the more recent development of drugs such as stimulants and glutamate activators. In the last ten years, increasing attention has been given to the use of cognitive enhancers, but up to now there is still only a limited amount of information concerning the use, effect and functioning of cognitive enhancement in daily life on healthy subjects. The first aim of this paper was to review current trends in the misuse of smart drugs (also known as Nootropics) presently available on the market focusing in detail on methylphenidate, trying to evaluate the potential risk in healthy individuals, especially teenagers and young adults. Moreover, the authors have explored the issue of cognitive enhancement compared to the use of Anabolic Androgenic Steroids (AAS) in sports. Finally, a brief overview of the ethical considerations surrounding human enhancement has been examined.

Smart Drugs and Synthetic Androgens for Cognitive and Physical Enhancement: Revolving Doors of Cosmetic Neurology

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Frati, Paola; Kyriakou, Chrystalla; Del Rio, Alessandro; Marinelli, Enrico; Vergallo, Gianluca Montanari; Zaami, Simona; Busardò, Francesco P.

2015-01-01

Cognitive enhancement can be defined as the use of drugs and/or other means with the aim to improve the cognitive functions of healthy subjects in particular memory, attention, creativity and intelligence in the absence of any medical indication. Currently, it represents one of the most debated topics in the neuroscience community. Human beings always wanted to use substances to improve their cognitive functions, from the use of hallucinogens in ancient civilizations in an attempt to allow them to better communicate with their gods, to the widespread use of caffeine under various forms (energy drinks, tablets, etc.), to the more recent development of drugs such as stimulants and glutamate activators. In the last ten years, increasing attention has been given to the use of cognitive enhancers, but up to now there is still only a limited amount of information concerning the use, effect and functioning of cognitive enhancement in daily life on healthy subjects. The first aim of this paper was to review current trends in the misuse of smart drugs (also known as Nootropics) presently available on the market focusing in detail on methylphenidate, trying to evaluate the potential risk in healthy individuals, especially teenagers and young adults. Moreover, the authors have explored the issue of cognitive enhancement compared to the use of Anabolic Androgenic Steroids (AAS) in sports. Finally, a brief overview of the ethical considerations surrounding human enhancement has been examined. PMID:26074739

Comparative study of drug use among undergraduate students at the University of São Paulo: São Paulo campus in 1996 and 2001 Estudo comparativo entre 1996 e 2001 do uso de drogas por alunos da graduação da Universidade de São Paulo: Campus São Paulo

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Vladimir de Andrade Stempliuk

2005-09-01

Full Text Available OBJECTIVE: To compare the rate of drug use prevalence and to investigate opinions regarding such use among undergraduate students at the University of São Paulo - São Paulo campus in 1996 and again in 2001. METHODS: Both studies followed the same procedures of sampling and data collection. A random sample of undergraduate students, divided into the areas Humanities, Exact Sciences and Biologic Sciences, responded to an anonymous and self-report survey regarding the use of licit and illicit drugs within the last 30 days, within the last 12 months and over the lifetime of the subject. The two surveys were compared through the construction of (95% confidence intervals for the prevalence differences for each substance by area and by total number of students. The Wald test for homogeneity was applied in order to compare the prevalences. RESULTS: High approval of regularly trying and using cocaine, crack, amphetamines and inhalants was observed. The drugs that showed statistic significant increasing were:lifetime use: alcohol, tobacco, marijuana, inhalants, hallucinogens, amphetamines, anticholines, barbiturics and any illicit drug;last-12-month use: marijuana, inhalants, amphetamines, hallucinogens and any illicit drug;last-30-day use: marijuana, inhalants, amphetamines and any illicit drug. DISCUSSON: The observed difference in the use of some drugs between the two surveys appears to be a consequence of the higher rates of favorable opinions regarding trying and regularly using some psychoactive substances, a finding that mirrors global trends in drug use.OBJETIVO: Esta pesquisa teve como objetivo comparar as prevalências de uso de diversas drogas e as opiniões sobre esses usos entre estudantes de graduação da Universidade de São Paulo (USP nos anos de 1996 e 2001. MÉTODOS: Os dois estudos seguiram as mesmas metodologias de amostragem e coleta de dados. Os alunos foram randomicamente selecionados de acordo com suas áreas de estudo (Biol

Clinical Interpretations of Patient Experience in a Trial of Psilocybin-Assisted Psychotherapy for Alcohol Use Disorder

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Michael P. Bogenschutz

2018-02-01

Full Text Available After a hiatus of some 40 years, clinical research has resumed on the use of classic hallucinogens to treat addiction. Following completion of a small open-label feasibility study, we are currently conducting a double-blind placebo-controlled clinical trial of psilocybin-assisted treatment of alcohol use disorder. Although treatment effects cannot be analyzed until the study is complete, descriptive case studies provide a useful window into the therapeutic process of psychedelic-assisted treatment of addiction. Here we describe treatment trajectories of three participants in the ongoing trial to illustrate the range of experiences and persisting effects of psilocybin treatment. Although it is difficult to generalize from a few cases, several qualitative conclusions can be drawn from the data presented here. Although participants often find it difficult to describe much of their psilocybin experience, pivotal moments tend to be individualized, extremely vivid, and memorable. Often, the qualitative content extends beyond the clinical problem that is being addressed. The participants discussed in this paper experienced acute and lasting alterations in their perceptions of self, in the quality of their baseline consciousness, and in their relationship with alcohol and drinking. In these cases, experiences of catharsis, forgiveness, self-compassion, and love were at least as salient as classic mystical content. Finally, feelings of increased “spaciousness” or mindfulness, and increased control over choices and behavior were reported following the drug administration sessions. Ultimately, psilocybin-assisted treatment appears to elicit experiences that are extremely variable, yet seem to meet the particular needs of the individual.

Magic truffles or Philosopher's stones: a legal way to sell psilocybin?

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Pellegrini, Manuela; Rotolo, Maria Concetta; Marchei, Emilia; Pacifici, Roberta; Saggio, Francesco; Pichini, Simona

2013-03-01

"Magic mushrooms" is the most common name given to hallucinogenic fungi containing the psychoactive alkaloids psilocybin and psilocin. In recent years, fungis' sclerotia, commonly called "magic truffles" have become a form of supply of psychoactive Psilocybe alkaloids since Psilocybe sclerotia are not specifically included in the laws banning the sale, the purchase and the use of such substances and mushrooms containing them. A liquid chromatography -tandem mass spectrometry (LC-MS/MS) method was developed for the rapid determination of psilocybin and psilocin in Psilocybe sclerotia. Following a simple step extraction with methanol, the alkaloids were separated on a reversed-phase column using a gradient of 0.1% formic acid - acetonitrile s a mobile phase at a flow rate of 0.2 mL/min.. Separated analytes were detected by electrospray ionization tandem mass spectrometry in the positive ion mode using multiple reaction monitoring. The developed method was linear over the calibration range for all two substances under investigation, with a r(2)  > 0.99. The detection and quantification limits were 0.3 µg and 1 µg per 100 mg truffles, for both psilocin and psilocybin and the intra- and inter-day coefficients of variation were always better than 15%. Using this method, the presence of only psilocybin was demonstrated in examined Psilocybe sclerotia. The content of psilocybin was found to vary over a concentration range of 59.3 to 167.8 µg per 100 mg of fresh sclerotia. Copyright © 2012 John Wiley & Sons, Ltd.

Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers.

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Kraehenmann, Rainer; Preller, Katrin H; Scheidegger, Milan; Pokorny, Thomas; Bosch, Oliver G; Seifritz, Erich; Vollenweider, Franz X

2015-10-15

The amygdala is a key structure in serotonergic emotion-processing circuits. In healthy volunteers, acute administration of the serotonin 1A/2A/2C receptor agonist psilocybin reduces neural responses to negative stimuli and induces mood changes toward positive states. However, it is little-known whether psilocybin reduces amygdala reactivity to negative stimuli and whether any change in amygdala reactivity is related to mood change. This study assessed the effects of acute administration of the hallucinogen psilocybin (.16 mg/kg) versus placebo on amygdala reactivity to negative stimuli in 25 healthy volunteers using blood oxygen level-dependent functional magnetic resonance imaging. Mood changes were assessed using the Positive and Negative Affect Schedule and the state portion of the State-Trait Anxiety Inventory. A double-blind, randomized, cross-over design was used with volunteers counterbalanced to receive psilocybin and placebo in two separate sessions at least 14 days apart. Amygdala reactivity to negative and neutral stimuli was lower after psilocybin administration than after placebo administration. The psilocybin-induced attenuation of right amygdala reactivity in response to negative stimuli was related to the psilocybin-induced increase in positive mood state. These results demonstrate that acute treatment with psilocybin decreased amygdala reactivity during emotion processing and that this was associated with an increase of positive mood in healthy volunteers. These findings may be relevant to the normalization of amygdala hyperactivity and negative mood states in patients with major depression. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Psilocybin-induced spiritual experiences and insightfulness are associated with synchronization of neuronal oscillations.

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Kometer, Michael; Pokorny, Thomas; Seifritz, Erich; Volleinweider, Franz X

2015-10-01

During the last years, considerable progress has been made toward understanding the neuronal basis of consciousness by using sophisticated behavioral tasks, brain-imaging techniques, and various psychoactive drugs. Nevertheless, the neuronal mechanisms underlying some of the most intriguing states of consciousness, including spiritual experiences, remain unknown. To elucidate state of consciousness-related neuronal mechanisms, human subjects were given psilocybin, a naturally occurring serotonergic agonist and hallucinogen that has been used for centuries to induce spiritual experiences in religious and medical rituals. In this double-blind, placebo-controlled study, 50 healthy human volunteers received a moderate dose of psilocybin, while high-density electroencephalogram (EEG) recordings were taken during eyes-open and eyes-closed resting states. The current source density and the lagged phase synchronization of neuronal oscillations across distributed brain regions were computed and correlated with psilocybin-induced altered states of consciousness. Psilocybin decreased the current source density of neuronal oscillations at 1.5-20 Hz within a neural network comprising the anterior and posterior cingulate cortices and the parahippocampal regions. Most intriguingly, the intensity levels of psilocybin-induced spiritual experience and insightfulness correlated with the lagged phase synchronization of delta oscillations (1.5-4 Hz) between the retrosplenial cortex, the parahippocampus, and the lateral orbitofrontal area. These results provide systematic evidence for the direct association of a specific spatiotemporal neuronal mechanism with spiritual experiences and enhanced insight into life and existence. The identified mechanism may constitute a pathway for modulating mental health, as spiritual experiences can promote sustained well-being and psychological resilience.

The 5-HT2A/1A agonist psilocybin disrupts modal object completion associated with visual hallucinations.

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Kometer, Michael; Cahn, B Rael; Andel, David; Carter, Olivia L; Vollenweider, Franz X

2011-03-01

Recent findings suggest that the serotonergic system and particularly the 5-HT2A/1A receptors are implicated in visual processing and possibly the pathophysiology of visual disturbances including hallucinations in schizophrenia and Parkinson's disease. To investigate the role of 5-HT2A/1A receptors in visual processing the effect of the hallucinogenic 5-HT2A/1A agonist psilocybin (125 and 250 μg/kg vs. placebo) on the spatiotemporal dynamics of modal object completion was assessed in normal volunteers (n = 17) using visual evoked potential recordings in conjunction with topographic-mapping and source analysis. These effects were then considered in relation to the subjective intensity of psilocybin-induced visual hallucinations quantified by psychometric measurement. Psilocybin dose-dependently decreased the N170 and, in contrast, slightly enhanced the P1 component selectively over occipital electrode sites. The decrease of the N170 was most apparent during the processing of incomplete object figures. Moreover, during the time period of the N170, the overall reduction of the activation in the right extrastriate and posterior parietal areas correlated positively with the intensity of visual hallucinations. These results suggest a central role of the 5-HT2A/1A-receptors in the modulation of visual processing. Specifically, a reduced N170 component was identified as potentially reflecting a key process of 5-HT2A/1A receptor-mediated visual hallucinations and aberrant modal object completion potential. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Effects of psilocybin on time perception and temporal control of behaviour in humans.

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Wittmann, Marc; Carter, Olivia; Hasler, Felix; Cahn, B Rael; Grimberg, Ulrike; Spring, Philipp; Hell, Daniel; Flohr, Hans; Vollenweider, Franz X

2007-01-01

Hallucinogenic psilocybin is known to alter the subjective experience of time. However, there is no study that systematically investigated objective measures of time perception under psilocybin. Therefore, we studied dose-dependent effects of the serotonin (5-HT)2A/1A receptor agonist psilocybin (4-phosphoryloxy-N, N-dimethyltryptamine) on temporal processing, employing tasks of temporal reproduction, sensorimotor synchronization and tapping tempo. To control for cognitive and subjective changes, we assessed spatial working memory and conscious experience. Twelve healthy human volunteers were tested under placebo, medium (115 microg/kg), and high (250 microg/kg) dose conditions, in a double-blind experimental design. Psilocybin was found to significantly impair subjects' ability to (1) reproduce interval durations longer than 2.5 sec, (2) to synchronize to inter-beat intervals longer than 2 sec and (3) caused subjects to be slower in their preferred tapping rate. These objective effects on timing performance were accompanied by working-memory deficits and subjective changes in conscious state, namely increased reports of 'depersonalization' and 'derealization' phenomena including disturbances in subjective 'time sense.' Our study is the first to systematically assess the impact of psilocybin on timing performance on standardized measures of temporal processing. Results indicate that the serotonin system is selectively involved in duration processing of intervals longer than 2 to 3 seconds and in the voluntary control of the speed of movement. We speculate that psilocybin's selective disruption of longer intervals is likely to be a product of interactions with cognitive dimensions of temporal processing -presumably via 5-HT2A receptor stimulation.

Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance.

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Griffiths, R R; Richards, W A; McCann, U; Jesse, R

2006-08-01

Although psilocybin has been used for centuries for religious purposes, little is known scientifically about its acute and persisting effects. This double-blind study evaluated the acute and longer-term psychological effects of a high dose of psilocybin relative to a comparison compound administered under comfortable, supportive conditions. The participants were hallucinogen-naïve adults reporting regular participation in religious or spiritual activities. Two or three sessions were conducted at 2-month intervals. Thirty volunteers received orally administered psilocybin (30 mg/70 kg) and methylphenidate hydrochloride (40 mg/70 kg) in counterbalanced order. To obscure the study design, six additional volunteers received methylphenidate in the first two sessions and unblinded psilocybin in a third session. The 8-h sessions were conducted individually. Volunteers were encouraged to close their eyes and direct their attention inward. Study monitors rated volunteers' behavior during sessions. Volunteers completed questionnaires assessing drug effects and mystical experience immediately after and 2 months after sessions. Community observers rated changes in the volunteer's attitudes and behavior. Psilocybin produced a range of acute perceptual changes, subjective experiences, and labile moods including anxiety. Psilocybin also increased measures of mystical experience. At 2 months, the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained positive changes in attitudes and behavior consistent with changes rated by community observers. When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences. The ability to occasion such experiences prospectively will allow rigorous scientific investigations of their causes and consequences.

Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects.

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Griffiths, Roland R; Johnson, Matthew W; Richards, William A; Richards, Brian D; McCann, Una; Jesse, Robert

2011-12-01

This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. This double-blind study evaluated psilocybin (0, 5, 10, 20, 30 mg/70 kg, p.o.) administered under supportive conditions. Participants were 18 adults (17 hallucinogen-naïve). Five 8-h sessions were conducted individually for each participant at 1-month intervals. Participants were randomized to receive the four active doses in either ascending or descending order (nine participants each). Placebo was scheduled quasi-randomly. During sessions, volunteers used eyeshades and were instructed to direct their attention inward. Volunteers completed questionnaires assessing effects immediately after and 1 month after each session, and at 14 months follow-up. Psilocybin produced acute perceptual and subjective effects including, at 20 and/or 30 mg/70 kg, extreme anxiety/fear (39% of volunteers) and/or mystical-type experience (72% of volunteers). One month after sessions at the two highest doses, volunteers rated the psilocybin experience as having substantial personal and spiritual significance, and attributed to the experience sustained positive changes in attitudes, mood, and behavior, with the ascending dose sequence showing greater positive effects. At 14 months, ratings were undiminished and were consistent with changes rated by community observers. Both the acute and persisting effects of psilocybin were generally a monotonically increasing function of dose, with the lowest dose showing significant effects. Under supportive conditions, 20 and 30 mg/70 kg psilocybin occasioned mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. Implications for therapeutic trials are discussed.

Clinical Interpretations of Patient Experience in a Trial of Psilocybin-Assisted Psychotherapy for Alcohol Use Disorder.

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Bogenschutz, Michael P; Podrebarac, Samantha K; Duane, Jessie H; Amegadzie, Sean S; Malone, Tara C; Owens, Lindsey T; Ross, Stephen; Mennenga, Sarah E

2018-01-01

After a hiatus of some 40 years, clinical research has resumed on the use of classic hallucinogens to treat addiction. Following completion of a small open-label feasibility study, we are currently conducting a double-blind placebo-controlled clinical trial of psilocybin-assisted treatment of alcohol use disorder. Although treatment effects cannot be analyzed until the study is complete, descriptive case studies provide a useful window into the therapeutic process of psychedelic-assisted treatment of addiction. Here we describe treatment trajectories of three participants in the ongoing trial to illustrate the range of experiences and persisting effects of psilocybin treatment. Although it is difficult to generalize from a few cases, several qualitative conclusions can be drawn from the data presented here. Although participants often find it difficult to describe much of their psilocybin experience, pivotal moments tend to be individualized, extremely vivid, and memorable. Often, the qualitative content extends beyond the clinical problem that is being addressed. The participants discussed in this paper experienced acute and lasting alterations in their perceptions of self, in the quality of their baseline consciousness, and in their relationship with alcohol and drinking. In these cases, experiences of catharsis, forgiveness, self-compassion, and love were at least as salient as classic mystical content. Finally, feelings of increased "spaciousness" or mindfulness, and increased control over choices and behavior were reported following the drug administration sessions. Ultimately, psilocybin-assisted treatment appears to elicit experiences that are extremely variable, yet seem to meet the particular needs of the individual.

A Bayesian hierarchical model for demand curve analysis.

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Ho, Yen-Yi; Nhu Vo, Tien; Chu, Haitao; Luo, Xianghua; Le, Chap T

2018-07-01

Drug self-administration experiments are a frequently used approach to assessing the abuse liability and reinforcing property of a compound. It has been used to assess the abuse liabilities of various substances such as psychomotor stimulants and hallucinogens, food, nicotine, and alcohol. The demand curve generated from a self-administration study describes how demand of a drug or non-drug reinforcer varies as a function of price. With the approval of the 2009 Family Smoking Prevention and Tobacco Control Act, demand curve analysis provides crucial evidence to inform the US Food and Drug Administration's policy on tobacco regulation, because it produces several important quantitative measurements to assess the reinforcing strength of nicotine. The conventional approach popularly used to analyze the demand curve data is individual-specific non-linear least square regression. The non-linear least square approach sets out to minimize the residual sum of squares for each subject in the dataset; however, this one-subject-at-a-time approach does not allow for the estimation of between- and within-subject variability in a unified model framework. In this paper, we review the existing approaches to analyze the demand curve data, non-linear least square regression, and the mixed effects regression and propose a new Bayesian hierarchical model. We conduct simulation analyses to compare the performance of these three approaches and illustrate the proposed approaches in a case study of nicotine self-administration in rats. We present simulation results and discuss the benefits of using the proposed approaches.

