Cannabinoid exposure during zebra finch sensorimotor vocal learning persistently alters expression of endocannabinoid signaling elements and acute agonist responsiveness

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Lichtman Aron H

2011-01-01

Full Text Available Abstract Background Previously we have found that cannabinoid treatment of zebra finches during sensorimotor stages of vocal development alters song patterns produced in adulthood. Such persistently altered behavior must be attributable to changes in physiological substrates responsible for song. We are currently working to identify the nature of such physiological changes, and to understand how they contribute to altered vocal learning. One possibility is that developmental agonist exposure results in altered expression of elements of endocannabinoid signaling systems. To test this hypothesis we have studied effects of the potent cannabinoid receptor agonist WIN55212-2 (WIN on endocannabinoid levels and densities of CB1 immunostaining in zebra finch brain. Results We found that late postnatal WIN treatment caused a long-term global disregulation of both levels of the endocannabinoid, 2-arachidonyl glycerol (2-AG and densities of CB1 immunostaining across brain regions, while repeated cannabinoid treatment in adults produced few long-term changes in the endogenous cannabinoid system. Conclusions Our findings indicate that the zebra finch endocannabinoid system is particularly sensitive to exogenous agonist exposure during the critical period of song learning and provide insight into susceptible brain areas.

Cannabinoid Receptor 1 Gene Polymorphisms and Marijuana Misuse Interactions On White Matter and Cognitive Deficits in Schizophrenia

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Ho, Beng-Choon; Wassink, Thomas H.; Ziebell, Steven; Andreasen, Nancy C.

2011-01-01

Marijuana exposure during the critical period of adolescent brain maturation may disrupt neuro-modulatory influences of endocannabinoids and increase schizophrenia susceptibility. Cannabinoid receptor 1 (CB1/CNR1) is the principal brain receptor mediating marijuana effects. No study to-date has systematically investigated the impact of CNR1 on quantitative phenotypic features in schizophrenia and inter-relationships with marijuana misuse. We genotyped 235 schizophrenia patients using 12 tag s...

Cannabinoid-induced conditioned place preference in the spontaneously hypertensive rat-an animal model of attention deficit hyperactivity disorder.

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Pandolfo, Pablo; Vendruscolo, Leandro F; Sordi, Regina; Takahashi, Reinaldo N

2009-08-01

Cannabis preparations are the most widely consumed illicit drugs, and their use typically begins in adolescence. The prevalence of cannabis abuse is higher in patients with attention deficit/hyperactivity disorder (ADHD) than in the general population, yet, knowledge about the motivational properties of cannabinoids in animal models of ADHD are lacking. To compare the motivational effects of the synthetic cannabinoid agonist WIN55,212-2 (WIN) in adolescent and adult spontaneously hypertensive rats (SHR), a validated animal model of ADHD, and Wistar rats, representing a "normal" genetically heterogeneous population. We also asked whether the effects of WIN depended (1) on the activation of the cerebral subtype of cannabinoid receptors, namely, the CB(1) cannabinoid receptor and (2) on putative changes by WIN in blood pressure. WIN was tested under an unbiased conditioned place preference (CPP) paradigm. Blood pressure after WIN administration was also monitored in additional groups of rats. In the Wistar rats, WIN produced place aversion only in the adult but not adolescent rats. In contrast, WIN produced CPP in both adolescent and adult SHR rats. The behavioral effects of WIN were CB(1)-mediated and not related to blood pressure. The contrasting effects of WIN in Wistar and SHR, and the higher resistance of adolescent rats to the aversive and rewarding effects of WIN in these two strains suggests that both adolescence and the ADHD-like profile exhibited by the SHR strain constitute factors that influence the motivational properties of cannabinoids.

Synthetic Cannabinoids

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Aslihan Okan Ibiloglu

2017-09-01

Full Text Available Synthetic cannabinoids which is a subgroup of cannabinoids are commonly used for recreational drug use throughout the whole world. Although both marijuana and synthetic cannabinoids stimulate the same receptors, cannabinoid receptor 1 (CB1 and cannabinoid receptor 2 (CB2, studies have shown that synthetic cannabinoids are much more potent than marijuana. The longer use of synthetic cannabinoids can cause severe physical and psychological symptoms that might even result in death, similar to many known illicit drugs. Main treatment options mostly involve symptom management and supportive care. The aim of this article is to discuss clinical and pharmacological properties of the increasingly used synthetic cannabinoids. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2017; 9(3.000: 317-328

Early cannabinoid exposure influences neuroendocrine and reproductive functions in male mice: I. Prenatal exposure.

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Dalterio, S; Steger, R; Mayfield, D; Bartke, A

1984-01-01

Maternal exposure to delta 9-tetrahydrocannabinol (THC), the major psychoactive constituent in marihuana, or to the non-psychoactive cannabinol (CBN) or cannabidiol (CBD) alters endocrine functions and concentrations of brain biogenic amines in their male offspring. Prenatal CBN exposure on day 18 of gestation resulted in decreased plasma FSH levels, testicular testosterone (T) concentrations, and seminal vesicles weights, but increased plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) post-castration in adulthood. Prenatal exposure to THC significantly enhanced the responsiveness of the testes to intratesticular LH injection in vivo and tended to increase human chorionic gonadotropin (hCG)-stimulated T production by decapsulated testes in vitro. In the CBN-exposed mice, hCG-stimulated T production was enhanced, while CBD exposure had no effect. Prenatal THC exposure altered the negative feedback effects of exogenous gonadal steroids in castrated adults, with lower plasma T and FSH levels after 20 micrograms T than in castrated controls. In contrast, CBD-exposed mice had higher levels of LH in plasma post-castration. In CBN-exposed adults, two weeks post-castration the concentration of norepinephrine (NE) and dopamine (DA) in hypothalamus and remaining brain were reduced, while levels of serotonin (5-HT) and its metabolite, 5-HIAA, were elevated compared to that in castrated OIL-controls. Prenatal CBD-exposure also reduced NE and elevated 5-HT and 5-HIAA, but did not affect DA levels post-castration. Concentrations of brain biogenic amines were not influenced by prenatal THC exposure in the present study. A single prenatal exposure to psychoactive or non-psychoactive components of marihuana results in long term alterations in the function of the hypothalamo-pituitary-gonadal axis. Changes in the concentrations of brain biogenic amines may be related to these effects of prenatal cannabinoids on endocrine function in adult male mice.

The Endocannabinoid System, Aggression, and the Violence of Synthetic Cannabinoid Use, Borderline Personality Disorder, Antisocial Personality Disorder, and Other Psychiatric Disorders.

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Kolla, Nathan J; Mishra, Achal

2018-01-01

Endogenous and exogenous cannabinoids bind to central cannabinoid receptors to control a multitude of behavioral functions, including aggression. The first main objective of this review is to dissect components of the endocannabinoid system, including cannabinoid 1 and cannabinoid 2 receptors; the endogenous cannabinoids anandamide and 2-arachidonoylglycerol; and the indirect cannabinoid modulators fatty acid amide hydrolase and monoacylglycerol lipase; that have shown abnormalities in basic research studies investigating mechanisms of aggression. While most human research has concluded that the active ingredient of marijuana, Δ9-tetrahydrocannabinol, tends to dampen rather than provoke aggression in acute doses, recent evidence supports a relationship between the ingestion of synthetic cannabinoids and emergence of violent or aggressive behavior. Thus, another objective is to evaluate the emerging clinical data. This paper also discusses the relationship between prenatal and perinatal exposure to cannabis as well as use of cannabis in adolescence on aggressive outcomes. A final objective of the paper is to discuss endocannabinoid abnormalities in psychotic and affective disorders, as well as clinically aggressive populations, such as borderline personality disorder and antisocial personality disorder. With regard to the former condition, decreased anandamide metabolites have been reported in the cerebrospinal fluid, while some preliminary evidence suggests that fatty acid amide hydrolase genetic polymorphisms are linked to antisocial personality disorder and impulsive-antisocial psychopathic traits. To summarize, this paper will draw upon basic and clinical research to explain how the endocannabinoid system may contribute to the genesis of aggressive behavior.

The Endocannabinoid System, Aggression, and the Violence of Synthetic Cannabinoid Use, Borderline Personality Disorder, Antisocial Personality Disorder, and Other Psychiatric Disorders

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Nathan J. Kolla

2018-03-01

Full Text Available Endogenous and exogenous cannabinoids bind to central cannabinoid receptors to control a multitude of behavioral functions, including aggression. The first main objective of this review is to dissect components of the endocannabinoid system, including cannabinoid 1 and cannabinoid 2 receptors; the endogenous cannabinoids anandamide and 2-arachidonoylglycerol; and the indirect cannabinoid modulators fatty acid amide hydrolase and monoacylglycerol lipase; that have shown abnormalities in basic research studies investigating mechanisms of aggression. While most human research has concluded that the active ingredient of marijuana, Δ9-tetrahydrocannabinol, tends to dampen rather than provoke aggression in acute doses, recent evidence supports a relationship between the ingestion of synthetic cannabinoids and emergence of violent or aggressive behavior. Thus, another objective is to evaluate the emerging clinical data. This paper also discusses the relationship between prenatal and perinatal exposure to cannabis as well as use of cannabis in adolescence on aggressive outcomes. A final objective of the paper is to discuss endocannabinoid abnormalities in psychotic and affective disorders, as well as clinically aggressive populations, such as borderline personality disorder and antisocial personality disorder. With regard to the former condition, decreased anandamide metabolites have been reported in the cerebrospinal fluid, while some preliminary evidence suggests that fatty acid amide hydrolase genetic polymorphisms are linked to antisocial personality disorder and impulsive-antisocial psychopathic traits. To summarize, this paper will draw upon basic and clinical research to explain how the endocannabinoid system may contribute to the genesis of aggressive behavior.

Synaptic neurotransmission depression in ventral tegmental dopamine neurons and cannabinoid-associated addictive learning.

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Liu, Zhiqiang; Han, Jing; Jia, Lintao; Maillet, Jean-Christian; Bai, Guang; Xu, Lin; Jia, Zhengping; Zheng, Qiaohua; Zhang, Wandong; Monette, Robert; Merali, Zul; Zhu, Zhou; Wang, Wei; Ren, Wei; Zhang, Xia

2010-12-20

Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses) of the midbrain ventral tegmental area (VTA) following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids), the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction.

Synaptic neurotransmission depression in ventral tegmental dopamine neurons and cannabinoid-associated addictive learning.

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Zhiqiang Liu

2010-12-01

Full Text Available Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP and long-term depression (LTD. Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses of the midbrain ventral tegmental area (VTA following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids, the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction.

Synaptic Neurotransmission Depression in Ventral Tegmental Dopamine Neurons and Cannabinoid-Associated Addictive Learning

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Liu, Zhiqiang; Han, Jing; Jia, Lintao; Maillet, Jean-Christian; Bai, Guang; Xu, Lin; Jia, Zhengping; Zheng, Qiaohua; Zhang, Wandong; Monette, Robert; Merali, Zul; Zhu, Zhou; Wang, Wei; Ren, Wei; Zhang, Xia

2010-01-01

Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses) of the midbrain ventral tegmental area (VTA) following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids), the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction. PMID:21187978

The role of the cannabinoid receptor in adolescents' processing of facial expressions.

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Ewald, Anais; Becker, Susanne; Heinrich, Angela; Banaschewski, Tobias; Poustka, Luise; Bokde, Arun; Büchel, Christian; Bromberg, Uli; Cattrell, Anna; Conrod, Patricia; Desrivières, Sylvane; Frouin, Vincent; Papadopoulos-Orfanos, Dimitri; Gallinat, Jürgen; Garavan, Hugh; Heinz, Andreas; Walter, Henrik; Ittermann, Bernd; Gowland, Penny; Paus, Tomáš; Martinot, Jean-Luc; Paillère Martinot, Marie-Laure; Smolka, Michael N; Vetter, Nora; Whelan, Rob; Schumann, Gunter; Flor, Herta; Nees, Frauke

2016-01-01

The processing of emotional faces is an important prerequisite for adequate social interactions in daily life, and might thus specifically be altered in adolescence, a period marked by significant changes in social emotional processing. Previous research has shown that the cannabinoid receptor CB1R is associated with longer gaze duration and increased brain responses in the striatum to happy faces in adults, yet, for adolescents, it is not clear whether an association between CBR1 and face processing exists. In the present study we investigated genetic effects of the two CB1R polymorphisms, rs1049353 and rs806377, on the processing of emotional faces in healthy adolescents. They participated in functional magnetic resonance imaging during a Faces Task, watching blocks of video clips with angry and neutral facial expressions, and completed a Morphed Faces Task in the laboratory where they looked at different facial expressions that switched from anger to fear or sadness or from happiness to fear or sadness, and labelled them according to these four emotional expressions. A-allele versus GG-carriers in rs1049353 displayed earlier recognition of facial expressions changing from anger to sadness or fear, but not for expressions changing from happiness to sadness or fear, and higher brain responses to angry, but not neutral, faces in the amygdala and insula. For rs806377 no significant effects emerged. This suggests that rs1049353 is involved in the processing of negative facial expressions with relation to anger in adolescence. These findings add to our understanding of social emotion-related mechanisms in this life period. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Cannabinoid mitigation of neuronal morphological change important to development and learning: insight from a zebra finch model of psychopharmacology.

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Soderstrom, Ken; Gilbert, Marcoita T

2013-03-19

Normal CNS development proceeds through late-postnatal stages of adolescent development. The activity-dependence of this development underscores the significance of CNS-active drug exposure prior to completion of brain maturation. Exogenous modulation of signaling important in regulating normal development is of particular concern. This mini-review presents a summary of the accumulated behavioral, physiological and biochemical evidence supporting such a key regulatory role for endocannabinoid signaling during late-postnatal CNS development. Our focus is on the data obtained using a unique zebra finch model of developmental psychopharmacology. This animal has allowed investigation of neuronal morphological effects essential to establishment and maintenance of neural circuitry, including processes related to synaptogenesis and dendritic spine dynamics. Altered neurophysiology that follows exogenous cannabinoid exposure during adolescent development has the potential to persistently alter cognition, learning and memory. Copyright © 2012 Elsevier Inc. All rights reserved.

Cannabinoids and Pain

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J Michael Walker

2001-01-01

Full Text Available Cannabinoids have been used to treat pain for many centuries. However, only during the past several decades have rigorous scientific methods been applied to understand the mechanisms of cannabinoid action. Cannabinoid receptors were discovered in the late 1980s and have been found to mediate the effects of cannabinoids on the nervous system. Several endocannabinoids were subsequently identified. Many studies of cannabinoid analgesia in animals during the past century showed that cannabinoids block all types of pain studied. These effects were found to be due to the suppression of spinal and thalamic nociceptive neurons, independent of any actions on the motor systems. Spinal, supraspinal and peripheral sites of cannabinoid analgesia have been identified. Endocannabinoids are released upon electrical stimulation of the periaqueductal gray, and in response to inflammation in the extremities. These observations and others thus suggest that a natural function of cannabinoid receptors and their endogenous ligands is to regulate pain sensitivity. The therapeutic potential of cannabinoids remains an important topic for future investigations, with previous work suggesting utility in clinical studies of cancer and surgical pain. New modes of delivery and/or new compounds lacking the psychotropic properties of the standard cannabinoid ligands offer promise for cannabinoid therapeutics for pain.

Safety Issues Concerning the Medical Use of Cannabis and Cannabinoids

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Mark A Ware

2005-01-01

Full Text Available Safety issues are a major barrier to the use of cannabis and cannabinoid medications for clinical purposes. Information on the safety of herbal cannabis may be derived from studies of recreational cannabis use, but cannabis exposure and effects may differ widely between medical and recreational cannabis users. Standardized, quality-controlled cannabinoid products are available in Canada, and safety profiles of approved medications are available through the Canadian formulary. In the present article, the evidence behind major safety issues related to cannabis use is summarized, with the aim of promoting informed dialogue between physicians and patients in whom cannabinoid therapy is being considered. Caution is advised in interpreting these data, because clinical experience with cannabinoid use is in the early stages. There is a need for long-term safety monitoring of patients using cannabinoids for a wide variety of conditions, to further guide therapeutic decisions and public policy.

Novel molecular changes induced by Nrg1 hypomorphism and Nrg1-cannabinoid interaction in adolescence: a hippocampal proteomic study in mice.

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Jarrah R Spencer

2013-02-01

Full Text Available Neuregulin 1 (NRG1 is linked to an increased risk of developing schizophrenia and cannabis dependence. Mice that are hypomorphic for Nrg1 (Nrg1 HET mice display schizophrenia-relevant behavioural phenotypes and aberrant expression of serotonin and glutamate receptors. Nrg1 HET mice also display idiosyncratic responses to the main psychoactive constituent of cannabis, Δ9-tetrahydrocannabinol (THC. To gain traction on the molecular pathways disrupted by Nrg1 hypomorphism and Nrg1-cannabinoid interactions we conducted a proteomic study. Adolescent wildtype (WT and Nrg1 HET mice were exposed to repeated injections of vehicle or THC and their hippocampi were submitted to 2D gel proteomics. Comparison of WT and Nrg1 HET mice identified proteins linked to molecular changes in schizophrenia that have not been previously associated with Nrg1. These proteins are involved in vesicular release of neurotransmitters such as SNARE proteins; enzymes impacting serotonergic neurotransmission, and; proteins affecting growth factor expression. Nrg1 HET mice treated with THC expressed a distinct protein expression signature compared to WT mice. Replicating prior findings, THC caused proteomic changes in WT mice suggestive of greater oxidative stress and neurodegeneration. We have previously observed that THC selectively increased hippocampal NMDA receptor binding of adolescent Nrg1 HET mice. Here we observed outcomes consistent with heightened NMDA-mediated glutamatergic neurotransmission. This included differential expression of proteins involved in NMDA receptor trafficking to the synaptic membrane; lipid raft stabilization of synaptic NMDA receptors; and homeostatic responses to dampen excitotoxicity. These findings uncover for the first time novel proteins altered in response to Nrg1 hypomorphism and Nrg1-cannabinoid interactions that improves our molecular understanding of Nrg1 signaling and Nrg1-mediated genetic vulnerability to the neurobehavioural effects

The influence of cannabinoids on learning and memory processes of the dorsal striatum.

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Goodman, Jarid; Packard, Mark G

2015-11-01

Extensive evidence indicates that the mammalian endocannabinoid system plays an integral role in learning and memory. Our understanding of how cannabinoids influence memory comes predominantly from studies examining cognitive and emotional memory systems mediated by the hippocampus and amygdala, respectively. However, recent evidence suggests that cannabinoids also affect habit or stimulus-response (S-R) memory mediated by the dorsal striatum. Studies implementing a variety of maze tasks in rats indicate that systemic or intra-dorsolateral striatum infusions of cannabinoid receptor agonists or antagonists impair habit memory. In mice, cannabinoid 1 (CB1) receptor knockdown can enhance or impair habit formation, whereas Δ(9)THC tolerance enhances habit formation. Studies in human cannabis users also suggest an enhancement of S-R/habit memory. A tentative conclusion based on the available data is that acute disruption of the endocannabinoid system with either agonists or antagonists impairs, whereas chronic cannabinoid exposure enhances, dorsal striatum-dependent S-R/habit memory. CB1 receptors are required for multiple forms of striatal synaptic plasticity implicated in memory, including short-term and long-term depression. Interactions with the hippocampus-dependent memory system may also have a role in some of the observed effects of cannabinoids on habit memory. The impairing effect often observed with acute cannabinoid administration argues for cannabinoid-based treatments for human psychopathologies associated with a dysfunctional habit memory system (e.g. post-traumatic stress disorder and drug addiction/relapse). In addition, the enhancing effect of repeated cannabinoid exposure on habit memory suggests a novel neurobehavioral mechanism for marijuana addiction involving the dorsal striatum-dependent memory system. Copyright © 2015 Elsevier Inc. All rights reserved.

Contact highs and urinary cannabinoid excretion after passive exposure to marijuana smoke.

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Cone, E J; Johnson, R E

1986-09-01

Five healthy men were passively exposed under pre- and postplacebo controlled conditions to sidestream smoke from four and 16 standard marijuana cigarettes (2.8% delta-9-tetrahydrocannabinol [delta-9-THC]) for 1 hour each day for 6 consecutive days. Subjective effects produced by the 16-cigarette exposure conditions were similar to those observed after active smoking of one 2.8% delta-9-THC marijuana cigarette. Effects after the four-cigarette condition were less pronounced. Concurrent physiologic measurements showed no clear trends or effects of smoke exposure for either condition. Daily mean plasma levels of delta-9-THC ranged from 2.4 to 7.4 ng/ml with an individual high of 18.8 ng/ml for the 16-cigarette condition. With the use of EMIT cannabinoid assays with 20 ng/ml (EMIT 20) and 100 ng/ml (EMIT 100) cutoffs, urines positive per subject under the four- and 16-cigarette passive exposure conditions were 4.6 +/- 2.2 and 35.2 +/- 3.8, respectively, for the EMIT 20 and 0.0 and 1.0 +/- 0.8, respectively, for the EMIT 100 assay. From the results of these studies, caution is clearly indicated for individuals who might be substantially exposed to heavy marijuana cigarette smoke environments and for those interpreting marijuana screening data.

Cannabinoids ameliorate impairments induced by chronic stress to synaptic plasticity and short-term memory.

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Abush, Hila; Akirav, Irit

2013-07-01

Repeated stress is one of the environmental factors that precipitates and exacerbates mental illnesses like depression and anxiety as well as cognitive impairments. We have previously shown that cannabinoids can prevent the effects of acute stress on learning and memory. Here we aimed to find whether chronic cannabinoid treatment would alleviate the long-term effects of exposure to chronic restraint stress on memory and plasticity as well as on behavioral and neuroendocrine measures of anxiety and depression. Late adolescent rats were exposed to chronic restraint stress for 2 weeks followed each day by systemic treatment with vehicle or with the CB1/2 receptor agonist WIN55,212-2 (1.2 mg/kg). Thirty days after the last exposure to stress, rats demonstrated impaired long-term potentiation (LTP) in the ventral subiculum-nucleus accumbens (NAc) pathway, impaired performance in the prefrontal cortex (PFC)-dependent object-recognition task and the hippocampal-dependent spatial version of this task, increased anxiety levels, and significantly reduced expression of glucocorticoid receptors (GRs) in the amygdala, hippocampus, PFC, and NAc. Chronic WIN55,212-2 administration prevented the stress-induced impairment in LTP levels and in the spatial task, with no effect on stress-induced alterations in unconditioned anxiety levels or GR levels. The CB1 antagonist AM251 (0.3 mg/kg) prevented the ameliorating effects of WIN55,212-2 on LTP and short-term memory. Hence, the beneficial effects of WIN55,212-2 on memory and plasticity are mediated by CB1 receptors and are not mediated by alterations in GR levels in the brain areas tested. Our findings suggest that cannabinoid receptor activation could represent a novel approach to the treatment of cognitive deficits that accompany a variety of stress-related neuropsychiatric disorders.

The consequence of fetal ethanol exposure and adolescent odor re-exposure on the response to ethanol odor in adolescent and adult rats

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Molina Juan C

2009-01-01

Full Text Available Abstract Background An epidemiologic predictive relationship exists between fetal ethanol exposure and the likelihood for adolescent use. Further, an inverse relationship exists between the age of first experience and the probability of adult abuse. Whether and how the combined effects of prenatal and adolescent ethanol experiences contribute to this progressive pattern remains unknown. Fetal ethanol exposure directly changes the odor attributes of ethanol important for both ethanol odor preference behavior and ethanol flavor perception. These effects persist only to adolescence. Here we tested whether adolescent ethanol odor re-exposure: (Experiment 1 augments the fetal effect on the adolescent behavioral response to ethanol odor; and/or (Experiment 2 perpetuates previously observed adolescent behavioral and neurophysiological responses into adulthood. Methods Pregnant rats received either an ethanol or control liquid diet. Progeny (observers experienced ethanol odor in adolescence via social interaction with a peer (demonstrators that received an intragastric infusion of either 1.5 g/kg ethanol or water. Social interactions were scored for the frequency that observers followed their demonstrator. Whole-body plethysmography evaluated the unconditioned behavioral response of observers to ethanol odor in adolescence (P37 or adulthood (P90. The olfactory epithelium of adults was also examined for its neural response to five odorants, including ethanol. Results Experiment 1: Relative to fetal or adolescent exposure alone, adolescent re-exposure enhanced the behavioral response to ethanol odor in P37 animals. Compared to animals with no ethanol experience, rats receiving a single experience (fetal or adolescent show an enhanced, yet equivalent, ethanol odor response. Fetal ethanol experience also increased olfactory-guided following of an intoxicated peer. Experiment 2: Combined exposure yielded persistence of the behavioral effects only in adult

Cannabinoids on the Brain

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Andrew J. Irving

2002-01-01

Full Text Available Cannabis has a long history of consumption both for recreational and medicinal uses. Recently there have been significant advances in our understanding of how cannabis and related compounds (cannabinoids affect the brain and this review addresses the current state of knowledge of these effects. Cannabinoids act primarily via two types of receptor, CB1 and CB2, with CB1 receptors mediating most of the central actions of cannabinoids. The presence of a new type of brain cannabinoid receptor is also indicated. Important advances have been made in our understanding of cannabinoid receptor signaling pathways, their modulation of synaptic transmission and plasticity, the cellular targets of cannabinoids in different central nervous system (CNS regions and, in particular, the role of the endogenous brain cannabinoid (endocannabinoid system. Cannabinoids have widespread actions in the brain: in the hippocampus they influence learning and memory; in the basal ganglia they modulate locomotor activity and reward pathways; in the hypothalamus they have a role in the control of appetite. Cannabinoids may also be protective against neurodegeneration and brain damage and exhibit anticonvulsant activity. Some of the analgesic effects of cannabinoids also appear to involve sites within the brain. These advances in our understanding of the actions of cannabinoids and the brain endocannabinoid system have led to important new insights into neuronal function which are likely to result in the development of new therapeutic strategies for the treatment of a number of key CNS disorders.

Deuterium labeled cannabinoids

International Nuclear Information System (INIS)

Driessen, R.A.

1979-01-01

Complex reactions involving ring opening, ring closure and rearrangements hamper complete understanding of the fragmentation processes in the mass spectrometric fragmentation patterns of cannabinoids. Specifically labelled compounds are very powerful tools for obtaining more insight into fragmentation mechanisms and ion structures and therefore the synthesis of specifically deuterated cannabinoids was undertaken. For this, it was necessary to investigate the preparation of cannabinoids, appropriately functionalized for specific introduction of deuterium atom labels. The results of mass spectrometry with these labelled cannabinoids are described. (Auth.)

Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers

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Hirvonen, J; Goodwin, RS; Li, C-T; Terry, GE; Zoghbi, SS; Morse, C; Pike, VW; Volkow, ND; Huestis, MA; Innis, RB

2011-01-01

Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB1 (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in human subjects who chronically smoke ca...

Adolescent alcohol exposure and persistence of adolescent-typical phenotypes into adulthood: a mini-review

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Spear, Linda Patia; Swartzwelder, H. Scott

2014-01-01

Alcohol use is typically initiated during adolescence, which, along with young adulthood, is a vulnerable period for the onset of high-risk drinking and alcohol abuse. Given across-species commonalities in certain fundamental neurobehavioral characteristics of adolescence, studies in laboratory animals such as the rat have proved useful to assess persisting consequences of repeated alcohol exposure. Despite limited research to date, reports of long-lasting effects of adolescent ethanol exposure are emerging, along with certain common themes. One repeated finding is that adolescent exposure to ethanol sometimes results in the persistence of adolescent-typical phenotypes into adulthood. Instances of adolescent -like persistence have been seen in terms of baseline behavioral, cognitive, electrophysiological and neuroanatomical characteristics, along with the retention of adolescent-typical sensitivities to acute ethanol challenge. These effects are generally not observed after comparable ethanol exposure in adulthood. Persistence of adolescent-typical phenotypes is not always evident, and may be related to regionally-specific ethanol influences on the interplay between CNS excitation and inhibition critical for the timing of neuroplasticity. PMID:24813805

Vaping Synthetic Cannabinoids: A Novel Preclinical Model of E-Cigarette Use in Mice

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Timothy W Lefever

2017-03-01

Full Text Available Smoking is the most common route of administration for cannabis; however, vaping cannabis extracts and synthetic cannabinoids (“fake marijuana” in electronic cigarette devices has become increasingly popular. Yet, most animal models used to investigate biological mechanisms underlying cannabis use employ injection as the route of administration. This study evaluated a novel e-cigarette device that delivers aerosolized cannabinoids to mice. The effects of aerosolized and injected synthetic cannabinoids (CP 55,940, AB-CHMINACA, XLR-11, and JWH-018 in mice were compared in a battery of bioassays in which psychoactive cannabinoids produce characteristic effects. The most potent cannabinoids (CP 55,940 and AB-CHMINACA produced the full cannabinoid profile (ie, hypothermia, hypolocomotion, and analgesia, regardless of the route of administration. In contrast, aerosolized JWH-018 and XLR-11 did not produce the full profile of cannabimimetic effects. Results of time course analysis for hypothermia showed that aerosol exposure to CP 55,940 and AB-CHMINACA produced faster onset of effects and shorter duration of action than injection. The ability to administer cannabinoids to rodents using the most common route of administration among humans provides a method for collecting preclinical data with enhanced translational relevance.

Vaping Synthetic Cannabinoids: A Novel Preclinical Model of E-Cigarette Use in Mice.

Science.gov (United States)

Lefever, Timothy W; Marusich, Julie A; Thomas, Brian F; Barrus, Daniel G; Peiper, Nicholas C; Kevin, Richard C; Wiley, Jenny L

2017-01-01

Smoking is the most common route of administration for cannabis; however, vaping cannabis extracts and synthetic cannabinoids ("fake marijuana") in electronic cigarette devices has become increasingly popular. Yet, most animal models used to investigate biological mechanisms underlying cannabis use employ injection as the route of administration. This study evaluated a novel e-cigarette device that delivers aerosolized cannabinoids to mice. The effects of aerosolized and injected synthetic cannabinoids (CP 55,940, AB-CHMINACA, XLR-11, and JWH-018) in mice were compared in a battery of bioassays in which psychoactive cannabinoids produce characteristic effects. The most potent cannabinoids (CP 55,940 and AB-CHMINACA) produced the full cannabinoid profile (ie, hypothermia, hypolocomotion, and analgesia), regardless of the route of administration. In contrast, aerosolized JWH-018 and XLR-11 did not produce the full profile of cannabimimetic effects. Results of time course analysis for hypothermia showed that aerosol exposure to CP 55,940 and AB-CHMINACA produced faster onset of effects and shorter duration of action than injection. The ability to administer cannabinoids to rodents using the most common route of administration among humans provides a method for collecting preclinical data with enhanced translational relevance.

Adolescent exposure to food advertising on television.

Science.gov (United States)

Powell, Lisa M; Szczypka, Glen; Chaloupka, Frank J

2007-10-01

Television viewing is hypothesized to contribute to obesity among children and adolescents through several mechanisms that include the displacement of physical activity, snacking while watching TV, and the influence of food advertising. This study drew on television ratings to examine the distribution of food advertising exposure among adolescents aged 12 through 17 based on 170 top-rated shows across network, cable and syndicated TV stations over the 9-month period from September 2003 to May 2004. A total of 238,353 30-second equivalent advertisements on the top-rated shows were assessed. Each advertisement was weighted by its rating to measure actual exposure to advertisements. The results showed that among total nonprogram content time, food-related products accounted for roughly one fifth of advertising exposure. Excluding TV promotions and public service announcements, as a proportion of all product advertising, total food-related advertising made up 26% of advertised products viewed by adolescents. By race, the proportion of advertising exposure to food products was 14% greater for African-American versus white adolescents and total exposure to food advertising would be even larger for African-American teens given that, on average, they watched more TV. Fast food was the most frequently viewed food product category comprising 23% of all food-related advertisements among adolescents. Food ads made up just over one quarter of TV ads viewed by adolescents with the most commonly viewed products of fast food, sweets, and beverage products well within the reach of their own purchasing power.

Exposure of US adolescents to extremely violent movies.

Science.gov (United States)

Worth, Keilah A; Gibson Chambers, Jennifer; Nassau, Daniel H; Rakhra, Balvinder K; Sargent, James D

2008-08-01

Despite concerns about exposure to violent media, there are few data on youth exposure to violent movies. In this study we examined such exposure among young US adolescents. We used a random-digit-dial survey of 6522 US adolescents aged 10 to 14 years fielded in 2003. Using previously validated methods, we determined the percentage and number of US adolescents who had seen each of 534 recently released movies. We report results for the 40 that were rated R for violence by the Motion Picture Association of America, UK 18 by the British Board of Film Classification and coded for extreme violence by trained content coders. The 40 violent movies were seen by a median of 12.5% of an estimated 22 million US adolescents aged 10 to 14 years. The most popular violent movie, Scary Movie, was seen by >10 million (48.1%) children, 1 million of whom were 10 years of age. Watching extremely violent movies was associated with being male, older, nonwhite, having less-educated parents, and doing poorly in school. Black male adolescents were at particularly high risk for seeing these movies; for example Blade, Training Day, and Scary Movie were seen, respectively, by 37.4%, 27.3%, and 48.1% of the sample overall versus 82.0%, 81.0%, and 80.8% of black male adolescents. Violent movie exposure was also associated with measures of media parenting, with high-exposure adolescents being significantly more likely to have a television in their bedroom and to report that their parents allowed them to watch R-rated movies. This study documents widespread exposure of young US adolescents to movies with extreme graphic violence from movies rated R for violence and raises important questions about the effectiveness of the current movie-rating system.

Exposure of US Adolescents to Extremely Violent Movies

Science.gov (United States)

Worth, Keilah A.; Chambers, Jennifer Gibson; Nassau, Daniel H.; Rakhra, Balvinder K.; Sargent, James D.

2009-01-01

Objective Despite concerns about exposure to violent media, there are few data on youth exposure to violent movies. In this study we examined such exposure among young US adolescents. Methods We used a random-digit-dial survey of 6522 US adolescents aged 10 to 14 years fielded in 2003. Using previously validated methods, we determined the percentage and number of US adolescents who had seen each of 534 recently released movies. We report results for the 40 that were rated R for violence by the Motion Picture Association of America, UK 18 by the British Board of Film Classification and coded for extreme violence by trained content coders. Results The 40 violent movies were seen by a median of 12.5% of an estimated 22 million US adolescents aged 10 to 14 years. The most popular violent movie, Scary Movie, was seen by >10 million (48.1%) children, 1 million of whom were 10 years of age. Watching extremely violent movies was associated with being male, older, nonwhite, having less-educated parents, and doing poorly in school. Black male adolescents were at particularly high risk for seeing these movies; for example Blade, Training Day, and Scary Movie were seen, respectively, by 37.4%, 27.3%, and 48.1% of the sample overall versus 82.0%, 81.0%, and 80.8% of black male adolescents. Violent movie exposure was also associated with measures of media parenting, with high-exposure adolescents being significantly more likely to have a television in their bedroom and to report that their parents allowed them to watch R-rated movies. Conclusions This study documents widespread exposure of young US adolescents to movies with extreme graphic violence from movies rated R for violence and raises important questions about the effectiveness of the current movie-rating system. PMID:18676548

Violence Exposure and Victimization among Rural Adolescents

Science.gov (United States)

Mykota, David B.; Laye, Adele

2015-01-01

Violence exposure is a serious public health concern for adolescents in schools today. Violence exposure can be quite severe and frequent with multiple acts of indirect and direct victimization having lasting effects on the physical, emotional, and intellectual well-being of adolescents. The purpose of the present study is to examine the rates of…

Exposure to teachers smoking and adolescent smoking behaviour

DEFF Research Database (Denmark)

Poulsen, L H; Osler, M; Roberts, C

2002-01-01

To determine whether adolescent smoking behaviour is associated with their perceived exposure to teachers or other pupils smoking at school, after adjustment for exposure to smoking at home, in school, and best friends smoking.......To determine whether adolescent smoking behaviour is associated with their perceived exposure to teachers or other pupils smoking at school, after adjustment for exposure to smoking at home, in school, and best friends smoking....

Noise Exposures of Rural Adolescents

Science.gov (United States)

Humann, Michael; Sanderson, Wayne; Flamme, Greg; Kelly, Kevin M.; Moore, Genna; Stromquist, Ann; Merchant, James A.

2011-01-01

Purpose: This project was conducted to characterize the noise exposure of adolescents living in rural and agricultural environments. Methods: From May to October, 25 adolescents ages 13 through 17, living either on a farm or a rural nonfarm, were enrolled in the study. Subjects received training on the correct operation and use of personal noise…

PHARMACOLOGY OF CANNABINOIDS

Directory of Open Access Journals (Sweden)

Ilonka Ferjan

2015-06-01

Full Text Available The discovery of cannabinoid receptors and endocannabinoid system has led to the potential therapeutic use of cannabis derivatives. Cannabinoids acting through the CB1 receptors modulate the release of other neurotransmitters in central nervous system, whereas the activation of peripheral CB2 receptors results in decreased inflammatory response and increased apoptosis of some tumor cells populations. The cannabinoids have been authorized for chemotherapy-induced nausea and vomiting; stimulation of appetite; to alleviate neuropathic pain and spasticity in multiple sclerosis, and to reduce pain in cancer patients. Efficacy in other diseases and clinical conditions should be proven in ongoing or future clinical trials. Isolation and identification of different cannabinoids from cannabis and synthesis of novel, more selective, derivatives widens their therapeutic potential. However, there are numerous adverse effects reported, especially when cannabinoids formulations with unknown quantitative and qualitative composition are used. Addiction, tolerance, withdrawal symptoms, increased risk of acute myocardial re-infarction, and increased risk of psychosis or worsening of psychosis are the most common adverse effects of cannabinoids. Acute adverse effects e. g. severe central nervous system depression, are more pronounced in children than in adults. Potential cannabinoid medicines should be subject to the same regulations as other potential drugs. Safety and efficacy of any potential drug candidate, regardless whether it is plant-derived or synthesized, should be proven in non-clinical studies and clinical trials, as well as the marketing authorization must be issued by the appropriate drug authority. Patients deserve a quality manufactured product, which always contains the specified amount of "Remedium cardinale."

Rimonabant, a selective cannabinoid1 receptor antagonist, protects against light-induced retinal degeneration in vitro and in vivo.

Science.gov (United States)

Imamura, Tomoyo; Tsuruma, Kazuhiro; Inoue, Yuki; Otsuka, Tomohiro; Ohno, Yuta; Ogami, Shiho; Yamane, Shinsaku; Shimazawa, Masamitsu; Hara, Hideaki

2017-05-15

The endocannabinoid system is involved in some neurodegenerative diseases such as Alzheimer's disease. An endogenous constellation of proteins related to cannabinoid 1 receptor signaling, including free fatty acids, diacylglycerol lipase, and N-acylethanolamine-hydrolyzing acid amidase, are localized in the murine retina. Moreover, the expression levels of endogenous agonists of cannabinoid receptors are changed in the vitreous fluid. However, the role of the endocannabinoid system in the retina, particularly in the light-induced photoreceptor degeneration, remains unknown. Therefore, we investigated involvement of the cannabinoid 1 receptor in light-induced retinal degeneration using in vitro and in vivo models. To evaluate the effect of cannabinoid 1 receptors in light irradiation-induced cell death, the mouse retinal cone-cell line (661W) was treated with a cannabinoid 1 receptor antagonist, rimonabant. Time-dependent changes of expression and localization of retinal cannabinoid 1 receptors were measured using Western blot and immunostaining. Retinal damage was induced in mice by exposure to light, followed by intravitreal injection of rimonabant. Electroretinograms and histologic analyses were performed. Rimonabant suppressed light-induced photoreceptor cell death. Cannabinoid 1 receptor expression was upregulated by light exposure. Treatment with rimonabant improved both a- and b-wave amplitudes and the thickness of the outer nuclear layer. These results suggest that the cannabinoid 1 receptor is involved in light-induced retinal degeneration and it may represent a therapeutic target in the light-induced photoreceptor degeneration related diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

The effects of adolescent methamphetamine exposure

Directory of Open Access Journals (Sweden)

Jordan M Buck

2015-04-01

Full Text Available Methamphetamine use among adolescents is a significant social and public health concern. Despite increased awareness of methamphetamine use among younger people, relatively little research has examined the effects of adolescent methamphetamine use compared to adult use. Thus much remains to be learned about how methamphetamine alters adolescent brain function and behavior. In this article we review recent trends in adolescent methamphetamine use and data examining the effects of adolescent methamphetamine use on the dopaminergic system and behavior in humans and animal models. Future research is warranted to expand our understanding of the effects of adolescent methamphetamine exposure and how those effects differ from those seen in adults.

Synthetic Cannabinoids.

Science.gov (United States)

Mills, Brooke; Yepes, Andres; Nugent, Kenneth

2015-07-01

Synthetic cannabinoids (SCBs), also known under the brand names of "Spice," "K2," "herbal incense," "Cloud 9," "Mojo" and many others, are becoming a large public health concern due not only to their increasing use but also to their unpredictable toxicity and abuse potential. There are many types of SCBs, each having a unique binding affinity for cannabinoid receptors. Although both Δ-tetrahydrocannabinol (THC) and SCBs stimulate the same receptors, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), studies have shown that SCBs are associated with higher rates of toxicity and hospital admissions than is natural cannabis. This is likely due to SCBs being direct agonists of the cannabinoid receptors, whereas THC is a partial agonist. Furthermore, the different chemical structures of SCBs found in Spice or K2 may interact in unpredictable ways to elicit previously unknown, and the commercial products may have unknown contaminants. The largest group of users is men in their 20s who participate in polydrug use. The most common reported toxicities with SCB use based on studies using Texas Poison Control records are tachycardia, agitation and irritability, drowsiness, hallucinations, delusions, hypertension, nausea, confusion, dizziness, vertigo and chest pain. Acute kidney injury has also been strongly associated with SCB use. Treatment mostly involves symptom management and supportive care. More research is needed to identify which contaminants are typically found in synthetic marijuana and to understand the interactions between different SBCs to better predict adverse health outcomes.

Outdoor ultraviolet exposure of children and adolescents

International Nuclear Information System (INIS)

Diffey, B.L.; Gibson, C.J.

1996-01-01

The weekday and weekend outdoor ultraviolet exposure of young people from primary and secondary schools in three geographically distinct regions of England was determined over a 3-month period in summer. Ultraviolet exposure was measured using personal film badges worn by each young person and time spent outdoors, in hourly intervals, assessed using exposure records. In each area a class of 9-10 year-old children from a primary school and a class of 14-15-year-old adolescents from a secondary school took part, giving a total of 180 subjects. We found that primary school children received higher outdoor ultraviolet exposure than young people in secondary schools, and geographical differences in exposure could not be accounted for solely by differences in ambient ultraviolet. There was little difference between the exposure of males and females. Children and adolescents did not behave as homogeneous groups with regard to exposure. (Author)

Critical appraisal of the potential use of cannabinoids in cancer management

Directory of Open Access Journals (Sweden)

Cridge BJ

2013-08-01

Full Text Available Belinda J Cridge, Rhonda J Rosengren Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand Abstract: Cannabinoids have been attracting a great deal of interest as potential anticancer agents. Originally derived from the plant Cannabis sativa, there are now a number of endo-, phyto- and synthetic cannabinoids available. This review summarizes the key literature to date around the actions, antitumor activity, and mechanisms of action for this broad range of compounds. Cannabinoids are largely defined by an ability to activate the cannabinoid receptors – CB1 or CB2. The action of the cannabinoids is very dependent on the exact ligand tested, the dose, and the duration of exposure. Some cannabinoids, synthetic or plant-derived, show potential as therapeutic agents, and evidence across a range of cancers and evidence in vitro and in vivo is starting to be accumulated. Studies have now been conducted in a wide range of cell lines, including glioma, breast, prostate, endothelial, liver, and lung. This work is complemented by an increasing body of evidence from in vivo models. However, many of these results remain contradictory, an issue that is not currently able to be resolved through current knowledge of mechanisms of action. While there is a developing understanding of potential mechanisms of action, with the extracellular signal-regulated kinase pathway emerging as a critical signaling juncture in combination with an important role for ceramide and lipid signaling, the relative importance of each pathway is yet to be determined. The interplay between the intracellular pathways of autophagy versus apoptosis is a recent development that is discussed. Overall, there is still a great deal of conflicting evidence around the future utility of the cannabinoids, natural or synthetic, as therapeutic agents. Keywords: cancer, cannabinoid, endocannabinoid, tetrahydrocannabinol, JWH-133, WIN-55,212-2

Cannabinoid-Induced Hyperemesis: A Conundrum—From Clinical Recognition to Basic Science Mechanisms

Directory of Open Access Journals (Sweden)

Nissar A. Darmani

2010-07-01

Full Text Available Cannabinoids are used clinically on a subacute basis as prophylactic agonist antiemetics for the prevention of nausea and vomiting caused by chemotherapeutics. Cannabinoids prevent vomiting by inhibition of release of emetic neurotransmitters via stimulation of presynaptic cannabinoid CB1 receptors. Cannabis-induced hyperemesis is a recently recognized syndrome associated with chronic cannabis use. It is characterized by repeated cyclical vomiting and learned compulsive hot water bathing behavior. Although considered rare, recent international publications of numerous case reports suggest the contrary. The syndrome appears to be a paradox and the pathophysiological mechanism(s underlying the induced vomiting remains unknown. Although some traditional hypotheses have already been proposed, the present review critically explores the basic science of these explanations in the clinical setting and provides more current mechanisms for the induced hyperemesis. These encompass: (1 pharmacokinetic factors such as long half-life, chronic exposure, lipid solubility, individual variation in metabolism/excretion leading to accumulation of emetogenic cannabinoid metabolites, and/or cannabinoid withdrawal; and (2 pharmacodynamic factors including switching of the efficacy of Δ9-THC from partial agonist to antagonist, differential interaction of Δ9-THC with Gs and Gi signal transduction proteins, CB1 receptor desensitization or downregulation, alterations in tissue concentrations of endocannabinoid agonists/inverse agonists, Δ9-THC-induced mobilization of emetogenic metabolites of the arachidonic acid cascade, brainstem versus enteric actions of Δ9-THC, and/or hypothermic versus hyperthermic actions of Δ9-THC. In addition, human and animal findings suggest that chronic exposure to cannabis may not be a prerequisite for the induction of vomiting but is required for the intensity of emesis.

Contrasting protective effects of cannabinoids against oxidative stress and amyloid-β evoked neurotoxicity in vitro.

Science.gov (United States)

Harvey, Benjamin S; Ohlsson, Katharina S; Mååg, Jesper L V; Musgrave, Ian F; Smid, Scott D

2012-01-01

Cannabinoids have been widely reported to have neuroprotective properties in vitro and in vivo. In this study we compared the effects of CB1 and CB2 receptor-selective ligands, the endocannabinoid anandamide and the phytocannabinoid cannabidiol, against oxidative stress and the toxic hallmark Alzheimer's protein, β-amyloid (Aβ) in neuronal cell lines. PC12 or SH-SY5Y cells were selectively exposed to either hydrogen peroxide, tert-butyl hydroperoxide or Aβ, alone or in the presence of the CB1 specific agonist arachidonyl-2'-chloroethylamide (ACEA), CB2 specific agonist JWH-015, anandamide or cannabidiol. Cannabidiol improved cell viability in response to tert-butyl hydroperoxide in PC12 and SH-SY5Y cells, while hydrogen peroxide-mediated toxicity was unaffected by cannabidiol pretreatment. Aβ exposure evoked a loss of cell viability in PC12 cells. Of the cannabinoids tested, only anandamide was able to inhibit Aβ-evoked neurotoxicity. ACEA had no effect on Aβ-evoked neurotoxicity, suggesting a CB1 receptor-independent effect of anandamide. JWH-015 pretreatment was also without protective influence on PC12 cells from either pro-oxidant or Aβ exposure. None of the cannabinoids directly inhibited or disrupted preformed Aβ fibrils and aggregates. In conclusion, the endocannabinoid anandamide protects neuronal cells from Aβ exposure via a pathway unrelated to CB1 or CB2 receptor activation. The protective effect of cannabidiol against oxidative stress does not confer protection against Aβ exposure, suggesting divergent pathways for neuroprotection of these two cannabinoids. Copyright © 2011 Elsevier Inc. All rights reserved.

Cannabinoids prevent the differential long-term effects of exposure to severe stress on hippocampal- and amygdala-dependent memory and plasticity.

Science.gov (United States)

Shoshan, Noa; Segev, Amir; Abush, Hila; Mizrachi Zer-Aviv, Tomer; Akirav, Irit

2017-10-01

Exposure to excessive or uncontrolled stress is a major factor associated with various diseases including posttraumatic stress disorder (PTSD). The consequences of exposure to trauma are affected not only by aspects of the event itself, but also by the frequency and severity of trauma reminders. It was suggested that in PTSD, hippocampal-dependent memory is compromised while amygdala-dependent memory is strengthened. Several lines of evidence support the role of the endocannabinoid (eCB) system as a modulator of the stress response. In this study we aimed to examine cannabinoids modulation of the long-term effects (i.e., 1 month) of exposure to a traumatic event on memory and plasticity in the hippocampus and amygdala. Following exposure to the shock and reminders model of PTSD in an inhibitory avoidance light-dark apparatus rats demonstrated: (i) enhanced fear retrieval and impaired inhibitory extinction (Ext), (ii) no long-term potentiation (LTP) in the CA1, (iii) impaired hippocampal-dependent short-term memory in the object location task, (iv) enhanced LTP in the amygdala, and (v) enhanced amygdala-dependent conditioned taste aversion memory. The cannabinoid CB1/2 receptor agonist WIN55-212,2 (0.5mg/kg, i.p.) and the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.3mg/kg, i.p.), administered 2 hr after shock exposure prevented these opposing effects on hippocampal- and amygdala-dependent processes. Moreover, the effects of WIN55-212,2 and URB597 on Ext and acoustic startle were prevented by co-administration of a low dose of the CB1 receptor antagonist AM251 (0.5mg/kg, i.p.), suggesting that the preventing effects of both drugs are mediated by CB1 receptors. Exposure to shock and reminders increased CB1 receptor levels in the CA1 and basolateral amygdala 1 month after shock exposure and this increase was also prevented by administering WIN55-212,2 or URB597. Taken together, these findings suggest the involvement of the eCB system, and specifically CB1

Exposure to Advertisements and Marijuana Use Among US Adolescents.

Science.gov (United States)

Dai, Hongying

2017-11-30

This study examined whether exposure to marijuana advertisements was associated with current marijuana use and frequency of use among US adolescents in grades 8, 10, and 12. Weighted estimates of exposure to marijuana advertisements and marijuana use from the 2014 and 2015 Monitoring the Future studies were investigated. Factors associated with the prevalence and frequency of marijuana use were analyzed by using logistic regression and linear regression models, respectively. Of all respondents (n = 12,988), 13.8% reported marijuana use in the past 30 days. Exposure to marijuana advertisements was prevalent among adolescents, with 52.8% reporting exposure from internet advertisements, 32.1% from television advertisements, 24.1% from magazine or newspaper advertisements, 19.7% from radio advertisements, 19.0% from advertisements on storefronts, and 16.6% from billboards. In the multivariable analysis, current use of marijuana among adolescents was associated with exposure to marijuana advertisements on storefronts (adjusted odds ratio [OR] = 1.4, P < .001), magazines or newspapers (adjusted OR = 1.6, P < .001), billboards (adjusted OR = 1.4, P = .002), internet (adjusted OR = 1.8, P < .001), television (adjusted OR = 1.4, P < .001) and radio (adjusted OR = 1.7, P < .001). Exposure to marijuana advertisements from the internet was associated with increased use of marijuana (β = 0.3, P = .04). Exposure to marijuana advertisements was associated with higher odds of current marijuana use among adolescents. Regulations that limit marijuana advertisements to adolescents and educational campaigns on harmfulness of illicit marijuana use are needed.

Critical appraisal of the potential use of cannabinoids in cancer management

International Nuclear Information System (INIS)

Cridge, Belinda J; Rosengren, Rhonda J

2013-01-01

Cannabinoids have been attracting a great deal of interest as potential anticancer agents. Originally derived from the plant Cannabis sativa, there are now a number of endo-, phyto- and synthetic cannabinoids available. This review summarizes the key literature to date around the actions, antitumor activity, and mechanisms of action for this broad range of compounds. Cannabinoids are largely defined by an ability to activate the cannabinoid receptors – CB 1 or CB 2 . The action of the cannabinoids is very dependent on the exact ligand tested, the dose, and the duration of exposure. Some cannabinoids, synthetic or plant-derived, show potential as therapeutic agents, and evidence across a range of cancers and evidence in vitro and in vivo is starting to be accumulated. Studies have now been conducted in a wide range of cell lines, including glioma, breast, prostate, endothelial, liver, and lung. This work is complemented by an increasing body of evidence from in vivo models. However, many of these results remain contradictory, an issue that is not currently able to be resolved through current knowledge of mechanisms of action. While there is a developing understanding of potential mechanisms of action, with the extracellular signal-regulated kinase pathway emerging as a critical signaling juncture in combination with an important role for ceramide and lipid signaling, the relative importance of each pathway is yet to be determined. The interplay between the intracellular pathways of autophagy versus apoptosis is a recent development that is discussed. Overall, there is still a great deal of conflicting evidence around the future utility of the cannabinoids, natural or synthetic, as therapeutic agents

Critical appraisal of the potential use of cannabinoids in cancer management

Energy Technology Data Exchange (ETDEWEB)

Cridge, Belinda J; Rosengren, Rhonda J, E-mail: rhonda.rosengren@otago.ac.nz [Department of Pharmacology and Toxicology, University of Otago, Dunedin (New Zealand)

2013-08-30

Cannabinoids have been attracting a great deal of interest as potential anticancer agents. Originally derived from the plant Cannabis sativa, there are now a number of endo-, phyto- and synthetic cannabinoids available. This review summarizes the key literature to date around the actions, antitumor activity, and mechanisms of action for this broad range of compounds. Cannabinoids are largely defined by an ability to activate the cannabinoid receptors – CB{sub 1} or CB{sub 2}. The action of the cannabinoids is very dependent on the exact ligand tested, the dose, and the duration of exposure. Some cannabinoids, synthetic or plant-derived, show potential as therapeutic agents, and evidence across a range of cancers and evidence in vitro and in vivo is starting to be accumulated. Studies have now been conducted in a wide range of cell lines, including glioma, breast, prostate, endothelial, liver, and lung. This work is complemented by an increasing body of evidence from in vivo models. However, many of these results remain contradictory, an issue that is not currently able to be resolved through current knowledge of mechanisms of action. While there is a developing understanding of potential mechanisms of action, with the extracellular signal-regulated kinase pathway emerging as a critical signaling juncture in combination with an important role for ceramide and lipid signaling, the relative importance of each pathway is yet to be determined. The interplay between the intracellular pathways of autophagy versus apoptosis is a recent development that is discussed. Overall, there is still a great deal of conflicting evidence around the future utility of the cannabinoids, natural or synthetic, as therapeutic agents.

Child and adolescent exposure to alcohol advertising in Australia's major televised sports.

Science.gov (United States)

Carr, Sherilene; O'Brien, Kerry S; Ferris, Jason; Room, Robin; Livingston, Michael; Vandenberg, Brian; Donovan, Robert J; Lynott, Dermot

2016-07-01

Exposure to alcohol advertising is associated with greater alcohol consumption in children and adolescents, and alcohol advertising is common in Australian sport. We examine child, adolescent and young adult exposure to alcohol advertising during three televised sports in Australia: Australian Football League (AFL), cricket and the National Rugby League (NRL). Alcohol advertising and audience viewing data were purchased for all AFL, cricket and NRL TV programs in Australia for 2012. We estimated children and adolescents (0-17 years) and young adults (18-29 years) exposure to alcohol advertising during AFL, cricket and NRL programs in the daytime (06:00-20:29 h), and night-time (20:30-23:59 h). There were 3544 alcohol advertisements in AFL (1942), cricket (941) and NRL programs (661), representing 60% of all alcohol advertising in sport TV, and 15% of all alcohol advertisements on Australian TV. These programs had a cumulative audience of 26.9 million children and adolescents, and 32 million young adults. Children and adolescents received 51 million exposures to alcohol advertising, with 47% of this exposure occurring during the daytime. Children and adolescents exposure to alcohol advertising was similar to young adults and peaked after 8.30pm. Child and adolescent and young adult's exposure to alcohol advertising is high when viewing sport TV in Australia in the daytime and night-time. Current alcohol advertising regulations are not protecting children and adolescents from exposure, particularly in prominent televised sports. The regulations should be changed to reduce children and adolescent excessive exposure to alcohol advertising when watching sport. [Carr S, O'Brien KS, Ferris J, Room R, Livingston M, Vandenberg B, Donovan RJ, Lynott D. Child and adolescent exposure to alcohol advertising in Australia's major televised sports. Drug Alcohol Rev 2016;35:406-411]. © 2015 Australasian Professional Society on Alcohol and other Drugs.

Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers.

Science.gov (United States)

Hirvonen, J; Goodwin, R S; Li, C-T; Terry, G E; Zoghbi, S S; Morse, C; Pike, V W; Volkow, N D; Huestis, M A; Innis, R B

2012-06-01

Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB(1) (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB(1) receptors in human subjects who chronically smoke cannabis. Downregulation correlated with years of cannabis smoking and was selective to cortical brain regions. After ∼4 weeks of continuously monitored abstinence from cannabis on a secure research unit, CB(1) receptor density returned to normal levels. This is the first direct demonstration of cortical cannabinoid CB(1) receptor downregulation as a neuroadaptation that may promote cannabis dependence in human brain.

Violence Exposure as a Mediator Between Parenting and Adolescent Mental Health.

Science.gov (United States)

Moed, Anat; Gershoff, Elizabeth T; Bringewatt, Elizabeth H

2017-04-01

For youth exposed to community violence, parenting has been found to play a significant role in protecting adolescents from associated mental health symptoms. Yet little is known about the potential of parenting to prevent such exposure in the first place and thereby reduce the likelihood of adolescents' mental health symptoms. This study examined two parental practices that have often been examined as moderators, but not yet as predictors, of youth exposure to community violence associations with adolescent mental health, namely parental control and parental harshness. Analyses of self-reported data from 908 adolescents (M age  = 16.5, SD = 1.71; 52 % girls; 13 % non-Hispanic White) revealed that harsh parenting was indirectly associated with youth mental health symptoms through higher levels of exposure to community violence, whereas links between controlling parenting and mental health symptoms were either non-significant or mediated through lower levels of adolescent violence exposure. These findings highlight the potential positive role parental control may play by preventing adolescents from exposure to potentially dangerous situations. Conversely, our results suggest that harsh parenting appears to pose a risk for adolescents by driving youth away from the home environment and potentially into places where violence may be more prevalent.

Hispanic adolescent farmworkers' perceptions associated with pesticide exposure.

