ArticleLiterature Review

A review of the published literature into cannabis withdrawal symptoms in human users

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Abstract

Recent experimental papers have been published suggesting the appearance of withdrawal symptoms upon the cessation of cannabis use in human users and proposing the introduction of a diagnostic category for such symptoms. Research also continues to be published into the physiological effects of cannabis on animals via self-administration paradigms and the use of cannabinoid antagonists. Animal research does not provide a clear picture of a consistent withdrawal effect. The literature on withdrawal symptoms appearing in human users following the cessation of cannabis is investigated in this paper to clarify this issue further and enhance the scientific and lay debate on the status of the drug. Methodological weaknesses in the literature are highlighted. These include variable levels of drug-dose administered in laboratory conditions, lack of controlled studies and the absence of definitions of the withdrawal syndrome sought. It is suggested that the studies conducted to date do not provide a strong evidence base for the drawing of any conclusions as to the existence of a cannabis withdrawal syndrome in human users, or as to the cause of symptoms reported by those abstaining from the drug. On the basis of current research cannabis cannot be said to provide as clear a withdrawal pattern as other drugs of abuse, such as opiates. However, cannabis also highlights the need for a further defining of withdrawal, in particular the position that rebound effects occupy in this phenomenon. It is concluded that more controlled research might uncover a diagnosable withdrawal syndrome in human users and that there may be a precedent for the introduction of a cannabis withdrawal syndrome before the exact root of it is known.

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... Whereas there has been little controversy about the existence and pre- valence of cannabis abuse, and harmful use, respectively (according to ICD-10; Dilling, Mombour & Schmidt, 1991), there has been a lively debate about the existence and clinical relevance of a cannabis dependence syndrome. In particular, the development of a physiological dependence with tolerance and withdrawal has been controversially discussed (Farrell, 1999;Smith, 2002;WHO, 1997). Recently, a great body of literature including animal studies and human experimental, clinical, and epidemiological studies has provided evidence for cannabis dependence, at least in terms of DSM-IV diagnostic criteria (e. g. ...
... The studies show several major methodological weaknesses: a) small sample sizes (Budney et al., 2000;Sinha et al., 2003), b) soft inclusion criteria concerning cannabis use and related problems (Stephens et al., 1994;, c) a potential selection bias due to recruiting and monetary deposit (Stephens et al., 1994;2002), d) variance in the experience of therapists and no randomization across treatment conditions (Stephens et al., 2000;Copeland et al., 2001), e) a complete or partial lack of urinary drug screenings to confirm self-report data (Stephens, et al., 1994;2002), and f) the lack of follow-up investigations (Budney et al., 2001). g) Despite high rates of comorbidity among those with cannabis use disorders, cannabis users with comorbid problems often were restrictively excluded or mental disorders were not considered in treatment (e. g. ...
... The studies show several major methodological weaknesses: a) small sample sizes (Budney et al., 2000;Sinha et al., 2003), b) soft inclusion criteria concerning cannabis use and related problems (Stephens et al., 1994;, c) a potential selection bias due to recruiting and monetary deposit (Stephens et al., 1994;2002), d) variance in the experience of therapists and no randomization across treatment conditions (Stephens et al., 2000;Copeland et al., 2001), e) a complete or partial lack of urinary drug screenings to confirm self-report data (Stephens, et al., 1994;2002), and f) the lack of follow-up investigations (Budney et al., 2001). g) Despite high rates of comorbidity among those with cannabis use disorders, cannabis users with comorbid problems often were restrictively excluded or mental disorders were not considered in treatment (e. g. ...
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Aim: To review the literature on the psychotherapeutic treatment of cannabis abuse and dependence. Results: Since the mid 1990s, efficacy studies with specific focus on the treatment for cannabis disorders have been carried out within the US and Australia. Methods, results, and limitations of eight identified studies are described. Motivational enhancement therapy, cognitive-behavioral therapy, contingency management, and various types of family therapy for younger problematic cannabis users have been found to be effective treatment components. Conclusion: Overall, these studies represent a growing evidence for the need and potential efficacy of treatments tailored specifically to cannabis dependent and problematic users. However, there is still a considerable deficiency of research on specific psychological interventions in this field. Particularly in Europe, intervention studies on the treatment for cannabis disorders and the development of treatment programs suitable for routine use in substance use services are completely lacking.
... The symptoms and time course of cannabis withdrawal are well documented and described in earlier literature reviews [5,6,[22][23][24]. Here, we provide a brief overview. ...
... Since the publication of initial formative reviews [5,6,22,24], use of high temporal resolution assessment measures (i.e., ecological momentary assessment [EMA]) have recently been incorporated into the study of cannabis withdrawal [36,37] and add to the literature by examining immediate antecedents to drug use in the natural environment in contrast to controlled research settings. In one study, Buckner et al. utilized EMA to explore factors close in proximity to cannabis use among participants initiating an unassisted quit attempt [36]. ...
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Purpose of review: This report provides an updated overview of pre-clinical and clinical research on the etiology and biological substrates of the cannabis withdrawal syndrome. Recent findings: Long-term cannabis use is associated with downregulation of type-1 cannabinoid receptors (CB1). Reduced CB1 receptor density is related to increased withdrawal during early abstinence, and the reduction in CB1 receptor density reverses with extended abstinence. Females have been shown to have increased rate and severity of a subset of cannabis withdrawal symptoms compared with men. Summary: Recent studies have extended knowledge of the biological processes and individual difference variables that influence cannabis withdrawal. However, caveats include small sample sizes in clinical studies, participant samples that are predominantly male, and limited examinations of endocannabinoids, enzymes that degrade endocannabinoids, negative allosteric modulators, and other neurobiological systems that may directly impact cannabis withdrawal symptom expression.
... Those in the severe symptom class had elevated probabilities of symptom endorsement among all withdrawal symptoms except sweating. Consistent with these findings, prior work has noted that sweating is a relatively uncommon symptom of cannabis withdrawal [23,46]. Aligned with prior work finding sleep problems to be one of the most frequently endorsed cannabis withdrawal symptoms [20,27,46], this symptom had a relatively high probability of endorsement across the latent classes. ...
... Consistent with these findings, prior work has noted that sweating is a relatively uncommon symptom of cannabis withdrawal [23,46]. Aligned with prior work finding sleep problems to be one of the most frequently endorsed cannabis withdrawal symptoms [20,27,46], this symptom had a relatively high probability of endorsement across the latent classes. ...
Article
Background and aims: Research from cohorts of individuals with recreational cannabis use indicates that cannabis withdrawal symptoms are reported by more than 40% of those using regularly. Withdrawal symptoms are not well understood in those who use cannabis for medical purposes. Therefore, we prospectively examined the stability of withdrawal symptoms in individuals using cannabis to manage chronic pain. Design, setting, participants: Using latent class analysis (LCA) we examined baseline cannabis withdrawal to derive symptom profiles. Then, using latent transition analysis (LTA) we examined the longitudinal course of withdrawal symptoms across the time points. Exploratory analyses examined demographic and clinical characteristics predictive of withdrawal class and transitioning to more or fewer withdrawal symptoms over time. A cohort of 527 adults with chronic pain seeking medical cannabis certification or re-certification was recruited between February 2014 and June 2015. Participants were recruited from medical cannabis clinic waiting rooms in Michigan, USA. Participants were predominantly white (82%) and 49% identified as male, with an average age of 45.6 years (standard deviation = 12.8). Measurements: Baseline, 12-month and 24-month assessments of withdrawal symptoms using the Marijuana Withdrawal Checklist-revised. Findings: A three-class LCA model including a mild (41%), moderate (34%) and severe (25%) symptom class parsimoniously represented withdrawal symptoms experienced by people using medical cannabis. Stability of withdrawal symptoms using a three-class LTA at 12 and 24 months ranged from 0.58 to 0.87, with the most stability in the mild withdrawal class. Younger age predicted greater severity and worsening of withdrawal over time. Conclusions: Adults with chronic pain seeking medical cannabis certification or re-certification appear to experience mild to severe withdrawal symptoms. Withdrawal symptoms tend to be stable over a 2-year period, but younger age is predictive of worse symptoms and of an escalating withdrawal trajectory.
... This review cited (1) the lack of controlled studies, (2) absence of definitions of withdrawal, (3) poor ecological validity, (4) failure to document severity of symptoms, and (5) inconsistent onset and offset of symptoms as the lacunae in research. [52] There are some human experimental and animal researches on this area after the review by Smith [52] has been published. Three rigorous outpatient studies have been reported. ...
... This review cited (1) the lack of controlled studies, (2) absence of definitions of withdrawal, (3) poor ecological validity, (4) failure to document severity of symptoms, and (5) inconsistent onset and offset of symptoms as the lacunae in research. [52] There are some human experimental and animal researches on this area after the review by Smith [52] has been published. Three rigorous outpatient studies have been reported. ...
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Since its inception cannabis has been observed to be associated with various psycho-pathology. In this paper, the authors have reviewed the advancement made in this area over the last decade. The association between cannabis and schizophrenia has been researched more intensively. The controversy regarding the reliability, clinical utility, and the existence of a cannabis withdrawal syndrome has also been settled. Recent studies also buttressed the possibility of acute and chronic effect of cannabis on various cognitive functions. There has been a plethora of research regarding the treatment for cannabis use disorders. But the new and most interesting area of research is concentrated on the endocannabinoid system and its contribution in various psychiatric disorders.
... Substantial individual differences exist in terms of the nature and severity of withdrawal symptoms. Smith (2002) conducted a literature review and concluded that, "there is not a strong evidence base for the drawing of any conclusions as to the existence of a cannabis withdrawal syndrome in human users" (Smith, 2002;p. 621). ...
... Substantial individual differences exist in terms of the nature and severity of withdrawal symptoms. Smith (2002) conducted a literature review and concluded that, "there is not a strong evidence base for the drawing of any conclusions as to the existence of a cannabis withdrawal syndrome in human users" (Smith, 2002;p. 621). ...
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I review the scientific evidence between cannabis use and traffic collisions and the validity of biological drug tests (i.e. blood, oral fluids and urine) to detect cannabis impairment.
... 2016). A number studies, including self-report and laboratory studies, have consistently demonstrated that marijuana withdrawal may lead to irritability and aggression (Budney, Moore, Vandrey, & Hughes, 2003;Chung, Martin, Cornelius, & Clark, 2008;Haney, Ward, Comer, Foltin, & Fischman, 1999;Lee et al., 2014;Moore & Stuart, 2005;Moore et al., 2008;N. T. Smith, 2002;Tomlinson et al., 2016). One of the most comprehensive early studies on marijuana withdrawal demonstrated that self-reported aggression increased significantly on Day 4 of marijuana abstinence and reached its highest point on Day 6 compared with aggression levels of regular marijuana users (Budney et al., 2003). Similar results were foun ...