Alternative drugs of abuse.

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Sutter, M E; Chenoweth, J; Albertson, T E

2014-02-01

The incidence of drug abuse with alternative agents is increasing. The term "alternative drugs of abuse" is a catch-all term for abused chemicals that do not fit into one of the classic categories of drugs of abuse. The most common age group abusing these agents range from 17 to 25 years old and are often associated with group settings. Due to their diverse pharmacological nature, legislative efforts to classify these chemicals as a schedule I drug have lagged behind the development of new alternative agents. The potential reason for abuse of these agents is their hallucinogenic, dissociative, stimulant, anti-muscarinic, or sedative properties. Some of these drugs are easily obtainable such as Datura stramonium (Jimson Weed) or Lophophora williamsii (Peyote) because they are natural plants indigenous to certain regions. The diverse pharmacology and clinical effects of these agents are so broad that they do not produce a universal constellation of signs and symptoms. Detailed physical exams are essential for identifying clues leading one to suspect an alternative drug of abuse. Testing for the presence of these agents is often limited, and even when available, the results do not return in a timely fashion. Intoxications from these agents pose unique challenges for health care providers. Physician knowledge of the physiological effects of these alternative agents and the local patterns of drug of abuse are important for the accurate diagnosis and optimal care of poisoned patients. This review summarizes the current knowledge of alternative drugs of abuse and highlights their clinical presentations.

Prevalence of hospitalized live births affected by alcohol and drugs and parturient women diagnosed with substance abuse at liveborn delivery: United States, 1999-2008.

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Pan, I-Jen; Yi, Hsiao-ye

2013-05-01

To describe prevalence trends in hospitalized live births affected by placental transmission of alcohol and drugs, as well as prevalence trends among parturient women hospitalized for liveborn delivery and diagnosed with substance abuse problems in the United States from 1999 to 2008. Comparison of the two sets of trends helps determine whether the observed changes in neonatal problems over time were caused by shifts in maternal substance abuse problems. This study independently identified hospitalized live births and maternal live born deliveries from discharge records in the Nationwide Inpatient Sample, one of the largest hospital administrative databases. Substance-related diagnosis codes on the records were used to identify live births affected by alcohol and drugs and parturient women with substance abuse problems. The analysis calculated prevalence differences and percentage changes over the 10 years, with Loess curves fitted to 10-year prevalence estimates to depict trend patterns. Linear and quadratic trends in prevalence were simultaneously tested using logistic regression analyses. The study also examined data on costs, primary expected payer, and length of hospital stays. From 1999 to 2008, prevalence increased for narcotic- and hallucinogen-affected live births and neonatal drug withdrawal syndrome but decreased for alcohol- and cocaine-affected live births. Maternal substance abuse at delivery showed similar trends, but prevalence of alcohol abuse remained relatively stable. Substance-affected live births required longer hospital stays and higher medical expenses, mostly billable to Medicaid. The findings highlight the urgent need for behavioral intervention and early treatment for substance-abusing pregnant women to reduce the number of substance-affected live births.

Interaction between LSD and dopamine D2/3 binding sites in pig brain.

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Minuzzi, Luciano; Nomikos, George G; Wade, Mark R; Jensen, Svend B; Olsen, Aage K; Cumming, Paul

2005-06-15

The psychoactive properties of the hallucinogen LSD have frequently been attributed to high affinity interactions with serotonin 5HT2 receptors in brain. Possible effects of LSD on dopamine D2/3 receptor availability have not previously been investigated in living brain. Therefore, we used PET to map the binding potential (pB) of [11C]raclopride in brain of three pigs, first in a baseline condition, and again at 1 and 4 h after administration of LSD (2.5 microg/kg, i.v.). There was a progressive treatment effect in striatum, where the pB was significantly reduced by 19% at 4 h after LSD administration. Concomitant maps of cerebral blood flow did not reveal significant changes in perfusion during this interval. Subsequent in vitro studies showed that LSD displaced [3H]raclopride (2 nM) from pig brain cryostat sections with an IC50 of 275 nM according to a one-site model. Fitting of a two-site model to the data suggested the presence of a component of the displacement curves with a subnanomolar IC50, comprising 20% of the total [3H]raclopride binding. In microdialysis experiments, LSD at similar and higher doses did not evoke changes in the interstitial concentration of dopamine or its acidic metabolites in rat striatum. Together, these results are consistent with a direct interaction between LSD and a portion of dopamine D2/3 receptors in pig brain, possibly contributing to the psychopharmacology of LSD. (c) 2005 Wiley-Liss, Inc.

Modern Clinical Research on LSD.

Science.gov (United States)

Liechti, Matthias E

2017-10-01

All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT 2A receptor. LSD increased feelings of closeness to others, openness, trust, and suggestibility. LSD impaired the recognition of sad and fearful faces, reduced left amygdala reactivity to fearful faces, and enhanced emotional empathy. LSD increased the emotional response to music and the meaning of music. LSD acutely produced deficits in sensorimotor gating, similar to observations in schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma cortisol, prolactin, and oxytocin levels. Resting-state functional magnetic resonance studies showed that LSD acutely reduced the integrity of functional brain networks and increased connectivity between networks that normally are more dissociated. LSD increased functional thalamocortical connectivity and functional connectivity of the primary visual cortex with other brain areas. The latter effect was correlated with subjective hallucinations. LSD acutely induced global increases in brain entropy that were associated with greater trait openness 14 days later. In patients with anxiety associated with life-threatening disease, anxiety was reduced for 2 months after two doses of LSD. In medical settings, no complications of LSD administration were observed. These data should contribute to further investigations of the therapeutic potential of LSD in psychiatry.

(+)Lysergic acid diethylamide, but not its nonhallucinogenic congeners, is a potent serotonin 5HT1C receptor agonist

International Nuclear Information System (INIS)

Burris, K.D.; Breeding, M.; Sanders-Bush, E.

1991-01-01

Activation of central serotonin 5HT2 receptors is believed to be the primary mechanism whereby lysergic acid diethylamide (LSD) and other hallucinogens induce psychoactive effects. This hypothesis is based on extensive radioligand binding and electrophysiological and behavioral studies in laboratory animals. However, the pharmacological profiles of 5HT2 and 5HT1C receptors are similar, making it difficult to distinguish between effects due to activation of one or the other receptor. For this reason, it was of interest to investigate the interaction of LSD with 5HT1C receptors. Agonist-stimulated phosphoinositide hydrolysis in rat choroid plexus was used as a direct measure of 5HT1C receptor activation. (+)LSD potently stimulated phosphoinositide hydrolysis in intact choroid plexus and in cultures of choroid plexus epithelial cells, with EC50 values of 9 and 26 nM, respectively. The effect of (+)LSD in both systems was blocked by 5HT receptor antagonists with an order of activity consistent with interaction at 5HT1C receptors. Neither (+)-2-bromo-LSD nor lisuride, two nonhallucinogenic congeners of LSD, were able to stimulate 5HT1C receptors in cultured cells or intact choroid plexus. In contrast, lisuride, like (+)LSD, is a partial agonist at 5HT2 receptors in cerebral cortex slices and in NIH 3T3 cells transfected with 5HT2 receptor cDNA. The present finding that (+)LSD, but not its nonhallucinogenic congeners, is a 5HT1C receptor agonist suggests a possible role for these receptors in mediating the psychoactive effects of LSD

Dynamic changes in prefrontal cortex gene expression following lysergic acid diethylamide administration.

Science.gov (United States)

Nichols, Charles D; Garcia, Efrain E; Sanders-Bush, Elaine

2003-03-17

Lysergic acid diethylamide (LSD) is a psychoactive drug that transiently alters human perception, behavior, and mood at extremely low doses. Certain aspects of the behavior elicited by acute doses of LSD closely resemble symptoms of mental disorders such as schizophrenia. Characterizing gene expression profiles after LSD will be important for understanding how it alters behavior, and will lead to novel insights into disorders, such as schizophrenia, whose behavioral symptoms resemble the temporary effects of hallucinogenic drugs. We previously identified a small collection of genes within the rat prefrontal cortex that respond to LSD. Many of the products of these genes are involved in the process of synaptic plasticity. In the current report, we present a detailed analysis of the expression of these genes within the brain using RNase protection analysis. We find that the gene response to LSD is quite dynamic. The expression of some genes increases rapidly and decreases rapidly, while other genes change more gradually. Dose-response studies show two classes of expression; gene expression maximally stimulated at lower doses, versus gene expression that continues to rise at the higher doses. The role of the 5-HT(1A) and 5-HT(2A) receptor in mediating the increases in gene expression was examined in a series of experiments using receptor specific antagonists. Most expression increases were due to activation of the 5-HT(2A) receptor, however expression of two genes had neither a 5-HT(1A) nor a 5-HT(2A) receptor component.

Surveillance of drug use among young people attending a music festival in Australia, 2005-2008.

Science.gov (United States)

Lim, Megan S C; Hellard, Margaret E; Hocking, Jane S; Spelman, Tim D; Aitken, Campbell K

2010-03-01

In order to monitor trends in illicit drug use among youth, surveillance of drug use behaviours among a variety of populations in different settings is required. We monitored drug use among music festival attendees. Cross-sectional studies of young people's reported drug use were performed at a music festival in Melbourne from 2005 to 2008. Self-administered questionnaires collected information on drug use, demographics and other risk behaviour. From 2005 to 2008, over 5000 questionnaires were completed by people aged 16-29; 2273 men and 3011 women. Overall, use of any illicit drug in the past month was reported by 44%. After adjusting for demographic and behavioural characteristics, the prevalence of recent illicit drug use decreased significantly from 46% in 2005 to 43% in 2008 (OR 0.92, 95% CI 0.87-0.97). After adjusting for age and sex the downwards trend was repeated for amphetamines and cannabis, but a significant increase in prevalence was observed in hallucinogen, ecstasy and inhalant use. Drug use was more common among men, older participants and those engaging in high-risk sexual behaviour. Illicit drug use was much more common in this sample than in the National Drug Strategy Household survey, but the direction of trends in drug use were similar; drug use prevalences were much lower than in the Ecstasy and Related Drugs Reporting System, the Illicit Drug Reporting System or National Needle and Syringe Program Survey. Music festival attendees are a potentially useful group for monitoring trends in illicit drug use.

Evaluation of herbal dietary supplements marketed on the internet for recreational use.

Science.gov (United States)

Dennehy, Cathi E; Tsourounis, Candy; Miller, Amy E

2005-10-01

The Internet is a popular tool for marketing and purchasing herbal dietary supplements (DS). Various Web sites sell these products purely for recreational use. To describe the content of Web sites that advertise and market herbal DS for recreational use (ie, for the purpose of altering mood/behavior/or perception, "getting high," or as a substitute for a drug of abuse). Four major search engines and the search terms "buy herbal high" and "buy legal high" were used to identify Web sites selling herbal DS for recreational use. Web sites were evaluated for their country of origin and for compliance with the Dietary Supplement Health and Education Act (DSHEA). Products were evaluated for their ingredient lists, effect claims, comparisons with illicit drugs, adverse effects, drug interactions, and contraindications. Twenty-eight unique Web sites with 119 products were evaluated. Most sites were in the US (54%) and were in compliance with DSHEA. Forty-seven percent of the products were likened to illicit drugs, typically marijuana (48%) or 3-,4-methylene dioxyamphetamine (Ecstasy; 23%). The most common product ingredients were ephedra alkaloids (27%), Salvia divinorum (17%), kava (10%), guarana (10%), Acorus calamus (10%), and damiana (10%). Effect claims frequently involved the products' use as a hallucinogen (51%) or stimulant (39%). Sixty-four percent of the sites mentioned adverse effects, and 54% mentioned drug interactions. This study demonstrates that herbal DS are being marketed for use as legal alternatives to illicit drugs of abuse. Healthcare professionals need to be aware of this trend and the products that are involved.

The paradoxical psychological effects of lysergic acid diethylamide (LSD).

Science.gov (United States)

Carhart-Harris, R L; Kaelen, M; Bolstridge, M; Williams, T M; Williams, L T; Underwood, R; Feilding, A; Nutt, D J

2016-05-01

Lysergic acid diethylamide (LSD) is a potent serotonergic hallucinogen or psychedelic that modulates consciousness in a marked and novel way. This study sought to examine the acute and mid-term psychological effects of LSD in a controlled study. A total of 20 healthy volunteers participated in this within-subjects study. Participants received LSD (75 µg, intravenously) on one occasion and placebo (saline, intravenously) on another, in a balanced order, with at least 2 weeks separating sessions. Acute subjective effects were measured using the Altered States of Consciousness questionnaire and the Psychotomimetic States Inventory (PSI). A measure of optimism (the Revised Life Orientation Test), the Revised NEO Personality Inventory, and the Peter's Delusions Inventory were issued at baseline and 2 weeks after each session. LSD produced robust psychological effects; including heightened mood but also high scores on the PSI, an index of psychosis-like symptoms. Increased optimism and trait openness were observed 2 weeks after LSD (and not placebo) and there were no changes in delusional thinking. The present findings reinforce the view that psychedelics elicit psychosis-like symptoms acutely yet improve psychological wellbeing in the mid to long term. It is proposed that acute alterations in mood are secondary to a more fundamental modulation in the quality of cognition, and that increased cognitive flexibility subsequent to serotonin 2A receptor (5-HT2AR) stimulation promotes emotional lability during intoxication and leaves a residue of 'loosened cognition' in the mid to long term that is conducive to improved psychological wellbeing.

The additive effects of depressive symptoms and polysubstance use on HIV risk among gay, bisexual, and other men who have sex with men.

Science.gov (United States)

Card, Kiffer G; Lachowsky, Nathan J; Armstrong, Heather L; Cui, Zishan; Wang, Lu; Sereda, Paul; Jollimore, Jody; Patterson, Thomas L; Corneil, Trevor; Hogg, Robert S; Roth, Eric A; Moore, David M

2018-07-01

Among gay, bisexual, and other men who have sex with men (GBM), collinearity between polysubstance use and mental health concerns has obscured their combined effects on HIV risk with multivariable results often highlighting only one or the other. We used mediation and moderation analyses to examine the effects of polysubstance use and depressive symptoms on high-risk sex (i.e., condomless anal sex with serodiscordant/unknown status partner) in a sample of sexually-active GBM, aged ≥16 years, recruited in Metro Vancouver using respondent driven sampling. Hospital Anxiety and Depression Scale scores assessed mental health. Alcohol Use Disorder Identification Test scores assessed alcohol disorders. Poly-use of multiple drug types (e.g., stimulants, sedatives, opiates, hallucinogens) was assessed over the previous six months. Among 719 predominantly white (68.0%), gay-identified (80.7%) GBM, alcohol use was not associated with increased prevalence of high-risk sex. Controlling for demographic factors and partner number, an interaction between polysubstance use and depressive symptoms revealed that the combined effects were additively associated with increased odds for high-risk sex. Mediation models showed that polysubstance use partially mediated the relationship between depressive symptoms and high-risk sex. An interaction effect between polysubstance use (defined by using 3 or more substances in the past six months) and depressive symptoms (defined by HADS scores) revealed that the combination of these factors was associated with increased risk for high-risk sex - supporting a syndemic understanding of the production of HIV risk. Copyright © 2018 Elsevier Ltd. All rights reserved.

Quantitative determination of 3,4-methylenedioxymethamphetamine by thin-layer chromatography in ecstasy illicit pills in Tehran.

Science.gov (United States)

Shetab Boushehri, Seyed Vahid; Tamimi, Maryam; Kebriaeezadeh, Abbas

2009-11-01

3,4-Methylenedioxymethamphetamine (MDMA) is the major ingredient of ecstasy illicit pills. It is a hallucinogen, central nervous system stimulant, and serotonergic neurotoxin that strongly releases serotonin from serotonergic nerves terminals. Moreover, it releases norepinephrine and dopamine from nerves terminal, but to a lesser extent than serotonin. Poisoning and even death from abusing MDMA-containing ecstasy illicit pills among abusers is usual. Thus, quantitative determination of MDMA content of ecstasy illicit pills in illicit drug bazaar must be done regularly to find the most high dose ecstasy illicit pills and removing them from illicit drug bazaar. In the present study, MDMA contents of 13 most abundant ecstasy illicit pills were determined by quantitative thin-layer chromatography (TLC). Two procedures for quantitative determination of MDMA contents of ecstasy illicit pills by TLC were used: densitometric and so-called 'scraping off' methods. The former was done in a reflection mode at 285 nm and the latter was done by absorbance measurement of eluted scraped off spots. Limit of detection (LOD), considering signal-to-noise ratio (S/N) of 2, and limit of quantification (LOQ), regarding S/N of 10, of densitometric and scraping off methods were 0.40 microg, 1.20 microg, and 6.87 mug, 20.63 microg, respectively. Repeatabilities (within-laboratory error) of densitometric and scraping off methods were 0.5% and 3.6%, respectively. The results showed that the ecstasy illicit pills contained 24-124.5 mg and 23.9-122.2 mg MDMA by densitometric and scraping off methods, respectively.

[Salvia divinorum--representation of a new drug in the Internet].

Science.gov (United States)

Siemann, H; Specka, M; Schifano, F; Deluca, P; Scherbaum, N

2006-05-01

The German pages of the Internet were searched for the presence of the hallucinogenic herbal drug Salvia divinorum, which is not dealt with in current addiction medicine or psychiatric text books. The investigation is part of the EU sponsored project "Psychonaut" as preparatory work for the development of an Internet-based early warning system. The first 100 websites of the search using "Salvia divinorum" were compared with the search results for "cannabis" and "LSD". The following aspects of the sites were especially analyzed: the originator, marketing of drugs, and the attitude towards drug use. Salvia was offered for sale on approximately a third of the sites (29%); cannabis and LSD were not marketed on any sites. Official websites such as those from governmental organizations or universities were seldom found when searching for "Salvia divinorum", and then only under the last hits. The percentage of institutional sites (e. g. public organizations) were 12% with Salvia, 21% with cannabis, and 38% with LSD. A drug-friendly attitude was found at 64 % of the sites with regard to Salvia, 58% for cannabis, and 24% for LSD. The drug help system must be aware of that the Internet is a source of drug-related information, and of drug trade. As this investigation shows, sites often have a drug-friendly attitude. The low availability of official information on Salvia divinorum (also outside the Internet) relative to the presence of drug-friendly or drug trading sites is an indication that new trends of drug consumption can be tracked in the Internet before they will be found in official literature.