Science.gov (United States)

Salazar, Mary K; Napolitano, Marie; Scherer, Jennifer A; McCauley, Linda A

2004-03-01

The migrant farmworker population in the United States is a vulnerable and understudied population whose characteristics are constantly shifting. The number of youth involved in agriculture work is increasing, and they, in particular, may be at increased risk for occupational hazards, such as pesticide exposure. The present study utilized an ecological framework for focus group discussions with 33 adolescent migrant farmworkers in Oregon. Adolescents' risk perception and health beliefs associated with pesticide exposure are examined on four levels of environmental influence: microenvironment, organizational environment, social/community environment, and macroenvironment. Adolescents provided insight on such topics as perceived vulnerability of illness due to pesticide exposure, attitudes toward farmwork, influence of their boss, knowledge of occupational hazards, safety training, and barriers to occupational choice. Cultural influences on occupational safety and health are discussed and increased attention to safety training is recommended.

Personal radiofrequency electromagnetic field exposure measurements in Swiss adolescents.

Science.gov (United States)

Roser, Katharina; Schoeni, Anna; Struchen, Benjamin; Zahner, Marco; Eeftens, Marloes; Fröhlich, Jürg; Röösli, Martin

2017-02-01

Adolescents belong to the heaviest users of wireless communication devices, but little is known about their personal exposure to radiofrequency electromagnetic fields (RF-EMF). The aim of this paper is to describe personal RF-EMF exposure of Swiss adolescents and evaluate exposure relevant factors. Furthermore, personal measurements were used to estimate average contributions of various sources to the total absorbed RF-EMF dose of the brain and the whole body. Personal exposure was measured using a portable RF-EMF measurement device (ExpoM-RF) measuring 13 frequency bands ranging from 470 to 3600MHz. The participants carried the device for three consecutive days and kept a time-activity diary. In total, 90 adolescents aged 13 to 17years participated in the study conducted between May 2013 and April 2014. In addition, personal measurement values were combined with dose calculations for the use of wireless communication devices to quantify the contribution of various RF-EMF sources to the daily RF-EMF dose of adolescents. Main contributors to the total personal RF-EMF measurements of 63.2μW/m 2 (0.15V/m) were exposures from mobile phones (67.2%) and from mobile phone base stations (19.8%). WLAN at school and at home had little impact on the personal measurements (WLAN accounted for 3.5% of total personal measurements). According to the dose calculations, exposure from environmental sources (broadcast transmitters, mobile phone base stations, cordless phone base stations, WLAN access points, and mobile phones in the surroundings) contributed on average 6.0% to the brain dose and 9.0% to the whole-body dose. RF-EMF exposure of adolescents is dominated by their own mobile phone use. Environmental sources such as mobile phone base stations play a minor role. Copyright © 2016 Elsevier Ltd. All rights reserved.

Seventh European Workshop on Cannabinoid Research and IACM Eighth Conference on Cannabinoids in Medicine

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Cheer, Joseph F.; Maccarrone, Mauro; Piomelli, Daniele

2016-01-01

Abstract The joint 7th European Workshop on Cannabinoid Research and IACM 8th Conference on Cannabinoids in Medicine was held in the beach town of Sestri Levante, Italy, on September 17?19, 2015. In this beautiful setting, world-leading investigators in the field of (endo)cannabinoid research presented exciting new data spanning a broad array of preclinical and clinical topics?from cellular electrophysiology to drug discovery and from potential indications for the therapeutic use of cannabis ...

The Analgesic Potential of Cannabinoids

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Elikottil, Jaseena; Gupta, Pankaj; Gupta, Kalpna

2013-01-01

Historically and anecdotally cannabinoids have been used as analgesic agents. In recent years, there has been an escalating interest in developing cannabis-derived medications to treat severe pain. This review provides an overview of the history of cannabis use in medicine, cannabinoid signaling pathways, and current data from preclinical as well as clinical studies on using cannabinoids as potential analgesic agents. Clinical and experimental studies show that cannabis-derived compounds act as anti-emetic, appetite modulating and analgesic agents. However, the efficacy of individual products is variable and dependent upon the route of administration. Since opioids are the only therapy for severe pain, analgesic ability of cannabinoids may provide a much-needed alternative to opioids. Moreover, cannabinoids act synergistically with opioids and act as opioid sparing agents, allowing lower doses and fewer side effects from chronic opioid therapy. Thus, rational use of cannabis based medications deserves serious consideration to alleviate the suffering of patients due to severe pain. PMID:20073408

A Review of the Therapeutic Antitumor Potential of Cannabinoids.

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Bogdanović, Višnja; Mrdjanović, Jasminka; Borišev, Ivana

2017-11-01

The aim of this review is to discuss cannabinoids from a preclinical and clinical oncological perspective and provide the audience with a concise, retrospective overview of the most significant findings concerning the potential use of cannabinoids in cancer treatment. A literature survey of medical and scientific databases was conducted with a focus on the biological and medical potential of cannabinoids in cancer treatment. Cannabis sativa is a plant rich in more than 100 types of cannabinoids. Besides exogenous plant cannabinoids, mammalian endocannabinoids and synthetic cannabinoid analogues have been identified. Cannabinoid receptors type 1 (CB1) and type 2 (CB2) have been isolated and characterized from mammalian cells. Through cannabinoid receptor and non-receptor signaling pathways, cannabinoids show specific cytotoxicity against tumor cells, while protecting healthy tissue from apoptosis. The dual antiproliferative and proapoptotic effects of cannabinoids and associated signaling pathways have been investigated on a large panel of cancer cell lines. Cannabinoids also display potent anticancer activity against tumor xenografts, including tumors that express high resistance to standard chemotherapeutics. Few studies have investigated the possible synergistic effects of cannabinoids with standard oncology therapies, and are based on the preclinically confirmed concept of "cannabinoid sensitizers." Also, clinical trials aimed to confirm the antineoplastic activity of cannabinoids have only been evaluated on a small number of subjects, with no consensus conclusions regarding their effectiveness. A large number of cannabinoid compounds have been discovered, developed, and used to study the effects of cannabinoids on cancers in model systems. However, few clinical trials have been conducted on the use of cannabinoids in the treatment of cancers in humans. Further studies require extensive monitoring of the effects of cannabinoids alone or in combination with

Cannabis use during adolescent development: susceptibility to psychiatric illness

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Benjamin eChadwick

2013-10-01

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

New approaches in the management of spasticity in multiple sclerosis patients: role of cannabinoids

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Paul F Smith

2010-02-01

Full Text Available Paul F SmithDepartment of Pharmacology and Toxicology, School of Medical Sciences, University of Otago, Dunedin, New ZealandAbstract: Cannabinoids such as Cannabis-based medicinal extracts (CBMEs are increasingly being used in the treatment of spasticity associated with multiple sclerosis (MS. They have been shown to have a beneficial effect on spasticity; however, this evidence is largely based on subjective rating scales. Objective measurements using the Ashworth scale have tended to show no significant effect; however, the validity of this scale has been questioned. The available clinical trial data suggest that the adverse side effects associated with using CBMEs are generally mild, such as dry mouth, dizziness, somnolence, nausea and intoxication. However, most of these trials were run over a period of months and it is possible that other adverse side effects could develop with long-term use. There may be reason to be concerned about the use of therapeutic cannabinoids by adolescents, people predisposed to psychosis and pregnant women.Keywords: multiple sclerosis, spasticity, cannabinoids, Cannabis

Clinical Effects of Synthetic Cannabinoid Receptor Agonists Compared with Marijuana in Emergency Department Patients with Acute Drug Overdose.

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Zaurova, Milana; Hoffman, Robert S; Vlahov, David; Manini, Alex F

2016-12-01

Synthetic cannabinoid receptor agonists (SCRAs) are heterogeneous compounds originally intended as probes of the endogenous cannabinoid system or as potential therapeutic agents. We assessed the clinical toxicity associated with recent SCRA use in a large cohort of drug overdose patients. This subgroup analysis of a large (n = 3739) drug overdose cohort study involved consecutive ED patients at two urban teaching hospitals collected between 2009 and 2013. Clinical characteristics of patients with the exposure to SCRAs (SRCA subgroup) were compared with those from patients who smoked traditional cannabinoids (marijuana subgroup). Data included demographics, exposure details, vital signs, mental status, and basic chemistries gathered as part of routine clinical care. Study outcomes included altered mental status and cardiotoxicity. Eighty-seven patients reported exposure to any cannabinoid, of whom 17 reported SCRAs (17 cases, 70 controls, mean age 38.9 years, 77 % males, 31 % Hispanic). There were no significant differences between SRCA and marijuana with respect to demographics (age, gender, and race/ethnicity), exposure history (suicidality, misuse, and intent), vital signs, or serum chemistries. Mental status varied between SRCA and marijuana, with agitation significantly more likely in SCRA subgroup (OR = 3.8, CI = 1.2-11.9). Cardiotoxicity was more pronounced in the SCRA subgroup with dysrhythmia significantly more likely (OR = 9.2, CI = 1.0-108). In the first clinical study comparing the adverse effects of SCRA overdose vs. marijuana controls in an ED population, we found that SCRA overdoses had significantly pronounced neurotoxicity and cardiotoxicity compared with marijuana.

Exploring associations between exposure to sexy online self-presentations and adolescents' sexual attitudes and behavior.

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van Oosten, Johanna M F; Peter, Jochen; Boot, Inge

2015-05-01

Previous research suggests that adolescents' social network site use is related to their sexual development. However, the associations between adolescents' exposure to sexy self-presentations of others on social network sites and their sexual attitudes and experience have not yet been empirically supported. This study investigated reciprocal longitudinal relationships between adolescents' exposure to others' sexy self-presentations on social network sites and their sexual attitudes (i.e., sexual objectification of girls and instrumental attitudes towards sex) and sexual experience. We further tested whether these associations depended on adolescents' age and gender. Results from a representative two-wave panel study among 1,636 Dutch adolescents (aged 13-17, 51.5 % female) showed that exposure to sexy online self-presentations of others predicted changes in adolescents' experience with oral sex and intercourse 6 months later, but did not influence their sexual attitudes. Adolescents' instrumental attitudes towards sex, in turn, did predict their exposure to others' sexy online self-presentations. Sexual objectification increased such exposure for younger adolescents, but decreased exposure for older adolescents. In addition, adolescents' experience with genital touching as well as oral sex (only for adolescents aged 13-15) predicted their exposure to sexy self-presentations of others. These findings tentatively suggest that the influence on adolescents' sexual attitudes previously found for sexual media content may not hold for sexy self-presentations on social network sites. However, exposure to sexy self-presentations on social network sites is motivated by adolescents' sexual attitudes and behavior, especially among young adolescents.

Cannabinoids: Medical implications.

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Schrot, Richard J; Hubbard, John R

2016-01-01

Herbal cannabis has been used for thousands of years for medical purposes. With elucidation of the chemical structures of tetrahydrocannabinol (THC) and cannabidiol (CBD) and with discovery of the human endocannabinoid system, the medical usefulness of cannabinoids has been more intensively explored. While more randomized clinical trials are needed for some medical conditions, other medical disorders, like chronic cancer and neuropathic pain and certain symptoms of multiple sclerosis, have substantial evidence supporting cannabinoid efficacy. While herbal cannabis has not met rigorous FDA standards for medical approval, specific well-characterized cannabinoids have met those standards. Where medical cannabis is legal, patients typically see a physician who "certifies" that a benefit may result. Physicians must consider important patient selection criteria such as failure of standard medical treatment for a debilitating medical disorder. Medical cannabis patients must be informed about potential adverse effects, such as acute impairment of memory, coordination and judgment, and possible chronic effects, such as cannabis use disorder, cognitive impairment, and chronic bronchitis. In addition, social dysfunction may result at work/school, and there is increased possibility of motor vehicle accidents. Novel ways to manipulate the endocannbinoid system are being explored to maximize benefits of cannabinoid therapy and lessen possible harmful effects.

Enhanced novelty-induced corticosterone spike and upregulated serotonin 5-HT1A and cannabinoid CB1 receptors in adolescent BTBR mice.

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Gould, Georgianna G; Burke, Teresa F; Osorio, Miguel D; Smolik, Corey M; Zhang, Wynne Q; Onaivi, Emmanuel S; Gu, Ting-Ting; DeSilva, Mauris N; Hensler, Julie G

2014-01-01

Hypothalamic pituitary adrenal (HPA) axis responses to change and social challenges during adolescence can influence mental health and behavior into adulthood. To examine how HPA tone in adolescence may contribute to psychopathology, we challenged male adolescent (5 weeks) and adult (16 weeks) BTBR T(+)tf/J (BTBR) and 129S1/SvImJ (129S) mice with novelty in sociability tests. In prior studies these strains had exaggerated or altered HPA stress responses and low sociability relative to C57BL/6J mice in adulthood. In adolescence these strains already exhibited similar or worse sociability deficits than adults or age-matched C57 mice. Yet BTBR adolescents were less hyperactive and buried fewer marbles than adults. Novelty-induced corticosterone (CORT) spikes in adolescent BTBR were double adult levels, and higher than 129S or C57 mice at either age. Due to their established role in HPA feedback, we hypothesized that hippocampal Gαi/o-coupled serotonin 5-HT1A and cannabinoid CB1 receptor function might be upregulated in BTBR mice. Adolescent BTBR mice had higher hippocampal 5-HT1A density as measured by [(3)H] 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) binding than C57 mice, and adult BTBR 8-OH-DPAT-stimulated GTPγS binding was higher than in either C57 or 129S mice in this region. Further, BTBR hippocampal CB1 density measured by [(3)H]CP55,940 binding was 15-20% higher than in C57. CP55,940-stimulated GTPγS binding in adult BTBR dentate gyrus was 30% higher then 129S (p<0.05), but was not a product of greater neuronal or cell density defined by NeuN and DAPI staining. Hence hyperactive HPA responsiveness during adolescence may underlie 5-HT1A and CB1 receptor up-regulation and behavioral phenotype of BTBR mice. Copyright © 2013 Elsevier Ltd. All rights reserved.

Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD.

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Han, Jing; Kesner, Philip; Metna-Laurent, Mathilde; Duan, Tingting; Xu, Lin; Georges, Francois; Koehl, Muriel; Abrous, Djoher Nora; Mendizabal-Zubiaga, Juan; Grandes, Pedro; Liu, Qingsong; Bai, Guang; Wang, Wei; Xiong, Lize; Ren, Wei; Marsicano, Giovanni; Zhang, Xia

2012-03-02

Impairment of working memory is one of the most important deleterious effects of marijuana intoxication in humans, but its underlying mechanisms are presently unknown. Here, we demonstrate that the impairment of spatial working memory (SWM) and in vivo long-term depression (LTD) of synaptic strength at hippocampal CA3-CA1 synapses, induced by an acute exposure of exogenous cannabinoids, is fully abolished in conditional mutant mice lacking type-1 cannabinoid receptors (CB(1)R) in brain astroglial cells but is conserved in mice lacking CB(1)R in glutamatergic or GABAergic neurons. Blockade of neuronal glutamate N-methyl-D-aspartate receptors (NMDAR) and of synaptic trafficking of glutamate α-amino-3-hydroxy-5-methyl-isoxazole propionic acid receptors (AMPAR) also abolishes cannabinoid effects on SWM and LTD induction and expression. We conclude that the impairment of working memory by marijuana and cannabinoids is due to the activation of astroglial CB(1)R and is associated with astroglia-dependent hippocampal LTD in vivo. Copyright © 2012 Elsevier Inc. All rights reserved.

Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid

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Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E.; Redhi, Godfrey H.; Panlilio, Leigh V.; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D.; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R.

2013-01-01

In the reward circuitry of the brain, alpha-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of delta-9-tetrahydrocannabinol (THC), marijuana’s main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by re-exposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are currently no medications approved for treatment of marijuana dependence. Modulation of KYNA provides a novel pharmacological strategy for achieving abstinence from marijuana and preventing relapse. PMID:24121737

Adolescents' media exposure may increase their cyberbullying behavior: a longitudinal study.

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den Hamer, Anouk H; Konijn, Elly A

2015-02-01

The aim of this study was to examine the effect of adolescents' exposure to media portraying antisocial and risk behavior on cyberbullying behavior over time. Previous research established relatively high prevalence of cyberbullying behavior among adolescents, although not much is known about the possible predictors of cyberbullying behavior. This study examines the long-term effects of media exposure herein. Furthermore, we examined whether boys and girls differ in this respect. The long-term effects were tested in a longitudinal design with three waves (N = 1,005; age range, 11-17 years; 49% boys). Measured variables: cyberbullying behavior and exposure to media with antisocial and risk behavior content. Results of mixed-model analyses showed that higher levels of exposure to media with antisocial and risk behavior content significantly contributed to higher initial rates of cyberbullying behavior. Moreover, an increase in exposure to antisocial media content was significantly related to an increase in cyberbullying behavior over time. For both boys and girls, higher exposure to antisocial and risk behavior media content increases cyberbullying behavior over time though more clearly for boys than for girls. This study provided empirical support for the amplifying effect of exposure to antisocial media content on adolescents' cyberbullying behavior over time. Results are discussed in view of adolescents' media use and the larger theoretical framework. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Trauma Exposure and Externalizing Disorders in Adolescents: Results From the National Comorbidity Survey Adolescent Supplement.

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Carliner, Hannah; Gary, Dahsan; McLaughlin, Katie A; Keyes, Katherine M

2017-09-01

Exposure to violence and other forms of potentially traumatic events (PTEs) are common among youths with externalizing psychopathology. These associations likely reflect both heightened risk for the onset of externalizing problems in youth exposed to PTEs and elevated risk for experiencing PTEs among youth with externalizing disorders. In this study, we disaggregate the associations between exposure to PTEs and externalizing disorder onset in a population-representative sample of adolescents. We analyzed data from 13- to 18-year-old participants in the National Comorbidity Survey Replication-Adolescent Supplement (NCS-A) (N = 6,379). Weighted survival models estimated hazard ratios (HRs) for onset of oppositional defiant disorder (ODD), conduct disorder (CD), and substance use disorders (SUDs) associated with PTEs, and for exposure to PTEs associated with prior-onset externalizing disorders. Multiplicative interaction terms tested for effect modification by sex, race/ethnicity, and household income. All types of PTEs were associated with higher risk for SUD (HRs = 1.29-2.21), whereas only interpersonal violence (HR = 2.49) was associated with onset of CD and only among females. No associations were observed for ODD. Conversely, ODD and CD were associated with elevated risk for later exposure to interpersonal violence and other/nondisclosed events (HRs = 1.45-1.75). Externalizing disorders that typically begin in adolescence, including SUDs and CD, are more likely to emerge in adolescents with prior trauma. ODD onset, in contrast, is unrelated to trauma exposure but is associated with elevated risk of experiencing trauma later in development. CD and interpersonal violence exposure exhibit reciprocal associations. These findings have implications for interventions targeting externalizing and trauma-related psychopathology. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Exposure to alcohol advertising and alcohol consumption among Australian adolescents.

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Jones, Sandra C; Magee, Christopher A

2011-01-01

Underage drinking is a major problem in Australia and may be influenced by exposure to alcohol advertising. The objective of the present study was to collect data on 12-17 year old Australian adolescents' exposure to different types of alcohol advertising and examine the association between exposure to advertising and alcohol consumption. A cross-sectional survey of 1113 adolescents aged 12-17 years recruited with a variety of methods to gain a cross-section of participants across metropolitan, regional and rural New South Wales (including independent schools, mall intercepts and online). Participants answered a series of questions assessing adolescents' exposure to alcohol advertising across eight media (including television, Internet and point-of-sale). Alcohol consumption was assessed using three questions (initiation, recent consumption and frequency of consumption in the previous 12 months). The majority indicated that they had been exposed to alcohol advertisements on television, in newspapers and magazines, on the Internet, on billboards/posters and promotional materials and in bottleshops, bars and pubs; exposure to some of these types of alcohol advertisements was associated with increased alcohol consumption, with differences by age and gender. The results are consistent with studies from other countries and suggest that exposure to alcohol advertisements among Australian adolescents is strongly associated with drinking patterns. Given current high levels of drinking among Australian youth, these findings suggest the need to address the high levels of young people's exposure to alcohol advertising.

Cytotoxicity of synthetic cannabinoids on primary neuronal cells of the forebrain: the involvement of cannabinoid CB1 receptors and apoptotic cell death

International Nuclear Information System (INIS)

Tomiyama, Ken-ichi; Funada, Masahiko

2014-01-01

The abuse of herbal products containing synthetic cannabinoids has become an issue of public concern. The purpose of this paper was to evaluate the acute cytotoxicity of synthetic cannabinoids on mouse brain neuronal cells. Cytotoxicity induced by synthetic cannabinoid (CP-55,940, CP-47,497, CP-47,497-C8, HU-210, JWH-018, JWH-210, AM-2201, and MAM-2201) was examined using forebrain neuronal cultures. These synthetic cannabinoids induced cytotoxicity in the forebrain cultures in a concentration-dependent manner. The cytotoxicity was suppressed by preincubation with the selective CB 1 receptor antagonist AM251, but not with the selective CB 2 receptor antagonist AM630. Furthermore, annexin-V-positive cells were found among the treated forebrain cells. Synthetic cannabinoid treatment induced the activation of caspase-3, and preincubation with a caspase-3 inhibitor significantly suppressed the cytotoxicity. These synthetic cannabinoids induced apoptosis through a caspase-3-dependent mechanism in the forebrain cultures. Our results indicate that the cytotoxicity of synthetic cannabinoids towards primary neuronal cells is mediated by the CB 1 receptor, but not by the CB 2 receptor, and further suggest that caspase cascades may play an important role in the apoptosis induced by these synthetic cannabinoids. In conclusion, excessive synthetic cannabinoid abuse may present a serious acute health concern due to neuronal damage or deficits in the brain. - Highlights: • Synthetic cannabinoids (classical cannabinoids, non-classical cannabinoids, and aminoalkylindole derivatives) induce cytotoxicity in mouse forebrain cultures. • Synthetic cannabinoid-induced cytotoxicity towards forebrain cultures is mediated by the CB 1 receptor, but not by the CB 2 receptor, and involves caspase-dependent apoptosis. • A high concentration of synthetic cannabinoids may be toxic to neuronal cells that express CB 1 receptors

Functional role of cannabinoid receptors in urinary bladder

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Pradeep Tyagi

2010-01-01

Full Text Available Cannabinoids, the active components of Cannabis sativa (marijuana, and their derivatives produce a wide spectrum of central and peripheral effects, some of which may have clinical applications. The discovery of specific cannabinoid receptors and a family of endogenous ligands of those receptors has attracted much attention to the general cannabinoid pharmacology. In recent years, studies on the functional role of cannabinoid receptors in bladder have been motivated by the therapeutic effects of cannabinoids on voiding dysfunction in multiple sclerosis patients. In this review, we shall summarize the literature on the expression of cannabinoid receptors in urinary bladder and the peripheral influence of locally and systemically administered cannabinoids in the bladder. The ongoing search for cannabinoid-based therapeutic strategies devoid of psychotropic effects can be complemented with local delivery into bladder by the intravesical route. A greater understanding of the role of the peripheral CB 1 and CB 2 receptor system in lower urinary tract is necessary to allow the development of new treatment for pelvic disorders.

Cannabis and Cannabinoids for Chronic Pain.

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Romero-Sandoval, E Alfonso; Kolano, Ashley L; Alvarado-Vázquez, P Abigail

2017-10-05

The purpose of this study was to provide the most up-to-date scientific evidence of the potential analgesic effects, or lack thereof, of the marijuana plant (cannabis) or cannabinoids, and of safety or tolerability of their long-term use. We found that inhaled (smoked or vaporized) cannabis is consistently effective in reducing chronic non-cancer pain. Oral cannabinoids seem to improve some aspects of chronic pain (sleep and general quality of life), or cancer chronic pain, but they do not seem effective in acute postoperative pain, abdominal chronic pain, or rheumatoid pain. The available literature shows that inhaled cannabis seems to be more tolerable and predictable than oral cannabinoids. Cannabis or cannabinoids are not universally effective for pain. Continued research on cannabis constituents and improving bioavailability for oral cannabinoids is needed. Other aspects of pain management in patients using cannabis require further open discussion: concomitant opioid use, medical vs. recreational cannabis, abuse potential, etc.

Preclinical Science Regarding Cannabinoids as Analgesics: An Overview

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ME Lynch

2005-01-01

Full Text Available Modern pharmacology of cannabinoids began in 1964 with the isolation and partial synthesis of delta-9-tetrahydrocannabinol, the main psychoactive agent in herbal cannabis. Since then, potent antinociceptive and antihyperalgesic effects of cannabinoid agonists in animal models of acute and chronic pain; the presence of cannabinoid receptors in pain-processing areas of the brain, spinal cord and periphery; and evidence supporting endogenous modulation of pain systems by cannabinoids has provided support that cannabinoids exhibit significant potential as analgesics. The present article presents an overview of the preclinical science.

Exposure to Domestic and Community Violence and Subjective Well-Being in Adolescents

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Doralúcia Gil da Silva

Full Text Available Abstract There is major exposure to domestic and community violence during adolescence, which has been negatively related to well-being. This work aimed to identify relationships between domestic and community violence and the levels of subjective well-being perceived by adolescents, considering sex and age. The participants were 426 adolescents from public schools in the south of Brazil; 62% were girls, with a mean age of 14.91 years old ( SD = 1.65, who answered one instrument about exposure to violence and another about well-being. Results indicated greater domestic violence exposure among girls and greater community exposure among boys. The age range from 16 to 18 years old was the most exposed to domestic violence. Boys reported greater well-being and less negative affect. Differences in violence exposure may be related to roles of gender in our society. Well-being promotion is highlighted as a resource for confronting violence among adolescents.

Secondhand Smoke Exposure, Restless Sleep, and Sleep Duration in Adolescents

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Jennifer Schwartz

2014-01-01

Full Text Available Purpose. To examine whether secondhand smoke (SHS exposure is associated with restless sleep and/or nighttime sleep duration among adolescents. Methods. Data were analyzed from 1,592 adolescents who completed an internet-delivered survey as part of the British Columbia Adolescent Substance Use Survey cohort study. Ordinal logistic and linear regression models were used to examine associations between frequency of SHS exposure in the past month and frequency of restless sleep and nighttime sleep duration, respectively. Results. SHS exposure was significantly positively associated with restless sleep and significantly negatively associated with sleep duration. In fully adjusted models, compared with students who reported never being exposed to SHS in the past month, students who reported a low, medium, or high frequency of SHS exposure were 1.53, 1.76, and 2.51 times as likely, respectively, to report more frequent restless sleep (OR=1.53, 95% CI 1.08–2.16; OR=1.76, 95% CI 1.22–2.53; OR=2.51, 95% CI 1.59–3.98. With regard to sleep duration, as frequency of SHS exposure increased by one category, nighttime sleep duration during the week and weekend decreased by 4 minutes (B=-0.06, 95% CI=-0.01–-0.11 and 6 minutes (B=-0.09, 95% CI=-0.03–-0.14, respectively. Conclusions. This study suggests that frequency of SHS exposure has a significant dose-response relationship with restless sleep and sleep duration in adolescents.

Cytotoxicity of synthetic cannabinoids on primary neuronal cells of the forebrain: the involvement of cannabinoid CB{sub 1} receptors and apoptotic cell death

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Tomiyama, Ken-ichi; Funada, Masahiko, E-mail: mfunada@ncnp.go.jp

2014-01-01

The abuse of herbal products containing synthetic cannabinoids has become an issue of public concern. The purpose of this paper was to evaluate the acute cytotoxicity of synthetic cannabinoids on mouse brain neuronal cells. Cytotoxicity induced by synthetic cannabinoid (CP-55,940, CP-47,497, CP-47,497-C8, HU-210, JWH-018, JWH-210, AM-2201, and MAM-2201) was examined using forebrain neuronal cultures. These synthetic cannabinoids induced cytotoxicity in the forebrain cultures in a concentration-dependent manner. The cytotoxicity was suppressed by preincubation with the selective CB{sub 1} receptor antagonist AM251, but not with the selective CB{sub 2} receptor antagonist AM630. Furthermore, annexin-V-positive cells were found among the treated forebrain cells. Synthetic cannabinoid treatment induced the activation of caspase-3, and preincubation with a caspase-3 inhibitor significantly suppressed the cytotoxicity. These synthetic cannabinoids induced apoptosis through a caspase-3-dependent mechanism in the forebrain cultures. Our results indicate that the cytotoxicity of synthetic cannabinoids towards primary neuronal cells is mediated by the CB{sub 1} receptor, but not by the CB{sub 2} receptor, and further suggest that caspase cascades may play an important role in the apoptosis induced by these synthetic cannabinoids. In conclusion, excessive synthetic cannabinoid abuse may present a serious acute health concern due to neuronal damage or deficits in the brain. - Highlights: • Synthetic cannabinoids (classical cannabinoids, non-classical cannabinoids, and aminoalkylindole derivatives) induce cytotoxicity in mouse forebrain cultures. • Synthetic cannabinoid-induced cytotoxicity towards forebrain cultures is mediated by the CB{sub 1} receptor, but not by the CB{sub 2} receptor, and involves caspase-dependent apoptosis. • A high concentration of synthetic cannabinoids may be toxic to neuronal cells that express CB{sub 1} receptors.

Impact of cannabis, cannabinoids and endocannabinoids in the lungs

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Caroline Turcotte

2016-09-01

Full Text Available Since the identification of cannabinoid receptors in the 1990s, a research field has been dedicated to exploring the role of the cannabinoid system in immunity and the inflammatory response in human tissues and animal models. Although the cannabinoid system is present and crucial in many human tissues, studying the impact of cannabinoids on the lungs is particularly relevant because of their contact with exogenous cannabinoids is the context of marijuana consumption. In the past two decades, the scientific community has gathered a large body of evidence supporting that the activation of the cannabinoid system alleviates pain and reduces inflammation. In the context of lung inflammation, exogenous and endogenous cannabinoids have shown therapeutic potential because of their inhibitory effects on immune cell recruitment and functions. On the other hand, cannabinoids were shown to be deleterious to lung function and to impact respiratory pathogen clearance. In this review, we present the existing data on the regulation of lung immunity and inflammation by phytocannabinoids, synthetic cannabinoids and endocannabinoids.

Secondhand tobacco smoke exposure among adolescents in an Ethiopian school

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Sabit Abazinab Ababulgu

2016-05-01

Full Text Available Tobacco use is responsible for 6 million deaths globally per year, of which 600,000 deaths are due to secondhand smoke (SHS mainly among women and children. This study aims to determine the prevalence of SHS exposure among school-going adolescents and highlights the essential determinants in developing successful strategies to prevent adverse health effects in Ethiopia. The analysis is based on a school based cross sectional study where 1673 students with 98.2% of response rate from grade 9-12, aged 13-19 were included. Data was collected by a self-administered questionnaire that is adapted from the global youth tobacco survey questionnaire. Proportions and 95% confidence intervals were obtained as estimates of prevalence. Bivariate and multivariate analyses were made using logistic regression on SPSS version 20.0 software in order to predict factors associated with SHS exposure. About 17% of adolescents were exposed to tobacco smoke in their home, whereas more than half (60.8% of adolescents were exposed to tobacco smoke in public places. In multivariate analysis, sex, parent smoking, peer smoking, and absence of discussion in the classroom about dangers of smoking were seen significantly associated with SHS exposure. The prevalence of SHS exposure among adolescents in Ethiopia is highest. Moreover, exposure to SHS in public places is much higher than at home.

Therapeutic Mechanisms for Cannabinoid-Promoted Survival of Oligodendrocytes

Science.gov (United States)

2013-06-21

Studies in vivo were performed to characterize the effect of a novel synthetic cannabinoid compound in preventing inflammation, demyelination and...studied as a possible treatment for MS and one class of compounds that is showing particular promise are the cannabinoids. Cannabis, or marijuana , as it...thus differing in their chemical structures (77). The third class of cannabinoids relates to the synthetic cannabinoids. These synthetic

Adolescent violence exposure, gender issues and impact.

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Munni, Ray; Malhi, P

2006-07-01

Youth violence is a growing problem worldwide. Research on adolescent violence in India is limited. Fifteen hundred high school students were investigated to study the prevalence and demographic characteristics of witnesses, victims and perpetrators of violence and to see the impact of violence exposure on their psychosocial adjustments. Sixty nine percent of students had witnessed violence in real life and 28% were of serious nature. Media violence exposure was universal. The prevalence of victims and perpetrators was 27% and 13% respectively. Bullying was prevalent. Male sex was the most important predictive risk factor for witnessing and perpetrating violence (P gender differences exist. Its impact on their psychosocial adjustments is detrimental. Early identification and corrective interventions of these adolescents is vital.

Gender-specific effects of prenatal and adolescent exposure to tobacco smoke on auditory and visual attention.

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Jacobsen, Leslie K; Slotkin, Theodore A; Mencl, W Einar; Frost, Stephen J; Pugh, Kenneth R

2007-12-01

Prenatal exposure to active maternal tobacco smoking elevates risk of cognitive and auditory processing deficits, and of smoking in offspring. Recent preclinical work has demonstrated a sex-specific pattern of reduction in cortical cholinergic markers following prenatal, adolescent, or combined prenatal and adolescent exposure to nicotine, the primary psychoactive component of tobacco smoke. Given the importance of cortical cholinergic neurotransmission to attentional function, we examined auditory and visual selective and divided attention in 181 male and female adolescent smokers and nonsmokers with and without prenatal exposure to maternal smoking. Groups did not differ in age, educational attainment, symptoms of inattention, or years of parent education. A subset of 63 subjects also underwent functional magnetic resonance imaging while performing an auditory and visual selective and divided attention task. Among females, exposure to tobacco smoke during prenatal or adolescent development was associated with reductions in auditory and visual attention performance accuracy that were greatest in female smokers with prenatal exposure (combined exposure). Among males, combined exposure was associated with marked deficits in auditory attention, suggesting greater vulnerability of neurocircuitry supporting auditory attention to insult stemming from developmental exposure to tobacco smoke in males. Activation of brain regions that support auditory attention was greater in adolescents with prenatal or adolescent exposure to tobacco smoke relative to adolescents with neither prenatal nor adolescent exposure to tobacco smoke. These findings extend earlier preclinical work and suggest that, in humans, prenatal and adolescent exposure to nicotine exerts gender-specific deleterious effects on auditory and visual attention, with concomitant alterations in the efficiency of neurocircuitry supporting auditory attention.

Exposure to smoking imagery in popular films and adolescent smoking in Mexico.

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Thrasher, James F; Jackson, Christine; Arillo-Santillán, Edna; Sargent, James D

2008-08-01

Exposure to smoking imagery in films is consistently associated with smoking behavior and its psychological antecedents among adolescents in high-income countries, but its association with adolescent smoking in middle-income countries is unknown. In 2006, a cross-sectional sample of 3876 Mexican adolescents in secondary school was surveyed on smoking behavior, smoking risk factors, and exposure to 42 popular films that contained smoking. Participants were classified into quartiles of exposure to smoking imagery across all films they reported having seen. Models were estimated to determine associations among quartiles of film-smoking exposure, smoking behavior, and the psychological antecedents of smoking, adjusting for age, gender, sensation seeking, self-esteem, parental smoking, sibling smoking, best-friend smoking, having a bedroom TV, and private versus public school attendance. Analyses were conducted in 2007. Adolescents were exposed to an average of 51.7 (SE=1.3) minutes of smoking in the films they viewed. Crude and adjusted ORs indicated positive associations between quartiles of film-smoking exposure and both current smoking (AOR4v1=3.13; pantecedents of smoking uptake. Crude and adjusted coefficients indicated significant, positive associations between exposure and susceptibility to smoking (AOR4v1=1.66; p<0.05); favorable attitudes toward smoking (Adjusted B4v1=0.44; p<0.0001); and perceived peer prevalence of smoking (Adjusted B4v1=0.26; p<0.0001). Exposure to smoking in films appears associated with smoking among Mexican adolescents. Policies could aim to decrease youth exposure to smoking in nationally and internationally distributed films.

Plant cannabinoids: a neglected pharmacological treasure trove.

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Mechoulam, Raphael

2005-12-01

Most of the cannabinoids in Cannabis sativa L. have not been fully evaluated for their pharmacological activity. A publication in this issue presents evidence that a plant cannabinoid, Delta(9)-tetrahydrocannabivarin is a potent antagonist of anandamide, a major endogenous cannabinoid. It seems possible that many of the non-psychoactive constituents of this plant will be of biological interest.

Multigenerational effects of adolescent morphine exposure on dopamine D2 receptor function.

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Byrnes, John J; Johnson, Nicole L; Carini, Lindsay M; Byrnes, Elizabeth M

2013-05-01

The use and misuse of prescription opiates in adolescent populations, and in particular, adolescent female populations, has increased dramatically in the past two decades. Given the significant role that opioids play in neuroendocrine function, exposure to opiates during this critical developmental period could have significant consequences for the female, as well as her offspring. In the current set of studies, we utilized the female rat to model the transgenerational impact of adolescent opiate exposure. We examined locomotor sensitization in response to the dopamine D2/D3 receptor agonist quinpirole in the adult male progeny (F1 and F2 generations) of females exposed to morphine during adolescence. All females were drug-free for at least 3 weeks prior to conception, eliminating the possibility of direct fetal exposure to morphine. Both F1 and F2 progeny of morphine-exposed females demonstrated attenuated locomotor sensitization following repeated quinpirole administration. These behavioral effects were coupled with increased quinpirole-induced corticosterone secretion and upregulated kappa opioid receptor and dopamine D2 receptor (D2R) gene expression within the nucleus accumbens. These results suggest significant modifications in response to repeated D2R activation in the progeny of females exposed to opiates during adolescence. Given the significant role that the D2R plays in psychopathology, adolescent opiate exposure could shift the vulnerability of future offspring to psychological disorders, including addiction. Moreover, that effects are also observed in the F2 generation suggests that adolescent opiate exposure can trigger transgenerational epigenetic modifications impacting systems critical for motivated behavior.

Adolescent Initiation of Drug Use: Effects of Prenatal Cocaine Exposure

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Richardson, Gale A.; Larkby, Cynthia; Goldschmidt, Lidush; Day, Nancy L.

2013-01-01

Objective: To investigate the direct effects of prenatal cocaine exposure (PCE) on adolescent drug use, while controlling for other predictors of adolescent use. Method: Data are from a longitudinal study of PCE in which women and their offspring were assessed throughout childhood. Adolescents were interviewed at 15 years about their age at…

Examining the Pathologic Adaptation Model of Community Violence Exposure in Male Adolescents of Color

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Gaylord-Harden, Noni K.; So, Suzanna; Bai, Grace J.; Henry, David B.; Tolan, Patrick H.

2017-01-01

The current study examined a model of desensitization to community violence exposure—the pathologic adaptation model—in male adolescents of color. The current study included 285 African American (61%) and Latino (39%) male adolescents (W1 M age = 12.41) from the Chicago Youth Development Study to examine the longitudinal associations between community violence exposure, depressive symptoms, and violent behavior. Consistent with the pathologic adaptation model, results indicated a linear, positive association between community violence exposure in middle adolescence and violent behavior in late adolescence, as well as a curvilinear association between community violence exposure in middle adolescence and depressive symptoms in late adolescence, suggesting emotional desensitization. Further, these effects were specific to cognitive-affective symptoms of depression and not somatic symptoms. Emotional desensitization outcomes, as assessed by depressive symptoms, can occur in male adolescents of color exposed to community violence and these effects extend from middle adolescence to late adolescence. PMID:27653968

Modulation of limbic noradrenergic circuits by cannabinoids

OpenAIRE

Carvalho, Ana Raquel Franky Gomes

2010-01-01

Tese de doutoramento Medicina The endocannabinoid system has been implicated in the regulation of several physiological functions. The widespread distribution of the endocannabinoid system in the central nervous system (CNS) accounts for many effects attributed to cannabinoids. Importantly, cannabinoids have been shown to modulate mood, cognition and memory. There is growing evidence suggesting that cannabinoids can interact with the noradrenergic system. Noradrenergic trans...

Exposure to Smoking Imagery in Popular Films and Adolescent Smoking in Mexico

Science.gov (United States)

Thrasher, James F.; Jackson, Christine; Arillo-Santillán, Edna; Sargent, James D.

2008-01-01

Background Exposure to smoking imagery in films is consistently associated with smoking behavior and its psychological antecedents among adolescents in high-income countries, but its association with adolescent smoking in middle-income countries is unknown. Methods In 2006, a cross-sectional sample of 3876 Mexican adolescents in secondary school was surveyed on smoking behavior, smoking risk factors, and exposure to 42 popular films that contained smoking. Participants were classified into quartiles of exposure to smoking imagery across all films they reported having seen. Models were estimated to determine associations among quartiles of film-smoking exposure, smoking behavior, and the psychological antecedents of smoking, adjusting for age, gender, sensation seeking, self-esteem, parental smoking, sibling smoking, best-friend smoking, having a bedroom TV, and private versus public school attendance. Analyses were conducted in 2007. Results Adolescents were exposed to an average of 51.7 (SE=1.3) minutes of smoking in the films they viewed. Crude and adjusted ORs indicated positive associations between quartiles of film-smoking exposure and both current smoking (AOR4v1=3.13; pantecedents of smoking uptake. Crude and adjusted coefficients indicated significant, positive associations between exposure and susceptibility to smoking (AOR4v1=1.66; p<0.05); favorable attitudes toward smoking (Adjusted B4v1=0.44; p<0.0001); and perceived peer prevalence of smoking (Adjusted B4v1=0.26; p<0.0001). Conclusions Exposure to smoking in films appears associated with smoking among Mexican adolescents. Policies could aim to decrease youth exposure to smoking in nationally and internationally distributed films. PMID:18617078

Caregiver and adolescent responses to food and beverage marketing exposures through an online survey.

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Kumar, Gayathri; Zytnick, Deena; Onufrak, Stephen; Harris, Jennifer L; Wethington, Holly; Kingsley, Beverly; Park, Sohyun

2014-02-01

The Institute of Medicine noted that current food and beverage marketing practices promote unhealthful diets. However, little public health research has been conducted on food marketing directed toward adolescents, especially using caregiver- and adolescent-reported data. We assessed perceived frequency of food/beverage advertising exposure and common locations of food/beverage marketing exposure for adolescents using 2012 Summer ConsumerStyles and YouthStyles survey data on US adults ≥18 years of age and their children ages 12-17 (n=847), respectively. Exposure to advertisements for fast food, soda, fruit drinks, sports drinks, energy drinks, and bottled water were categorized as food/beverage categories with the highest, at least daily, exposure reported for fast food. Caregivers more frequently reported that adolescents viewed all food/beverage advertisements ≥1 time/day than the adolescents reported (chi-square tests, pfood/beverage marketing most frequently on television followed by at the supermarket. Our study showed that adolescents reported lower frequency of food and beverage advertising exposure than their caregivers. Further research may be needed to verify self-reported exposure data on food and beverage advertising as a way to obtain data for use in research on its relationship with diet quality and obesity.

The Pharmacologic and Clinical Effects of Illicit Synthetic Cannabinoids.

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White, C Michael

2017-03-01

This article presents information on illicitly used synthetic cannabinoids. Synthetic cannabinoids are structurally heterogeneous and commonly used drugs of abuse that act as full agonists of the cannabinoid type-1 receptor but have a variety of additional pharmacologic effects. There are numerous cases of patient harm and death in the United States, Europe, and Australia with many psychological, neurological, cardiovascular, pulmonary, and renal adverse events. Although most users prefer using cannabis, there are convenience, legal, and cost reasons driving the utilization of synthetic cannabinoids. Clinicians should be aware of pharmacologic and clinical similarities and differences between synthetic cannabinoid and cannabis use, the limited ability to detect synthetic cannabinoids in the urine or serum, and guidance to treat adverse events. © 2016, The American College of Clinical Pharmacology.

Comparison of outcome expectancies for synthetic cannabinoids and botanical marijuana.

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Lauritsen, Kirstin J; Rosenberg, Harold

2016-07-01

Although initially developed for medical purposes, synthetic cannabinoids have also been consumed for recreational purposes. To evaluate whether agreement with positive and negative outcome expectancies differed for synthetic cannabinoids versus botanical marijuana, and assess reported reasons for using synthetic cannabinoids. Using a web-based recruitment and data collection procedure, 186 adults who had used both synthetic cannabinoids and botanical marijuana and 181 adults who had used botanical marijuana but not synthetic cannabinoids, completed measures of outcome expectancies and other relevant questionnaires. A significant interaction revealed that participants who had used both synthetic cannabinoids and botanical marijuana indicated lower agreement with positive expectancies for synthetic cannabinoids, and higher agreement with positive expectancies for botanical marijuana, than did those participants who used only botanical marijuana. There was no interaction between type of drug and use history on agreement with negative expectancies, and participants agreed more strongly with negative outcome expectancies for synthetic cannabinoids than for botanical marijuana whether they had used one or both types of these drugs. The most frequently provided reasons for using synthetic cannabinoids included availability, perceived legality, cost, curiosity, and social interaction. Given growing public acceptance of recreational and medical marijuana, coupled with negative perceptions and increasing regulation of synthetic cannabinoid compounds, botanical marijuana is likely to remain more available and more popular than synthetic cannabinoids.

Does Exposure to Music Videos Predict Adolescents' Sexual Attitudes?

NARCIS (Netherlands)

Beentjes, J.W.J.; Konig, R.P.

2013-01-01

This study investigates whether exposure to music videos predicts adolescents' sexual attitudes when controlled for relevant characteristics of individuals and their social environment. Sexual attitudes are related to their music video use (i.e. exposure to music videos, peer group talk about music

Repeated Exposure to the “Spice” Cannabinoid JWH-018 Induces Tolerance and Enhances Responsiveness to 5-HT1A Receptor Stimulation in Male Rats

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Joshua S. Elmore

2018-02-01

Full Text Available Naphthalen-1-yl-(1-pentylindol-3-ylmethanone (JWH-018 is a synthetic compound found in psychoactive “spice” products that activates cannabinoid receptors. Preclinical evidence suggests that exposure to synthetic cannabinoids increases 5-HT2A/2C receptor function in the brain, an effect which might contribute to psychotic symptoms. Here, we hypothesized that repeated exposures to JWH-018 would enhance behavioral responsiveness to the 5-HT2A/2C receptor agonist DOI. Male Sprague-Dawley rats fitted with subcutaneously (sc temperature transponders received daily injections of JWH-018 (1.0 mg/kg, sc or its vehicle for seven consecutive days. Body temperature and catalepsy scores were determined at 1, 2, and 4 h post-injection each day. At 1 and 7 days after the final repeated treatment, rats received a challenge injection of either DOI (0.1 mg/kg, sc or the 5-HT1A receptor agonist 8-OH-DPAT (0.3 mg/kg, sc, then temperature and behavioral responses were assessed. Behaviors induced by DOI included wet dog shakes and back muscle contractions (i.e., skin jerks, while behaviors induced by 8-OH-DPAT included ambulation, forepaw treading, and flat body posture. On the first day of repeated treatment, JWH-018 produced robust hypothermia and catalepsy which lasted up to 4 h, and these effects were significantly blunted by day 7 of treatment. Repeated exposure to JWH-018 did not affect behaviors induced by DOI, but behavioral and hypothermic responses induced by 8-OH-DPAT were significantly augmented 1 day after cessation of JWH-018 treatment. Collectively, our findings show that repeated treatment with JWH-018 produces tolerance to its hypothermic and cataleptic effects, which is accompanied by transient enhancement of 5-HT1A receptor sensitivity in vivo.

Emerging Role of (EndoCannabinoids in Migraine

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Pinja Leimuranta

2018-04-01

Full Text Available In this mini-review, we summarize recent discoveries and present new hypotheses on the role of cannabinoids in controlling trigeminal nociceptive system underlying migraine pain. Individual sections of this review cover key aspects of this topic, such as: (i the current knowledge on the endocannabinoid system (ECS with emphasis on expression of its components in migraine related structures; (ii distinguishing peripheral from central site of action of cannabinoids, (iii proposed mechanisms of migraine pain and control of nociceptive traffic by cannabinoids at the level of meninges and in brainstem, (iv therapeutic targeting in migraine of monoacylglycerol lipase and fatty acid amide hydrolase, enzymes which control the level of endocannabinoids; (v dual (possibly opposing actions of cannabinoids via anti-nociceptive CB1 and CB2 and pro-nociceptive TRPV1 receptors. We explore the cannabinoid-mediated mechanisms in the frame of the Clinical Endocannabinoid Deficiency (CECD hypothesis, which implies reduced tone of endocannabinoids in migraine patients. We further discuss the control of cortical excitability by cannabinoids via inhibition of cortical spreading depression (CSD underlying the migraine aura. Finally, we present our view on perspectives of Cannabis-derived (extracted or synthetized marijuana components or novel endocannabinoid therapeutics in migraine treatment.

Adolescent cannabis use : What is the evidence for functional brain alteration?

NARCIS (Netherlands)

Lorenzetti, V; Alonso-Lana, S.; Youssef, G. J.; Verdejo-Garcia, A.; Suo, C.; Cousijn, J.; Takagi, M.; Yücel, M.; Solowij, N.

2016-01-01

Background: Cannabis use typically commences during adolescence, a period during which the brain undergoes profound remodeling in areas that are high in cannabinoid receptors and that mediate cognitive control and emotion regulation. It is therefore important to determine the impact of adolescent

Somatic symptoms among US adolescent females: associations with sexual and physical violence exposure.

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Halpern, Carolyn Tucker; Tucker, Christine M; Bengtson, Angela; Kupper, Lawrence L; McLean, Samuel A; Martin, Sandra L

2013-12-01

The objective of this study is to examine the association between physical and sexual violence exposure and somatic symptoms among female adolescents. We studied a nationally representative sample of 8,531 females, aged 11-21 years, who participated in the 1994-1995 Wave I of the National Longitudinal Study of Adolescent Health (Add Health). Female adolescents were asked how often they had experienced 16 specific somatic symptoms during the past 12 months. Two summary categorical measures were constructed based on tertiles of the distributions for the entire female sample: (a) total number of different types of symptoms experienced, and (b) number of frequent (once a week or more often) different symptoms experienced. Groups were mutually exclusive. We examined associations between adolescents' violence exposure and somatic symptoms using multinomial logistic regression analyses. About 5 % of adolescent females reported both sexual and non-sexual violence, 3 % reported sexual violence only, 36 % reported non-sexual violence only, and 57 % reported no violence. Adolescents who experienced both sexual and non-sexual violence were the most likely to report many different symptoms and to experience very frequent or chronic symptoms. Likelihood of high symptomatology was next highest among adolescents who experienced sexual violence only, followed by females who experienced non-sexual violence only. Findings support an exposure-response association between violence exposure and somatic symptoms, suggesting that symptoms can be markers of victimization. Treating symptoms alone, without addressing the potential violence experienced, may not adequately improve adolescents' somatic complaints and well-being.

Cannabinoides y su posible uso en el glaucoma Cannabinoids and their possible use in the treatment of glaucoma

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Beatriz Zozaya Aldana

2011-09-01

Full Text Available Aunque la planta Cannabis sativa ha sido empleada desde la más remota antigüedad con fines medicinales, uno de sus derivados, la marihuana, se ha convertido en la droga de uso ilegal más consumida en el mundo. Asimismo tanto el Cannabis como sus cannabinoides se emplean como terapéutico en pocas enfermedades generalmente neurológicas. Se realizó una revisión bibliográfica para exponer el posible uso de los cannabinoides en la terapéutica del glaucoma. Para ello se tuvo en cuenta la literatura disponible sobre el tema, durante el período enero a septiembre de 2010. Se ha comprobado el efecto hipotensor ocular de los cannabinoides al disminuir la producción de humor acuoso, y aumentar la excreción de humor acuoso a través de la malla trabecular y la vía uveoescleral, efecto compatible con el hallazgo de elevadas concentraciones de receptores de cannabinoides rCB1 y rCB2; además, el tetrahidrocannabinol ha demostrado disminuir el efecto neurodegenerativo en modelos de isquemia cerebral en ratas y se evidenció también el efecto beneficioso de los cannabinoides al disminuir la degeneración secundaria asociada al glaucoma mediada por la excitotoxicidad del glutamato. Estos hallazgos sobre el efecto beneficioso de los cannabinoides como hipotensores oculares y por su efecto neuroprotector, transmiten un mensaje esperanzador sobre la función que estos podrían desempeñar en el campo del glaucoma, aunque para mayor seguridad y eficacia serían necesarios ensayos clínicos encaminados a valorar su aplicabilidad en la práctica clínica diaria.Although the Cannabis Sativa plant has been used since the most remote ancient times for medicinal purposes, one of its derivatives, marijuana, has become the most commonly used illegal drug in the world. Similarly, both Cannabis and the cannabinoids are used therapeutically in a small number of general neurological pathologies. Literature review was made to set forth the possible use of

Health Risk Behaviors With Synthetic Cannabinoids Versus Marijuana.

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Clayton, Heather B; Lowry, Richard; Ashley, Carmen; Wolkin, Amy; Grant, Althea M

2017-04-01

Data are limited on the behavioral risk correlates of synthetic cannabinoid use. The purpose of this study was to compare the behavioral risk correlates of synthetic cannabinoid use with those among marijuana users. Data from the 2015 Youth Risk Behavior Survey, a cross-sectional survey conducted in a nationally representative sample of students in grades 9 through 12 ( N = 15 624), were used to examine the association between self-reported type of marijuana use (ie, never use of marijuana and synthetic cannabinoids, ever use of marijuana only, and ever use of synthetic cannabinoids) and self-report of 36 risk behaviors across 4 domains: substance use, injury/violence, mental health, and sexual health. Multivariable models were used to calculate adjusted prevalence ratios. Students who ever used synthetic cannabinoids had a significantly greater likelihood of engaging in each of the behaviors in the substance use and sexual risk domains compared with students who ever used marijuana only. Students who ever used synthetic cannabinoids were more likely than students who ever used marijuana only to have used marijuana before age 13 years, to have used marijuana ≥1 times during the past 30 days, and to have used marijuana ≥20 times during the past 30 days. Several injury/violence behaviors were more prevalent among students who ever used synthetic cannabinoids compared with students who ever used marijuana only. Health professionals and school-based substance use prevention programs should include strategies focused on the prevention of both synthetic cannabinoids and marijuana. Copyright © 2017 by the American Academy of Pediatrics.

Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines.

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Massi, Paola; Vaccani, Angelo; Ceruti, Stefania; Colombo, Arianna; Abbracchio, Maria P; Parolaro, Daniela

2004-03-01

Recently, cannabinoids (CBs) have been shown to possess antitumor properties. Because the psychoactivity of cannabinoid compounds limits their medicinal usage, we undertook the present study to evaluate the in vitro antiproliferative ability of cannabidiol (CBD), a nonpsychoactive cannabinoid compound, on U87 and U373 human glioma cell lines. The addition of CBD to the culture medium led to a dramatic drop of mitochondrial oxidative metabolism [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide test] and viability in glioma cells, in a concentration-dependent manner that was already evident 24 h after CBD exposure, with an apparent IC(50) of 25 microM. The antiproliferative effect of CBD was partially prevented by the CB2 receptor antagonist N-[(1S)-endo-1,3,3-trimethylbicyclo[2,2,1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528; SR2) and alpha-tocopherol. By contrast, the CB1 cannabinoid receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR141716; SR1), capsazepine (vanilloid receptor antagonist), the inhibitors of ceramide generation, or pertussis toxin did not counteract CBD effects. We also show, for the first time, that the antiproliferative effect of CBD was correlated to induction of apoptosis, as determined by cytofluorimetric analysis and single-strand DNA staining, which was not reverted by cannabinoid antagonists. Finally, CBD, administered s.c. to nude mice at the dose of 0.5 mg/mouse, significantly inhibited the growth of subcutaneously implanted U87 human glioma cells. In conclusion, the nonpsychoactive CBD was able to produce a significant antitumor activity both in vitro and in vivo, thus suggesting a possible application of CBD as an antineoplastic agent.

The anabolic steroid nandrolone alters cannabinoid self-administration and brain CB1 receptor density and function.

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Struik, Dicky; Fadda, Paola; Zara, Tamara; Zamberletti, Erica; Rubino, Tiziana; Parolaro, Daniela; Fratta, Walter; Fattore, Liana

2017-01-01

Clinical and pre-clinical observations indicate that anabolic-androgenic steroids can induce neurobiological changes that alter the rewarding effects of drugs of abuse. In this study, we investigated the effect of the anabolic steroid nandrolone on the rewarding properties of the cannabinoid CB 1 receptor agonist WIN55,212-2 (WIN) in rats. Lister Hooded male rats were treated intramuscularly with nandrolone (15mg/kg) or vehicle for 14 consecutive days, and then allowed to self-administer WIN (12.5μg/kg/infusion) intravenously. After reaching stable drug intake, self-administration behavior was extinguished to examine drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Other behavioral parameters presumed to influence drug-taking and drug-seeking behaviors were examined to gain more insight into the behavioral specificity of nandrolone treatment. Finally, animals were sacrificed for analysis of CB 1 receptor density and function in selected brain areas. We found that nandrolone-treated rats self-administered up to 2 times more cannabinoid than vehicle-treated rats, but behaved similarly to control rats when tested for drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Enhanced cannabinoid intake by nandrolone-treated rats was not accompanied by changes in locomotor activity, sensorimotor gating, or memory function. However, our molecular data show that after chronic WIN self-administration nandrolone-treated rats display altered CB 1 receptor density and function in selected brain areas. We hypothesize that increased cannabinoid self-administration in nandrolone-treated rats results from a nandrolone-induced decrease in reward function, which rats seem to compensate by voluntarily increasing their cannabinoid intake. Altogether, our findings corroborate the hypothesis that chronic exposure to anabolic-androgenic steroids induces dysfunction of the reward pathway in rats and might represent a potential risk factor for abuse of

Interactions of Cannabinoids With Biochemical Substrates

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Brian F Thomas

2017-05-01

Full Text Available Recent decades have seen much progress in the identification and characterization of cannabinoid receptors and the elucidation of the mechanisms by which derivatives of the Cannabis sativa plant bind to receptors and produce their physiological and psychological effects. The information generated in this process has enabled better understanding of the fundamental physiological and psychological processes controlled by the central and peripheral nervous systems and has fostered the development of natural and synthetic cannabinoids as therapeutic agents. A negative aspect of this decades-long effort is the proliferation of clandestinely synthesized analogs as recreational street drugs with dangerous effects. Currently, the interactions of cannabinoids with their biochemical substrates are extensively but inadequately understood, and the clinical application of derived and synthetic receptor ligands remains quite limited. The wide anatomical distribution and functional complexity of the cannabinoid system continue to indicate potential for both therapeutic and side effects, which offers challenges and opportunities for medicinal chemists involved in drug discovery and development.

Exposure to teasing on popular television shows and associations with adolescent body satisfaction.