... & White, 2004). However, early studies did not examine the effects of marijuana withdrawal on violence perpetration. More recent studies have consistently demonstrated that marijuana withdrawal may lead to irritability and aggression (Budney et al., 2003;Chung et al., 2008;Haney et al., 1999;Lee et al., 2014;Moore & Stuart, 2005;Moore et al., 2008;N. T. Smith, 2002;Tomlinson et al., 2016). Theoretically, individuals could be using alcohol to self-medicate the withdrawal symptoms of marijuana, which could increase the likelihood of aggression and violence even further. Additional evidence in support of this association was found by Mercado-Crespo and Mbah (2013): They examined marijuana and alcohol ...
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Early research has revealed that patterns of aggression and antisocial behavior are present among polydrug users. Often missing from this discourse is the examination of whether polydrug users are quantitatively different from monodrug users in their use of aggression. Theoretical perspectives are often centered on the psychopharmacological effects of substance use on behavior. Consideration of possible poly- versus monodrug use differences and their impact on aggression has not been investigated. Data from this study were derived from a sample of Midwestern university students (N = 793). The relationship between violence, aggression, and concurrent polydrug use in the last year is assessed with a series of multivariate ordinary least squares (OLS) regression models. Results demonstrate that higher incidents of physical and verbal aggression are reported among polydrug users compared to monodrug users and abstainers. When analyses were broken down by polydrug users (those who engaged in alcohol/marijuana and alcohol/NMUPD [nonmedical use of prescription drugs] stimulants), polydrug users reported higher levels of physical aggression compared to monodrug users. Similarly, monodrug users reported higher levels of physical aggression compared to nonusers. This research extends our understanding of aggression among users from two different subcategories: polydrug users in comparison to those who only engage in one form of substance use. Scholars and practitioners who work with violent offenders should consider patterns of drug use behavior when addressing substance use–related aggression.
... Increased irritability is prevalent during cannabis abstinence in humans [24,96]. We were surprised to find that relatively few irritability-like behaviors were altered in our bottle brush test assay. ...
Article
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Withdrawal symptoms are observed upon cessation of cannabis use in humans. Although animal studies have examined withdrawal symptoms following exposure to delta-9-tetrahydrocannabinol (THC), difficulties in obtaining objective measures of spontaneous withdrawal using paradigms that mimic cessation of use in humans have slowed research. The neuromodulator dopamine (DA) is affected by chronic THC treatment and plays a role in many behaviors related to human THC withdrawal symptoms. These symptoms include sleep disturbances that often drive relapse, and emotional behaviors like irritability and anhedonia. We examined THC withdrawal-induced changes in striatal DA release and the extent to which sleep disruption and behavioral maladaptation manifest during abstinence in a mouse model of chronic THC exposure. Using a THC treatment regimen known to produce tolerance, we measured electrically elicited DA release in acute brain slices from different striatal subregions during early and late THC abstinence. Long-term polysomnographic recordings from mice were used to assess vigilance state and sleep architecture before, during, and after THC treatment. We additionally assessed how behaviors that model human withdrawal symptoms are altered by chronic THC treatment in early and late abstinence. We detected altered striatal DA release, sleep disturbances that mimic clinical observations, and behavioral maladaptation in mice following tolerance to THC. Altered striatal DA release, sleep, and affect-related behaviors associated with spontaneous THC abstinence were more consistently observed in male mice. These findings provide a foundation for preclinical study of directly translatable non-precipitated THC withdrawal symptoms and the neural mechanisms that affect them.
... Typical patterns of cannabis use appear to be non-optimal conditions to get an obvious withdrawal syndrome, though less obvious symptoms may be relevant when treating cannabis-dependent patients. Smith (2002) points out that these symptoms are not specific for cannabis (they can be observed with tobacco) and vary with the psychological profile of the individual. Coffey et al. (2002), argue that tolerance might be useless in clinical assessment of cannabis dependence. ...
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Accessible en ligne sur le site EMCDDA : http://www.emcdda.europa.eu/publications/monographs/cannabis
... Notably, the cannabis-specific substance factor was moderately defined by the two withdrawal symptoms. While it is has been previously shown that withdrawal symptoms are commonly reported among cannabis users (7), it has been suggested that there is no evidence to support a clear cannabis withdrawal syndrome (34). In recent years, however, there has been increasing evidence in both the human and animal literature of physical and psychological effects associated with cannabis withdrawal (26). ...
... The existence or severity of a cannabis withdrawal syndrome remains under debate [ 151,152 ] . In contrast to reported withdrawal sequelae in recreational users [ 153 ] , 24 subjects with MS who volunteered to discontinue Sativex after a year or more suffered no withdrawal symptoms meeting Budney criteria. ...
Chapter
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It is a curious fact that we owe a great deal of our insight into pharmacological treatment of pain to the plant world. Willow bark from Salix spp. led to development of aspirin and eventual elucidation of the analgesic effects of prostaglandins and their role in inflammation. The opium poppy (Papaver somniferum) provided the prototypic narcotic analgesic morphine, the first alkaloid discovered, and stimulated the much later discovery of the endorphin and enkephalin systems. Similarly, the pharmacological properties of cannabis (Cannabis sativa) prompted the isolation of Δ9-tetrahydrocannabinol (THC), the major psychoactive ingredient in cannabis, in 1964. It is this breakthrough that subsequently prompted the more recent discovery of the body’s own cannabis-like system, the endocannabinoid system (ECS), which modulates pain under physiological conditions.
... Abbildung 12: typische Entzugssymptome Diese Symptome sind selten schwer ausgeprägt(Wiesbeck et al 1996, Budney et al 1999, Smith 2002, so dass sie in der Regel keine pharmakologische Behandlung benötigen. Sieprofitieren zunächst von den allgemeinen physikalischen und pflegerischen Maßnahmen einer qualifizierten Entzugssyndrombehandlung. ...
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... Synthetic cannabinoids' stronger potency (Atwood et al., 2010) may explain the apparent discrepancy in terms of hangover symptoms. (Smith, 2002) showed that the overall research is highly ambiguous, which is believed to reflect the influence of non-substance-specific factors like personality. ...
Article
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Background Synthetic cannabinoids in smoking mixtures (such as Spice) or as raw powder are sold for recreational use as an alternative to herbal cannabis (hashish and marijuana). Although clinical case studies have documented an array of side effects, there is also information available at Internet based drug discussion forums. Aim Our study investigates experiences of side effects from use of synthetic cannabinoids, as described and anonymously shared on Swedish online discussion forums. Methods A systematic search yielded 254 unique and publicly available self-reports from the Swedish forum flashback.org. These texts were analysed thematically, which resulted in 32 sub-themes, which were combined into three overarching themes. Results & Conclusion The experiences of negative side effects were described as (1) Adverse reactions during acute intoxication; (2) Hangover the day after intoxication; (3) Dependency and withdrawal after long-term use. The first theme was characterized by an array of fierce and unpredictable side effects as tachycardia, anxiety, fear and nausea. The acute intoxication reactions were congruent with the side effects published in clinical case studies. The day after intoxication included residual effects of dullness, apathy, nausea and headache. Long-term use resulted in dependency and experiences of being emotionally numb and disconnected. Furthermore, withdrawal was described as sweating, shaking, loss of appetite and insomnia. Both the hangover and the long-term effects have previously been given little scientific attention and need to be investigated further. Drug related Internet discussion forums constitute an overlooked source of information which can aid in the identification of previously unknown risks and effects.
... The existence or severity of a cannabis withdrawal syndrome remains under debate (Smith, 2002;Budney et al., 2004). In contrast to reported withdrawal sequelae in recreational users (Solowij et al., 2002), 24 subjects with MS who volunteered to discontinue nabiximols after a year or more suffered no withdrawal symptoms meeting Budney criteria. ...
Article
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This overview covers a wide range of cannabis topics, initially examining issues in dispensaries and self-administration, plus regulatory requirements for production of cannabis-based medicines, particularly the Food and Drug Administration “Botanical Guidance.” The remainder pertains to various cannabis controversies that certainly require closer examination if the scientific, consumer, and governmental stakeholders are ever to reach consensus on safety issues, specifically: whether botanical cannabis displays herbal synergy of its components, pharmacokinetics of cannabis and dose titration, whether cannabis medicines produce cyclo-oxygenase inhibition, cannabis-drug interactions, and cytochrome P450 issues, whether cannabis randomized clinical trials are properly blinded, combatting the placebo effect in those trials via new approaches, the drug abuse liability (DAL) of cannabis-based medicines and their regulatory scheduling, their effects on cognitive function and psychiatric sequelae, immunological effects, cannabis and driving safety, youth usage, issues related to cannabis smoking and vaporization, cannabis concentrates and vape-pens, and laboratory analysis for contamination with bacteria and heavy metals. Finally, the issue of pesticide usage on cannabis crops is addressed. New and disturbing data on pesticide residues in legal cannabis products in Washington State are presented with the observation of an 84.6% contamination rate including potentially neurotoxic and carcinogenic agents. With ongoing developments in legalization of cannabis in medical and recreational settings, numerous scientific, safety, and public health issues remain.
... Debate continues as to the existence of a clinically signifi cant cannabis withdrawal syndrome with proponents (Budney et al 2004), and questioners (Smith 2002). While withdrawal effects have been reported in recreational cannabis smokers (Solowij et al 2002), 24 volunteers with MS who abruptly stopped Sativex after more than a year of continuous usage displayed no withdrawal symptoms meeting Budney's criteria. ...
Article
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This article reviews recent research on cannabinoid analgesia via the endocannabinoid system and non-receptor mechanisms, as well as randomized clinical trials employing canna- binoids in pain treatment. Tetrahydrocannabinol (THC, Marinol ® ) and nabilone (Cesamet ® ) are currently approved in the United States and other countries, but not for pain indications. Other synthetic cannabinoids, such as ajulemic acid, are in development. Crude herbal cannabis remains illegal in most jurisdictions but is also under investigation. Sativex ® , a cannabis derived oromucosal spray containing equal proportions of THC (partial CB 1 receptor agonist ) and can- nabidiol (CBD, a non-euphoriant, anti-infl ammatory analgesic with CB 1 receptor antagonist and endocannabinoid modulating effects) was approved in Canada in 2005 for treatment of central neuropathic pain in multiple sclerosis, and in 2007 for intractable cancer pain. Numer- ous randomized clinical trials have demonstrated safety and effi cacy for Sativex in central and peripheral neuropathic pain, rheumatoid arthritis and cancer pain. An Investigational New Drug application to conduct advanced clinical trials for cancer pain was approved by the US FDA in January 2006. Cannabinoid analgesics have generally been well tolerated in clinical trials with acceptable adverse event profi les. Their adjunctive addition to the pharmacological armamentarium for treatment of pain shows great promise.