Analysis of the phenomenon of over-the-counter drug abuse and not controlled herbs trade by polish adolescents: Part I

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Daria Suchecka

2017-06-01

Full Text Available The phenomenon of stupefying by the use of available over-the-counter drugs (OTC among adolescents is an essential problem in both Poland and throughout the world. Popular analgesics, cold medicine and antihistamines contain psychedelic substances, such as dextromethorphan (DXM, pseudoephedrine/ephedrine, codeine (methylmorphine, dimenhydrinate, paracetamol (acetaminophren and others. Cases of fatal addiction to dextromethorphan, one of the active substances contained in medicines, e.g., the common cold, have been reported. The test results cited by the authors clearly indicate that the use of OTC drugs, whose turnover is not controlled is a domain of females. The extent of use of drugs not prescribed by a doctor has remained for many years at a constant level. The most common poisonings with OTC drugs are caused by those that affect the respiratory system or exert analgesic or antipyretic effects. They are also used in attempted suicides, especially among females. Analyzing poisonings caused by OTC medications their seasonality has been observed. Their number increases during spring–autumn. A territorial differentiation in areas of OTC drug trade in terms of their quantities, with the predominance of southern regions is also noted. Intoxication with psychoactive substances causes the deterioration of relations between young people. In the reviewed studies there is no detailed information on the composition of non-prescription medicines. Moreover, young people have easy access to mushroom fungi, growing in nearby forests and meadows that may have hallucinogenic effects and are available in pharmacies and on the Internet. Med Pr 2017;68(3:413–422

Acute cognitive effects of high doses of dextromethorphan relative to triazolam in humans

Science.gov (United States)

Carter, Lawrence P.; Reissig, Chad J.; Johnson, Matthew W.; Klinedinst, Margaret A.; Griffiths, Roland R.

2012-01-01

BACKGROUND Although concerns surrounding high-dose dextromethorphan (DXM) abuse have recently increased, few studies have examined the acute cognitive effects of high doses of DXM. The aim of this study was to compare the cognitive effects of DXM with those of triazolam and placebo. METHODS Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg /70 kg), and placebo were administered p.o. to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Effects on cognitive performance were examined at baseline and after drug administration for up to 6 hours. RESULTS Both triazolam and DXM produced acute impairments in attention, working memory, episodic memory, and metacognition. Impairments observed following doses of 100-300 mg/70 kg DXM were generally smaller in magnitude than those observed after 0.5 mg/70 kg triazolam. Doses of DXM that impaired performance to the same extent as triazolam were in excess of 10-30 times the therapeutic dose of DXM. CONCLUSION The magnitude of the doses required for these effects and the absence of effects on some tasks within the 100-300 mg/70 kg dose range of DXM, speak to the relatively broad therapeutic window of over-the-counter DXM preparations when used appropriately. However, the administration of supratherapeutic doses of DXM resulted in acute cognitive impairments on all tasks that were examined. These findings are likely relevant to cases of high-dose DXM abuse. PMID:22989498

[Sacred psychoactive seeds and ritual sacrifices in the Moche culture].

Science.gov (United States)

Carod-Artal, F J; Vázquez-Cabrera, C B

Archaeological findings have confirmed the existence of representations of ritual human sacrifices on pottery belonging to the Moche culture (100-750 AD) in northern Peru; until recently these images were thought to be mythological narrations. We review the archaeological and ethno-historical data concerning Moche sacrifices and we attempt to identify the psychoactive seeds and plants used during such rites. Ethno-historical data from different chronicles of the New World written in the 16th century state that hamala seeds (belonging to the species Nectandra) were used for their analgesic, sedative, narcotic and anticoagulating properties, and that chamico, or stramonium, had an intoxicating effect on those who took it. There were two kinds of Moche rituals, that is, sacrifices as offerings to divinities and as exemplary punishments. Methods of sacrifice included slitting victims' throats, dismembering them and throwing them off mountains. The sacrifices of the Moche were part of a complex and elaborate ritual which consisted in capturing prisoners, parading them with nooses around their necks, making offerings, preparing the officiants and the community, consummation of the sacrifice and presenting the blood to the priest in a chalice. Human sacrifices were part of the propitiatory ceremonies held in honour of the gods in order to favour human fertility, obtain good harvests and preserve a plentiful supply of water for irrigating the valleys. The therapeutic properties of the seeds of the Nectandra species favoured their utilisation in the ritual sacrifices of the Moche culture. Their use was probably associated with stramonium and San Pedro cactus, which contain extracts rich in hallucinogenic alkaloids.

Naming a phantom - the quest to find the identity of Ulluchu, an unidentified ceremonial plant of the Moche culture in Northern Peru.

Science.gov (United States)

Bussmann, Rainer W; Sharon, Douglas

2009-03-31

The botanical identification of Ulluchu, an iconic fruit frequently depicted in the art of the pre-Columbian Moche culture that flourished from A.D. 100-800 on the Peruvian north coast, has eluded scientists since its documentation in ceramics in the 1930s. Moche fine-line drawings of Ulluchu normally depict seed-pods or seeds floating in the air in sacrificial scenes, associated with runners and messengers or intoxicated priests. It is a grooved, comma-shaped fruit with an enlarged calyx found mainly in fine-line scenes painted on Moche ceramics. The term first appeared without linguistic explanation in the work of pioneer Moche scholar Rafael Larco Hoyle, and the identification of the plant was seen as the largest remaining challenge in current archaebotany at the Peruvian North coast. The name Ulluchu seems to have been coined by Larco. According to his description, the name originated in the Virú River valley, and is supposedly of Mochica origin. However, there is no linguistic evidence that such a term indeed existed in the Mochica or Yunga language.We conclude that Ulluchu can be identified as a group of species of the genus Guarea (Meliaceae) based on morphological characteristics. In addition, the chemical composition of the plant's compounds supports the thesis that it was used in a sacrificial context to improve the extraction of blood from sacrificial victims. We also suggest that a ground preparation of Guarea seeds, when inhaled, may have been used as a hallucinogen. However, more detailed phytochemical research is needed to corroborate the latter hypothesis.

Naming a phantom – the quest to find the identity of Ulluchu, an unidentified ceremonial plant of the Moche culture in Northern Peru

Science.gov (United States)

Bussmann, Rainer W; Sharon, Douglas

2009-01-01

The botanical identification of Ulluchu, an iconic fruit frequently depicted in the art of the pre-Columbian Moche culture that flourished from A.D. 100–800 on the Peruvian north coast, has eluded scientists since its documentation in ceramics in the 1930s. Moche fine-line drawings of Ulluchu normally depict seed-pods or seeds floating in the air in sacrificial scenes, associated with runners and messengers or intoxicated priests. It is a grooved, comma-shaped fruit with an enlarged calyx found mainly in fine-line scenes painted on Moche ceramics. The term first appeared without linguistic explanation in the work of pioneer Moche scholar Rafael Larco Hoyle, and the identification of the plant was seen as the largest remaining challenge in current archaebotany at the Peruvian North coast. The name Ulluchu seems to have been coined by Larco. According to his description, the name originated in the Virú River valley, and is supposedly of Mochica origin. However, there is no linguistic evidence that such a term indeed existed in the Mochica or Yunga language. We conclude that Ulluchu can be identified as a group of species of the genus Guarea (Meliaceae) based on morphological characteristics. In addition, the chemical composition of the plant's compounds supports the thesis that it was used in a sacrificial context to improve the extraction of blood from sacrificial victims. We also suggest that a ground preparation of Guarea seeds, when inhaled, may have been used as a hallucinogen. However, more detailed phytochemical research is needed to corroborate the latter hypothesis. PMID:19335907

Self-reported cannabis products and other illicit drugs consumption in older school-age children in Northern Lithuania: a comparison between 2006 and 2012.

Science.gov (United States)

Miniauskienė, Dalia; Jurgaitienė, Dalia; Strukčinskienė, Birutė

2014-01-01

Cannabis use is widespread among young people in Europe. The aim of this study was to analyze and to compare the associations between the self-reported consumption of cannabis products and other illicit drugs among older schoolchildren in 2006 and in 2012. Two cross-sectional surveys were conducted in 2006 and 2012 in Northern Lithuania. In total 3447 young people aged 17-19 years were investigated (1585 male and 1862 female). For this survey, the ESPAD questionnaire was used. In Northern Lithuania, the schoolchildren aged 17-19 years self-reported that 16.7% in 2006 and 23.9% in 2012 of them tried cannabis products. The consumption of cannabis products in the age group of 17 years increased from 14.9% in 2006 to 21.5% in 2012. The consumption of cannabis together with alcohol increased from 7.6% to 14.3%. Cannabis consumers more often tried amphetamines, heroin, LSD, cocaine, crack, ecstasy, hallucinogenic mushrooms, and injective drugs. In 2012, cannabis consumers girls less than boys used only crack and injective drugs; all other illicit drugs they used the same often as boys. The cannabis products consumption in schoolchildren has increased by 7%. Nearly twofold increase was observed in the consumption of cannabis together with alcohol. Young people who used cannabis products more often tried other illicit drugs. There were no differences by gender in the consumption of illicit drugs among cannabis consumers. Copyright © 2014 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

[Peer group influence and illicit drug use among adolescent students in Brazil: a cross-sectional study].

Science.gov (United States)

Jorge, Kelly Oliva; Ferreira, Raquel Conceição; Ferreira, Efigênia Ferreira E; Kawachi, Ichiro; Zarzar, Patrícia Maria; Pordeus, Isabela Almeida

2018-03-08

The aim of the present cross-sectional study was to examine illicit drug use and associations with socioeconomic factors as well as peer group influence among Brazilian adolescents aged 15 to 19 years. Two-stage cluster sampling was adopted, involving the random selection of public and private schools from the nine administrative districts of a Brazilian state capital and the random selection of classrooms at each school. Illicit drug use was the outcome and was measured through the question: "Have you ever used any illicit drugs (marijuana, inhalants, hypnotics, cocaine/crack, hallucinogens, amphetamines and opioids) in your life?". The most important group of friends was ranked as school, family, religious activities and sports/culture. The area-based Health Vulnerability Index (HVI) was used to assess socioeconomic status. Data from 891 adolescents were analyzed using the chi-squared test and logistic regression. The overall rate of illicit drug use was 15.2%. Gender heterogeneity within groups (OR = 3.14; 95%CI: 1.63-6.06), religion-based friendships (OR = 0.36; 95%CI: 0.17-0.75) and sports/culture-based friendships (OR = 0.44; 95%CI: 0.22-0.87) remained significantly associated with illicit drug use. Adolescents who lived in less vulnerable areas had higher chance of drug use in comparison with those living in more vulnerable areas. Religion-based and sports/culture-based friendships seem to demonstrate a protective effect against lifetime illicit drug use. Gender heterogeneity within groups and residing in a less vulnerable area increased the chances of adolescents reporting illicit drug use.

Novel Psychoactive Substances—Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs

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Zurina Hassan

2017-08-01

Full Text Available A feature of human culture is that we can learn to consume chemical compounds, derived from natural plants or synthetic fabrication, for their psychoactive effects. These drugs change the mental state and/or the behavioral performance of an individual and can be instrumentalized for various purposes. After the emergence of a novel psychoactive substance (NPS and a period of experimental consumption, personal and medical benefits and harm potential of the NPS can be estimated on evidence base. This may lead to a legal classification of the NPS, which may range from limited medical use, controlled availability up to a complete ban of the drug form publically accepted use. With these measures, however, a drug does not disappear, but frequently continues to be used, which eventually allows an even better estimate of the drug’s properties. Thus, only in rare cases, there is a final verdict that is no more questioned. Instead, the view on a drug can change from tolerable to harmful but may also involve the new establishment of a desired medical application to a previously harmful drug. Here, we provide a summary review on a number of NPS for which the neuropharmacological evaluation has made important progress in recent years. They include mitragynine (“Kratom”, synthetic cannabinoids (e.g., “Spice”, dimethyltryptamine and novel serotonergic hallucinogens, the cathinones mephedrone and methylone, ketamine and novel dissociative drugs, γ-hydroxybutyrate, γ-butyrolactone, and 1,4-butanediol. This review shows not only emerging harm potentials but also some potential medical applications.

When good times go bad: managing ‘legal high’ complications in the emergency department

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Caffrey CR

2017-12-01

Full Text Available Charles R Caffrey, Patrick M Lank Department of Emergency Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Abstract: Patients can use numerous drugs that exist outside of existing regulatory statutes in order to get “legal highs.” Legal psychoactive substances represent a challenge to the emergency medicine physician due to the sheer number of available agents, their multiple toxidromes and presentations, their escaping traditional methods of analysis, and the reluctance of patients to divulge their use of these agents. This paper endeavors to cover a wide variety of “legal highs,” or uncontrolled psychoactive substances that may have abuse potential and may result in serious toxicity. These agents include not only some novel psychoactive substances aka “designer drugs,” but also a wide variety of over-the-counter medications, herbal supplements, and even a household culinary spice. The care of patients in the emergency department who have used “legal high” substances is challenging. Patients may misunderstand the substance they have been exposed to, there are rarely any readily available laboratory confirmatory tests for these substances, and the exact substances being abused may change on a near-daily basis. This review will attempt to group legal agents into expected toxidromes and discuss associated common clinical manifestations and management. A focus on aggressive symptom-based supportive care as well as management of end-organ dysfunction is the mainstay of treatment for these patients in the emergency department. Keywords: legal highs, novel psychoactive substances, toxicology, opioid toxidrome, anticholinergic toxidrome, sympathomimetic toxidrome, hallucinogens, inhalants

Naming a phantom – the quest to find the identity of Ulluchu, an unidentified ceremonial plant of the Moche culture in Northern Peru

Directory of Open Access Journals (Sweden)

Bussmann Rainer W

2009-03-01

Full Text Available Abstract The botanical identification of Ulluchu, an iconic fruit frequently depicted in the art of the pre-Columbian Moche culture that flourished from A.D. 100–800 on the Peruvian north coast, has eluded scientists since its documentation in ceramics in the 1930s. Moche fine-line drawings of Ulluchu normally depict seed-pods or seeds floating in the air in sacrificial scenes, associated with runners and messengers or intoxicated priests. It is a grooved, comma-shaped fruit with an enlarged calyx found mainly in fine-line scenes painted on Moche ceramics. The term first appeared without linguistic explanation in the work of pioneer Moche scholar Rafael Larco Hoyle, and the identification of the plant was seen as the largest remaining challenge in current archaebotany at the Peruvian North coast. The name Ulluchu seems to have been coined by Larco. According to his description, the name originated in the Virú River valley, and is supposedly of Mochica origin. However, there is no linguistic evidence that such a term indeed existed in the Mochica or Yunga language. We conclude that Ulluchu can be identified as a group of species of the genus Guarea (Meliaceae based on morphological characteristics. In addition, the chemical composition of the plant's compounds supports the thesis that it was used in a sacrificial context to improve the extraction of blood from sacrificial victims. We also suggest that a ground preparation of Guarea seeds, when inhaled, may have been used as a hallucinogen. However, more detailed phytochemical research is needed to corroborate the latter hypothesis.

Ayahuasca: Psychological And Physiologic Effects, Pharmacology And Potential Uses In Addiction And Mental Illness.

Science.gov (United States)

Hamill, Jonathan; Hallak, Jaime; Dursun, Serdar M; Baker, Glen

2018-01-24

Ayahuasca, a traditional Amazonian decoction with psychoactive properties, is made from bark of the Banisteriopsis caapi vine (contains beta-carboline alkaloids) and leaves of the Psychotria viridis bush (supply the hallucinogen N,N-dimethyltryptamine (DMT)). Originally used by indigenous shamans for the purposes of spirit communication, magical experiences, healing, and religious rituals, across several South American countries ayahuasca has been incorporated into folk medicine and spiritual healing, and several Brazilian churches use it routinely to foster spiritual experience. More recently it is being used in Europe and North America, not only for religious or healing reasons, but also for recreation. To review ayahuasca's behavioral effects, possible adverse effects, proposed mechanisms of action and potential clinical uses in mental illness. We searched Medline, in English, using the terms ayahuasca, dimethytryptamine, Banisteriopsis caapi, and Psychotria viridis and reviewed the relevant publications. The following aspects of ayahuasca are summarized: Political and legal factors; acute and chronic psychological effects; electrophysiological studies and imaging; physiological effects, safety and adverse effects; pharmacology; potential psychiatric uses. Many years of shamanic wisdom have indicated potential therapeutic uses for ayahuasca, and many present day studies suggest that it may be useful for treating various psychiatric disorders and addictions. The side effect profile appears to be relatively mild, but more detailed studies need to be done. Several prominent researchers feel that government regulations with regard to ayahuasca should be relaxed so that it could be provided more readily to recognized credible researchers to conduct comprehensive clinical trials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effects of the South American psychoactive beverage ayahuasca on regional brain electrical activity in humans: a functional neuroimaging study using low-resolution electromagnetic tomography.

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Riba, Jordi; Anderer, Peter; Jané, Francesc; Saletu, Bernd; Barbanoj, Manel J

2004-01-01

Ayahuasca, a South American psychotropic plant tea obtained from Banisteriopsis caapi and Psychotria viridis, combines monoamine oxidase-inhibiting beta-carboline alkaloids with N,N-dimethyltryptamine (DMT), a psychedelic agent showing 5-HT(2A) agonist activity. In a clinical research setting, ayahuasca has demonstrated a combined stimulatory and psychedelic effect profile, as measured by subjective effect self-assessment instruments and dose-dependent changes in spontaneous brain electrical activity, which parallel the time course of subjective effects. In the present study, the spatial distribution of ayahuasca-induced changes in brain electrical activity was investigated by means of low-resolution electromagnetic tomography (LORETA). Electroencephalography recordings were obtained from 18 volunteers after the administration of a dose of encapsulated freeze-dried ayahuasca containing 0.85 mg DMT/kg body weight and placebo. The intracerebral power density distribution was computed with LORETA from spectrally analyzed data, and subjective effects were measured by means of the Hallucinogen Rating Scale (HRS). Statistically significant differences compared to placebo were observed for LORETA power 60 and 90 min after dosing, together with increases in all six scales of the HRS. Ayahuasca decreased power density in the alpha-2, delta, theta and beta-1 frequency bands. Power decreases in the delta, alpha-2 and beta-1 bands were found predominantly over the temporo-parieto-occipital junction, whereas theta power was reduced in the temporomedial cortex and in frontomedial regions. The present results suggest the involvement of unimodal and heteromodal association cortex and limbic structures in the psychological effects elicited by ayahuasca. Copyright 2004 S. Karger AG, Basel

Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats.

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Favaro, Vanessa Manchim; Yonamine, Maurício; Soares, Juliana Carlota Kramer; Oliveira, Maria Gabriela Menezes

2015-01-01

Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT) from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs) induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM), fear conditioning and elevated plus maze (EPM) performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes.