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Eisenberg, Marla E; Ward, Ellen; Linde, Jennifer A; Gollust, Sarah E; Neumark-Sztainer, Dianne

2017-12-01

This study uses a novel mixed methods design to examine the relationship between incidents of teasing in popular television shows and body satisfaction of adolescent viewers. Survey data were used to identify 25 favorite television shows in a large population-based sample of Minnesota adolescents (N=2793, age=14.4years). Data from content analysis of teasing incidents in popular shows were linked to adolescent survey data. Linear regression models examined associations between exposure to on-screen teasing in adolescents' own favorite shows and their body satisfaction. Effect modification by adolescent weight status was tested using interaction terms. Teasing on TV was common, with 3.3 incidents per episode; over one-quarter of teasing was weight/shape-related. Exposure to weight/shape-related teasing (β=-0.43, p=0.008) and teasing with overweight targets (β=-0.03, p=0.02) was inversely associated with girls' body satisfaction; no associations were found for boys. Findings were similar regardless of the adolescent viewer's weight status. Families, health care providers, media literacy programs and the entertainment industry are encouraged to consider the negative effects exposure to weight stigmatization can have on adolescent girls. Copyright © 2017 Elsevier Inc. All rights reserved.

Early Adolescent Exposure to Alcohol Advertising and Its Relationship to Underage Drinking

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Collins, Rebecca L.; Ellickson, Phyllis L.; McCaffrey, Daniel; Hambarsoomians, Katrin

2009-01-01

Purpose To determine whether early adolescents who are exposed to alcohol marketing are subsequently more likely to drink. Recent studies suggest that exposure to alcohol ads has a limited influence on drinking in mid-adolescence. Early adolescents may be more vulnerable to alcohol advertising effects. Methods Two in-school surveys of 1,786 South Dakota youth measured exposure to television beer advertisements, alcohol ads in magazines, in-store beer displays and beer concessions, radio-listening time, and ownership of beer promotional items during sixth grade, and drinking intentions and behavior at seventh grade. Multivariate regression equations predicted the two drinking outcomes using the advertising exposure variables and controlling for psychosocial factors and prior drinking. Results After adjusting for covariates, the joint effect of exposure to advertising from all six sources at Grade 6 was strongly predictive of Grade 7 drinking and Grade 7 intentions to drink. Youth in the 75th percentile of alcohol marketing exposure had a predicted probability of drinking that was 50% greater than that of youth in the 25th percentile. Conclusions Although causal effects are uncertain, policy makers should consider limiting a variety of marketing practices that could contribute to drinking in early adolescence. PMID:17531759

Cannabinoids in the management of spasticity associated with multiple sclerosis

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Anna Maria Malfitano

2008-08-01

Full Text Available Anna Maria Malfitano, Maria Chiara Proto, Maurizio BifulcoDipartimento di Scienze Farmaceutiche, Università degli Studi di SalernoAbstract: The endocannabinoid system and cannabinoid-based treatments have been involved in a wide number of diseases. In particular, several studies suggest that cannabinoids and endocannabinoids may have a key role in the pathogenesis and therapy of multiple sclerosis (MS. In this study we highlight the main findings reported in literature about the relevance of cannabinoid drugs in the management and treatment of MS. An increasing body of evidence suggests that cannabinoids have beneficial effects on the symptoms of MS, including spasticity and pain. In this report we focus on the effects of cannabinoids in the relief of spasticity describing the main findings in vivo, in the mouse experimental allergic encephalomyelitis model of MS. We report on the current treatments used to control MS symptoms and the most recent clinical studies based on cannabinoid treatments, although long-term studies are required to establish whether cannabinoids may have a role beyond symptom amelioration in MS.Keywords: cannabinoids, multiple sclerosis, spasticity

Sensitive Quantification of Cannabinoids in Milk by Alkaline Saponification-Solid Phase Extraction Combined with Isotope Dilution UPLC-MS/MS.

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Wei, Binnian; McGuffey, James E; Blount, Benjamin C; Wang, Lanqing

2016-01-01

Maternal exposure to marijuana during the lactation period-either active or passive-has prompted concerns about transmission of cannabinoids to breastfed infants and possible subsequent adverse health consequences. Assessing these health risks requires a sensitive analytical approach that is able to quantitatively measure trace-level cannabinoids in breast milk. Here, we describe a saponification-solid phase extraction approach combined with ultra-high-pressure liquid chromatography-tandem mass spectrometry for simultaneously quantifying Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) in breast milk. We demonstrate for the first time that constraints on sensitivity can be overcome by utilizing alkaline saponification of the milk samples. After extensively optimizing the saponification procedure, the validated method exhibited limits of detections of 13, 4, and 66 pg/mL for THC, CBN, and CBD, respectively. Notably, the sensitivity achieved was significantly improved, for instance, the limits of detection for THC is at least 100-fold more sensitive compared to that previously reported in the literature. This is essential for monitoring cannabinoids in breast milk resulting from passive or nonrecent active maternal exposure. Furthermore, we simultaneously acquired multiple reaction monitoring transitions for 12 C- and 13 C-analyte isotopes. This combined analysis largely facilitated data acquisition by reducing the repetitive analysis rate for samples exceeding the linear limits of 12 C-analytes. In addition to high sensitivity and broad quantitation range, this method delivers excellent accuracy (relative error within ±10%), precision (relative standard deviation <10%), and efficient analysis. In future studies, we expect this method to play a critical role in assessing infant exposure to cannabinoids through breastfeeding.

Adolescent substance use in Israel: The roles of exposure to political traumas and posttraumatic stress symptoms.

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Schiff, Miriam; Fang, Lin

2014-06-01

Previous studies have not examined the potential mediating role of posttraumatic stress symptoms (PTS) and moderating roles of gender and ethnicity among adolescents in the aftermath of political traumas, especially in the Middle East. This study of Israeli adolescents aimed to begin bridging these gaps in knowledge. We addressed the following hypotheses: (a) greater exposure to multiple political traumas would be associated with adolescent substance use; (b) greater PTS would be associated with adolescent substance use; (c) PTS would mediate the association of exposure to multiple political traumas on substance use; and (d) gender and ethnicity would moderate the pathways from exposure and PTS to substance use. A nationally representative sample included 4,733 Grade 10 and 11 students (half were females; 36.8% were Arabs). Results of bootstrapping estimations found a significant direct link between exposure to multiple political traumas and substance use, as well as an indirect link through PTS. Gender moderated the relationship between PTS and substance use, while ethnicity moderated the association between exposure and substance use. Specifically, female adolescent substance use decreased when their PTS increased. Arab adolescents who had greater exposure to multiple political traumas used more substances. PTS may be an important mechanism by which trauma exposure is associated with increased substance use. Screening adolescents for PTS and substance use, shortly after political trauma, is essential to address the potential risk factors in vulnerable adolescents.

Effects of Adolescent Intermittent Alcohol Exposure on the Expression of Endocannabinoid Signaling-Related Proteins in the Spleen of Young Adult Rats

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Vázquez, Mariam; Sánchez, Laura; Rivera, Patricia; Gavito, Ana; Mela, Virginia; Alén, Francisco; Decara, Juan; Suárez, Juan; Giné, Elena; López-Moreno, José Antonio; Chowen, Julie; Rodríguez-de-Fonseca, Fernando; Serrano, Antonia; Viveros, María Paz

2016-01-01

Intermittent alcohol exposure is a common pattern of alcohol consumption among adolescents and alcohol is known to modulate the expression of the endocannabinoid system (ECS), which is involved in metabolism and inflammation. However, it is unknown whether this pattern may have short-term consequences on the ECS in the spleen. To address this question, we examined the plasma concentrations of metabolic and inflammatory signals and the splenic ECS in early adult rats exposed to alcohol during adolescence. A 4-day drinking in the dark (DID) procedure for 4 weeks was used as a model of intermittent forced-alcohol administration (20%, v/v) in female and male Wistar rats, which were sacrificed 2 weeks after the last DID session. First, there was no liver damage or alterations in plasma metabolic parameters. However, certain plasma inflammatory signals were altered according to sex and alcohol exposition. Whereas fractalkine [chemokine (C-X3-C motif) ligand 1] was only affected by sex with lower concentration in male rats, there was an interaction between sex and alcohol exposure in the TNF-α and interleukin-6 concentrations and only female rats displayed changes. Regarding the mRNA and protein expression of the ECS, the receptors and endocannabinoid-synthesizing enzymes were found to be altered with area-specific expression patterns in the spleen. Overall, whereas the expression of the cannabinoid receptor CB1 and the nuclear peroxisome proliferator-activated receptor PPARα were lower in alcohol-exposed rats compared to control rats, the CB2 expression was higher. Additionally, the N-acyl-phosphatidylethanolamine-specific phospholipase D expression was high in female alcohol-exposed rats and low in male alcohol-exposed rats. In conclusion, intermittent alcohol consumption during adolescence may be sufficient to induce short-term changes in the expression of splenic endocannabinoid signaling-related proteins and plasma pro-inflammatory cytokines in young adult rats

Effects of Adolescent Intermittent Alcohol Exposure on the Expression of Endocannabinoid Signaling-Related Proteins in the Spleen of Young Adult Rats.

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Francisco Javier Pavón

Full Text Available Intermittent alcohol exposure is a common pattern of alcohol consumption among adolescents and alcohol is known to modulate the expression of the endocannabinoid system (ECS, which is involved in metabolism and inflammation. However, it is unknown whether this pattern may have short-term consequences on the ECS in the spleen. To address this question, we examined the plasma concentrations of metabolic and inflammatory signals and the splenic ECS in early adult rats exposed to alcohol during adolescence. A 4-day drinking in the dark (DID procedure for 4 weeks was used as a model of intermittent forced-alcohol administration (20%, v/v in female and male Wistar rats, which were sacrificed 2 weeks after the last DID session. First, there was no liver damage or alterations in plasma metabolic parameters. However, certain plasma inflammatory signals were altered according to sex and alcohol exposition. Whereas fractalkine [chemokine (C-X3-C motif ligand 1] was only affected by sex with lower concentration in male rats, there was an interaction between sex and alcohol exposure in the TNF-α and interleukin-6 concentrations and only female rats displayed changes. Regarding the mRNA and protein expression of the ECS, the receptors and endocannabinoid-synthesizing enzymes were found to be altered with area-specific expression patterns in the spleen. Overall, whereas the expression of the cannabinoid receptor CB1 and the nuclear peroxisome proliferator-activated receptor PPARα were lower in alcohol-exposed rats compared to control rats, the CB2 expression was higher. Additionally, the N-acyl-phosphatidylethanolamine-specific phospholipase D expression was high in female alcohol-exposed rats and low in male alcohol-exposed rats. In conclusion, intermittent alcohol consumption during adolescence may be sufficient to induce short-term changes in the expression of splenic endocannabinoid signaling-related proteins and plasma pro-inflammatory cytokines in

The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids.

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McAllister, Sean D; Soroceanu, Liliana; Desprez, Pierre-Yves

2015-06-01

As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Δ(9)-tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor subtypes. Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy. During the last decade, however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers. In addition to THC, there are many other cannabinoids found in CS, and a majority produces little to no psychoactivity due to the inability to activate cannabinoid receptors. For example, the second most abundant cannabinoid in CS is the non-psychoactive cannabidiol (CBD). Using animal models, CBD has been shown to inhibit the progression of many types of cancer including glioblastoma (GBM), breast, lung, prostate and colon cancer. This review will center on mechanisms by which CBD, and other plant-derived cannabinoids inefficient at activating cannabinoid receptors, inhibit tumor cell viability, invasion, metastasis, angiogenesis, and the stem-like potential of cancer cells. We will also discuss the ability of non-psychoactive cannabinoids to induce autophagy and apoptotic-mediated cancer cell death, and enhance the activity of first-line agents commonly used in cancer treatment.

Modifying exposure to smoking depicted in movies: a novel approach to preventing adolescent smoking.

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Sargent, James D; Dalton, Madeline A; Heatherton, Todd; Beach, Mike

2003-07-01

Most behavioral approaches to adolescent smoking address the behavior directly. We explore an indirect approach: modifying exposure to portrayals of smoking in movies. To describe adolescents' exposure to smoking in movies and to examine factors that could modify such exposure. Occurrences of smoking were counted in each of 601 popular movies. Four thousand nine hundred ten northern New England junior high school students were asked to report which movies they had seen from a randomly generated subsample of 50 films, and responses were used to estimate exposure to the entire sample. Analysis The outcome variable was exposure to movie smoking, defined as the number of smoking occurrences seen. Risk factors for exposure included access to movies (movie channels, videotape use, and movie theater); parenting (R [restricted]-rated movie restrictions, television restrictions, parenting style); and characteristics of the child (age, sex, school performance, sensation-seeking propensity, rebelliousness, and self-esteem). We used multiple regression to assess the association between risk factors and exposure to movie smoking. Subjects had seen an average of 30% of the movie sample (interquartile range, 20%-44%), from which they were exposed to 1160 (interquartile range, 640-1970) occurrences of smoking. In a multivariate model, exposure to movie smoking increased (all P values Parent restriction on viewing R-rated movies resulted in a 50% reduction in exposure to movie smoking. There was no association between parenting style and exposure to movie smoking. Much of the protective effect of parent R-rated movie restriction on adolescent smoking was mediated through lower exposure to movie smoking. Adolescents see thousands of smoking depictions in movies, and this influences their attitudes and behavior. Exposure to movie smoking is reduced when parents limit movie access. Teaching parents to monitor and enforce movie access guidelines could reduce adolescent smoking in an

Consequences of adolescent ethanol exposure in male Sprague-Dawley rats on fear conditioning and extinction in adulthood

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Broadwater, Margaret A.

Some evidence suggests that adolescents are more vulnerable than adults to alcohol-induced cognitive deficits and that these deficits may persist into adulthood. Five experiments were conducted to assess long-term consequences of ethanol exposure on tone and context Pavlovian fear conditioning in male Sprague-Dawley rats. Experiment 1 examined age-related differences in sensitivity to ethanol-induced disruptions of fear conditioning to a pre-conditioning ethanol challenge. Experiments 2 examined fear conditioning 22 days after early-mid adolescent (P28-48) or adult (P70-90) exposure to 4 g/kg i.g. ethanol or water given every other day (total of 11 exposures). In Experiment 3, mid-late adolescents (P35-55) were exposed in the same manner to assess whether timing of ethanol exposure within the adolescent period would differentially affect later fear conditioning. Experiment 4 assessed the influence of prior adolescent or adult ethanol exposure on the disrupting effects of a pre-conditioning ethanol challenge. In Experiment 5, neurogenesis (doublecortin---DCX) and cholinergic (choline acetyltransferase---ChAT) markers were measured to assess potential long-term ethanol-induced changes in neural mechanisms important for learning and memory. Results indicated that the long-lasting behavioral effects of ethanol exposure varied depending on exposure age, with early-mid adolescent exposed animals showing attenuated context fear retention (a relatively hippocampal-dependent task), whereas mid-late adolescent and adult exposed animals showed slower context extinction (thought to be reliant on the mPFC). Early-mid adolescent ethanol-exposed animals also had significantly less DCX and ChAT expression than their water-exposed counterparts, possibly contributing to deficits in context fear. Tone fear was not influenced by prior ethanol exposure at any age. In terms of age differences in ethanol sensitivity, adolescents were less sensitive than adults to ethanol

How important are sex differences in cannabinoid action?

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Fattore, Liana; Fratta, Walter

2010-06-01

In humans as in animals, males and females are dissimilar in their genetic and hormonally driven behaviour; they process information differently, perceive experience and emotions in different ways, display diverse attitudes, language and social skills, and show sex-related differences in the brain anatomy and organization. Drug addiction is a widespread relapsing illness that affects both men and women. Sex-dependent differences have been frequently observed in the biological and behavioural effects of substances of abuse, including cannabis. Beside sex differences observed in the cannabinoid-induced effects related to cannabis abuse and dependence, cannabinoids have been shown to exert sex-dependent effects also in other physiological and behavioural aspects, such as food intake and energy balance (more evident in males), or anxiety and depression (more evident in females). Research has just begun to identify factors which could provide a neurobiological basis for gender-based differences in cannabinoid effects, among which, gonadal hormones seem to play a crucial role. Yet, cannabinoid pharmacodynamic and pharmacokinetic may also be important, as sex differences in cannabinoid effects might be due, at least in part, to differences in muscle mass and fat tissue distribution between males and females. Here, we will review both clinical and laboratory-based research evidence revealing important sex-related differences in cannabinoid effects, and put forward some suggestions for future studies to fill the gap in our knowledge of gender-specific bias in cannabinoid pharmacology.

Exposure to radio-frequency electromagnetic fields and behavioural problems in Bavarian children and adolescents

International Nuclear Information System (INIS)

Thomas, Silke; Heinrich, Sabine; Kries, Ruediger von; Radon, Katja

2010-01-01

Only few studies have so far investigated possible health effects of radio-frequency electromagnetic fields (RF EMF) in children and adolescents, although experts discuss a potential higher vulnerability to such fields. We aimed to investigate a possible association between measured exposure to RF EMF fields and behavioural problems in children and adolescents. 1,498 children and 1,524 adolescents were randomly selected from the population registries of four Bavarian (South of Germany) cities. During an Interview data on participants' mental health, socio-demographic characteristics and potential confounders were collected. Mental health behaviour was assessed using the German version of the Strengths and Difficulties Questionnaire (SDQ). Using a personal dosimeter, we obtained radio-frequency EMF exposure profiles over 24 h. Exposure levels over waking hours were expressed as mean percentage of the reference level. Overall, exposure to radiofrequency electromagnetic fields was far below the reference level. Seven percent of the children and 5% of the adolescents showed an abnormal mental behaviour. In the multiple logistic regression analyses measured exposure to RF fields in the highest quartile was associated to overall behavioural problems for adolescents (OR 2.2; 95% CI 1.1-4.5) but not for children (1.3; 0.7-2.6). These results are mainly driven by one subscale, as the results showed an association between exposure and conduct problems for adolescents (3.7; 1.6-8.4) and children (2.9; 1.4-5.9). As this is one of the first studies that investigated an association between exposure to mobile telecommunication networks and mental health behaviour more studies using personal dosimetry are warranted to confirm these findings.

Cannabinoids modulate hippocampal memory and plasticity.

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Abush, Hila; Akirav, Irit

2010-10-01

Considerable evidence demonstrates that cannabinoid agonists impair whereas cannabinoid antagonists improve memory and plasticity. However, recent studies suggest that the effects of cannabinoids on learning do not necessarily follow these simple patterns, particularly when emotional memory processes are involved. We investigated the involvement of the cannabinoid system in hippocampal learning and plasticity using the fear-related inhibitory avoidance (IA) and the non-fear-related spatial learning paradigms, and cellular models of learning and memory, i.e., long-term potentiation (LTP) and long-term depression (LTD). We found that microinjection into the CA1 of the CB1/CB2 receptor agonist WIN55,212-2 (5 μg/side) and an inhibitor of endocannabinoid reuptake and breakdown AM404 (200 ng/side) facilitated the extinction of IA, while the CB1 receptor antagonist AM251 (6 ng/side) impaired it. WIN55,212-2 and AM251 did not affect IA conditioning, while AM404 enhanced it, probably due to a drug-induced increase in pain sensitivity. However, in the water maze, systemic or local CA1 injections of AM251, WIN55,212-2, and AM404 all impaired spatial learning. We also found that i.p. administration of WIN55,212-2 (0.5 mg/kg), AM404 (10 mg/kg), and AM251 (2 mg/kg) impaired LTP in the Schaffer collateral-CA1 projection, whereas AM404 facilitated LTD. Our findings suggest diverse effects of the cannabinoid system on CA1 memory and plasticity that cannot be categorized simply into an impairing or an enhancing effect of cannabinoid activation and deactivation, respectively. Moreover, they provide preclinical support for the suggestion that targeting the endocannabinoid system may aid in the treatment of disorders associated with impaired extinction-like processes, such as post-traumatic stress disorder. © 2009 Wiley-Liss, Inc.

Secondhand Smoke Exposure and Depressive Symptoms among Korean Adolescents: JS High School Study.

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Na Hyun Kim

Full Text Available Increasing evidence suggests that secondhand smoke exposure (SHSE may affect not only physical health, but also mental health. Therefore, we evaluated the association between SHSE and depressive symptoms among Korean adolescents.The JS High School Study enrolled 1071 high school freshmen from a rural community of South Korea. The current analysis was limited to 989 adolescents (495 male and 494 female adolescents, after excluding 48 ever-smokers, 3 students with physician-diagnosed depression, and 31 students who did not complete the depression questionnaire. SHSE was assessed using a self-reported questionnaire and was classified into three groups: none, occasional exposure, and regular exposure. Depressive symptoms were assessed according to the Beck Depression Inventory (BDI score, ranging from 0 to 63, and the presence of depressive symptoms was defined as a BDI score ≥10.Overall, adolescents with SHSE were more likely to have depressive symptoms than those without SHSE (p = 0.042.In a sex-specific analysis treating the BDI score as a continuous variable, regular SHSE was independently associated with higher BDI scores in male adolescents (β = 2.25, p = 0.026, but not in female adolescents (β = 1.11, p = 0.253. Compared to no SHSE, the odds ratio for having depressive symptoms among male adolescents with regular SHSE was 2.17 (95% confidence interval, 1.11 to 4.25 after adjusting for age, body mass index, and study year, and 3.65 (95% confidence interval, 1.52 to 8.73 after adjusting for age, body mass index, study year, exercise, and household income.Regular exposure to secondhand smoke was associated with having depressive symptoms among Korean male adolescents.

Secondhand Smoke Exposure and Depressive Symptoms among Korean Adolescents: JS High School Study.

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Kim, Na Hyun; Park, Ji Hye; Choi, Dong Phil; Lee, Joo Young; Kim, Hyeon Chang

2016-01-01

Increasing evidence suggests that secondhand smoke exposure (SHSE) may affect not only physical health, but also mental health. Therefore, we evaluated the association between SHSE and depressive symptoms among Korean adolescents. The JS High School Study enrolled 1071 high school freshmen from a rural community of South Korea. The current analysis was limited to 989 adolescents (495 male and 494 female adolescents), after excluding 48 ever-smokers, 3 students with physician-diagnosed depression, and 31 students who did not complete the depression questionnaire. SHSE was assessed using a self-reported questionnaire and was classified into three groups: none, occasional exposure, and regular exposure. Depressive symptoms were assessed according to the Beck Depression Inventory (BDI) score, ranging from 0 to 63, and the presence of depressive symptoms was defined as a BDI score ≥10. Overall, adolescents with SHSE were more likely to have depressive symptoms than those without SHSE (p = 0.042).In a sex-specific analysis treating the BDI score as a continuous variable, regular SHSE was independently associated with higher BDI scores in male adolescents (β = 2.25, p = 0.026), but not in female adolescents (β = 1.11, p = 0.253). Compared to no SHSE, the odds ratio for having depressive symptoms among male adolescents with regular SHSE was 2.17 (95% confidence interval, 1.11 to 4.25) after adjusting for age, body mass index, and study year, and 3.65 (95% confidence interval, 1.52 to 8.73) after adjusting for age, body mass index, study year, exercise, and household income. Regular exposure to secondhand smoke was associated with having depressive symptoms among Korean male adolescents.

Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex.

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Rubino, Tiziana; Prini, Pamela; Piscitelli, Fabiana; Zamberletti, Erica; Trusel, Massimo; Melis, Miriam; Sagheddu, Claudia; Ligresti, Alessia; Tonini, Raffaella; Di Marzo, Vincenzo; Parolaro, Daniela

2015-01-01

Current concepts suggest that exposure to THC during adolescence may act as a risk factor for the development of psychiatric disorders later in life. However, the molecular underpinnings of this vulnerability are still poorly understood. To analyze this, we investigated whether and how THC exposure in female rats interferes with different maturational events occurring in the prefrontal cortex during adolescence through biochemical, pharmacological and electrophysiological means. We found that the endocannabinoid system undergoes maturational processes during adolescence and that THC exposure disrupts them, leading to impairment of both endocannabinoid signaling and endocannabinoid-mediated LTD in the adult prefrontal cortex. THC also altered the maturational fluctuations of NMDA subunits, leading to larger amounts of gluN2B at adulthood. Adult animals exposed to THC during adolescence also showed increased AMPA gluA1 with no changes in gluA2 subunits. Finally, adolescent THC exposure altered cognition at adulthood. All these effects seem to be triggered by the disruption of the physiological role played by the endocannabinoid system during adolescence. Indeed, blockade of CB1 receptors from early to late adolescence seems to prevent the occurrence of pruning at glutamatergic synapses. These results suggest that vulnerability of adolescent female rats to long-lasting THC adverse effects might partly reside in disruption of the pivotal role played by the endocannabinoid system in the prefrontal cortex maturation. Copyright © 2014 Elsevier Inc. All rights reserved.

Exposure to a Highly Caloric Palatable Diet during the Perinatal Period Affects the Expression of the Endogenous Cannabinoid System in the Brain, Liver and Adipose Tissue of Adult Rat Offspring.

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María Teresa Ramírez-López

Full Text Available Recent studies have linked gestational exposure to highly caloric diets with a disrupted endogenous cannabinoid system (ECS. In the present study, we have extended these studies by analyzing the impact of the exposure to a palatable diet during gestation and lactation on a the adult expression of endocannabinoid-related behaviors, b the metabolic profile of adult offspring and c the mRNA expression of the signaling machinery of the ECS in the hypothalamus, the liver and the adipose tissue of adult offspring of both sexes. Exposure to a palatable diet resulted in a sex-dimorphic and perinatal diet specific feeding behaviors, including the differential response to the inhibitory effects of the cannabinoid receptor inverse agonist AM251, b features of metabolic syndrome including increased adiposity, hyperleptinemia, hypertriglyceridemia and hypercholesterolemia and c tissue and sex-specific changes in the expression of both CB1 and CB2 receptors and in that of the endocannabinoid-degrading enzymes FAAH and MAGL, being the adipose tissue the most affected organ analyzed. Since the effects were observed in adult animals that were weaned while consuming a normal diet, the present results indicate that the ECS is one of the targets of maternal programming of the offspring energy expenditure. These results clearly indicate that the maternal diet has long-term effects on the development of pups through multiple alterations of signaling homeostatic pathways that include the ECS. The potential relevance of these alterations for the current obesity epidemic is discussed.

Prenatal, perinatal, and adolescent exposure to marijuana: Relationships with aggressive behavior.

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Barthelemy, Olivier J; Richardson, Mark A; Cabral, Howard J; Frank, Deborah A

This manuscript reviews research exploring the relationship between prenatal, perinatal, and adolescent exposure to marijuana and aggressive behavior, including physical aggression. Areas of inquiry include animal research, as well as human research, on prenatal exposure and on marijuana use during adolescence. Potential psychosocial and psychopharmacological mechanisms are identified, as well as relevant confounds. The prenatal marijuana exposure literature provides minimal support for a direct relationship with aggressive behavior in childhood. The adolescent use literature suggests a marginal (at best) association between acute intoxication and aggressive behavior, and an association between chronic use and aggressive behavior heavily influenced by demographic variables, rather than direct, psychopharmacological mechanisms. Cannabis withdrawal symptoms also may include aggression and anger, but there is little evidence to suggest that these effects are large or specific to withdrawal from marijuana compared to other substances. This review will offer recommendations for clinical care and public policy, as well as important questions for future research. Copyright © 2016 Elsevier Inc. All rights reserved.

Adolescents' exposure to sexy media does not hasten the initiation of sexual intercourse.

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Steinberg, Laurence; Monahan, Kathryn C

2011-03-01

It is widely believed that exposure to sexy content in the mass media leads teenagers to become sexually active. Although most research linking sexy media exposure to adolescents' sexual behavior is cross-sectional, several recent, well-publicized longitudinal studies purport to find a causal connection, which has alarmed the public and prompted criticism of the entertainment industry for its corrupting influence on youth. One problem in research on media effects on sexual activity, however, is that outcomes that are presumed to result from media exposure may actually be due to factors that differentially predispose adolescents to have different degrees of media exposure and are themselves related to sexual activity. We reanalyzed data from one of these longitudinal studies (Brown et al., 2006) using propensity score matching to control for preexisting differences between adolescents with and without high exposure to sexy media. With such controls for differential selection in place, we found no evidence that the initiation of sexual intercourse is hastened by exposure to sexy media. PsycINFO Database Record (c) 2011 APA, all rights reserved.

Preclinical and Clinical Assessment of Cannabinoids as Anti-Cancer Agents

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Daniel A. Ladin

2016-10-01

Full Text Available Cancer is the second leading cause of death in the United States with 1.7 million new cases estimated to be diagnosed in 2016. This disease remains a formidable clinical challenge and represents a substantial financial burden to the US health care system. Therefore, research and development of novel therapeutics for the treatment of cancer is of high priority. Cannabinoids and their derivatives have been utilized for their medicinal and therapeutic properties throughout history. Cannabinoid activity is regulated through the endocannabinoid system, which is comprised of cannabinoid receptors, transporters, and enzymes involved in cannabinoid synthesis and breakdown. More recently, cannabinoids have gained special attention for their role in cancer development and reduction. However, many studies investigated these roles using in vitro models which may not adequately mimic tumor growth and metastasis. As such, this article aims to review study results which evaluated effects of cannabinoids from plant, synthetic and endogenous origins on cancer development in preclinical models and to examine the current standing of cannabinoids currently being tested in human cancer patients.

European longitudinal study on the relationship between adolescents' alcohol marketing exposure and alcohol use

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Bruijn, A. de; Tanghe, J.; Leeuw, R.N.H. de; Engels, R.C.M.E.; Anderson, P.D.; Beccaria, F.; Bujalski, M.; Celata, C.; Gosselt, J.; Schreckenberg, D.; Slodownik, L.; Wothge, J.; Dalen, W. van

2016-01-01

Background and aims: This is the first study to examine the effect of alcohol marketing exposure on adolescents' drinking in a cross-national context. The aim was to examine reciprocal processes between exposure to a wide range of alcohol marketing types and adolescent drinking, controlled for

Drug- and cue-induced reinstatement of cannabinoid-seeking behaviour in male and female rats: influence of ovarian hormones.

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Fattore, L; Spano, M S; Altea, S; Fadda, P; Fratta, W

2010-06-01

Animal and human studies have shown that sex and hormones are key factors in modulating addiction. Previously, we have demonstrated that self-administration of the cannabinoid CB(1) receptor agonist WIN55,212-2 (WIN; 12.5 microg.kg(-1) per infusion) is dependent on sex, intact female rats being more sensitive than males to the reinforcing properties of cannabinoids, and on the oestrous cycle, ovariectomized (OVX) females being less responsive than intact females. This follow-up study investigated whether sex and ovarian function also affect reinstatement of cannabinoid-seeking in rats after exposure to drug or cue priming. After priming with 0.15 or 0.3 mg.kg(-1) WIN, intact female rats exhibited stronger reinstatement than males and OVX females. Responses of intact female rats were higher than those of male and OVX rats even after priming with a drug-associated visual (Light) or auditory (Tone) cue, or a WIN + Light combination. However, latency to the first response did not differ between intact and OVX female rats, and males showed the longest latency to initiate lever-pressing activity. Our study provides compelling evidence for a pivotal role of sex and the oestrous cycle in modulating cannabinoid-seeking, with ovariectomy diminishing drug and cue-induced reinstatement. However, it is possible that sex differences during self-administration training are responsible for sex differences in reinstatement. Finding that not only drug primings but also acute exposure to drug-associated cues can reinstate responding in rats could have significant implications for the development of pharmacological and behavioural treatments of abstinent female and male marijuana smokers.

Adolescents on the Front Line: Exposure to Shelling Via Television and the Parental Role.

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Lavi, Tamar; Itzhaky, Liat; Menachem, Mazal; Solomon, Zahava

2016-01-01

Research suggests that exposure to traumatic content via television inadvertently increases posttraumatic stress symptoms (PTSS) as well as psychological distress, especially among adolescent viewers. The aim of the current study was to assess the effect of news consumption on PTSS and general distress among adolescents who live in a war area, as well as to examine the role of parents as intermediaries of news broadcasting. A total of 65 adolescents who live in a war zone filled out the Child Post Traumatic Stress Reaction Index, the Brief Symptoms Inventory, and a scale measuring the level of real-life exposure, news broadcast consumption, and parents as intermediaries of news broadcasting. A main effect for real-life exposure on both PTSS and general distress was revealed. Interestingly, a three-way interaction between real-life exposure, television exposure, and parents as intermediators was found for general distress. Only under low real-life exposure did parents as intermediaries buffer the effect of television exposure on general distress. Parental intermediation of news broadcasting of traumatic events, especially in situations of continuous, real-life exposure, is essential.

Emergency Physicians' Knowledge of Cannabinoid Designer Drugs

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Patrick M Lank

2013-09-01

Full Text Available Introduction: The use of synthetic drugs of abuse in the United States has grown in the last few years, with little information available on how much physicians know about these drugs and how they are treating patients using them. The objective of this study was to assess emergency physician (EP knowledge of synthetic cannabinoids (SC.Methods: A self-administered internet-based survey of resident and attending EPs at a large urban emergency department (ED was administered to assess familiarity with the terms Spice or K2 and basic knowledge of SC, and to describe some practice patterns when managing SC intoxication in the ED.Results: Of the 83 physicians invited to participate, 73 (88% completed surveys. The terms “Spice” and “K2” for SC were known to 25/73 (34% and 36/73 (49% of respondents. Knowledge of SC came most commonly (72% from non-medical sources, with lay publications and the internet providing most respondents with information. Among those with previous knowledge of synthetic cannabinoids, 25% were not aware that SC are synthetic drugs, and 17% did not know they are chemically most similar to marijuana. Among all participants, 80% felt unprepared caring for a patient in the ED who had used synthetic cannabinoids.Conclusion: Clinically active EPs are unfamiliar with synthetic cannabinoids. Even those who stated they had heard of synthetic cannabinoids answered poorly on basic knowledge questions. More education is needed among EPs of all ages and levels of training on synthetic cannabinoids. [West J Emerg Med. 2013;14(5:467–470.

Exposure to Violence during Adolescence as a Predictor of Perceived Stress Trajectories in Emerging Adulthood.

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Heinze, Justin E; Stoddard, Sarah A; Aiyer, Sophie M; Eisman, Andria B; Zimmerman, Marc A

2017-01-01

Early exposure to violence during adolescence is related to negative psycho-social outcomes later in life. In the present study, we examined the influence of cumulative exposure to violence during adolescence and trajectories of perceived stress in emerging adulthood in a sample of at-risk urban youth ( N = 850; 80.1% African American; 50% female). Growth curve modeling indicated an overall decrease in reported stress as individuals aged. Baseline levels of violence exposure ( M age = 14.9) were associated with higher perceived stress levels in emerging adulthood ( M age = 20.1), but also slightly more negative perceived stress slopes from adolescence into emerging adulthood ( M age = 15.9-22.1). Individuals reporting increased violence exposure over time during adolescence also reported higher perceived stress levels in emerging adulthood ( M age = 20.1). Associations held after controlling for demographics and baseline functioning variables. The results suggest that violence exposure may disrupt normative adaptation to daily stressors in emerging adulthood.

Cannabinoids and Innate Immunity: Taking a Toll on Neuroinflammation

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Eric J. Downer

2011-01-01

Full Text Available The biologically active components of cannabis have therapeutic potential in neuroinflammatory disorders due to their anti-inflammatory propensity. Cannabinoids influence immune function in both the peripheral and the central nervous system (CNS, and the components of the cannabinoid system, the cannabinoid receptors and their endogenous ligands (endocannabinoids, have been detected on immune cells as well as in brain glia. Neuroinflammation is the complex innate immune response of neural tissue to control infection and eliminate pathogens, and Toll-like receptors (TLRs, a major family of pattern recognition receptors (PRRs that mediate innate immunity, have emerged as players in the neuroinflammatory processes underpinning various CNS diseases. This review will highlight evidence that cannabinoids interact with the immune system by impacting TLR-mediated signaling events, which may provide cues for devising novel therapeutic approaches for cannabinoid ligands.

A vapourized Δ(9)-tetrahydrocannabinol (Δ(9)-THC) delivery system part II: comparison of behavioural effects of pulmonary versus parenteral cannabinoid exposure in rodents.

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Manwell, Laurie A; Ford, Brittany; Matthews, Brittany A; Heipel, Heather; Mallet, Paul E

2014-01-01

Studies of the rewarding and addictive properties of cannabinoids using rodents as animal models of human behaviour often fail to replicate findings from human studies. Animal studies typically employ parenteral routes of administration, whereas humans typically smoke cannabis, thus discrepancies may be related to different pharmacokinetics of parenteral and pulmonary routes of administration. Accordingly, a novel delivery system of vapourized Δ(9)-tetrahydrocannabinol (Δ(9)-THC) was developed and assessed for its pharmacokinetic, pharmacodynamic, and behavioural effects in rodents. A commercially available vapourizer was used to assess the effects of pulmonary (vapourized) administration of Δ(9)-THC and directly compared to parenteral (intraperitoneal, IP) administration of Δ(9)-THC. Sprague-Dawley rats were exposed to pure Δ(9)-THC vapour (1, 2, 5, 10, and 20mg/pad), using a Volcano® vapourizing device (Storz and Bickel, Germany) or IP-administered Δ(9)-THC (0.1, 0.3, 0.5, 1.0mg/kg), and drug effects on locomotor activity, food and water consumption, and cross-sensitization to morphine (5mg/kg) were measured. Vapourized Δ(9)-THC significantly increased feeding during the first hour following exposure, whereas IP-administered Δ(9)-THC failed to produce a reliable increase in feeding at all doses tested. Acute administration of 10mg of vapourized Δ(9)-THC induced a short-lasting stimulation in locomotor activity compared to control in the first of four hours of testing over 7days of repeated exposure; this chronic exposure to 10mg of vapourized Δ(9)-THC did not induce behavioural sensitization to morphine. These results suggest vapourized Δ(9)-THC administration produces behavioural effects qualitatively different from those induced by IP administration in rodents. Furthermore, vapourized Δ(9)-THC delivery in rodents may produce behavioural effects more comparable to those observed in humans. We conclude that some of the conflicting findings in animal

European longitudinal study on the relationship between adolescents' alcohol marketing exposure and alcohol use.

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de Bruijn, Avalon; Tanghe, Jacqueline; de Leeuw, Rebecca; Engels, Rutger; Anderson, Peter; Beccaria, Franca; Bujalski, Michał; Celata, Corrado; Gosselt, Jordy; Schreckenberg, Dirk; Słodownik, Luiza; Wothge, Jördis; van Dalen, Wim

2016-10-01

This is the first study to examine the effect of alcohol marketing exposure on adolescents' drinking in a cross-national context. The aim was to examine reciprocal processes between exposure to a wide range of alcohol marketing types and adolescent drinking, controlled for non-alcohol branded media exposure. Prospective observational study (11-12- and 14-17-month intervals), using a three-wave autoregressive cross-lagged model. School-based sample in 181 state-funded schools in Germany, Italy, Netherlands, Poland. A total of 9075 eligible respondents participated in the survey (mean age 14 years, 49.5% male. Adolescents reported their frequency of past-month drinking and binge drinking. Alcohol marketing exposure was measured by a latent variable with 13 items measuring exposure to online alcohol marketing, televised alcohol advertising, alcohol sport sponsorship, music event/festival sponsorship, ownership alcohol-branded promotional items, reception of free samples and exposure to price offers. Confounders were age, gender, education, country, internet use, exposure to non-alcohol sponsored football championships and television programmes without alcohol commercials. The analyses showed one-directional long-term effects of alcohol marketing exposure on drinking (exposure T1 on drinking T2: β = 0.420 (0.058), P  0.05). Similar results were found in the binge drinking model (exposure T1 on binge T2: β = 0.409 (0.054), P  0.05). There appears to be a one-way effect of alcohol marketing exposure on adolescents' alcohol use over time, which cannot be explained by either previous drinking or exposure to non-alcohol-branded marketing. © 2016 Society for the Study of Addiction.

Computer modeling of Cannabinoid receptor type 1

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Sapundzhi Fatima

2018-01-01

Full Text Available Cannabinoid receptors are important class of receptors as they are involved in various physiological processes such as appetite, pain-sensation, mood, and memory. It is important to design receptor-selective ligands in order to treat a particular disorder. The aim of the present study is to model the structure of cannabinoid receptor CB1 and to perform docking between obtained models and known ligands. Two models of CBR1 were prepared with two different methods (Modeller of Chimera and MOE. They were used for docking with GOLD 5.2. It was established a high correlation between inhibitory constant Ki of CB1 cannabinoid ligands and the ChemScore scoring function of GOLD, which concerns both models. This suggests that the models of the CB1 receptors obtained could be used for docking studies and in further investigation and design of new potential, selective and active cannabinoids with the desired effects.

Associations between exposure to information and communication technology (ICT) and reported discomfort among adolescents.

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Palmer, Kristy; Ciccarelli, Marina; Falkmer, Torbjorn; Parsons, Richard

2014-01-01

Use of Information and Communication Technologies (ICT) are common among adolescents in their daily activities.Exposure to ICT has been associated with discomfort and musculoskeletal disorders in adults, with growing concern about the potential risks to children and adolescents' physical health. The objectives of this study were to (i) quantify self-reported discomfort and exposure to ICT among adolescents; and (ii) determine if associations exist between discomfort and levels of exposure. The participant group comprised 33 Australian adolescents aged 12-15 years. The study used self-reports by participants for a one week period. Intensity and location of discomfort was reported via a written discomfort log. ICT exposure and physical activity were reported through an electronic time-use diary. The most common ICT types reported by participants were television, mobile phones and desktop and laptop computers. Discomfort was reported by 86% of participants. The most frequently reported areas were the legs, head/neck, back and shoulders. There was no statistical association found between ICT exposure and discomfort. The majority of participants exceeded the recommended 60 minutes per day of moderate to vigorous physical activity. High exposure to ICT and high prevalence of low level discomfort was reported by the participants. Participating in regular physical activity may have some protective effect against ICT-related discomfort.

The multidrug transporter ABCG2 (BCRP) is inhibited by plant-derived cannabinoids.

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Holland, M L; Lau, D T T; Allen, J D; Arnold, J C

2007-11-01

Cannabinoids are used therapeutically for the palliation of the adverse side effects associated with cancer chemotherapy. However, cannabinoids also inhibit both the activity and expression of the multidrug transporter, P-glycoprotein in vitro. Here we address the interaction of cannabinol (CBN), cannabidiol (CBD) and delta 9-tetrahydrocannabinol (THC) with the related multidrug transporter, ABCG2. Cannabinoid inhibition of Abcg2/ABCG2 was assessed using flow cytometric analysis of substrate accumulation and ATPase activity assays. The cytotoxicity and chemosensitization by cannabinoids was determined with cell viability assays. Expression of cannabinoid and vanilloid receptors was assessed using reverse transcriptase polymerase chain reaction, and cannabinoid modulation of ABCG2 expression was examined using immunoblotting. CBN, CBD and THC increased the intracellular accumulation of the Abcg2/ABCG2 substrate, mitoxantrone, in an over-expressing cell line. The THC metabolite, (-)-11-nor-9-carboxy-delta 9-THC was much less potent. The plant cannabinoids inhibited both basal and substrate stimulated ATPase activity of human ABCG2. Cannabinoid cytotoxicity occurred in the absence of known cannabinoid cell surface receptors, and only at concentrations higher than those required for Abcg2/ABCG2 inhibition. Sub-toxic concentrations of the cannabinoids resensitized the overexpressing cell line to the cytotoxic effect of Abcg2/ABCG2 substrates, mitoxantrone and topotecan. This occurred in the absence of any effect on ABCG2 expression. Cannabinoids are novel Abcg2/ABCG2 inhibitors, reversing the Abcg2-mediated multidrug-resistant phenotype in vitro. This finding may have implications for the co-administration of cannabinoids with pharmaceuticals that are ABCG2 substrates.

Influences of tobacco advertising exposure and conduct problems on smoking behaviors among adolescent males and females.

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Mays, Darren; Gilman, Stephen E; Rende, Richard; Luta, George; Tercyak, Kenneth P; Niaura, Raymond S

2014-06-01

Adolescents with conduct problems are more likely to smoke, and tobacco advertising exposure may exacerbate this risk. Males' excess risk for conduct problems and females' susceptibility to advertising suggest gender-specific pathways to smoking. We investigated the associations between gender, conduct problems, and lifetime smoking and adolescents' exposure to tobacco advertising, and we examined prospective relationships with smoking behaviors. Adolescents completed baseline (2001-2004; n = 541) and 5-year follow-up (2007-2009; n =320) interviews for a family study of smoking risk. Baseline interviews assessed conduct problems and tobacco advertising exposure; smoking behavior was assessed at both timepoints. Generalized linear models analyzed gender differences in the relationship between conduct problems, advertising exposure, and smoking behavior at baseline and longitudinally. At baseline, among males, conduct problems were associated with greater advertising exposure independent of demographics and lifetime smoking. Among females at baseline, conduct problems were associated with greater advertising exposure only among never-smokers after adjusting for demographics. In longitudinal analyses, baseline advertising exposure predicted subsequent smoking initiation (i.e., smoking their first cigarette between baseline and follow-up) for females but not for males. Baseline conduct problems predicted current (i.e., daily or weekly) smoking at follow-up for all adolescents in adjusted models. The findings of this study reinforce that conduct problems are a strong predictor of subsequent current smoking for all adolescents and reveal important differences between adolescent males and females in the relationship between conduct problems, tobacco advertising behavior, and smoking behavior. The findings suggest gender-specific preventive interventions targeting advertising exposure may be warranted.

Cannabinoids inhibit angiogenic capacities of endothelial cells via release of tissue inhibitor of matrix metalloproteinases-1 from lung cancer cells.

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Ramer, Robert; Fischer, Sascha; Haustein, Maria; Manda, Katrin; Hinz, Burkhard

2014-09-15

Cannabinoids inhibit tumor neovascularization as part of their tumorregressive action. However, the underlying mechanism is still under debate. In the present study the impact of cannabinoids on potential tumor-to-endothelial cell communication conferring anti-angiogenesis was studied. Cellular behavior of human umbilical vein endothelial cells (HUVEC) associated with angiogenesis was evaluated by Boyden chamber, two-dimensional tube formation and fibrin bead assay, with the latter assessing three-dimensional sprout formation. Viability was quantified by the WST-1 test. Conditioned media (CM) from A549 lung cancer cells treated with cannabidiol, Δ(9)-tetrahydrocannabinol, R(+)-methanandamide or the CB2 agonist JWH-133 elicited decreased migration as well as tube and sprout formation of HUVEC as compared to CM of vehicle-treated cancer cells. Inhibition of sprout formation was further confirmed for cannabinoid-treated A549 cells co-cultured with HUVEC. Using antagonists to cannabinoid-activated receptors the antimigratory action was shown to be mediated via cannabinoid receptors or transient receptor potential vanilloid 1. SiRNA approaches revealed a cannabinoid-induced expression of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) as well as its upstream trigger, the intercellular adhesion molecule-1, to be causally linked to the observed decrease of HUVEC migration. Comparable anti-angiogenic effects were not detected following direct exposure of HUVEC to cannabinoids, but occurred after addition of recombinant TIMP-1 to HUVEC. Finally, antimigratory effects were confirmed for CM of two other cannabinoid-treated lung cancer cell lines (H460 and H358). Collectively, our data suggest a pivotal role of the anti-angiogenic factor TIMP-1 in intercellular tumor-endothelial cell communication resulting in anti-angiogenic features of endothelial cells. Copyright © 2014 Elsevier Inc. All rights reserved.

Exposure to smoking in films and own smoking among Scottish adolescents: a cross-sectional study

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Hunt, Kate; Henderson, Marion; Wight, Daniel; Sargent, James D

2013-01-01

Background Evidence of high exposure of UK youth to images of smoking in films has led to calls for an 18 rating for films with smoking to reduce smoking in youth. However, the only study to date in the UK to test for an association showed no relation between film-smoking exposure and smoking among young adults. Objective To assess whether there is an association between exposure to film images of smoking and own smoking among UK adolescents and whether repeated viewings of films has an impact. Design Cross-sectional study. Participants 1999 pupils aged 15–16 years from 13 Scottish schools. Outcome Smoked tobacco in the past year. Exposure measure Film-smoking exposure was assessed using the Beach method; account for repeated viewings of films was then used to modify estimated exposure. Covariates included: media usage, parental restriction on and context of TV/film viewing, family connectedness, parental monitoring and friends' smoking. Results Most (71%) students had not smoked in the past year. About half reported no parental restrictions on TV/film viewing. Many reported repeated viewings of films; accounting for this more than doubled exposure estimates and strengthened the association with smoking. Adolescents with high exposure to film smoking were more likely to have smoked than those with low exposure (adjusted odds ratio (AOR) 2.08, 95% CI 1.22 to 3.55). Additionally, adolescents who reported parental rules about TV/film watching were less likely to smoke (AOR 0.37 (0.27 to 0.52)) than those who did not. Adolescents who mainly watched films with friends had higher exposure to film smoking and were more likely to smoke (AOR 2.19 (1.10 to 4.38)). Conclusions Exposure to film smoking is associated with smoking among Scottish adolescents. These data lend support to calls for an 18 rating for films with images of smoking. PMID:21764893

Consequences of repeated ethanol exposure during early or late adolescence on conditioned taste aversions in rats

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Jessica Saalfield

2015-12-01

Full Text Available Alcohol use is prevalent during adolescence, yet little is known about possible long-lasting consequences. Recent evidence suggests that adolescents are less sensitive than adults to ethanol's aversive effects, an insensitivity that may be retained into adulthood after repeated adolescent ethanol exposure. This study assessed whether intermittent ethanol exposure during early or late adolescence (early-AIE or late-AIE, respectively would affect ethanol conditioned taste aversions 2 days (CTA1 and >3 weeks (CTA2 post-exposure using supersaccharin and saline as conditioning stimuli (CS, respectively. Pair-housed male Sprague-Dawley rats received 4 g/kg i.g. ethanol (25% or water every 48 h from postnatal day (P 25–45 (early AIE or P45-65 (late AIE, or were left non-manipulated (NM. During conditioning, 30 min home cage access to the CS was followed by 0, 1, 1.5, 2 or 2.5 g/kg ethanol i.p., with testing 2 days later. Attenuated CTA relative to controls was seen among early and late AIE animals at both CTA1 and CTA2, an effect particularly pronounced at CTA1 after late AIE. Thus, adolescent exposure to ethanol was found to induce an insensitivity to ethanol CTA seen soon after exposure and lasting into adulthood, and evident with ethanol exposures not only early but also later in adolescence.

The therapeutic potential of cannabis and cannabinoids.

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Grotenhermen, Franjo; Müller-Vahl, Kirsten

2012-07-01

Cannabis-based medications have been a topic of intense study since the endogenous cannabinoid system was discovered two decades ago. In 2011, for the first time, a cannabis extract was approved for clinical use in Germany. Selective literature review. Cannabis-based medications exert their effects mainly through the activation of cannabinoid receptors (CB1 and CB2). More than 100 controlled clinical trials of cannabinoids or whole-plant preparations for various indications have been conducted since 1975. The findings of these trials have led to the approval of cannabis-based medicines (dronabinol, nabilone, and a cannabis extract [THC:CBD=1:1]) in several countries. In Germany, a cannabis extract was approved in 2011 for the treatment of moderate to severe refractory spasticity in multiple sclerosis. It is commonly used off label for the treatment of anorexia, nausea, and neuropathic pain. Patients can also apply for government permission to buy medicinal cannabis flowers for self-treatment under medical supervision. The most common side effects of cannabinoids are tiredness and dizziness (in more than 10% of patients), psychological effects, and dry mouth. Tolerance to these side effects nearly always develops within a short time. Withdrawal symptoms are hardly ever a problem in the therapeutic setting. There is now clear evidence that cannabinoids are useful for the treatment of various medical conditions.

Cannabinoid Hyperemesis Relieved by Compulsive Bathing

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Chang, Yoon Hee; Windish, Donna M.

2009-01-01

Cannabinoid hyperemesis is a clinical syndrome characterized by repeated vomiting and associated learned compulsive hot water bathing behavior due to long-term marijuana use. Research has indentified type 1 cannabinoid receptors in the intestinal nerve plexus that have an inhibitory effect on gastrointestinal motility. This inhibitory effect may lead to hyperemesis in marijuana users. The thermoregulatory role of endocannabinoids may be responsible for the patient's need to take hot showers. ...

Chronic intermittent ethanol exposure during adolescence: effects on social behavior and ethanol sensitivity in adulthood.

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Varlinskaya, Elena I; Truxell, Eric; Spear, Linda P

2014-08-01

This study assessed long-lasting consequences of repeated ethanol exposure during two different periods of adolescence on 1) baseline levels of social investigation, play fighting, and social preference and 2) sensitivity to the social consequences of acute ethanol challenge. Adult male and female Sprague-Dawley rats were tested 25 days after repeated exposure to ethanol (3.5 g/kg intragastrically [i.g.], every other day for a total of 11 exposures) in a modified social interaction test. Early-mid adolescent intermittent exposure (e-AIE) occurred between postnatal days (P) 25 and 45, whereas late adolescent intermittent exposure (l-AIE) was conducted between P45 and P65. Significant decreases in social investigation and social preference were evident in adult male rats, but not their female counterparts following e-AIE, whereas neither males nor females demonstrated these alterations following l-AIE. In contrast, both e-AIE and l-AIE produced alterations in sensitivity to acute ethanol challenge in males tested 25 days after adolescent exposure. Ethanol-induced facilitation of social investigation and play fighting, reminiscent of that normally seen during adolescence, was evident in adult males after e-AIE, whereas control males showed an age-typical inhibition of social behavior. Males after l-AIE were found to be insensitive to the socially suppressing effects of acute ethanol challenge, suggesting the development of chronic tolerance in these animals. In contrast, females showed little evidence for alterations in sensitivity to acute ethanol challenge following either early or late AIE. The results of the present study demonstrate a particular vulnerability of young adolescent males to long-lasting detrimental effects of repeated ethanol. Retention of adolescent-typical sensitivity to the socially facilitating effects of ethanol could potentially make ethanol especially appealing to these males, therefore promoting relatively high levels of ethanol intake later

The novelty-seeking phenotype modulates the long-lasting effects of adolescent MDMA exposure.

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Rodríguez-Arias, Marta; Vaccaro, Sonia; Arenas, M Carmen; Aguilar, María A; Miñarro, José

2015-03-15

Exposure to drugs such as ethanol or cocaine during adolescence induces alterations in the central nervous system that are modulated by the novelty-seeking trait. Our aim was to evaluate the influence of this trait on the long-term effects of MDMA administration during adolescence on spontaneous behavior and conditioned rewarding effects in adulthood. Adolescent mice were classified as high or low novelty seekers (HNS or LNS) according to the hole-board test and received either MDMA (0, 10 or 20mg/kg PND 33-42) or saline. Three weeks later, having entered adulthood (PND>68), one set of mice performed the elevated plus maze and social interaction tests, while another set performed the conditioning place preference (CPP) test induced by cocaine-(1mg/kg) or MDMA-(1mg/kg). Only HNS mice treated with MDMA during adolescence acquired CPP in adulthood with a non-effective dose of cocaine or MDMA. Although it did not produce changes in motor activity, exposure to MDMA during adolescence was associated with more aggressive behaviors (threat and attack) and increased social contacts in HNS mice, while an anxiolytic effect was noted in LNS mice pre-treated with the highest dose of MDMA (20mg/kg). Administration of MDMA (10 or 20mg/kg) induced a decrease in DA levels in the striatum in LNS mice only and lower striatal serotonin levels in mice treated with the highest MDMA dose. Our findings show that adolescent MDMA exposure results in higher sensitivity to the conditioned reinforcing properties of MDMA and cocaine in adult HNS mice, which suggests that the relationship between exposure to MDMA in adolescence and a higher probability of substance is a feature of high novelty seekers only. Copyright © 2015. Published by Elsevier Inc.

Exposure to environmental tobacco smoke among adolescents in ...

African Journals Online (AJOL)

Objective: To estimate the prevalence of environmental tobacco smoke (ETS) inside or outside the home among school-going adolescents in Kampala, Uganda. Methods: Data from the Kampala Global Youth Tobacco Survey (GYTS) of 2002 was used. We estimated frequencies and proportions of self reported exposure to ...

Impact of exposure to idealised male images on adolescent boys' body image.

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Humphreys, Paul; Paxton, Susan J

2004-09-01

Research examining the impact on adolescent boys of exposure to muscular, athletic, idealised male images has been limited. This research had two aims (i) to investigate the mean effect on state body satisfaction and mood of exposure to idealised male images in adolescent boys, and, (ii) to identify individual attributes that predicted change in state body satisfaction, depression and anxiety following image exposure. One hundred and six boys (mean age=15.6 years) completed a self-report questionnaire on body image attitudes and psychological status. One week later, participants were divided into two groups, one that viewed idealised male images (experimental condition) while the other viewed non-figure advertising images (control condition). Three body satisfaction Visual Analogue Scale (VAS), and a depression and anxiety VAS were completed immediately prior to and following image exposure. In the experimental compared to control condition, there were no significant changes on Want Toned Body, Want to Change Body Shape, Depression and Anxiety VAS following image exposure. However, there was a significant improvement in Like Body Shape VAS. In the experimental group, high internalisation of the muscular, athletic ideal predicted more negative response to viewing images on the body image and Depression VAS. Prior body dissatisfaction significantly predicted negative response to Body Shape Liking and Anxiety VAS. While on average, adolescent boys in this research were not negatively affected by exposure to idealised male images, reaction to exposure is dependent on individual attributes.

The Relationship between Community Violence Exposure and Mental Health Symptoms in Urban Adolescents

OpenAIRE

McDonald, Catherine C.; Richmond, Therese R.

2008-01-01

Urban adolescents are exposed to a substantial amount of community violence which has the potential to influence psychological functioning. To examine the relationship between community violence exposure and mental health symptoms in urban adolescents, a literature review using MEDLINE, CINAHL, PubMed, PsycINFO, CSA Social Services, and CSA Sociological Abstracts was conducted. Search terms included adolescent/adolescence, violence, urban, mental health, well-being, emotional distress, depres...

Cannabinoids reduce markers of inflammation and fibrosis in pancreatic stellate cells.

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Christoph W Michalski

2008-02-01

Full Text Available While cannabinoids have been shown to ameliorate liver fibrosis, their effects in chronic pancreatitis and on pancreatic stellate cells (PSC are unknown.The activity of the endocannabinoid system was evaluated in human chronic pancreatitis (CP tissues. In vitro, effects of blockade and activation of cannabinoid receptors on pancreatic stellate cells were characterized. In CP, cannabinoid receptors were detected predominantly in areas with inflammatory changes, stellate cells and nerves. Levels of endocannabinoids were decreased compared with normal pancreas. Cannabinoid-receptor-1 antagonism effectuated a small PSC phenotype and a trend toward increased invasiveness. Activation of cannabinoid receptors, however, induced de-activation of PSC and dose-dependently inhibited growth and decreased IL-6 and MCP-1 secretion as well as fibronectin, collagen1 and alphaSMA levels. De-activation of PSC was partially reversible using a combination of cannabinoid-receptor-1 and -2 antagonists. Concomitantly, cannabinoid receptor activation specifically decreased invasiveness of PSC, MMP-2 secretion and led to changes in PSC phenotype accompanied by a reduction of intracellular stress fibres.Augmentation of the endocannabinoid system via exogenously administered cannabinoid receptor agonists specifically induces a functionally and metabolically quiescent pancreatic stellate cell phenotype and may thus constitute an option to treat inflammation and fibrosis in chronic pancreatitis.