... Relatedly, marijuana use increases heart rate, and the physiological arousal associated with an increased heart rate may increase the likelihood of aggressive behavior (Moore and Stuart, 2005). A fourth explanation relates to symptoms of withdrawal; which may contribute to irritability and, therefore, increase the risk for conflict and aggression (Moore and Stuart, 2005;Smith et al., 2013;Smith, 2002;Testa and Brown, 2015). ...
Article
Background: As restrictions on marijuana are loosened, there is concern of a coming increase in marijuana use among adolescents and emerging adults, which could be coupled with commensurate increases in behavioral problems associated with use, such as physical dating violence (PDV). To summarize what is known about the association between marijuana use and PDV victimization and perpetration among 11-21year olds, we conducted a systematic review and meta-analysis of the relevant literature published between 2003 and 2015. Methods: Candidate articles were identified with a systematic search, and we used inclusion and exclusion criteria to review titles, abstracts, and the full text of studies for consideration. There were 13 articles examining marijuana in association with PDV; five addressed victimization and 11 addressed perpetration. Results: Findings suggest that marijuana use is associated with a 54% increase in the odds PDV victimization, and a 45% increase in the odds of perpetration. Conclusions: Findings suggest that dating violence is a correlate of marijuana use, and that association is strongest among adolescents (vs. emerging adults) and girls (vs. boys). Therefore, it should be routinely included as a core data item in marijuana surveillance systems, so as to allow for behavioral monitoring.
... Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-V; American Psychiatric Association [APA], 2013) is the first to include a diagnostic code for cannabis withdrawal (criteria for DSM-5 cannabis withdrawal appear in Table 1). This decision was based on findings that cannabis withdrawal was a distinct symptom of cannabis dependence (independent of tolerance) and a source of rapid relapse (use of cannabis to relieve withdrawal symptoms) in laboratory and outpatient studies (Agrawal, Pergadia, & Lynskey, 2008;Budney & Hughes, 2006;Copersino et al., 2006;Cornelius, Chung, Martin, Wood, & Clark, 2008;Kouri & Pope, 2000;Levin et al., 2010;Smith, 2002). Currently, the DSM-5 cites that a person would need to report experiencing three or more symptoms (including psychological, behavioral, and physiological) 1 week after cessation of heavy use to be diagnosed with cannabis withdrawal (Gorelick et al., 2012). ...
Article
Background: Very little prospective research investigates how cannabis withdrawal is associated with treatment outcomes, and this work has not used the DSM-5 thresholds for cannabis withdrawal. Methods: The sample included 110 Emerging Adults entering outpatient substance use treatment who were heavy cannabis users with no other drug use and limited alcohol use. We used survival analyses to predict days to first use of cannabis and logistic regression to predict whether participants were abstinent and living in the community at three months. Results: Those meeting criteria for cannabis withdrawal were more likely to return to use sooner than those not meeting criteria for cannabis withdrawal. However, the presence of cannabis withdrawal was not a significant predictor of three month abstinence. Conclusions: Emerging Adults with DSM-5 cannabis withdrawal may have difficulty initiating abstinence in the days following their intake assessment, implying the need for strategies to mitigate their more rapid return to cannabis use.
... Recreational cannabis abuse and dependence remain hot-button issues, with recent description of the elements of a cannabis withdrawal syndrome (123), while other authorities questioned its validity (124). The addictive potential of a drug is determined by its degree of intoxication, reinforcement, tolerance, withdrawal, and dependency. ...
... [121][122][123] Like opioids, chronic cannabis exposure induces the development of tolerance, physical dependence, and withdrawal symptoms during abstinence. Patients commonly report that cannabis withdrawal symptoms, most commonly anger, aggression, irritability, anxiety, decreased appetite, weight loss, restlessness, and sleeping difficulties, [124][125][126][127][128][129] are similar to those produced by nicotine withdrawal. 129 Comparatively, the magnitude and severity of cannabis withdrawal are significantly and substantially more benign than opioid withdrawal. ...
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Introduction: The opioid epidemic has become an immense problem in North America, and despite decades of research on the most effective means to treat opioid use disorder (OUD), overdose deaths are at an all-time high, and relapse remains pervasive. Discussion: Although there are a number of FDA-approved opioid replacement therapies and maintenance medications to help ease the severity of opioid withdrawal symptoms and aid in relapse prevention, these medications are not risk free nor are they successful for all patients. Furthermore, there are legal and logistical bottlenecks to obtaining traditional opioid replacement therapies such as methadone or buprenorphine, and the demand for these services far outweighs the supply and access. To fill the gap between efficacious OUD treatments and the widespread prevalence of misuse, relapse, and overdose, the development of novel, alternative, or adjunct OUD treatment therapies is highly warranted. In this article, we review emerging evidence that suggests that cannabis may play a role in ameliorating the impact of OUD. Herein, we highlight knowledge gaps and discuss cannabis' potential to prevent opioid misuse (as an analgesic alternative), alleviate opioid withdrawal symptoms, and decrease the likelihood of relapse. Conclusion: The compelling nature of these data and the relative safety profile of cannabis warrant further exploration of cannabis as an adjunct or alternative treatment for OUD.
... For years, the proposed existence of a cannabis withdrawal syndrome was met with great skepticism, and one early review of the literature concluded that the combination of methodological limitations of published findings and lack of controlled research rendered the recognition of a cannabis withdrawal syndrome as being premature [75]. However, an extensive body of research has now clearly demonstrated that the cannabis withdrawal syndrome is valid, reliable, and pharmacologically specific and produces distress and impairment in important areas of functioning [12,14,42]. ...
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Cessation from daily cannabis use reliably elicits a valid withdrawal syndrome characterized by a constellation of behavioral, somatic, and mood symptoms. The onset of these symptoms closely follows cessation, mostly persists for 2–3 weeks, and can produce clinically significant distress that contributes to the maintenance of frequent cannabis use. Cannabis withdrawal develops as a result of neurobiological changes in the endogenous cannabinoid system that result from prolonged cannabis use and are pharmacologically specific to activity at the CB1 receptor. Individual differences in the expression of cannabis withdrawal are apparent, and several experiments have demonstrated robust sex differences in the frequency and severity of withdrawal. The presence of psychiatric comorbidity may complicate symptom intensity and time course. Cannabis withdrawal significantly influences treatment outcomes and is a prime target of continued efforts to develop effective pharmacological interventions for cannabis use disorder.
... Cannabis withdrawal symptoms were assessed with a list of 40 withdrawal symptoms based on published literature. [16][17][18][19] Each symptom was rated as present or absent; if present, intensity was rated on a 5-point Likert scale and any actions taken to relieve that symptom were assessed. Cannabis withdrawal syndrome was diagnosed by DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) criteria (3 symptoms from a list of 7; see Table 2), including only symptoms for which some action was taken to relieve, as a surrogate for the DSM-5 requirement that a symptom generate distress or disability. ...
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Background: Cannabis use is common among opioid-dependent individuals, but little is known about cannabis withdrawal in this population. Methods: Thirty inpatients (57% men) completed the Marijuana Quit Questionnaire (MJQQ) after completing acute heroin detoxification treatment in Saint Petersburg, Russia. The MJQQ collected data on motivations for quitting, withdrawal symptoms, and coping strategies used to help maintain abstinence during their most "serious" (self-defined) quit attempt made without formal treatment outside a controlled environment. Results: At the start of their quit attempt, 70% of participants smoked cannabis at least weekly (40% daily), averaging [SD] 2.73 [1.95] joints daily; 60% were heroin dependent. Subjects with heroin dependence were significantly older at the start of their quit attempt (22.9 [3.6] vs. 19.1 [2.9] years), were significantly less likely to report withdrawal irritability/anger/aggression (22% vs. 58%), restlessness (0% vs. 25%), or physical symptoms (6% vs. 33%), or to meet diagnostic criteria for DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) cannabis withdrawal syndrome (6% vs. 33%), and had shorter duration of abstinence (29.6 [28.7] vs 73.7 [44.1] months) than those without heroin dependence. Conclusion: Cannabis users with opioid dependence are less likely to experience cannabis withdrawal, suggesting that opiate use may prevent or mask the experience of cannabis withdrawal. RESULTS should be considered preliminary due to small convenience sample and retrospective data.
... Presumably, different routes lead from cocaine use and cannabis use to IPV perpetration [25]. For cocaine it is hypothesized that its psychopharmacological effects directly increase aggressive behavior (e.g., [28,29]), whereas for cannabis it is assumed that irritability as a result of withdrawal may lead to committing IPV [30]. To our knowledge, it has not been studied yet whether successful treatment of cannabis and cocaine use disorders in patients who are referred for substance use treatment and commit IPV, also reduces IPV perpetration. ...
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Research has shown that treatments that solely addressed intimate partner violence (IPV) perpetration were not very effective in reducing IPV, possibly due to neglecting individual differences between IPV perpetrators. A large proportion of IPV perpetrators is diagnosed with co-occurring substance use disorders and it has been demonstrated that successful treatment of alcohol dependence among alcohol dependent IPV perpetrators also led to less IPV. The current study investigated the relative effectiveness of Integrated treatment for Substance abuse and Partner violence (I-StoP) to cognitive behavioral treatment addressing substance use disorders including only one session addressing partner violence (CBT-SUD+) among patients in substance abuse treatment who repeatedly committed IPV. Substance use and IPV perpetration were primary outcome measures. Patients who entered substance abuse treatment were screened for IPV. Patients who disclosed at least 7 acts of physical IPV in the past year (N = 52) were randomly assigned to either I-StoP or CBT-SUD+. Patients in both conditions received 16 treatment sessions. Substance use and IPV perpetration were assessed at pretreatment, halfway treatment and posttreatment in blocks of 8 weeks. Both completers and intention-to-treat (ITT) analyses were performed. Patients (completers and ITT) in both conditions significantly improved regarding substance use and IPV perpetration at posttreatment compared with pretreatment. There were no differences in outcome between conditions. Completers in both conditions almost fully abstained from IPV in 8 weeks before the end of treatment. Both I-StoP and CBT-SUD+ were effective in reducing substance use and IPV perpetration among patients in substance abuse treatment who repeatedly committed IPV and self-disclosed IPV perpetration. Since it is more cost and time-effective to implement CBT-SUD+ than I-StoP, it is suggested to treat IPV perpetrators in substance abuse treatment with CBT-SUD+.