Methodology for and the determination of the major constituents and metabolites of the Amazonian botanical medicine ayahuasca in human urine.

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McIlhenny, Ethan H; Riba, Jordi; Barbanoj, Manel J; Strassman, Rick; Barker, Steven A

2011-09-01

Ayahuasca, also known as caapi or yage among various South American groups, holds a highly esteemed and millennia-old position in these cultures' medical and religious pharmacopeia. There is now an increasing interest in the potential for modern medical applications of ayahuasca, as well as concerns regarding its increasing potential for abuse. Toxicological and clinical research to address these issues will require information regarding its metabolism and clearance. Thus, a rapid, sensitive and specific method for characterization and quantitation of the major constituents and of the metabolites of ayahuasca in urine is needed. The present research provides a protocol for conducting such analyses. The characteristics of the method, conducted by sample dilution and using HPLC-electrospray ionization (ESI)-selected reaction monitoring (SRM)-tandem mass spectrometry, are presented. The application of the analytical protocol to urine samples collected from three individuals that were administered ayahuasca has also been demonstrated. The data show that the major metabolite of the hallucinogenic component of ayahuasca, N,N-dimethyltryptamine (DMT), is the corresponding N-oxide, the first time this metabolite has been described in in vivo studies in humans. Further, very little DMT was detected in urine, despite the inhibition of monoamine oxidase afforded by the presence of the harmala alkaloids in ayahuasca. The major harmala alkaloid excreted was tetrahydroharmine. Other excretion products and metabolites were also identified and quantified. The method described would be suitable for use in further toxicological and clinical research on ayahuasca. Copyright © 2010 John Wiley & Sons, Ltd.

Psychedelics as medicines for substance abuse rehabilitation: evaluating treatments with LSD, Peyote, Ibogaine and Ayahuasca.

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Winkelman, Michael

2014-01-01

Substances known as psychedelics, hallucinogens and entheogens have been employed in ethnomedical traditions for thousands of years, but after promising uses in the 1950's and 1960's they were largely prohibited in medical treatment and human research starting in the 1970's as part of the fallout from the war on drugs. Nonetheless, there are a number of studies which suggest that these substances have potential applications in the treatment of addictions. While these substances are generally classified as Schedule I, alleging no established medical uses and a high drug abuse potential, there is nonetheless evidence indicating they might be safe and effective tools for short term interventions in addictions treatment. Evidence suggests that the psychedelics have a much greater safety profile than the major addictive drugs, having extremely low levels of mortality, and producing little if any physical dependence. This paper reviews studies evaluating the use of LSD, peyote, ibogaine and ayahuasca in the treatment of dependencies and the possible mechanisms underlying the indications of effectiveness. Evidence suggests that these substances help assist recovery from drug dependency through a variety of therapeutic mechanisms, including a notable "after-glow" effect that in part reflects their action on the serotonin neurotransmitter system. Serotonin has been long recognized as central to the psychedelics' well-known phenomenological, physical, emotional and cognitive dynamics. These serotonin-based dynamics are directly relevant to treatment of addiction because of depressed serotonin levels found in addict populations, as well as the role of serotonin as a neuromodulators affecting many other neurotransmitter systems.

Novel Psychoactive Substances—Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs

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Hassan, Zurina; Bosch, Oliver G.; Singh, Darshan; Narayanan, Suresh; Kasinather, B. Vicknasingam; Seifritz, Erich; Kornhuber, Johannes; Quednow, Boris B.; Müller, Christian P.

2017-01-01

A feature of human culture is that we can learn to consume chemical compounds, derived from natural plants or synthetic fabrication, for their psychoactive effects. These drugs change the mental state and/or the behavioral performance of an individual and can be instrumentalized for various purposes. After the emergence of a novel psychoactive substance (NPS) and a period of experimental consumption, personal and medical benefits and harm potential of the NPS can be estimated on evidence base. This may lead to a legal classification of the NPS, which may range from limited medical use, controlled availability up to a complete ban of the drug form publically accepted use. With these measures, however, a drug does not disappear, but frequently continues to be used, which eventually allows an even better estimate of the drug’s properties. Thus, only in rare cases, there is a final verdict that is no more questioned. Instead, the view on a drug can change from tolerable to harmful but may also involve the new establishment of a desired medical application to a previously harmful drug. Here, we provide a summary review on a number of NPS for which the neuropharmacological evaluation has made important progress in recent years. They include mitragynine (“Kratom”), synthetic cannabinoids (e.g., “Spice”), dimethyltryptamine and novel serotonergic hallucinogens, the cathinones mephedrone and methylone, ketamine and novel dissociative drugs, γ-hydroxybutyrate, γ-butyrolactone, and 1,4-butanediol. This review shows not only emerging harm potentials but also some potential medical applications. PMID:28868040

Using selected scenes from Brazilian films to teach about substance use disorders, within medical education

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João Mauricio Castaldelli-Maia

Full Text Available CONTEXT AND OBJECTIVES: Themes like alcohol and drug abuse, relationship difficulties, psychoses, autism and personality dissociation disorders have been widely used in films. Psychiatry and psychiatric conditions in various cultural settings are increasingly taught using films. Many articles on cinema and psychiatry have been published but none have presented any methodology on how to select material. Here, the authors look at the portrayal of abusive use of alcohol and drugs during the Brazilian cinema revival period (1994 to 2008. DESIGN AND SETTING: Qualitative study at two universities in the state of São Paulo. METHODS: Scenes were selected from films available at rental stores and were analyzed using a specifically designed protocol. We assessed how realistic these scenes were and their applicability for teaching. One author selected 70 scenes from 50 films (graded for realism and teaching applicability > 8. These were then rated by another two judges. Rating differences among the three judges were assessed using nonparametric tests (P 8 were defined as "quality scenes". RESULTS: Thirty-nine scenes from 27 films were identified as "quality scenes". Alcohol, cannabis, cocaine, hallucinogens and inhalants were included in these. Signs and symptoms of intoxication, abusive/harmful use and dependence were shown. CONCLUSIONS: We have produced rich teaching material for discussing psychopathology relating to alcohol and drug use that can be used both at undergraduate and at postgraduate level. Moreover, it could be seen that certain drug use behavioral patterns are deeply rooted in some Brazilian films and groups.

Reducing risk for illicit drug use and prescription drug misuse: High school gay-straight alliances and lesbian, gay, bisexual, and transgender youth.

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Heck, Nicholas C; Livingston, Nicholas A; Flentje, Annesa; Oost, Kathryn; Stewart, Brandon T; Cochran, Bryan N

2014-04-01

Previous research suggests that lesbian, gay, bisexual, and transgender (LGBT) youth are at elevated risk for using illicit drugs and misusing prescription drugs relative to heterosexual youth. Previous research also indicates that LGBT youth who attend high schools with a gay-straight alliance (GSA) report having fewer alcohol problems and lower levels of cigarette smoking. The present study investigates whether the absence of a GSA is associated with risk for illicit drug use and prescription drug misuse in a sample of 475 LGBT high school students (M age=16.79) who completed an online survey. After controlling for demographic variables and risk factors associated with illicit drug use, the results of 12 logistic regression analyses revealed that LGBT youth attending a high school without a GSA evidenced increased risk for using cocaine (adjusted odds ratio [adjOR]=3.11; 95% confidence interval [95% CI]=1.23-7.86), hallucinogens (adjOR=2.59; 95% CI=1.18-5.70), and marijuana (adjOR=2.22; 95% CI=1.37-3.59) relative to peers attending a high school with a GSA. Youth without a GSA also evidenced increased risk for the misuse of ADHD medication (adjOR=2.00; 95% CI=1.02-3.92) and prescription pain medication (adjOR=2.00; 95% CI=1.10-3.65). These findings extend the research base related to GSAs and further demonstrate the importance of providing LGBT youth with opportunities for socialization and support within the school setting. Important limitations of the present study are reviewed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats.

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Vanessa Manchim Favaro

Full Text Available Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM, fear conditioning and elevated plus maze (EPM performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes.

Phosphodiesterase 9A regulates central cGMP and modulates responses to cholinergic and monoaminergic perturbation in vivo.

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Kleiman, Robin J; Chapin, Douglas S; Christoffersen, Curt; Freeman, Jody; Fonseca, Kari R; Geoghegan, Kieran F; Grimwood, Sarah; Guanowsky, Victor; Hajós, Mihály; Harms, John F; Helal, Christopher J; Hoffmann, William E; Kocan, Geralyn P; Majchrzak, Mark J; McGinnis, Dina; McLean, Stafford; Menniti, Frank S; Nelson, Fredrick; Roof, Robin; Schmidt, Anne W; Seymour, Patricia A; Stephenson, Diane T; Tingley, Francis David; Vanase-Frawley, Michelle; Verhoest, Patrick R; Schmidt, Christopher J

2012-05-01

Cyclic nucleotides are critical regulators of synaptic plasticity and participate in requisite signaling cascades implicated across multiple neurotransmitter systems. Phosphodiesterase 9A (PDE9A) is a high-affinity, cGMP-specific enzyme widely expressed in the rodent central nervous system. In the current study, we observed neuronal staining with antibodies raised against PDE9A protein in human cortex, cerebellum, and subiculum. We have also developed several potent, selective, and brain-penetrant PDE9A inhibitors and used them to probe the function of PDE9A in vivo. Administration of these compounds to animals led to dose-dependent accumulation of cGMP in brain tissue and cerebrospinal fluid, producing a range of biological effects that implied functional significance for PDE9A-regulated cGMP in dopaminergic, cholinergic, and serotonergic neurotransmission and were consistent with the widespread distribution of PDE9A. In vivo effects of PDE9A inhibition included reversal of the respective disruptions of working memory by ketamine, episodic and spatial memory by scopolamine, and auditory gating by amphetamine, as well as potentiation of risperidone-induced improvements in sensorimotor gating and reversal of the stereotypic scratching response to the hallucinogenic 5-hydroxytryptamine 2A agonist mescaline. The results suggested a role for PDE9A in the regulation of monoaminergic circuitry associated with sensory processing and memory. Thus, PDE9A activity regulates neuronal cGMP signaling downstream of multiple neurotransmitter systems, and inhibition of PDE9A may provide therapeutic benefits in psychiatric and neurodegenerative diseases promoted by the dysfunction of these diverse neurotransmitter systems.

Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later.

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Griffiths, Rr; Richards, Wa; Johnson, Mw; McCann, Ud; Jesse, R

2008-08-01

Psilocybin has been used for centuries for religious purposes; however, little is known scientifically about its long-term effects. We previously reported the effects of a double-blind study evaluating the psychological effects of a high psilocybin dose. This report presents the 14-month follow-up and examines the relationship of the follow-up results to data obtained at screening and on drug session days. Participants were 36 hallucinogen-naïve adults reporting regular participation in religious/ spiritual activities. Oral psilocybin (30 mg/70 kg) was administered on one of two or three sessions, with methylphenidate (40 mg/70 kg) administered on the other session(s). During sessions, volunteers were encouraged to close their eyes and direct their attention inward. At the 14-month follow-up, 58% and 67%, respectively, of volunteers rated the psilocybin-occasioned experience as being among the five most personally meaningful and among the five most spiritually significant experiences of their lives; 64% indicated that the experience increased well-being or life satisfaction; 58% met criteria for having had a 'complete' mystical experience. Correlation and regression analyses indicated a central role of the mystical experience assessed on the session day in the high ratings of personal meaning and spiritual significance at follow-up. Of the measures of personality, affect, quality of life and spirituality assessed across the study, only a scale measuring mystical experience showed a difference from screening. When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences that, at 14-month follow-up, were considered by volunteers to be among the most personally meaningful and spiritually significant of their lives.

E-cigarette use of young adults motivations and associations with combustible cigarette alcohol, marijuana, and other illicit drugs.

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Temple, Jeff R; Shorey, Ryan C; Lu, Yu; Torres, Elizabeth; Stuart, Gregory L; Le, Vi D

2017-06-01

Although the prevalence of e-cigarette use among adolescents and young adults has caught up to or eclipsed that of combustible cigarette use, there is relatively little known about (a) the link between e-cigarettes and other substances and (b) the reasons underlying this increase in e-cigarette use. To address this gap in knowledge, the current study examined associations between e-cigarette use and other substances and identified motives for e-cigarette use among young adults. Participants included an ethnically diverse sample of African American, White, and Hispanic young adults (N = 662; 61% female) who were participating in an ongoing survey-based longitudinal study of health and risky behaviors. Hispanic, White, and male young adults reported significantly greater past year e-cigarette use compared to their African American and female counterparts. Bivariate correlations showed that use of e-cigarettes was positively associated with use of combustible cigarettes, alcohol, marijuana, cocaine, amphetamines, inhalants, hallucinogens, ecstasy, and misuse of over-the-counter and prescription medications. Furthermore, e-cigarette users reported a higher prevalence of substance use relative to those who did not use e-cigarettes. The taste of e-cigarettes was identified as an important motive for use. Although the potential harm associated with e-cigarettes remains largely unknown, e-cigarettes appear to be a risk marker for the use of substances that are known to pose substantial health problems. Health care providers should screen for e-cigarette use, and youth substance use prevention programs should target the reduction of e-cigarette use with particular attention to addressing their taste appeal. (Am J Addict 2017;26:343-348). © 2017 American Academy of Addiction Psychiatry.

Prevalence of Hospitalized Live Births Affected by Alcohol and Drugs and Parturient Women Diagnosed with Substance Abuse at Liveborn Delivery: United States, 1999–2008

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Pan, I-Jen; Yi, Hsiao-ye

2015-01-01

Objective To describe prevalence trends in hospitalized live births affected by placental transmission of alcohol and drugs, as well as prevalence trends among parturient women hospitalized for liveborn delivery and diagnosed with substance abuse problems in the United States from 1999 to 2008. Comparison of the two sets of trends helps determine whether the observed changes in neonatal problems over time were caused by shifts in maternal substance abuse problems. Methods This study independently identified hospitalized live births and maternal live born deliveries from discharge records in the Nationwide Inpatient Sample, one of the largest hospital administrative databases. Substance-related diagnosis codes on the records were used to identify live births affected by alcohol and drugs and parturient women with substance abuse problems. The analysis calculated prevalence differences and percentage changes over the 10 years, with Loess curves fitted to 10-year prevalence estimates to depict trend patterns. Linear and quadratic trends in prevalence were simultaneously tested using logistic regression analyses. The study also examined data on costs, primary expected payer, and length of hospital stays. Results From 1999 to 2008, prevalence increased for narcotic- and hallucinogen-affected live births and neonatal drug withdrawal syndrome but decreased for alcohol- and cocaine-affected live births. Maternal substance abuse at delivery showed similar trends, but prevalence of alcohol abuse remained relatively stable. Substance-affected live births required longer hospital stays and higher medical expenses, mostly billable to Medicaid. Conclusions The findings highlight the urgent need for behavioral intervention and early treatment for substance-abusing pregnant women to reduce the number of substance-affected live births. PMID:22688539

Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers

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Quednow, Boris B; Kometer, Michael; Geyer, Mark A; Vollenweider, Franz X

2012-01-01

The serotonin-2A receptor (5-HT2AR) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT2AR or 5-HT1AR agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT2A/2CR antagonist ketanserin. A total of 16 healthy participants received placebo, ketanserin (40 mg p.o.), psilocybin (260 μg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT2AR stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT2AR system. PMID:21956447

E-cigarette Use of Young Adults: Motivations and Associations with Combustible Cigarette, Alcohol, Marijuana, and Other Illicit Drugs

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Temple, Jeff R.; Shorey, Ryan C.; Lu, Yu; Torres, Elizabeth; Stuart, Gregory L.; Le, Vi D.

2017-01-01

Background and Objectives Although the prevalence of e-cigarette use among adolescents and young adults has caught up to or eclipsed that of combustible cigarette use, there is relatively little known about (a) the link between e-cigarettes and other substances and (b) the reasons underlying this increase in e-cigarette use. To address this gap in knowledge, the current study examined associations between e-cigarette use and other substances and identified motives for e-cigarette use among young adults. Methods Participants included an ethnically diverse sample of African American, White, and Hispanic young adults (N=662; 61% female) who were participating in an ongoing survey-based longitudinal study of health and risky behaviors. Results Hispanic, White, and male young adults reported significantly greater past year e-cigarette use compared to their African American and female counterparts. Bivariate correlations showed that use of e-cigarettes was positively associated with use of combustible cigarettes, alcohol, marijuana, cocaine, amphetamines, inhalants, hallucinogens, ecstasy, and misuse of over-the-counter and prescription medications. Furthermore, e-cigarette users reported a higher prevalence of substance use relative to those who did not use e-cigarettes. The taste of e-cigarettes was identified as an important motive for use. Conclusions and Significance Although the potential harm associated with e-cigarettes remains largely unknown, e-cigarettes appear to be a risk marker for the use of substances that are known to pose substantial health problems. Health care providers should screen for e-cigarette use, and youth substance use prevention programs should target the reduction of e-cigarette use with particular attention to addressing their taste appeal. PMID:28370717

Ketamine-associated lower urinary tract destruction: a new radiological challenge

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Mason, K., E-mail: k.mason@doctors.org.u [Bristol Royal Infirmary, Bristol (United Kingdom); Cottrell, A.M. [North Bristol NHS Trust, Bristol (United Kingdom); Corrigan, A.G. [Bristol Royal Infirmary, Bristol (United Kingdom); Gillatt, D.A.; Mitchelmore, A.E. [North Bristol NHS Trust, Bristol (United Kingdom)

2010-10-15

Aim: Ketamine is a short-acting dissociative anaesthetic whose hallucinogenic side effects have led to an increase in its illicit use amongst club and party goers. There is a general misconception amongst users that it is a safe drug with few long term side effects, however ketamine abuse is associated with severe urinary tract dysfunction. Presenting symptoms include urinary frequency, nocturia, dysuria, haematuria and incontinence. Materials and methods: We describe the radiological findings found in a series of 23 patients, all with a history of ketamine abuse, who presented with severe lower urinary tract symptoms (LUTS). Imaging techniques used included ultrasonography (US), intravenous urography (IVU), and computed tomography (CT). These examinations were reviewed to identify common imaging findings. All patients with positive imaging findings had also undergone cystoscopy and bladder wall biopsies, which confirmed the diagnosis. The patients in this series have consented to the use of their data in the ongoing research into ketamine-induced bladder pathology. Results: Ultrasound demonstrated small bladder volume and wall thickening. CT revealed marked, generalized bladder wall thickening, mucosal enhancement, and perivesical inflammation. Ureteric wall thickening and enhancement were also observed. In advanced cases ureteric narrowing and strictures were identified using both CT and IVU. Correlation of clinical history, radiological and pathological findings was performed to confirm the diagnosis. Conclusion: This case series illustrates the harmful effects of ketamine on the urinary tract and the associated radiological findings. Delayed diagnosis can result in irreversible renal tract damage requiring surgical intervention. It is important that radiologists are aware of this emerging clinical entity as early diagnosis and treatment are essential for successful management.