Influence of tobacco marketing and exposure to smokers on adolescent susceptibility to smoking.

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Evans, N; Farkas, A; Gilpin, E; Berry, C; Pierce, J P

1995-10-18

Today the uptake of smoking is primarily an adolescent pursuit. Awareness of tobacco advertising and promotion is high, and evidence suggests that it plays a role in adolescent smoking uptake. We evaluated the influence of tobacco advertising and promotion and exposure to smokers on never-smoking adolescents' susceptibility to smoking. We used data on 3536 adolescent never smokers (those who had never even puffed on a cigarette) from the 1993 California Tobacco Survey. That survey questioned adolescents about smoking history and inclinations. For this analysis, we defined as susceptible to smoking those never smokers who said on the survey that they could not rule out independently deciding to try a cigarette soon or smoking one offered by a friend. Also for this analysis, we devised two indices: 1) a 5-point index of an individual's receptivity to tobacco advertising as determined by the number of positive responses to five survey items (recognition of advertising messages, having a favorite advertisement, naming a brand he/she might buy, owning a tobacco-related promotional item, and willingness to use a tobacco-related promotional item) and 2) an index classifying an individual's reported exposure to family and peer smoking into one of four levels. Using logistic regression, we assessed the independent importance of our indices in predicting susceptibility to smoking after adjustment for sociodemographic variables, including age, sex, and race/ethnicity, and for perceived school performance. Tests of statistical significance were two-sided. Receptivity to tobacco advertising and exposure to smokers were independently associated with susceptibility to smoking, but the relationship appeared stronger for receptivity to advertising. Adolescents exposed to family members and peers (n = 489) who smoked were 1.89 (95% confidence interval [CI] = 1.30-2.74) times as likely to be susceptible, whereas adolescents who scored 4 or more on the Index of Receptivity to Tobacco

Effects of maternal exposure to bisphenol AF on emotional behaviors in adolescent mice offspring.

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Gong, Miao; Huai, Ziqing; Song, Han; Cui, Lingyu; Guo, Qingjun; Shao, Juan; Gao, Yuan; Shi, Haishui

2017-11-01

Exposure to bisphenol A (BPA), one kind of environmental endocrine disruptors (EEDs), exerted significantly detrimental effects on neuro-endocrinological system and related disorders, such as memory dysfunction and depression. Bisphenol AF (BPAF),a newly introduced chemical structurally related to BPA, is used extensively. BPAF has stronger estrogenic activities than BPA. However, the potential neurotoxicological effects of BPAF are still elusive. The present study aimed to investigate the potential effects of maternal BPAF exposure during pregnancy on emotional behaviors of adolescent mice offspring. In male adolescent offspring, maternal exposure to BPAF (0.4, 4.0 mg kg -1 , intragastrically administration) induced significant anxiety- and depressive-like behaviors, assessed by open field test (OFT), novelty-suppressed feeding test (NSF), sucrose preference test (SPT), tail suspension test (TST) and forced swimming test (FST). In female adolescent offspring, BPAF exposure at 0.4 mg kg -1 dose reduced the latency to feeding in the NSF test, while increased the floating time in the FST. Maternal BPAF exposure decreased the recognition index in the long term memory (LTM) test in both sexes, while only decreased the freezing time of male offspring in the contextual fear conditioning (CFC) task. These results indicate that maternal exposure to BPAF significantly affect emotion-related behaviors in adolescent mice offspring, and the male offspring with a higher probability to develop symptoms of anxiety and depression and to suffer memory impairment after maternal exposure to BPAF. Copyright © 2017 Elsevier Ltd. All rights reserved.

Consequences of repeated ethanol exposure during early or late adolescence on conditioned taste aversions in rats.

Science.gov (United States)

Saalfield, Jessica; Spear, Linda

2015-12-01

Alcohol use is prevalent during adolescence, yet little is known about possible long-lasting consequences. Recent evidence suggests that adolescents are less sensitive than adults to ethanol's aversive effects, an insensitivity that may be retained into adulthood after repeated adolescent ethanol exposure. This study assessed whether intermittent ethanol exposure during early or late adolescence (early-AIE or late-AIE, respectively) would affect ethanol conditioned taste aversions 2 days (CTA1) and >3 weeks (CTA2) post-exposure using supersaccharin and saline as conditioning stimuli (CS), respectively. Pair-housed male Sprague-Dawley rats received 4g/kg i.g. ethanol (25%) or water every 48 h from postnatal day (P) 25-45 (early AIE) or P45-65 (late AIE), or were left non-manipulated (NM). During conditioning, 30 min home cage access to the CS was followed by 0, 1, 1.5, 2 or 2.5g/kg ethanol i.p., with testing 2 days later. Attenuated CTA relative to controls was seen among early and late AIE animals at both CTA1 and CTA2, an effect particularly pronounced at CTA1 after late AIE. Thus, adolescent exposure to ethanol was found to induce an insensitivity to ethanol CTA seen soon after exposure and lasting into adulthood, and evident with ethanol exposures not only early but also later in adolescence. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Risky choice and brain CRF after adolescent ethanol vapor exposure and social stress in adulthood.

Science.gov (United States)

Boutros, Nathalie; Der-Avakian, Andre; Semenova, Svetlana; Lee, Soon; Markou, Athina

2016-09-15

Adolescent ethanol exposure increases risky choice and alters corticotropin releasing factor (CRF) systems in adulthood. The impact of stress on risky choice after adolescent intermittent ethanol (AIE) exposure is not known. We investigated time-specific effects of AIE vapor exposure during early adolescence on risky choice after stress or no stress in adulthood. Male Wistar rats were exposed to air or AIE vapor on postnatal days 28-42 (adolescence) and were exposed to 10days of social defeat or no stress on postnatal days 172-181 (adulthood). Risky choice was assessed in the probability discounting task under baseline conditions and after days 1 and 10 of social defeat. CRF and CRF receptor 1 (CRFR1) mRNA levels were assessed in the prefrontal cortex (PFC) and the central nucleus of the amygdala (CeA) 24h post-stress to evaluate persistent effects of stress on the brain. AIE exposure had no effect on risky choice either at baseline or after social defeat. Additionally, neither acute nor chronic social defeat affected risky choice in air-exposed rats. In the PFC, chronic social defeat selectively decreased CRF mRNA levels in air-exposed rats and increased CRFR1 mRNA levels in all rats. AIE exposure increased CRF mRNA levels in the CeA with no effect of social stress. Our results indicate no effect of ethanol exposure via vapor during early adolescence on risky choice, while our previous findings indicated that AIE exposure via gavage affected risky choice. Both AIE exposure and social defeat altered CRF and CRFR1 mRNA levels in the brain. Copyright © 2016 Elsevier B.V. All rights reserved.

Exposure to Advertisements and Marijuana Use Among US Adolescents

OpenAIRE

Dai, Hongying

2017-01-01

Introduction This study examined whether exposure to marijuana advertisements was associated with current marijuana use and frequency of use among US adolescents in grades 8, 10, and 12. Methods Weighted estimates of exposure to marijuana advertisements and marijuana use from the 2014 and 2015 Monitoring the Future studies were investigated. Factors associated with the prevalence and frequency of marijuana use were analyzed by using logistic regression and linear regression models, respective...

Trends in exposure to television food advertisements among children and adolescents in the United States.

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Powell, Lisa M; Szczypka, Glen; Chaloupka, Frank J

2010-09-01

To examine the trends in food advertising seen by American children and adolescents. Trend analysis of children's and adolescents' exposure to food advertising in 2003, 2005, and 2007, including separate analyses by race. Children aged 2 to 5 years and 6 to 11 years and adolescents aged 12 to 17 years. Television ratings. Exposure to total food advertising and advertising by food category. Between 2003 and 2007 daily average exposure to food ads fell by 13.7% and 3.7% among young children aged 2 to 5 and 6 to 11 years, respectively, but increased by 3.7% among adolescents aged 12 to 17 years. Exposure to sweets ads fell 41%, 29.3%, and 12.1%, respectively, for 2- to 5-, 6- to 11-, and 12- to 17-year-olds and beverage ads were down by about 27% to 30% across these age groups, with substantial decreases in exposure to ads for the most heavily advertised sugar-sweetened beverages-fruit drinks and regular soft drinks. Exposure to fast food ads increased by 4.7%, 12.2%, and 20.4% among children aged 2 to 5, 6 to 11, and 12 to 17 years, respectively, between 2003 and 2007. The racial gap in exposure to food advertising grew between 2003 and 2007, particularly for fast food ads. A number of positive changes have occurred in children's exposure to food advertising. Continued monitoring of food advertising exposure along with nutritional analyses is needed to further assess self-regulatory pledges.

Youth violence in South Africa: exposure, attitudes, and resilience in Zulu adolescents.

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Choe, Daniel Ewon; Zimmerman, Marc A; Devnarain, Bashi

2012-01-01

Exposure to violence is common in South Africa. Yet, few studies examine how violence exposure contributes to South African adolescents' participation in youth violence. The aims of this study were to examine effects of different violence exposures on violent attitudes and behavior, to test whether attitudes mediated effects of violence exposures on violent behavior, and to test whether adult involvement had protective or promotive effects. Questionnaires were administered to 424 Zulu adolescents in township high schools around Durban, South Africa. Structural equation modeling (SEM) was used to test associations among violence exposures and both violent attitudes and behavior. Victimization, witnessing violence, and friends' violent behavior contributed directly to violent behavior. Only family conflict and friends' violence influenced violent attitudes. Attitudes mediated effects of friends' violence on violent behavior. Multiple-group SEM indicated that adult involvement fit a protective model of resilience. These findings are discussed regarding their implications for prevention.

Does self-complexity moderate the effects of exposure to political violence for adolescents?

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Slone, Michelle; Roziner, Ilan

2013-01-01

This study examined the moderating role of self-complexity (SC) on well-being (WB) and psychopathology among Israeli adolescents exposed to the Second Lebanon War (2006). Adolescents (N=584, mean age 16.41) completed a SC measure, Political and Negative Life Events (NLE) scales, Brief Symptom Inventory and Satisfaction with Life Scale. The theoretical model analyzed the function of SC as a moderator of exposure effects to political life events (PLE), while controlling for general NLE. Results corroborated the model with SC moderating the effects of the war-related PLE. Adolescents with low SC are at risk for damaged WB and psychiatric consequences from political violence exposure. This opens a diagnostic avenue for identification of at-risk adolescents in this socio-political context toward whom clinical programs should be directed.

Multitype violence exposures and adolescent antiretroviral nonadherence in South Africa.

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Cluver, Lucie; Meinck, Franziska; Toska, Elona; Orkin, F Mark; Hodes, Rebecca; Sherr, Lorraine

2018-05-15

HIV-positive adolescents have low-ART adherence, with consequent increased risks of mortality, morbidity, and viral resistance. Despite high rates of violence against children in the Africa region, no known studies have tested impacts on HIV-positive adolescents. We examine associations of ART adherence with adolescent violence victimization by caregivers, teachers, peers, community members, and healthcare providers. HIV-positive adolescents were interviewed (n = 1060), and clinic biomarker data collected. We sampled all 10-19-year olds ever ART-initiated within 53 clinics in 180 South African communities (90.1% reached). Analyses examined associations between nonadherence and nine violence types using sequential multivariate logistic regressions. Interactive and additive effects were tested with regression and marginal effects. Past-week self-reported ART nonadherence was 36%. Nonadherence correlated strongly with virologic failure (OR 2.3, CI 1.4-3.8) and symptomatic pulmonary tuberculosis (OR 1.49, CI 1.18-2.05). Four violence types were independently associated with nonadherence: physical abuse by caregivers (OR 1.5, CI 1.1-2.1); witnessing domestic violence (OR 1.8, CI 1.22-2.66); teacher violence (OR 1.51, CI 1.16-1.96,) and verbal victimization by healthcare staff (OR 2.15, CI 1.59-2.93). Past-week nonadherence rose from 25% with no violence to 73.5% with four types of violence exposure. Violence exposures at home, school, and clinic are major and cumulating risks for adolescent antiretroviral nonadherence. Prevention, mitigation, and protection services may be essential for the health and survival of HIV-positive adolescents.

Leptin Receptor Deficiency is Associated With Upregulation of Cannabinoid 1 Receptors in Limbic Brain Regions

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THANOS, PANAYOTIS K.; RAMALHETE, ROBERTO C.; MICHAELIDES, MICHAEL; PIYIS, YIANNI K.; WANG, GENE-JACK; VOLKOW, NORA D.

2009-01-01

Leptin receptor dysfunction results in overeating and obesity. Leptin regulates hypothalamic signaling that underlies the motivation to hyperphagia, but the interaction between leptin and cannabinoid signaling is poorly understood. We evaluated the role of cannabinoid 1 receptors (CB1R) in overeating and the effects of food deprivation on CB1R in the brain. One-month-old Zucker rats were divided into unrestricted and restricted (fed 70% of unrestricted rats) diet groups and maintained until adulthood (4 months). Levels of relative binding sites of CB1R (CB1R binding levels) were assessed using [3H] SR141716A in vitro autoradiography. These levels were higher (except cerebellum and hypothalamus) at 4 months than at 1 month of age. One month CB1R binding levels for most brain regions did not differ between Ob and Lean (Le) rats (except in frontal and cingulate cortices in Le and in the hypothalamus in Ob). Four month Ob rats had higher CB1R binding levels than Le in most brain regions and food restriction was associated with higher CB1R levels in all brain regions in Ob, but not in Le rats. CB1R binding levels increased between adolescence and young adulthood which we believe was influenced by leptin and food availability. The high levels of CB1R in Ob rats suggest that leptin's inhibition of food-intake is in part mediated by downregulation of CB1R and that leptin interferes with CB1R upregulation under food-deprivation conditions. These results are consistent with prior findings showing increased levels of endogenous cannabinoids in the Ob rats corroborating the regulation of cannabinoid signaling by leptin. PMID:18563836

Skin Tone Dissatisfaction, Sun Exposure, and Sun Protection in Australian Adolescents.

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Hutchinson, Amanda D; Prichard, Ivanka; Ettridge, Kerry; Wilson, Carlene

2015-08-01

This study aimed to assess the adoption of sun protection and sun exposure behaviors, the extent to which these behaviors group together, and the relationship between skin tone dissatisfaction and sun-related behaviors in South Australian adolescents (aged 12-17). A total of 2,875 secondary school students (1,461 male and 1,414 female) completed a questionnaire including questions about sun protection and sun exposure behaviors and skin tone dissatisfaction. Regular adoption of sun protection behaviors was low and ranged from 20% (wearing protective clothing) to 44% (sunscreen use). A principal components analysis identified four subgroups of sun-related behaviors: sun protection, appearance enhancement, sun avoidance, and sun exposure. Females had significantly higher skin tone dissatisfaction than males. Skin tone dissatisfaction was associated with decreased sun protection and avoidance and increased appearance enhancement and sun exposure in both males and females. Skin tone dissatisfaction plays an important role in Australian adolescents' sun-related behavior. Appearance-based interventions may be effective in reducing skin cancer risk through reduced sun exposure.

Cannabinoids enhance gastric X/A-like cells activity.

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Bogusław Sawicki

2008-06-01

Full Text Available It has been reported that cannabinoids may cause overeating in humans and in laboratory animals. Although, endogenous cannabinoids and their receptors (CB1 have been found in the hypothalamus, and recently also in gastrointestinal tract, the precise mechanism of appetite control by cannabinoids remains unknown. Recently, ghrelin--a hormone secreted mainly from the stomach X/A-like cells was proposed to be an appetite stimulating agent. The aim of this study was the evaluation of the influence of a single ip injection of a stable analogue of endogenous cannabinoid--anandamide, R-(+-methanandamide (2.5 mg/kg and CP 55,940 (0.25 mg/kg, an exogenous agonist of CB1 receptors, on ghrelin plasma concentration and on ghrelin immunoreactivity in the gastric mucosa of male Wistar rats. Four hours after a single injection of both cannabinoids or vehicle, the animals were anaesthetized and blood was taken from the abdominal aorta to determinate plasma ghrelin concentration by RIA. Subsequently, the animals underwent resection of distal part of stomach. Immunohistochemical study of gastric mucosa, using the EnVision method and specific monoclonal antibodies against ghrelin was performed. The intensity of ghrelin immunoreactivity in X/A-like cells was analyzed using Olympus Cell D image analysis system. The attenuation of ghrelin-immunoreactivity of gastric mucosa, after a single injection of R-(+-methanandamide and CP 55,940 was accompanied by a significant increase of ghrelin plasma concentration. These results indicate that stimulation of appetite exerted by cannabinoids may be connected with an increase of ghrelin secretion from gastric X/A-like cells.

ADHD Symptoms in Middle Adolescence Predict Exposure to Person-Related Life Stressors in Late Adolescence in 5-HTTLPR S-allele Homozygotes.

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Brinksma, Djûke M; Hoekstra, Pieter J; de Bildt, Annelies; Buitelaar, Jan K; van den Hoofdakker, Barbara J; Hartman, Catharina A; Dietrich, Andrea

2017-12-19

Literature suggests that life stressors predict attention-deficit/hyperactivity disorder (ADHD) symptoms and that this relationship is moderated by the serotonin transporter polymorphism (5-HTTLPR). It is less clear whether, on reverse, ADHD symptoms may influence the risk of exposure to life stressors. Furthermore, the role of life stressors may vary across development depending on the type of life stressor. We used threewave longitudinal data of 1,306 adolescents from the general population and clinicreferred cohort of the TRacking Adolescents' Individual Lives Survey. The 5-HTTLPR genotype (SS, LS, LL), parent-reported ADHD symptoms at three time points (T1: Mage = 11.2; T2: Mage = 13.5; T3: Mage = 16.2 years), and the number of personrelated ('dependent') and environment-related ('independent') life stressors occurring between measurements (T1-T2, T2-T3) were assessed. Using path analyses, we examined bidirectional relations between exposure to these life stressors and ADHD symptoms between the separate waves moderated by 5-HTTLPR status. Exposure to life stressors did not predict ADHD symptoms. Rather, we found that in 5-HTTLPR Sallele homozygotes, ADHD symptoms in middle adolescence (T2) predicted exposure to the number of person-related life stressors later in adolescence (T2-T3, p = 0.001). There was no relation with environment-related life stressors. Our study suggests that S-allele homozygotes with higher levels of ADHD symptoms in middle adolescence are more vulnerable to becoming exposed to person-related ('dependent') life stressors in late adolescence. Findings emphasize the need to be aware of social-emotional adversities that may occur in genetically vulnerable adolescents with ADHD symptoms in the transition into adulthood.

Haloperidol, a Novel Treatment for Cannabinoid Hyperemesis Syndrome.

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Witsil, Joanne C; Mycyk, Mark B

Cannabinoid hyperemesis syndrome (CHS) is typically unresponsive to conventional pharmacologic antiemetics, and patients often require excessive laboratory and radiographic testing and hospital admission. We report 4 cases of CHS that failed standard emergency department therapy but improved significantly after treatment with haloperidol. Although the exact mechanism for CHS remains unclear, dysregulation at cannabinoid type 1 seems to play a role. Recent animal data demonstrate complex interactions between dopamine and cannabinoid type 1 signaling, a potential mechanism for haloperidol success in patients with CHS. Our success with haloperidol in these 4 patients warrants further investigation of haloperidol as an emergency department treatment for CHS.

Factors associated with younger adolescents' exposure to online alcohol advertising.

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D'Amico, Elizabeth J; Martino, Steven C; Collins, Rebecca L; Shadel, William G; Tolpadi, Anagha; Kovalchik, Stephanie; Becker, Kirsten M

2017-03-01

Little is known about the extent and nature of youth exposure to online alcohol advertising, or factors that may be associated with exposure. The current study recruited middle school students who completed a paper survey and then logged each alcohol advertisement that they encountered over a 2-week period using cell phones as part of an ecological momentary assessment design. We examined the percentage of youth who reported exposure to online alcohol advertising in the past 2 weeks, average weekly rate of exposure, types of online alcohol advertisements youth reported seeing, and factors that increased youths' risk of exposure to online alcohol advertising. Analyses are based on 485 participants (47% female; 25% Hispanic, 25% White, 27% Black; 6% Asian, 16% other). Youth logged exposures to a total of 3,966 (16,018 weighted for underreporting) alcohol advertisements across the monitoring period; 154 (568 weighted) or 3.6% were online ads. Seventeen percent of youth reported seeing any online alcohol ad; the majority of online ads seen were video commercials (44.8%) and banner/side ads (26.6%). Factors associated with greater ad exposure were being older, rebellious, and Black race; greater parental monitoring and more hours spent on social media were associated with less exposure. Findings provide important information about adolescents' exposure to online alcohol advertising and what might contribute to a greater likelihood of exposure. Given that online ad exposure is linked to drinking behavior, prevention programming for younger adolescents should continue to address this issue to help youth make healthy choices regarding alcohol use. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Does Exposure to Music Videos Predict Adolescents' Sexual Attitudes?

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Beentjes, J.W.J.; Konig, R.P.

2013-01-01

This study investigates whether exposure to music videos predicts adolescents' sexual attitudes when controlled for relevant characteristics of individuals and their social environment. Sexual attitudes are related to their music video use (i.e. exposure to music videos, peer group talk about music videos, and perceived realism of these videos), personal factors and the sexual norms they perceive in their social environment (i.e. sexual norms of their parents and friends). A survey among Dutc...

Lifetime secondhand smoke exposure and childhood and adolescent asthma: findings from the PIAMA cohort.

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Milanzi, Edith B; Brunekreef, Bert; Koppelman, Gerard H; Wijga, Alet H; van Rossem, Lenie; Vonk, Judith M; Smit, Henriëtte A; Gehring, Ulrike

2017-02-23

Secondhand smoke (SHS) exposure is a modifiable risk factor associated with childhood asthma. Associations with adolescent asthma and the relevance of the timing and patterns of exposure are unclear. Knowledge of critical windows of exposure is important for targeted interventions. We used data until age 17 from 1454 children of the Dutch population-based PIAMA birth cohort. Residential SHS exposure was assessed through parental questionnaires completed at ages 3 months, 1-8 (yearly), 11, 14, and 17 years. Lifetime exposure was determined as; a) time window-specific exposure (prenatal, infancy, preschool, primary school, and secondary school); b) lifetime cumulative exposure; c) longitudinal exposure patterns using latent class growth modeling (LCGM). Generalized estimation equations and logistic regression were used to analyze associations between exposure and asthma at ages 4 to 17 years, adjusting for potential confounders. With all three methods, we consistently found no association between SHS exposure and asthma at ages 4 to 17 years e.g. adjusted overall odds ratio (95% confidence interval) 0.67 (0.41-1.12), 1.00 (0.66-1.51) and 0.67 (0.41-1.11) for prenatal maternal active smoking, infancy, and preschool school time window exposures, respectively. We assessed lifetime SHS exposure using different methods. Different timing and patterns of SHS exposure were not associated with an increased risk of asthma in childhood and adolescence in our study. More longitudinal studies could investigate effects of lifetime SHS exposure on asthma in adolescence and later life.

The impact of Australian legislative changes on synthetic cannabinoid exposures reported to the New South Wales Poisons Information Centre.

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Cairns, Rose; Brown, Jared A; Gunja, Naren; Buckley, Nicholas A

2017-05-01

The emergence of new psychoactive substances (NPS), including synthetic cannabinoid receptor agonists (SCRAs) poses novel challenges for drug regulation and public health. Misconceptions of safety and legality, coupled with the fact that NPS are undetectable on routine drugs screens contributes to their popularity. Concerns over the unpredictable toxicity and abuse potential of NPS has led to a variety of legislative responses worldwide. We wish to describe Australian trends in SCRA use, examining the effects of legislative changes on calls to Australia's largest poisons centre. A retrospective review of calls to the New South Wales Poisons Information Centre (NSWPIC). Cases occurring between 1 January 2010 and 30 June 2015 with documented use of SCRAs were included. There were 146 exposures to SCRAs recorded in the NSWPIC database. Federal bans of specific SCRA compounds in 2011/2012 had little impact on call volumes. State-based legislation introduced in 2013 banning specific brand names of SCRA products was followed by a dramatic, sustained decrease in exposures. The most common symptoms reported with SCRA use were tachycardia, vomiting, drowsiness, anxiety/panic, decreased level of consciousness, chest pain, agitation, hallucinations, confusion, seizures and hypertension. Banning of specific brand names of SCRA (timed with raids and social media campaigns) appears effective at reducing SCRA exposures. We postulate that this raised awareness within the community of the illegality of these substances while also reducing supply through bricks-and-mortar shops. These results could help inform future legislative responses. Copyright © 2017 Elsevier B.V. All rights reserved.

Exposure to the Tips From Former Smokers Campaign Among Adolescents in the United States.

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Zhao, Xiaoquan; Cai, Xiaomei

2016-05-01

Evaluation of the Tips from Former Smokers (Tips) campaign in the United States so far has focused exclusively on adult smokers. This study provides evidence on the level of exposure to Tips among adolescents in the United States, an important secondary audience for the campaign. Data came from the 2013 National Youth Tobacco Survey (N = 18 406). Exposure to Tips was measured by ad recall. Characteristics of adolescents reporting exposure versus no exposure were examined through a series of bivariate analysis linking exposure to smoking status, demographics, and important risk factors. Most adolescents in the United States (63%, 95% confidence interval [CI] = 60.6%, 65.3%) were exposed to at least one Tips ad. Current smokers (70.6%, 95% CI = 67.7%, 73.4%), noncurrent smokers (67.7%, 95% CI = 65.5%, 69.7%), and high-risk never-smokers (63.8%, 95% CI = 60.2%, 67.2%) reported greater exposure than low-risk never-smokers (60.7%, 95% CI = 57.8%, 63.5%; all P advertising from one or more sources; and have skipped classes in the past 30 days. Tips has significant reach among adolescents in the United States, particularly among those with smoking experience and those whose life environments include more pro-smoking influences. Close monitoring of the Tips' impact on this important population is needed. This study shows substantial adolescent awareness of the Tips campaign in the United States. This evidence has important implications for the comprehensive evaluation of the public health impact of Tips. So far research on Tips has focused almost entirely on adult smokers. Findings of this study suggest that the potential impact of Tips on adolescents, particularly those at high risk of smoking, should become an integral part of the evaluation research agenda. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Current smoking and secondhand smoke exposure and depression among Korean adolescents: analysis of a national cross-sectional survey.

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Lee, Kyung-Jae

2014-02-06

To examine the association between cigarette smoke exposure and depression among Korean adolescents using the seventh Korea Youth Risk Behavior Web-based Survey (KYRBWS). Cross-sectional study. A nationally representative sample of middle and high school students across South Korea. 75 643 eligible participants across the country. Current smoking, secondhand smoke exposure and depression. Data were analysed from a nationally representative survey of 75 643 participants (37 873 men and 37 770 women). Data were gathered on extensive information including current smoking, secondhand smoke exposure and depression in adolescence. Multiple logistic regression analysis was used to estimate the association between current smoking, secondhand smoke exposure and depression in Korean adolescents. Among those who had never smoked, secondhand smoke exposure was positively associated with depression in male and female adolescents in a dose-response relation (OR 1.27, OR 1.52 in males; OR 1.25, OR 1.72 in females). Similar associations were observed among currently smoking men and women in a dose-response manner (OR 1.29, OR 1.55 in males; OR 1.22, OR 1.41 in females). These significant trends were consistently observed even after adjustments. We suggested that current smoking and secondhand smoke exposure were positively associated with depression in male and female adolescents. Efforts to encourage no smoking and no secondhand smoke exposure will be established for adolescents.

Duration and Timing of Exposure to Neighborhood Poverty and the Risk of Adolescent Parenthood

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Wodtke, Geoffrey T.

2013-01-01

Theory suggests that the impact of neighborhood poverty depends on both the duration and timing of exposure. Previous research, however, does not properly analyze the sequence of neighborhoods to which children are exposed throughout the early life course. This study investigates the effects of different longitudinal patterns of exposure to disadvantaged neighborhoods on the risk of adolescent parenthood. It follows a cohort of children in the PSID from age 4 to 19 and uses novel methods for time-varying exposures that overcome critical limitations of conventional regression when selection processes are dynamic. Results indicate that sustained exposure to poor neighborhoods substantially increases the risk of becoming a teen parent and that exposure to neighborhood poverty during adolescence may be more consequential than exposure earlier during childhood. PMID:23720166

Expression and function of cannabinoid receptors CB1 and CB2 and their cognate cannabinoid ligands in murine embryonic stem cells.

Directory of Open Access Journals (Sweden)

Shuxian Jiang

2007-07-01

Full Text Available Characterization of intrinsic and extrinsic factors regulating the self-renewal/division and differentiation of stem cells is crucial in determining embryonic stem (ES cell fate. ES cells differentiate into multiple hematopoietic lineages during embryoid body (EB formation in vitro, which provides an experimental platform to define the molecular mechanisms controlling germ layer fate determination and tissue formation.The cannabinoid receptor type 1 (CB1 and cannabinoid receptor type 2 (CB2 are members of the G-protein coupled receptor (GPCR family, that are activated by endogenous ligands, the endocannabinoids. CB1 receptor expression is abundant in brain while CB2 receptors are mostly expressed in hematopoietic cells. However, the expression and the precise roles of CB1 and CB2 and their cognate ligands in ES cells are not known. We observed significant induction of CB1 and CB2 cannabinoid receptors during the hematopoietic differentiation of murine ES (mES-derived embryoid bodies. Furthermore, mES cells as well as ES-derived embryoid bodies at days 7 and 14, expressed endocannabinoids, the ligands for both CB1 and CB2. The CB1 and CB2 antagonists (AM251 and AM630, respectively induced mES cell death, strongly suggesting that endocannabinoids are involved in the survival of mES cells. Treatment of mES cells with the exogenous cannabinoid ligand Delta(9-THC resulted in the increased hematopoietic differentiation of mES cells, while addition of AM251 or AM630 blocked embryoid body formation derived from the mES cells. In addition, cannabinoid agonists induced the chemotaxis of ES-derived embryoid bodies, which was specifically inhibited by the CB1 and CB2 antagonists.This work has not been addressed previously and yields new information on the function of cannabinoid receptors, CB1 and CB2, as components of a novel pathway regulating murine ES cell differentiation. This study provides insights into cannabinoid system involvement in ES cell

Traditional marijuana, high-potency cannabis and synthetic cannabinoids: increasing risk for psychosis.

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Murray, Robin M; Quigley, Harriet; Quattrone, Diego; Englund, Amir; Di Forti, Marta

2016-10-01

Epidemiological evidence demonstrates that cannabis use is associated with an increased risk of psychotic outcomes, and confirms a dose-response relationship between the level of use and the risk of later psychosis. High-potency cannabis and synthetic cannabinoids carry the greatest risk. Experimental administration of tetrahydrocannabinol, the active ingredient of cannabis, induces transient psychosis in normal subjects, but this effect can be ameliorated by co-administration of cannabidiol. This latter is a constituent of traditional hashish, but is largely absent from modern high-potency forms of cannabis. Argument continues over the extent to which genetic predisposition is correlated to, or interacts with, cannabis use, and what proportion of psychosis could be prevented by minimizing heavy use. As yet, there is not convincing evidence that cannabis use increases risk of other psychiatric disorders, but there are no such doubts concerning its detrimental effect on cognitive function. All of the negative aspects are magnified if use starts in early adolescence. Irrespective of whether use of cannabis is decriminalized or legalized, the evidence that it is a component cause of psychosis is now sufficient for public health messages outlining the risk, especially of regular use of high-potency cannabis and synthetic cannabinoids. © 2016 World Psychiatric Association.

Traditional marijuana, high‐potency cannabis and synthetic cannabinoids: increasing risk for psychosis

Science.gov (United States)

Murray, Robin M.; Quigley, Harriet; Quattrone, Diego; Englund, Amir; Di Forti, Marta

2016-01-01

Epidemiological evidence demonstrates that cannabis use is associated with an increased risk of psychotic outcomes, and confirms a dose‐response relationship between the level of use and the risk of later psychosis. High‐potency cannabis and synthetic cannabinoids carry the greatest risk. Experimental administration of tetrahydrocannabinol, the active ingredient of cannabis, induces transient psychosis in normal subjects, but this effect can be ameliorated by co‐administration of cannabidiol. This latter is a constituent of traditional hashish, but is largely absent from modern high‐potency forms of cannabis. Argument continues over the extent to which genetic predisposition is correlated to, or interacts with, cannabis use, and what proportion of psychosis could be prevented by minimizing heavy use. As yet, there is not convincing evidence that cannabis use increases risk of other psychiatric disorders, but there are no such doubts concerning its detrimental effect on cognitive function. All of the negative aspects are magnified if use starts in early adolescence. Irrespective of whether use of cannabis is decriminalized or legalized, the evidence that it is a component cause of psychosis is now sufficient for public health messages outlining the risk, especially of regular use of high‐potency cannabis and synthetic cannabinoids. PMID:27717258

Influences of Tobacco Advertising Exposure and Conduct Problems on Smoking Behaviors Among Adolescent Males and Females

Science.gov (United States)

2014-01-01

Introduction: Adolescents with conduct problems are more likely to smoke, and tobacco advertising exposure may exacerbate this risk. Males’ excess risk for conduct problems and females’ susceptibility to advertising suggest gender-specific pathways to smoking. We investigated the associations between gender, conduct problems, and lifetime smoking and adolescents’ exposure to tobacco advertising, and we examined prospective relationships with smoking behaviors. Methods: Adolescents completed baseline (2001–2004; n = 541) and 5-year follow-up (2007–2009; n =320) interviews for a family study of smoking risk. Baseline interviews assessed conduct problems and tobacco advertising exposure; smoking behavior was assessed at both timepoints. Generalized linear models analyzed gender differences in the relationship between conduct problems, advertising exposure, and smoking behavior at baseline and longitudinally. Results: At baseline, among males, conduct problems were associated with greater advertising exposure independent of demographics and lifetime smoking. Among females at baseline, conduct problems were associated with greater advertising exposure only among never-smokers after adjusting for demographics. In longitudinal analyses, baseline advertising exposure predicted subsequent smoking initiation (i.e., smoking their first cigarette between baseline and follow-up) for females but not for males. Baseline conduct problems predicted current (i.e., daily or weekly) smoking at follow-up for all adolescents in adjusted models. Conclusions: The findings of this study reinforce that conduct problems are a strong predictor of subsequent current smoking for all adolescents and reveal important differences between adolescent males and females in the relationship between conduct problems, tobacco advertising behavior, and smoking behavior. The findings suggest gender-specific preventive interventions targeting advertising exposure may be warranted. PMID:24590388

Sustainable production of cannabinoids with supercritical carbon dioxide technologies

NARCIS (Netherlands)

Perrotin-Brunel, H.

2011-01-01

This thesis concerns the production of natural compounds from plant material for pharmaceutical and food applications. It describes the production (extraction and isolation) of cannabinoids, the active components present in cannabis. Many cannabinoids have medicinal properties but not all

Sustainable Production of Cannabinoids with Supercritical Carbon Dioxide Technologies

NARCIS (Netherlands)

Perrotin-Brunel, H.

2011-01-01

This thesis concerns the production of natural compounds from plant material for pharmaceutical and food applications. It describes the production (extraction and isolation) of cannabinoids, the active components present in cannabis. Many cannabinoids have medicinal properties but not all

Exposure to Domestic and Community Violence and Subjective Well-Being in Adolescents

OpenAIRE

Silva, Doralúcia Gil da; Dell'Aglio, Débora Dalbosco

2016-01-01

Abstract There is major exposure to domestic and community violence during adolescence, which has been negatively related to well-being. This work aimed to identify relationships between domestic and community violence and the levels of subjective well-being perceived by adolescents, considering sex and age. The participants were 426 adolescents from public schools in the south of Brazil; 62% were girls, with a mean age of 14.91 years old ( SD = 1.65), who answered one instrument about exposu...

Tracking Adolescents With Global Positioning System-Enabled Cell Phones to Study Contextual Exposures and Alcohol and Marijuana Use: A Pilot Study.

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Byrnes, Hilary F; Miller, Brenda A; Wiebe, Douglas J; Morrison, Christopher N; Remer, Lillian G; Wiehe, Sarah E

2015-08-01

Measuring activity spaces, places adolescents spend time, provides information about relations between contextual exposures and risk behaviors. We studied whether contextual exposures in adolescents' activity spaces differ from contextual risks present in residential contexts and examined relationships between contextual exposures in activity spaces and alcohol/marijuana use. Adolescents (N = 18) aged 16-17 years carried global positioning system (GPS)-enabled smartphones for 1 week, with locations tracked. Activity spaces were created by connecting global positioning system points sequentially and adding buffers. Contextual exposure data (e.g., alcohol outlets) were connected to routes. Adolescents completed texts regarding behaviors. Adolescent activity spaces intersected 24.3 census tracts and contained nine times more alcohol outlets than that of residential census tracts. Outlet exposure in activity spaces was related to drinking. Low-socioeconomic status exposure was related to marijuana use. Findings suggest substantial differences between activity spaces and residential contexts and suggest that activity spaces are relevant for adolescent risk behaviors. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Physical Activity, a Critical Exposure Factor of Environmental Pollution in Children and Adolescents Health Risk Assessment.

Science.gov (United States)

Dong, Jingmei; Zhang, Su; Xia, Li; Yu, Yi; Hu, Shuangshuang; Sun, Jingyu; Zhou, Ping; Chen, Peijie

2018-01-23

It is an extremely urgent problem that physical fitness promotion must face not only the increasing air pollution but also the decline of physical activity level of children and adolescents worldwide at present, which is the major reason that forms an inactive lifestyle and does harm to adolescents' health. Thus, it is necessary to focus on the exposure factor in environmental health risk assessment (EHRA) which conducts supervision of environmental pollution and survey of adolescents' activity patterns according to the harmful characteristics of air pollutant and relationship between dose and response. Some countries, such as USA, Canada and Australia, regard both respiratory rate and physical activity pattern as main exposure factors for adolescents in both air pollution health risk assessment and exercise risk assessment to forecast a safe exposing condition of pollutant for adolescents while they are doing exercise outdoors. In addition, it suggests that the testing indexes and testing methods of these two exposure factors, such as investigating the time of daily physical activity, strength, and characteristic of frequency, help to set up the quantitative relationship between environmental pollution index and the time, strength, frequency of daily activities, and formulate children's and adolescents' activity instructions under different levels of environmental pollutions. As smog becomes increasingly serious at present, it is meaningful to take physical activity as a critical composition of exposure factor and establish physical activity guideline, so as to reduce the risk of air pollution, and promote physical health of children and adolescents effectively.

Direct antigonadal activity of cannabinoids: suppression of rat granulosa cell functions.

Science.gov (United States)

Adashi, E Y; Jones, P B; Hsueh, A J

1983-02-01

The direct effects of delta 9-tetrahydrocannabinol (THC) and related cannabinoids on ovarian granulosa cells were studied in vitro. Granulosa cells from immature, hypophysectomized, estrogen-treated rats were cultured for 2 days in an androstenedione-supplemented medium in the presence or absence of follicle-stimulating hormone (FSH) (10 ng/ml) with or without cannabinoids. FSH treatment increased progesterone and estrogen biosynthesis, whereas concomitant treatment with THC led to a dose-dependent inhibition of the FSH-stimulated accumulation of progesterone and estrogen with ED50 values of 3.5 +/- 0.3 X 10(-7) and 1.8 +/- 0.2 X 10(-6) M, respectively. Treatment with related but nonpsychoactive cannabinoids (cannabidiol, cannabinol, cannabigerol, or cannabichromene) was equally effective. The THC-induced inhibition of progesterone production was reversible and was associated with an inhibition of pregnenolone biosynthesis and a decrease of 3 beta-hydroxysteroid dehydrogenase activity. In addition, treatment with THC brought about a dose-dependent inhibition of the FSH-induced increase in luteinizing hormone (LH) receptors. The inhibitory effects of THC were not associated with changes in cell number, protein content, or cell viability. Thus, THC exerts direct inhibitory effects on FSH-dependent functions related to steroidogenesis and the acquisition of LH receptors, all of which are essential to follicular maturation. Because plasma concentrations of THC similar to those used in this study have been reported in human beings, repeated exposure of female users to THC may lead to ovarian dysfunction, due in part, to the direct antigonadal activity to THC.

Noise exposure at school and blood pressure in adolescents

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Fadhilah Ihsani

2017-01-01

Full Text Available Background The increasing prevalence of primary hypertension has motivated researchers to identify influencing factors, one of which is noise. There have been few studies on a relationships between noise exposure and blood pressure in children, and none have dealt exclusively with adolescents. Objective To assess for an association between noise exposure at school and blood pressure in adolescents.   Methods To identify noisy and quiet schools, the mean noise levels of 192 senior high schools in Medan were measured using sound level meters. One noisy school and one quiet school were randomly selected for inclusion (mean noise levels of  68.2 and  53.8 dB, respectively. Students from both schools underwent blood pressure measurements by mercury sphygmomanometer. Their Body weights and heights were obtained for body mass index calculations. Subjects filled questionnaires and their parents were interviewed regarding history of illnesses. Results Of the 271 adolescents recruited, 136 (50.2% were from the noisy school. Adolescents from the noisy school had higher mean systolic and diastolic blood pressures [121.6 (SD 13.87 mmHg and 71.1 (SD 8.15 mmHg, respectively], than those from the quiet school [111.8 (SD 12.61 mmHg and 63.8 (SD 8.05 mmHg, respectively]. After adjusting for other factors, noise had a significant, moderate, positive association with systolic and diastolic blood pressures [β = 0.452; B = 6.21 (95% CI 3.86-8.55 mmHg; and β = 0.473; B = 4.18 (95% CI 2.41 to 5.94 mmHg, respectively]. Conclusion Adolescents from a noisy school have a greater risk of higher systolic and diastolic blood pressures than those from a quiet school.

Chronic intermittent ethanol exposure in early adolescent and adult male rats: effects on tolerance, social behavior, and ethanol intake.

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Broadwater, Margaret; Varlinskaya, Elena I; Spear, Linda P

2011-08-01

Given the prevalence of alcohol use in adolescence, it is important to understand the consequences of chronic ethanol exposure during this critical period in development. The purpose of this study was to assess possible age-related differences in susceptibility to tolerance development to ethanol-induced sedation and withdrawal-related anxiety, as well as voluntary ethanol intake after chronic exposure to relatively high doses of ethanol during adolescence or adulthood. Juvenile/adolescent and adult male Sprague-Dawley rats were assigned to one of five 10-day exposure conditions: chronic ethanol (4 g/kg every 48 hours), chronic saline (equivalent volume every 24 hours), chronic saline/acutely challenged with ethanol (4 g/kg on day 10), nonmanipulated/acutely challenged with ethanol (4 g/kg on day 10), or nonmanipulated. For assessment of tolerance development, duration of the loss of righting reflex (LORR) and blood ethanol concentrations (BECs) upon regaining of righting reflex (RORR) were tested on the first and last ethanol exposure days in the chronic ethanol group, with both saline and nonmanipulated animals likewise challenged on the last exposure day. Withdrawal-induced anxiety was indexed in a social interaction test 24 hours after the last ethanol exposure, with ethanol-naïve chronic saline and nonmanipulated animals serving as controls. Voluntary intake was assessed 48 hours after the chronic exposure period in chronic ethanol, chronic saline and nonmanipulated animals using an 8-day 2 bottle choice, limited-access ethanol intake procedure. In general, adolescent animals showed shorter durations of LORR and higher BECs upon RORR than adults on the first and last ethanol exposure days, regardless of chronic exposure condition. Adults, but not adolescents, developed chronic tolerance to the sedative effects of ethanol, tolerance that appeared to be metabolic in nature. Social deficits were observed after chronic ethanol in both adolescents and adults

Exposure to Family Violence and Internalizing and Externalizing Problems Among Spanish Adolescents.

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Izaguirre, Ainhoa; Calvete, Esther

2018-04-01

Exposure to intimate partner violence (IPV) and child maltreatment may have devastating consequences on children's development. The aim of this research was to examine the predictive associations between exposure to violence at home (witnessing violence against the mother and/or direct victimization by the parents) and adolescent internalizing and externalizing problems. A total of 613 Spanish adolescents (13-18 years) took part in this study. Results indicate that psychological victimization by the parents predicted an increase in anxious/depressive symptoms, aggressive and rule-breaking behavior, and substance abuse at Time 2. In addition, rule-breaking behavior predicted an increase in adolescents' substance abuse at Time 2. Concerning gender, psychological victimization predicted an increase in anxiety/depression, aggressive behavior, rule-breaking behavior, and substance abuse in boys; whereas in girls, psychological victimization only predicted an increase in anxiety/depression.

Pesticide-related poison center exposures in children and adolescents aged ≤19 years in Texas, 2000-2013.

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Trueblood, Amber B; Forrester, Mathias B; Han, Daikwon; Shipp, Eva M; Cizmas, Leslie H

2016-11-01

Although national poison center data show that pesticides were the 8th most commonly reported substance category (3.27%) for children aged ≤5 years in 2014, there is limited information on childhood and adolescent pesticide exposures. This study assessed pesticide-related poison center exposures in children and adolescents aged ≤19 years from 2000-2013 in Texas to characterize the potential burden of pesticides. Pesticide-related poison center exposures among children and adolescents aged ≤19 years reported to Texas poison centers were identified. The distribution of exposures was estimated by gender, age category, medical outcome, management site, exposure route, and pesticide category. From 2000 to 2013, there were 61,147 pesticide-related poison center exposures in children and adolescents aged ≤19 years. The prevalence was highest among males at 864.24 per 100,000 population. The prevalence of unintentional exposures was highest among children aged ≤5 years at 2310.69 per 100,000 population, whereas the prevalence of intentional exposures was highest among adolescents aged 13-19 years at 13.82 per 100,000 population. A majority of medical outcomes reported were classified as having no effect (30.24%) and not followed, but minimal clinical effects possible (42.74%). Of all the exposures, 81.24% were managed on site. However, 57% of intentional exposures were referred to or treated at a health-care facility. The most common routes of exposure were ingestion (80.83%) and dermal (17.21%). The most common pesticide categories included rodenticides (30.02%), pyrethrins/pyrethroids (20.69%), and other and unspecified insecticides (18.14%). The study found differences in the frequency of exposures by intent for sex and age categories, and identified the most common medical outcomes, management site, exposure route, and pesticide category. Through characterizing pesticide-related poison center exposures, future interventions can be designed to address groups

The Study of Destructive Effects of Exposure to WIN 55212-2, an Agonist of Cannabinoid Receptor, during Pregnancy on CNS Function of Rats’ Offspring

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Mohammad Shabani

2011-08-01

Full Text Available Introduction: Cannabinoid consumption including hashish and WIN55212-2 during pregnancy has destructive affect on the development of fetus and the performance of CNS. Method: WIN treated group received daily 0.5 or 1mg/kg WIN suspended in 1% tween 80 saline (s.c. at a volume of 1 ml/kg from days 5 to 20 of pregnancy. Third, fifth and seventh weeks after birth, the effects of maternal WIN consumption on infants body weight, mortality, histological changes, motor performance and memory function were assessed. Results: Prenatal WIN consumption associated with atrophy of cerebellum cortex in granular and Purkinje cells layers. WIN treatment of pregnant rats produced a significant decrease in the rearing frequency of the offspring, but significantly increased the grooming frequency at 22, 36 and 50 days of age. During the acquisition trials, approach latencies were not significantly different between all groups of rats (50 days old.When the trial was repeated 24 hours and seven days later (retention trial, the avoidance latencies of the WIN-exposed group were significantly shorter than those of control and sham animals. The mortality percent was increased significantly and litter size was decreased significantly in WIN (1mg/kg treated rats compared to the control, sham and WIN (0/5 mg/kg treatment groups. Conclusion: These findings suggest that prenatal exposure to WIN, cannabinoid agonist, induces possibly a long-term alteration on histological, motor performance and learning and memory parameters.

Synthetic cannabinoid: prevalence, mechanisms of addiction development, mental disorders associated with the use of synthetic cannabinoid

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Antsyborov A.V.

2017-04-01

Full Text Available according to the authors among the new psychoactive substances, the number of which is growing every year, despite the measures aimed at the obstacles to their dissemination there discovered the most frequent violations of psychotic conditions associated with use of synthetic cannabinoid in clinical practice. On the black market, they are distributed through online shops, under the guise of herbal mixtures for Smoking. When ingested, this group of drugs at the peak of intoxication raises a number of mental (different according to the depth of impaired consciousness, auditory and visual hallucinations, panic attacks, acute psychotic paranoid disorders, catatonic stupor, polar affective disorders, acute polythematic delusional symptoms and somatic disorders (disorders of heart rhythm and conduction, acute ischemic disorders, hypertension, depression of respiratory activity, violation of thermoregulation, development of acute renal failure, vomiting, expressed cephalgia, clinic of hypokalemia. In the reviewed literature and authors own observations there have been discovered some cases of mental addiction development to synthetic cannabinoids. The analysis of new literature data and own clinical observations helped the authors to compare the psychotropic effects caused by this group of drugs, relative to other known surfactants. The toxic effects of CSC on the body greatly exceeds the use of plant cannabinoids, and it has almost the same effects as the synthetic cathinone’s. The speed of formation of psychological dependence is lower compared to synthetic cathinone. Developing current strategies for diagnosis, treatment, and rehabilitation of patients who use synthetic cannabinoids remains an important task for practical healthcare.

Chronic Δ⁸-THC Exposure Differently Affects Histone Modifications in the Adolescent and Adult Rat Brain.

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Prini, Pamela; Penna, Federica; Sciuccati, Emanuele; Alberio, Tiziana; Rubino, Tiziana

2017-10-04

Adolescence represents a vulnerable period for the psychiatric consequences of delta9-tetrahydrocannabinol (Δ⁸-THC) exposure, however, the molecular underpinnings of this vulnerability remain to be established. Histone modifications are emerging as important epigenetic mechanisms involved in the etiopathogenesis of psychiatric diseases, thus, we investigated the impact of chronic Δ⁸-THC exposure on histone modifications in different brain areas of female rats. We checked histone modifications associated to both transcriptional repression (H3K9 di- and tri-methylation, H3K27 tri-methylation) and activation (H3K9 and H3K14 acetylation) after adolescent and adult chronic Δ⁸-THC exposure in the hippocampus, nucleus accumbens, and amygdala. Chronic exposure to increasing doses of Δ⁸-THC for 11 days affected histone modifications in a region- and age-specific manner. The primary effect in the adolescent brain was represented by changes leading to transcriptional repression, whereas the one observed after adult treatment led to transcriptional activation. Moreover, only in the adolescent brain, the primary effect was followed by a homeostatic response to counterbalance the Δ⁸-THC-induced repressive effect, except in the amygdala. The presence of a more complex response in the adolescent brain may be part of the mechanisms that make the adolescent brain vulnerable to Δ⁸-THC adverse effects.

Secondhand smoke exposure and endothelial stress in children and adolescents.

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Groner, Judith A; Huang, Hong; Nagaraja, Haikady; Kuck, Jennifer; Bauer, John Anthony

2015-01-01

Links between secondhand smoke exposure and cardiovascular disease in adults are well established. Little is known about the impact of this exposure on cardiovascular status during childhood. The purpose of this study was to investigate relationships between secondhand smoke exposure in children and adolescents and cardiovascular disease risk--systemic inflammation, endothelial stress, and endothelial repair. A total of 145 subjects, aged 9 to 18 years, were studied. Tobacco smoke exposure was determined by hair nicotine level. Cardiovascular risk was assessed by markers of systemic inflammation (C-reactive protein [CRP] and adiponectin); by soluble intercellular adhesion molecule 1 (s-ICAM1), which measures endothelial activation after surface vascular injury; and by endothelial repair. This was measured by prevalence of endothelial progenitor cells (EPCs), which are bone marrow-derived cells that home preferentially to sites of vascular damage. Hair nicotine was directly correlated with s-ICAM1 (r = 0.4090, P Secondhand smoke exposure during childhood and adolescence is detrimental to vascular health because s-ICAM1 is a marker for endothelial activation and stress after vascular surface injury, and EPCs contribute to vascular repair. The fact that body mass index is also a factor in the model predicting s-ICAM1 is concerning, in that 2 risk factors may both contribute to endothelial stress. Copyright © 2015 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Lifetime secondhand smoke exposure and childhood and adolescent asthma : findings from the PIAMA cohort

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Milanzi, Edith B.; Brunekreef, Bert; Koppelman, Gerard H.; Wijga, Alet H.; van Rossem, Lenie; Vonk, Judith M.; Smit, Henriette A.; Gehring, Ulrike

2017-01-01

Background: Secondhand smoke (SHS) exposure is a modifiable risk factor associated with childhood asthma. Associations with adolescent asthma and the relevance of the timing and patterns of exposure are unclear. Knowledge of critical windows of exposure is important for targeted interventions.

Lifetime secondhand smoke exposure and childhood and adolescent asthma : findings from the PIAMA cohort

NARCIS (Netherlands)

Milanzi, Edith B; Brunekreef, Bert; Koppelman, Gerard H; Wijga, Alet H; van Rossem, Lenie; Vonk, Judith M; Smit, Henriëtte A; Gehring, Ulrike

2017-01-01

BACKGROUND: Secondhand smoke (SHS) exposure is a modifiable risk factor associated with childhood asthma. Associations with adolescent asthma and the relevance of the timing and patterns of exposure are unclear. Knowledge of critical windows of exposure is important for targeted interventions.

Prenatal and adolescent exposure to tobacco smoke modulates the development of white matter microstructure.

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Jacobsen, Leslie K; Picciotto, Marina R; Heath, Christopher J; Frost, Stephen J; Tsou, Kristen A; Dwan, Rita A; Jackowski, Marcel P; Constable, Robert T; Mencl, W Einar

2007-12-05

Prenatal exposure to maternal smoking has been linked to cognitive and auditory processing deficits in offspring. Preclinical studies have demonstrated that exposure to nicotine disrupts neurodevelopment during gestation and adolescence, possibly by disrupting the trophic effects of acetylcholine. Given recent clinical and preclinical work suggesting that neurocircuits that support auditory processing may be particularly vulnerable to developmental disruption by nicotine, we examined white matter microstructure in 67 adolescent smokers and nonsmokers with and without prenatal exposure to maternal smoking. The groups did not differ in age, educational attainment, IQ, years of parent education, or symptoms of inattention. Diffusion tensor anisotropy and anatomical magnetic resonance images were acquired, and auditory attention was assessed, in all subjects. Both prenatal exposure and adolescent exposure to tobacco smoke was associated with increased fractional anisotropy (FA) in anterior cortical white matter. Adolescent smoking was also associated with increased FA of regions of the internal capsule that contain auditory thalamocortical and corticofugal fibers. FA of the posterior limb of the left internal capsule was positively correlated with reaction time during performance of an auditory attention task in smokers but not in nonsmokers. Development of anterior cortical and internal capsule fibers may be particularly vulnerable to disruption in cholinergic signaling induced by nicotine in tobacco smoke. Nicotine-induced disruption of the development of auditory corticofugal fibers may interfere with the ability of these fibers to modulate ascending auditory signals, leading to greater noise and reduced efficiency of neurocircuitry that supports auditory processing.

Adolescent delta-9-tetrahydrocannabinol (THC) exposure fails to affect THC-induced place and taste conditioning in adult male rats.

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Wakeford, Alison G P; Flax, Shaun M; Pomfrey, Rebecca L; Riley, Anthony L

2016-01-01

Adolescent initiation of drug use has been linked to problematic drug taking later in life and may represent an important variable that changes the balance of the rewarding and/or aversive effects of abused drugs which may contribute to abuse vulnerability. The current study examined the effects of adolescent THC exposure on THC-induced place preference (rewarding effects) and taste avoidance (aversive effects) conditioning in adulthood. Forty-six male Sprague-Dawley adolescent rats received eight injections of an intermediate dose of THC (3.2mg/kg) or vehicle. After these injections, animals were allowed to mature and then trained in a combined CTA/CPP procedure in adulthood (PND ~90). Animals were given four trials of conditioning with intervening water-recovery days, a final CPP test and then a one-bottle taste avoidance test. THC induced dose-dependent taste avoidance but did not produce place conditioning. None of these effects was impacted by adolescent THC exposure. Adolescent exposure to THC had no effect on THC taste and place conditioning in adulthood. The failure to see an effect of adolescent exposure was addressed in the context of other research that has assessed exposure of drugs of abuse during adolescence on drug reactivity in adulthood. Copyright © 2015 Elsevier Inc. All rights reserved.

The Structure–Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation

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Bow, Eric W.; Rimoldi, John M.

2016-01-01

The cannabinoids are members of a deceptively simple class of terpenophenolic secondary metabolites isolated from Cannabis sativa highlighted by (−)-Δ9-tetrahydrocannabinol (THC), eliciting distinct pharmacological effects mediated largely by cannabinoid receptor (CB1 or CB2) signaling. Since the initial discovery of THC and related cannabinoids, synthetic and semisynthetic classical cannabinoid analogs have been evaluated to help define receptor binding modes and structure–CB1/CB2 functional activity relationships. This perspective will examine the classical cannabinoids, with particular emphasis on the structure–activity relationship of five regions: C3 side chain, phenolic hydroxyl, aromatic A-ring, pyran B-ring, and cyclohexenyl C-ring. Cumulative structure–activity relationship studies to date have helped define the critical structural elements required for potency and selectivity toward CB1 and CB2 and, more importantly, ushered the discovery and development of contemporary nonclassical cannabinoid modulators with enhanced physicochemical and pharmacological profiles. PMID:27398024

Cannabinoid-Induced Changes in the Activity of Electron Transport Chain Complexes of Brain Mitochondria.

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Singh, Namrata; Hroudová, Jana; Fišar, Zdeněk

2015-08-01

The aim of this study was to investigate changes in the activity of individual mitochondrial respiratory chain complexes (I, II/III, IV) and citrate synthase induced by pharmacologically different cannabinoids. In vitro effects of selected cannabinoids on mitochondrial enzymes were measured in crude mitochondrial fraction isolated from pig brain. Both cannabinoid receptor agonists, Δ(9)-tetrahydrocannabinol, anandamide, and R-(+)-WIN55,212-2, and antagonist/inverse agonists of cannabinoid receptors, AM251, and cannabidiol were examined in pig brain mitochondria. Different effects of these cannabinoids on mitochondrial respiratory chain complexes and citrate synthase were found. Citrate synthase activity was decreased only by Δ(9)-tetrahydrocannabinol and AM251. Significant increase in the complex I activity was induced by anandamide. At micromolar concentration, all the tested cannabinoids inhibited the activity of electron transport chain complexes II/III and IV. Stimulatory effect of anandamide on activity of complex I may participate on distinct physiological effects of endocannabinoids compared to phytocannabinoids or synthetic cannabinoids. Common inhibitory effect of cannabinoids on activity of complex II/III and IV confirmed a non-receptor-mediated mechanism of cannabinoid action on individual components of system of oxidative phosphorylation.