... The occurrence of cannabis withdrawal symptoms (CWS) or syndrome in response to cessation of regular cannabis use was contentious during the 1970s through the 1990s (Budney & Hughes, 2006;Rohr et al., 1989), despite reports of withdrawal symptoms as early as the 1940s (Bouquet, 1944;Fraser, 1949;Williams et al., 1946). These early reports were largely ignored, possibly because of contrasting findings in other studies (Gaskill, 1945;Leite & Carlini, 1974), and the relative mildness of the reported withdrawal symptoms when compared to other narcotic drugs (Smith, 2002). Likewise, it is possible that the withdrawal symptoms experienced by cannabis users in the early twentieth century and earlier may have been milder than later in the century and current times because of the much lower THC content, and thereby potency, of the cannabis being consumed earlier in the century (ElSohly et al., 2016;Hart, 1984;Turner, 1983). ...
Article
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Cannabis sativa is the most widely used illicit drug in the world. Its main psychoactive component is delta-9-tetrahydrocannabinol (THC), one of over 100 phytocannabinoid compounds produced by the cannabis plant. THC is the primary compound that drives cannabis abuse potential and is also used and prescribed medically for therapeutic qualities. Despite its therapeutic potential, a significant subpopulation of frequent cannabis or THC users will develop a drug use syndrome termed cannabis use disorder. Individuals suffering from cannabis use disorder exhibit many of the hallmarks of classical addictions including cravings, tolerance, and withdrawal symptoms. Currently there are no efficacious treatments for cannabis use disorder or withdrawal symptoms. This makes both clinical and preclinical research on the neurobiological mechanisms of these syndromes ever more pertinent. Indeed, basic research using animal models has provided valuable evidence of the neural molecular and cellular actions of cannabis that mediate its behavioral effects. One of the main components being central action on the cannabinoid type-one receptor and downstream intracellular signaling related to the endogenous cannabinoid system. Back-translational studies have provided insight linking preclinical basic and behavioral biology research to better understand symptoms observed at the clinical level. This narrative review aims to summarize major research elucidating the molecular, cellular, and behavioral manifestations of cannabis/THC use that play a role in cannabis use disorder and withdrawal.
... The findings from the six studies presented here should be viewed with caution, given that few of the many factors that can influence neuropsychological performance in cannabis users were controlled for. These factors include the potency of the cannabis (∆ 9 -THC concentrations), duration, amount, route and frequency of use, the timing of the assessment (Stage 1: Acute ⩽ 4 hours after use; Stage 2: During the withdrawal stage when symptoms like reduced concentration and irritability may be prominent 25,26 ; and Stage 3: Post-withdrawal, but with cannabinoids still present), and the presence of other drugs. In addition, the reliability of the findings needs bolstering, as five of the six studies come from the same research group. ...
Article
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Given data showing that cannabis (herbal drug from the Cannabis sativa plant) can impair cognition in healthy subjects, the possibility that it may also do so in people with multiple sclerosis (MS) should be cause for concern. Approximately 20% of people with MS inhale or ingest cannabis for a variety of symptoms, or as a lifestyle choice. In addition, pharmaceutically manufactured cannabis (in capsules or spray) is prescribed most often for pain and spasticity; however, there is a dearth of literature on the cognitive effects of cannabis. Furthermore, methodological limitations introduce a cautionary note when interpreting the data. The evidence, which must therefore be considered preliminary, suggests that smoked cannabis may further compromise information processing speed and memory, with magnetic resonance imaging (fMRI) demonstrating more inefficient patterns of cerebral activation during task performance. The findings related to pharmaceutically manufactured cannabis are equivocal. There is a pressing need for further research to inform clinical opinion, which at present reflects a combination of uncertainty and dogma.
Article
Basierend auf Patientenberichten, Ergebnissen aus Tiermodellen und In-vitro-Untersuchungen ergab sich eine Reihe von Hinweisen auf einen positiven Effekt von Cannabinoiden als symptomatische Therapie der Spastik und Schmerzen bei multipler Sklerose. Mit der so genannten CAMS-Studie wurde kürzlich die erste multizentrische, randomisierte, placebokontrollierte Phase-III-Studie über die Wirkung von Cannabinoiden bei Symptomen der MS publiziert. Im primären Studienendpunkt, der Veränderung objektiv messbarer Spastizität, die in der so genannten Ashworth-Skala ausgewertet wurde, wurde zwar kein signifikanter Behandlungseffekt der Cannabinoide festgestellt, bei den sekundären Endpunkten, den subjektiven Patientenberichten, wurden dagegen signifikante Effekte auf Spastizität und Schmerz dokumentiert. Ein Hauptproblem dieser Untersuchung war die einfache Entblindung der Patienten in der aktiven Behandlungsgruppe. Die Ergebnisse der CAMS-Studie werden im Kontext mit früheren Studien, dem möglichen Wirkmechanismus sowie dem Nebenwirkungsprofil diskutiert.
Article
Context: The role of a dynamic legal, medical, and social setting in affecting the perceived risk associated with smoking marijuana has not been well studied. We sought to determine whether there has been a change in the perceived risk associated with marijuana use over time. Methods: A cross-sectional study was conducted using the 2002-2012 National Survey on Drug Use and Health. Respondents were asked to classify the risk of smoking marijuana. Regression analysis and the Mann-Whitney U test were used to analyze the data. Results: A total of 614579 respondents were identified. Between 2002 and 2012, the percent of respondents who characterized regular marijuana use as being associated with "great risk" decreased from 51.3% to 40.3%, while the percent of respondents who characterized it as being associated with "no risk" increased from 5.7% to 11.7%. The percent of respondents who characterized occasional use as "great risk" decreased from 38.2% to 30.7%, while the percent of respondents who characterized it as "no risk" increased from 10% to 16.3%. There was a significant negative temporal trend in the perceived risk for both occasional and regular use of marijuana from 2002 to 2012 after controlling for age and gender (p < 0.001 for both). Increasing age was significantly associated with increased perceived risk for both occasional and regular marijuana use (p < 0.001). Males have a significantly lower perceived risk for regular marijuana use as compared with females (p < 0.001). Individuals who used marijuana during the preceding month reported a lower risk perception in both regular and occasional use. Conclusion: Between 2002 and 2012, there was a significant decrease in the perceived risk associated with occasional and regular marijuana use. Younger age, male gender, and past month use were also associated with decreased perceived risk.
Book
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Anais do "Simpósio Internacional: Por uma Agência Brasileira da Cannabis Medicinal?", evento realizado em maio de 2010 pelo Centro Brasileiro de Informações sobre Drogas Psicotrópicas (CEBRID), na Universidade Federal de São Paulo (UNIFESP).
Article
El cannabis es la droga ilícita que más se cultiva y consume en el mundo, pero subsisten lagunas importantes en nuestra comprensión de sus mercados mundiales. Por ejemplo, parece que se ha hecho más potente en los últimos años el cannabis llamado "sinsemilla" de primera calidad, producido con frecuencia en interiores en los países de consumo y que en algunas regiones va creciendo su cuota de mercado. Es posible que ello esté conduciendo a una mayor localización de los mercados del producto. Tal vez explique también el aumento a nivel internacional del número de consumidores sometidos a tratamiento. Sin embargo, la evaluación del alcance de esta tendencia y sus efectos se ve obstaculizada por la falta de normas internacionales sobre cuestiones como la terminología y por problemas sin resolver en el plano de la investigación. A fin de estimar con exactitud el alcance mundial de la producción se requieren más datos científicos sobre el rendimiento del cannabis. En el plano de la demanda se precisa más información sobre las dosis y los volúmenes de cannabis utilizados por los consumidores ocasionales y habituales. No se trata de una droga de tipo homogéneo: es preciso investigar las consecuencias de consumirla en diversos grados de potencia y distintas composiciones químicas. Aunque los problemas relativos al cannabis se han evaluado ya muchas veces, sigue tratándose de una planta muy adaptable y, en consecuencia, de una droga dinámica, que exige reevaluación permanente.
Research
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Cannabinoids are a group of terpenophenolic compounds present in Cannabis (Cannabis sativa L). The broader definition of cannabinoids refers to a group of substances that are structurally related to delta-9-tetrahydrocannabinol (Δ9-THC) or that bind to cannabinoid receptors. Before the 1980’s, it was often speculated that cannabinoids produced their physiological and behavioral effects via nonspecific interaction with cell membranes, instead of interacting with specific membrane-bound receptors. The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate. These receptors are common in animals, and have been found in mammals, birds, fish, and reptiles. There are currently two known types of cannabinoid receptors, termed CB1 and CB2. The cannabinoid system has been around for over 600 million years…even before the dinosaurs!! The cannabinoid system is present in species such as hydra, mollusks, and insects, leading to speculation on the physiological importance of such a system preserved throughout evolution. To date, the presence in the central nervous system of specific lipids that bind naturally to the CB1/CB2 cannabinoid receptors has been documented. Pharmacological experiments have shown that injection of those compounds induces cannabimimetic effects. The family of endogenous cannabinoids or endocannabinoids comprises Arachidonoylethanolamine, 2-araquidonylglycerol, Virodhamine, noladinether and N-arachidonyldopamine. The endocannabinoids have an active role in modulating diverse neurobiological functions, such as learning and memory, feeding, pain perception and sleep generation. The system of endogenous cannabinoids is present in several species, including humans, leading to speculation regarding the neurobiological role of the endocannabinoid system in diverse functions. Hence, I thought it was time to bring out an editorial book on the subject containing advanced and up-to-date scientific information on this special and exclusive topic. I expect that such a book is likely to attain global circulation among students, teachers and researchers alike. Fortunately, in response to our appeal, a number of leading scientists in the field across the globe agreed to contribute to the book. Thus, this book deals with various aspects of the cannabinoid and endocannabinoid system, from phenomena to molecular processes. I am sincerely grateful to all the contributors for keeping. The purpose of the book is to provide a comprehensive understanding of the endocannabinoid system with adequate emphasis on the pharmacological and molecular foundation and is directed at all who are interested in cannabinoid research.
Chapter
Vorbemerkung: Die Zusammenfassung psychotroper Stoffe unterschiedlichster chemischer Struktur und Anwendungsformen unter Oberbegriffen erfolgt in diesem Buch in erster Linie im Hinblick auf vergleichbare durch sie ausgelöste psychische Wirkungen.