Principal component analysis of early alcohol, drug and tobacco use with major depressive disorder in US adults.

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Wang, Kesheng; Liu, Ying; Ouedraogo, Youssoufou; Wang, Nianyang; Xie, Xin; Xu, Chun; Luo, Xingguang

2018-05-01

Early alcohol, tobacco and drug use prior to 18 years old are comorbid and correlated. This study included 6239 adults with major depressive disorder (MDD) in the past year and 72,010 controls from the combined data of 2013 and 2014 National Survey on Drug Use and Health (NSDUH). To deal with multicollinearity existing among 17 variables related to early alcohol, tobacco and drug use prior to 18 years old, we used principal component analysis (PCA) to infer PC scores and then use weighted multiple logistic regression analyses to estimate the associations of potential factors and PC scores with MDD. The odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. The overall prevalence of MDD was 6.7%. The first four PCs could explain 57% of the total variance. Weighted multiple logistic regression showed that PC 1 (a measure of psychotherapeutic drugs and illicit drugs other than marijuana use), PC 2 (a measure of cocaine and hallucinogens), PC 3 (a measure of early alcohol, cigarettes, and marijuana use), and PC 4 (a measure of cigar, smokeless tobacco use and illicit drugs use) revealed significant associations with MDD (OR = 1.12, 95% CI = 1.08-1.16, OR = 1.08, 95% CI = 1.04-1.12, OR = 1.13, 95% CI = 1.07-1.18, and OR = 1.15, 95% CI = 1.09-1.21, respectively). In conclusion, PCA can be used to reduce the indicators in complex survey data. Early alcohol, tobacco and drug use prior to 18 years old were found to be associated with increased odds of adult MDD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Persistent effects of chronic clozapine on the cellular and behavioral responses to LSD in mice

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Moreno, José L.; Holloway, Terrell; Umali, Adrienne; Rayannavar, Vinayak; Sealfon, Stuart C.

2013-01-01

Rationale In schizophrenia patients, optimal treatment with antipsychotics requires weeks to months of sustained drug therapy. However, single administration of antipsychotic drugs can reverse schizophrenia-like behavioral alterations in rodent models of psychosis. This raises questions about the physiological relevance of such antipsychotic-like activity. Objective This study evaluates the effects of chronic treatment with clozapine on the cellular and behavioral responses induced by the hallucinogenic serotonin 5-HT2A receptor agonist lysergic acid diethylamide (LSD) as a mouse model of psychosis. Method Mice were treated chronically (21 days) with 25 mg/kg/day clozapine. Experiments were conducted 1, 7, 14, and 21 days after the last clozapine administration. [3H]Ketanserin binding and 5-HT2A mRNA expression were determined in mouse somatosensory cortex. Head-twitch behavior, expression of c-fos, which is induced by all 5-HT2A agonists, and expression of egr-1 and egr-2, which are LSD-like specific, were assayed. Results Head-twitch response was decreased and [3H]ketanserin binding was downregulated in 1, 7, and 14 days after chronic clozapine. 5-HT2A mRNA was reduced 1 day after chronic clozapine. Induction of c-fos, but not egr-1 and egr-2, was rescued 7 days after chronic clozapine. These effects were not observed after short treatment (2 days) with clozapine or chronic haloperidol (1 mg/kg/day). Conclusion Our findings provide a murine model of chronic atypical antipsychotic drug action and suggest downregulation of the 5-HT2A receptor as a potential mechanism involved in these persistent therapeutic-like effects. PMID:22842765

Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later

Science.gov (United States)

Griffiths, Roland R.; Richards, William A.; Johnson, Matthew W.; McCann, Una D.; Jesse, Robert

2010-01-01

Psilocybin has been used for centuries for religious purposes; however little is known scientifically about its long-term effects. We previously reported the effects of a double-blind study evaluating the psychological effects of a high psilocybin dose. This report presents the 14-month follow-up and examines the relationship of the follow-up results to data obtained at screening and on drug session days. Participants were 36 hallucinogen-naïve adults reporting regular participation in religious/spiritual activities. Oral psilocybin (30 mg/70kg) was administered on one of two or three sessions, with methylphenidate (40 mg/70kg) administered on the other session(s). During sessions, volunteers were encouraged to close their eyes and direct their attention inward. At the 14-month follow-up, 58% and 67%, respectively, of volunteers rated the psilocybin-occasioned experience as being among the five most personally meaningful and among the five most spiritually significant experiences of their lives; 64% indicated the experience increased well-being or life satisfaction; 58% met criteria for having had a “complete” mystical experience. Correlation and regression analyses indicated a central role of the mystical experience assessed on the session day in the high ratings of personal meaning and spiritual significance at follow-up. Of the measures of personality, affect, quality of life, and spirituality assessed across the study, only a scale measuring mystical experience showed a difference from screening. When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously-occurring mystical experiences that, at 14-month follow-up, were considered by volunteers to be among the most personally meaningful and spiritually significant of their lives. PMID:18593735

Hypotheses about geoglyphs at Nasca, Peru: new discoveries

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Jaroslav Klokočník

2016-07-01

Full Text Available The known hypotheses about the reasons why the geoglyphs in the Nasca and Palpa region of Peru were created are many: roads/paths, rituals/ceremonials, use of hallucinogens, astronomical meaning, influence of extraterrestrials, underground water… and so on. We present a new hypothesis, formulated by J. Sonnek (first published in 2011 in the context of all previous hypotheses.1 Sonnek explains the geoglyphs as tidied work areas for the production of rope and nets, although he goes much further than Stierlin. This eccentric hypothesis now has not only experimental but also archaeological and ethnographical support, which is presented here. Geoglyphs of a special shape were discovered in the pampas; they may represent technical objects – different types of ‘rope twisters’. Following this idea, Sonnek made technical devices (using today’s materials and tested them in practice; they work perfectly, see his YouTube videos.2 In November 2012, wooden pieces, which may be the remnants of ropemaking, were collected from the pampa near the towns of Nasca and Palpa, in vicinity of these hypothetic ropemaking places. Radiocarbon testing by 14C standardized radio-carbon age according to Stuiver-Polach convention and Accelerator Mass Spectroscopy (AMS of these wood pieces shows the age to be in a wide range from Early Nasca to the 17th century (and to our epoch with a fake geoglyph, too, thus supporting (but surely not proving the new hypothesis. Moreover, in the Quechua language, the word huasca, waskha (read: uasca means a rope or cord or place where these are produced. This word is very similar to ‘nasca’.

Pharmacokinetic study of harmane and its 10 metabolites in rat after intravenous and oral administration by UPLC-ESI-MS/MS.

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Li, Shuping; Teng, Liang; Liu, Wei; Cheng, Xuemei; Jiang, Bo; Wang, Zhengtao; Wang, Chang-Hong

2016-09-01

Context The β-carboline alkaloid harmane is widely distributed in common foods, beverages and hallucinogenic plants. Harmane exerts potential in therapies for Alzheimer's and depression diseases. However, little information on its dynamic metabolic profiles and pharmacokinetics in vivo is currently available. Objective This study investigates the dynamic metabolic profiles and pharmacokinetic properties of harmane and its metabolites in rats in vivo. Materials and methods A highly selective, sensitive and rapid ultra-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method was developed and well-validated for simultaneous quantitative determination of harmane and its uncertain endogenous metabolite harmine, as well as for semiquantitative determination of 10 harmane metabolites in rats after intravenous injection and oral administration of harmane at 1.0 and 30.0 mg/kg, respectively. Results The calibration curves of harmane and harmine showed excellent linearity within the concentration range of 1-2000 ng/mL with acceptable accuracy, precision, selectivity, recovery, matrix effect and stability. Ten metabolites, including harmane but not harmine, were detected and identified after intravenous and oral administration of harmane. The absolute bioavailability of harmane following an oral dose was 19.41 ± 3.97%. According to the AUC0-t values of all the metabolites, the metabolic levels of phase II metabolites were higher than those of phase I metabolites, and the sulphation pathways were the dominant metabolic routes for harmane in both routes of administration. Discussion and conclusion The pharmacokinetic properties of harmane and its 10 metabolites in rats were determined. Sulphate conjugation was the predominant metabolic process of harmane in rats.

Illicit and nonmedical drug use among Asian Americans, Native Hawaiians/Pacific Islanders, and mixed-race individuals

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Wu, Li-Tzy; Blazer, Dan G.; Swartz, Marvin S.; Burchett, Bruce; Brady, Kathleen T.

2013-01-01

Background The racial/ethnic composition of the United States is shifting rapidly, with non-Hispanic Asian-Americans, Native Hawaiians/Pacific Islanders (NHs/PIs), and mixed-race individuals the fastest growing segments of the population. We determined new drug use estimates for these rising groups. Prevalences among Whites were included as a comparison. Methods Data were from the 2005–2011 National Surveys on Drug Use and Health. Substance use among respondents aged ≥12 years was assessed by computer-assisted self-interviewing methods. Respondents’ self-reported race/ethnicity, age, gender, household income, government assistance, county type, residential stability, major depressive episode, history of being arrested, tobacco use, and alcohol use were examined as correlates. We stratified the analysis by race/ethnicity and used logistic regression to estimate odds of drug use. Results Prevalence of past-year marijuana use among Whites increased from 10.7% in 2005 to 11.6–11.8% in 2009–2011 (PAsian-Americans, NHs/PIs, and mixed-race people; but use of any drug, especially marijuana, was prevalent among NHs/PIs and mixed-race people (21.2% and 23.3%, respectively, in 2011). Compared with Asian-Americans, NHs/PIs had higher odds of marijuana use, and mixed-race individuals had higher odds of using marijuana, cocaine, hallucinogens, stimulants, sedatives, and tranquilizers. Compared with Whites, mixed-race individuals had greater odds of any drug use, mainly marijuana, and NHs/PIs resembled Whites in odds of any drug use. Conclusions Findings reveal alarmingly prevalent drug use among NHs/PIs and mixed-race people. Research on drug use is needed in these rising populations to inform prevention and treatment efforts. PMID:23890491

Deaths due to abuse of dextromethorphan sold over-the-counter in Pakistan

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Humera Shafi

2016-09-01

Full Text Available Dextromethorphan is the most commonly used over-the-counter anti-tussive and expectorant medicine at therapeutic doses. Due to easy availability, euphoric high and hallucinogenic effects at larger doses, dextromethorphan popularity amongst the drug abusers is growing day by day. It is often mixed with alcohol, opiates, cannabinoids or other drugs of abuse for recreational purposes despite their lethal synergistic effects. More than 50 deaths were reported the first time in Pakistan after consuming cough syrups containing dextromethorphan, manufactured by two local pharmaceutical industries. All deceased had the history of drug abuse. We report the deaths of nineteen males, ages ranged from 17 to 45 years, in two major cities of Pakistan who purposefully ingested large doses of dextromethorphan for recreational purposes and died as a result of direct toxic effects of the drug. Toxicological analysis revealed high levels of dextromethorphan ranging from 7.3 to 41.7 mg/L in the peripheral blood, 4.2–92.6 mg/kg in the liver and 9.9–349.6 mg/L in the gastric content by high performance liquid chromatography. The dextromethorphan concentrations in all subjects significantly exceeded the therapeutic range and were consistent with concentrations reported in other cases of dextromethorphan abuse and toxicity. Besides dextromethorphan other drugs of abuse like cannabinoids, opiates, benzodiazepines, ethanol and chlorpheniramine were also detected. The cause of death was determined to be acute dextromethorphan intoxication with lethal synergistic effect of other co-ingested drugs of abuse. The deaths resulted in the prosecution of all individuals involved in manufacturing, distribution or sale of the cough syrup.

Predictors of attrition with buprenorphine/naloxone treatment in opioid dependent youth☆

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Warden, Diane; Subramaniam, Geetha A.; Carmody, Thomas; Woody, George E.; Minhajuddin, Abu; Poole, Sabrina A.; Potter, Jennifer; Fishman, Marc; Bogenschutz, Michael; Patkar, Ashwin; Trivedi, Madhukar H.

2012-01-01

Background In opioid dependent youth there is substantial attrition from medication-assisted treatment. If youth at risk for attrition can be identified at treatment entry or early in treatment, they can be targeted for interventions to help retain them in treatment. Methods Opioid dependent adolescents and young adults (n=152), aged 15–21, were randomized to 12 weeks (BUP, n=74) or 2 weeks of detoxification (DETOX, n=78) with buprenorphine/naloxone (Bup/Nal), both in combination with 12 weeks of psychosocial treatment. Baseline and early treatment related predictors of treatment attrition were identified in each group using bivariate and multivariate logistic regression. Results In the DETOX group 36% left between weeks 2 and 4, at the end of the dose taper, while in the BUP group only 8% left by week 4. In the BUP group, early adherence to Bup/Nal, early opioid negative urines, use of any medications in the month prior to treatment entry, and lifetime non-heroin opioid use were associated with retention while prior 30-day hallucinogen use was associated with attrition. In the DETOX group, only use of sleep medications was associated with retention although not an independent predictor. A broad range of other pre-treatment characteristics was unrelated to attrition. Conclusions Prompt attention to those with early non-adherence to medication or an early opioid positive urine, markers available in the first 2 weeks of treatment, may improve treatment retention. Extended Bup/ Nal treatment appeared effective in improving treatment retention for youth with opioid dependence across a wide range of demographics, and pre-treatment clinical characteristics. PMID:22626890

Predictors of attrition with buprenorphine/naloxone treatment in opioid dependent youth.

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Warden, Diane; Subramaniam, Geetha A; Carmody, Thomas; Woody, George E; Minhajuddin, Abu; Poole, Sabrina A; Potter, Jennifer; Fishman, Marc; Bogenschutz, Michael; Patkar, Ashwin; Trivedi, Madhukar H

2012-09-01

In opioid dependent youth there is substantial attrition from medication-assisted treatment. If youth at risk for attrition can be identified at treatment entry or early in treatment, they can be targeted for interventions to help retain them in treatment. Opioid dependent adolescents and young adults (n=152), aged 15-21, were randomized to 12 weeks (BUP, n=74) or 2 weeks of detoxification (DETOX, n=78) with buprenorphine/naloxone (Bup/Nal), both in combination with 12 weeks of psychosocial treatment. Baseline and early treatment related predictors of treatment attrition were identified in each group using bivariate and multivariate logistic regression. In the DETOX group 36% left between weeks 2 and 4, at the end of the dose taper, while in the BUP group only 8% left by week 4. In the BUP group, early adherence to Bup/Nal, early opioid negative urines, use of any medications in the month prior to treatment entry, and lifetime non-heroin opioid use were associated with retention while prior 30-day hallucinogen use was associated with attrition. In the DETOX group, only use of sleep medications was associated with retention although not an independent predictor. A broad range of other pre-treatment characteristics was unrelated to attrition. Prompt attention to those with early non-adherence to medication or an early opioid positive urine, markers available in the first 2 weeks of treatment, may improve treatment retention. Extended Bup/Nal treatment appeared effective in improving treatment retention for youth with opioid dependence across a wide range of demographics, and pre-treatment clinical characteristics. Copyright © 2012 Elsevier Ltd. All rights reserved.

Association between alcohol, cannabis, and other illicit substance abuse and risk of developing schizophrenia: a nationwide population based register study.

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Nielsen, S M; Toftdahl, N G; Nordentoft, M; Hjorthøj, C

2017-07-01

Several studies have examined whether use of substances can cause schizophrenia. However, due to methodological limitations in the existing literature (e.g. selection bias and lack of adjustment of co-abuse) uncertainties still remain. We aimed to investigate whether substance abuse increases the risk of developing schizophrenia, addressing some of these limitations. The longitudinal, nationwide Danish registers were linked to establish a cohort of 3 133 968 individuals (105 178 673 person-years at risk), identifying 204 505 individuals diagnosed with substance abuse and 21 305 diagnosed with schizophrenia. Information regarding substance abuse was extracted from several registers and did not include psychotic symptoms caused by substance abuse in the definition. This resulted in a large, generalizable sample of exposed individuals. The data was analysed using Cox regression analyses, and adjusted for calendar year, gender, urbanicity, co-abuse, other psychiatric diagnosis, parental substance abuse, psychiatric history, immigration and socioeconomic status. A diagnosis of substance abuse increased the overall risk of developing schizophrenia [hazard ratio (HR) 6.04, 95% confidence interval (CI) 5.84-6.26]. Cannabis (HR 5.20, 95% CI 4.86-5.57) and alcohol (HR 3.38, 95% CI 3.24-3.53) presented the strongest associations. Abuse of hallucinogens (HR 1.86, 95% CI 1.43-2.41), sedatives (HR 1.68, 95% CI 1.49-1.90), and other substances (HR 2.85, 95% CI 2.58-3.15) also increased the risk significantly. The risk was found to be significant even 10-15 years subsequent to a diagnosis of substance abuse. Our results illustrate robust associations between almost any type of substance abuse and an increased risk of developing schizophrenia later in life.

Substance use disorders and adoption: findings from a national sample.

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Gihyun Yoon

Full Text Available BACKGROUND: Prior research has shown that adoptees have a higher rate of substance use disorders (SUDs than nonadoptees. But these findings have not been verified with a population-based sample of adult adoptees in the United States. Also, no previous adoption study has measured the prevalence of each specific substance use disorder (SUD. We aimed to compare lifetime prevalence rates and odds ratios of SUDs in adopted and nonadopted adults. METHODS AND FINDINGS: The data come from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC. The main outcome measure was the prevalence of lifetime SUDs in adopted (n = 378 and nonadopted adults (n = 42503. Adoptees and nonadoptees were compared to estimate the odds of lifetime SUDs using logistic regression analysis. Adoptees had higher prevalence rates of lifetime SUDs than nonadoptees. Overall, adoptees had a 1.87-fold increase (adjusted odds ratio [AOR] 1.87, 95% CI 1.51-2.31 in the odds of any lifetime SUD compared to nonadoptees. For each SUD, adoptees had higher odds for alcohol abuse/dependence (AOR 1.84, nicotine dependence (AOR 1.78, cannabis abuse/dependence (AOR 1.77, cocaine abuse/dependence (AOR 2.54, amphetamine abuse/dependence (AOR 3.14, hallucinogen abuse/dependence (AOR 2.85, opioid abuse/dependence (AOR 2.21, and other drug abuse/dependence (AOR 2.87 compared to nonadoptees. This study also identified two adoption-specific risk factors (Hispanic, never married associated with any lifetime SUD. CONCLUSIONS: This study demonstrated an increased risk of lifetime SUDs in adopted adults. The findings can be useful for clinicians and policy makers to provide education, prevention, and support for adoptees and their families.

A "refugee paradox" for substance use disorders?