Association between Exposure to Smartphones and Ocular Health in Adolescents.

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Kim, Joowon; Hwang, Yunji; Kang, Seungheon; Kim, Minhye; Kim, Tae-Shin; Kim, Jay; Seo, Jeongmin; Ahn, Hyojeong; Yoon, Sungjoon; Yun, Jun Pil; Lee, Yae Lim; Ham, Hyunsoo; Yu, Hyeong Gon; Park, Sue K

2016-08-01

Smartphone use has dramatically increased in recent years. Smartphones may have adverse health effects, particularly on the eyes, because users stare at the screen for a much longer time than they do with ordinary mobile phones. The objective of this study was to elucidate the relationship between smartphone use and ocular symptoms among adolescents. Information on smartphone use and ocular symptoms (blurring, redness, visual disturbance, secretion, inflammation, lacrimation and dryness) related to eye fatigue and strain from 715 adolescent subjects from three cities in Korea was obtained using a structured questionnaire. Ocular health was scored using number of ocular symptoms. Odds ratios (ORs), 95% confidence intervals (95% CIs) and p-values for ocular symptoms were calculated with binomial and multinomial logistic regression models. Higher prevalence rates for ocular symptoms were observed in groups with greater exposure to smartphones (p 2 hours daily and ≤2 hours continuously) and excessive/persistent use (>2 hours daily and >2 hours continuously) compared to shorter use (<2 hours daily) were associated with multiple ocular symptoms (OR 2.18, 95% CI 1.09-4.39; OR 2.26, 95% CI 1.11-4.57, respectively). A higher lifetime exposure to smartphones was associated with a higher likelihood of having multiple ocular symptoms (OR 3.05, 95% CI 1.51-6.19; p = 0.001). Increasing exposure to smartphones can have a negative impact on ocular health in adolescents.

Hippocampal cell fate regulation by chronic cocaine during periods of adolescent vulnerability: Consequences of cocaine exposure during adolescence on behavioral despair in adulthood.

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García-Cabrerizo, R; Keller, B; García-Fuster, M J

2015-09-24

Given that adolescence represents a critical moment for shaping adult behavior and may predispose to disease vulnerability later in life, the aim of this study was to find a vulnerable period during adolescence in which hippocampal cell fate regulation was altered by cocaine exposure, and to evaluate the long-term consequences of a cocaine experience during adolescence in affecting hippocampal plasticity and behavioral despair in adulthood. Study I: Male rats were treated with cocaine (15mg/kg, i.p.) or saline for 7 consecutive days during adolescence (early post-natal day (PND) 33-39, mid PND 40-46, late PND 47-53). Hippocampal plasticity (i.e., cell fate regulation, cell genesis) was evaluated 24h after the last treatment dose during the course of adolescence (PND 40, PND 47, PND 54). Study II: The consequences of cocaine exposure during adolescence (PND 33-39 or PND 33-46; 7 or 14days) were measured in adulthood at the behavioral (i.e., forced swim test, PND 62-63) and molecular (hippocampal cell markers, PND 64) levels. Chronic cocaine during early adolescence dysregulated FADD forms only in the hippocampus (HC), as compared to other brain regions, and during mid adolescence, impaired cell proliferation (Ki-67) and increased PARP-1 cleavage (a cell death maker) in the HC. Interestingly, chronic cocaine exposure during adolescence did not alter the time adult rats spent immobile in the forced swim test. These results suggest that this paradigm of chronic cocaine administration during adolescence did not contribute to the later manifestation of behavioral despair (i.e., one pro-depressive symptom) as measured by the forced swim test in adulthood. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Timing of first exposure to maternal depression and adolescent emotional disorder in a national Canadian cohort.

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Kiyuri Naicker

Full Text Available Correlations have been reported between behavioral and cognitive outcomes in adolescence and exposure to maternal depression during the first postpartum year, but the effects of timing of maternal depression during subsequent exposure periods have rarely been controlled for. This study aims to methodically investigate the importance of timing of initial exposure to maternal depression with respect to adolescent mental health outcomes.This study used data on 937 children from the National Longitudinal Study of Children and Youth (NLSCY, a nationally-representative longitudinal survey established in 1994 by Statistics Canada. Ordinal logistic regression was used to confirm associations between adolescent emotional disorder (at 12-13 years and initial exposure to maternal depression during 2-year intervals from birth to adolescence. Following their initial exposure to maternal depression, children were dropped from subsequent cycles. Stressful life events, chronic health conditions, maternal alcohol use, maternal marital status, gender, and SES were included as covariates.The results indicated that adolescents who were initially exposed to maternal depression between the ages of 2-3 years and 4-5 years had a two-fold increase in odds of emotional disorder. No increase in odds was observed in those initially exposed during the first postpartum year or later in childhood.The results demonstrate that a sensitive period of initial exposure to maternal depression may occur between the ages of 2 and 5, and not during the first year of life indicated by previous research. These findings are congruent with the literature on emotional and behavioral development in early childhood.

Political violence exposure, adolescent school violence, and drug use: The mediating role of school support and posttraumatic stress.

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Fang, Lin; Schiff, Miriam; Benbenishty, Rami

2016-01-01

Adolescents may engage in risk behaviors to cope with the negative psychological impacts resulting from exposure to political violence. Guided by the Deterioration Deterrence Model and General Strain Theory, the present study assessed the mediating role of school support and posttraumatic stress (PTS) on two adolescent risk behaviors (i.e., school violence and drug use) among Arab and Jewish Israeli adolescents. We analyzed data from a nationally representative survey that consisted of 4,733 Israeli high school students (54.5% females; 63.2% Jewish) following the Second Lebanon War. Structural equation modeling using weighted data bootstrapped with 2,000 iterations evaluated the mediated effects of school support and PTS. The results showed that both school support and PTS mediated the pathways from political violence exposure to school violence and drug use. However, although school support and PTS fully mediated the relationship between political violence exposure and these risk behaviors for Jewish students, school support and PTS only partially mediated the relationships for Arab students. While school support can help decrease the detrimental effect of exposure to terrorism and war, Israeli adolescents exposed to more political violence may perceive receiving less school support than those experiencing less exposure. Findings of this study provide evidence for the theorized mediated pathways between political violence exposure and adolescent risk behaviors by PTS and school support. The study serves as a basis for future research that can unpack the relationship between exposure to political violence and adolescent risk-taking behaviors. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

[Cannabinoids in pain medicine].

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Karst, M

2018-06-07

The endocannabinoid system (ECS) controls a large number of vital functions. Suboptimal tone of the ECS in certain regions of the nervous system may be associated with disorders that are also associated with pain. Pain and inflammation processes can be modulated by the exogenous supply of cannabinoids. Low-to-moderate pain-relieving effects and in individual cases large pain-relieving effects were observed in randomized, controlled studies of various types of chronic pain. People with chronic neuropathic pain and stress symptoms seem to particularly benefit. The therapeutic range of cannabinoids is small; often small doses are sufficient for clinically significant effects. The "Cannabis-als-Medizin-Gesetz" (cannabis as medicine law) allows the prescription of cannabis preparations under certain conditions. Available data indicate good long-term efficacy and tolerability. However, there is little systematic long-term experience from clinical studies.

Exposure to Community Violence and Political Socialization among Adolescents in Northern Ireland

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Shepherd, Linda

2007-01-01

This study evaluates the effects of adolescent exposure to cross-community violence, intense paramilitary operations, aggression, and intimidation in Northern Ireland. Using publicly available survey data gathered by agencies in Northern Ireland, the research examines the effects of exposure to political violence with focus upon the manner by…

Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System

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Shenglong Zou

2018-03-01

Full Text Available The biological effects of cannabinoids, the major constituents of the ancient medicinal plant Cannabis sativa (marijuana are mediated by two members of the G-protein coupled receptor family, cannabinoid receptors 1 (CB1R and 2. The CB1R is the prominent subtype in the central nervous system (CNS and has drawn great attention as a potential therapeutic avenue in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Furthermore, cannabinoids also modulate signal transduction pathways and exert profound effects at peripheral sites. Although cannabinoids have therapeutic potential, their psychoactive effects have largely limited their use in clinical practice. In this review, we briefly summarized our knowledge of cannabinoids and the endocannabinoid system, focusing on the CB1R and the CNS, with emphasis on recent breakthroughs in the field. We aim to define several potential roles of cannabinoid receptors in the modulation of signaling pathways and in association with several pathophysiological conditions. We believe that the therapeutic significance of cannabinoids is masked by the adverse effects and here alternative strategies are discussed to take therapeutic advantage of cannabinoids.

Sex and Adolescent Ethanol Exposure Influence Pavlovian Conditioned Approach.

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Madayag, Aric C; Stringfield, Sierra J; Reissner, Kathryn J; Boettiger, Charlotte A; Robinson, Donita L

2017-04-01

Alcohol use among adolescents is widespread and a growing concern due to long-term behavioral deficits, including altered Pavlovian behavior, that potentially contribute to addiction vulnerability. We tested the hypothesis that adolescent intermittent ethanol (AIE) exposure alters Pavlovian behavior in males and females as measured by a shift from goal-tracking to sign-tracking. Additionally, we investigated GLT-1, an astrocytic glutamate transporter, as a potential contributor to a sign-tracking phenotype. Male and female Sprague-Dawley rats were exposed to AIE (5 g/kg, intragastric) or water intermittently 2 days on and 2 days off from postnatal day (P) 25 to 54. Around P70, animals began 20 daily sessions of Pavlovian conditioned approach (PCA), where they learned that a cue predicted noncontingent reward delivery. Lever pressing indicated interaction with the cue, or sign-tracking, and receptacle entries indicated approach to the reward delivery location, or goal-tracking. To test for effects of AIE on nucleus accumbens (NAcc) excitatory signaling, we isolated membrane subfractions and measured protein levels of the glutamate transporter GLT-1 after animals completed behavior as a measure of glutamate homeostasis. Females exhibited elevated sign-tracking compared to males with significantly more lever presses, faster latency to first lever press, and greater probability to lever press in a trial. AIE significantly increased lever pressing while blunting goal-tracking, as indicated by fewer cue-evoked receptacle entries, slower latency to receptacle entry, and lower probability to enter the receptacle in a trial. No significant sex-by-exposure interactions were observed in sign- or goal-tracking metrics. Moreover, we found no significant effects of sex or exposure on membrane GLT-1 expression in the NAcc. Females exhibited enhanced sign-tracking compared to males, while AIE decreased goal-tracking compared to control exposure. Our findings support the

The Role of Cannabinoid Receptors in the Descending Modulation of Pain

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Francesco Rossi

2010-08-01

Full Text Available The endogenous antinociceptive descending pathway represents a circuitry of the supraspinal central nervous system whose task is to counteract pain. It includes the periaqueductal grey (PAG-rostral ventromedial medulla (RVM-dorsal horn (DH axis, which is the best characterized pain modulation system through which pain is endogenously inhibited. Thus, an alternative rational strategy for silencing pain is the activation of this anatomical substrate. Evidence of the involvement of cannabinoid receptors (CB in the supraspinal modulation of pain can be found in several studies in which intra-cerebral microinjections of cannabinoid ligands or positive modulators have proved to be analgesic in different pain models, whereas cannabinoid receptor antagonists or antisense nucleotides towards CB1 receptors have facilitated pain. Like opioids, cannabinoids produce centrally-mediated analgesia by activating a descending pathway which includes PAG and its projection to downstream RVM neurons, which in turn send inhibitory projections to the dorsal horn of the spinal cord. Indeed, several studies underline a supraspinal regulation of cannabinoids on g-aminobutyric acid (GABA and glutamate release which inhibit and enhance the antinociceptive descending pathway, respectively. Cannabinoid receptor activation expressed on presynaptic GABAergic terminals reduces the probability of neurotransmitter release thus dis-inhibiting the PAG-RVM-dorsal horn antinociceptive pathway. Cannabinoids seem to increase glutamate release (maybe as consequence of GABA decrease and to require glutamate receptor activation to induce antinociception. The consequent outcome is behavioral analgesia, which is reproduced in several pain conditions, from acute to chronic pain models such as inflammatory and neuropathic pain. Taken together these findings would suggest that supraspinal cannabinoid receptors have broad applications, from pain control to closely related central nervous system

Exposure to violence in childhood is associated with higher body mass index in adolescence.

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Gooding, Holly C; Milliren, Carly; Austin, S Bryn; Sheridan, Margaret A; McLaughlin, Katie A

2015-12-01

To determine whether different types of childhood adversity are associated with body mass index (BMI) in adolescence, we studied 147 adolescents aged 13-17 years, 41% of whom reported exposure to at least one adversity (maltreatment, abuse, peer victimization, or witness to community or domestic violence). We examined associations between adversity type and age- and sex-specific BMI z-scores using linear regression and overweight and obese status using logistic regression. We adjusted for potential socio-demographic, behavioral, and psychological confounders and tested for effect modification by gender. Adolescents with a history of sexual abuse, emotional abuse, or peer victimization did not have significantly different BMI z-scores than those without exposure (p>0.05 for all comparisons). BMI z-scores were higher in adolescents who had experienced physical abuse (β=0.50, 95% CI 0.12-0.91) or witnessed domestic violence (β=0.85, 95% CI 0.30-1.40). Participants who witnessed domestic violence had almost 6 times the odds of being overweight or obese (95% CI: 1.09-30.7), even after adjustment for potential confounders. No gender-by-adversity interactions were found. Exposure to violence in childhood is associated with higher adolescent BMI. This finding highlights the importance of screening for violence in pediatric practice and providing obesity prevention counseling for youth. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of cannabinoids Δ(9)-tetrahydrocannabinol, Δ(9)-tetrahydrocannabinolic acid and cannabidiol in MPP+ affected murine mesencephalic cultures.

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Moldzio, Rudolf; Pacher, Thomas; Krewenka, Christopher; Kranner, Barbara; Novak, Johannes; Duvigneau, Johanna Catharina; Rausch, Wolf-Dieter

2012-06-15

Cannabinoids derived from Cannabis sativa demonstrate neuroprotective properties in various cellular and animal models. Mitochondrial impairment and consecutive oxidative stress appear to be major molecular mechanisms of neurodegeneration. Therefore we studied some major cannabinoids, i.e. delta-9-tetrahydrocannabinolic acid (THCA), delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in mice mesencephalic cultures for their protective capacities against 1-methyl-4-phenyl pyridinium (MPP(+)) toxicity. MPP(+) is an established model compound in the research of parkinsonism that acts as a complex I inhibitor of the mitochondrial respiratory chain, resulting in excessive radical formation and cell degeneration. MPP(+) (10 μM) was administered for 48 h at the 9th DIV with or without concomitant cannabinoid treatment at concentrations ranging from 0.01 to 10 μM. All cannabinoids exhibited in vitro antioxidative action ranging from 669 ± 11.1 (THC), 16 ± 3.2 (THCA) to 356 ± 29.5 (CBD) μg Trolox (a vitamin E derivative)/mg substance in the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay. Cannabinoids were without effect on the morphology of dopaminergic cells stained by tyrosine hydroxylase (TH) immunoreaction. THC caused a dose-dependent increase of cell count up to 17.3% at 10 μM, whereas CBD only had an effect at highest concentrations (decrease of cell count by 10.1-20% at concentrations of 0.01-10 μM). It influenced the viability of the TH immunoreactive neurons significantly, whereas THCA exerts no influence on dopaminergic cell count. Exposure of cultures to 10 μM of MPP(+) for 48 h significantly decreased the number of TH immunoreactive neurons by 44.7%, and shrunken cell bodies and reduced neurite lengths could be observed. Concomitant treatment of cultures with cannabinoids rescued dopaminergic cells. Compared to MPP(+) treated cultures, THC counteracted toxic effects in a dose-dependent manner. THCA and CBD treatment at a concentration of 10 �

Adolescent cocaine exposure simplifies orbitofrontal cortical dendritic arbors

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Lauren M DePoy

2014-10-01

Full Text Available Cocaine and amphetamine remodel dendritic spines within discrete cortico-limbic brain structures including the orbitofrontal cortex (oPFC. Whether dendrite structure is similarly affected, and whether pre-existing cellular characteristics influence behavioral vulnerabilities to drugs of abuse, remain unclear. Animal models provide an ideal venue to address these issues because neurobehavioral phenotypes can be defined both before, and following, drug exposure. We exposed mice to cocaine from postnatal days 31-35, corresponding to early adolescence, using a dosing protocol that causes impairments in an instrumental reversal task in adulthood. We then imaged and reconstructed excitatory neurons in deep-layer oPFC. Prior cocaine exposure shortened and simplified arbors, particularly in the basal region. Next, we imaged and reconstructed orbital neurons in a developmental-genetic model of cocaine vulnerability – the p190rhogap+/- mouse. p190RhoGAP is an actin cytoskeleton regulatory protein that stabilizes dendrites and dendritic spines, and p190rhogap+/- mice develop rapid and robust locomotor activation in response to cocaine. Despite this, oPFC dendritic arbors were intact in drug-naïve p190rhogap+/- mice. Together, these findings provide evidence that adolescent cocaine exposure has long-term effects on dendrite structure in the oPFC, and they suggest that cocaine-induced modifications in dendrite structure may contribute to the behavioral effects of cocaine more so than pre-existing structural abnormalities in this cell population.

The effects of exposure to violence and victimization across life domains on adolescent substance use.

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Wright, Emily M; Fagan, Abigail A; Pinchevsky, Gillian M

2013-11-01

This study uses longitudinal data from the Project on Human Development in Chicago Neighborhoods (PHDCN) to examine the effects of exposure to school violence, community violence, child abuse, and parental intimate partner violence (IPV) on youths' subsequent alcohol and marijuana use. We also examine the cumulative effects of being exposed to violence across these domains. Longitudinal data were obtained from 1,655 adolescents and their primary caregivers participating in the PHDCN. The effects of adolescents' exposure to various forms of violence across different life domains were examined relative to adolescents' frequency of alcohol and marijuana use three years later. Multivariate statistical models were employed to control for a range of child, parent, and family risk factors. Exposure to violence in a one-year period increased the frequency of substance use three years later, though the specific relationships between victimization and use varied for alcohol and marijuana use. Community violence and child abuse, but not school violence or exposure to IPV, were predictive of future marijuana use. None of the independent measures of exposure to violence significantly predicted future alcohol use. Finally, the accumulation of exposure to violence across life domains was detrimental to both future alcohol and marijuana use. The findings support prior research indicating that exposure to multiple forms of violence, across multiple domains of life, negatively impacts adolescent outcomes, including substance use. The findings also suggest that the context in which exposure to violence occurs should be considered in future research, since the more domains in which youth are exposed to violence, the fewer "safe havens" they have available. Finally, a better understanding of the types of violence youth encounter and the contexts in which these experiences occur can help inform intervention efforts aimed at reducing victimization and its negative consequences. Copyright

The Effects of Synthetic Cannabinoids on Alveolar-Arterial Oxygen Gradient

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Egemen Kucuk

2016-09-01

Full Text Available Aim: Synthetic cannabinoids are chemicals that produce several marijuana-like effects in humans. Aim of this study is to investigate the effects of synthetic cannabinoids on to alveolar-arterial oxygen gradient. Material and Method: A total of 112 patients, who admitted directly to emergency clinic with synthetic cannabinoid usage, were determined between February 2014 and August 2014. Blood gases of 41 patients were determined as arterial blood gases on room air, and included in to study. Patients were evaluated according to age, sex, decade, partial pressure of arterial oxygen, partial pressure of arterial carbon dioxide, pH, bicarbonate, metabolic status, age consistent expected alveolar-arterial oxygen gradient and calculated alveolar-arterial oxygen gradient. Results: Synthetic cannabinoid using was higher in males, mean age of patients was 23.32±6.14 years. Number of patients in the third decade were significantly higher than the other decades. The calculated alveolar-arterial oxygen gradient value of patients was significantly higher than age consistent expected alveolar-arterial oxygen gradient value. Respiratory acidosis, was significantly higher than the other types of the metabolic disorders. The best cutoff point for calculated alveolar-arterial oxygen gradient was 12.70, with sensitivity of 90% and specifity of 85%. Area under curve was 0.70 for calculated alveolar-arterial oxygen gradient. Discussion: The value of alveolar-arterial oxygen gradient has been increased due to synthetic cannabinoid usage. This can be used as a supportive parameter in the diagnosis of synthetic cannabinoid usage.

Differential Exposure and Reactivity to Interpersonal Stress Predict Sex Differences in Adolescent Depression

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Shih, Josephine H.; Eberhart, Nicole K.; Hammen, Constance L.; Brennan, Patricia A.

2006-01-01

This study tested the hypothesis that higher rates of depression in adolescent girls are explained by their greater exposure and reactivity to stress in the interpersonal domain in a large sample of 15-year-olds. Findings indicate that adolescent girls experienced higher levels of total and interpersonal episodic stress, whereas boys experienced…

Cannabinoid Receptor Signaling in Central Regulation of Feeding Behavior: A Mini-Review

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Marco Koch

2017-05-01

Full Text Available Cannabinoids are lipid messengers that modulate a variety of physiological processes and modify the generation of specific behaviors. In this regard, the cannabinoid receptor type 1 (CB1 represents the most relevant target molecule of cannabinoids so far. One main function of central CB1 signaling is to maintain whole body energy homeostasis. Thus, cannabinoids functionally interact with classical neurotransmitters in neural networks that control energy metabolism and feeding behavior. The promotion of CB1 signaling can increase appetite and stimulate feeding, while blockade of CB1 suppresses hunger and induces hypophagia. However, in order to treat overeating, pharmacological blockade of CB1 by the inverse agonist rimonabant not only suppressed feeding but also resulted in psychiatric side effects. Therefore, research within the last decade focused on deciphering the underlying cellular and molecular mechanisms of central cannabinoid signaling that control feeding and other behaviors, with the overall aim still being the identification of specific targets to develop safe pharmacological interventions for the treatment of obesity. Today, many studies unraveled the subcellular localization of CB1 and the function of cannabinoids in neurons and glial cells within circumscribed brain regions that represent integral parts of neural circuitries controlling feeding behavior. Here, these novel experimental findings will be summarized and recent advances in understanding the mechanisms of CB1-dependent cannabinoid signaling being relevant for central regulation of feeding behavior will be highlighted. Finally, presumed alternative pathways of cannabinoids that are not driven by CB1 activation but also contributing to control of feeding behavior will be introduced.

Mechanism of the Interaction of Cannabinoid System in Central Amygdale with Opioid System

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S. Sarahroodi

2008-01-01

Full Text Available Background and objectivesCannabinoids which are active compounds of marijuana show some pharmacological effects similar to the opioids. There are also functional interactions between both cannabinoid and opioid systems. In this study we investigated the role of cannabinoid receptors in central amygdala and its interaction with opioid system.MethodsIn the present study, we investigated the effects of intraperitoneal injection of opioid drugs on response-induced by intra-amygdala (intra-Amyg microinjection of cannabinoid agents in rats, using elevated plus-maze test of anxiety. ResultsIntraperitoneal injection of morphine (3, 6 and 9 mg/kg increased %OAT and %OAE, but not locomotor activity, showing an anxiolytic response. However, some doses of the opioid receptor antagonist, naloxone reduced %OAT and locomotor activity as well. Intra-Amyg administration of CB1 cannabinoid receptor agonist, ACPA (at the dose of 1.25 and 5 ng/rat increased %OAT and %OAE but not locomotor activity, thus showing an anxiolytic response, which was increased by morphine (6 mg/kg, i.p. without any interaction. Naloxone also reduced ACPA effects. Intra-Amyg administration of CB1 cannabinoid receptor antagonist, AM251 (2.5, 25 and 100 ng/rat did not alter %OAT and %OAE but higher doses of drug (25 and 100 ng/rat reduced locomotor activity. However, the drug in combination of morphine anxiolytic response and with naloxone decreased anxiety.ConclusionThe results may indicate an anxiolytic for CB1 cannabinoid. Our results also showed that opioid system may have interaction with cannabinoid receptor in the amygdale. Keywords: Cannabinoids, Morphine; Naloxone, Anxiety, Elevated Plus-Maze

Adolescent pre-exposure prophylaxis for HIV prevention: current perspectives

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Machado DM

2017-11-01

Full Text Available Daisy Maria Machado,1 Alexandre Machado de Sant’Anna Carvalho,2 Rachel Riera3 1Disciplina de Infectologia Pediátrica, Departamento de Pediatria, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2Universidade Federal do Rio de Janeiro, Rio de Janeiro, 3Disciplina de Medicina Baseada em Evidências, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil Abstract: Adolescents are a critical population that is disproportionately impacted by the HIV epidemic. More than 2 million adolescents between the age group of 10 and 19 years are living with HIV, and millions are at risk of infection. HIV risks are considerably higher among girls, especially in high-prevalence settings such as eastern and southern Africa. In addition to girls, there are other vulnerable adolescent subgroups, such as teenagers, who use intravenous (IV drugs, gay and bisexual boys, transgender youth, male sex workers, and people who fall into more than one of these categories. Pre-exposure prophylaxis (PrEP is a new intervention for people at high risk for acquiring HIV, with an estimated HIV incidence of >3%. Recent data from trials show evidence of the efficacy of PrEP as a powerful HIV prevention tool in high-risk populations, including men who have sex with men, HIV-1-serodiscordant heterosexual couples, and IV drug users. The reported efficacy in those trials of the daily use of oral tenofovir, alone or in combination with emtricitabine, to prevent HIV infection ranged from 44% to 75% and was heavily dependent on adherence. Despite the proven efficacy of PrEP in adult trials, concerns remain about its feasibility in real-life scenarios due to stigma, cost, and limited clinician experience with PrEP delivery. Recent studies are attempting to expand the inquiry into the efficacy of such HIV prophylaxis approaches in adolescent populations, but there are still many gaps in knowledge, and no

Adolescent Exposure to Methylphenidate Increases Impulsive Choice Later in Life

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Zarish Abbas

2017-10-01

Full Text Available Background: The psychostimulant methylphenidate (MPH is known to temporarily reduce impulsive choice and promote self-control. What is not sufficiently understood is how repeated treatment with MPH affects impulsive choice in the long run, and whether any such effect is contingent on exposure at certain developmental stages.Methods: Using an animal model for impulsive choice, we examined first whether giving MPH through early adolescence alters delay discounting, an operational measure of impulsive choice, later in adulthood. We then tested whether equivalent long-term effects are observed if exposure to the drug occurred during adulthood. Starting on postnatal day 25 or postnatal day 60, male rats received one of a range of doses of MPH for 10 consecutive days. Twenty-six days later, all rats were trained to choose between a lever that produced a small immediate reward and a lever that produced a large reward after a range of delays.Results: Rats showed a long-term decrease in the selection of the delayed larger reward when treated with moderate doses of MPH during early adolescence, but not when treated with the lower or higher doses. In contrast, no differences were observed in the selection of the delayed larger reward in animals that were treated with various doses of MPH during adulthood.Conclusions: Our findings suggest effects of MPH on impulsive choice that are contingent on dosage and on the developmental period of exposure. When administered during adolescence, moderate doses of MPH increase impulsive choice long after the end of treatment, whereas these same doses administered during adulthood were without effect

Exposure to cannabis in popular music and cannabis use among adolescents.

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Primack, Brian A; Douglas, Erika L; Kraemer, Kevin L

2010-03-01

Cannabis use is referenced frequently in American popular music, yet it remains uncertain whether exposure to these references is associated with actual cannabis use. We aimed to determine if exposure to cannabis in popular music is associated independently with current cannabis use in a cohort of urban adolescents. We surveyed all 9th grade students at three large US urban high schools. We estimated participants' exposure to lyrics referent to cannabis with overall music exposure and content analyses of their favorite artists' songs. Outcomes included current (past 30 days) and ever use of cannabis. We used multivariable regression to assess independent associations between exposures and outcomes while controlling for important covariates. Each of the 959 participants was exposed to an estimated 27 cannabis references per day [correction added on 19 January 2010, after first online publication: 40 has been changed to 27] (standard deviation = 73 [correction added on 19 January 2010, after first online publication: 104 has been changed to 73]). Twelve per cent (n = 108) were current cannabis users and 32% (n = 286) had ever used cannabis. Compared with those in the lowest tertile of total cannabis exposure in music, those in the highest tertile of exposure were almost twice as likely to have used cannabis in the past 30 days (odds ratio = 1.83; 95% confidence interval = 1.04, 3.22), even after adjusting for socio-demographic variables, personality characteristics and parenting style. As expected, however, there was no significant relationship between our cannabis exposure variable and a sham outcome variable of alcohol use. This study supports an independent association between exposure to cannabis in popular music and early cannabis use among urban American adolescents.

Secondhand Smoke Exposure Among Nonsmoking Adolescents in West Africa

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Veeranki, Sreenivas P.; Kioko, David M.; Ogwell Ouma, Ahmed E.

2015-01-01

Objectives. We estimated the prevalence and determinants of secondhand smoke (SHS) exposure among nonsmoking adolescents in 9 West African countries. Methods. We conducted a pooled analysis with nationally representative 2006 to 2009 Global Youth Tobacco Survey data. We used descriptive statistics to determine the prevalence of SHS exposure and inferential statistics using a multivariable logistic regression model to determine factors associated with SHS exposure. We investigated average marginal effect results that show the probability of SHS exposure, adjusting for all other attributes. Results. SHS exposure inside the home ranged from 13.0% to 45.0%; SHS exposure outside the home ranged from 24.7% to 80.1%. Parental or peer smoking behaviors were significantly associated with higher probability of SHS exposure in all 9 countries. Knowledge of smoking harm, support for smoking bans, exposure to antismoking media messages, and receptivity of school tobacco education were significantly associated with higher SHS exposure in most countries. Conclusions. West African policymakers should adopt policies consistent with Article 8 of the World Health Organization Framework Convention on Tobacco Control and its guidelines and public health education to promote smoke-free households. PMID:26180960

Association of established smoking among adolescents with timing of exposure to smoking depicted in movies.

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Primack, Brian A; Longacre, Meghan R; Beach, Michael L; Adachi-Mejia, Anna M; Titus, Linda J; Dalton, Madeline A

2012-04-04

It is not known whether exposure to smoking depicted in movies carries greater influence during early or late adolescence. We aimed to quantify the independent relative contribution to established smoking of exposure to smoking depicted in movies during both early and late adolescence. We prospectively assessed 2049 nonsmoking students recruited from 14 randomly selected public schools in New Hampshire and Vermont. At baseline enrollment, students aged 10-14 years completed a written survey to determine personal, family, and sociodemographic characteristics and exposure to depictions of smoking in the movies (early exposure). Seven years later, we conducted follow-up telephone interviews to ascertain follow-up exposure to movie smoking (late exposure) and smoking behavior. We used multiple regression models to assess associations between early and late exposure and development of established smoking. One-sixth (17.3%) of the sample progressed to established smoking. In analyses that controlled for covariates and included early and late exposure in the same model, we found that students in the highest quartile for early exposure had 73% greater risk of established smoking than those in the lowest quartile for early exposure (27.8% vs 8.6%; relative risk for Q4 vs Q1 = 1.73, 95% confidence interval = 1.14 to 2.62). However, late exposure to depictions of smoking in movies was not statistically significantly associated with established smoking (22.1% vs 14.0%; relative risk for Q4 vs Q1 = 1.13, 95% confidence interval = 0.89 to 1.44). Whereas 31.6% of established smoking was attributable to early exposure, only an additional 5.3% was attributable to late exposure. Early exposure to smoking depicted in movies is associated with established smoking among adolescents. Educational and policy-related interventions should focus on minimizing early exposure to smoking depicted in movies.

What Are Synthetic Cannabinoids?

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... years, synthetic cannabinoid mixtures have been easy to buy in drug paraphernalia shops, novelty stores, gas stations, and over ... abuse, authorities have made it illegal to sell, buy, or possess some of ... use is that standard drug tests cannot easily detect many of the chemicals ...

Daily exposure to either a high- or low-energy-dense snack food reduces its reinforcing value in adolescents.

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Temple, Jennifer L; Van der Kloet, Erika; Atkins, Amanda M; Crandall, Amanda K; Ziegler, Amanda M

2017-02-01

To examine the impact of daily exposure to a low-energy-dense (LED) or a high-energy-dense (HED) snack food on its reinforcing value (RRV) in adolescents with healthy weight, overweight, or obesity. A parallel-group, randomized trial was used to assess RRV of LED or HED snack food at baseline and again after exposure to that snack food daily for 2 weeks in 77 adolescents, aged 13 to 17 years. Information on eating-related subject characteristics was also collected at baseline. After 2 weeks of daily exposure, the RRV of the snack foods was significantly reduced in all participants, regardless of energy density or participant weight status. Among individuals who were high in dietary restraint only, those randomized to LED food found their snack food less reinforcing at baseline than those who were randomized to HED food. Baseline eating-related variables also differed as a function of weight status. Daily exposure to snack food in adolescents reduces the RRV of that food regardless of snack food energy density or weight status of the adolescent. This finding differs from adults, suggesting that increases in RRV of HED food after repeated exposure may develop after adolescence. © 2017 The Obesity Society.

Beyond THC: the new generation of cannabinoid designer drugs

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Liana eFattore

2011-09-01

Full Text Available Synthetic cannabinoids are functionally similar to delta9-tetrahydrocannabinol (THC, the psychoactive principle of cannabis, and bind to the same cannabinoid receptors in the brain and peripheral organs. From 2008, synthetic cannabinoids were detected in herbal smoking mixtures sold on websites and in head shops under the brand name of Spice Gold, Yucatan Fire, Aroma, and others. Although these products (also known as Spice drugs or legal highs do not contain tobacco or cannabis, when smoked they produce effects similar to THC. Intoxication, withdrawal, psychosis and death have been recently reported after consumption, posing difficult social, political and health challenges. More than 140 different Spice products have been identified to date. The ability to induce strong cannabis-like psychoactive effects, along with the fact that they are readily available on the Internet, still legal in many countries, marketed as natural safe substances, and undetectable by conventional drug screening tests, has rendered these drugs very popular and particularly appealing to young and drug-naïve individuals seeking new experiences. An escalating number of compounds with cannabinoid receptor activity are currently being found as ingredients of Spice, of which almost nothing is known in terms of pharmacology, toxicology and safety. Since legislation started to control the synthetic cannabinoids identified in these herbal mixtures, many new analogs have appeared on the market. New cannabimimetic compounds are likely to be synthesized in the near future to replace banned synthetic cannabinoids, leading to a dog chasing its tail situation. Spice smokers are exposed to drugs that are extremely variable in composition and potency, and are at risk of serious, if not lethal, outcomes. Social and health professionals should maintain a high degree of alertness for Spice use and its possible psychiatric effects in vulnerable people.

Multiple sclerosis following treatment with a cannabinoid receptor-1 antagonist

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van Oosten, B. W.; Killestein, J.; Mathus-Vliegen, E. M. H.; Polman, C. H.

2004-01-01

Laboratory research including animal models of human disease suggests that cannabinoids might have therapeutic potential in multiple sclerosis (MS). We have recently seen a 46-year-old woman who developed MS after starting treatment with a cannabinoid receptor antagonist for obesity. The occurrence

Exposure to violence and mental health of adolescents: South African Health and Well-being Study

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Stansfeld, Stephen A.; Rothon, Catherine; Das-Munshi, Jayati; Mathews, Cathy; Adams, Arlene; Clark, Charlotte; Lund, Crick

2017-01-01

Background Material and social environmental stressors affect mental health in adolescence. Protective factors such as social support from family and friends may help to buffer the effects of adversity. Aims The association of violence exposure and emotional disorders was examined in Cape Town adolescents. Method A total of 1034 Grade 8 high school students participated from seven government co-educational schools in Cape Town, South Africa. Exposure to violence in the past 12 months and post...

Child and adolescent exposure to food and beverage brand appearances during prime-time television programming.

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Speers, Sarah E; Harris, Jennifer L; Schwartz, Marlene B

2011-09-01

The food industry disproportionately markets to young people through product placements. Children and adolescents may be more susceptible to these disguised persuasive attempts. Quantify incidence and youth exposure to food and beverage brand appearances within shows on prime-time TV. Data on the number of food, beverage, and restaurant brand appearances within shows during prime-time programming in 2008 were purchased from Nielsen and analyzed by product category and company in 2010. Exposure to these brand appearances by children, adolescents, and adults were examined and compared with exposure to prime-time TV advertisements for the same categories and companies using additional Nielsen data. Food, beverage, and restaurant brands appeared a total of 35,000 times within prime-time TV programming examined by Nielsen in 2008. Regular soft drinks, traditional restaurants (i.e., not quickserve), and energy/sports drinks made up 60% of all brand appearances. Young people viewed relatively few of these appearances with one notable exception. Coca-Cola products were seen 198 times by the average child and 269 times by the average adolescent during prime-time shows over the year, accounting for 70% of child exposure and 61% of adolescent exposure to brand appearances. One show, American Idol, accounted for more than 95% of these exposures. Exposure of children to Coca-Cola products through traditional advertisements was much less common. Brand appearances for most food industry companies, except for Coca-Cola, are relatively rare during prime-time programming with large youth audiences. Coca-Cola has pledged to refrain from advertising to children, yet the average child views almost four Coke appearances on prime-time TV every week. This analysis reveals a substantial, potential loophole in current food industry self-regulatory pledges to advertise only better-for-you foods to children. Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc

Hearing and loud music exposure in 14-15 years old adolescents

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Mario R Serra

2014-01-01

The participants consisted in 172 14-15 years old adolescents from a technical high school. Conventional and extended high frequency audiometry, transient evoked otoacoustic emissions and questionnaire on recreational habits were administered. Hearing threshold levels (HTLs were classified as: normal (Group 1, slightly shifted (Group 2, and significantly shifted (Group 3. The musical general exposure (MGE, from participation in recreational musical activities, was categorized in low, moderate, and high exposure. The results revealed an increase of HTL in Group 2 compared with Group 1 (P < 0.01, in Group 3 compared with Group 2 (P < 0.05 only in extended high frequency range, in Group 3 compared with Group 1 (P < 0.01. Besides, a decrease in mean global amplitude, reproducibility and in frequencies amplitude in Group 2 compared with Group 1 (P < 0.05 and in Group 3 compared with Group 1 (P < 0.05. A significant difference (P < 0.05 was found in Group 1′s HTL between low and high exposure, showing higher HTL in high exposure. The sound immission measured in nightclubs (107.8-112.2 dBA and PMPs (82.9-104.6 dBA revealed sound levels risky for hearing health according to exposure times. It demonstrates the need to implement preventive and hearing health promoting actions in adolescents.

Cannabinoids for Medical Use A Systematic Review and Meta-analysis

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Whiting, Penny F.; Wolff, Robert F.; Deshpande, Sohan; Di Nisio, Marcello; Duffy, Steven; Hernandez, Adrian V.; Keurentjes, J. Christiaan; Lang, Shona; Misso, Kate; Ryder, Steve; Schmidlkofer, Simone; Westwood, Marie; Kleijnen, Jos

2015-01-01

IMPORTANCE Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear. OBJECTIVE To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids. DATA SOURCES Twenty-eight databases from

Case Series of Synthetic Cannabinoid Intoxication from One Toxicology Center

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Kenneth D. Katz

2016-05-01

Full Text Available Synthetic cannabinoid use has risen at alarming rates. This case series describes 11 patients exposed to the synthetic cannabinoid, MAB-CHMINACA who presented to an emergency department with life-threatening toxicity including obtundation, severe agitation, seizures and death. All patients required sedatives for agitation, nine required endotracheal intubation, three experienced seizures, and one developed hyperthermia. One developed anoxic brain injury, rhabdomyolysis and died. A significant number were pediatric patients. The mainstay of treatment was aggressive sedation and respiratory support. Synthetic cannabinoids pose a major public health risk. Emergency physicians must be aware of their clinical presentation, diagnosis and treatment.

The medicinal use of cannabis and cannabinoids--an international cross-sectional survey on administration forms.

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Hazekamp, Arno; Ware, Mark A; Muller-Vahl, Kirsten R; Abrams, Donald; Grotenhermen, Franjo

2013-01-01

Cannabinoids, including tetrahydrocannabinol and cannabidiol, are the most important active constituents of the cannabis plant. Over recent years, cannabinoid-based medicines (CBMs) have become increasingly available to patients in many countries, both as pharmaceutical products and as herbal cannabis (marijuana). While there seems to be a demand for multiple cannabinoid-based therapeutic products, specifically for symptomatic amelioration in chronic diseases, therapeutic effects of different CBMs have only been directly compared in a few clinical studies. The survey presented here was performed by the International Association for Cannabinoid Medicines (IACM), and is meant to contribute to the understanding of cannabinoid-based medicine by asking patients who used cannabis or cannabinoids detailed questions about their experiences with different methods of intake. The survey was completed by 953 participants from 31 countries, making this the largest international survey on a wide variety of users of cannabinoid-based medicine performed so far. In general, herbal non-pharmaceutical CBMs received higher appreciation scores by participants than pharmaceutical products containing cannabinoids. However, the number of patients who reported experience with pharmaceutical products was low, limiting conclusions on preferences. Nevertheless, the reported data may be useful for further development of safe and effective medications based on cannabis and single cannabinoids.

Relation between aggression exposure in adolescence and adult posttraumatic stress symptoms: Moderating role of the parasympathetic nervous system.

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Barry, Samantha A; Rabkin, Ari N; Olezeski, Christy L; Rivers, Alison J; Gordis, Elana B

2015-03-15

The present study examines the impact of the parasympathetic nervous system (PNS), as measured by respiratory sinus arrhythmia (RSA), on the link between family aggression experienced during adolescence and posttraumatic stress symptoms during young adulthood. Participants completed retrospective self-report measures of interparental aggression and harsh parenting exposure during adolescence and measures of current posttraumatic stress symptoms. RSA indexed PNS activity. Among females, the three-way interaction between harsh parenting, interparental aggression, and resting RSA was significant in accounting for young adulthood PTSD symptoms. At higher values of resting RSA and higher levels of interparental aggression exposure, harsh parenting experienced during adolescence was positively associated with adulthood PTSD symptoms. Among males, adolescent aggression exposure and resting RSA did not significantly account for variation in adulthood PTSD symptoms. Thus, this study suggests that resting PNS activity may play an important role in the relationship between stressors during adolescence and later PTSD in females. Copyright © 2015 Elsevier Inc. All rights reserved.

Precipitated withdrawal counters the adverse effects of subchronic cannabinoid administration on male rat sexual behavior.

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Riebe, Caitlin J; Lee, Tiffany T; Hill, Matthew N; Gorzalka, Boris B

2010-03-26

In the present study, sexual behavior of male rats was assessed following prolonged treatment with the CB(1) receptor agonist, HU-210 (0.1mg/mg/day for 10 days) under conditions of drug maintenance, spontaneous withdrawal and precipitated withdrawal (induced via administration of the CB(1) receptor antagonist AM251; 1mg/kg). Following subchronic cannabinoid treatment, sexual activity in male rats was impaired under both the drug maintenance and spontaneous withdrawal conditions, as revealed by a reduction in frequency of both intromissions and ejaculations. Notably, the induction of precipitated drug withdrawal reversed the negative effects of subchronic HU-210 treatment on sexual activity as seen by a reversal of the suppression of ejaculations. These data illustrate that, contrary to expectations, the impairments in male sexual activity following protracted cannabinoid administration are not due to drug withdrawal, per se, but are likely mediated by neuroadaptive changes provoked by repeated drug exposure. 2010 Elsevier Ireland Ltd. All rights reserved.

Friendly fire: Longitudinal effects of exposure to violent video games on aggressive behavior in adolescent friendship dyads

NARCIS (Netherlands)

Verheijen, G.P.; Burk, W.J.; Stoltz, S.E.M.J.; Berg, Y.H.M. van den; Cillessen, A.H.N.

2018-01-01

Research on gaming effects has focused on adolescence, a developmental period in which peer relationships become increasingly salient. However, the impact of peers on the effects of violent gaming on adolescents has been understudied. This study examined whether adolescents' exposure to violent

Exposure to Violence Predicting Cortisol Response During Adolescence and Early Adulthood: Understanding Moderating Factors

Science.gov (United States)

Heinze, Justin E.; Miller, Alison L.; Stoddard, Sarah A.; Zimmerman, Marc A.

2014-01-01

Previous research on the association between violence and biological stress regulation has been largely cross-sectional, and has also focused on childhood. Using longitudinal data from a low-income, high-risk, predominantly African-American sample (n = 266; 57 % female), we tested hypotheses about the influence of cumulative exposure to violence during adolescence and early adulthood on cortisol responses in early adulthood. We found that cumulative exposure to violence predicted an attenuated cortisol response. Further, we tested whether sex, mothers’ support, or fathers’ support moderated the effect of exposure to violence on cortisol responses. We found that the effect of cumulative exposure to violence on cortisol was modified by sex; specifically, males exposed to violence exhibited a more attenuated response pattern. In addition, the effect of cumulative exposure to violence on cortisol was moderated by the presence of fathers’ support during adolescence. The findings contribute to a better understanding of how cumulative exposure to violence influences biological outcomes, emphasizing the need to understand sex and parental support as moderators of risk. PMID:24458765

Adolescents' Exposure to Community Violence: Are Neighborhood Youth Organizations Protective?

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Gardner, Margo; Brooks-Gunn, Jeanne

2009-01-01

Using data from the Project on Human Development in Chicago Neighborhoods (PHDCN), we identified a significant inverse association between the variety of youth organizations available at the neighborhood level and adolescents' exposure to community violence. We examined two non-competing explanations for this finding. First, at the individual…

Predicting Adolescent Dating Violence Perpetration: Role of Exposure to Intimate Partner Violence and Parenting Practices.

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Latzman, Natasha E; Vivolo-Kantor, Alana M; Holditch Niolon, Phyllis; Ghazarian, Sharon R

2015-09-01

Exposure to adult intimate partner violence (IPV) places youth at risk for a range of outcomes, including perpetration of adolescent dating violence (ADV). However, there is variability in the effect of IPV exposure, as many youth who are exposed to IPV do not go on to exhibit problems. Thus, research is needed to examine contextual factors, such as parenting practices, to more fully explain heterogeneity in outcomes and better predict ADV perpetration. The current research draws from a multisite study to investigate the predictive power of IPV exposure and parenting practices on subsequent ADV perpetration. Participants included 417 adolescents (48.7% female) drawn from middle schools in high-risk, urban communities. IPV exposure, two types of parenting practices (positive parenting/involvement and parental knowledge of their child's dating), and five types of ADV perpetration (threatening behaviors, verbal/emotional abuse, relational abuse, physical abuse, and sexual abuse) were assessed at baseline (2012) and approximately 5 months later (2013) via adolescent report. Analyses (conducted in 2015) used a structural equation modeling approach. Structural models indicated that IPV exposure was positively related only to relational abuse at follow-up. Further, adolescents who reported parents having less knowledge of dating partners were more likely to report perpetrating two types of ADV (physical and verbal/emotional abuse) at follow-up. Analyses did not demonstrate any significant interaction effects. Results fill a critical gap in understanding of important targets to prevent ADV in middle school and highlight the important role that parents may play in ADV prevention. Published by Elsevier Inc.

75 FR 71635 - Schedules of Controlled Substances: Temporary Placement of Five Synthetic Cannabinoids Into...

Science.gov (United States)

2010-11-24

... these THC-like synthetic cannabinoids are marketed as ``legal'' alternatives to marijuana and are being...] Schedules of Controlled Substances: Temporary Placement of Five Synthetic Cannabinoids Into Schedule I... intent to temporarily place five synthetic cannabinoids into the Controlled Substances Act (CSA) pursuant...

Synthetic Cannabinoid and Mitragynine Exposure of Law Enforcement Agents During the Raid of an Illegal Laboratory - Nevada, 2014.

Science.gov (United States)

Tapp, Loren; Ramsey, Jessica G; Wen, Anita; Gerona, Roy

2017-12-01

Synthetic cannabinoids (SCs), commonly known by the street name "Spice," are designer drugs of abuse that mimic the psychoactive effects of marijuana. Intentional SC use has resulted in multiple toxicities (1,2), but little is known about occupational SC exposure. After a federal agency's law enforcement personnel in Nevada reported irritability and feeling "high" after raiding illegal SC laboratories and processing seized SCs, a request for a health hazard evaluation was made by the agency to CDC's National Institute for Occupational Safety and Health (NIOSH) in 2014 to evaluate agents' occupational SC exposures. After making the request for a health hazard evaluation, federal agents conducted a raid of an illegal SC laboratory, with assistance from local law enforcement and Drug Enforcement Administration (DEA) personnel and with NIOSH investigators observing from a distance. After the raid, agents collected and processed material evidence. NIOSH investigators tested agents' urine for SC levels before and after the raid and measured SCs in the air and on surfaces after the raid. DEA determined that AB-PINACA (an SC compound) and mitragynine (a plant material with opium-like effects, also known as "kratom") were present in the illegal laboratory. AB-PINACA, its metabolites, and mitragynine were not detected in agents' urine before the raid; however, one or more of these substances was found in the urine of six of nine agents after the raid and processing of the SC evidence. AB-PINACA was detected in one surface wipe sample from the SC laboratory; none was detected in the air in the laboratory or in the offices of the law enforcement agency where the materials were processed after the raid. No policies were in place regarding work practices and use of personal protective equipment (PPE) during raids and evidence processing. To protect agents from SC exposures, NIOSH recommended that the agency require agents to wear a minimum level of PPE (e.g., protective gloves

Exposure to Childhood Poverty and Mental Health Symptomatology in Adolescence: A Role of Coping Strategies.

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Kim, Pilyoung; Neuendorf, Cynthia; Bianco, Hannah; Evans, Gary W

2016-12-01

Childhood poverty is associated with stress dysregulation which contributes to psychological illness in later ages. The adverse effects of childhood poverty on stress regulation may be mediated in part by the use of disengaging strategies to cope with stress. However, the relations among childhood poverty, coping strategies and psychopathology throughout childhood to adolescence have not been explored. This prospective, longitudinal study included 185 low- and middle-income adolescents at age 17. Chronic exposure to poverty from birth to early adolescence (age 13) was prospectively associated with increases in the use of disengagement versus engagement coping four years later. Increased use of disengagement coping between the ages of 13 and 17 explained the indirect link between poverty exposure since birth and both externalizing and internalizing symptoms at age 17. The findings provide evidence for a coping pathway underlying the link between prolonged exposure to childhood poverty and mental health sequelae. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Regulation of actions and habits by ventral hippocampal trkB and adolescent corticosteroid exposure.

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Barfield, Elizabeth T; Gerber, Kyle J; Zimmermann, Kelsey S; Ressler, Kerry J; Parsons, Ryan G; Gourley, Shannon L

2017-11-01

In humans and rodents, stress promotes habit-based behaviors that can interfere with action-outcome decision-making. Further, developmental stressor exposure confers long-term habit biases across rodent-primate species. Despite these homologies, mechanisms remain unclear. We first report that exposure to the primary glucocorticoid corticosterone (CORT) in adolescent mice recapitulates multiple neurobehavioral consequences of stressor exposure, including long-lasting biases towards habit-based responding in a food-reinforced operant conditioning task. In both adolescents and adults, CORT also caused a shift in the balance between full-length tyrosine kinase receptor B (trkB) and a truncated form of this neurotrophin receptor, favoring the inactive form throughout multiple corticolimbic brain regions. In adolescents, phosphorylation of the trkB substrate extracellular signal-regulated kinase 42/44 (ERK42/44) in the ventral hippocampus was also diminished, a long-term effect that persisted for at least 12 wk. Administration of the trkB agonist 7,8-dihydroxyflavone (7,8-DHF) during adolescence at doses that stimulated ERK42/44 corrected long-lasting corticosterone-induced behavioral abnormalities. Meanwhile, viral-mediated overexpression of truncated trkB in the ventral hippocampus reduced local ERK42/44 phosphorylation and was sufficient to induce habit-based and depression-like behaviors. Together, our findings indicate that ventral hippocampal trkB is essential to goal-directed action selection, countering habit-based behavior otherwise facilitated by developmental stress hormone exposure. They also reveal an early-life sensitive period during which trkB-ERK42/44 tone determines long-term behavioral outcomes.

Tolerance to the Diuretic Effects of Cannabinoids and Cross-Tolerance to a κ-Opioid Agonist in THC-Treated Mice.

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Chopda, Girish R; Parge, Viraj; Thakur, Ganesh A; Gatley, S John; Makriyannis, Alexandros; Paronis, Carol A

2016-08-01

Daily treatment with cannabinoids results in tolerance to many, but not all, of their behavioral and physiologic effects. The present studies investigated the effects of 7-day exposure to 10 mg/kg daily of Δ(9)-tetrahydrocannabinol (THC) on the diuretic and antinociceptive effects of THC and the synthetic cannabinoid AM4054. Comparison studies determined diuretic responses to the κ-opioid agonist U50,488 and furosemide. After determination of control dose-response functions, mice received 10 mg/kg daily of THC for 7 days, and dose-response functions were re-determined 24 hours, 7 days, or 14 days later. THC and AM4054 had biphasic diuretic effects under control conditions with maximum effects of 30 and 35 ml/kg of urine, respectively. In contrast, antinociceptive effects of both drugs increased monotonically with dose to >90% of maximal possible effect. Treatment with THC produced 9- and 7-fold rightward shifts of the diuresis and antinociception dose-response curves for THC and, respectively, 7- and 3-fold rightward shifts in the AM4054 dose-response functions. U50,488 and furosemide increased urine output to >35 ml/kg under control conditions. The effects of U50,488 were attenuated after 7-day treatment with THC, whereas the effects of furosemide were unaltered. Diuretic effects of THC and AM4054 recovered to near-baseline levels within 14 days after stopping daily THC injections, whereas tolerance to the antinociceptive effects persisted longer than 14 days. The tolerance induced by 7-day treatment with THC was accompanied by a 55% decrease in the Bmax value for cannabinoid receptors (CB1). These data indicate that repeated exposure to THC produces similar rightward shifts in the ascending and descending limbs of cannabinoid diuresis dose-effect curves and to antinociceptive effects while resulting in a flattening of the U50,488 diuresis dose-effect function. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Feeding induced by cannabinoids is mediated independently of the melanocortin system.

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Puspha Sinnayah

2008-05-01

Full Text Available Cannabinoids, the active components of marijuana, stimulate appetite, and cannabinoid receptor-1 (CB1-R antagonists suppress appetite and promote weight loss. Little is known about how CB1-R antagonists affect the central neurocircuitry, specifically the melanocortin system that regulates energy balance.Here, we show that peripherally administered CB1-R antagonist (AM251 or agonist equally suppressed or stimulated feeding respectively in A(y , which lack a functional melanocortin system, and wildtype mice, demonstrating that cannabinoid effects on feeding do not require melanocortin circuitry. CB1-R antagonist or agonist administered into the ventral tegmental area (VTA equally suppressed or stimulated feeding respectively, in both genotypes. In addition, peripheral and central cannabinoid administration similarly induced c-Fos activation in brain sites suggesting mediation via motivational dopaminergic circuitry. Amperometry-detected increases in evoked dopamine (DA release by the CB1-R antagonist in nucleus accumbens slices indicates that AM251 modulates DA release from VTA terminals.Our results demonstrate that the effects of cannabinoids on energy balance are independent of hypothalamic melanocortin circuitry and is primarily driven by the reward system.

Moderating the Effects of Childhood Exposure to Intimate Partner Violence: The Roles of Parenting Characteristics and Adolescent Peer Support.

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Tajima, Emiko A; Herrenkohl, Todd I; Moylan, Carrie A; Derr, Amelia S

2011-06-01

We investigate parenting characteristics and adolescent peer support as potential moderators of the effects of childhood exposure to intimate partner violence (IPV) on adolescent outcomes. Lehigh Longitudinal Study (N=416) data include parent and adolescent reports of childhood IPV exposure. Exposure to IPV predicted nearly all adverse outcomes examined, however after accounting for co-occurring child abuse and early child behavior problems, IPV predicted only one outcome. Several moderator effects were identified. Parental "acceptance" of the child moderated the effects of IPV exposure on the likelihood of teenage pregnancy and running away from home. Both peer communication and peer trust moderated the relationship between exposure to IPV and depression and running from home. Peer communication also moderated the effects of IPV exposure on high school dropout. Interventions that influence parenting practices and strengthen peer support for youth exposed to IPV may increase protection and decrease risk of several tested outcomes.

Predictive model accuracy in estimating last Δ9-tetrahydrocannabinol (THC) intake from plasma and whole blood cannabinoid concentrations in chronic, daily cannabis smokers administered subchronic oral THC.

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Karschner, Erin L; Schwope, David M; Schwilke, Eugene W; Goodwin, Robert S; Kelly, Deanna L; Gorelick, David A; Huestis, Marilyn A

2012-10-01

Determining time since last cannabis/Δ9-tetrahydrocannabinol (THC) exposure is important in clinical, workplace, and forensic settings. Mathematical models calculating time of last exposure from whole blood concentrations typically employ a theoretical 0.5 whole blood-to-plasma (WB/P) ratio. No studies previously evaluated predictive models utilizing empirically-derived WB/P ratios, or whole blood cannabinoid pharmacokinetics after subchronic THC dosing. Ten male chronic, daily cannabis smokers received escalating around-the-clock oral THC (40-120 mg daily) for 8 days. Cannabinoids were quantified in whole blood and plasma by two-dimensional gas chromatography-mass spectrometry. Maximum whole blood THC occurred 3.0 h after the first oral THC dose and 103.5h (4.3 days) during multiple THC dosing. Median WB/P ratios were THC 0.63 (n=196), 11-hydroxy-THC 0.60 (n=189), and 11-nor-9-carboxy-THC (THCCOOH) 0.55 (n=200). Predictive models utilizing these WB/P ratios accurately estimated last cannabis exposure in 96% and 100% of specimens collected within 1-5h after a single oral THC dose and throughout multiple dosing, respectively. Models were only 60% and 12.5% accurate 12.5 and 22.5h after the last THC dose, respectively. Predictive models estimating time since last cannabis intake from whole blood and plasma cannabinoid concentrations were inaccurate during abstinence, but highly accurate during active THC dosing. THC redistribution from large cannabinoid body stores and high circulating THCCOOH concentrations create different pharmacokinetic profiles than those in less than daily cannabis smokers that were used to derive the models. Thus, the models do not accurately predict time of last THC intake in individuals consuming THC daily. Published by Elsevier Ireland Ltd.

Low Vagal Tone Magnifies the Association Between Psychosocial Stress Exposure and Internalizing Psychopathology in Adolescents

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McLaughlin, Katie A.; Rith-Najarian, Leslie; Dirks, Melanie A.; Sheridan, Margaret A.