Article
Systems of classifying alcohol and drug problems have developed through the disease model of the 19th century, which allows categorical diagnosis and facilitated the 12-step approach to behavioural models and to socioeconomic models where substance use is seen as part of the environment in which an individual functions. DSM and ICD classified drug and alcohol use separately in their early versions, although they are now subject to the same criteria and both systems make a distinction between dependant and non-dependant use. DSM-IV and ICD-10 classify dependence as a cluster of cognitive, behavioural and physiological systems applicable across all substances. The criteria are broadly tolerance and withdrawal, impaired control and compulsion and salience and continued use despite harm. Dependence symptoms, substance-related problems and consumption form separate but related axes. Both DSM-IV and ICD-10 contain categories of abuse and harmful use respectively for substance users who do not meet the criteria for dependence. ICD-10 has a greater emphasis on the physical and psychological consequences of substance abuse. A substantial body of work on the validity of the dependence syndrome has generally found the dependence abuse model to be useful across the range of substances, although for cannabis the there are problems defining the withdrawal syndrome. Recent work to define DSM-V may change classification systems. Other forms of typology which are clinically useful also exist; for instance, the distinction between injecting and non-injecting drug users, and systems that detect substance-related problems rather than diagnostic criteria.
Article
The problem of cannabis-associated disorders and their treatment has moved to the foreground with the growth of cannabis consumption in recent years. Germany lacks programs corresponding to those that exist already in the USA. Because our results are not yet sure, if we want to do justice to the problem of cannabis consumption and associated disorders we have to increase our efforts to develop such programs in Germany. Above all cannabis dependence plays a substantial role, but also states of intoxication, withdrawal syndromes, and especially cognitive disorders and psychoses can only be efficiently treated when the effective treatment strategies become clear to us. The programs DRIP and MOBI, developed in our clinic, are first steps in that direction.
Chapter
Marco ist 23 Jahre alt. Nach dem Abitur hat er ein Pädagogikstudium begonnen, das er durch einen Nebenjob in einem Zeitschriftenladen finanziert. Cannabis konsumiert er seit acht Jahren, zunächst nur auf Partys mit Freunden, dann aber zunehmend auch alleine daheim. Mittlerweile raucht er täglich mehrere Male, in der Regel beginnt er gleich nach dem Aufstehen damit den Tag. Häufig schläft er dann gleich wieder ein, sodass es ihm teilweise schwerfällt, Termine an der Uni einzuhalten. Auch auf der Arbeitsstelle gibt es Probleme. Aufgrund von Unpünktlichkeit wurde er mehrmals abgemahnt. Durch den Cannabiskonsum ist er sehr lethargisch geworden.
Article
Background There is a high prevalence of substance use disorders, especially among men, in Iran and is associated with a high burden on families. We aimed to systematically review the association between illicit drug use and spouse and child abuse in Iran. Method Comprehensive terms were used to search three international databases (ISI, Medline, and Scopus) and a national database of Scientific Information Database up to September 2019. The retrieved citations were screened based on the eligibility criteria and then data were extracted, and the risk of bias was assessed by two independent investigators. Data were analyzed using random-effects model to estimate pooled odds ratios ( ORs) and the heterogeneity of studies. Results The search yielded 18 articles that met the inclusion criteria. Illicit substance use in husbands was associated with increased odds of current violence ( OR = 3.50; 95% CI [2.09, 5.86]), current physical violence ( OR = 5.41; 95% CI [3.50, 8.35]), current psychological violence ( OR = 6.20; 95% CI [3.74, 10.30]), and current sexual violence ( OR = 7.23; 95% CI [4.06, 12.87]) against spouse. In studies on child abuse, the odds of current physical child abuse by parents who used an illicit substance was 3.88 times (95% CI [1.50, 10.01]) higher than parents who did not use any illicit substance. Conclusion The results of the current study showed that illicit substance use is associated with an increased risk of spouse and child abuse. This is an important social and health consequence of drug use and should be addressed in all drug control plans.
Chapter
Cannabis is the most frequently abused recreational drug worldwide. Its major psychoactive component, ∆9-tetrahydrocannabinol (∆9-THC), interacts with specific cannabinoid (CB) receptors in the brain. Until today distinct neuropathological alterations have not been described. Opioids are the most frequently consumed drugs of abuse causing death by central respiratory depression. CNS findings include hypoxic-ischemic leukoencephalopathy, spongiform leukoencephalopathy, and a broad spectrum of CNS infections. Fatalities after the consumption of psychostimulants (cocaine, amphetamines, methamphetamine, and related synthetic drugs) have been reported in several autopsy series with cardiovascular and cerebrovascular events as the most frequent causes of death. The latter include intracerebral and subarachnoid hemorrhages as well as hemorrhagic or ischemic stroke. Alterations of neurotransmitters, receptors, second messengers signal transduction systems, and oxidative status have been reported for all of the abovementioned drugs but the findings are fragmentary and inconclusive. Designer drugs and new psychoactive substances (NPS) are a heterogeneous class of noncontrolled substances. The major classes include synthetic opioids, synthetic cannabinoid receptor agonists (“spice”), psychostimulant NPS (“bath salts”), hallucinogenic NPS, dissociative substances, and designer benzodiazepines. Most of these substances mimic the effects of well-established drugs of abuse. However, their consumption is associated with a high incidence of intoxications or fatalities, especially in the context of polydrug abuse. Detailed neuropathological investigations are lacking so far.
Article
Purpose of review: Cannabis enjoys a unique social status, widely perceived as a relatively harmless drug, with several benefits reported by the people who use it. Several jurisdictions have opened up access to cannabis to their populations for medicinal and/or recreational reasons. Given this changing regulatory environment, this article is intended to prompt debate about what is known about cannabis dependence and what has still to be revealed. Recent findings: Evidence suggests that 1 in 10 cannabis users are at risk of developing dependence. However, investigation of the way risk is estimated and the diagnosis of cannabis use disorder is constructed highlight some methodological problems, which call into question the incidence and prevalence of this diagnosis. Summary: There is scope to improve the way cannabis dependence is defined and counted in at-risk populations. Improving our understanding of this risk could lead to identifying who might be at risk of developing dependence prior to exposure to the drug.
Chapter
Vorbemerkung: Die Zusammenfassung psychotroperStoffe unterschiedlichster chemischer Struktur und Anwendungsformen unter Oberbegriffen erfolgt in diesem Buch in erster Linie im Hinblick auf vergleichbare durch sie ausgelöste psychische Wirkungen.
Chapter
Vorbemerkung: Die Zusammenfassung psychotroper 1Stoffe 2 unterschiedlichster chemischer Struktur und Anwendungsformen unter Oberbegriffen erfolgt in diesem Buch in erster Linie im Hinblick auf vergleichbare durch sie ausgelöste psychische Wirkungen.
Chapter
In Europa war Hanf lange als Kulturpflanze zur Gewinnung von Fasern bekannt, ehe im 19. Jahrhundert die Rauschwirkung bestimmter Sorten bekannt wurde. Heute ist Cannabis das am weitesten verbreitete illegale Rauschmittel in Deutschland. Laut Jahresbericht des Bundesgesundheitsministeriums fur das Jahr 2004 haben 32% der 12- bis 25-Jährigen schon einmal illegale Drogen probiert. 24% der Jugendlichen haben ausschließlich Cannabis konsumiert. Ein wichtiger Kofaktor für den Konsum von Cannabis sind Alkohol und Nikotin. Jugendliche, die rauchen und Erfahrung mit einem Alkoholrausch haben, nehmen laut des Berichts deutlich häufiger Cannabis ein als Jugendliche ohne diese Erfahrungen. Auch gilt Cannabis weiterhin als Einstiegsdroge zu den sogenannten harten Drogen wie Kokain und Heroin (BZGA 2004).
Article
Although the proposition that repeated marijuana use can lead to marijuana dependence has long been accepted, only recently has evidence emerged suggesting that abstinence leads to clinically significant withdrawal symptoms. Converging evidence from human and animal studies has increased our understanding of cannabinoid dependence. One of the most powerful tools to advance this area of research is the CB1 cannabinoid receptor antagonist SR 141716A, which reliably precipitates withdrawal syndromes in mice, rats, and dogs that have been treated repeatedly with cannabinoids. In addition, the use of CB1 receptor knockout mice has revealed that not only cannabinoid dependence is mediated through a CB1 receptor mechanism of action, but CB1 receptors also modulate opioid dependence. Moreover, the results of other genetically altered mouse models suggest the existence of a reciprocal relationship between cannabinoid and opioid systems in drug dependence. Undoubtedly, these animal models will play pivotal roles in further characterizing cannabinoid dependence and elucidating the mechanisms of action, as well us developing potential pharmacotherapies for cannabinoid dependence. Journal of Clinical Pharmacology, 2002.
Article
The legalization of cannabis in many countries, as well as the decrease in perceived risks of cannabis, have contributed to the increase in cannabis use medicinally and recreationally. Like many drugs of abuse, cannabis and cannabis-derived drugs are prone to misuse, and long-term usage can lead to drug tolerance and the development of Cannabis Use Disorder (CUD). These drugs signal through cannabinoid receptors, which are expressed in brain regions involved in the neural processing of reward, habit formation, and cognition. Despite the widespread use of cannabis and cannabinoids as therapeutic agents, little is known about the neurobiological mechanisms associated with CUD and cannabinoid drug use. In this article, we discuss the advances in research spanning animal models to humans on cannabis and synthetic cannabinoid actions on synaptic transmission, highlighting the neurobiological mechanisms following acute and chronic drug exposure. This article also highlights the need for more research elucidating the neurobiological mechanisms associated with CUD and cannabinoid drug use.
Article
Particularly in the last years, IS research started to analyze threats due to technology, like the unhealthy misuse of the social network Facebook. This research examines withdrawal symptoms due to cessation and develops a Facebook withdrawal scale (FWS). At first, we identified withdrawal symptoms from substance related and behavioral addictions, which have been tested by scales from medicine and psychology research. In a second step, we developed the Facebook Cessation Model. Results of a controlled field experiment with 26 Facebook users being isolated from Facebook for in total 120h reveal that different withdrawal symptoms can occur: Agitation, annoyance, anxiety, increased appetite, difficulties in concentrating, craving for Facebook, disturbance of social contacts, not feeling happy or calm, fluctuation in mood, feeling left out, hostility, impatientness, inattentiveness, irritability, memory lapses, restlessness and feeling slowed down. Our results offer an opportunity to assess addiction and withdrawal without relying on participants' self-reporting their behavior.
Technical Report
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Essa publicação reuniu todas as Diretrizes relacionadas ao consumo de substâncias psicoativas produzidas pela AMB, a partir da nossa coordenação.