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Salas-Wright, Christopher P; Vaughn, Michael G

2014-09-01

Few, if any, studies have systematically examined the link between nativity and substance use disorders (SUD) among refugees using national samples. As such, it remains uncertain if the "immigrant paradox" for substance use can be extended to include refugees in the United States. Employing data from the National Epidemiologic Survey on Alcohol and Related Conditions, we examine the lifetime prevalence of SUDs among refugees (n=428) in contrast with non-refugee immigrants (n=4955) and native-born Americans (n=29,267). We also examine the impact of gender and refugee duration on the relationship between nativity, refugee status, and SUDs. Refugees were between 3 and 6 times less likely than native-born Americans meet criteria for all SUDs examined, and significantly less likely than non-refugee immigrants to meet criteria for alcohol (AOR=0.44, 95% CI=0.41-0.47), cocaine (AOR=0.54, 95% CI=0.50-0.59), hallucinogen (AOR=0.66, 95% CI=0.58-0.74), and opioid/heroin (AOR=0.62, 95% CI=0.58-0.66) use disorders. The refugee-SUD link was significantly moderated by gender. Duration as a refugee was associated with increased risk for alcohol use disorder and decreased risk of cannabis and illicit drug use disorders. Study findings provide evidence in support of a "refugee paradox" for SUDs among adults in the United States. Refugees are substantially less likely than native-born Americans to meet criteria for all SUDs examined and, albeit with weaker effects, significantly less likely than non-refugee immigrants to meet criteria for a variety of SUDs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

[Psychophysiological regin for rehabilition of chronic polydrug users in the Center of the Le Patriarche. 446 cases (author's transl)].

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Laffont, F; Engelmajer, L; Vourc'h, G; Nahas, G

1980-01-01

From 1974 to 1979, the rehabilitation centers of the association "Le Patriarche" located in the country side of southern France, have received 446 chronic polydrugs users who has consumed at one time or an other cannabis (marihuana, hashish) (87 p. cent), LSD (66 p. cent) and other hallucinogens (35 p. cent), psychodepressants (55 p. cent), psychostimulants (amphetamines, 85 p. cent; cocaïne, 50 p. cent) and opium and its derivatives (brown sugar, 47 p. cent; opiates, 67 p. cent; heroin, 50 p. cent). The dominant addictive drug was heroin and opiates, 52 p. cent, psychodepressants (barbitutiques and benzodiazepines, 33 p. cent, psychostimulants, 15 p. cent. Males were twice as numerous as female. Average age was 21 (range 14-38). Mean duration of drug abuse was 7 years. All these drug abusers display at entrance withdrawal symptoms. These were treated successfully by a drug free, psycho-physiological regimen comprising: 1. An elimination of all psychoactive drugs, including coffee, and alcohol. Tobacco was permitted. 2. Physical therapy (bath, exercise, massage) and forced fluid diuresis. 3. A supportive psychotherapy dispensed by rehabilitated addicts who had undergone successfully a similar regimen. This non-pharmacological method of treating withdrawal symptoms associated with opium, barbiturate and amphetamine addiction, was successful, and was not associated with any major clinical symptoms threatening the vital signs. Mean duration of detoxification was 5 days for opiates, 6 days for amphetamines and 10 days for barbiturates. 78 p. cent of these subjects remained in the centers from 3 months to 2 years, partaking in physical occupational and physiological rehabilitation paograms which allowed then to adopt a drug free life style and prepared them for social reinsertion.

Clinical pharmacokinetics of non-opiate abused drugs.

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Busto, U; Bendayan, R; Sellers, E M

1989-01-01

The present review discusses the available data on the kinetic properties of non-opiate abused drugs including psychomotor stimulants, hallucinogens and CNS-depressants. Some of the drugs of abuse reviewed here are illicit drugs (e.g. cannabis, cocaine), while others are effective pharmacological agents but have the potential to be abused (e.g. benzodiazepines). Although some of the drugs mentioned in this review have been in use for centuries (e.g. caffeine, nicotine, cocaine, cannabis), knowledge of their kinetics and metabolism is very recent and in some cases still incomplete. This is partially due to the difficulties inherent in studying drugs of abuse in humans, and to the complex metabolism of some of these drugs (e.g. cannabis, caffeine) which has made it difficult to develop sensitive assays to determine biological pathways. Although drugs of abuse may have entirely different intrinsic pharmacological effects, the kinetic properties of such drugs are factors contributing to abuse and dependence. The pharmacokinetic properties that presumably contribute to self-administration and drug abuse include rapid delivery of the drug into the central nervous system and high free drug clearance. Kinetic characteristics also play an important role in the development of physical dependence and on the appearance of a withdrawal syndrome: the longer the half-life, the greater the likelihood of the development of physical dependence; the shorter the half-life, the earlier and more severe the withdrawal. The balance between these 2 factors, which has not yet been carefully studied, will also influence abuse patterns. The clinical significance of kinetic characteristics with respect to abuse is discussed where possible.

The current state of research on ayahuasca: A systematic review of human studies assessing psychiatric symptoms, neuropsychological functioning, and neuroimaging.

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Dos Santos, Rafael G; Balthazar, Fermanda M; Bouso, José C; Hallak, Jaime Ec

2016-12-01

In recent decades, the use of ayahuasca (AYA) - a β-carboline- and dimethyltryptamine-rich hallucinogenic botanical preparation traditionally used by Northwestern Amazonian tribes for ritual and therapeutic purposes - has spread from South America to Europe and the USA, raising concerns about its possible toxicity and hopes of its therapeutic potential. Thus, it is important to analyze the acute, subacute, and long-term effects of AYA to assess its safety and toxicity. The purpose of this study was to conduct a systematic review of human studies assessing AYA effects on psychiatric symptoms, neuropsychological functioning, and neuroimaging. Papers published until 16 December 2015 were included from PubMed, LILACS and SciELO databases following a comprehensive search strategy and pre-determined set of criteria for article selection. The review included 28 full-text articles. Acute AYA administration was well tolerated, increased introspection and positive mood, altered visual perceptions, activated frontal and paralimbic regions and decreased default mode network activity. It also improved planning and inhibitory control and impaired working memory, and showed antidepressive and antiaddictive potentials. Long-term AYA use was associated with increased cortical thickness of the anterior cingulate cortex and cortical thinning of the posterior cingulate cortex, which was inversely correlated to age of onset, intensity of prior AYA use, and spirituality. Subacute and long-term AYA use was not associated with increased psychopathology or cognitive deficits, being associated with enhanced mood and cognition, increased spirituality, and reduced impulsivity. Acute, subacute, and long-term AYA use seems to have low toxicity. Preliminary studies about potential therapeutic effects of AYA need replication due to their methodological limitations. © The Author(s) 2016.

Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study.

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Sanches, Rafael Faria; de Lima Osório, Flávia; Dos Santos, Rafael G; Macedo, Ligia R H; Maia-de-Oliveira, João Paulo; Wichert-Ana, Lauro; de Araujo, Draulio Barros; Riba, Jordi; Crippa, José Alexandre S; Hallak, Jaime E C

2016-02-01

Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine, a 5-HT2A receptor agonist, and harmine, a monoamine-oxidase A inhibitor. Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients. The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow. In an open-label trial conducted in an inpatient psychiatric unit, 17 patients with recurrent depression received an oral dose of ayahuasca (2.2 mL/kg) and were evaluated with the Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale, the Brief Psychiatric Rating Scale, the Young Mania Rating Scale, and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1, 7, 14, and 21 days after drug intake. Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography. Ayahuasca administration was associated with increased psychoactivity (Clinician Administered Dissociative States Scale) and significant score decreases in depression-related scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale) from 80 minutes to day 21. Increased blood perfusion in the left nucleus accumbens, right insula and left subgenual area, brain regions implicated in the regulation of mood and emotions, were observed after ayahuasca intake. Ayahuasca was well tolerated. Vomiting was the only adverse effect recorded, being reported by 47% of the volunteers. Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties. These results should be replicated in randomized, double-blind, placebo-controlled trials.

Salvinorin-A Induces Intense Dissociative Effects, Blocking External Sensory Perception and Modulating Interoception and Sense of Body Ownership in Humans.

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Maqueda, Ana Elda; Valle, Marta; Addy, Peter H; Antonijoan, Rosa Maria; Puntes, Montserrat; Coimbra, Jimena; Ballester, Maria Rosa; Garrido, Maite; González, Mireia; Claramunt, Judit; Barker, Steven; Johnson, Matthew W; Griffiths, Roland R; Riba, Jordi

2015-06-05

Salvinorin-A is a terpene with agonist properties at the kappa-opioid receptor, the binding site of endogenous dynorphins. Salvinorin-A is found in Salvia divinorum, a psychoactive plant traditionally used by the Mazatec people of Oaxaca, Mexico, for medicinal and spiritual purposes. Previous studies with the plant and salvinorin-A have reported psychedelic-like changes in perception, but also unusual changes in body awareness and detachment from external reality. Here we comprehensively studied the profiles of subjective effects of increasing doses of salvinorin-A in healthy volunteers, with a special emphasis on interoception. A placebo and three increasing doses of vaporized salvinorin-A (0.25, 0.50, and 1mg) were administered to eight healthy volunteers with previous experience in the use of psychedelics. Drug effects were assessed using a battery of questionnaires that included, among others, the Hallucinogen Rating Scale, the Altered States of Consciousness, and a new instrument that evaluates different aspects of body awareness: the Multidimensional Assessment for Interoceptive Awareness. Salvinorin-A led to a disconnection from external reality, induced elaborate visions and auditory phenomena, and modified interoception. The lower doses increased somatic sensations, but the highest dose led to a sense of a complete loss of contact with the body. Salvinorin-A induced intense psychotropic effects characterized by a dose-dependent gating of external audio-visual information and an inverted-U dose-response effect on body awareness. These results suggest a prominent role for the kappa opioid receptor in the regulation of sensory perception, interoception, and the sense of body ownership in humans. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Differences in behavioral health disorders and unmet treatment needs between medical marijuana users and recreational marijuana users: Results from a national adult sample.

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Park, Ji-Yeun; Wu, Li-Tzy

2017-11-01

Available data suggest that medical marijuana users may have more mental health problems than recreational marijuana users. There is limited information about differences in behavioral health disorders and unmet treatment needs between medical and recreational marijuana users. We compared past-year prevalence of behavioral health disorders and unmet treatment needs across three marijuana subgroups (recreational use only, medical use only, and both). Sex-stratified logistic regression was performed to determine their associations with marijuana use status. We analyzed data from adults (≥18 years) who used marijuana in the past year (N=15,440) from 2013 to 2014 National Surveys on Drug Use and Health. Among 15,440 past-year marijuana users, 90.2% used recreational marijuana only, 6.2% used medical marijuana only, and 3.6% used both. Both users had the highest prevalence of behavioral health disorders and unmet treatment needs overall, with no significant sex differences. In the sex-specific logistic regression analysis, medical only users and both users showed somewhat different patterns of associations (reference group=recreational only users). Medical only users had decreased odds of alcohol or drug use disorders, and unmet need for alcohol or drug treatment among males and females. Additionally, female medical only users had decreased odds of opioid use disorder. Both users had increased odds of major depressive episode, hallucinogen use disorder, and unmet need for mental health services among males, and cocaine use disorder among females. Different approaches tailored to individuals' sex and motives for marijuana use is needed for the prevention and treatment of behavioral health problems. Copyright © 2017 Elsevier B.V. All rights reserved.

海洛因依赖者《美国精神障碍诊断与统计手册(第四版)》轴Ⅰ障碍的终身患病情况分析%Axis Ⅰ comorbidity of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders among heroin-dependent patients

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杨梅; 廖艳辉; 王强; 王红; Vasish Kavi; 刘铁桥; 郝伟

2013-01-01

Objective To provide lifetime rates of axis Ⅰ conorbidities of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) among patients with heroin dependence.Methods A cross-section study was conducted.Subjects were 1002 heroin-dependent patients who were consecutively admitted into three drug rehabilitation settings in Hunan province.A questionnaire was developed to get demographic and drug use-related information of the subjects.Structured Clinical Interview for DSM-IV-TR Axis Ⅰ Disorders-Patient Edition (SCID-I/P) was used for making lifetime DSM-Ⅳ axis Ⅰ diagnoses.Results Among the subjects,mood disorder was the most common type of cooccurring axis Ⅰ non-substance use mental disorders (191,19.1％),followed by anxiety disorder (128,12.8％).Major depression (135,13.5％) was the most common diagnosis among co-occurring mood disorders,whereas post-traumatic stress disorder (PTSD,81,8.1％) was the most common diagnosis among anxiety disorders.579 (57.8％) subjects had other substance (non-opioid,other than tobacco) use disorders.The most frequent diagnoses of other substance use disorders were sedative-hypnotics use disorder and alcohol use disorder,with lifetime rates of 30.3％ (303) and 27.5％ (275) respectively,followed by stimulant and hallucinogen use disorder,with a lifetime rate of 14.8％ (148) for stimulant use disorder and a lifetime rate of 12.7％ (127) for hallucinogen use disorder.Conclusions Co-occurring non-substance use mental disorders and other substance use disorders among heroin-dependent patients in China are highly prevalent,to which great importance should be attached in the process of diagnosis and treatment.%目的 调查我国海洛因依赖者中《美国精神障碍诊断与统计手册(第4版)》(DSM-Ⅳ)轴Ⅰ精神障碍和其他物质使用障碍的终身患病情况.方法 对湖南省3家戒毒机构的1002�

The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval.

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Vollenweider, Franz X; Csomor, Philipp A; Knappe, Bernhard; Geyer, Mark A; Quednow, Boris B

2007-09-01

Schizophrenia patients exhibit impairments in prepulse inhibition (PPI) of the startle response. Hallucinogenic 5-HT(2A) receptor agonists are used for animal models of schizophrenia because they mimic some symptoms of schizophrenia in humans and induce PPI deficits in animals. Nevertheless, one report indicates that the 5-HT(2A) receptor agonist psilocybin increases PPI in healthy humans. Hence, we investigated these inconsistent results by assessing the dose-dependent effects of psilocybin on PPI in healthy humans. Sixteen subjects each received placebo or 115, 215, and 315 microg/kg of psilocybin at 4-week intervals in a randomized and counterbalanced order. PPI at 30-, 60-, 120-, 240-, and 2000-ms interstimulus intervals (ISIs) was measured 90 and 165 min after drug intake, coinciding with the peak and post-peak effects of psilocybin. The effects of psilocybin on psychopathological core dimensions and sustained attention were assessed by the Altered States of Consciousness Rating Scale (5D-ASC) and the Frankfurt Attention Inventory (FAIR). Psilocybin dose-dependently reduced PPI at short (30 ms), had no effect at medium (60 ms), and increased PPI at long (120-2000 ms) ISIs, without affecting startle reactivity or habituation. Psilocybin dose-dependently impaired sustained attention and increased all 5D-ASC scores with exception of Auditory Alterations. Moreover, psilocybin-induced impairments in sustained attention performance were positively correlated with reduced PPI at the 30 ms ISI and not with the concomitant increases in PPI observed at long ISIs. These results confirm the psilocybin-induced increase in PPI at long ISIs and reveal that psilocybin also produces a decrease in PPI at short ISIs that is correlated with impaired attention and consistent with deficient PPI in schizophrenia.

Evolution of the toxins muscarine and psilocybin in a family of mushroom-forming fungi.

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Pawel Kosentka

Full Text Available Mushroom-forming fungi produce a wide array of toxic alkaloids. However, evolutionary analyses aimed at exploring the evolution of muscarine, a toxin that stimulates the parasympathetic nervous system, and psilocybin, a hallucinogen, have never been performed. The known taxonomic distribution of muscarine within the Inocybaceae is limited, based only on assays of species from temperate regions of the northern hemisphere. Here, we present a review of muscarine and psilocybin assays performed on species of Inocybaceae during the last fifty years. To supplement these results, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS to determine whether muscarine was present in 30 new samples of Inocybaceae, the majority of which have not been previously assayed or that originated from either the tropics or temperate regions of the southern hemisphere. Our main objective is to test the hypothesis that the presence of muscarine is a shared ancestral feature of the Inocybaceae. In addition, we also test whether species of Inocyabceae that produce psilocybin are monophyletic. Our findings suggest otherwise. Muscarine has evolved independently on several occasions, together with several losses. We also detect at least two independent transitions of muscarine-free lineages to psilocybin-producing states. Although not ancestral for the family as a whole, muscarine is a shared derived trait for an inclusive clade containing three of the seven major lineages of Inocybaceae (the Inocybe, Nothocybe, and Pseudosperma clades, the common ancestor of which may have evolved ca. 60 million years ago. Thus, muscarine represents a conserved trait followed by several recent losses. Transitions to psilocybin from muscarine-producing ancestors occurred more recently between 10-20 million years ago after muscarine loss in two separate lineages. Statistical analyses firmly reject a single origin of muscarine-producing taxa.

Psilocybin-induced deficits in automatic and controlled inhibition are attenuated by ketanserin in healthy human volunteers.

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Quednow, Boris B; Kometer, Michael; Geyer, Mark A; Vollenweider, Franz X

2012-02-01

The serotonin-2A receptor (5-HT(2A)R) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT(2A)R or 5-HT(1A)R agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT(2A/2C)R antagonist ketanserin. A total of 16 healthy participants received placebo, ketanserin (40 mg p.o.), psilocybin (260 μg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT(2A)R stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT(2A)R system.

Evolution of the toxins muscarine and psilocybin in a family of mushroom-forming fungi.

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Kosentka, Pawel; Sprague, Sarah L; Ryberg, Martin; Gartz, Jochen; May, Amanda L; Campagna, Shawn R; Matheny, P Brandon

2013-01-01

Mushroom-forming fungi produce a wide array of toxic alkaloids. However, evolutionary analyses aimed at exploring the evolution of muscarine, a toxin that stimulates the parasympathetic nervous system, and psilocybin, a hallucinogen, have never been performed. The known taxonomic distribution of muscarine within the Inocybaceae is limited, based only on assays of species from temperate regions of the northern hemisphere. Here, we present a review of muscarine and psilocybin assays performed on species of Inocybaceae during the last fifty years. To supplement these results, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine whether muscarine was present in 30 new samples of Inocybaceae, the majority of which have not been previously assayed or that originated from either the tropics or temperate regions of the southern hemisphere. Our main objective is to test the hypothesis that the presence of muscarine is a shared ancestral feature of the Inocybaceae. In addition, we also test whether species of Inocyabceae that produce psilocybin are monophyletic. Our findings suggest otherwise. Muscarine has evolved independently on several occasions, together with several losses. We also detect at least two independent transitions of muscarine-free lineages to psilocybin-producing states. Although not ancestral for the family as a whole, muscarine is a shared derived trait for an inclusive clade containing three of the seven major lineages of Inocybaceae (the Inocybe, Nothocybe, and Pseudosperma clades), the common ancestor of which may have evolved ca. 60 million years ago. Thus, muscarine represents a conserved trait followed by several recent losses. Transitions to psilocybin from muscarine-producing ancestors occurred more recently between 10-20 million years ago after muscarine loss in two separate lineages. Statistical analyses firmly reject a single origin of muscarine-producing taxa.