2014-01-01

Vagal tone is a measure of cardiovascular function that facilitates adaptive responses to environmental challenge. Low vagal tone is associated with poor emotional and attentional regulation in children and has been conceptualized as a marker of sensitivity to stress. We investigated whether the associations of a wide range of psychosocial stressors with internalizing and externalizing psychopathology were magnified in adolescents with low vagal tone. Resting heart period data were collected from a diverse community sample of adolescents (ages 13–17; N =168). Adolescents completed measures assessing internalizing and externalizing psychopathology and exposure to stressors occurring in family, peer, and community contexts. Respiratory sinus arrhythmia (RSA) was calculated from the interbeat interval time series. We estimated interactions between RSA and stress exposure in predicting internalizing and externalizing symptoms and evaluated whether interactions differed by gender. Exposure to psychosocial stressors was associated strongly with psychopathology. RSA was unrelated to internalizing or externalizing problems. Significant interactions were observed between RSA and child abuse, community violence, peer victimization, and traumatic events in predicting internalizing but not externalizing symptoms. Stressors were positively associated with internalizing symptoms in adolescents with low RSA but not in those with high RSA. Similar patterns were observed for anxiety and depression. These interactions were more consistently observed for male than female individuals. Low vagal tone is associated with internalizing psychopathology in adolescents exposed to high levels of stressors. Measurement of vagal tone in clinical settings might provide useful information about sensitivity to stress in child and adolescent clients. PMID:24156380

Cannabinoids cases in polish athletes

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A Pokrywka

2009-07-01

Full Text Available The aim of this study was to investigate the number of cases and the profiles of Polish athletes who had occasionally been using marijuana or hashish throughout the period of 1998-2004, with respect to: sex, age, and discipline of sport as well as the period of testing (in- and out-of-competition. Results of the study were compared with some data reported by other WADA accredited anti-doping laboratories. Totally, 13 631 urine samples taken from Polish athletes of both sexes, aged 10-67 years, performing 46 disciplines of sport were tested. Cannabinoids were detected in 267 samples. Among Polish athletes the relative number of positive THC (tetrahydrocannabinol samples was one of the highest in Europe. The group of young Polish athletes (aged 16-24 years was the most THC-positive. THC-positive cases were noted more frequently in male athletes tested during out of competitions. The so-called contact sports (rugby, ice hockey, skating, boxing, badminton, body building and acrobatic sports were those sports, where the higher risk of cannabis use was observed. The legal interpretation of some positive cannabinoids results would be difficult because of some accidental and unintentional use of the narcotics by sportsmen. It was concluded that national anti-doping organizations (NADO’s, which are competent to judge whether the anti-doping rules were violated, should take into account the possibility of non-intentional doping use of cannabinoids via passive smoking of marijuana.

Adolescents' Exposure to Sexy Media Does Not Hasten the Initiation of Sexual Intercourse

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Steinberg, Laurence; Monahan, Kathryn C.

2011-01-01

It is widely believed that exposure to sexy content in the mass media leads teenagers to become sexually active. Although most research linking sexy media exposure to adolescents' sexual behavior is cross-sectional, several recent, well-publicized longitudinal studies purport to find a causal connection, which has alarmed the public and prompted…

Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition

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Flores Juana M

2010-07-01

Full Text Available Abstract Background ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond to these treatments and most of them eventually relapse. The existence of this population of particularly aggressive and non-responding or relapsing patients urges the search for novel therapies. The purpose of this study was to determine whether cannabinoids might constitute a new therapeutic tool for the treatment of ErbB2-positive breast tumors. We analyzed their antitumor potential in a well established and clinically relevant model of ErbB2-driven metastatic breast cancer: the MMTV-neu mouse. We also analyzed the expression of cannabinoid targets in a series of 87 human breast tumors. Results Our results show that both Δ9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana, and JWH-133, a non-psychotropic CB2 receptor-selective agonist, reduce tumor growth, tumor number, and the amount/severity of lung metastases in MMTV-neu mice. Histological analyses of the tumors revealed that cannabinoids inhibit cancer cell proliferation, induce cancer cell apoptosis, and impair tumor angiogenesis. Cannabinoid antitumoral action relies, at least partially, on the inhibition of the pro-tumorigenic Akt pathway. We also found that 91% of ErbB2-positive tumors express the non-psychotropic cannabinoid receptor CB2. Conclusions Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.

Quantification of Cannabinoid Content in Cannabis

Science.gov (United States)

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

2015-09-01

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

Treatment of Tourette Syndrome with Cannabinoids

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Kirsten R. Müller-Vahl

2013-01-01

Full Text Available Cannabinoids have been used for hundred of years for medical purposes. To day, the cannabinoid delta-9-tetrahydrocannabinol (THC and the cannabis extract nabiximols are approved for the treatment of nausea, anorexia and spasticity, respectively. In Tourette syndrome (TS several anecdotal reports provided evidence that marijuana might be effective not only in the suppression of tics, but also in the treatment of associated behavioural problems. At the present time there are only two controlled trials available investigating the effect of THC in the treatment of TS. Using both self and examiner rating scales, in both studies a significant tic reduction could be observed after treatment with THC compared to placebo, without causing significant adverse effects. Available data about the effect of THC on obsessive-compulsive symptoms are inconsistent. According to a recent Cochrane review on the efficacy of cannabinoids in TS, definite conclusions cannot be drawn, because longer trials including a larger number of patients are missing. Notwithstanding this appraisal, by many experts THC is recommended for the treatment of TS in adult patients, when first line treatments failed to improve the tics. In treatment resistant adult patients, therefore, treatment with THC should be taken into consideration.

Differential physiological and behavioral cues observed in individuals smoking botanical marijuana versus synthetic cannabinoid drugs.

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Chase, Peter B; Hawkins, Jeff; Mosier, Jarrod; Jimenez, Ernest; Boesen, Keith; Logan, Barry K; Walter, Frank G

2016-01-01

Synthetic cannabinoid use has increased in many states, and medicinal and/or recreational marijuana use has been legalized in some states. These changes present challenges to law enforcement drug recognition experts (DREs) who determine whether drivers are impaired by synthetic cannabinoids or marijuana, as well as to clinical toxicologists who care for patients with complications from synthetic cannabinoids and marijuana. Our goal was to compare what effects synthetic cannabinoids and marijuana had on performance and behavior, including driving impairment, by reviewing records generated by law enforcement DREs who evaluated motorists arrested for impaired driving. Data were from a retrospective, convenience sample of de-identified arrest reports from impaired drivers suspected of using synthetic cannabinoids (n = 100) or marijuana (n = 33). Inclusion criteria were arrested drivers who admitted to using either synthetic cannabinoids or marijuana, or who possessed either synthetic cannabinoids or marijuana; who also had a DRE evaluation at the scene; and whose blood screens were negative for alcohol and other drugs. Exclusion criteria were impaired drivers arrested with other intoxicants found in their drug or alcohol blood screens. Blood samples were analyzed for 20 popular synthetic cannabinoids by using liquid chromatography-tandem mass spectrometry. Delta-9-tetrahydrocannabinol (THC) and THC-COOH were quantified by gas chromatography-mass spectrometry. Statistical significance was determined by using Fisher's exact test or Student's t-test, where appropriate, to compare the frequency of characteristics of those in the synthetic cannabinoid group versus those in the marijuana group. 16 synthetic cannabinoid and 25 marijuana records met selection criteria; the drivers of these records were arrested for moving violations. Median age for the synthetic cannabinoid group (n = 16, 15 males) was 20 years (IQR 19-23 years). Median age for the marijuana group (n = 25, 21

Exposure to Online Alcohol Marketing and Adolescents' Drinking: A Cross-sectional Study in Four European Countries.

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de Bruijn, Avalon; Engels, Rutger; Anderson, Peter; Bujalski, Michal; Gosselt, Jordy; Schreckenberg, Dirk; Wohtge, Jördis; de Leeuw, Rebecca

2016-09-01

The Internet is the leading medium among European adolescents in contemporary times; even more time is spent on the Internet than watching television. This study investigates associations between online alcohol marketing exposure and onset of drinking and binge drinking among adolescents in four European countries. A total of 9038 students with a mean age of 14.05 (SD 0.82) participated in a school-based survey in Germany, Italy, the Netherlands and Poland. Logistic regression analyses of cross-sectional cross-country survey data were undertaken. Exposure to online alcohol marketing, televised alcohol advertising and ownership of alcohol-branded items was estimated to be controlled for relevant confounders. Onset of drinking and binge drinking in the past 30 days were included in the study as outcome variables. Adjusted for relevant confounders, higher exposure to (online) alcohol marketing exposure was found to be related to the odds of starting to drink (p four countries. Active engagement with online alcohol marketing was found to interact more strongly with drinking outcomes than passive exposure to online alcohol marketing. Youngsters in the four European countries report frequent exposure to online alcohol marketing. The association between this exposure and adolescents' drinking was robust and seems consistent across national contexts. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Friendly fire: Longitudinal effects of exposure to violent video games on aggressive behavior in adolescent friendship dyads.

Science.gov (United States)

Verheijen, Geert P; Burk, William J; Stoltz, Sabine E M J; van den Berg, Yvonne H M; Cillessen, Antonius H N

2018-05-01

Research on gaming effects has focused on adolescence, a developmental period in which peer relationships become increasingly salient. However, the impact of peers on the effects of violent gaming on adolescents has been understudied. This study examined whether adolescents' exposure to violent video games predicted their own and their friend's aggression one year later. Among 705 gaming adolescents, 141 dyads were identified based on reciprocated best friend nominations (73.8% male, M age  = 13.98). Actor-Partner Interdependence Models indicated that adolescent males' (but not females') exposure to violent games positively predicted the aggression of their best friend 1 year later. This effect appeared regardless of whether the friends played video games together or not. The study illustrates the importance of peers in the association between violent gaming and aggression. © 2018 The Authors. Aggressive Behavior Published by Wiley Periodicals, Inc.

Sex Differences in Adolescent Depression: Stress Exposure and Reactivity Models

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Hankin, Benjamin L.; Mermelstein, Robin; Roesch, Linda

2007-01-01

Stress exposure and reactivity models were examined as explanations for why girls exhibit greater levels of depressive symptoms than boys. In a multiwave, longitudinal design, adolescents' depressive symptoms, alcohol usage, and occurrence of stressors were assessed at baseline, 6, and 12 months later (N=538; 54.5% female; ages 13-18, average…

Cannabinoid receptors activation and glucocorticoid receptors deactivation in the amygdala prevent the stress-induced enhancement of a negative learning experience.

Science.gov (United States)

Ramot, Assaf; Akirav, Irit

2012-05-01

The enhancement of emotional memory is clearly important as emotional stimuli are generally more significant than neutral stimuli for surviving and reproduction purposes. Yet, the enhancement of a negative emotional memory following exposure to stress may result in dysfunctional or intrusive memory that underlies several psychiatric disorders. Here we examined the effects of stress exposure on a negative emotional learning experience as measured by a decrease in the magnitude of the expected quantity of reinforcements in an alley maze. In contrast to other fear-related negative experiences, reward reduction is more associated with frustration and is assessed by measuring the latency to run the length of the alley to consume the reduced quantity of reward. We also examined whether the cannabinoid receptors agonist WIN55,212-2 (5 μg/side) and the glucocorticoid receptors (GRs) antagonist RU-486 (10 ng/side) administered into the rat basolateral amygdala (BLA) could prevent the stress-induced enhancement. We found that intra-BLA RU-486 or WIN55,212 before stress exposure prevented the stress-induced enhancement of memory consolidation for reduction in reward magnitude. These findings suggest that cannabinoid receptors and GRs in the BLA are important modulators of stress-induced enhancement of emotional memory. Copyright © 2012 Elsevier Inc. All rights reserved.

Cannabinoids as modulators of cancer cell viability, neuronal differentiation, and embryonal development

OpenAIRE

Gustafsson, Sofia

2012-01-01

Cannabinoids (CBs) are compounds that activate the CB1 and CB2 receptors. CB receptors mediate many different physiological functions, and cannabinoids have been reported to decrease tumor cell viability, proliferation, migration, as well as to modulate metastasis. In this thesis, the effects of cannabinoids on human colorectal carcinoma Caco-2 cells (Paper I) and mouse P19 embryonal carcinoma (EC) cells (Paper III) were studied.  In both cell lines, the compounds examined produced a concentr...

Cannabinoid modulation of executive functions

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Pattij, T.; Wiskerke, J.; Schoffelmeer, A.N.M.

2008-01-01

Executive functions are higher-order cognitive processes such as attention, behavioural flexibility, decision-making, inhibitory control, planning, time estimation and working memory that exert top-down control over behaviour. In addition to the role of cannabinoid signaling in other cognitive

Adolescent context of exposure to prescription opioids and substance use disorder symptoms at age 35: A national longitudinal study

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McCabe, Sean Esteban; Veliz, Philip; Schulenberg, John E.

2016-01-01

The objective of this study was to examine the association of context of prescription opioid exposure (i.e., medical and/or nonmedical) in adolescence with the subsequent risk of nonmedical use of prescription opioids (NMUPO) and substance use disorder (SUD) symptoms at age 35. Multiple cohorts of nationally representative probability samples of U.S. high school seniors (n = 4072) were surveyed via self-administered questionnaires and followed longitudinally from adolescence (modal age 18, graduating classes 1976–1996) to age 35 (1993–2013). Main outcome measures were past-year NMUPO and SUD symptoms. The medical and nonmedical use of prescription opioids during adolescence was significantly associated with NMUPO at age 35. Relative to no prescription opioid exposure, medical use of prescription opioids without any history of NMUPO during adolescence was not associated with SUD symptoms at age 35. In contrast, compared with no prescription opioid exposure during adolescence, the adjusted odds ratios (AORs) associated with SUD symptoms at age 35 were greater among those with a history of both medical use of prescription opioids and NMUPO during adolescence, AOR = 1.49 (95% confidence interval [CI], 1.13–1.97); and among those who reported NMUPO only, AOR = 2.61 (95% CI, 1.88–3.61). The findings indicate medical use of prescription opioids without any history of NMUPO in adolescence is not associated with SUD symptoms at age 35 while any NMUPO in adolescence predicts SUD symptoms at age 35. Screening instruments and preventative intervention programs to reduce NMUPO and SUDs must account for the context associated with prescription opioid exposure during adolescence. PMID:27227693

Television and music video exposure and risk of adolescent alcohol use.

Science.gov (United States)

Robinson, T N; Chen, H L; Killen, J D

1998-11-01

Alcohol use is frequently portrayed in television programming and advertising. Exposure to media portrayals of alcohol use may lead to increased drinking. To address this issue, we examined prospectively the associations between media exposure and alcohol use in adolescents. Prospective cohort study. Setting. Six public high schools in San Jose, California. Participants. Ninth-grade students (N = 1533; mean age = 14.6 years). Students reported hours of television, music video, and videotape viewing; computer and video game use; and lifetime and past 30 days' alcohol use at baseline and 18 months later. Associations between baseline media exposure and subsequent alcohol use were examined with multiple logistic regression. During the 18-month follow-up, 36.2% of baseline nondrinkers began drinking and 50.7% of baseline drinkers continued to drink. Onset of drinking was significantly associated with baseline hours of television viewing (odds ratio [OR] = 1.09; 95% confidence interval [95% CI] = 1.01-1.18), music video viewing (OR = 1.31; 95% CI = 1. 17-1.47), and videotape viewing (OR = 0.89; 95% CI = 0.79-0.99), controlling for age, sex, ethnicity, and other media use. Computer and video game use was not significantly associated with the subsequent onset of drinking. Among baseline drinkers, there were no significant associations between baseline media use and maintenance of drinking. Increased television and music video viewing are risk factors for the onset of alcohol use in adolescents. Attempts to prevent adolescent alcohol use should address the adverse influences of alcohol use in the media.

Screen Media Exposure and Obesity in Children and Adolescents.

Science.gov (United States)

Robinson, Thomas N; Banda, Jorge A; Hale, Lauren; Lu, Amy Shirong; Fleming-Milici, Frances; Calvert, Sandra L; Wartella, Ellen

2017-11-01

Obesity is one of the best-documented outcomes of screen media exposure. Many observational studies find relationships between screen media exposure and increased risks of obesity. Randomized controlled trials of reducing screen time in community settings have reduced weight gain in children, demonstrating a cause and effect relationship. Current evidence suggests that screen media exposure leads to obesity in children and adolescents through increased eating while viewing; exposure to high-calorie, low-nutrient food and beverage marketing that influences children's preferences, purchase requests, consumption habits; and reduced sleep duration. Some evidence also suggests promise for using interactive media to improve eating and physical activity behaviors to prevent or reduce obesity. Future interdisciplinary research is needed to examine the effects of newer mobile and other digital media exposures on obesity; to examine the effectiveness of additional interventions to mitigate the adverse effects of media exposures on obesity and possible moderators and mediators of intervention effects; to effectively use digital media interventions to prevent and reduce obesity; and to uncover the mechanisms underlying the causal relationships and interactions between obesity-related outcomes and media content, characteristics, and context. Copyright © 2017 by the American Academy of Pediatrics.

Screen Media Exposure and Obesity in Children and Adolescents

Science.gov (United States)

Robinson, Thomas N.; Banda, Jorge A.; Hale, Lauren; Lu, Amy Shirong; Fleming-Milici, Frances; Calvert, Sandra L.; Wartella, Ellen

2018-01-01

Obesity is one of the best-documented outcomes of screen media exposure. Many observational studies find relationships between screen media exposure and increased risks of obesity. Randomized controlled trials of reducing screen time in community settings have reduced weight gain in children, demonstrating a cause and effect relationship. Current evidence suggests that screen media exposure leads to obesity in children and adolescents through increased eating while viewing; exposure to high-calorie, low-nutrient food and beverage marketing that influences children’s preferences, purchase requests, consumption habits; and reduced sleep duration. Some evidence also suggests promise for using interactive media to improve eating and physical activity behaviors to prevent or reduce obesity. Future interdisciplinary research is needed to examine the effects of newer mobile and other digital media exposures on obesity; to examine the effectiveness of additional interventions to mitigate the adverse effects of media exposures on obesity and possible moderators and mediators of intervention effects; to effectively use digital media interventions to prevent and reduce obesity; and to uncover the mechanisms underlying the causal relationships and interactions between obesity-related outcomes and media content, characteristics, and context. PMID:29093041

An evaluation of four measures of adolescents' exposure to cigarette marketing in stores.

Science.gov (United States)

Feighery, Ellen C; Henriksen, Lisa; Wang, Yun; Schleicher, Nina C; Fortmann, Stephen P

2006-12-01

This study evaluates four measures of exposure to retail cigarette marketing in relation to adolescent smoking behavior. The measures are (a) shopping frequency in types of stores known to carry more cigarette advertising than other store types, (b) shopping frequency in specific stores that sell cigarettes in the study community, (c) the amount of exposure to cigarette brand impressions in stores where students shopped, and (d) perceived exposure to cigarette advertising. The study combined data from classroom surveys administered to 6th-, 7th-, and 8th-grade students in three California middle schools, and direct store observations quantifying cigarette marketing materials and product placement in stores where students shopped. Logistic regression models were used to examine how each exposure measure related to the odds of ever smoking and susceptibility to smoke, controlling for grade, gender, ethnicity, school performance, unsupervised time, and exposure to household and friend smoking. Frequent exposure to retail cigarette marketing as defined by each of the four measures was independently associated with a significant increase in the odds of ever smoking. All but the measure of exposure to store types was associated with a significant increase in the odds of susceptibility to smoke. Four measures of exposure to retail cigarette marketing may serve equally well to predict adolescent smoking but may vary in cost, complexity, and meaning. Depending on the outcomes of interest, the most useful measure may be a combination of self-reported exposure to types of stores that contain cigarette marketing and perceived exposure to such messages.

Cannabis, cannabinoids, and health.

Science.gov (United States)

Lafaye, Genevieve; Karila, Laurent; Blecha, Lisa; Benyamina, Amine

2017-09-01

Cannabis (also known as marijuana) is the most frequently used illicit psychoactive substance in the world. Though it was long considered to be a "soft" drug, studies have proven the harmful psychiatric and addictive effects associated with its use. A number of elements are responsible for the increased complications of cannabis use, including the increase in the potency of cannabis and an evolution in the ratio between the two primary components, Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (toward a higher proportion of Δ 9 -THC), Synthetic cannabinoid (SC) use has rapidly progressed over the last few years, primarily among frequent cannabis users, because SCs provide similar psychoactive effects to cannabis. However, their composition and pharmacological properties make them dangerous substances. Cannabis does have therapeutic properties for certain indications. These therapeutic applications pertain only to certain cannabinoids and their synthetic derivatives. The objective of this article is to summarize current developments concerning cannabis and the spread of SCs. Future studies must further explore the benefit-risk profile of medical cannabis use.

Exposure to teachers smoking and adolescent smoking behaviour: analysis of cross sectional data from Denmark

DEFF Research Database (Denmark)

Poulsen, Lis Hentze; Osler, M; Roberts, C

2002-01-01

OBJECTIVE: To determine whether adolescent smoking behaviour is associated with their perceived exposure to teachers or other pupils smoking at school, after adjustment for exposure to smoking at home, in school, and best friends smoking. DESIGN: Logistic regression analysis of cross sectional data...... from students in Denmark. SUBJECTS: 1515 grade 9 students (mean age 15.8) from 90 classes in 48 Danish schools. Outcome measure: Self reported smoking behaviour; daily smoking and heavy smoking, defined as those smoking more than 20 cigarettes per week. RESULTS: Of the students in this study, 62...... that they had seen other students smoking outdoors on the school premises. Adolescents' perceived exposure to teachers smoking outdoors on the school premises was significantly associated with daily smoking, having adjusted for sex, exposure to teachers smoking indoors at school and pupils smoking outdoors...

Association between food marketing exposure and adolescents' food choices and eating behaviors.

Science.gov (United States)

Scully, Maree; Wakefield, Melanie; Niven, Philippa; Chapman, Kathy; Crawford, David; Pratt, Iain S; Baur, Louise A; Flood, Victoria; Morley, Belinda

2012-02-01

The present study examined associations between food marketing exposure and adolescents' food choices and reported consumption of energy-dense and nutrient-poor (EDNP) foods. A cross-sectional survey of 12,188 Australian secondary students aged 12-17 years was conducted, using a web-based self-report questionnaire. Measures included students' level of exposure to commercial television and non-broadcast types of food marketing, whether they had tried a new product or requested a product they had seen advertised, and their reported consumption of fast food, sugary drinks and sweet and salty snacks. Results indicated greater exposure to commercial television, print/transport/school food marketing and digital food marketing were all independently associated with students' food choices. High commercial television viewers (>2h/day) were more likely to report higher consumption of EDNP foods (ORs ranged from 1.31 for fast food to 1.91 for sweet snacks). Some associations between digital food marketing exposure and students' eating behaviors were found; however, print/transport/school food marketing was only related to sweet snack consumption. These study results suggest that cumulative exposure to television food advertising and other food marketing sources are positively linked to adolescents' food choices and eating behaviors. Policy changes to restrict food marketing to young people should include both television and non-broadcast media. Copyright © 2011 Elsevier Ltd. All rights reserved.

Comorbidity Among Depression, Conduct Disorder, and Drug Use From Adolescence to Young Adulthood: Examining the Role of Violence Exposures

Science.gov (United States)

Cerdá, Magdalena; Tracy, Melissa; Sánchez, Brisa N.; Galea, Sandro

2012-01-01

We assessed relations among depression, conduct disorder, and drug use from adolescence to young adulthood, and evaluated whether exposure to violence contributed to disorder co-occurrence. We used data from the Project on Human Development in Chicago Neighborhoods. Respondents were 12–15 years old in 1995–1997 (N = 1,517), and were reinterviewed in 1997–2000 (n = 1,315), and 2000–2002 (n = 1,210). We examined exposure to violence at ages 12–15 and 14–17, and depression, conduct disorder, and drug use at ages 14–17 and 17–20. Multivariate transition models revealed an association between prior conduct disorder and drug use, as well as a relationship between prior depression and conduct disorder. Adolescent exposure to violence was associated with higher odds of conduct disorder and drug use but not depression. Comorbid relations between conduct disorder and drug use were independent of prior exposure to violence. Although preventing adolescent exposure to violence may reduce the risk of conduct disorder and drug use by young adulthood, future research needs to investigate alternative determinants of sequential comorbidity among depression, conduct disorder, and drug use in adolescence and young adulthood. PMID:22147426

How does exposure to cigarette advertising contribute to smoking in adolescents? The role of the developing self-concept and identification with advertising models.

Science.gov (United States)

Shadel, William G; Tharp-Taylor, Shannah; Fryer, Craig S

2009-11-01

Increased exposure to cigarette advertisements is associated with increases in adolescent smoking but the reasons for this association are not well established. This study evaluated whether self-concept development (operationalized as level of self-conflict) and identifying with the models used in cigarette print advertising contributed to smoking intentions among adolescents. Ninety-five adolescents (ages 11-17) participated in this two session study. In session 1, they rated the extent to which they identified with the models used in 10 current cigarette print ads (the models were isolated digitally from the cigarette advertisements) and their level of self-conflict was assessed. In session 2, participants viewed each of the 10 cigarette advertisements from which the models were drawn and rated their intentions to smoke following exposure to each ad. Model identification was associated with similar levels of post ad exposure smoking intentions for both younger and older adolescents when they also exhibited no self-conflict. A contrasting set of findings emerged for younger and older adolescents when they exhibited high levels of self-conflict: Young adolescents who strongly identified with the models used in cigarette advertisements had higher post ad exposure smoking intentions compared to younger adolescents who weakly identified with the models used in the advertisements; in contrast, older adolescents who weakly identified with the models used in cigarette advertisements had stronger post ad exposure smoking intentions compared to older adolescents who strongly identified with the models used in the advertisements. These results point to the importance of examining developmentally-relevant moderators for the effects of cigarette advertising exposure.

Exposure of adolescent girls to cigar images in women's magazines, 1992-1998.

Science.gov (United States)

Feit, M N

2001-01-01

OBJECTIVES: This study assessed the exposure of adolescent girls to cigar images in women's magazines from 1992 to 1998. METHODS: Data were obtained from the 5 women's magazines with the highest readership of adolescent girls. RESULTS: We found a significant upward trend in cigar images portrayed in women's magazines and a significant increase in the portrayal of women cigar smokers over the period observed. Cigar images were less likely than cigarette images to promote tobacco or nontobacco products. Among advertisements, nearly all those that featured cigars promoted nontobacco products; advertisements featuring cigarettes overwhelmingly promoted tobacco products. CONCLUSIONS: Between 1992 and 1998, adolescent readers of women's magazines were increasingly exposed to images of cigars. PMID:11211640

77 FR 12508 - Schedules of Controlled Substances: Placement of Five Synthetic Cannabinoids Into Schedule I

Science.gov (United States)

2012-03-01

... constituent of marijuana. ``Synthetic cannabinoids'' are a large family of chemically unrelated structures... that is more common in current usage, ``marijuana.'' The emergence of these five synthetic cannabinoids... cannabinoids with a potential for abuse similar to the Schedule I substances marijuana and THC. These synthetic...

Exposure to online alcohol marketing and adolescents' drinking : A cross-sectional study in four European countries

NARCIS (Netherlands)

de Bruijn, Avalon; Engels, Rutger; Anderson, Peter; Bujalski, Michal; Gosselt, Jordi F.; Schreckenberg, Dirk; Wohtge, Jördis; de Leeuw, Rebecca

2016-01-01

Aims: The Internet is the leading medium among European adolescents in contemporary times even more time is spent on the Internet than watching television. This study investigates associations between online alcohol marketing exposure and onset of drinking and binge drinking among adolescents in

Exposure to online alcohol marketing and adolescents' drinking: A cross-sectional study in four European countries

NARCIS (Netherlands)

Bruijn, A. de; Engels, R.C.M.E.; Anderson, P.D.; Bujalski, M.; Gosselt, J.; Schreckenberg, D.; Wohtge, J.; Leeuw, R.N.H. de

2016-01-01

Aims: The Internet is the leading medium among European adolescents in contemporary times; even more time is spent on the Internet than watching television. This study investigates associations between online alcohol marketing exposure and onset of drinking and binge drinking among adolescents in

Friendly fire: Longitudinal effects of exposure to violent video games on aggressive behavior in adolescent friendship dyads

Science.gov (United States)

Burk, William J.; Stoltz, Sabine E. M. J.; van den Berg, Yvonne H. M.; Cillessen, Antonius H. N.

2018-01-01

Research on gaming effects has focused on adolescence, a developmental period in which peer relationships become increasingly salient. However, the impact of peers on the effects of violent gaming on adolescents has been understudied. This study examined whether adolescents’ exposure to violent video games predicted their own and their friend's aggression one year later. Among 705 gaming adolescents, 141 dyads were identified based on reciprocated best friend nominations (73.8% male, Mage = 13.98). Actor‐Partner Interdependence Models indicated that adolescent males’ (but not females’) exposure to violent games positively predicted the aggression of their best friend 1 year later. This effect appeared regardless of whether the friends played video games together or not. The study illustrates the importance of peers in the association between violent gaming and aggression. PMID:29363767

Studies of the brain cannabinoid system using positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Gatley, S.J.; Volkow, N.D.

1995-10-01

Studies using radiolabeled psychoactive drugs in conjunction with positron emission tomography (PET) have permitted the imaging of binding sites in the human brain. Similar studies of marijuana have been hampered by the unsuitability of radiolabeled THC for PET studies, and the current unavailability of other in vivo imaging agents for cannabinoid receptors. Recent developments in medicinal chemistry suggest that a PET radiotracer for cannabinoid receptors will soon become available. This chapter briefly reviews these developments, together with the results of PET studies of the effects of marijuana and other abused drugs on brain metabolism. It also reviews PET studies of cocaine binding sites, to demonstrate the kind of investigations that will be possible when a cannabinoid receptor PET radioligand becomes available.

Studies of the brain cannabinoid system using positron emission tomography

International Nuclear Information System (INIS)

Gatley, S.J.; Volkow, N.D.

1995-01-01

Studies using radiolabeled psychoactive drugs in conjunction with positron emission tomography (PET) have permitted the imaging of binding sites in the human brain. Similar studies of marijuana have been hampered by the unsuitability of radiolabeled THC for PET studies, and the current unavailability of other in vivo imaging agents for cannabinoid receptors. Recent developments in medicinal chemistry suggest that a PET radiotracer for cannabinoid receptors will soon become available. This chapter briefly reviews these developments, together with the results of PET studies of the effects of marijuana and other abused drugs on brain metabolism. It also reviews PET studies of cocaine binding sites, to demonstrate the kind of investigations that will be possible when a cannabinoid receptor PET radioligand becomes available

Human metabolites of synthetic cannabinoids JWH-018 and JWH-073 bind with high affinity and act as potent agonists at cannabinoid type-2 receptors

International Nuclear Information System (INIS)

Rajasekaran, Maheswari; Brents, Lisa K.; Franks, Lirit N.; Moran, Jeffery H.; Prather, Paul L.

2013-01-01

K2 or Spice is an emerging drug of abuse that contains synthetic cannabinoids, including JWH-018 and JWH-073. Recent reports indicate that monohydroxylated metabolites of JWH-018 and JWH-073 retain high affinity and activity at cannabinoid type-1 receptors (CB 1 Rs), potentially contributing to the enhanced toxicity of K2 compared to marijuana. Since the parent compounds also bind to cannabinoid type-2 receptors (CB 2 Rs), this study investigated the affinity and intrinsic activity of JWH-018, JWH-073 and several monohydroxylated metabolites at human CB 2 Rs (hCB 2 Rs). The affinity of cannabinoids for hCB 2 Rs was determined by competition binding studies employing CHO-hCB 2 membranes. Intrinsic activity of compounds was assessed by G-protein activation and adenylyl cyclase (AC)-inhibition in CHO-hCB 2 cells. JWH-073, JWH-018 and several of their human metabolites exhibit nanomolar affinity and act as potent agonists at hCB 2 Rs. Furthermore, a major omega hydroxyl metabolite of JWH-073 (JWH-073-M5) binds to CB 2 Rs with 10-fold less affinity than the parent molecule, but unexpectedly, is equipotent in regulating AC-activity when compared to the parent molecule. Finally, when compared to CP-55,940 and Δ 9 -tetrahydrocannabinol (Δ 9 -THC), JWH-018, JWH-018-M5 and JWH-073-M5 require significantly less CB 2 R occupancy to produce similar levels of AC-inhibition, indicating that these compounds may more efficiently couple CB 2 Rs to AC than the well characterized cannabinoid agonists examined. These results indicate that JWH-018, JWH-073 and several major human metabolites of these compounds exhibit high affinity and demonstrate distinctive signaling properties at CB 2 Rs. Therefore, future studies examining pharmacological and toxicological properties of synthetic cannabinoids present in K2 products should consider potential actions of these drugs at both CB 1 and CB 2 Rs. - Highlights: • JWH-018 and JWH-073 are synthetic cannabinoids present in abused K2

Dyadic and Social Network Influences on Adolescent Exposure to Pregnancy Risk.

Science.gov (United States)

Jorgensen, Stephen R.; And Others

1980-01-01

Analysis indicates qualities of the interpersonal relationship of the adolescent dyad are consistently associated with exposure to pregnancy risk. Certain qualities have a counterbalancing influence on pregnancy risk in that they are positively related to the frequency of sexual intercourse while being positively related to regularity of effective…

Active and realistic passive marijuana exposure tested by three immunoassays and GC/MS in urine

International Nuclear Information System (INIS)

Mule, S.J.; Lomax, P.; Gross, S.J.

1988-01-01

Human urine samples obtained before and after active and passive exposure to marijuana were analyzed by immune kits (Roche, Amersham, and Syva) and gas chromatography/mass spectrometry (GC/MS). Seven of eight subjects were positive for the entire five-day test period with one immune kit. The latter correlated with GC/MS in 98% of the samples. Passive inhalation experiments under conditions likely to reflect realistic exposure resulted consistently in less than 10 ng/mL of cannabinoids. The 10-100-ng/mL cannabinoid concentration range essential for detection of occasional and moderate marijuana users is thus unaffected by realistic passive inhalation

Active and realistic passive marijuana exposure tested by three immunoassays and GC/MS in urine

Energy Technology Data Exchange (ETDEWEB)

Mule, S.J.; Lomax, P.; Gross, S.J.

1988-05-01

Human urine samples obtained before and after active and passive exposure to marijuana were analyzed by immune kits (Roche, Amersham, and Syva) and gas chromatography/mass spectrometry (GC/MS). Seven of eight subjects were positive for the entire five-day test period with one immune kit. The latter correlated with GC/MS in 98% of the samples. Passive inhalation experiments under conditions likely to reflect realistic exposure resulted consistently in less than 10 ng/mL of cannabinoids. The 10-100-ng/mL cannabinoid concentration range essential for detection of occasional and moderate marijuana users is thus unaffected by realistic passive inhalation.

Early adolescent boys’ exposure to Internet pornography: relationships to pubertal timing, sensation seeking, and academic performance

NARCIS (Netherlands)

Beyens, I.; Vandenbosch, L.; Eggermont, S.

2015-01-01

Research has demonstrated that adolescents regularly use Internet pornography. This two-wave panel study aimed to test an integrative model in early adolescent boys (Mage = 14.10; N = 325) that (a) explains their exposure to Internet pornography by looking at relationships with pubertal timing and

The antitumor activity of plant-derived non-psychoactive cannabinoids

OpenAIRE

McAllister, Sean D.; Soroceanu, Liliana; Desprez, Pierre-Yves

2015-01-01

As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Δ9-tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor subtypes. Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy. During the last decade, however, several studies have now shown tha...

Cannabinoids and glucocorticoids modulate emotional memory after stress.

Science.gov (United States)

Akirav, Irit

2013-12-01

Bidirectional and functional relationships between glucocorticoids and the endocannabinoid system have been demonstrated. Here, I review the interaction between the endocannabinoid and glucocorticoid/stress systems. Specifically, stress is known to produce rapid changes in endocannabinoid signaling in stress-responsive brain regions. In turn, the endocannabinoid system plays an important role in the downregulation and habituation of hypothalamic-pituitary-adrenocortical (HPA) axis activity in response to stress. Glucocorticoids also recruit the endocannabinoid system to exert rapid negative feedback control of the HPA axis during stress. It became increasingly clear, however, that cannabinoid CB1 receptors are also abundantly expressed in the basolateral amygdala (BLA) and other limbic regions where they modulate emotional arousal effects on memory. Enhancing cannabinoids signaling using exogenous CB1 receptor agonists prevent the effects of acute stress on emotional memory. I propose a model suggesting that the ameliorating effects of exogenously administered cannabinoids on emotional learning after acute stress are mediated by the decrease in the activity of the HPA axis via GABAergic mechanisms in the amygdala. Copyright © 2013 Elsevier Ltd. All rights reserved.

Inverse association of intellectual function with very low blood lead but not with manganese exposure in Italian adolescents

Energy Technology Data Exchange (ETDEWEB)

Lucchini, Roberto G., E-mail: lucchini@med.unibs.it [Department of Preventive Medicine, Mount Sinai School of Medicine, NY (United States); Section of Occupational Medicine, University of Brescia, P.le Spedali Civili 1, 25123 Brescia (Italy); Zoni, Silvia [Section of Occupational Medicine, University of Brescia, P.le Spedali Civili 1, 25123 Brescia (Italy); Guazzetti, Stefano [Public Health Service, Reggio Emilia (Italy); Bontempi, Elza [INSTM and Chemistry for Technologies Laboratory, University of Brescia (Italy); Micheletti, Serena [Cognition Psychology Neuroscience lab., University of Pavia and Unit of Child Neurology and Psychiatry, Civil Hospital of Brescia (Italy); Broberg, Karin [Division of Occupational and Environmental Medicine, Lund University (Sweden); Parrinello, Giovanni [Statistics and Biometry, University of Brescia (Italy); Smith, Donald R. [Microbiology and Environmental Toxicology, University of California at Santa Cruz (United States)

2012-10-15

Background: Pediatric lead (Pb) exposure impacts cognitive function and behavior and co-exposure to manganese (Mn) may enhance neurotoxicity. Objectives: To assess cognitive and behavioral function in adolescents with environmental exposure to Pb and Mn. Methods: In this cross sectional study, cognitive function and behavior were examined in healthy adolescents with environmental exposure to metals. The Wechsler Intelligence Scale for Children (WISC) and the Conners-Wells' Adolescent Self-Report Scale Long Form (CASS:L) were used to assess cognitive and behavioral function, respectively. ALAD polymorphisms rs1800435 and rs1139488 were measured as potential modifiers. Results: We examined 299 adolescents (49.2% females) aged 11-14 years. Blood lead (BPb) averaged 1.71 {mu}g/dL (median 1.5, range 0.44-10.2), mean Blood Manganese (BMn) was 11.1 {mu}g/dL (median 10.9, range 4.00-24.1). Average total IQ was 106.3 (verbal IQ=102, performance IQ=109.3). According to a multiple regression model considering the effect of other covariates, a reduction of about 2.4 IQ points resulted from a two-fold increase of BPb. The Benchmark Level of BPb associated with a loss of 1 IQ-point (BML01) was 0.19 {mu}g/dL, with a lower 95% confidence limit (BMLL01) of 0.11 {mu}g/dL. A very weak correlation resulted between BPb and the ADHD-like behavior (Kendall's tau rank correlation=0.074, p=0.07). No influence of ALAD genotype was observed on any outcome. Manganese was not associated with cognitive and behavioral outcomes, nor was there any interaction with lead. Conclusions: These findings demonstrate that very low level of lead exposure has a significant negative impact on cognitive function in adolescent children. Being an essential micro-nutrient, manganese may not cause cognitive effects at these low exposure levels.

Inverse association of intellectual function with very low blood lead but not with manganese exposure in Italian adolescents

International Nuclear Information System (INIS)

Lucchini, Roberto G.; Zoni, Silvia; Guazzetti, Stefano; Bontempi, Elza; Micheletti, Serena; Broberg, Karin; Parrinello, Giovanni; Smith, Donald R.

2012-01-01

Background: Pediatric lead (Pb) exposure impacts cognitive function and behavior and co-exposure to manganese (Mn) may enhance neurotoxicity. Objectives: To assess cognitive and behavioral function in adolescents with environmental exposure to Pb and Mn. Methods: In this cross sectional study, cognitive function and behavior were examined in healthy adolescents with environmental exposure to metals. The Wechsler Intelligence Scale for Children (WISC) and the Conners-Wells’ Adolescent Self-Report Scale Long Form (CASS:L) were used to assess cognitive and behavioral function, respectively. ALAD polymorphisms rs1800435 and rs1139488 were measured as potential modifiers. Results: We examined 299 adolescents (49.2% females) aged 11–14 years. Blood lead (BPb) averaged 1.71 μg/dL (median 1.5, range 0.44–10.2), mean Blood Manganese (BMn) was 11.1 μg/dL (median 10.9, range 4.00–24.1). Average total IQ was 106.3 (verbal IQ=102, performance IQ=109.3). According to a multiple regression model considering the effect of other covariates, a reduction of about 2.4 IQ points resulted from a two-fold increase of BPb. The Benchmark Level of BPb associated with a loss of 1 IQ-point (BML01) was 0.19 μg/dL, with a lower 95% confidence limit (BMLL01) of 0.11 μg/dL. A very weak correlation resulted between BPb and the ADHD-like behavior (Kendall's tau rank correlation=0.074, p=0.07). No influence of ALAD genotype was observed on any outcome. Manganese was not associated with cognitive and behavioral outcomes, nor was there any interaction with lead. Conclusions: These findings demonstrate that very low level of lead exposure has a significant negative impact on cognitive function in adolescent children. Being an essential micro-nutrient, manganese may not cause cognitive effects at these low exposure levels.

Adolescent Idiopathic Scoliosis

Science.gov (United States)

... Radiation Exposure in Scoliosis Kyphosis Adolescent Back Pain Spondylolysis For Adolescents For Adults Common Questions & Glossary Resources ... Radiation Exposure in Scoliosis Kyphosis Adolescent Back Pain Spondylolysis For Adolescents For Adults Juvenile Idiopathic Scoliosis Diagnosed ...

Brief Report: Do Delinquency and Community Violence Exposure Explain Internalizing Problems in Early Adolescent Gang Members?

Science.gov (United States)

Madan, Anjana; Mrug, Sylvie; Windle, Michael

2011-01-01

Adolescent gang members are at higher risk for internalizing problems as well as exposure to community violence and delinquency. This study examined whether gang membership in early adolescence is associated with internalizing problems (depression, anxiety, and suicidal behavior) and whether these associations are mediated by delinquency and…

Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials

OpenAIRE

Lynch, Mary E; Campbell, Fiona

2011-01-01

Effective therapeutic options for patients living with chronic pain are limited. The pain relieving effect of cannabinoids remains unclear. A systematic review of randomized controlled trials (RCTs) examining cannabinoids in the treatment of chronic non-cancer pain was conducted according to the PRISMA statement update on the QUORUM guidelines for reporting systematic reviews that evaluate health care interventions. Cannabinoids studied included smoked cannabis, oromucosal extracts of cannabi...

Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats

Directory of Open Access Journals (Sweden)

Fernando B. R. da Silva

2018-05-01

Full Text Available Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures’ morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF, pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.

Adolescent pre-exposure prophylaxis for HIV prevention: current perspectives

Science.gov (United States)

Machado, Daisy Maria; de Sant’Anna Carvalho, Alexandre Machado; Riera, Rachel

2017-01-01

Adolescents are a critical population that is disproportionately impacted by the HIV epidemic. More than 2 million adolescents between the age group of 10 and 19 years are living with HIV, and millions are at risk of infection. HIV risks are considerably higher among girls, especially in high-prevalence settings such as eastern and southern Africa. In addition to girls, there are other vulnerable adolescent subgroups, such as teenagers, who use intravenous (IV) drugs, gay and bisexual boys, transgender youth, male sex workers, and people who fall into more than one of these categories. Pre-exposure prophylaxis (PrEP) is a new intervention for people at high risk for acquiring HIV, with an estimated HIV incidence of >3%. Recent data from trials show evidence of the efficacy of PrEP as a powerful HIV prevention tool in high-risk populations, including men who have sex with men, HIV-1-serodiscordant heterosexual couples, and IV drug users. The reported efficacy in those trials of the daily use of oral tenofovir, alone or in combination with emtricitabine, to prevent HIV infection ranged from 44% to 75% and was heavily dependent on adherence. Despite the proven efficacy of PrEP in adult trials, concerns remain about its feasibility in real-life scenarios due to stigma, cost, and limited clinician experience with PrEP delivery. Recent studies are attempting to expand the inquiry into the efficacy of such HIV prophylaxis approaches in adolescent populations, but there are still many gaps in knowledge, and no country has yet approved it for use with adolescents. The aim of this review was to identify and summarize the evidence from studies on PrEP for adolescents. We have compiled and reviewed published studies focusing on safety, feasibility, adherence to therapeutics, self-perception, and legal issues related to PrEP in people aged between 10 and 24 years. PMID:29238237

Cannabinoid Hyperemesis Syndrome: A Paradoxical Cannabis Effect

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Ivonne Marie Figueroa-Rivera

2015-01-01

Full Text Available Despite well-established antiemetic properties of marijuana, there has been increasing evidence of a paradoxical effect in the gastrointestinal tract and central nervous system, given rise to a new and underrecognized clinical entity called the Cannabinoid Hyperemesis Syndrome. Reported cases in the medical literature have established a series of patients exhibiting a classical triad of symptoms: cyclic vomiting, chronic marijuana use, and compulsive bathing. We present a case of a 29-year-old man whose clinical presentation strongly correlates with cannabinoid hyperemesis syndrome. Despite a diagnosis of exclusion, this syndrome should be considered plausible in the setting of a patient with recurrent intractable vomiting and a strong history of cannabis use as presented in this case.

Pharmacological activation/inhibition of the cannabinoid system affects alcohol withdrawal-induced neuronal hypersensitivity to excitotoxic insults.

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Marina Rubio

Full Text Available Cessation of chronic ethanol consumption can increase the sensitivity of the brain to excitotoxic damages. Cannabinoids have been proposed as neuroprotectants in different models of neuronal injury, but their effect have never been investigated in a context of excitotoxicity after alcohol cessation. Here we examined the effects of the pharmacological activation/inhibition of the endocannabinoid system in an in vitro model of chronic ethanol exposure and withdrawal followed by an excitotoxic challenge. Ethanol withdrawal increased N-methyl-D-aspartate (NMDA-evoked neuronal death, probably by altering the ratio between GluN2A and GluN2B NMDA receptor subunits. The stimulation of the endocannabinoid system with the cannabinoid agonist HU-210 decreased NMDA-induced neuronal death exclusively in ethanol-withdrawn neurons. This neuroprotection could be explained by a decrease in NMDA-stimulated calcium influx after the administration of HU-210, found exclusively in ethanol-withdrawn neurons. By contrast, the inhibition of the cannabinoid system with the CB1 receptor antagonist rimonabant (SR141716 during ethanol withdrawal increased death of ethanol-withdrawn neurons without any modification of NMDA-stimulated calcium influx. Moreover, chronic administration of rimonabant increased NMDA-stimulated toxicity not only in withdrawn neurons, but also in control neurons. In summary, we show for the first time that the stimulation of the endocannabinoid system is protective against the hyperexcitability developed during alcohol withdrawal. By contrast, the blockade of the endocannabinoid system is highly counterproductive during alcohol withdrawal.

Adolescent anabolic/androgenic steroids: Aggression and anxiety during exposure predict behavioral responding during withdrawal in Syrian hamsters (Mesocricetus auratus).

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Ricci, Lesley A; Morrison, Thomas R; Melloni, Richard H

2013-11-01

In the U.S. and worldwide anabolic/androgenic steroid use remains high in the adolescent population. This is concerning given that anabolic/androgenic steroid use is associated with a higher incidence of aggressive behavior during exposure and anxiety during withdrawal. This study uses pubertal Syrian hamsters (Mesocricetus auratus) to investigate the hypothesis that an inverse behavioral relationship exists between anabolic/androgenic steroid-induced aggression and anxiety across adolescent exposure and withdrawal. In the first experiment, we examined aggression and anxiety during adolescent anabolic/androgenic steroid exposure and withdrawal. Adolescent anabolic/androgenic steroid administration produced significant increases in aggression and decreases in anxiety during the exposure period followed by significant decreases in aggression and increases in anxiety during anabolic/androgenic steroid withdrawal. In a second experiment, anabolic/androgenic steroid exposed animals were separated into groups based on their aggressive response during the exposure period and then tested for anxiety during exposure and then for both aggression and anxiety during withdrawal. Data were analyzed using a within-subjects repeated measures predictive analysis. Linear regression analysis revealed that the difference in aggressive responding between the anabolic/androgenic steroid exposure and withdrawal periods was a significant predictor of differences in anxiety for both days of testing. Moreover, the combined data suggest that the decrease in aggressive behavior from exposure to withdrawal predicts an increase in anxiety-like responding within these same animals during this time span. Together these findings indicate that early anabolic/androgenic steroid exposure has potent aggression- and anxiety-eliciting effects and that these behavioral changes occur alongside a predictive relationship that exists between these two behaviors over time. © 2013.

Violence Exposure Subtypes Differentially Mediate the Relation between Callous-Unemotional Traits and Adolescent Delinquency.

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Oberth, Carla; Zheng, Yao; McMahon, Robert J

2017-11-01

Research with children and adolescents has established a link between callous-unemotional (CU) traits and delinquency, as well as a link between violence exposure (witnessing and direct victimization) and diverse negative and antisocial outcomes. Little attention has been paid to investigating the association among CU traits, violence exposure, and various forms of delinquency. Using a sample of 753 adolescents (male =58%; African American =46%), the current study aimed to elucidate the mediating role of violence exposure (measured in grades 7, 8, 10, 11) on the relationship between CU traits measured in grade 7 and later delinquency (i.e., property, violent, drug, and sexual) assessed in grade 12. Total violence exposure (witnessing and direct victimization) mediated the association between CU traits and all forms of delinquency. When looking at witnessing and direct victimization separately, however, only witnessing violence mediated the relationship between CU traits and all forms of delinquency. These results highlight the importance of violence exposure in the CU-delinquency link, and showed the differential roles of indirect and direct forms of violence exposure on the association. Witnessing and direct victimization may involve different underlying mechanisms influencing developmental outcomes in youth. These findings have important implications for understanding developmental models of violence exposure, CU traits, and delinquency, as well as interventions for youth who have experienced both indirect and direct forms of violence.

Associations between authoritative parenting and the sun exposure and sun protective behaviours of adolescents and their friends.

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Mewse, Avril J; Lea, Stephen E G; Ntala, Eleni; Eiser, J Richard

2011-05-01

Associations between the sun exposure and sun protective behaviours of adolescents and their friends were examined along with the role played by authoritative parenting and other family and peer socialisation factors. Four hundred and two adolescents (198 males, 204 females) participated in the research. It was found that these adolescents and their friends shared similar sun exposure and sun protective behaviours and had similar parenting backgrounds. Parental authoritativeness was positively associated with the use of sun protection, even after the effects of other familial and peer variables were controlled, but not with the time spent sunbathing which was associated with friends' behaviours. The theoretical and practical implications of these findings are discussed.

Alcohol and cannabinoids differentially affect HIV infection and function of human monocyte-derived dendritic cells (MDDC

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Marisela eAgudelo

2015-12-01

Full Text Available During human immunodeficiency virus (HIV infection, alcohol has been known to induce inflammation while cannabinoids have been shown to have an anti-inflammatory role. For instance cannabinoids have been shown to reduce susceptibility to HIV-1 infection and attenuate HIV replication in macrophages. Recently, we demonstrated that alcohol induces cannabinoid receptors and regulates cytokine production by monocyte-derived dendritic cells (MDDC. However, the ability of alcohol and cannabinoids to alter MDDC function during HIV infection has not been clearly elucidated yet. In order to study the potential impact of alcohol and cannabinoids on differentiated MDDC infected with HIV, monocytes were cultured for 7 days with GM-CSF and IL-4, differentiated MDDC were infected with HIV-1Ba-L and treated with EtOH (0.1 and 0.2%, THC (5 and 10 uM, or JWH-015 (5 and 10 uM for 4-7 days. HIV infection of MDDC was confirmed by p24 and Long Terminal Repeats (LTR estimation. MDDC endocytosis assay and cytokine array profiles were measured to investigate the effects of HIV and substances of abuse on MDDC function. Our results show the HIV+EtOH treated MDDC had the highest levels of p24 production and expression when compared with the HIV positive controls and the cannabinoid treated cells. Although both cannabinoids, THC and JWH-015 had lower levels of p24 production and expression, the HIV+JWH-015 treated MDDC had the lowest levels of p24 when compared to the HIV+THC treated cells. In addition, MDDC endocytic function and cytokine production were also differentially altered after alcohol and cannabinoid treatments. Our results show a differential effect of alcohol and cannabinoids, which may provide insights into the divergent inflammatory role of alcohol and cannabinoids to modulate MDDC function in the context of HIV infection.

Using the Integrative Model to Explain How Exposure to Sexual Media Content Influences Adolescent Sexual Behavior

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Bleakley, Amy; Hennessy, Michael; Fishbein, Martin; Jordan, Amy

2011-01-01

Published research demonstrates an association between exposure to media sexual content and a variety of sex-related outcomes for adolescents. What is not known is the mechanism through which sexual content produces this "media effect" on adolescent beliefs, attitudes, and behavior. Using the Integrative Model of Behavioral Prediction, this…

Exposure to the Above the Influence antidrug advertisements and adolescent marijuana use in the United States, 2006-2008.

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Carpenter, Christopher S; Pechmann, Cornelia

2011-05-01

We examined the relationship between exposure to the Above the Influence antidrug campaign in 210 US media markets and adolescent marijuana and alcohol use from 2006 to 2008. We analyzed monthly advertising exposure (targeted rating points) data from the Office of National Drug Control Policy and drug use data from the Monitoring the Future study. We estimated multivariate logistic regression models of marijuana use for students in grades 8, 10, and 12, with controls for individual, family, and media market characteristics and year and regional fixed effects. For eighth-grade adolescent girls, greater exposure to antidrug advertisements was associated with lower rates of past-month marijuana use (adjusted odds ratio [AOR] = 0.67; 95% confidence interval [CI] = 0.52, 0.87) and lower rates of lifetime marijuana use (AOR = 0.76; 95% CI = 0.62, 0.93), but not alcohol use (AOR = 1.00; 95% CI = 0.84, 1.19). Associations were not significant for adolescent boys or for students in grades 10 and 12. Antidrug advertising may be an effective way to dissuade eighth-grade adolescent girls from initiating marijuana use.

Stability of cannabinoids in urine in three storage temperatures.

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Golding Fraga, S; Díaz-Flores Estévez, J; Díaz Romero, C

1998-01-01

Stability of cannabinoid compounds in urine samples were evaluated using several storage temperatures. Appreciable losses (> 22.4 percent) were observed in some urine samples, after being stored at room temperature for 10 days. Lower losses (8.1 percent) were observed when the urine samples were refrigerated for 4 weeks. The behavior of urine samples depended on the analyzed urine. This could be due to the different stability of the cannabinoids present in each urine sample. Important losses of 8.0 +/- 10.6, 15.8 +/- 4.2, and 19.6 +/- 6.7 percent were found when the urine samples were frozen during 40 days, 1 year, and 3 years, respectively. Average losses (> > 5 percent) can be observed after one day which could mainly be due to the decrease of the solubility of 11-nor-U9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) or adsorption process of cannabinoid molecules to the plastic storage containers.

[Testing the pharmacological activity of some synthetic cannabinoids in mice (author's transl)].

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Ganz, A J; Waser, P G

1980-01-01

A series of synthetic cannabinoids were tested in mice for analgesic, anticonvulsant, sedative and reserpine antagonistic properties as well as for influence on body temperature and on motor coordination and compared with the natural delta 9-tetrahydrocannabinol (delta 9-THC), delta 8-tetrahydrocannabinol (delta 8-THC) and cannabidiol (CBD). All cannabinoids were injected s.c. or i.p. in mice as solutions in olive oil. The synthetic cannabinoids, with the exception of the lipophilic ones, were less active than the natural delta 9-THC. 1',1'-dimethyl-delta 8-tetrahydrocannabinol (DM-delta 8-THC) has an analgesic ED 50 of 16 mg/kg s.c. (writhing test) and is three times more active than delta 9-THC, but also eight times less active than morphine. The lipophilic derivatives of delta 8-THC prolonged pentobarbitone narcosis and diminished locomotor activity in mice. Anticonvulsant activities could never be detected; all cannabinoids slightly diminished body temperature and antagonized weakly the hypothermia induced by reserpine. The trained capacity of remaining on the rotating rod was severely shortened for a long time after application of all cannabinoids but mainly by the lipophilic ones. The influence of derivation on the activity of delta 9-THC is discussed.

Long-Term Exposure to Ambient Air Pollution in Childhood-Adolescence and Lung Function in Adulthood.

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Dubrowski, A; Kliś, K; Żurawiecka, M; Dereń, K; Barszcz, M; Nowakowski, D; Wronka, I

2018-02-15

The aim of the study was to evaluate the effect of air pollution in the dwelling place during childhood-adolescence on respiratory function in early adulthood. The study was conducted in 220 female and 160 male university undergraduates in the cities of Cracow and Wroclaw in Poland and consisted of spirometry to assess lung function. The subjects' exposure to pollution during childhood-adolescence was assessed from the data acquired by the Polish Chief Inspectorate for Environmental Protection. We found differences in all spirometry variables depending on benz[a]piren exposure, in FVC% and FEV 1 /%FVC depending on PM 2.5 content, and in FVC% depending on NO 2 content . Statistically significant differences in spirometry variables were also found in relation to the degree of urbanization of the place of living during the early life period in question. The higher the urbanization, the higher is FEV 1 % and FCV%, and the lower FEV 1 /%FVC. Additionally, undergraduates of Cracow University had worse lung function compared to those of Wroclaw University. In conclusion, air pollution in the dwelling place during childhood-adolescence has an impact on lung function in early adulthood, independently of the current exposure to pollutants.

Qualitative assessment of adolescents' views about improving exposure to internet-delivered interventions

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Crutzen, R.; de Nooijer, J.; Brouwer, W.; Oenema, A.; Brug, J.

2008-01-01

Purpose - The purpose of this paper is to gain first insight into factors which might be associated with exposure to internet-delivered interventions. Design/methodology/approach - Semi-structured focus group interviews were conducted with five groups of Dutch adolescents (n=54), aged 12-17 years.

Sex and Age Differences in Exposure to Secondhand Smoke at Home among Korean Adolescents: A Nationally Representative Survey.

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Hwang, Jun Hyun; Park, Soon-Woo

2016-02-19

The authors assessed sex and age differences in secondhand smoke (SHS) exposure among vulnerable adolescent populations. Data from the 2013 Korea Youth Risk Behavior Web-based Survey of 64,499 non-smokers aged 13-18 years were analyzed using multiple logistic regression. Girls were exposed 1.26 times (95% confidence interval, 1.21-1.32) more to home SHS than boys, and the younger adolescents were more likely to be exposed to home SHS than were the older, regardless of sex (p exposure at home. Girls living with current smokers were more likely to be exposed to SHS at home than boys regardless age. Girls and younger adolescents, populations vulnerable to smoke exposure, were more likely to be exposed to SHS at home, even though they should be more protected. It is necessary to improve home SHS awareness, especially among these vulnerable populations.