Article
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Cannabis remains the most commonly used and trafficked illicit drug in the world. Its use is largely concentrated among young people (15- to 34-year-olds). There is a variety of cannabis use patterns, ranging from experimental use to dependent use. Men are more likely than women to report both early initiation and frequent use of cannabis. Due to the high prevalence of cannabis use, the impact of cannabis on public health may be significant. A range of acute and chronic health problems associated with cannabis use has been identified. Cannabis can frequently have negative effects in its users, which may be amplified by certain demographic and/or psychosocial factors. Acute adverse effects include hyperemesis syndrome, impaired coordination and performance, anxiety, suicidal ideations/tendencies, and psychotic symptoms. Acute cannabis consumption is also associated with an increased risk of motor vehicle crashes, especially fatal collisions. Evidence indicates that frequent and prolonged use of cannabis can be detrimental to both mental and physical health. Chronic effects of cannabis use include mood disorders, exacerbation of psychotic disorders in vulnerable people, cannabis use disorders, withdrawal syndrome, neurocognitive impairments, cardiovascular and respiratory and other diseases.
Article
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Background SR141716, a recently developed CB1 cannabinoid receptor antagonist, blocks acute effects of Δ-9-tetrahydrocannabinol (THC) and other CB1 cannabinoid agonists in vitro and in animals. These findings suggest that CB1 receptors mediate many of the effects of marijuana, but this has not been evaluated in humans.Methods Sixty-three healthy men with a history of marijuana use were randomly assigned to receive oral SR141716 or a placebo in an escalating dose (1, 3, 10, 30, and 90 mg) design. Each subject smoked an active (2.64% THC) or placebo marijuana cigarette 2 hours later. Psychological effects associated with marijuana intoxication and heart rate were measured before and after antagonist and marijuana administration.Results Single oral doses of SR141716 produced a significant dose-dependent blockade of marijuana-induced subjective intoxication and tachycardia. The 90-mg dose produced 38% to 43% reductions in visual analog scale ratings of "How high do you feel now?" "How stoned on marijuana are you now?" and "How strong is the drug effect you feel now?" and produced a 59% reduction in heart rate. SR141716 alone produced no significant physiological or psychological effects and did not affect peak THC plasma concentration or the area under the time × concentration curve. SR141716 was well tolerated by all subjects.Conclusions SR141716 blocked acute psychological and physiological effects of smoked marijuana without altering THC pharmacokinetics. These findings confirm, for the first time in humans, the central role of CB1 receptors in mediating the effects of marijuana.
Article
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Studying prevalence of Diagnostic and Statistical Manual of Mental Disorders-III-Revised (DSM-III-R) drug dependence among Americans 15–54 yrs old, the authors found about 1 in 4 (24%) had a history of tobacco dependence; about 1 in 7 (14%) had a history of alcohol dependence, and about 1 in 13 (7.5%) had a history of dependence on an inhalant or controlled drug. About one third of tobacco smokers had developed tobacco dependence and about 15% of drinkers had become alcohol dependent. Among users of the other drugs, about 15% had become dependent. Many more Americans age 15–54 have been affected by dependence on psychoactive substances than by other psychiatric disturbances now accorded a higher priority in mental health service delivery systems, prevention, and sponsored research programs. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
Research conducted on many different laboratory animals, including fish, birds, rats, dogs and monkeys, shows that tolerance to THC develops. These findings are in agreement with observations in man, especially in heavy cannabis smokers in India and Greece. Physical dependence on THC has been demonstrated in monkeys. A review of the literature indicates that withdrawal symptoms may also occur in heavy cannabis smokers.
Article
Developmental, social, and clinical studies of dependency have produced remarkably consistent results. A review and integration of these findings allow strong conclusions to be drawn regarding the etiology and dynamics of dependency The etiology of dependency appears to lie in overprotective, authoritarian parenting. In social settings, dependency is associated with suggestibility, conformity, compliance, interpersonal yielding, affiliative behavior, and sensitivity to interpersonal cues. Dependency predicts the onset of certain psychological disorders and follows the onset of others. h seems that the fundamental motivation of the dependent person, from which the behaviors that are exhibited in different situations are derived, is a strong desire to obtain and maintain nurturant, supportive relationships. Implications of these findings for different theoretical models of dependency are discussed.
Article
Contents: Preface. Introduction and Overview. Reviewing the Influence of Social Roles on Drug Use During the Transition to Young Adulthood. Examining Roles and Experiences During the Post-High School Years--Sample Characteristics and Analysis Strategy. Changes in Cigarette Use. Changes in Alcohol Use. Changes in Marijuana Use. Changes in Cocaine Use. Summary, Conclusions, and Implications.
Article
A review of the empirical literature examining the comorbidity of dependent personality disorder (DPD) and other psychological disorders indicated that DPD shows high rates of comorbidity with eating disorders, anxiety disorders, somatization disorder, and the majority of DSM-III-R Axis II personality disorders (i.e., schizoid, avoidant, schizotypal, borderline, histrionic, passive-aggressive and self-defeating). However, DPD showed only moderate overlap with dysthymia and major depression, and showed virtually no overlap with substance use disorders. These findings offer mixed support for the assertions of the DSM-III-R regarding the comorbidity of DPD and other Axis I and Axis II disorders. In general, studies that used categorical approaches to assessing DPD comorbidity obtained lower comorbidity rates than studies that used dimensional analysis. The diagnostic, methodological, and theoretical implications of these findings are discussed.
Article
• The relation between marijuana consumption and the development of tolerance was investigated during a 31-day study. Volunteers with a history of moderate or heavy marijuana use were given access to one-gram (2.1% δ9 tetrahydrocannabinol [THC]) marijuana cigarettes during a 21-day smoking period. Both groups tended to increase consumption during this time. Heavy users averaged 5.7 cigarettes per day and indicated a progressive decline in ratings of intoxication and duration of pulse rate effect. Moderate users averaged 3.2 cigarettes per day but showed no changes in either of these reactions during this time. Results suggested that tolerance does not develop to the two most reliable indexes of marijuana intoxication unless heavy doses of δ9 THC are self-administered repeatedly. Also, the tendency to increase consumption during this time is not necessarily associated with the development of tolerance.
Article
A review of the empirical literature suggests that having a dependent personality orientation increases the risk for a variety of physical disorders. Evidence also indicates that dependent persons are more likely than independent people to view their problems in somatic terms and to seek professional help for physical symptoms. The implications of these findings are discussed. The etiology of the dependent personality is considered in terms of problematic and disrupted parent-child relationships. Some issues warranting further clarification and additional empirical study are described.
Article
In this study, groups of ‘alcoholic’ subjects were independently rated as to their degree of dependence by a technique previously validated. The two groups of moderately and severely dependent subjects were then given the 101-item EPQ. In keeping with other similar studies, the data suggested that high N, high P and low E in men were related to the Clinical Alcohol Personality. Further analysis of these and other data suggest that whilst raised N scores may be a spurious artefact which is a consequence of heavy alcohol consumption, the E and P findings may reflect stable predispositions. There were no sex differences, but there was a major group difference on P, with both severely dependent men and women scoring significantly higher than their less dependent counterparts.
Article
Five chimpanzees were given Delta 9-tetrahydrocannabinol (Delta 9THC): 1.0 milligram per kilogram of body weight for 21 days and 4.0 milligrams per kilogram of body weight for 42 days. Although accuracy and speed of performance on a delayed matching-to-sample task were significantly affected by both doses, tolerance to Delta 9THC THC did not develop. No long-term behavioral effects of Delta 9 THC were observed after termination of the drug regimens.
Article
The present study examined withdrawal symptoms and their intensities across a range of traditional and non-traditional addictive substances/losses (i.e., alcohol, nicotine, caffeine, food, and social/love relationship). Study one administered the Withdrawal Symptom Survey to Alcoholics Anonymous members and college students. Seven symptoms (irritability, restlessness, impatience, anxiousness, trouble concentrating, depression, and anger) were rated in the top 10 of symptom intensity by all experimental groups and six addictive substance/loss categories. Irritability had the highest rank orders and means across the addictions. Similarity of withdrawal response patterns across substances/losses was further demonstrated by high correlations between mean symptom pattern profiles across the addictive substances/losses. In addition, an individual's response to withdrawal from one substance was moderately predictive of the individual's withdrawal responses to other substances/losses. Study two compared responses/symptoms associated with feelings during an enjoyable evening with those associated with a broken relationship or food deprivation. The symptom patterns for relationship breakup and food deprivation replicated those of Study one and were independent of those associated with a positive situation. Findings support the conclusion that a high degree of similarity in withdrawal symptom patterns exists across addictive categories and relationship loss and that individual differences in symptom intensity operate across addiction/loss categories.
Article
The prevalence of cannabis use is rising among adolescents, many of whom perceive little risk from cannabis. However, clinicians who treat adolescent substance users hear frequent reports of serious cannabis-use disorders and problems. This study asked whether cannabis produced dependence and withdrawal among such patients, and whether patients' reports supported previous laboratory findings of reinforcing effects from cannabis. This was a screening and diagnostic study of serial treatment admissions. The diagnostic standard was the DSM-III-R dependence criteria, and the setting was a university-based adolescent substance treatment program with male residential and female outpatient services. The patients were 165 males and 64 females from consecutive samples of 255 male and 85 female 13–19-year-olds referred for substance and conduct problems (usually from social service or criminal justice agencies). Eighty-seven patients were not evaluated, usually due to early elopement. Twenty-four others did not meet study admission criteria: ≥one dependence diagnoses and ≥three lifetime conduct-disorder symptoms. The main measures were items from diagnostic interview instruments for substance dependence, psychiatric disorders, and patterns of substance use. Diagnoses were substance dependence, 100%; current conduct disorder, 82.1%; major depression, 17.5%; attention-deficit/hyperactivity disorder, 14.8%. The results show that most patients claimed serious problems from cannabis, and 78.6% met standard adult criteria for cannabis dependence. Two-thirds of cannabis-dependent patients reported withdrawal. Progression from first to regular cannabis use was as rapid as tobacco progression, and more rapid than that of alcohol, suggesting that cannabis is a reinforcer. The data indicate that for adolescents with conduct problems cannabis use is not benign, and that the drug potently reinforces cannabis-taking, producing both dependence and withdrawal. However, findings from this severely affected clinical population should not be generalized broadly to all other adolescents.
Article
This article first appeared as FSS Technical Note No. 780 (Accession No. 71900), January 1993. Information on the purity of illegal drugs is used for various purposes including: valuation for sentencing; profiling and sample comparison; and studies of the economics of the illicit market. The most commonly-used measure for powders is the arithmetic mean purity, but this statistic has several drawbacks. In the case of amphetamine, the mean (10% in 1995) has been consistently higher than the mode (4% in 1995), and it is a function of seizure size, region and time. Heroin purity, as measured by the diamorphine content (mean=42% in 1995) could also be an unreliable guide to potency if other opium alkaloids and `active' adulterants are present. The mean purities of cocaine and crack in 1995 were 51% and 85%, respectively. A further source of confusion can arise when a distinction is not made with respect to the chemical form of the drug (i.e. salt or base).