Studies on cannabis, 3

International Nuclear Information System (INIS)

Shimomura, Hiroko; Kuriyama, Etsuko; Tomizawa, Atsuko

1976-01-01

The seedlings from Cannabis sativa L. seeds irradiated with different doses of γ-rays were examined, in order to determine the dose sufficient to kill the young plants naturally, before their hallucinnogenic component increases. The seeds of ''Minamioshihara No. 1'', which were harvested in 1972 in Tochigi Prefecture, were irradiated with eight different doses of 60 Co γ-rays in January 17, 1973, and the seedlings were examined several times during the subsequent 9 months, from March to November 1973, and their morphological and histological effects were examined, and the results are summarized as follows: Samples irradiated with 1500 and 1000 krads developed radicles about 3 mm in length. Samples irradiated with 500, 200, and 50 krads grew into young plants with the first set of leaves, without lateral roots. Samples irradiated with 30 krads grew to about 10 cm high with a few lateral roots, and the epicotyls about 1 cm in length. These young plants from the irradiated seeds stayed in the same condition and then died. Samples irradiated with 15 and 5 krads grew in the same way as the controls until the stage of flowering. Samples irradiated with 500, 200, 50, and 30 krads showerd the cell membranes of endodermis and pericycle to be partially lignified and suberized. The degree of change was related to the dose of γ-rays. Samples irradiated with 30 krads showed withered cells near the end of the lateral nerves on the first and second set of leaves. The economical dose of 60 Co γ-rays for inhibiting young plants from developing into adult ones was a minimum of 30 krads which made the young plants die. Irradiation with 50 krads of γ-rays will be required to kill the young plants completely before they develop the hallucinogenic component. (auth.)

Discrete memory impairments in largely pure chronic users of MDMA.

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Wunderli, Michael D; Vonmoos, Matthias; Fürst, Marina; Schädelin, Katrin; Kraemer, Thomas; Baumgartner, Markus R; Seifritz, Erich; Quednow, Boris B

2017-10-01

Chronic use of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") has repeatedly been associated with deficits in working memory, declarative memory, and executive functions. However, previous findings regarding working memory and executive function are inconclusive yet, as in most studies concomitant stimulant use, which is known to affect these functions, was not adequately controlled for. Therefore, we compared the cognitive performance of 26 stimulant-free and largely pure (primary) MDMA users, 25 stimulant-using polydrug MDMA users, and 56 MDMA/stimulant-naïve controls by applying a comprehensive neuropsychological test battery. Neuropsychological tests were grouped into four cognitive domains. Recent drug use was objectively quantified by 6-month hair analyses on 17 substances and metabolites. Considerably lower mean hair concentrations of stimulants (amphetamine, methamphetamine, methylphenidate, cocaine), opioids (morphine, methadone, codeine), and hallucinogens (ketamine, 2C-B) were detected in primary compared to polydrug users, while both user groups did not differ in their MDMA hair concentration. Cohen's d effect sizes for both comparisons, i.e., primary MDMA users vs. controls and polydrug MDMA users vs. controls, were highest for declarative memory (d primary =.90, d polydrug =1.21), followed by working memory (d primary =.52, d polydrug =.96), executive functions (d primary =.46, d polydrug =.86), and attention (d primary =.23, d polydrug =.70). Thus, primary MDMA users showed strong and relatively discrete declarative memory impairments, whereas MDMA polydrug users displayed broad and unspecific cognitive impairments. Consequently, even largely pure chronic MDMA use is associated with decreased performance in declarative memory, while additional deficits in working memory and executive functions displayed by polydrug MDMA users are likely driven by stimulant co-use. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Studies on cannabis. III. Young plants from the seed irradiated with /sup 60/Co gamma rays for inhibiting their development after seeding

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Shimomura, H; Kuriyama, E; Tomizawa, A [Tokyo Coll. of Pharmacy (Japan)

1976-01-01

The seedlings from Cannabis sativa L. seeds irradiated with different doses of ..gamma..-rays were examined, in order to determine the dose sufficient to kill the young plants naturally, before their hallucinnogenic component increases. The seeds of ''Minamioshihara No. 1'', which were harvested in 1972 in Tochigi Prefecture, were irradiated with eight different doses of /sup 60/Co ..gamma..-rays in January 17, 1973, and the seedlings were examined several times during the subsequent 9 months, from March to November 1973, and their morphological and histological effects were examined, and the results are summarized as follows: Samples irradiated with 1500 and 1000 krads developed radicles about 3 mm in length. Samples irradiated with 500, 200, and 50 krads grew into young plants with the first set of leaves, without lateral roots. Samples irradiated with 30 krads grew to about 10 cm high with a few lateral roots, and the epicotyls about 1 cm in length. These young plants from the irradiated seeds stayed in the same condition and then died. Samples irradiated with 15 and 5 krads grew in the same way as the controls until the stage of flowering. Samples irradiated with 500, 200, 50, and 30 krads showerd the cell membranes of endodermis and pericycle to be partially lignified and suberized. The degree of change was related to the dose of ..gamma..-rays. Samples irradiated with 30 krads showed withered cells near the end of the lateral nerves on the first and second set of leaves. The economical dose of /sup 60/Co ..gamma..-rays for inhibiting young plants from developing into adult ones was a minimum of 30 krads which made the young plants die. Irradiation with 50 krads of ..gamma..-rays will be required to kill the young plants completely before they develop the hallucinogenic component.

5-Hydroxytryptamine (serotonin)2A receptors in rat anterior cingulate cortex mediate the discriminative stimulus properties of d-lysergic acid diethylamide.

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Gresch, Paul J; Barrett, Robert J; Sanders-Bush, Elaine; Smith, Randy L

2007-02-01

d-Lysergic acid diethylamide (LSD), an indoleamine hallucinogen, produces profound alterations in mood, thought, and perception in humans. The brain site(s) that mediates the effects of LSD is currently unknown. In this study, we combine the drug discrimination paradigm with intracerebral microinjections to investigate the anatomical localization of the discriminative stimulus of LSD in rats. Based on our previous findings, we targeted the anterior cingulate cortex (ACC) to test its involvement in mediating the discriminative stimulus properties of LSD. Rats were trained to discriminate systemically administered LSD (0.085 mg/kg s.c.) from saline. Following acquisition of the discrimination, bilateral cannulae were implanted into the ACC (AP, +1.2 mm; ML, +/-1.0 mm; DV, -2.0 mm relative to bregma). Rats were tested for their ability to discriminate varying doses of locally infused LSD (0.1875, 0.375, and 0.75 microg/side) or artificial cerebrospinal fluid (n = 3-7). LSD locally infused into ACC dose-dependently substituted for systemically administered LSD, with 0.75 microg/side LSD substituting completely (89% correct). Systemic administration of the selective 5-hydroxytryptamine (serotonin) (5-HT)(2A) receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol (M100907; 0.4 mg/kg) blocked the discriminative cue of LSD (0.375 microg/side) infused into ACC (from 68 to 16% drug lever responding). Furthermore, M100907 (0.5 microg/microl/side) locally infused into ACC completely blocked the stimulus effects of systemic LSD (0.04 mg/kg; from 80 to 12% on the LSD lever). Taken together, these data indicate that 5-HT(2A) receptors in the ACC are a primary target mediating the discriminative stimulus properties of LSD.

Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera in healthy volunteers

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Ashwinikumar A Raut

2012-01-01

Full Text Available Ashwagandha (Withania somnifera (WS, a "rasayana" drug, is recommended for balavardhan and mamsavardhan. The study was intended to evaluate dose-related tolerability, safety, and activity of WS formulation in normal individuals. The design was prospective, open-labeled, variable doses in volunteers. Eighteen apparently healthy volunteers (12M:6F, age:18-30 years, and BMI: 19-30 were enrolled. After baseline investigations, they received WS capsules (Rx (aqueous extract, 8:1 daily in two divided doses with increase in daily dosage every 10 days for 30 days (750 mg/day x10 days, 1 000 mg/day x 10 days, 1 250 mg/day x 10 days. Volunteers were assessed for symptoms/signs, vital functions, hematological and biochemical organ function tests. Muscle activity was measured by hand grip strength, quadriceps strength, and back extensor force. Exercise tolerance was determined using cycle ergometry. Lean body weight and fat% were computed from skin fold thickness measurement. Adverse events were recorded, as volunteered by the subjects. Repeated measures ANOVA, McNemar′s test, and paired t test were employed. All but one volunteer tolerated WS without any adverse event. One volunteer showed increased appetite, libido, and hallucinogenic effects with vertigo at the lowest dose and was withdrawn from study. In six subjects, improvement in quality of sleep was found. Organ function tests were in normal range before and after the intervention. Reduction in total- and LDL- cholesterol and increase of strength in muscle activity was significant. Total body fat percentage showed a reduction trend. WS, in escalated dose, was tolerated well. The formulation appeared safe and strengthened muscle activity. In view of its traditional Rasayana use, further studies are planned to evaluate potential of this drug in patients of sarcopenia.

Noncompetitive inhibition of indolethylamine-N-methyltransferase by N,N-dimethyltryptamine and N,N-dimethylaminopropyltryptamine.

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Chu, Uyen B; Vorperian, Sevahn K; Satyshur, Kenneth; Eickstaedt, Kelsey; Cozzi, Nicholas V; Mavlyutov, Timur; Hajipour, Abdol R; Ruoho, Arnold E

2014-05-13

Indolethylamine-N-methyltransferase (INMT) is a Class 1 transmethylation enzyme known for its production of N,N-dimethyltryptamine (DMT), a hallucinogen with affinity for various serotonergic, adrenergic, histaminergic, dopaminergic, and sigma-1 receptors. DMT is produced via the action of INMT on the endogenous substrates tryptamine and S-adenosyl-l-methionine (SAM). The biological, biochemical, and selective small molecule regulation of INMT enzyme activity remain largely unknown. Kinetic mechanisms for inhibition of rabbit lung INMT (rabINMT) by the product, DMT, and by a new novel tryptamine derivative were determined. After Michaelis-Menten and Lineweaver-Burk analyses had been applied to study inhibition, DMT was found to be a mixed competitive and noncompetitive inhibitor when measured against tryptamine. The novel tryptamine derivative, N-[2-(1H-indol-3-yl)ethyl]-N',N'-dimethylpropane-1,3-diamine (propyl dimethyl amino tryptamine or PDAT), was shown to inhibit rabINMT by a pure noncompetitive mechanism when measured against tryptamine with a Ki of 84 μM. No inhibition by PDAT was observed at 2 mM when it was tested against structurally similar Class 1 methyltransferases, such as human phenylethanolamine-N-methyltransferase (hPNMT) and human nicotinamide-N-methyltransferase (hNNMT), indicating selectivity for INMT. The demonstration of noncompetitive mechanisms for INMT inhibition implies the presence of an inhibitory allosteric site. In silico analyses using the computer modeling software Autodock and the rabINMT sequence threaded onto the human INMT (hINMT) structure (Protein Data Bank entry 2A14 ) identified an N-terminal helix-loop-helix non-active site binding region of the enzyme. The energies for binding of DMT and PDAT to this region of rabINMT, as determined by Autodock, were -6.34 and -7.58 kcal/mol, respectively. Assessment of the allosteric control of INMT may illuminate new biochemical pathway(s) underlying the biology of INMT.

'Special K' and a Loss of Cell-To-Cell Adhesion in Proximal Tubule-Derived Epithelial Cells: Modulation of the Adherens Junction Complex by Ketamine

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Hills, Claire E.; Jin, Tianrong; Siamantouras, Eleftherios; Liu, Issac K-K; Jefferson, Kieran P.; Squires, Paul E.

2013-01-01

Ketamine, a mild hallucinogenic class C drug, is the fastest growing ‘party drug’ used by 16–24 year olds in the UK. As the recreational use of Ketamine increases we are beginning to see the signs of major renal and bladder complications. To date however, we know nothing of a role for Ketamine in modulating both structure and function of the human renal proximal tubule. In the current study we have used an established model cell line for human epithelial cells of the proximal tubule (HK2) to demonstrate that Ketamine evokes early changes in expression of proteins central to the adherens junction complex. Furthermore we use AFM single-cell force spectroscopy to assess if these changes functionally uncouple cells of the proximal tubule ahead of any overt loss in epithelial cell function. Our data suggests that Ketamine (24–48 hrs) produces gross changes in cell morphology and cytoskeletal architecture towards a fibrotic phenotype. These physical changes matched the concentration-dependent (0.1–1 mg/mL) cytotoxic effect of Ketamine and reflect a loss in expression of the key adherens junction proteins epithelial (E)- and neural (N)-cadherin and β-catenin. Down-regulation of protein expression does not involve the pro-fibrotic cytokine TGFβ, nor is it regulated by the usual increase in expression of Slug or Snail, the transcriptional regulators for E-cadherin. However, the loss in E-cadherin can be partially rescued pharmacologically by blocking p38 MAPK using SB203580. These data provide compelling evidence that Ketamine alters epithelial cell-to-cell adhesion and cell-coupling in the proximal kidney via a non-classical pro-fibrotic mechanism and the data provides the first indication that this illicit substance can have major implications on renal function. Understanding Ketamine-induced renal pathology may identify targets for future therapeutic intervention. PMID:24009666

Alterations of consciousness and mystical-type experiences after acute LSD in humans.

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Liechti, Matthias E; Dolder, Patrick C; Schmid, Yasmin

2017-05-01

Lysergic acid diethylamide (LSD) is used recreationally and in clinical research. Acute mystical-type experiences that are acutely induced by hallucinogens are thought to contribute to their potential therapeutic effects. However, no data have been reported on LSD-induced mystical experiences and their relationship to alterations of consciousness. Additionally, LSD dose- and concentration-response functions with regard to alterations of consciousness are lacking. We conducted two placebo-controlled, double-blind, cross-over studies using oral administration of 100 and 200 μg LSD in 24 and 16 subjects, respectively. Acute effects of LSD were assessed using the 5 Dimensions of Altered States of Consciousness (5D-ASC) scale after both doses and the Mystical Experience Questionnaire (MEQ) after 200 μg. On the MEQ, 200 μg LSD induced mystical experiences that were comparable to those in patients who underwent LSD-assisted psychotherapy but were fewer than those reported for psilocybin in healthy subjects or patients. On the 5D-ASC scale, LSD produced higher ratings of blissful state, insightfulness, and changed meaning of percepts after 200 μg compared with 100 μg. Plasma levels of LSD were not positively correlated with its effects, with the exception of ego dissolution at 100 μg. Mystical-type experiences were infrequent after LSD, possibly because of the set and setting used in the present study. LSD may produce greater or different alterations of consciousness at 200 μg (i.e., a dose that is currently used in psychotherapy in Switzerland) compared with 100 μg (i.e., a dose used in imaging studies). Ego dissolution may reflect plasma levels of LSD, whereas more robustly induced effects of LSD may not result in such associations.

Development and validation of an ultra-fast and sensitive microflow liquid chromatography-tandem mass spectrometry (MFLC-MS/MS) method for quantification of LSD and its metabolites in plasma and application to a controlled LSD administration study in humans.

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Steuer, Andrea E; Poetzsch, Michael; Stock, Lorena; Eisenbeiss, Lisa; Schmid, Yasmin; Liechti, Matthias E; Kraemer, Thomas

2017-05-01

Lysergic acid diethylamide (LSD) is a semi-synthetic hallucinogen that has gained popularity as a recreational drug and has been investigated as an adjunct to psychotherapy. Analysis of LSD represents a major challenge in forensic toxicology due to its instability, low drug concentrations, and short detection windows in biological samples. A new, fast, and sensitive microflow liquid chromatography (MFLC) tandem mass spectrometry method for the validated quantification of LSD, iso-LSD, 2-oxo 3-hydroxy-LSD (oxo-HO-LSD), and N-desmethyl-LSD (nor-LSD) was developed in plasma and applied to a controlled pharmacokinetic (PK) study in humans to test whether LSD metabolites would offer for longer detection windows. Five hundred microlitres of plasma were extracted by solid phase extraction. Analysis was performed on a Sciex Eksigent MFLC system coupled to a Sciex 5500 QTrap. The method was validated according to (inter)-national guidelines. MFLC allowed for separation of the mentioned analytes within 3 minutes and limits of quantification of 0.01 ng/mL. Validation criteria were fulfilled for all analytes. PK data could be calculated for LSD, iso-LSD, and oxo-HO-LSD in all participants. Additionally, hydroxy-LSD (HO-LSD) and HO-LSD glucuronide could be qualitatively detected and PK determined in 11 and 8 subjects, respectively. Nor-LSD was only sporadically detected. Elimination half-lives of iso-LSD (median 12 h) and LSD metabolites (median 9, 7.4, 12, and 11 h for oxo-HO-LSD, HO-LSD, HO-LSD-gluc, and nor-LSD, respectively) exceeded those of LSD (median 4.2 h). However, screening for metabolites to increase detection windows in plasma seems not to be constructive due to their very low concentrations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effects of chronic delta-9-tetrahydrocannabinol (THC) administration on neurotransmitter concentrations and receptor binding in the rat brain

International Nuclear Information System (INIS)

Ali, S.F.; Newport, G.D.; Scallet, A.C.; Gee, K.W.; Paule, M.G.; Brown, R.M.; Slikker, W. Jr.

1989-01-01

THC is the major psychoactive constituent of marijuana and is also known as an hallucinogenic compound. Numerous reports have shown that large doses of THC produce significant alterations in various neurotransmitter systems. The present study was designed to determine whether chronic exposure to THC produces significant alterations in selected neurotransmitter systems (dopamine, serotonin, acetylcholine, GABAergic, benzodiazepine, and opiate) in the rat brain. In Experiment 1, male Sprague-Dawley rats were gavaged with vehicle, 10 or 20 mg THC/kg body weight daily, 5 days/week for 90 days. Animals were killed either 24 hours or two months after the last dose. Brains were dissected into different regions for neurochemical analyses. Two months after the cessation of chronic administration, there was a significant decrease in GABA receptor binding in the hippocampus of animals in the high dose group. However, no other significant changes were found in neurotransmitter receptor binding characteristics in the hippocampus or in neurotransmitter concentrations in the caudate nucleus, hypothalamus or septum after chronic THC administration. In an attempt to replicate the GABA receptor binding changes and also to determine the [35S]TBPS binding in hippocampus, we designed Experiment 2. In this experiment, we dosed the animals by gavage with 0, 5, 10 or 20 mg THC/kg daily, 5 days/week or with 20 mg THC/kg Monday through Thursday and 60 mg/kg on Friday for 90 days. Results from this experiment failed to replicate the dose-dependent effect of THC on GABA receptor binding in hippocampus. Modulation of [35S]TBPS binding by GABA or 3 alpha-OH-DHP or inhibition by cold TBPS in frontal cortex did not show any significant dose-related effects

[3H]-DOB(4-bromo-2,5-dimethoxyphenylisopropylamine) and [3H] ketanserin label two affinity states of the cloned human 5-hydroxytryptamine2 receptor

International Nuclear Information System (INIS)

Branchek, T.; Adham, N.; Macchi, M.; Kao, H.T.; Hartig, P.R.