Human metabolites of synthetic cannabinoids JWH-018 and JWH-073 bind with high affinity and act as potent agonists at cannabinoid type-2 receptors

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Rajasekaran, Maheswari; Brents, Lisa K.; Franks, Lirit N. [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Moran, Jeffery H. [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Arkansas Department of Public Health, Public Health Laboratory, Little Rock, AR 72205 (United States); Prather, Paul L., E-mail: pratherpaull@uams.edu [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

2013-06-01

K2 or Spice is an emerging drug of abuse that contains synthetic cannabinoids, including JWH-018 and JWH-073. Recent reports indicate that monohydroxylated metabolites of JWH-018 and JWH-073 retain high affinity and activity at cannabinoid type-1 receptors (CB{sub 1}Rs), potentially contributing to the enhanced toxicity of K2 compared to marijuana. Since the parent compounds also bind to cannabinoid type-2 receptors (CB{sub 2}Rs), this study investigated the affinity and intrinsic activity of JWH-018, JWH-073 and several monohydroxylated metabolites at human CB{sub 2}Rs (hCB{sub 2}Rs). The affinity of cannabinoids for hCB{sub 2}Rs was determined by competition binding studies employing CHO-hCB{sub 2} membranes. Intrinsic activity of compounds was assessed by G-protein activation and adenylyl cyclase (AC)-inhibition in CHO-hCB{sub 2} cells. JWH-073, JWH-018 and several of their human metabolites exhibit nanomolar affinity and act as potent agonists at hCB{sub 2}Rs. Furthermore, a major omega hydroxyl metabolite of JWH-073 (JWH-073-M5) binds to CB{sub 2}Rs with 10-fold less affinity than the parent molecule, but unexpectedly, is equipotent in regulating AC-activity when compared to the parent molecule. Finally, when compared to CP-55,940 and Δ{sup 9}-tetrahydrocannabinol (Δ{sup 9}-THC), JWH-018, JWH-018-M5 and JWH-073-M5 require significantly less CB{sub 2}R occupancy to produce similar levels of AC-inhibition, indicating that these compounds may more efficiently couple CB{sub 2}Rs to AC than the well characterized cannabinoid agonists examined. These results indicate that JWH-018, JWH-073 and several major human metabolites of these compounds exhibit high affinity and demonstrate distinctive signaling properties at CB{sub 2}Rs. Therefore, future studies examining pharmacological and toxicological properties of synthetic cannabinoids present in K2 products should consider potential actions of these drugs at both CB{sub 1} and CB{sub 2}Rs. - Highlights: • JWH-018

One Minute of Marijuana Secondhand Smoke Exposure Substantially Impairs Vascular Endothelial Function.

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Wang, Xiaoyin; Derakhshandeh, Ronak; Liu, Jiangtao; Narayan, Shilpa; Nabavizadeh, Pooneh; Le, Stephenie; Danforth, Olivia M; Pinnamaneni, Kranthi; Rodriguez, Hilda J; Luu, Emmy; Sievers, Richard E; Schick, Suzaynn F; Glantz, Stanton A; Springer, Matthew L

2016-07-27

Despite public awareness that tobacco secondhand smoke (SHS) is harmful, many people still assume that marijuana SHS is benign. Debates about whether smoke-free laws should include marijuana are becoming increasingly widespread as marijuana is legalized and the cannabis industry grows. Lack of evidence for marijuana SHS causing acute cardiovascular harm is frequently mistaken for evidence that it is harmless, despite chemical and physical similarity between marijuana and tobacco smoke. We investigated whether brief exposure to marijuana SHS causes acute vascular endothelial dysfunction. We measured endothelial function as femoral artery flow-mediated dilation (FMD) in rats before and after exposure to marijuana SHS at levels similar to real-world tobacco SHS conditions. One minute of exposure to marijuana SHS impaired FMD to a comparable extent as impairment from equal concentrations of tobacco SHS, but recovery was considerably slower for marijuana. Exposure to marijuana SHS directly caused cannabinoid-independent vasodilation that subsided within 25 minutes, whereas FMD remained impaired for at least 90 minutes. Impairment occurred even when marijuana lacked cannabinoids and rolling paper was omitted. Endothelium-independent vasodilation by nitroglycerin administration was not impaired. FMD was not impaired by exposure to chamber air. One minute of exposure to marijuana SHS substantially impairs endothelial function in rats for at least 90 minutes, considerably longer than comparable impairment by tobacco SHS. Impairment of FMD does not require cannabinoids, nicotine, or rolling paper smoke. Our findings in rats suggest that SHS can exert similar adverse cardiovascular effects regardless of whether it is from tobacco or marijuana. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

A Gut Gone to Pot: A Case of Cannabinoid Hyperemesis Syndrome due to K2, a Synthetic Cannabinoid

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Anene Ukaigwe

2014-01-01

Full Text Available Cannabinoid Hyperemesis Syndrome (CHS was first described in 2004. Due to its novelty, CHS is often unrecognized by clinicians leading to expensive workup of these patients with cyclical symptoms. It may take up to 9 years to diagnose CHS. CHS is characterized by cyclical nausea and vomiting, abdominal pain, and an unusual compulsion to take hot showers in the presence of chronic use of cannabinoids. Cannabicyclohexanol is a synthetic cannabinoid, popularly known as K2 spice. It is a popular marijuana alternative among teenagers and young adults since it is readily available as herbal incense. Unlike marijuana, many users know that K2 is not detected in conventional urine drug screens, allowing those users to conceal their intake from typical detection methods. Serum or urine gas chromatography mass spectrophotometry is diagnostic, though not widely available. Thus, it is imperative for clinicians to recognize CHS, even with negative UDS, to provide cost-effective care. We present a 38-year-old man with a 10-year history of cannabis, and 1-year history of K2 abuse admitted with 1-week history of episodes of nausea, vomiting of clear fluids, and epigastric discomfort. Symptoms are relieved only by hot showers. Extensive laboratory, radiologic, and endoscopic evaluation was unrevealing. CHS was diagnosed, based on proposed criteria by Simonetti et al.

EFFECT OF CANNABINOIDS ON TESTICULAR ISCHEMIA-REPERFUSION INJURY IN RAT

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H. Sepehri

2006-11-01

Full Text Available Anandamide is an endogenous ligand for cannabinoid receptors and has endothelial protective effect against ischemic preconditioning. The purpose of this study was to investigate the effects of cannabinoids on reperfusion injury due to testicular torsion-detorsion (T/D. A total of 36 adult male Sprague-Dawley rats were divided into 6 groups. Testicular ischemia was achieved by twisting the right testes 720◦ counters clockwise for 1 hour and reperfusion was allowed for 4 hours after detorsion. In baseline (normal group, bilateral orchiectomies performed after anesthesia. Sham operated group was served as a control group. Torsion/detorsion group underwent 1 hour testicular torsion and 4 hours of detorsion. Anandamide (cannabinoid agonist group received pretreatment with intraperitoneally anandamide 30 min before torsion. AM251 (CB1 antagonist group, received intraperitoneally injection of AM251 45 min before torsion. Anandamid/AM251 (An/AM group received administrations of AM251 45 min before torsion and anandamide 30 min before torsion. The ipsilateral malondialdehyde (MDA level in T/D group were significantly higher versus control and base line groups. Ipsilateral MDA values in anandamid group were significantly lower than T/D and An/AM groups. There were also significant decreases in catalase activity in T/D group compared with control and base line groups. These values were significantly higher in cannabinoid group versus T/D and An/AM groups. Anandamide increased ipsilateral intratesticular antioxidative markers and decreased free radicals formation during reperfusion phase after unilateral testicular torsion, which was reflected in lesser testicular MDA level. Furthermore, the effects of anandamide were mediated via cannabinoid receptors, since AM251 could abolish these effects.

Stimulation of cannabinoid receptor 2 (CB2 suppresses microglial activation

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Fernandez Francisco

2005-12-01

Full Text Available Abstract Background Activated microglial cells have been implicated in a number of neurodegenerative disorders, including Alzheimer's disease (AD, multiple sclerosis (MS, and HIV dementia. It is well known that inflammatory mediators such as nitric oxide (NO, cytokines, and chemokines play an important role in microglial cell-associated neuron cell damage. Our previous studies have shown that CD40 signaling is involved in pathological activation of microglial cells. Many data reveal that cannabinoids mediate suppression of inflammation in vitro and in vivo through stimulation of cannabinoid receptor 2 (CB2. Methods In this study, we investigated the effects of a cannabinoid agonist on CD40 expression and function by cultured microglial cells activated by IFN-γ using RT-PCR, Western immunoblotting, flow cytometry, and anti-CB2 small interfering RNA (siRNA analyses. Furthermore, we examined if the stimulation of CB2 could modulate the capacity of microglial cells to phagocytise Aβ1–42 peptide using a phagocytosis assay. Results We found that the selective stimulation of cannabinoid receptor CB2 by JWH-015 suppressed IFN-γ-induced CD40 expression. In addition, this CB2 agonist markedly inhibited IFN-γ-induced phosphorylation of JAK/STAT1. Further, this stimulation was also able to suppress microglial TNF-α and nitric oxide production induced either by IFN-γ or Aβ peptide challenge in the presence of CD40 ligation. Finally, we showed that CB2 activation by JWH-015 markedly attenuated CD40-mediated inhibition of microglial phagocytosis of Aβ1–42 peptide. Taken together, these results provide mechanistic insight into beneficial effects provided by cannabinoid receptor CB2 modulation in neurodegenerative diseases, particularly AD.

Cannabinoids: New Promising Agents in the Treatment of Neurological Diseases

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Sabrina Giacoppo

2014-11-01

Full Text Available Nowadays, Cannabis sativa is considered the most extensively used narcotic. Nevertheless, this fame obscures its traditional employ in native medicine of South Africa, South America, Turkey, Egypt and in many regions of Asia as a therapeutic drug. In fact, the use of compounds containing Cannabis and their introduction in clinical practice is still controversial and strongly limited by unavoidable psychotropic effects. So, overcoming these adverse effects represents the main open question on the utilization of cannabinoids as new drugs for treatment of several pathologies. To date, therapeutic use of cannabinoid extracts is prescribed in patients with glaucoma, in the control of chemotherapy-related vomiting and nausea, for appetite stimulation in patients with anorexia-cachexia syndrome by HIV, and for the treatment of multiple sclerosis symptoms. Recently, researcher efforts are aimed to employ the therapeutic potentials of Cannabis sativa in the modulation of cannabinoid receptor activity within the central nervous system, particularly for the treatment of neurodegenerative diseases, as well as psychiatric and non-psychiatric disorders. This review evaluates the most recent available data on cannabinoids utilization in experimental and clinical studies, and highlights their beneficial effects in the prevention of the main neurological diseases and for the clinical treatment of symptoms with them correlated.

[Consumption of cannabis in adolescents].

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Phan, O; Obradovic, I; Har, A

2017-01-01

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

Endogenous cannabinoid release within prefrontal-limbic pathways affects memory consolidation of emotional training

NARCIS (Netherlands)

Morena, M.; Roozendaal, B.; Trezza, V.; Ratano, P.; Peloso, A.; Hauer, D.; Atsak, P.; Trabace, L.; Cuomo, V.; McGaugh, J.L.; Schelling, G.; Campolongo, P.

2014-01-01

Previous studies have provided extensive evidence that administration of cannabinoid drugs after training modulates the consolidation of memory for an aversive experience. The present experiments investigated whether the memory consolidation is regulated by endogenously released cannabinoids. The

Oral fluid/plasma cannabinoid ratios following controlled oral THC and smoked cannabis administration.

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Lee, Dayong; Vandrey, Ryan; Milman, Garry; Bergamaschi, Mateus; Mendu, Damodara R; Murray, Jeannie A; Barnes, Allan J; Huestis, Marilyn A

2013-09-01

Oral fluid (OF) is a valuable biological alternative for clinical and forensic drug testing. Evaluating OF to plasma (OF/P) cannabinoid ratios provides important pharmacokinetic data on the disposition of drug and factors influencing partition between matrices. Eleven chronic cannabis smokers resided on a closed research unit for 51 days. There were four 5-day sessions of 0, 30, 60, and 120 mg oral ∆(9)-tetrahydrocannabinol (THC)/day followed by a five-puff smoked cannabis challenge on Day 5. Each session was separated by 9 days ad libitum cannabis smoking. OF and plasma specimens were analyzed for THC and metabolites. During ad libitum smoking, OF/P THC ratios were high (median, 6.1; range, 0.2-348.5) within 1 h after last smoking, decreasing to 0.1-20.7 (median, 2.1) by 13.0-17.1 h. OF/P THC ratios also decreased during 5-days oral THC dosing, and after the smoked cannabis challenge, median OF/P THC ratios decreased from 1.4 to 5.5 (0.04-245.6) at 0.25 h to 0.12 to 0.17 (0.04-5.1) at 10.5 h post-smoking. In other studies, longer exposure to more potent cannabis smoke and oromucosal cannabis spray was associated with increased OF/P THC peak ratios. Median OF/P 11-nor-9-carboxy-THC (THCCOOH) ratios were 0.3-2.5 (range, 0.1-14.7) ng/μg, much more consistent in various dosing conditions over time. OF/P THC, but not THCCOOH, ratios were significantly influenced by oral cavity contamination after smoking or oromucosal spray of cannabinoid products, followed by time-dependent decreases. Establishing relationships between OF and plasma cannabinoid concentrations is essential for making inferences of impairment or other clinical outcomes from OF concentrations.

Temporal Effects of Child and Adolescent Exposure to Neighborhood Disadvantage on Black/White Disparities in Young Adult Obesity.

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Kravitz-Wirtz, Nicole

2016-05-01

This study investigates the effects of duration and timing of exposure to neighborhood disadvantage from birth through age 17 years on obesity incidence in early adulthood and black/white disparities therein. Individual- and household-level data from the 1970-2011 waves of the Panel Study of Income Dynamics are merged with census data on respondents' neighborhoods (n = 1,498). Marginal structural models with inverse probability of treatment and censoring weights are used to quantify the probability of being obese at least once between ages 18 and 30 years as a function of cumulative exposure to neighborhood disadvantage throughout childhood and adolescence or during each of three developmental stages therein. Longer term exposure to neighborhood disadvantage from ages 0-17 years is more common among blacks than among whites and is associated with significantly greater odds of being obese at least once in early adulthood. Exposure to neighborhood-level deprivation during adolescence (ages 10-17 years) appears more consequential for future (young adult) obesity than exposure that occurs earlier in childhood. The duration and timing of exposure to neighborhood disadvantage during childhood and adolescence are associated with obesity incidence in early adulthood for both blacks and whites. However, given inequalities in the likelihood and persistence of experiencing neighborhood disadvantage as children and youth, such adverse effects are likely to be more concentrated among black versus white young adults. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Predicting violent behavior: The role of violence exposure and future educational aspirations during adolescence.

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Stoddard, Sarah A; Heinze, Justin E; Choe, Daniel Ewon; Zimmerman, Marc A

2015-10-01

Few researchers have explored future educational aspirations as a promotive factor against exposure to community violence in relation to adolescents' violent behavior over time. The present study examined the direct and indirect effect of exposure to community violence prior to 9th grade on attitudes about violence and violent behavior in 12th grade, and violent behavior at age 22 via 9th grade future educational aspirations in a sample of urban African American youth (n = 681; 49% male). Multi-group SEM was used to test the moderating effect of gender. Exposure to violence was associated with lower future educational aspirations. For boys, attitudes about violence directly predicted violent behavior at age 22. For boys, future educational aspirations indirectly predicted less violent behavior at age 22. Implications of the findings and suggestions for future research are discussed. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Prenatal Alcohol Exposure Is Associated with Conduct Disorder in Adolescence: Findings from a Birth Cohort

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Larkby, Cynthia A.; Goldschmidt, Lidush; Hanusa, Barbara H.; Day, Nancy L.

2011-01-01

Objective: To evaluate the association between prenatal alcohol exposure and the rate of conduct disorder in exposed compared with unexposed adolescents. Method: Data for these analyses are from a longitudinal study of prenatal substance exposures. Women were interviewed at their fourth and seventh prenatal months, and with their children, at…

Violence Exposure and Depressive Symptoms among Adolescents and Young Adults Disconnected from School and Work

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Mendelson, Tamar; Turner, Alezandria K.; Tandon, S. Darius

2010-01-01

The psychological effects of exposure to different types of violence among urban adolescents and young adults are not yet well understood. This study investigated exposure to neighborhood violence, relationship violence, and forced sex among 677 urban African Americans aged 16-23 enrolled at an employment and training center. We assessed…

Physical Activity, a Critical Exposure Factor of Environmental Pollution in Children and Adolescents Health Risk Assessment

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Zhang, Su; Xia, Li; Yu, Yi; Hu, Shuangshuang; Sun, Jingyu; Zhou, Ping; Chen, Peijie

2018-01-01

It is an extremely urgent problem that physical fitness promotion must face not only the increasing air pollution but also the decline of physical activity level of children and adolescents worldwide at present, which is the major reason that forms an inactive lifestyle and does harm to adolescents’ health. Thus, it is necessary to focus on the exposure factor in environmental health risk assessment (EHRA) which conducts supervision of environmental pollution and survey of adolescents’ activity patterns according to the harmful characteristics of air pollutant and relationship between dose and response. Some countries, such as USA, Canada and Australia, regard both respiratory rate and physical activity pattern as main exposure factors for adolescents in both air pollution health risk assessment and exercise risk assessment to forecast a safe exposing condition of pollutant for adolescents while they are doing exercise outdoors. In addition, it suggests that the testing indexes and testing methods of these two exposure factors, such as investigating the time of daily physical activity, strength, and characteristic of frequency, help to set up the quantitative relationship between environmental pollution index and the time, strength, frequency of daily activities, and formulate children’s and adolescents’ activity instructions under different levels of environmental pollutions. As smog becomes increasingly serious at present, it is meaningful to take physical activity as a critical composition of exposure factor and establish physical activity guideline, so as to reduce the risk of air pollution, and promote physical health of children and adolescents effectively. PMID:29360730

Physical Activity, a Critical Exposure Factor of Environmental Pollution in Children and Adolescents Health Risk Assessment

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Jingmei Dong

2018-01-01

Full Text Available It is an extremely urgent problem that physical fitness promotion must face not only the increasing air pollution but also the decline of physical activity level of children and adolescents worldwide at present, which is the major reason that forms an inactive lifestyle and does harm to adolescents’ health. Thus, it is necessary to focus on the exposure factor in environmental health risk assessment (EHRA which conducts supervision of environmental pollution and survey of adolescents’ activity patterns according to the harmful characteristics of air pollutant and relationship between dose and response. Some countries, such as USA, Canada and Australia, regard both respiratory rate and physical activity pattern as main exposure factors for adolescents in both air pollution health risk assessment and exercise risk assessment to forecast a safe exposing condition of pollutant for adolescents while they are doing exercise outdoors. In addition, it suggests that the testing indexes and testing methods of these two exposure factors, such as investigating the time of daily physical activity, strength, and characteristic of frequency, help to set up the quantitative relationship between environmental pollution index and the time, strength, frequency of daily activities, and formulate children’s and adolescents’ activity instructions under different levels of environmental pollutions. As smog becomes increasingly serious at present, it is meaningful to take physical activity as a critical composition of exposure factor and establish physical activity guideline, so as to reduce the risk of air pollution, and promote physical health of children and adolescents effectively.

Can oral fluid cannabinoid testing monitor medication compliance and/or cannabis smoking during oral THC and oromucosal Sativex administration?

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Lee, Dayong; Karschner, Erin L; Milman, Garry; Barnes, Allan J; Goodwin, Robert S; Huestis, Marilyn A

2013-06-01

We characterize cannabinoid disposition in oral fluid (OF) after dronabinol, synthetic oral Δ(9)-tetrahydrocannabinol (THC), and Sativex, a cannabis-extract oromucosal spray, and evaluate whether smoked cannabis relapse or Sativex compliance can be identified with OF cannabinoid monitoring. 5 and 15 mg synthetic oral THC, low (5.4 mg THC, 5.0 mg cannabidiol (CBD)) and high (16.2 mg THC, 15.0 mg CBD) dose Sativex, and placebo were administered in random order (n=14). Oral fluid specimens were collected for 10.5 h after dosing and analyzed for THC, CBD, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH). After oral THC, OF THC concentrations decreased over time from baseline, reflecting residual THC excretion from previously self-administered smoked cannabis. CBD and CBN also were rarely detected. After Sativex, THC, CBD and CBN increased greatly, peaking at 0.25-1 h. Median CBD/THC and CBN/THC ratios were 0.82-1.34 and 0.04-0.06, respectively, reflecting cannabinoids' composition in Sativex. THCCOOH/THC ratios within 4.5 h post Sativex were ≤ 1.6 pg/ng, always lower than after oral THC and placebo. THCCOOH/THC ratios increased throughout each dosing session. Lack of measurable THC, CBD and CBN in OF following oral THC, and high OF CBD/THC ratios after Sativex distinguish oral and sublingual drug delivery routes from cannabis smoking. Low THCCOOH/THC ratios suggest recent Sativex and smoked cannabis exposure. These data indicate that OF cannabinoid monitoring can document compliance with Sativex pharmacotherapy, and identify relapse to smoked cannabis during oral THC medication but not Sativex treatment, unless samples were collected shortly after smoking. Published by Elsevier Ireland Ltd.

Exposure to alcohol advertising and adolescents' drinking beliefs: Role of message interpretation.

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Collins, Rebecca L; Martino, Steven C; Kovalchik, Stephanie A; D'Amico, Elizabeth J; Shadel, William G; Becker, Kirsten M; Tolpadi, Anagha

2017-09-01

Recent research revealed momentary associations between exposure to alcohol advertising and positive beliefs about alcohol among adolescents (Martino et al., 2016). We reanalyzed those data to determine whether associations depend on adolescents' appraisal of ads. Over a 10-month period in 2013, 589 youth, ages 11-14, in the Los Angeles, CA, area, participated in a 14-day ecological momentary assessment, logging all exposures to alcohol advertisements as they occurred and completing brief assessments of their skepticism toward, liking of, and identification with any people in each ad, as well as their alcohol-related beliefs at the moment. Participants also completed measures of their alcohol- related beliefs at random moments of nonexposure throughout each day. Mixed-effects regression models compared beliefs about alcohol at moments of exposure to alcohol advertising that was appraised in a particular way (e.g., with liking, without liking) to beliefs at random moments. When youth encountered ads they appraised positively, their beliefs about alcohol were significantly more positive than when they were queried at random moments. Beliefs in the presence of ads that were not positively appraised were generally similar to beliefs at random moments. Youth are active participants in the advertising process. How they respond to and process alcohol advertising strongly moderates the association between exposure and alcohol-related beliefs. More effort is needed to identify attributes of alcohol advertisements, and of youth, that determine how youth process alcohol ads. This information can be used to either limit exposure to problematic ads or make youth more resilient to such exposure. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Synthetic cannabinoids found in "spice" products alter body temperature and cardiovascular parameters in conscious male rats.

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Schindler, Charles W; Gramling, Benjamin R; Justinova, Zuzana; Thorndike, Eric B; Baumann, Michael H

2017-10-01

The misuse of synthetic cannabinoids is a persistent public health concern. Because these drugs target the same cannabinoid receptors as the active ingredient of marijuana, Δ 9 -tetrahydrocannabinol (THC), we compared the effects of synthetic cannabinoids and THC on body temperature and cardiovascular parameters. Biotelemetry transmitters for the measurement of body temperature or blood pressure (BP) were surgically implanted into separate groups of male rats. THC and the synthetic cannabinoids CP55,940, JWH-018, AM2201 and XLR-11 were injected s.c., and rats were placed into isolation cubicles for 3h. THC and synthetic cannabinoids produced dose-related decreases in body temperature that were most prominent in the final 2h of the session. The rank order of potency was CP55,940>AM2201=JWH-018>THC=XLR-11. The cannabinoid inverse agonist rimonabant antagonized the hypothermic effect of all compounds. Synthetic cannabinoids elevated BP in comparison to vehicle treatment during the first h of the session, while heart rate was unaffected. The rank order of potency for BP increases was similar to that seen for hypothermia. Hypertensive effects of CP55,940 and JWH-018 were not antagonized by rimonabant or the neutral antagonist AM4113. However, the BP responses to both drugs were antagonized by pretreatment with either the ganglionic blocker hexamethonium or the α 1 adrenergic antagonist prazosin. Our results show that synthetic cannabinoids produce hypothermia in rats by a mechanism involving cannabinoid receptors, while they increase BP by a mechanism independent of these sites. The hypertensive effect appears to involve central sympathetic outflow. Published by Elsevier B.V.

Exposure to violence and mental health of adolescents: South African Health and Well-being Study

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Rothon, Catherine; Das-Munshi, Jayati; Mathews, Cathy; Adams, Arlene; Clark, Charlotte; Lund, Crick

2017-01-01

Background Material and social environmental stressors affect mental health in adolescence. Protective factors such as social support from family and friends may help to buffer the effects of adversity. Aims The association of violence exposure and emotional disorders was examined in Cape Town adolescents. Method A total of 1034 Grade 8 high school students participated from seven government co-educational schools in Cape Town, South Africa. Exposure to violence in the past 12 months and post-traumatic stress disorder (PTSD) symptoms were measured by the Harvard Trauma Questionnaire, depressive and anxiety symptoms by the Short Moods and Feelings Questionnaire and the Self-Rating Anxiety Scale. Results Exposure to violence was associated with high scores on depressive (odds ratio (OR)=6.23, 95% CI 4.2–9.2), anxiety (OR=5.40, 95% CI 2.4–12.4) and PTSD symptoms (OR=8.93, 95% CI 2.9–27.2) and increased risk of self-harm (OR=5.72, 95% CI 1.2–25.9) adjusting for gender and social support. Conclusions We found that high exposure to violence was associated with high levels of emotional disorders in adolescents that was not buffered by social support. There is an urgent need for interventions to reduce exposure to violence in young people in this setting. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:29093828

Glycine receptors in CNS neurons as a target for nonretrograde action of cannabinoids

NARCIS (Netherlands)

Lozovaya, N.; Yatsenko, N.; Beketov, A.; Tsintsadze, T.; Burnashev, N.

2005-01-01

At many central synapses, endocannabinoids released by postsynaptic cells act retrogradely on presynaptic G-protein-coupled cannabinoid receptors to inhibit neurotransmitter release. Here, we demonstrate that cannabinoids may directly affect the functioning of inhibitory glycine receptor (GlyR)

Early Adolescent Boys' Exposure to Internet Pornography: Relationships to Pubertal Timing, Sensation Seeking, and Academic Performance

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Beyens, Ine; Vandenbosch, Laura; Eggermont, Steven

2015-01-01

Research has demonstrated that adolescents regularly use Internet pornography. This two-wave panel study aimed to test an integrative model in early adolescent boys (M[subscript age] = 14.10; N = 325) that (a) explains their exposure to Internet pornography by looking at relationships with pubertal timing and sensation seeking, and (b) explores…

Adolescent opiate exposure in the female rat induces subtle alterations in maternal care and transgenerational effects on play behavior.

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Nicole L. Johnson

2011-06-01

Full Text Available The non-medical use of prescription opiates, such as Vicodin® and MSContin®, has increased dramatically over the past decade. Of particular concern is the rising popularity of these drugs in adolescent female populations. Use during this critical developmental period could have significant long-term consequences for both the female user as well as potential effects on her future offspring. To address this issue, we have begun modeling adolescent opiate exposure in female rats and have observed significant transgenerational effects despite the fact that all drugs are withdrawn several weeks prior to pregnancy. The purpose of the current set of studies was to determine whether adolescent morphine exposure modifies postpartum care. In addition, we also examined juvenile play behavior in both male and female offspring. The choice of the social play paradigm was based on previous findings demonstrating effects of both postpartum care and opioid activity on play behavior. The findings revealed subtle modifications in the maternal behavior of adolescent morphine-exposed females, primarily related to the amount of time females’ spend nursing and in non-nursing contact with their young. In addition, male offspring of adolescent morphine-exposed mothers (MOR-F1 demonstrate decreased rough and tumble play behaviors, with no significant differences in general social behaviors (i.e. social grooming and social exploration. Moreover, there was a tendency toward increased rough and tumble play in MOR-F1 females, demonstrating the sex-specific nature of these effects. Given the importance of the postpartum environment on neurodevelopment, it is possible that modifications in maternal-offspring interactions, related to a history of adolescent opiate exposure, plays a role in the observed transgenerational effects. Overall, these studies indicate that the long-term consequences of adolescent opiate exposure can impact both the female and her future offspring.

Novelty-induced emotional arousal modulates cannabinoid effects on recognition memory and adrenocortical activity

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Campolongo, P.; Morena, M.; Scaccianoce, S.; Trezza, V.; Chiarotti, F.; Schelling, G.; Cuomo, V.; Roozendaal, B.

2013-01-01

Although it is well established that cannabinoid drugs can influence cognitive performance, the findings-describing both enhancing and impairing effects-have been ambiguous. Here, we investigated the effects of posttraining systemic administration of the synthetic cannabinoid agonist WIN55,212-2

Changes in the Adult GluN2B Associated Proteome following Adolescent Intermittent Ethanol Exposure.

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H Scott Swartzwelder

Full Text Available Adolescent alcohol use is the strongest predictor for alcohol use disorders. In rodents, adolescents have distinct responses to acute ethanol, and prolonged alcohol exposure during adolescence can maintain these phenotypes into adulthood. One brain region that is particularly sensitive to the effects of both acute and chronic ethanol exposure is the hippocampus. Adolescent intermittent ethanol exposure (AIE produces long lasting changes in hippocampal synaptic plasticity and dendritic morphology, as well as in the susceptibility to acute ethanol-induced spatial memory impairment. Given the pattern of changes in hippocampal structure and function, one potential target for these effects is the ethanol sensitive GluN2B subunit of the NMDA receptor, which is known to be involved in synaptic plasticity and dendritic morphology. Thus we sought to determine if there were persistent changes in hippocampal GluN2B signaling cascades following AIE. We employed a previously validated GluN2B-targeted proteomic strategy that was used to identify novel signaling mechanisms altered by chronic ethanol exposure in the adult hippocampus. We collected adult hippocampal tissue (P70 from rats that had been given 2 weeks of AIE from P30-45. Tissue extracts were fractionated into synaptic and non-synaptic pools, immuno-precipitated for GluN2B, and then analyzed using proteomic methods. We detected a large number of proteins associated with GluN2B. AIE produced significant changes in the association of many proteins with GluN2B in both synaptic and non-synaptic fractions. Intriguingly the number of proteins changed in the non-synaptic fraction was double that found in the synaptic fraction. Some of these proteins include those involved in glutamate signaling cytoskeleton rearrangement, calcium signaling, and plasticity. Disruptions in these pathways may contribute to the persistent cellular and behavioral changes found in the adult hippocampus following AIE. Further

Substance exposure in utero and developmental consequences in adolescence

DEFF Research Database (Denmark)

Irner, Tina Birk

2012-01-01

Background: The impacts of maternal substance use have been observed in both research and clinical experience. Several studies have shown that preschool children are at heightened risk of developing various cognitive, behavioral, and socioemotional difficulties. Most knowledge has been generated...... brain-imaging studies have provided important evidence of serious effects of other substance exposure on the developing brain and recent follow-up studies have found an association with deficits in language, attention, areas of cognitive performance and delinquent behavior in adolescence....

Exposure to Violence, Posttraumatic Stress Symptoms, and Borderline Personality Pathology Among Adolescents in Residential Psychiatric Treatment: The Influence of Emotion Dysregulation.

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Buckholdt, Kelly E; Weiss, Nicole H; Young, John; Gratz, Kim L

2015-12-01

Exposure to violence during adolescence is a highly prevalent phenomenon associated with a range of deleterious outcomes. Theoretical literature suggests that emotion dysregulation is one consequence of exposure to violence associated with the manifestation of posttraumatic stress symptoms (PTSS) and borderline personality (BP) pathology. Thus, the goal of the present study was to examine the mediating role of emotion dysregulation in the relation between exposure to violence and both PTSS and BP pathology in a sample of 144 adolescents (age 10- to 17-years; 51% male; 55% African American) admitted to a psychiatric residential treatment center. Exposure to violence was associated with greater emotion dysregulation, which, in turn, was associated with greater PTSS and BP pathology. Furthermore, emotion dysregulation mediated the associations between exposure to violence and both PTSS and BP pathology. Findings suggest the importance of assessing and treating emotion dysregulation among violence-exposed adolescents in psychiatric residential treatment.

Are cannabinoids effective in multiple sclerosis?

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Rodrigo Meza

2017-03-01

Full Text Available Resumen En el último tiempo, se han descrito diversos beneficios con el uso de cannabinoides en diferentes situaciones clínicas. Dentro de ellas se ha planteado un posible efecto en el control de la esclerosis múltiple, pero la real utilidad clínica es tema de debate. Para responder a esta pregunta utilizamos la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples bases de datos. Identificamos 25 revisiones sistemáticas que en conjunto incluyen 35 estudios que responden la pregunta de interés, entre ellos 26 estudios aleatorizados. Extrajimos los datos, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Concluimos que el uso de cannabinoides en esclerosis múltiple no reduce la espasticidad ni el dolor, y probablemente se asocia a efectos adversos frecuentes.

Efecto neuroprotector de los cannabinoides en las enfermedades neurodegenerativas

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Carlos Suero-García

2015-01-01

Full Text Available Objetivos: Se analiza la situación actual de las investigaciones relacionadas con las sustancias cannabinoides, así como su interacción con el organismo, clasificación, efectos terapéuticos y su uso en las enfermedades neurodegenerativas. Métodos: Se realiza una exhaustiva revisión bibliográfica relacionada con las sustancias cannabinoides y sus derivados sintéticos, haciendo especial hincapié en la forma de interactuar con el organismo y los efectos que provocan dichas interacciones. Concretamente, se estudiarán sus efectos neuroantiinflamatorio y analgésico lo que conlleva al efecto neuroprotector en enfermedades neurodegenerativas tales como Alzheimer, Parkinson, Huntington, esclerosis múltiple y esclerosis lateral amiotrófica. Resultados: Desde hace miles de años la planta Cannabis Sativa ha sido utilizada por muchas culturas con distintos fines, de ocio, textiles, analgésicos, pero no es hasta finales del siglo XX cuando se empieza a incentivar los estudios científicos relacionados con ésta. La planta posee una mezcla de unos 400 componentes, de los cuales 60 pertenecen al grupo de los cannabinoides siendo los principales el cannabinol, cannabidiol y tetrahidrocannabinol. Con el descubrimiento de las sustancias cannabinoides, sus derivados, y los receptores que interactúan, se amplían las posibilidades terapéuticas teniendo un especial interés el efecto neuroprotector que estas sustancias contienen. Conclusiones. Se ha demostrado el gran potencial de los cannabinoides como sustancias terapéuticas más allá de su uso analgésico o antiemético, esto es, en enfermedades neurodegenerativas en las que pueden no solo disminuir los síntomas, sino frenar el proceso de la enfermedad. Otra posible aplicación puede ser en el campo oncológico, siendo particularmente intensa la actividad investigadora realizada en los últimos 15 años.

The role of cannabinoids in prostate cancer: Basic science perspective and potential clinical applications

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Juan A Ramos

2012-01-01

Full Text Available Prostate cancer is a global public health problem, and it is the most common cancer in American men and the second cause for cancer-related death. Experimental evidence shows that prostate tissue possesses cannabinoid receptors and their stimulation results in anti-androgenic effects. To review currently relevant findings related to effects of cannabinoid receptors in prostate cancer. PubMed search utilizing the terms "cannabis," "cannabinoids," "prostate cancer," and "cancer pain management," giving preference to most recent publications was done. Articles identified were screened for their relevance to the field of prostate cancer and interest to both urologist and pain specialists. Prostate cancer cells possess increased expression of both cannabinoid 1 and 2 receptors, and stimulation of these results in decrease in cell viability, increased apoptosis, and decreased androgen receptor expression and prostate-specific antigen excretion. It would be of interest to conduct clinical studies utilizing cannabinoids for patients with metastatic prostate cancer, taking advantage not only of its beneficial effects on prostate cancer but also of their analgesic properties for bone metastatic cancer pain.

Tobacco promotion 'below-the-line': exposure among adolescents and young adults in NSW, Australia.

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Perez, Donna A; Grunseit, Anne C; Rissel, Chris; Kite, James; Cotter, Trish; Dunlop, Sally; Bauman, Adrian

2012-06-12

Exposure to tobacco advertising and promotion increases the likelihood of smoking amongst young people. While there is a universal ban on traditional or ‘above-the-line’ advertising in Australia, the types and extent of exposure of young people to ‘below-the-line’ tobacco advertising and promotion is largely unknown. In this study we aim to identify levels of exposure of New South Wales (NSW) adolescents and young adults to tobacco promotion at the point-of-sale (PoS), on the internet, in entertainment media and at venues such as events or festivals and pubs, clubs, nightclubs, or bars; and to identify those most at risk of exposure. A telephone survey of 1000 NSW adolescents and young adults aged 12 to 24 years was conducted. Self-reported exposure to tobacco promotions or advertising in the last month were measured in four areas: (1) promotions or advertising at (a) events or festivals and (b) pubs, clubs, nightclubs or bars, (2) on the internet, (3) people smoking cigarettes in (a) movies, (b) TV shows, (c) video games and (d) on the internet, and (4) displays of cigarette packs for sale at (a) large supermarkets, (b) grocery stores or small supermarkets, (c) convenience stores, and (d) service or petrol stations. Smoking status and susceptibility to smoking was also assessed. A substantial proportion of the young people surveyed reported seeing tobacco promotion sometimes or often in the last month over most of the channels studied.The highest levels of exposure were at the PoS (approx. two-thirds) and to people smoking cigarettes in movies(77%). Lower levels of exposure to tobacco promotions and imagery were reported on the internet (20%); at events or festivals (22.5%); in pubs, clubs, nightclubs or bars (31%); and in video games (23%). However, the odds of exposure through video games increased by 8% for every additional hour spent on the internet per day. This study shows that adolescents and young adults in NSW are exposed to tobacco advertising or

The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews.

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Nielsen, Suzanne; Germanos, Rada; Weier, Megan; Pollard, John; Degenhardt, Louisa; Hall, Wayne; Buckley, Nicholas; Farrell, Michael

2018-02-13

Pharmaceutical cannabinoids such as nabiximols, nabilone and dronabinol, and plant-based cannabinoids have been investigated for their therapeutic potential in treating multiple sclerosis (MS) symptoms. This review of reviews aimed to synthesise findings from high quality systematic reviews that examined the safety and effectiveness of cannabinoids in multiple sclerosis. We examined the outcomes of disability and disability progression, pain, spasticity, bladder function, tremor/ataxia, quality of life and adverse effects. We identified 11 eligible systematic reviews providing data from 32 studies, including 10 moderate to high quality RCTs. Five reviews concluded that there was sufficient evidence that cannabinoids may be effective for symptoms of pain and/or spasticity in MS. Few reviews reported conclusions for other symptoms. Recent high quality reviews find cannabinoids may have modest effects in MS for pain or spasticity. Future research should include studies with non-cannabinoid comparators; this is an important gap in the evidence.

Social network media exposure and adolescent eating pathology in Fiji

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Becker, Anne E.; Fay, Kristen E.; Agnew-Blais, Jessica; Khan, A. Nisha; Striegel-Moore, Ruth H.; Gilman, Stephen E.

2011-01-01

Background Mass media exposure has been associated with an increased risk of eating pathology. It is unknown whether indirect media exposure – such as the proliferation of media exposure in an individual’s social network – is also associated with eating disorders. Aims To test hypotheses that both individual (direct) and social network (indirect) mass media exposures were associated with eating pathology in Fiji. Method We assessed several kinds of mass media exposure, media influence, cultural orientation and eating pathology by self-report among adolescent female ethnic Fijians (n = 523). We fitted a series of multiple regression models of eating pathology, assessed by the Eating Disorder Examination Questionnaire (EDE–Q), in which mass media exposures, sociodemographic characteristics and body mass index were entered as predictors. Results Both direct and indirect mass media exposures were associated with eating pathology in unadjusted analyses, whereas in adjusted analyses only social network media exposure was associated with eating pathology. This result was similar when eating pathology was operationalised as either a continuous or a categorical dependent variable (e.g. odds ratio OR = 1.60, 95% CI 1.15–2.23 relating social network media exposure to upper-quartile EDE–Q scores). Subsequent analyses pointed to individual media influence as an important explanatory variable in this association. Conclusions Social network media exposure was associated with eating pathology in this Fijian study sample, independent of direct media exposure and other cultural exposures. Findings warrant further investigation of its health impact in other populations. PMID:21200076

Cannabinoids Modulate Neuronal Activity and Cancer by CB1 and CB2 Receptor-Independent Mechanisms

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Ken Soderstrom

2017-10-01

Full Text Available Cannabinoids include the active constituents of Cannabis or are molecules that mimic the structure and/or function of these Cannabis-derived molecules. Cannabinoids produce many of their cellular and organ system effects by interacting with the well-characterized CB1 and CB2 receptors. However, it has become clear that not all effects of cannabinoid drugs are attributable to their interaction with CB1 and CB2 receptors. Evidence now demonstrates that cannabinoid agents produce effects by modulating activity of the entire array of cellular macromolecules targeted by other drug classes, including: other receptor types; ion channels; transporters; enzymes, and protein- and non-protein cellular structures. This review summarizes evidence for these interactions in the CNS and in cancer, and is organized according to the cellular targets involved. The CNS represents a well-studied area and cancer is emerging in terms of understanding mechanisms by which cannabinoids modulate their activity. Considering the CNS and cancer together allow identification of non-cannabinoid receptor targets that are shared and divergent in both systems. This comparative approach allows the identified targets to be compared and contrasted, suggesting potential new areas of investigation. It also provides insight into the diverse sources of efficacy employed by this interesting class of drugs. Obtaining a comprehensive understanding of the diverse mechanisms of cannabinoid action may lead to the design and development of therapeutic agents with greater efficacy and specificity for their cellular targets.

Association of cadmium and arsenic exposure with salivary telomere length in adolescents in Terai, Nepal

Energy Technology Data Exchange (ETDEWEB)

Fillman, Toki, E-mail: tokif@humeco.m.u-tokyo.ac.jp [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-0033 (Japan); Shimizu-Furusawa, Hana, E-mail: hana-shimizu@umin.ac.jp [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-0033 (Japan); Ng, Chris Fook Sheng, E-mail: chrisng-tky@umin.ac.jp [Department of Pediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki (Japan); Parajuli, Rajendra Prasad, E-mail: rp.parajuli@mcgill.ca [Basu Laboratory, CINE Building, Macdonald Campus, Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Quebec (Canada); Watanabe, Chiho, E-mail: chiho@humeco.m.u-tokyo.ac.jp [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-0033 (Japan)

2016-08-15

Background: Cadmium and arsenic are ubiquitous metals commonly found in the environment which can harm human health. A growing body of research shows telomere length as a potential biomarker of future disease risk. Few studies have examined the effects of metals on telomere length and none have focused on adolescents. Objectives: In this study, the impact of cadmium and arsenic on salivary telomere length was studied in adolescents in Terai, Nepal. Methods: Adolescents aged 12–16 years old (n=351)were recruited where questionnaire interviews and both saliva and urine collection took place. Telomere length was determined by quantitative polymerase chain reaction using DNA extracted from saliva. Urinary cadmium and arsenic concentration were measured by inductively coupled plasma mass spectrometry. Multivariable linear regression was used to examine associations between urinary metals and salivary telomere length. Results: The geometric means and standard deviations of cadmium and arsenic were 0.33±0.33 μg/g creatinine and 196.0±301.1 μg/g creatinine, respectively. Urinary cadmium concentration was negatively associated with salivary telomere length after adjustment for confounders (β=−0.24, 95% CI −0.42,−0.07). Arsenic showed positive associations with telomere length but did not reach statistical significance. Conclusions: This is the first study to demonstrate that cadmium may shorten adolescent telomeres, even at exposure levels that may be considered low. These results agree with prior experimental and adult epidemiological studies, and also help identify the mechanism of DNA damage by cadmium. This study expanded current evidence on the harmful effects of cadmium exposure on telomere length even to adolescents. - Highlights: • This is the first study examining metal exposure on telomere length in adolescents. • Urinary cadmium levels were similar to non-industrially polluted levels in Asia. • Urinary arsenic levels were as high as groundwater

Association of cadmium and arsenic exposure with salivary telomere length in adolescents in Terai, Nepal

International Nuclear Information System (INIS)

Fillman, Toki; Shimizu-Furusawa, Hana; Ng, Chris Fook Sheng; Parajuli, Rajendra Prasad; Watanabe, Chiho

2016-01-01

Background: Cadmium and arsenic are ubiquitous metals commonly found in the environment which can harm human health. A growing body of research shows telomere length as a potential biomarker of future disease risk. Few studies have examined the effects of metals on telomere length and none have focused on adolescents. Objectives: In this study, the impact of cadmium and arsenic on salivary telomere length was studied in adolescents in Terai, Nepal. Methods: Adolescents aged 12–16 years old (n=351)were recruited where questionnaire interviews and both saliva and urine collection took place. Telomere length was determined by quantitative polymerase chain reaction using DNA extracted from saliva. Urinary cadmium and arsenic concentration were measured by inductively coupled plasma mass spectrometry. Multivariable linear regression was used to examine associations between urinary metals and salivary telomere length. Results: The geometric means and standard deviations of cadmium and arsenic were 0.33±0.33 μg/g creatinine and 196.0±301.1 μg/g creatinine, respectively. Urinary cadmium concentration was negatively associated with salivary telomere length after adjustment for confounders (β=−0.24, 95% CI −0.42,−0.07). Arsenic showed positive associations with telomere length but did not reach statistical significance. Conclusions: This is the first study to demonstrate that cadmium may shorten adolescent telomeres, even at exposure levels that may be considered low. These results agree with prior experimental and adult epidemiological studies, and also help identify the mechanism of DNA damage by cadmium. This study expanded current evidence on the harmful effects of cadmium exposure on telomere length even to adolescents. - Highlights: • This is the first study examining metal exposure on telomere length in adolescents. • Urinary cadmium levels were similar to non-industrially polluted levels in Asia. • Urinary arsenic levels were as high as groundwater

Enhancing the activity of cannabidiol and other cannabinoids in vitro through modifications to drug combinations and treatment schedules.

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Scott, Katherine Ann; Shah, Sini; Dalgleish, Angus George; Liu, Wai Man

2013-10-01

Cannabinoids are the bioactive components of the Cannabis plant that display a diverse range of therapeutic qualities. We explored the activity of six cannabinoids, used both alone and in combination in leukaemic cells. Cannabinoids were cytostatic and caused a simultaneous arrest at all phases of the cell cycle. Re-culturing pre-treated cells in drug-free medium resulted in dramatic reductions in cell viability. Furthermore, combining cannabinoids was not antagonistic. We suggest that the activities of some cannabinoids are influenced by treatment schedules; therefore, it is important to carefully select the most appropriate strategy in order to maximise their efficacy.

From adolescent to elder rats: Motivation for palatable food and cannabinoids receptors.

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Amancio-Belmont, Octavio; Romano-López, Antonio; Ruiz-Contreras, Alejandra Evelin; Méndez-Díaz, Mónica; Prospéro-García, Oscar

2017-09-01

To analyze motivation, food self-administration and decision-making were evaluated in adolescent, adult, and aged rats. Subjects were trained to press a lever (fixed ratio, FR1 and FR5) in an operant chamber, to obtain chocolate flavor pellets. They assessed the progressive ratio (PR), extinction, and reinstatement of the behavior. To estimate decision-making for food, rats were trained in the conditioned place preference (CPP) paradigm: (a) associating one compartment with lab chow (LCh) one day and the other compartment with rice krisspies (RK), the next day. (b) Training similar to (a) but on the day RK was the reinforcer, it was delivered with a progressive delay. In addition, CB1 and CB2 receptor expression in the nucleus accumbens (NAcc) and prefrontal cortex (PFC) was estimated by means of Western blot. Adolescent rats consumed higher amounts of RK/body weight than adult and aged rats during FR1, FR5, and PR. Extinction was more prolonged for adolescent rats than for adult and aged rats. First CPP condition, all three groups of rats preferred the RK-associated compartment. Second CPP condition, adolescent rats developed equal preference to both compartments, while adult and aged rats preferred the RK-associated compartment. Rats per group ate a similar amount of either reinforcer. Adolescent rats exhibited low expression of CB1R in the NAcc and low expression of both CB1R and CB2R in the PFC compared with adult and aged rats. Adolescent rats display higher motivation for palatable food and an indiscriminate seeking behavior suggesting involvement of both homeostatic and hedonic systems in their decision-making processes. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 917-927, 2017. © 2016 Wiley Periodicals, Inc.

Socioeconomic status and adolescent e-cigarette use: The mediating role of e-cigarette advertisement exposure.

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Simon, Patricia; Camenga, Deepa R; Morean, Meghan E; Kong, Grace; Bold, Krysten W; Cavallo, Dana A; Krishnan-Sarin, Suchitra

2018-07-01

Among adolescents, low socioeconomic status (SES) is associated with greater exposure to tobacco cigarette advertising and cigarette use. However, associations among SES, e-cigarette advertising and e-cigarette use are not well understood. This study examined exposure to e-cigarette advertisements as a mediator of the relationship between SES and adolescent e-cigarette use. Adolescents (N = 3473; 51% Female) from 8 high schools in Connecticut completed an anonymous survey in Spring 2015. Mediation analysis was used to examine whether the total number of sources of recent e-cigarette advertising exposure (e.g., TV, radio, billboards, magazines, local stores [gas stations, convenience stores], vape shops, mall kiosks, tobacco shops, social media) mediated the association between SES (measured by the Family Affluence Scale) and past-month frequency of e-cigarette use. We clustered for school and controlled for other tobacco product use, age, sex, race/ethnicity and perceived social norms for e-cigarette use in the model. Our sample recently had seen advertisements via 2.1 (SD = 2.8) advertising channels. Mediation was supported (indirect effect: β = 0.01, SE = 0.00, 95% CI [0.001, 0.010], p = 0.02), such that higher SES was associated with greater recent advertising exposure, which, in turn, was associated with greater frequency of e-cigarette use. Our study suggests that regulations to reduce youth exposure to e-cigarette advertisement may be especially relevant to higher SES youth. Future research should examine these associations longitudinally and evaluate which types of advertisements target different SES groups. Copyright © 2018 Elsevier Inc. All rights reserved.

The association between socioeconomic status and exposure to mobile telecommunication networks in children and adolescents.

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Thomas, Silke; Heinrich, Sabine; Kühnlein, Anja; Radon, Katja

2010-01-01

A potential association between socioeconomic status (SES) and self-reported use of mobile phones has been investigated in a few studies. If measured exposure to mobile phone networks differs by SES in children, it has not yet been studied. Interview data of 1,481 children and 1,505 adolescents on participants' mobile phone use, socio-demographic characteristics and potential confounders were taken from the German MobilEe-study. Sociodemographic data was used to stratify participants into three "status groups" (low, middle, high). Using a personal dosimeter, we obtained an exposure profile over 24 h for each of the participants. Exposure levels during waking hours were expressed as mean percentage of the reference level. Children with a low SES were more likely to own a mobile phone (OR 2.1; 95% CI: 1.1-3.9) and also reported to use their mobile phone longer per day (OR 2.4; 95% CI: 1.1-5.4) than children with a high SES. For adolescents, self-reported duration of mobile phone use per day was also higher with a low SES (OR: 3.4; 95% CI: 1.4-8.4) compared with a high SES. No association between SES and measured exposure to mobile telecommunication networks was seen for children or adolescents. Mobile phone use may differ between status groups with higher use among disadvantaged groups. However, this does not result in higher overall exposure to mobile telecommunication networks. Whether short duration of own mobile phone use or the small numbers of participants with a low SES are causal, have to be investigated in further studies. (c) 2009 Wiley-Liss, Inc.

Long-term health consequences of violence exposure in adolescence: a 26–year prospective study

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Olofsson Niclas

2012-06-01

Full Text Available Abstract Background Violence victimization represents a serious risk factor for health related symptoms, for both men and women. The aim of this study was to evaluate the long-term effects of violence exposure in late adolescence and early adulthood on adult health, physical as well as mental, using a long-term prospective population-based study, with a follow up of 9, 19, and 26 years. Methods The primary data source is a longitudinal panel from one of the longest running social science surveys in the world, the Swedish Level-of-Living surveys (LNU. We analyzed three cohorts, individuals aged 15–19 in 1974 and 1981, and individuals aged 18–19 in 1991 which were followed up 2000. Structured interviews on childhood, family relationships, life-events, living conditions, health history and status, working conditions, behavioral, psychosocial, and demographic variables were repeatedly used in all cohorts. Results Multivariate models of violence exposures in adolescence in the 1974–91 cohorts as predictors of adult health in 2000 are reported for both men and women. Women exposed to violence had raised odds ratios for ill health, measured as heavy illness burden, and poor self rated health, after controlling for possible confounders. No such associations were found for men. Conclusions This study’s findings provide additional empirical support for the importance of policies and practices to identify and prevent violence exposure in adolescence and young adulthood and to supply treatments for adolescence exposed to violence and above all the young women.

Exposure to mobile telecommunication networks assessed using personal dosimetry and well-being in children and adolescents: the German MobilEe-study.

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Thomas, Silke; Kühnlein, Anja; Heinrich, Sabine; Praml, Georg; von Kries, Rüdiger; Radon, Katja

2008-11-04

Despite the increase of mobile phone use in the last decade and the growing concern whether mobile telecommunication networks adversely affect health and well-being, only few studies have been published that focussed on children and adolescents. Especially children and adolescents are important in the discussion of adverse health effects because of their possibly higher vulnerability to radio frequency electromagnetic fields. We investigated a possible association between exposure to mobile telecommunication networks and well-being in children and adolescents using personal dosimetry. A population-based sample of 1.498 children and 1.524 adolescents was assembled for the study (response 52%). Participants were randomly selected from the population registries of four Bavarian (South of Germany) cities and towns with different population sizes. During a Computer Assisted Personal Interview data on participants' well-being, socio-demographic characteristics and potential confounder were collected. Acute symptoms were assessed three times during the study day (morning, noon, evening).Using a dosimeter (ESM-140 Maschek Electronics), we obtained an exposure profile over 24 hours for three mobile phone frequency ranges (measurement interval 1 second, limit of determination 0.05 V/m) for each of the participants. Exposure levels over waking hours were summed up and expressed as mean percentage of the ICNIRP (International Commission on Non-Ionizing Radiation Protection) reference level. In comparison to non-participants, parents and adolescents with a higher level of education who possessed a mobile phone and were interested in the topic of possible adverse health effects caused by mobile telecommunication network frequencies were more willing to participate in the study. The median exposure to radio frequency electromagnetic fields of children and adolescents was 0.18% and 0.19% of the ICNIRP reference level respectively. In comparison to previous studies this is one of

Exposure to mobile telecommunication networks assessed using personal dosimetry and well-being in children and adolescents: the German MobilEe-study

Directory of Open Access Journals (Sweden)

von Kries Rüdiger

2008-11-01

Full Text Available Abstract Background Despite the increase of mobile phone use in the last decade and the growing concern whether mobile telecommunication networks adversely affect health and well-being, only few studies have been published that focussed on children and adolescents. Especially children and adolescents are important in the discussion of adverse health effects because of their possibly higher vulnerability to radio frequency electromagnetic fields. Methods We investigated a possible association between exposure to mobile telecommunication networks and well-being in children and adolescents using personal dosimetry. A population-based sample of 1.498 children and 1.524 adolescents was assembled for the study (response 52%. Participants were randomly selected from the population registries of four Bavarian (South of Germany cities and towns with different population sizes. During a Computer Assisted Personal Interview data on participants' well-being, socio-demographic characteristics and potential confounder were collected. Acute symptoms were assessed three times during the study day (morning, noon, evening. Using a dosimeter (ESM-140 Maschek Electronics, we obtained an exposure profile over 24 hours for three mobile phone frequency ranges (measurement interval 1 second, limit of determination 0.05 V/m for each of the participants. Exposure levels over waking hours were summed up and expressed as mean percentage of the ICNIRP (International Commission on Non-Ionizing Radiation Protection reference level. Results In comparison to non-participants, parents and adolescents with a higher level of education who possessed a mobile phone and were interested in the topic of possible adverse health effects caused by mobile telecommunication network frequencies were more willing to participate in the study. The median exposure to radio frequency electromagnetic fields of children and adolescents was 0.18% and 0.19% of the ICNIRP reference level respectively

Depressive symptoms, exposure to aggression and delinquency proneness in adolescence: Impact of two decades of war and political violence on adolescent mental health

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Pejović-Milovančević Milica

2013-01-01

Full Text Available Traumatic experiences in Serbia in the last two decades have caused significant psychological consequences in children and adolescents. The aim of this study was to investigate the relationship between depressive symptoms, exposure to aggression and delinquency proneness among high school and elementary school students in Belgrade, Serbia. The participants were 899 students (51.8% were female with no prior treatment for psychological problems, with a mean age of 16.70±1.95. All used instruments were taken from the modified Social and Health Assessment (SAHA. Our findings show that delinquent behavior or exposure to delinquency was significantly related to depressive symptoms. The strongest predictors of depression were variables concerning legal consequences, affiliation with delinquent peers, victimization by community violence and peer victimization. This study confirmed a strong correlation between depression and exposure to violence. Identifying adolescents with depressive symptoms is important for prevention of serious mental health consequences.

Psychological Symptoms Linking Exposure to Community Violence and Academic Functioning in African American Adolescents

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Busby, Danielle R.; Lambert, Sharon F.; Ialongo, Nicholas S.