Article
This second printing differs from the first (see 16: 3647) in the following respects: (1) the name has been changed from Schedule to Inventory; (2) the shape of the cards has been slightly altered; and (3) three new scoring keys have been added: paranoia, psychasthenia, and schizophrenia. The Inventory is now described as "a psychiatric measuring device for general medical practice." (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
Recent studies on the relationship between depression and the hypothalamic pituitary adrenal axis are of general interest from three points of view. Firstly, exactly the same adaptive changes are seen in depressed patients as in animals exposed to chronic stress: in both there is an increased central activation of the axis impaired negative feedback control and adrenal hypertrophy. The second general conclusion is that the environmental stressors which predispose towards depression in man also activate the HPA axis in animals and possibly in man as well. This suggests that activation of the HPA axis is a useful marker of environmental predisposition towards depression. The third general conclusion is that HPA activation may be a mediator as well as a marker of the environmental influence on depression. This is both for animal models of depression and for clinical depression which may be amenable to treatment with drugs which inhibit the synthesis of cortisol.
Article
Type and prevalence of Axis I and Axis II disorders (DSM-III) were assessed in a sample of 298 consecutive psychiatric outpatients. The instruments used were SCID and SIDP. About half of the Axis I diagnoses consisted of different subgroups of depression. Most patients had more than one diagnosis, anxiety being the second most common disorder. Eighty one percent of the subjects met the criteria for a personality disorder diagnosis; half of them obtained more than one Axis II diagnosis. Personality disorder was more common among men than among women. Avoidant and dependent personality disorders constituted the most frequent diagnoses.
Article
SummaryA retrospective survey of high frequency gamblers (members of Gamblers Anonymous) suggested that, on ceasing to bet, some 30–40 per cent reported significant disturbance of mood and/or behaviour. The content and frequency of these reported disturbances were similar to those reported by high frequency alcohol drinkers on cessation of drinking and it was suggested that in the context of a study of alcohol and related problems they would be labelled ‘withdrawal’ symptoms. Greater disturbance reported by individual gamblers was associated with aspects of previous gambling such as, betting just at the ‘off, or when a favourable price was quoted, being ‘extremely excited’ while listening to a race, exhibiting more than one behaviour out of the following, pacing around, fidgeting, shouting out, and ‘often’ changing his selection at the last moment. The level of disturbance was also associated with the difficulty experienced in suddenly trying to stop betting. The implications of these tentative findings were briefly explored in relation to the concept of addiction.
Article
The relationship of the adrenal hormone cortisol to arousal and personality was examined among 102 male college students and 4462 male military veterans. Students high in cortisol had high heart rates, and NEO-PI scores showed them to be anxious and depressed, solitary, and appreciative of fantasy, aesthetics, ideas, and values. Veterans high in cortisol had high heart rates and high systolic and diastolic blood pressures, and MMPI scores showed them to be anxious, depressed, introverted, masculine, and not manic. Results were consistent with the notion that high levels of cortisol are associated with high arousal, which is debilitating and leads subjects to avoid the further arousal that would come from encounters with novel persons and events. However, the sizes of the effects were small, especially among MMPI scores for the veterans.
Article
A suspension system for water-insoluble drugs was evaluated using the mouse tail-flick test for analgesia and schedule-controlled responding in rhesus monkeys. One group of monkeys was trained to respond for food reinforcement under a chain fixed-interval 9 min fixed-ratio 10 schedule of reinforcement (chain FIFR). Another group of monkeys was trained to respond for intravenous cocaine injections (100 μg/kg/inj) under an FR-10 schedule. Water-insoluble compounds were suspended in emulphor:ethanol:saline. The bioavailability of these drug suspensions was demonstrated to be equivalent to water-soluble compounds by comparing the activity of the water-soluble and water-insoluble salts of (+)-propoxyphene in the mouse tail-flick test. The behavioral effects of these drug suspension were also determined in the group of monkeys which was trained to respond for food under the chain FI-FR schedule. Dose-related decreases in responding were produced by (+)-propoxyphene HCl (water-soluble), (+)-propyxyphene napsylate (water-insoluble), and a cannabinoid, (±)-9-nor-9β-OH-hexahydrocannabinol (β-HHC) (water insoluble). Doses of (+)-propoxyphene HCl (in saline) and (+)-propoxyphene napsylate (in the emulphor suspension system) were equi-effective in disrupting food-reinforced responding. In addition, these two salts of propoxyphene were equi-effective as reinforcers of self-administration behavior in rhesus monkeys. β-HHC was more potent than (+)-propoxyphene in producing decreases in food-reinforced responding but failed to maintain self-administration behavior in the monkey.
Article
Based on previous observations that cannabidiol (CBD) blocks some effects of Δ9-tetrahydrocannabinol (Δ9-THC) in laboratory animals, the present work was carried out to study possible interaction between CBD and Δ9-THC in human beings. In a double blind procedure, 40 healthy male volunteers were assigned to 1 of 8 experimental groups, receiving per oral route, placebe, 30 mg Δ9-THC, 15 30 or 60 mg of CBD, and mixtures of 30 mg of Δ9-THC plus either 15, 30 or 60 mg of CBD respectively. Pulse rate, time production tasks and psychological logical reactions were measured at several time intervals after drug ingestion. 30 mg Δ9-THC alone increased pulse rate, disturbed time tasks and induced strong psychological reactions in the subjects. 15–60 mg of CBD alone provoked no effects. On the other hand, CBD was efficient in blocking most of the effects of Δ9-THC when both drugs were given together. CBD also decreased the anxiety component of Δ9-THC effects, in such a way that the subjects reported more pleasurable effects.
Article
Marijuana has a long history of abuse yet, as described here by Mary Abood and Billy Martin, there is little evidence that animals will self-administer the primary psychoactive constituent, tetrahydrocannabinol, or that marijuana stimulates brain reward pathways. While marked tolerance develops to marijuana, it has been difficult to demonstrate physical dependence, and until recently the mechanisms by which cannabinoids produced their behavioral effects were poorly defined. The development of new synthetic analogs played a critical role in the characterization and cloning of the cannabinoid receptor. Insight into cannabinoid receptors may lead to a better understanding of marijuana abuse in humans and provide new therapeutic strategies for several disorders.
Article
The clinical relevance of marijuana withdrawal has not been established. This study is the first to document the incidence and severity of perceived marijuana withdrawal symptoms in a clinical sample of marijuana-dependent adults. Fifty-four people seeking outpatient treatment for marijuana dependence completed a 22-item Marijuana Withdrawal Symptom checklist based on their most recent period of marijuana abstinence. The majority (57%) indicated that they had experienced > or = six symptoms of at least moderate severity and 47% experienced > or = four symptoms rated as severe. Withdrawal severity was greater in those with psychiatric symptomatology and more frequent marijuana use. This study provides further support for a cluster of withdrawal symptoms experienced following cessation of regular marijuana use. The affective and behavioral symptoms reported were consistent with those observed in previous laboratory and interview studies. Since withdrawal symptoms are frequently a target for clinical intervention with other substances of abuse, this may also be appropriate for marijuana.
Article
Arguments and data are presented establishing the rationale of using the K factor as a suppressor on certain MMPI clinical scales. Five scales, Pt, Sc, Hs, Pd, and Ma, are improved by the correction as indicated by increased correspondence between scores and clinical status. The scales Hy, D, Mf and Pa are not so treated nor is it established that the K-score should be taken into account subjectively in evaluating them. It is suggested that the K-correction should be made routinely by users of the MMPI and that old records should be scored and redrawn if any research or validation study is to be carried on.
Article
The clinical effects of intensive marihuana smoking on physically and mentally healthy male volunteers were studied in group sessions during a marihuana research project. The study was divided into three periods: presmoking, “wash-out” (4 weeks); smoking (4 weeks); and postsmoking, “wash-out” (4 weeks).Subjects exhibited mild referentiality because of confinement and observation even before smoking began. With light smoking, subjects reported pleasurable effects and enhanced sensitivity. group cohesiveness increased. With heavy smoking subjects became apathetic and withdrawn and markedly referential. This disappeared completely when smoking ceased. Subjects were felt to be clinically hyperirritable during the first week of withdrawal. This disappeared completely after the first withdrawal week. Because of conflicting opinions about the effects of abstinence after chronic heavy use, it is felt that improved design of mood rating scales is needed.
Article
The personality characteristics of 48 male volunteers were measured with the MMPI and were related to measures of cannabis withdrawal symptoms. Personality variables accounted for 25% of the variance in these symptoms. Neurotic introversion, a tendency not to deny anxiety, absence of sensation seeking and openness were traits found to relate positively to the intensity of cannabis abstinence symptoms.
Article
Marijuana related deficits in work performance are short lived when they are seen at all. The simple operant task employed in this study was not incompatible with smoking behavior. It is unclear how work output would be affected if smoking and working were made incompatible. Moreover, the extent to which the results may be applicable to sustained performance on a cmore complex task remains to be determined.
Article
The UCLA cannabis project has provided several interesting observations that contribute to our knowledge about this plant and its constituents. Some of the findings (reduction in intraocular pressure, bronchodilation) may have therapeutic significance in the future. Certain results (testosterone lowering, airway narrowing after heavy use) indicate that side effects are also a possibility. Other data (unchanged immune response, lack of chromosomal alterations) seem to controvert the reports of other investigators. Still other information obtained (hemispheric lateralization, electroencephalographic changes) appears to represent new knowledge about the effects of cannabis on humans.
Article
The relation between marijuana consumption and the development of tolerance was investigated during a 31-day study. Volunteers with a history of moderate or heavy marijuana use were given access to one-gram (2.1% delta9 tetrahydrocannabinol [THC]) marijuana cigarettes during a 21-day smoking period. Both groups tended to increase consumption during this time. Heavy users averaged 5.7 cigarettes per day and indicated a progressive decline in ratings of intoxication and duration of pulse rate effect. Moderate users averaged 3.2 cigarettes per day but showed no changes in either of these reactions during this time. Results suggested that tolerance does not develop to the two most reliable indexes of marijuana intoxication unless heavy doses of delta9 THC are self-administered repeatedly. Also, the tendency to increase consumption during this time is not necessarily associated with the development of tolerance.