1990-01-01

The binding properties of the 5-hydroxytryptamine2 (5-HT2) receptor have been the subject of much interest and debate in recent years. The hallucinogenic amphetamine derivative 4-bromo-2,5-dimethoxyphenylisopropylamine (DOB) has been shown to bind to a small number of binding sites with properties very similar to [3H]ketanserin-labeled 5-HT2 receptors, but with much higher agonist affinities. Some researchers have interpreted this as evidence for the existence of a new subtype of 5-HT2 receptor (termed 5-HT2A), whereas others have interpreted these data as indicative of agonist high affinity and agonist low affinity states for the 5-HT2 receptor. In this investigation, a cDNA clone encoding the serotonin 5-HT2 receptor was transiently transfected into monkey kidney Cos-7 cells and stably transfected into mouse fibroblast L-M(TK-) cells. In both systems, expression of this single serotonin receptor cDNA led to the appearance of both [3H]DOB and [3H]ketanserin binding sites with properties that matched their binding characteristics in mammalian brain homogenates. Addition of guanosine 5'-(beta, gamma-imido) triphosphate [Gpp(NH)p] to this system caused a rightward shift and steepening of agonist competition curves for [3H] ketanserin binding, converting a two-site binding curve to a single low affinity binding state. Gpp(NH)p addition also caused a 50% decrease in the number of high affinity [3H]DOB binding sites, with no change in the dissociation constant of the remaining high affinity states. These data on a single human 5-HT2 receptor cDNA expressed in two different transfection host cells indicate that [3H]DOB and [3H]ketanserin binding reside on the same gene product, apparently interacting with agonist and antagonist conformations of a single human 5-HT2 receptor protein

Feeling unreal: a depersonalization disorder update of 117 cases.

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Simeon, Daphne; Knutelska, Margaret; Nelson, Dorothy; Guralnik, Orna

2003-09-01

Despite a surge of interest and literature on depersonalization disorder in recent years, a large series of individuals with the disorder has not been described to date. In this report, we systematically elucidate the phenomenology, precipitants, antecedents, comorbidity, and treatment history in such a series. 117 adult subjects with depersonalization disorder (DSM-III-R/DSM-IV criteria) consecutively recruited to a number of depersonalization disorder research studies were administered structured and semistructured diagnostic interviews and the Dissociative Experiences Scale. Data were gathered from 1994 to 2000. The illness had an approximately 1:1 gender ratio with onset around 16 years of age. The course was typically chronic and often continuous. Illness characteristics such as onset, duration, and course were not associated with symptom severity. Mood, anxiety, and personality disorders were frequently comorbid, but none predicted depersonalization severity. The most common immediate precipitants of the disorder were severe stress, depression, panic, marijuana ingestion, and hallucinogen ingestion, and none of these predicted symptom severity. Negative affects, stress, perceived threatening social interaction, and unfamiliar environments were some of the more common factors leading to symptom exacerbation. Conversely, comforting interpersonal interactions, intense emotional or physical stimulation, and relaxation tended to diminish symptom intensity. There were no significant gender differences in the clinical features of the disorder. In this sample, depersonalization tended to be refractory to various medication and psychotherapy treatments. The characteristics of depersonalization disorder found in this sample, the largest described to date, are in good accord with previous literature. The study highlights the need for novel therapeutic approaches to treat depersonalization disorder. Novel medication classes, as well as novel psychotherapeutic techniques

Evaluating drug trafficking on the Tor Network: Silk Road 2, the sequel.

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Dolliver, Diana S

2015-11-01

Housing an illicit, online drug retail market generating sales in the millions of USD, the Silk Road was a profitable marketplace with a growing and loyal consumer base. Following its FBI-forced shut down in October 2013, the Silk Road enjoyed newfound fame that contributed to an increase in new users downloading and accessing the Tor Network; however, with this particular marketplace out of order, Silk Road 2 was launched to fill the void. The goals of this study were to (1) compare the metrics of Silk Road 2 to the original site, and to (2) determine if there were any indications of the presence of more sophisticated drug trafficking operations. Data were collected from Silk Road 2 during the months of August and September 2014 using webcrawling software. Silk Road 2 was a much smaller marketplace than the original Silk Road. Of the 1834 unique items for sale, 348 were drug items sold by 145 distinct vendors shipping from 19 countries. Of the drug items advertised, most were stimulants and hallucinogens. The United States is both the number one country of origin for drug sales on Silk Road 2 and the number one destination country. Interestingly, 73% of all vendor accounts on Silk Road 2 advertised drug items, even though drugs only constituted 19% of all items advertised. This study was the first to research Silk Road 2, the replacement illicit marketplace to the original virtual Silk Road. This study was also the first to examine indications of the presence of more coordinated drug trafficking efforts in an online setting. The findings indicated that while Silk Road 2 was not primarily a drug market, there were indications that some vendor accounts may have connections reaching beyond a base retail market. Copyright © 2015 Elsevier B.V. All rights reserved.

Contamination profiles, mass loadings, and sewage epidemiology of neuropsychiatric and illicit drugs in wastewater and river waters from a community in the Midwestern United States.

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Skees, Allie J; Foppe, Katelyn S; Loganathan, Bommanna; Subedi, Bikram

2018-08-01

In this study, residues of the neuropsychiatric and illicit drugs including stimulants, opioids, hallucinogens, antischizophrenics, sedatives, and antidepressants were determined in influent and effluent samples from a small wastewater treatment plant, a receiving creek, and river waters in the Four Rivers region of the Midwestern United States. Nineteen neuropsychiatric drugs, eight illicit drugs, and three metabolites of illicit drugs were detected and quantitated in the water samples using HPLC-MS/MS. Residual concentrations of the drugs varied from below the detection limit to sub-μg/L levels. The source of residual cocaine and benzoylecgonine in wastewater is primarily from human consumption of cocaine rather than direct disposal. Wastewater based epidemiology is utilized to estimate the community usage of drugs based on the concentration of drug residues in wastewater, wastewater inflow, and the population served by the centralized wastewater treatment plant. The per-capita consumption rate of methamphetamine (1740 mg/d/1000 people) and amphetamine (970 mg/d/1000 people) found in this study were the highest reported per-capita consumption rates in the USA. Antidepressant venlafaxine found to have the highest environmental emission from the WWTP (333 ± 160 mg/d/1000 people) followed by citalopram (132 ± 60.2 mg/d/1000 people), methamphetamine (111 ± 43.6 mg/d/1000 people), and hydrocodone (108 ± 90.1 mg/d/1000 people). Bee Creek, an immediate receiving water body, is found to be a source of several neuropsychiatric and illicit drugs including methamphetamine, methadone, alprazolam, oxazepam, temazepam, carbamazepine, venlafaxine, citalopram, sertraline, oxycodone, and hydrocodone (p < 0.036) in the Clarks River. Copyright © 2018 Elsevier B.V. All rights reserved.

William James, Gustav Fechner, and Early Psychophysics

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Stephanie L. Hawkins

2011-10-01

Full Text Available American psychologist and philosopher William James devoted the entirety of his career to exploring the nature of volition, as expressed by such phenomena as will, attention, and belief. As part of that endeavor, James's unorthodox scientific pursuits, from his experiments with nitrous oxide and hallucinogenic drugs to his investigation of spiritualist mediums, represent his attempt to address the "hard problems" of consciousness for which his training in brain physiology and experimental psychology could not entirely account. As a student, James's reading in chemistry and physics had sparked his interest in the concepts of energy and force, terms that he later deployed in his writing about consciousness and in his arguments against philosophical monism and scientific materialism, as he developed his radically empiricist ideas privileging discontinuity and plurality. Despite James's long campaign against scientific materialism, he was, however, convinced of the existence of a naturalistic explanation for the more "wayward and fitful" aspects of mind, including transcendent experiences associated with hysteria, genius, and religious ecstasy. In this paper, I examine aspects of James's thought that are still important for contemporary debates in psychology and neuroscience: his "transmission theory" of consciousness, his ideas on the "knowing of things together," and, finally, the related concept of "the compounding of consciousness," which postulates the theoretical possibility for individual entities within a conscious system of thought to "know" the thoughts of others within the system. Taken together, these ideas suggest that James, in spite of, or perhaps because of, his forays into metaphysics, was working toward a naturalistic understanding of consciousness, what I will term a "distributive model," based on his understanding of consciousness as an "awareness" that interacts dynamically within, and in relation to, its environment.

Recreational nitrous oxide use: Prevalence and risks.

Science.gov (United States)

van Amsterdam, Jan; Nabben, Ton; van den Brink, Wim

2015-12-01

Nitrous oxide (N2O; laughing gas) is clinically used as a safe anesthetic (dentistry, ambulance, childbirth) and appreciated for its anti-anxiety effect. Since five years, recreational use of N2O is rapidly increasing especially in the dance and festival scene. In the UK, N2O is the second most popular recreational drug after cannabis. In most countries, nitrous oxide is a legal drug that is widely available and cheap. Last month prevalence of use among clubbers and ravers ranges between 40 and almost 80 percent. Following one inhalation, mostly from a balloon, a euphoric, pleasant, joyful, empathogenic and sometimes hallucinogenic effect is rapidly induced (within 10 s) and disappears within some minutes. Recreational N2O use is generally moderate with most users taking less than 10 balloons of N2O per episode and about 80% of the users having less than 10 episodes per year. Side effects of N2O include transient dizziness, dissociation, disorientation, loss of balance, impaired memory and cognition, and weakness in the legs. When intoxicated accidents like tripping and falling may occur. Some fatal accidents have been reported due to due to asphyxia (hypoxia). Heavy or sustained use of N2O inactivates vitamin B12, resulting in a functional vitamin B12 deficiency and initially causing numbness in fingers, which may further progress to peripheral neuropathy and megaloblastic anemia. N2O use does not seem to result in dependence. Considering the generally modest use of N2O and its relative safety, it is not necessary to take legal measures. However, (potential) users should be informed about the risk of vitamin B12-deficiency related neurological and hematological effects associated with heavy use. Copyright © 2015 Elsevier Inc. All rights reserved.

Visualisation of serotonin-1A (5-HT{sub 1A}) receptors in the central nervous system

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Passchier, J.; Waarde, A. van [PET Center, University Hospital Groningen (Netherlands)

2001-01-01

The 5-HT{sub 1A} subtype of receptors for the neurotransmitter serotonin is predominantly located in the limbic forebrain and is involved in the modulation of emotion and the function of the hypothalamus. Since 5-HT{sub 1A} receptors are implicated in the pathogenesis of anxiety, depression, hallucinogenic behaviour, motion sickness and eating disorders, they are an important target for drug therapy. Here, we review the radioligands which are available for visualisation and quantification of this important neuroreceptor in the human brain, using positron emission tomography (PET) or single-photon emission tomography (SPET). More than 20 compounds have been labelled with carbon-11 (half-life 20 min), fluorine-18 (half-life 109.8 min) or iodine-123 (half-life 13.2 h): structural analogues of the agonist, 8-OH-DPAT, structural analogues of the antagonist, WAY 100635, and apomorphines. The most successful radioligands thus far are [carbonyl-{sup 11}C] WAY-100635 (WAY), [carbonyl-{sup 11}C]desmethyl-WAY-100635 (DWAY), p-[{sup 18}F]MPPF and [{sup 11}C]robalzotan (NAD-299). The high-affinity ligands WAY and DWAY produce excellent images of 5-HT{sub 1A} receptor distribution in the brain (even the raphe nuclei are visualised), but they cannot be distributed to remote facilities and they probably cannot be used to measure changes in endogenous serotonin. Binding of the moderate-affinity ligands MPPF and NAD-299 may be more sensitive to serotonin competition and MPPF can be distributed to PET centres within a flying distance of a few hours. Future research should be directed towards: (a) improvement of the metabolic stability in primates; (b) development of a fluorinated radioligand which can be produced in large quantities and (c) production of a radioiodinated or technetium-labelled ligand for SPET. (orig.)

Visualisation of serotonin-1A (5-HT1A) receptors in the central nervous system

International Nuclear Information System (INIS)

Passchier, J.; Waarde, A. van

2001-01-01

The 5-HT 1A subtype of receptors for the neurotransmitter serotonin is predominantly located in the limbic forebrain and is involved in the modulation of emotion and the function of the hypothalamus. Since 5-HT 1A receptors are implicated in the pathogenesis of anxiety, depression, hallucinogenic behaviour, motion sickness and eating disorders, they are an important target for drug therapy. Here, we review the radioligands which are available for visualisation and quantification of this important neuroreceptor in the human brain, using positron emission tomography (PET) or single-photon emission tomography (SPET). More than 20 compounds have been labelled with carbon-11 (half-life 20 min), fluorine-18 (half-life 109.8 min) or iodine-123 (half-life 13.2 h): structural analogues of the agonist, 8-OH-DPAT, structural analogues of the antagonist, WAY 100635, and apomorphines. The most successful radioligands thus far are [carbonyl- 11 C] WAY-100635 (WAY), [carbonyl- 11 C]desmethyl-WAY-100635 (DWAY), p-[ 18 F]MPPF and [ 11 C]robalzotan (NAD-299). The high-affinity ligands WAY and DWAY produce excellent images of 5-HT 1A receptor distribution in the brain (even the raphe nuclei are visualised), but they cannot be distributed to remote facilities and they probably cannot be used to measure changes in endogenous serotonin. Binding of the moderate-affinity ligands MPPF and NAD-299 may be more sensitive to serotonin competition and MPPF can be distributed to PET centres within a flying distance of a few hours. Future research should be directed towards: (a) improvement of the metabolic stability in primates; (b) development of a fluorinated radioligand which can be produced in large quantities and (c) production of a radioiodinated or technetium-labelled ligand for SPET. (orig.)

Acute Pharmacological Effects of 2C-B in Humans: An Observational Study

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Esther Papaseit

2018-03-01

Full Text Available 2,5-dimethoxy-4-bromophenethylamine (2C-B is a psychedelic phenylethylamine derivative, structurally similar to mescaline. It is a serotonin 5-hydroxytryptamine-2A (5-HT2A, 5-hydroxytryptamine-2B (5-HT2B, and 5-hydroxytryptamine-2C (5-HT2C receptor partial agonist used recreationally as a new psychoactive substance. It has been reported that 2C-B induces mild psychedelic effects, although its acute pharmacological effects and pharmacokinetics have not yet been fully studied in humans. An observational study was conducted to assess the acute subjective and physiological effects, as well as pharmacokinetics of 2C-B. Sixteen healthy, experienced drug users self-administered an oral dose of 2C-B (10, 15, or 20 mg. Vital signs (blood pressure and heart rate were measured at baseline 1, 2, 3, 4, and 6 hours (h. Each participant completed subjective effects using three rating scales: the visual analog scale (VAS, the Addiction Research Centre Inventory (ARCI, and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE at baseline, 2–3 and 6 h after self-administration (maximum effects along 6 h, and the Hallucinogenic Rating Scale (maximum effects along 6 h. Oral fluid (saliva was collected to assess 2C-B and cortisol concentrations during 24 h. Acute administration of 2C-B increased blood pressure and heart rate. Scores of scales related to euphoria increased (high, liking, and stimulated, and changes in perceptions (distances, colors, shapes, and lights and different body feelings/surrounding were produced. Mild hallucinating effects were described in five subjects. Maximum concentrations of 2C-B and cortisol were reached at 1 and 3 h after self-administration, respectively. Oral 2C-B at recreational doses induces a constellation of psychedelic/psychostimulant-like effects similar to those associated with serotonin-acting drugs.

Antidepressant effects of ketamine: mechanisms underlying fast-acting novel antidepressants

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Caroline Ann Browne

2013-12-01

Full Text Available Newer antidepressants are needed for the many individuals with major depressive disorder that do not respond adequately to treatment and because of a delay of weeks before the emergence of therapeutic effects. Recent evidence from clinical trials shows that the NMDA antagonist ketamine is a revolutionary novel antidepressant because it acts rapidly and is effective for treatment-resistant patients. A single infusion of ketamine alleviates depressive symptoms in treatment-resistant depressed patients within hours and these effects may be sustained for up to 2 weeks. Although the discovery of ketamine’s effects has reshaped drug discovery for antidepressants, the psychotomimetic properties of this compound limit the use of this therapy to the most severely ill patients. In order to develop additional antidepressants like ketamine, adequate preclinical behavioral screening paradigms for fast-acting antidepressants need to be established and used to identify the underlying neural mechanisms. This review examines the preclinical literature attempting to model the antidepressant-like effects of ketamine. Acute administration of ketamine has produced effects in behavioral screens for antidepressants like the forced swim test, novelty suppression of feeding and in rodent models for depression. Protracted behavioral effects of ketamine have been reported to appear after a single treatment that last for days. This temporal pattern is similar to its clinical effects and may serve as a new animal paradigm for rapid antidepressant effects in humans. In addition, protracted changes in molecules mediating synaptic plasticity have been implicated in mediating the antidepressant-like behavioral effects of ketamine. Current preclinical studies are examining compounds with more specific pharmacological effects at glutamate receptors and synapses in order to develop additional rapidly acting antidepressants without the hallucinogenic side effects or abuse

Pill testing or drug checking in Australia: Acceptability of service design features.

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Barratt, Monica J; Bruno, Raimondo; Ezard, Nadine; Ritter, Alison

2018-02-01

This study aimed to determine design features of a drug-checking service that would be feasible, attractive and likely to be used by Australian festival and nightlife attendees. Web survey of 851 Australians reporting use of psychostimulants and/or hallucinogens and attendance at licensed venues past midnight and/or festivals in the past year (70% male; median age 23 years). A drug-checking service located at festivals or clubs would be used by 94%; a fixed-site service external to such events by 85%. Most (80%) were willing to wait an hour for their result. Almost all (94%) would not use a service if there was a possibility of arrest, and a majority (64%) would not use a service that did not provide individual feedback of results. Drug-checking results were only slightly more attractive if they provided comprehensive quantitative results compared with qualitative results of key ingredients. Most (93%) were willing to pay up to $5, and 68% up to $10, per test. One-third (33%) reported willingness to donate a whole dose for testing: they were more likely to be male, younger, less experienced, use drugs more frequently and attend venues/festivals less frequently. In this sample, festival- or club-based drug-checking services with low wait times and low cost appear broadly attractive under conditions of legal amnesty and individualised feedback. Quantitative analysis of ecstasy pills requiring surrender of a whole pill may appeal to a minority in Australia where pills are more expensive than elsewhere. [Barratt MJ, Bruno R, Ezard N, Ritter A. Pill testing or drug checking in Australia: Acceptability of service design features. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.