2013-01-01

African American adolescents are exposed disproportionately to community violence, increasing their risk for emotional and behavioral symptoms that can detract from learning and undermine academic outcomes. The present study examined whether aggressive behavior and depressive and anxious symptoms mediated the association between exposure to community violence and academic functioning, and if the indirect effects of community violence on academic functioning differed for boys and girls, in a community sample of urban African American adolescents (N = 491; 46.6% female). Structural equation modeling was used to examine the indirect effect of exposure to community violence in grade 6 on grade 8 academic functioning. Results revealed that aggression in grade 7 mediated the association between grade 6 exposure to community violence and grade 8 academic functioning. There were no indirect effects through depressive and anxious symptoms, and gender did not moderate the indirect effect. Findings highlight the importance of targeting aggressive behavior for youth exposed to community violence to not only improve their behavioral adjustment but also their academic functioning. Implications for future research are discussed. PMID:23277294

Cannabinoid hyperemesis syndrome with extreme hydrophilia

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Enuh HA

2013-08-01

Full Text Available Hilary A Enuh,1 Julia Chin,1 Jay Nfonoyim21Department of Medicine, 2Critical Care Unit, Richmond University Medical Center, Staten Island, NY, USAAbstract: Marijuana is the most widely used recreational drug in the US. Hyperemetic hydrophilic syndrome is a previously described but infrequently recognized condition of cannabinoid abuse with hyperemesis and obsessive hot showering. We present a 47-year-old male known marijuana addict with intractable abdominal pain who could not wait for physical examination, meal, or medication, because of obsessive compulsive warm baths. He had a history of epilepsy and addiction to marijuana, which he took on the day of admission. He presented to the hospital with a seizure, complicated by nausea, vomiting, and severe abdominal pain. His examination was unremarkable, except for mild epigastric tenderness. His laboratory and radiological tests were within normal limits, except for a positive urine drug screen for marijuana and opiates. He took himself immediately to the bathroom and remained under a hot shower with the exception of two 15-minute breaks for the rest of the day. He stated that it made him feel better than medication. Receiving medication and even eating was a problem because of this compulsive showering. Abstinence from marijuana during the hospital stay made the patient's nausea and vomiting resolve significantly. Cannabinoid hyperemesis is a differential diagnosis among patients with intractable nausea, vomiting, and obsessive hot bathing. The syndrome is an unmistakable indication of marijuana addiction. A thorough history and observation is very valuable. Recognition of this entity will reduce unnecessary testing and utilization of health care resources.Keywords: cannabinoid, compulsive bathing, cyclic vomiting, hyperemesis, hydrophilia, marijuana

Molecular mechanisms underlying the effects of cannabinoids in the brain

OpenAIRE

Puighermanal Puigvert, Emma, 1983-

2011-01-01

El sistema endocannabinoid és un sistema neuromodulador endogen que regula diverses funcions fisiològiques, incloent el control del moviment, la memòria, l’ansietat i el dolor, entre altres. Els compostos cannabinoids es troben principalment a la planta Cannabis sativa i exerceixen els seus efectes actuant al sistema endocannabinoid. Els cannabinoids tenen potencial terapèutic, principalment per l’esclerosi múltiple, el dolor i l’èmesi, tot i que una limitació important pel seu ús recau en el...

Health effects of exposure to second- and third-hand marijuana smoke: a systematic review.

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Holitzki, Hannah; Dowsett, Laura E; Spackman, Eldon; Noseworthy, Tom; Clement, Fiona

2017-11-24

Recreational marijuana has been legalized in 11 jurisdictions; Canada will legalize marijuana by July 2018. With this changing landscape, there is a need to understand the public health risks associated with marijuana to support patient-care provider conversations, harm-reduction measures and evidence-informed policy. The objective of this work was to summarize the health effects of exposure to second- and third-hand marijuana smoke. In this systematic review, we searched 6 databases from inception to October 2017. Abstract and full-text review was conducted in duplicate. Studies were included if they were human, in vivo or in vitro studies with more than 1 case reported in English or French, and reported original, quantitative data. Three outcomes were extracted: 1) cannabinoids and cannabinoid metabolites in bodily fluids, 2) self-reported psychoactive effects and 3) eye irritation and discomfort. Of the 1701 abstracts identified, 60 proceeded to full-text review; the final data set contained 15 articles. All of the included studies were of good to poor quality as assessed with the Downs and Black checklist. There is evidence of a direct relation between the tetrahydrocannabinol content of marijuana and effects on those passively exposed. This relation is mediated by several environmental factors including the amount of smoke, ventilation, air volume, number of marijuana cigarettes lit and number of smokers present. No evidence was identified assessing exposure to third-hand marijuana smoke or the health effects of long-term exposure. Exposure to second-hand marijuana smoke leads to cannabinoid metabolites in bodily fluids, and people experience psychoactive effects after such exposure. Alignment of tobacco and marijuana smoking bylaws may result in the most effective public policies. More research is required to understand the impact of exposure to third-hand smoke and the health effects of long-term exposure to second-hand smoke. Copyright 2017, Joule Inc. or

Are Alcohol Anti-relapsing and Alcohol Withdrawal Drugs Useful in Cannabinoid Users?

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Kleczkowska, Patrycja; Smaga, Irena; Filip, Małgorzata; Bujalska-Zadrozny, Magdalena

2016-11-01

Cannabinoids are still classified as illegal psychoactive drugs despite their broad and increasingly acknowledged therapeutic potential. These substances are most famous for their wide recreational use, particularly among young adults to either alter the state of consciousness, intensify pleasure induced by other psychoactive substances or as an alternative to the previously abused drugs. It is important to emphasize that cannabinoids are often taken together with a variety of medications intended for the treatment of alcohol use disorder (AUD) or alcohol withdrawal syndrome (AWS). These medications include disulfiram, acamprosate, and naltrexone. In this paper, we summarize recent advances in the knowledge of possible beneficial effects and interactions between cannabinoids and drugs commonly used for treatment of AUD and AWS either comorbid or existing as a separate disorder.

Effects of Parental Monitoring and Exposure to Community Violence on Antisocial Behavior and Anxiety/Depression among Adolescents

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Bacchini, Dario; Miranda, Maria Concetta; Affuso, Gaetana

2011-01-01

The aim of the research was to investigate the influence of gender, exposure to community violence, and parental monitoring upon antisocial behavior and anxiety/depression in adolescence. Involved in the study were 489 adolescents (290 males and 189 females) from 4 secondary schools in the city of Naples, Italy. The age of participants ranged from…

Developmental aspects of anandamide: ontogeny of response and prenatal exposure.

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Fride, E; Mechoulam, R

1996-02-01

Recent breakthroughs in cannabinoid research, including the identification of two cannabinoid receptors (CB receptors) and a family of endogenous ligands, the anandamides, may shed new light on the sequelae of pre- and perinatal exposure to cannabinoid receptor ligands and enable the experimental manipulation of the endogenous ligand in the developing organism. In the present study we examined the behavioural response to anandamide (ANA) in developing mice from day 13 into adulthood. We observed that depression of ambulation in an open field and the analgetic response to ANA are not fully developed until adulthood. In a separate set of experiments, we administered five daily injections of ANA (SC, 20 mg/kg) during the last trimester of pregnancy. No effects on birth weight, litter size, sex ratio and eye opening were detected after maternal ANA treatment. Further, no effects on open field performance of the offspring were observed until 4 weeks of age. However, from 40 days of age, a number of differences between the prenatal ANA and control offspring were detected. Thus, the offspring from ANA-treated dams showed impaired responsiveness to a challenge with ANA or delta 0-THC expressed as a lack of immobility in the ring test for catalepsy, hypothermia and analgesia. On the other hand, without challenge, they exhibited a spontaneous decrease in open field activity, catalepsy, hypothermia and a hypoalgetic tendency. These data suggest that exposure to excessive amounts of ANA during gestation alters the functioning of the ANA-CB receptor system. Further experiments investigating responsivity of the immune system suggest an increased inflammatory response to arachidonic acid, and enhanced hypothermic response to lipopolysaccharide in prenatally treated offspring. The results are discussed in relation to other manipulations of the maternal milieu, especially prenatal stress. It is concluded that alterations induced by prenatal exposure to ANA, cannabinoids and other

Adolescents' exposure to paid alcohol advertising on television and their alcohol use: exploring associations during a 13-year period.

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White, Victoria; Azar, Denise; Faulkner, Agatha; Coomber, Kerri; Durkin, Sarah; Livingston, Michael; Chikritzhs, Tanya; Room, Robin; Wakefield, Melanie

2017-10-01

To determine (i) whether Australian adolescents' exposure to television alcohol advertisements changed between 1999 and 2011 and (ii) examine the association between television alcohol advertising and adolescent drinking behaviours. Cross-sectional surveys conducted every 3 years between 1999 and 2011. Analyses examined associations between advertising exposures and reported drinking. Five Australian major cities. Students aged 12-17 years participating in a triennial nationally representative school-based survey residing in the television advertising markets associated with the major cities (sample size range per survey: 12 644-16 004). Outcome measures were: drinking in the past month, past week and past-week risky drinking (5+ drinks on a day). The key predictor variable was past-month adolescent-directed alcohol advertising Targeted Rating Points (TRPs, a measure of television advertising exposure). Control measures included student-level characteristics, government alcohol-control advertising TRPs, road safety (drink-driving) TRPs and time of survey. Average monthly adolescent alcohol TRPs increased between 1999 (mean = 2371) to 2005 (mean = 2679) (P advertising variables showed a significant association between past-month alcohol TRPs and past-month drinking [odds ratio (OR) = 1.11, 95% confidence interval (CI) = 1.07-1.15), past-week drinking (OR = 1.10, 95% CI = 1.06-1.14) and past-week risky drinking (OR = 1.15, 95% CI = 1.09-1.22). Past-week risky drinking was associated inversely with road safety TRPs (OR = 0.69, 95% CI = 0.49-0.98). While Australian adolescents' exposure to alcohol advertising on television reduced between 1999 and 2011, higher levels of past-month television alcohol advertising were associated with an increased likelihood of adolescents' drinking. The reduction in television alcohol advertising in Australia in the late 2000s may have played a part in reducing adolescents' drinking prevalence. © 2017 Society

Binge Toluene Exposure Alters Glutamate, Glutamine and GABA in the Adolescent Rat Brain as Measured by Proton Magnetic Resonance Spectroscopy*

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Perrine, Shane A.; O'Leary-Moore, Shonagh K.; Galloway, Matthew P.; Hannigan, John H.; Bowen, Scott E.

2010-01-01

Despite the high incidence of toluene abuse in adolescents, little is known regarding the effect of binge exposure on neurochemical profiles during this developmental stage. In the current study, the effects of binge toluene exposure during adolescence on neurotransmitter levels were determined using high-resolution proton magnetic resonance spectroscopy ex vivo at 11.7 T. Adolescent male Sprague-Dawley rats were exposed to toluene (0, 8,000 , or 12,000 ppm) for 15 min twice daily from postnatal day 28 (P28) through P34 and then euthanized either one or seven days later (on P35 or P42) to assess glutamate, glutamine, and GABA levels in intact tissue punches from the medial prefrontal cortex (mPFC), anterior striatum and hippocampus. In the mPFC, toluene reduced glutamate one day after exposure, with no effect on GABA, while after seven days, glutamate was no longer affected but there was an increase in GABA levels. In the hippocampus, neither GABA nor glutamate was altered one day after exposure, whereas seven days after exposure, increases were observed in GABA and glutamate. Striatal glutamate and GABA levels measured after either one or seven days were not altered after toluene exposure. These findings show that one week of binge toluene inhalation selectively alters these neurotransmitters in the mPFC and hippocampus in adolescent rats, and that some of these effects endure at least one week after the exposure. The results suggest that age-dependent, differential neurochemical responses to toluene may contribute to the unique behavioral patterns associated with drug abuse among older children and young teens. PMID:21126832

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

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Zago, A. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Leão, R.M.; Carneiro-de-Oliveira, P.E. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil); Marin, M.T.; Cruz, F.C. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Planeta, C.S. [Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP (Brazil); Programa Interinstitucional de Pós-Graduação em Ciências Fisiológicas, Universidade Federal de São Carlos/Universidade Estadual de São Paulo, Araraquara, SP (Brazil)

2011-11-18

Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

International Nuclear Information System (INIS)

Zago, A.; Leão, R.M.; Carneiro-de-Oliveira, P.E.; Marin, M.T.; Cruz, F.C.; Planeta, C.S.

2011-01-01

Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although crosssensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

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A. Zago

2012-01-01

Full Text Available Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although cross-sensitization between stress- and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P 28-37 and adult (P60-67 rats received nicotine (0.4 mg/kg, sc or saline (0.9% NaCl, sc and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats.

Socioeconomic inequality in exposure to bullying during adolescence: a comparative, cross-sectional, multilevel study in 35 countries

DEFF Research Database (Denmark)

Due, Pernille; Merlo, Juan; Harel-Fisch, Yossi

2009-01-01

OBJECTIVES: We examined the socioeconomic distribution of adolescent exposure to bullying internationally and documented the contribution of the macroeconomic environment. METHODS: We used an international survey of 162,305 students aged 11, 13, and 15 years from nationally representative samples...... of 5998 schools in 35 countries in Europe and North America for the 2001-2002 school year. The survey used standardized measures of exposure to bullying and socioeconomic affluence. RESULTS: Adolescents from families of low affluence reported higher prevalence of being victims of bullying (odds ratio [OR......] = 1.13; 95% confidence interval [CI] = 1.10, 1.16). International differences in prevalence of exposure to bullying were not associated with the economic level of the country (as measured by gross national income) or the school, but wide disparities in affluence at a school and large economic...

Impact of alcohol advertising and media exposure on adolescent alcohol use: a systematic review of longitudinal studies.

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Anderson, Peter; de Bruijn, Avalon; Angus, Kathryn; Gordon, Ross; Hastings, Gerard

2009-01-01

To assess the impact of alcohol advertising and media exposure on future adolescent alcohol use. We searched MEDLINE, the Cochrane Library, Sociological Abstracts, and PsycLIT, from 1990 to September 2008, supplemented with searches of Google scholar, hand searches of key journals and reference lists of identified papers and key publications for more recent publications. We selected longitudinal studies that assessed individuals' exposure to commercial communications and media and alcohol drinking behaviour at baseline, and assessed alcohol drinking behaviour at follow-up. Participants were adolescents aged 18 years or younger or below the legal drinking age of the country of origin of the study, whichever was the higher. Thirteen longitudinal studies that followed up a total of over 38,000 young people met inclusion criteria. The studies measured exposure to advertising and promotion in a variety of ways, including estimates of the volume of media and advertising exposure, ownership of branded merchandise, recall and receptivity, and one study on expenditure on advertisements. Follow-up ranged from 8 to 96 months. One study reported outcomes at multiple time-points, 3, 5, and 8 years. Seven studies provided data on initiation of alcohol use amongst non-drinkers, three studies on maintenance and frequency of drinking amongst baseline drinkers, and seven studies on alcohol use of the total sample of non-drinkers and drinkers at baseline. Twelve of the thirteen studies concluded an impact of exposure on subsequent alcohol use, including initiation of drinking and heavier drinking amongst existing drinkers, with a dose response relationship in all studies that reported such exposure and analysis. There was variation in the strength of association, and the degree to which potential confounders were controlled for. The thirteenth study, which tested the impact of outdoor advertising placed near schools failed to detect an impact on alcohol use, but found an impact on

76 FR 11075 - Schedules of Controlled Substances: Temporary Placement of Five Synthetic Cannabinoids Into...

Science.gov (United States)

2011-03-01

... constituent of marijuana. ``Synthetic cannabinoids'' are a large family of chemically unrelated structures functionally (biologically) similar to THC, the active principle of marijuana. Two of the five synthetic...-like synthetic cannabinoids are perceived as ``legal'' alternatives to marijuana despite the fact that...

Cannabis, Cannabinoids, and Cerebral Metabolism: Potential Applications in Stroke and Disorders of the Central Nervous System.

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Latorre, Julius Gene S; Schmidt, Elena B

2015-09-01

No compound has generated more attention in both the scientific and recently in the political arena as much as cannabinoids. These diverse groups of compounds referred collectively as cannabinoids have both been vilified due to its dramatic and potentially harmful psychotropic effects and glorified due to its equally dramatic and potential application in a number of acute and chronic neurological conditions. Previously illegal to possess, cannabis, the plant where natural form of cannabinoids are derived, is now accepted in a growing number of states for medicinal purpose, and some even for recreational use, increasing opportunities for more scientific experimentation. The purpose of this review is to summarize the growing body of literature on cannabinoids and to present an overview of our current state of knowledge of the human endocannabinoid system in the hope of defining the future of cannabinoids and its potential applications in disorders of the central nervous system, focusing on stroke.

The role of depressive symptoms in treatment of adolescent cannabis use disorder with N-Acetylcysteine.

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Tomko, Rachel L; Gilmore, Amanda K; Gray, Kevin M

2018-05-21

Relative to adults, adolescents are at greater risk of developing a cannabis use disorder (CUD) and risk may be exacerbated by co-occurring depressive symptoms. N-Acetylcysteine (NAC), an over-the-counter antioxidant, is thought to normalize glutamate transmission. Oxidative stress and glutamate transmission are disrupted in both depression and CUD. Thus, NAC may be particularly effective at promoting cannabis abstinence among adolescents with elevated depressive symptoms. Secondary analyses were conducted using a sub-sample of adolescents with CUD (N = 74) who participated in an 8-week randomized placebo-controlled clinical trial examining the efficacy of NAC for cannabis cessation. It was hypothesized that NAC would reduce severity of depressive symptoms, and that decreases depressive symptom severity would mediate decreases in positive weekly urine cannabinoid tests (11-nor-9-carboxy-Δ9-tetrahydrocannabinol). Additionally, it was expected that adolescents with greater severity of baseline depressive symptoms would be more likely to become abstinent when assigned NAC relative to placebo. Results from linear mixed models and generalized estimating equations did not suggest that NAC reduced severity of depressive symptoms, and the hypothesis that NAC's effect on cannabis cessation would be mediated by reduced depressive symptoms was not supported. However, an interaction between treatment condition and baseline severity of depressive symptoms as a predictor of weekly urine cannabinoid tests was significant, suggesting that NAC was more effective at promoting abstinence among adolescents with heightened baseline depressive symptoms. These secondary findings, though preliminary, suggest a need for further examination of the role of depressive symptoms in treatment of adolescent CUD with NAC. Copyright © 2018. Published by Elsevier Ltd.

Cannabinoids and their possible use in the treatment of glaucoma

OpenAIRE

Zozaya Aldana, Beatriz; Medina Rodríguez, Isabel; Tamayo Pineda, Nirma

2011-01-01

Aunque la planta Cannabis sativa ha sido empleada desde la más remota antigüedad con fines medicinales, uno de sus derivados, la marihuana, se ha convertido en la droga de uso ilegal más consumida en el mundo. Asimismo tanto el Cannabis como sus cannabinoides se emplean como terapéutico en pocas enfermedades generalmente neurológicas. Se realizó una revisión bibliográfica para exponer el posible uso de los cannabinoides en la terapéutica del glaucoma. Para ello se tuvo en cuenta la literatura...

Brain tumors in children and adolescents and exposure to animals and farm life

DEFF Research Database (Denmark)

Christensen, Jeppe Schultz; Mortensen, Laust Hvas; Röösli, Martin

2012-01-01

The etiology of brain tumors in children and adolescents is largely unknown, and very few environmental risk factors have been identified. The aim of this study was to examine the relationship between pre- or postnatal animal contacts or farm exposures and the risk of childhood brain tumors (CBTs...

Cannabinoids facilitate the swallowing reflex elicited by the superior laryngeal nerve stimulation in rats.

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Mostafeezur, Rahman Md; Zakir, Hossain Md; Takatsuji, Hanako; Yamada, Yoshiaki; Yamamura, Kensuke; Kitagawa, Junichi

2012-01-01

Cannabinoids have been reported to be involved in affecting various biological functions through binding with cannabinoid receptors type 1 (CB1) and 2 (CB2). The present study was designed to investigate whether swallowing, an essential component of feeding behavior, is modulated after the administration of cannabinoid. The swallowing reflex evoked by the repetitive electrical stimulation of the superior laryngeal nerve in rats was recorded before and after the administration of the cannabinoid receptor agonist, WIN 55-212-2 (WIN), with or without CB1 or CB2 antagonist. The onset latency of the first swallow and the time intervals between swallows were analyzed. The onset latency and the intervals between swallows were shorter after the intravenous administration of WIN, and the strength of effect of WIN was dose-dependent. Although the intravenous administration of CB1 antagonist prior to intravenous administration of WIN blocked the effect of WIN, the administration of CB2 antagonist did not block the effect of WIN. The microinjection of the CB1 receptor antagonist directly into the nucleus tractus solitarius (NTS) prior to intravenous administration of WIN also blocked the effect of WIN. Immunofluorescence histochemistry was conducted to assess the co-localization of CB1 receptor immunoreactivity to glutamic acid decarboxylase 67 (GAD67) or glutamate in the NTS. CB1 receptor was co-localized more with GAD67 than glutamate in the NTS. These findings suggest that cannabinoids facilitate the swallowing reflex via CB1 receptors. Cannabinoids may attenuate the tonic inhibitory effect of GABA (gamma-aminobuteric acid) neurons in the central pattern generator for swallowing.

Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

International Nuclear Information System (INIS)

Massi, Paola; Valenti, Marta; Solinas, Marta; Parolaro, Daniela

2010-01-01

Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells

Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

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Massi, Paola [Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, Via Vanvitelli 32, 20129 Milan (Italy); Valenti, Marta; Solinas, Marta; Parolaro, Daniela [Department of Structural and Functional Biology, Section of Pharmacology, Center of Neuroscience, University of Insubria, Via A. da Giussano 10, 20152 Busto Arsizio, Varese (Italy)

2010-05-26

Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells.

Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

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Paola Massi

2010-05-01

Full Text Available Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells.

Effects of acute or chronic ethanol exposure during adolescence on behavioral inhibition and efficiency in a modified water maze task.

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Shawn K Acheson

Full Text Available Ethanol is well known to adversely affect frontal executive functioning, which continues to develop throughout adolescence and into young adulthood. This is also a developmental window in which ethanol is misused by a significant number of adolescents. We examined the effects of acute and chronic ethanol exposure during adolescence on behavioral inhibition and efficiency using a modified water maze task. During acquisition, rats were trained to find a stable visible platform onto which they could escape. During the test phase, the stable platform was converted to a visible floating platform (providing no escape and a new hidden platform was added in the opposite quadrant. The hidden platform was the only means of escape during the test phase. In experiment 1, adolescent animals received ethanol (1.0 g/kg 30 min before each session during the test phase. In experiment 2, adolescent animals received chronic intermittent ethanol (5.0 g/kg for 16 days (PND30 To PND46 prior to any training in the maze. At PND72, training was initiated in the same modified water maze task. Results from experiment 1 indicated that acute ethanol promoted behavioral disinhibition and inefficiency. Experiment 2 showed that chronic intermittent ethanol during adolescence appeared to have no lasting effect on behavioral disinhibition or new spatial learning during adulthood. However, chronic ethanol did promote behavioral inefficiency. In summary, results indicate that ethanol-induced promotion of perseverative behavior may contribute to the many adverse behavioral sequelae of alcohol intoxication in adolescents and young adults. Moreover, the long-term effect of adolescent chronic ethanol exposure on behavioral efficiency is similar to that observed after chronic exposure in humans.

Multiple Forms and Settings of Exposure to Violence and Values: Unique and Interactive Relationships With Antisocial Behavior in Adolescence.

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Bacchini, Dario; Affuso, Gaetana; Aquilar, Serena

2015-10-01

The general purpose of this study was to investigate the relationships between multiple forms and settings of exposure to violence (ETV) as well as personal values and antisocial behavior (ASB) in adolescence. The association of ETV as witness or victim in different contexts (family, school, or neighborhood) and the association of the selected values of power, universalism, and conformity with ASB were analyzed. In addition, the role of ETV in moderating the relationship between values and ASB was tested. A total of 369 adolescents participated in the study. Hierarchical multiple regression analysis was performed. Results revealed that ASB was independently affected by exposure to family violence as a victim, exposure to school violence as a witness, exposure to neighborhood violence as a witness, and by all three selected values. The associations of ASB with universalism and conformity were negative. Conversely, the association of ASB with power was positive. One interaction had statistically significant effects. Results revealed that exposure to school violence as a witness moderates the relationship between universalism and ASB. The results highlight a high percentage of explained variance by ETV and values on ASB and suggest the importance of adopting a socio-ecological framework in interpreting adolescent behavior. © The Author(s) 2014.

Small Molecules from Nature Targeting G-Protein Coupled Cannabinoid Receptors: Potential Leads for Drug Discovery and Development

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Charu Sharma

2015-01-01

Full Text Available The cannabinoid molecules are derived from Cannabis sativa plant which acts on the cannabinoid receptors types 1 and 2 (CB1 and CB2 which have been explored as potential therapeutic targets for drug discovery and development. Currently, there are numerous cannabinoid based synthetic drugs used in clinical practice like the popular ones such as nabilone, dronabinol, and Δ9-tetrahydrocannabinol mediates its action through CB1/CB2 receptors. However, these synthetic based Cannabis derived compounds are known to exert adverse psychiatric effect and have also been exploited for drug abuse. This encourages us to find out an alternative and safe drug with the least psychiatric adverse effects. In recent years, many phytocannabinoids have been isolated from plants other than Cannabis. Several studies have shown that these phytocannabinoids show affinity, potency, selectivity, and efficacy towards cannabinoid receptors and inhibit endocannabinoid metabolizing enzymes, thus reducing hyperactivity of endocannabinoid systems. Also, these naturally derived molecules possess the least adverse effects opposed to the synthetically derived cannabinoids. Therefore, the plant based cannabinoid molecules proved to be promising and emerging therapeutic alternative. The present review provides an overview of therapeutic potential of ligands and plants modulating cannabinoid receptors that may be of interest to pharmaceutical industry in search of new and safer drug discovery and development for future therapeutics.

Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat

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Blanco-Calvo, Eduardo; Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Pavón, Francisco Javier; Serrano, Antonia; Castilla-Ortega, Estela; Galeano, Pablo; Rubio, Leticia; Suárez, Juan; Rodriguez de Fonseca, Fernando

2014-01-01

Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation. To this end, we examined whether pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg) or CB2 receptors (AM630, 3 mg/kg) would affect cell proliferation [the cells were labeled with 5-bromo-2′-deoxyuridine (BrdU)] in the subventricular zone (SVZ) of the lateral ventricle and the dentate subgranular zone (SGZ). Additionally, we measured cell apoptosis (as monitored by the expression of cleaved caspase-3) and glial activation [by analyzing the expression of glial fibrillary acidic protein (GFAP) and Iba-1] in the striatum and hippocampus during acute and repeated (4 days) cocaine administration (20 mg/kg). The results showed that acute cocaine exposure decreased the number of BrdU-immunoreactive (ir) cells in the SVZ and SGZ. In contrast, repeated cocaine exposure reduced the number of BrdU-ir cells only in the SVZ. Both acute and repeated cocaine exposure increased the number of cleaved caspase-3-, GFAP- and Iba1-ir cells in the hippocampus, and this effect was counteracted by AM630 or Rimonabant, which increased the number of BrdU-, GFAP-, and Iba1-ir cells in the hippocampus. These results indicate that the changes in neurogenic, apoptotic and gliotic processes that were produced by repeated cocaine administration were normalized by pharmacological blockade of CB1 and CB2. The restorative effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with the prevention of the induction of conditioned

Novelty-induced emotional arousal modulates cannabinoid effects on recognition memory and adrenocortical activity.

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Campolongo, Patrizia; Morena, Maria; Scaccianoce, Sergio; Trezza, Viviana; Chiarotti, Flavia; Schelling, Gustav; Cuomo, Vincenzo; Roozendaal, Benno

2013-06-01

Although it is well established that cannabinoid drugs can influence cognitive performance, the findings-describing both enhancing and impairing effects-have been ambiguous. Here, we investigated the effects of posttraining systemic administration of the synthetic cannabinoid agonist WIN55,212-2 (0.1, 0.3, or 1.0 mg/kg) on short- and long-term retention of object recognition memory under two conditions that differed in their training-associated arousal level. In male Sprague-Dawley rats that were not previously habituated to the experimental context, WIN55,212-2 administered immediately after a 3-min training trial, biphasically impaired retention performance at a 1-h interval. In contrast, WIN55,212-2 enhanced 1-h retention of rats that had received extensive prior habituation to the experimental context. Interestingly, immediate posttraining administration of WIN55,212-2 to non-habituated rats, in doses that impaired 1-h retention, enhanced object recognition performance at a 24-h interval. Posttraining WIN55,212-2 administration to habituated rats did not significantly affect 24-h retention. In light of intimate interactions between cannabinoids and the hypothalamic-pituitary-adrenal axis, we further investigated whether cannabinoid administration might differently influence training-induced glucocorticoid activity in rats in these two habituation conditions. WIN55,212-2 administered after object recognition training elevated plasma corticosterone levels in non-habituated rats whereas it decreased corticosterone levels in habituated rats. Most importantly, following pretreatment with the corticosterone-synthesis inhibitor metyrapone, WIN55,212-2 effects on 1- and 24-h retention of non-habituated rats became similar to those seen in the low-aroused habituated animals, indicating that cannabinoid-induced regulation of adrenocortical activity contributes to the environmentally sensitive effects of systemically administered cannabinoids on short- and long

The Effects of Cannabinoids on Executive Functions: Evidence from Cannabis and Synthetic Cannabinoids—A Systematic Review

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Koby Cohen

2018-02-01

Full Text Available Background—Cannabis is the most popular illicit drug in the Western world. Repeated cannabis use has been associated with short and long-term range of adverse effects. Recently, new types of designer-drugs containing synthetic cannabinoids have been widespread. These synthetic cannabinoid drugs are associated with undesired adverse effects similar to those seen with cannabis use, yet, in more severe and long-lasting forms. Method—A literature search was conducted using electronic bibliographic databases up to 31 December 2017. Specific search strategies were employed using multiple keywords (e.g., “synthetic cannabinoids AND cognition,” “cannabis AND cognition” and “cannabinoids AND cognition”. Results—The search has yielded 160 eligible studies including 37 preclinical studies (5 attention, 25 short-term memory, 7 cognitive flexibility and 44 human studies (16 attention, 15 working memory, 13 cognitive flexibility. Both pre-clinical and clinical studies demonstrated an association between synthetic cannabinoids and executive-function impairment either after acute or repeated consumptions. These deficits differ in severity depending on several factors including the type of drug, dose of use, quantity, age of onset and duration of use. Conclusions—Understanding the nature of the impaired executive function following consumption of synthetic cannabinoids is crucial in view of the increasing use of these drugs.

Television food advertising viewed by preschoolers, children and adolescents: contributors to differences in exposure for black and white youth in the United States.

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Fleming-Milici, F; Harris, J L

2018-02-01

Public health experts raise concerns about adolescents' and black youth's greater exposure to TV advertising for unhealthy foods and beverages compared with children and white youth. Examine how television-viewing patterns and rates of advertising during targeted programming contribute to this greater exposure. Nielsen panel data provided viewing times and amount of food advertising viewed on U.S. television in 2008 and 2012. Researchers compared results by network type (black-, child- and youth-targeted), age group (preschoolers, children and adolescents) and race (black and white youth). Food advertising exposure increased with age for both black and white youth, but black youth viewed approximately 50% or more ads than did white youth of the same age. Higher rates of food advertising on youth-targeted networks explained greater adolescent exposure. However, greater television viewing and higher rates of advertising on youth- and black-targeted networks both contributed to black youth's greater exposure. From 2008 to 2012, increases in food-ads-per-hour increased exposure for all youth. Food advertisers and networks, especially those targeting adolescents and black youth, must do more to reduce advertising that negatively impacts young people's health. Furthermore, reducing commercial-television viewing by black youth may help reduce health disparities affecting their communities. © 2016 World Obesity Federation.

Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies

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Katia eBefort

2015-02-01

Full Text Available The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides (enkephalins, endorphins and dynorphins. The endogenous cannabinoid system comprises lipid neuromodulators (endocannabinoids, enzymes for their synthesis and their degradation and two well-characterized receptors, cannabinoid receptors CB1 and CB2. These systems play a major role in the control of pain as well as in mood regulation, reward processing and the development of addiction. Both opioid and cannabinoid receptors are coupled to G proteins and are expressed throughout the brain reinforcement circuitry. Extending classical pharmacology, research using genetically modified mice has provided important progress in the identification of the specific contribution of each component of these endogenous systems in vivo on reward process. This review will summarize available genetic tools and our present knowledge on the consequences of gene knockout on reinforced behaviors in both systems, with a focus on their potential interactions. A better understanding of opioid-cannabinoid interactions may provide novel strategies for therapies in addicted individuals.

Involvement of cannabinoid system in the nucleus accumbens on delay-based decision making in the rat.

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Fatahi, Zahra; Sadeghi, Bahman; Haghparast, Abbas

2018-01-30

The nucleus accumbens (NAc) plays a fundamental role in decision making and anticipation of reward. In addition, exogenous cannabinoids affect the behavior of humans and animals including disruption of short-term memory and cognitive impairments. Therefore, in this study, cannabinoid agonist and antagonist were administrated into the NAc to determine the effect of cannabinoid activation in the entire NAc on delay-based decision making. Rats were trained on a cost-benefit T-maze decision making task in which the animals were well-trained to choose between a small/immediate reward and a large/delay reward. After training, the animals were implanted with guide cannulae in the NAc. On test day, they received cannabinoid agonist (Win 55,212-2; 10, 50 and 100μM) and/or antagonist (AM251; 45μM) into the NAc. Percentage of high reward choice and latency of reward achievement were evaluated. Results showed that cannabinoid agonist administration caused a decrease in high reward choice such that rats selected small/immediate reward instead of large/delay reward. Moreover, in agonist-treated animals latency of reward achievement increased. Effects of cannabinoid activation on delay-based decision making with equivalent delays demonstrated that if the delay was equated on both arm goals, animals still had a preference for the high/delay reward, showing the results was not caused by an impairment of spatial preference or memory. These finding clarified that cannabinoid system activation in the entire NAc plays a critical role in the regulation of delay-based decision making. Copyright © 2017 Elsevier B.V. All rights reserved.

Chronic Nicotine Exposure Initiated in Adolescence and Unpaired to Behavioral Context Fails to Enhance Sweetened Ethanol Seeking

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Aric C. Madayag

2017-08-01

Full Text Available Nicotine use in adolescence is pervasive in the United States and, according to the Gateway Hypothesis, may lead to progression towards other addictive substances. Given the prevalence of nicotine and ethanol comorbidity, it is difficult to ascertain if nicotine is a gateway drug for ethanol. Our study investigated the relationship between adolescent exposure to nicotine and whether this exposure alters subsequent alcohol seeking behavior. We hypothesized that rats exposed to nicotine beginning in adolescence would exhibit greater alcohol seeking behavior than non-exposed siblings. To test our hypothesis, beginning at P28, female rats were initially exposed to once daily nicotine (0.4 mg/kg, SC or saline for 5 days. Following these five initial injections, animals were trained to nose-poke for sucrose reinforcement (10%, w/v, gradually increasing to sweetened ethanol (10% sucrose; 10% ethanol, w/v on an FR5 reinforcement schedule. Nicotine injections were administered after the behavioral sessions to minimize acute effects of nicotine on operant self-administration. We measured the effects of nicotine exposure on the following aspects of ethanol seeking: self-administration, naltrexone (NTX-induced decreases, habit-directed behavior, motivation, extinction and reinstatement. Nicotine exposure did not alter self-administration or the effectiveness of NTX to reduce alcohol seeking. Nicotine exposure blocked habit-directed ethanol seeking. Finally, nicotine did not alter extinction learning or cue-induced reinstatement to sweetened ethanol seeking. Our findings suggest that nicotine exposure outside the behavioral context does not escalate ethanol seeking. Further, the Gateway Hypothesis likely applies to scenarios in which nicotine is either self-administered or physiologically active during the behavioral session.

Are cannabinoids effective for Parkinson’s disease?

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Gonzalo A Bravo-Soto

2017-06-01

Full Text Available Resumen Se postula que los cannabinoides pudieran tener beneficios en la enfermedad de Parkinson. No obstante, su real efectividad clínica aún es discutida. Para responder a esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Identificamos seis revisiones sistemáticas que en conjunto incluyen ocho estudios, de los cuales cuatro corresponden a ensayos aleatorizados. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios y preparamos tablas de resumen de los resultados utilizando el método GRADE. Concluimos que los cannabinoides probablemente no disminuyen los síntomas ni las discinesias, y se asocian a efectos adversos frecuentes en pacientes con enfermedad de Parkinson

Associations between adolescent seatbelt non-use, normative perceptions and screen media exposure: results from a national US survey.

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Dunlop, Sally M; Romer, Daniel

2010-10-01

Failure to use seatbelts in motor vehicles is a major source of youth injuries, and previous research has noted the widespread non-use of seatbelts in popular media. To explore whether increased exposure to entertainment screen media was associated with inflated normative perceptions regarding seatbelt non-use, and to determine any associations between normative perceptions and seatbelt non-use. A nationally representative telephone survey of school-aged American adolescents (14-17 years, n=915) measuring: screen media exposure; normative perceptions with reference to friends' disapproval of non-use, and prevalence of non-use among friends, school peers and peers; and self-reported seatbelt non-use. Using structural equation modelling, analyses indicate that, after demographic and individual characteristics relevant to screen media exposure and seatbelt non-use had been controlled for, frequent exposure to entertainment media was associated with positive normative perceptions about seatbelt non-use for boys, but not for girls. Normative perceptions related to friends' and school peers' seatbelt use were associated with seatbelt non-use for both boys and girls. Attempts to increase adolescent seatbelt use could include public communication campaigns to alter normative perceptions. Broadcasting these campaigns in conjunction with the media that under-represent seatbelt use may be a successful strategy for reducing the influence of such media on male adolescents.

Racial/Ethnic and Income Disparities in Child and Adolescent Exposure to Food and Beverage Television Ads across U.S. Media Markets

OpenAIRE

Powell, Lisa M.; Wada, Roy; Kumanyika, Shiriki K.

2014-01-01

Obesity prevalence and related health burdens are greater among U.S. racial/ethnic minority and low-income populations. Targeted advertising may contribute to disparities. Designated market area (DMA) spot television ratings were used to assess geographic differences in child/adolescent exposure to food-related advertisements based on DMA-level racial/ethnic and income characteristics. Controlling for unobserved DMA-level factors and time trends, child/adolescent exposure to food-related ads,...

Mechanism of the Interaction of Cannabinoid System in Central Amygdale with Opioid System

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S Sarahroodi

2012-05-01

Full Text Available

Background and objectives

Cannabinoids which are active compounds of marijuana show some pharmacological effects similar to the opioids. There are also functional interactions between both cannabinoid and opioid systems. In this study we investigated the role of cannabinoid receptors in central amygdala and its interaction with opioid system.

Methods

In the present study, we investigated the effects of intraperitoneal injection of opioid drugs on response-induced by intra-amygdala (intra-Amyg microinjection of cannabinoid agents in rats, using elevated plus-maze test of anxiety.

Results

Intraperitoneal injection of morphine (3, 6 and 9 mg/kg increased %OAT and %OAE, but not locomotor activity, showing an anxiolytic response. However, some doses of the opioid receptor antagonist, naloxone reduced %OAT and locomotor activity as well. Intra-Amyg administration of CB1 cannabinoid receptor agonist, ACPA (at the dose of 1.25 and 5 ng/rat increased %OAT and %OAE but not locomotor activity, thus showing an anxiolytic response, which was increased by morphine (6 mg/kg, i.p. without any interaction. Naloxone also reduced ACPA effects.  

Intra-Amyg administration of CB1 cannabinoid receptor antagonist, AM251 (2.5, 25 and 100 ng/rat did not alter %OAT and %OAE but higher doses of drug (25 and 100 ng/rat reduced locomotor activity. However, the drug in combination of morphine anxiolytic response and with naloxone decreased anxiety.

Conclusion

The results may indicate an anxiolytic for CB1 cannabinoid. Our results also showed that opioid

Multiple sleep alterations in mice lacking cannabinoid type 1 receptors.

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Alessandro Silvani

Full Text Available Cannabinoid type 1 (CB1 receptors are highly expressed in the brain and play a role in behavior control. Endogenous cannabinoid signaling is modulated by high-fat diet (HFD. We investigated the consequences of congenital lack of CB1 receptors on sleep in mice fed standard diet (SD and HFD. CB1 cannabinoid receptor knock-out (KO and wild-type (WT mice were fed SD or HFD for 4 months (n = 9-10 per group. Mice were instrumented with electroencephalographic (EEG and electromyographic electrodes. Recordings were performed during baseline (48 hours, sleep deprivation (gentle handling, 6 hours, sleep recovery (18 hours, and after cage switch (insomnia model paradigm, 6 hours. We found multiple significant effects of genotype on sleep. In particular, KO spent more time awake and less time in non-rapid-eye-movement sleep (NREMS and rapid-eye-movement sleep (REMS than WT during the dark (active period but not during the light (rest period, enhancing the day-night variation of wake-sleep amounts. KO had slower EEG theta rhythm during REMS. REMS homeostasis after sleep deprivation was less effective in KO than in WT. Finally, KO habituated more rapidly to the arousing effect of the cage-switch test than WT. We did not find any significant effects of diet or of diet x genotype interaction on sleep. The occurrence of multiple sleep alterations in KO indicates important roles of CB1 cannabinoid receptors in limiting arousal during the active period of the day, in sleep regulation, and in sleep EEG in mice.

Using GPS and activity tracking to reveal the influence of adolescents' food environment exposure on junk food purchasing.

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Sadler, Richard C; Clark, Andrew F; Wilk, Piotr; O'Connor, Colleen; Gilliland, Jason A

2016-06-09

This study examines the influence of adolescents' exposure to unhealthy food outlets on junk food purchasing during trips between home and school, with particular attention to how exposure and purchasing differ according to child's biological sex, mode of transportation, and direction to or from school. Between 2010 and 2013, students (n = 654) aged 9-13 years from 25 schools in London and Middlesex County, ON, completed a socio-demographic survey and an activity diary (to identify food purchases), and were observed via a global positioning system for 2 weeks (to track routes for trips to/from school). Spatial data on routes and purchase data were integrated with a validated food outlet database in a geographic information system, and exposure was measured as the minutes a child spent within 50 m of an unhealthy food outlet (i.e., fast food restaurants, variety stores). For trips involving junk food exposure (n = 4588), multilevel logistic regression was used to assess the relationship between exposure and purchasing. Multilevel analyses indicated that adolescents' duration of exposure to unhealthy food outlets between home and school had a significant effect on the likelihood of junk food purchasing. This relationship remained significant when the data were stratified by sex (female/male), trip direction (to/from school) and travel mode (active/car), with the exception of adolescents who travelled by bus. Policies and programs that mitigate the concentration of unhealthy food outlets close to schools are critical for encouraging healthy eating behaviours among children and reducing diet-related health issues such as obesity.

Ecological Momentary Assessment of the Association Between Exposure to Alcohol Advertising and Early Adolescents' Beliefs About Alcohol.

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Martino, Steven C; Kovalchik, Stephanie A; Collins, Rebecca L; Becker, Kirsten M; Shadel, William G; D'Amico, Elizabeth J

2016-01-01

To evaluate the momentary association between exposure to alcohol advertising and middle-school students' beliefs about alcohol in real-world settings and to explore racial/ethnic differences in this association. Middle-school students (N = 588) carried handheld data collection devices for 14 days, recording their exposures to all forms of alcohol advertising during the assessment period. Students also responded to three investigator-initiated control prompts (programmed to occur randomly) on each day of the assessment period. After each exposure to advertising and at each control prompt, students reported their beliefs about alcohol. Mixed-effects regression models compared students' beliefs about alcohol between moments of exposure to alcohol advertising and control prompts. Students perceived the typical person their age who drinks alcohol (prototype perceptions) more favorably and perceived alcohol use as more normative at times of exposure to alcohol advertising than at times of nonexposure (i.e., at control prompts). Exposure to alcohol advertising was not associated with shifts in the perceived norms of black and Hispanic students, however, and the association between exposure and prototype perceptions was stronger among non-Hispanic students than among Hispanic students. Exposure to alcohol advertising is associated with acute shifts in adolescents' perceptions of the typical person that drinks alcohol and the normativeness of drinking. These associations are both statistically and substantively meaningful. Copyright © 2016 Society for Adolescent Health and Medicine. All rights reserved.

Prenatal cocaine exposure alters alpha2 receptor expression in adolescent rats

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Silvers Janelle M

2006-04-01

Full Text Available Abstract Background Prenatal cocaine exposure produces attentional deficits which to persist through early childhood. Given the role of norepinephrine (NE in attentional processes, we examined the forebrain NE systems from prenatal cocaine exposed rats. Cocaine was administered during pregnancy via the clinically relevant intravenous route of administration. Specifically, we measured α2-adrenergic receptor (α2-AR density in adolescent (35-days-old rats, using [3H]RX821002 (5 nM. Results Sex-specific alterations of α2-AR were found in the hippocampus and amygdala of the cocaine-exposed animals, as well as an upregulation of α2-AR in parietal cortex. Conclusion These data suggest that prenatal cocaine exposure results in a persistent alteration in forebrain NE systems as indicated by alterations in receptor density. These neurochemical changes may underlie behavioral abnormalities observed in offspring attentional processes following prenatal exposure to cocaine.

Sex differences, learning flexibility, and striatal dopamine D1 and D2 following adolescent drug exposure in rats

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Izquierdo, Alicia; Pozos, Hilda; De La Torre, Adrianna; DeShields, Simone; Cevallos, James; Rodriguez, Jonathan; Stolyarova, Alexandra

2016-01-01

Corticostriatal circuitry supports flexible reward learning and emotional behavior from the critical neurodevelopmental stage of adolescence through adulthood. It is still poorly understood how prescription drug exposure in adolescence may impact these outcomes in the long-term. We studied adolescent methylphenidate (MPH) and fluoxetine (FLX) exposure in rats and their impact on learning and emotion in adulthood. In Experiment 1, male and female rats were administered MPH, FLX, or saline (SAL), and compared with methamphetamine (mAMPH) treatment beginning in postnatal day (PND) 37. The rats were then tested on discrimination and reversal learning in adulthood. In Experiment 2, animals were administered MPH or SAL also beginning in PND 37 and later tested in adulthood for anxiety levels. In Experiment 3, we analyzed striatal dopamine D1 and D2 receptor expression in adulthood following either extensive learning (after Experiment 1) or more brief emotional measures (after Experiment 2). We found sex differences in discrimination learning and attenuated reversal learning after MPH and only sex differences in adulthood anxiety. In learners, there was enhanced striatal D1, but not D2, after either adolescent MPH or mAMPH. Lastly, also in learners, there was a sex x treatment group interaction for D2, but not D1, driven by the MPH-pretreated females, who expressed significantly higher D2 levels compared to SAL. These results show enduring effects of adolescent MPH on reversal learning in rats. Developmental psychostimulant exposure may interact with learning to enhance D1 expression in adulthood, and affect D2 expression in a sex-dependent manner. PMID:27091300

The Role of Cannabinoid Transmission in Emotional Memory Formation: Implications for Addiction and Schizophrenia

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Huibing eTan

2014-06-01

Full Text Available Emerging evidence from both basic and clinical research demonstrates an important role for endocannabinoid (ECB signaling in the processing of emotionally salient information, learning and memory. Cannabinoid transmission within neural circuits involved in emotional processing has been shown to modulate the acquisition, recall and extinction of emotionally salient memories and importantly, can strongly modulate the emotional salience of incoming sensory information. Two neural regions in particular, the medial prefrontal cortex (PFC and the basolateral nucleus of the amygdala (BLA, play important roles in emotional regulation and contain high levels of cannabinoid receptors. Furthermore, both regions show profound abnormalities in neuropsychiatric disorders such as addiction and schizophrenia. Considerable evidence has demonstrated that cannabinoid transmission functionally interacts with dopamine (DA, a neurotransmitter system that is of exceptional importance for both addictive behaviours and the neuropsychopathology of disorders like schizophrenia. Research in our laboratory has focused on how cannabinoid transmission both within and extrinsic to the mesolimbic DA system, including the BLAmPFC circuitry, can modulate both rewarding and aversive emotional information. In this review, we will summarize clinical and basic neuroscience research demonstrating the importance of cannabinoid signaling within this neural circuitry. In particular, evidence will be reviewed emphasizing the importance of cannabinoid signaling within the BLAmPFC circuitry in the context of emotional salience processing, memory formation and memory-related plasticity. We propose that aberrant states of hyper or hypoactive ECB signaling within the amygdala-prefrontal cortical circuit may lead to dysregulation of mesocorticolimbic DA transmission controlling the processing of emotionally salient information. These disturbances may in turn lead to emotional processing

Cannabinoids facilitate the swallowing reflex elicited by the superior laryngeal nerve stimulation in rats.

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Rahman Md Mostafeezur

Full Text Available Cannabinoids have been reported to be involved in affecting various biological functions through binding with cannabinoid receptors type 1 (CB1 and 2 (CB2. The present study was designed to investigate whether swallowing, an essential component of feeding behavior, is modulated after the administration of cannabinoid. The swallowing reflex evoked by the repetitive electrical stimulation of the superior laryngeal nerve in rats was recorded before and after the administration of the cannabinoid receptor agonist, WIN 55-212-2 (WIN, with or without CB1 or CB2 antagonist. The onset latency of the first swallow and the time intervals between swallows were analyzed. The onset latency and the intervals between swallows were shorter after the intravenous administration of WIN, and the strength of effect of WIN was dose-dependent. Although the intravenous administration of CB1 antagonist prior to intravenous administration of WIN blocked the effect of WIN, the administration of CB2 antagonist did not block the effect of WIN. The microinjection of the CB1 receptor antagonist directly into the nucleus tractus solitarius (NTS prior to intravenous administration of WIN also blocked the effect of WIN. Immunofluorescence histochemistry was conducted to assess the co-localization of CB1 receptor immunoreactivity to glutamic acid decarboxylase 67 (GAD67 or glutamate in the NTS. CB1 receptor was co-localized more with GAD67 than glutamate in the NTS. These findings suggest that cannabinoids facilitate the swallowing reflex via CB1 receptors. Cannabinoids may attenuate the tonic inhibitory effect of GABA (gamma-aminobuteric acid neurons in the central pattern generator for swallowing.

Violent online games exposure and cyberbullying/victimization among adolescents.

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Lam, Lawrence T; Cheng, Zaohuo; Liu, Xinmin

2013-03-01

This population-based cross-sectional survey examined the association between exposure to violent online games and cyberbullying and victimization in adolescents recruited from two large cities utilizing a stratified two-stage random cluster sampling technique. Cyberbullying and victimization were assessed by the E-victimization and E-bullying scales validated in a previous study. Exposure to violent online games was measured by self-nomination of the degree of violent content in the games played. Results indicated that the majority (74.3 percent) of respondents did not experience any cyberbullying or victimization in the last 7 days before the survey, 14.4 percent reported to be victimized via cyberspace, 2.9 percent admitted that they had bullied others, and 8.4 percent reported to be both perpetrators- and- victims. One hundred and eighty seven (15.3 percent) considered games they were playing were of moderate to severe violence. Students who had been involved in cyberbullying as well as being victimized were two times as likely to have been exposed to violent online games, and nearly four times as likely for those involved in bullying others. Exposure to violent online games was associated with being a perpetrator as well as a perpetrator-and-victim of cyberbullying. Parents and clinicians need to be aware of the potential harm of these exposures. The policy implications of results were also discussed.

BIASED AGONISM OF THREE DIFFERENT CANNABINOID RECEPTOR AGONISTS IN MOUSE BRAIN CORTEX

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Rebeca Diez-Alarcia

2016-11-01

Full Text Available Cannabinoid receptors are able to couple to different families of G-proteins when activated by an agonist drug. It has been suggested that different intracellular responses may be activated depending on the ligand. The goal of the present study was to characterize the pattern of G protein subunit stimulation triggered by three different cannabinoid ligands, THC, WIN55212-2 and ACEA in mouse brain cortex.Stimulation of the [35S]GTPS binding coupled to specific immunoprecipitation with antibodies against different subtypes of G proteins (Gαi1, Gαi2, Gαi3, Gαo, Gαz, Gαs, Gαq/11, and Gα12/13, in the presence of Δ9-THC, WIN55212-2 and ACEA (submaximal concentration 10 µM was determined by Scintillation Proximity Assay (SPA technique in mouse cortex of wild type, CB1 knock-out, CB2 knock-out and CB1/CB2 double knock-out mice. Results show that, in mouse brain cortex, cannabinoid agonists are able to significantly stimulate not only the classical inhibitory Gαi/o subunits but also other G subunits like Gαz, Gαq/11, and Gα12/13. Moreover, the specific pattern of G protein subunit activation is different depending on the ligand. In conclusion, our results demonstrate that, in mice brain native tissue, different exogenous cannabinoid ligands are able to selectively activate different inhibitory and non-inhibitory Gα protein subtypes, through the activation of CB1 and/or CB2 receptors. Results of the present study may help to understand the specific molecular pathways involved in the pharmacological effects of cannabinoid-derived drugs.

Independent and joint effects of prenatal maternal smoking and maternal exposure to second-hand smoke on the development of adolescent obesity: a longitudinal study.

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Wang, Liang; Mamudu, Hadii M; Alamian, Arsham; Anderson, James L; Brooks, Billy

2014-11-01

To examine associations of prenatal maternal smoking and second-hand smoke (SHS) exposure with the development of adolescent obesity. Longitudinal data (1991-2007) from National Institute of Child Health and Human Development Study of Early Child Care and Youth Development involving mothers that smoked and or exposed to SHS during the year before birth were analysed. Adolescent obesity in ages 12.0-15.9 years was defined as a BMI ≥ 95th percentile. Generalised estimating equations (GEE) were used for the analyses. Obesity was more prevalent among adolescents whose mothers smoked or had SHS exposure than those that did not smoke or exposed to SHS. After adjusting for maternal and child factors, GEE models showed that odds of adolescent obesity increased with prenatal maternal smoking (OR = 1.57, 95% CI = 1.03-2.39) and SHS exposure (OR = 1.53, 95% CI = 1.04-2.27). The odds for obesity increased more than two times among adolescents exposed to both maternal smoking and SHS (OR = 2.10, 95% CI = 1.24, 3.56) compared with those without exposure. Additionally, not breastfeeding, maternal obesity, and longer screen viewing hours per day were associated with increased odds of obesity. There is possibly a long-term joint effect of prenatal maternal smoke (smoking and SHS) exposure on obesity among adolescent offspring, and the effect is independent of birthweight. These findings suggest that adolescent obesity could possibly be curtailed with the development and promotion of smoking cessation programmes for families during the year before birth. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Analysis of 62 synthetic cannabinoids by gas chromatography-mass spectrometry with photoionization.

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Akutsu, Mamoru; Sugie, Ken-Ichi; Saito, Koichi

2017-01-01

Gas chromatography-mass spectrometry (GC-MS) in electron ionization (EI) mode is one of the most commonly used techniques for analysis of synthetic cannabinoids, because the GC-EI-MS spectra contain characteristic fragment ions for identification of a compound; however, the information on its molecular ions is frequently lacking. To obtain such molecular ion information, GC-MS in chemical ionization (CI) mode is frequently used. However, GC-CI-MS requires a relatively tedious process using reagent gas such as methane or isobutane. In this study, we show that GC-MS in photoionization (PI) mode provided molecular ions in all spectra of 62 synthetic cannabinoids, and 35 of the 62 compounds showed only the molecular radical cations. Except for the 35 compounds, the PI spectra showed very simple patterns with the molecular peak plus only a few fragment peak(s). An advantage is that the ion source for GC-PI-MS can easily be used for GC-EI-MS as well. Therefore, GC-EI/PI-MS will be a useful tool for the identification of synthetic cannabinoids contained in a dubious product. To the best of our knowledge, this is the first report to use GC-PI-MS for analysis of synthetic cannabinoids.

Cannabinoids and centrak neuropathic pain. A review (Cannabinoidi e dolore neuropatico centrale. Una rassegna

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Francesco Crestani

2014-03-01

Full Text Available Only recently, the medical community highlighted the pharmacological scientific bases of the effects of Cannabis. The most important active principle, Delta-9-tetrahydrocannabinol was identified in the second half of the last century, and receptors were subsequently identified and endogenous ligands, called endocannabinoids, were characterized. The effectiveness of the cannabinoids in the treatment of nausea and vomit due to anti-neoplastic chemotherapy and in the wasting-syndrome during AIDS is recognized. Moreover, the cannabinoids have shown analgesic properties, particularly interesting with regard to the central neuropathic pain. This article will review the current knowledge and will give practical guidance on how to proceed in prescribing cannabinoids.

Signal Peptide and Denaturing Temperature are Critical Factors for Efficient Mammalian Expression and Immunoblotting of Cannabinoid Receptors*

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WANG, Chenyun; WANG, Yingying; WANG, Miao; CHEN, Jiankui; YU, Nong; SONG, Shiping; KAMINSKI, Norbert E.; ZHANG, Wei

2013-01-01

Summary Many researchers employed mammalian expression system to artificially express cannabinoid receptors, but immunoblot data that directly prove efficient protein expression can hardly be seen in related research reports. In present study, we demonstrated cannabinoid receptor protein was not able to be properly expressed with routine mammalian expression system. This inefficient expression was rescued by endowing an exogenous signal peptide ahead of cannabinoid receptor peptide. In addition, the artificially synthesized cannabinoid receptor was found to aggregate under routine sample denaturing temperatures (i.e., ≥95°C), forming a large molecular weight band when analyzed by immunoblotting. Only denaturing temperatures ≤75°C yielded a clear band at the predicted molecular weight. Collectively, we showed that efficient mammalian expression of cannabinoid receptors need a signal peptide sequence, and described the requirement for a low sample denaturing temperature in immunoblot analysis. These findings provide very useful information for efficient mammalian expression and immunoblotting of membrane receptors. PMID:22528237

Safety and Toxicology of Cannabinoids

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Sachs, Jane; McGlade, Erin; Yurgelun-Todd, Deborah

2015-01-01

There is extensive research on the safety, toxicology, potency, and therapeutic potential of cannabis. However, uncertainty remains facilitating continued debate on medical and recreational cannabis policies at the state and federal levels. This review will include a brief description of cannabinoids and the endocannabinoid system; a summary of the acute and long-term effects of cannabis; and a discussion of the therapeutic potential of cannabis. The conclusions about safety and efficacy will...

LiCABEDS II. Modeling of ligand selectivity for G-protein-coupled cannabinoid receptors.

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Ma, Chao; Wang, Lirong; Yang, Peng; Myint, Kyaw Z; Xie, Xiang-Qun

2013-01-28

The cannabinoid receptor subtype 2 (CB2) is a promising therapeutic target for blood cancer, pain relief, osteoporosis, and immune system disease. The recent withdrawal of Rimonabant, which targets another closely related cannabinoid receptor (CB1), accentuates the importance of selectivity for the development of CB2 ligands in order to minimize their effects on the CB1 receptor. In our previous study, LiCABEDS (Ligand Classifier of Adaptively Boosting Ensemble Decision Stumps) was reported as a generic ligand classification algorithm for the prediction of categorical molecular properties. Here, we report extension of the application of LiCABEDS to the modeling of cannabinoid ligand selectivity with molecular fingerprints as descriptors. The performance of LiCABEDS was systematically compared with another popular classification algorithm, support vector machine (SVM), according to prediction precision and recall rate. In addition, the examination of LiCABEDS models revealed the difference in structure diversity of CB1 and CB2 selective ligands. The structure determination from data mining could be useful for the design of novel cannabinoid lead compounds. More importantly, the potential of LiCABEDS was demonstrated through successful identification of newly synthesized CB2 selective compounds.