Article
Tolerant and nontolerant dogs received one i.v. administration of 0.5 mg/kg of 3H-delta9-tetrahydrocannabinol 30 minutes before they were sacrificed. Plasma, peripheral and brain tissues, as well as subcellular fractions of brain tissues from both treatment groups, were analyzed for radioactivity. Throughout the time period before sacrifice, the plasma concentrations of radioactivity in the tolerant and nontolerant dogs were not significantly different. The percentage of radioactivity in brain and plasma that was due to either unchanged delta9-tetrahydrocannabinol or a major metabolite was the same in each group. Of the radioactivity in brain, 46% was identified as delta9-tetrahydrocannabinol. Regardless of treatment, there was a specific accumulation of radioactivity in adrenals, liver, kidney, heart and pancreas. The only significant differences in radioactivity between tolerant and nontolerant peripheral tissues were found in liver, kidney cortex, heart and lymph nodes. Although all brain areas from tolerant dogs contained less radioactivity than the comparable brain areas from nontolerant animals, only pituitary and putamen were significantly less. There was a specific accumulation of radioactivity in some brain areas that could be associated with behavioral effects. The concentration in cerebellar and cerebral gray was significantly greater than that in white, and there was a marked reduction in the concentration in gray after tolerance developed. The mean percentage of radioactivity in each subcellular fraction was as follows: 23% crude nuclei, 44% mitochondria, 8% cholinergic nerve endings, 7% noncholinergic nerve endings, 2% free mitochondria and 6% synaptic vesicles. The quantity of radioactivity in homogenates of brains from tolerant dogs was 17% less than brains of nontolerant animals, which was merely a reflection of the respective plasma concentrations. The distribution of radioactivity was similar in both groups, although most of the subcellular fractions from tolerant dogs contained a lesser amount of radioactivity. The most notable difference was observed in the synaptic vesicle fraction. The synaptic vesicle fraction of tolerant dogs contained 40% less radioactivity than did the same fraction from nontolerant dogs, which implied a possible mechanism of action. A comparison of the remaining subcellular fractions did not appear to explain the development of tolerance.
Article
Developmental, social, and clinical studies of dependency have produced remarkably consistent results. A review and integration of these findings allow strong conclusions to be drawn regarding the etiology and dynamics of dependency. The etiology of dependency appears to lie in overprotective, authoritarian parenting. In social settings, dependency is associated with suggestibility, conformity, compliance, interpersonal yielding, affiliative behavior, and sensitivity to interpersonal cues. Dependency predicts the onset of certain psychological disorders and follows the onset of others. It seems that the fundamental motivation of the dependent person, from which the behaviors that are exhibited in different situations are derived, is a strong desire to obtain and maintain nurturant, supportive relationships. Implications of these findings for different theoretical models of dependency are discussed.
Article
The aim of this study was to evaluate the moderating effect of several psychologically and biologically defined characteristics for both psychological and physiological indices of reactivity to and coping with lecturing stress. Student teachers were measured in two standardized lecturing situations: once at the start of a three-month practice period and once at the end of this period. Reactivity was operationalized as an increase in heart rate, cortisol excretion and subjective anxiety responses in anticipation of and at the start of the lecture. Coping was operationalized as the attunement of these responses during, or recovery after lecturing (short term coping), and as the adaptation of these responses across the three-month practice period (long term coping). It was found that reactivity to and (particularly long term) coping with the lecturing stressor could well be predicted by moderators such as physical fitness, extraversion, neuroticism, social anxiety and several coping styles. Specificity of predictor sets for sex and response parameters is discussed.
Article
A specific withdrawal syndrome resulting from the prolonged use of cannabis is presented. It is believed to be an underreported set of symptoms that are now emerging in the United States as a result of the increasing potency of the drug and greater numbers of long-term users. Two case studies are presented which illustrate the cannabis withdrawal syndrome in an otherwise healthy 25-year-old male and an exacerbation of a preexisting affective disorder in a 38-year-old male who prior to his resumption of cannabis use was asymptomatic for 3 years with antidepressant medications. The cannabis withdrawal sequela is presented with a discussion of differential diagnosis and implications for treatment and future research.
Article
The results presented describe a rather chronically anxious and depressed population of 119 long-term BZ users, with more than 90% having been given a psychiatric diagnosis. While for many patients BZ therapy appeared appropriate, for many others it was not, and other treatments, whether psychotherapeutic or psychopharmacologic, would appear to have been more appropriate. Most patients, besides suffering from anxiety and/or depression, also showed evidence of chronic psychiatric problems, and almost all were in need of a great deal of support and assurance. In fact, one hard-earned lesson is that long-term BZ users are in need of much more intensive psychiatric and social support than other anxious or depressed patients. A follow-up of 62 patients, 6 to 12 months after study participation, indicated that 24% of them were without medication, 37% had been treated with antidepressants, and 39% were still taking BZ's, frequently on an as-needed or low daily dosage. It was of interest to note that the subset of 10 patients without a psychiatric diagnosis had normal Hamilton Anxiety scores prior to discontinuation. In addition, while most of them experienced some withdrawal symptoms, the intensity was milder, and all were able to successfully withdraw. None of the 10 were in need of psychiatric medication after BZ discontinuation. This raises the intriguing possibility that the intensity of BZ withdrawal may be only partly a function of the chemistry of declining blood levels. Instead, the intensity of the BZ withdrawal syndrome may be partly a function of degree of psychopathology and other premorbid personality variables. This parallels the experience of Nelson et al. (1984) who found antidepressant side effects to be more correlated with premorbid psychopathology than actual antidepressant blood levels. Abrupt BZ discontinuation produced withdrawal symptoms in 82% of patients regardless of the type of BZ which they had been taking. Severity of withdrawal, however, was clearly related to benzodiazepine half-life, with short half-life BZ's producing a more severe withdrawal reaction during the first week of placebo substitution than long half-life BZ's. There was also a suggestion that the severity might be partly dependent on nonpharmacologic variables such as premorbid psychopathology. The results in general support the recommendation made earlier by this research group (Rickels, 1985a) that chronically anxious patients in need of BZ therapy should be treated only for short periods of time, their diagnosis should be frequently reassessed and, if found to be still in need of chronic BZ therapy, this should be offered on an intermittent rather than continuous basis. Emerging research suggests that optimum BZ therapy consists of just such judicious, circumspect, and critically monitored use of BZ's in terms of target symptoms and diagnoses. The very safety and effectiveness of BZ's have perhaps slowed the realization of these therapeutic goals.
Article
By interviewing and administering questionnaires to 63 patients one to five years after treatment for benzodiazepine dependence the long-term success rate was examined together with factors associated with outcome. Fifty-four per cent of patients had permanently withdrawn from medication at follow-up. Most of those who were successful continued to experience psychiatric symptoms after discharge. Significantly more women than men managed to withdraw from medication. Outcome was not related to previous benzodiazepine regimen, psychiatric history or experiences of withdrawal. It is argued that psychological adjuncts should be included in the treatment of benzodiazepine dependence in order to prevent relapse.
Article
This review will summarize the pharmacokinetic properties of Δ1-tetrahydrocannabinol mainly in man, since only limited information is available in experimental animals. We will also review the metabolites of Δ1-THC, with particular emphasis on those metabolites which have either psychotomimetic properties similar to Δ1-THC or which are eliminated in man. Metabolic tranformations have mainly been elucidated in various in vitro systems and in experimental animals. Only recently, more extensive information on the metabolism of Δ1-THC in man has become available. The pharmacokinetics of the isomer of Δ1-THC, viz. Δ6-THC, will be dealt with very briefly, because it only represents a minute constituent of marihuana. Two other major cannabinoids, cannabinol (CBN) and cannabidiol (CBD), will also only be briefly reviewed, because available data for these compounds is somewhat limited. We will review only more significant and recent results, since an extensive survey of all published material in the area would be too voluminous. Thus, much of the early literature not directly related to pharmacokinetics and metabolisms is referred to in review articles and in proceedings of symposia. Unfortunately, two almost equally popular numbering systems are in use today. The biogenetically based monoterpene system (Δ1-THC) is used in this survey since it is applicable to both Δ1-THC, CBD, and CBN. The dibenzopyran (Δ9-THC) system which is also shown cannot be used for CBD but has lately been adopted by Chemical Abstracts. The use of these two systems has caused even more confusion when dealing with the metabolites. The chemistry of cannabinoids has been reviewed recently by Mechoulam and Harvey. Of more than 60 cannabinoids - the term cannabinoid is used for the typical C21-compounds and their transformation products - only Δ1-THC has profound psychoactive properties. CBN i.v. shows about 1/10 the potency of Δ1-THC in man, whereas CBD is devoid of psychotomimetic properties. Δ6-THC is about equipotent with Δ1-THC itself but is usually present in very small amounts compared to Δ1-THC, CBD, and CBN. The latter three compounds occur in marihuana-type cannabis preparations in concentrations usually around 1 to 2%.
Article
The pharmacology of the cannabinoids is characterized by at least two very provocative phenomena. First, the multiplicity of effects. As I have mentioned throughout this review, most of these effects are due to actions on the central nervous system. The major problem in the search for a therapeutic agent in this series has been due to the inability to find a cannabinoid with the therapeutic action at doses below those that produce side effects. The high lipid solubility of the cannabinoids allows them to be distributed throughout the brain at reasonable doses. The second aspect of their pharmacology worthy of special mention is their low toxicity. Throughout this review, I have indicated that the minimal effective dose of delta 9-THC for a particular pharmacological effect in animals was higher than that usually consumed by man. Yet, in almost all cases, it was much lower than the dose which produced toxic effects in the same species. These two characteristics of the animal pharmacology of cannabinoids carry over to humans. For instance, each of the cannabinoids tested in man causes many side effects at active doses and lethal effects of overdose by humans are nonexistent or rare. Toxicity following chronic use may be a different issue. A great deal of work has been carried out in an attempt to characterize the pharmacological effects of cannabinoids. It is clear from the material reviewed in this article that most if not all of the predominant effects of cannabinoids in whole animals are due to the direct effects of these compounds on the central nervous system. Our state of knowledge is too limited to rule out the possibility that they also produce effects on certain peripheral organs. It is expected that the majority of these effects will be shown to be due to the interaction of the cannabinoids with the neuronal innervation of the organ rather than directly with the organ tissue itself. Very high doses of cannabinoids just like all active drugs have an effect on many organ systems. These are toxicologic not pharmacologic and are nonspecific. The effects of cannabinoids at the molecular level have been reviewed by Martin (182a) in this series. This type of research is expected to elucidate the mechanism of action of cannabinoids at the cellular level. It is clear that the cannabinoids produce a unique behavioral syndrome in laboratory animals and in man.(ABSTRACT TRUNCATED AT 400 WORDS)
Article
Harnessed rhesus monkeys, surgically prepared with indwelling jugular catheters, were given access by means of remotely controlled infusion pumps to unlimited quantities of delta-9-trans-tetrahydrocannabinol. Naive monkeys as well as monkeys which were automatically infused with THC for over 28 days did not self-administer THC. Monkeys which had a history of multiple drug self-administration also did not self-infuse THC.