humulene and Substance-Withdrawal-Syndrome

This review summarizes treatments for cannabis use disorder (CUD) in adolescents. The best supported CUD treatments are cognitive behavioral psychotherapies, including family-based models that facilitate environmental changes and youth-focused models that incorporate skills training, motivational interviewing, and contingency management to promote reductions in cannabis use. Some medications show promise in reducing cannabis craving and withdrawal symptoms. Further research is needed on the efficacy and implementation of existing treatments given the changes in cannabis use trends over time and on emerging technologies that may expand access to evidence-based CUD treatments.

Topics: Adolescent; Cannabis; Humans; Marijuana Abuse; Motivational Interviewing; Substance Withdrawal Syndrome; Substance-Related Disorders

Cannabis withdrawal is a well-characterized phenomenon that occurs in approximately half of regular and dependent cannabis users after abrupt cessation or significant reductions in cannabis products that contain Δ. Narrative review of literature.. Symptom onset typically occurs 24-48 hours after cessation and most symptoms generally peak at days 2-6, with some symptoms lasting up to 3 weeks or more in heavy cannabis users. The most common features of cannabis withdrawal are anxiety, irritability, anger or aggression, disturbed sleep/dreaming, depressed mood and loss of appetite. Less common physical symptoms include chills, headaches, physical tension, sweating and stomach pain. Despite limited empirical evidence, supportive counselling and psychoeducation are the first-line approaches in the management of cannabis withdrawal. There are no medications currently approved specifically for medically assisted withdrawal (MAW). Medications have been used to manage short-term symptoms (e.g. anxiety, sleep, nausea). A number of promising pharmacological agents have been examined in controlled trials, but these have been underpowered and positive findings not reliably replicated. Some (e.g. cannabis agonists) are used 'off-label' in clinical practice. Inpatient admission for MAW may be clinically indicated for patients who have significant comorbid mental health disorders and polysubstance use to avoid severe complications.. The clinical significance of cannabis withdrawal is that its symptoms may precipitate relapse to cannabis use. Complicated withdrawal may occur in people with concurrent mental health and polysubstance use.

Topics: Analgesics; Cannabinoid Receptor Agonists; Cannabis; Dronabinol; Hallucinogens; Humans; Marijuana Abuse; Substance Withdrawal Syndrome

While six U.S. states have already officially authorized cannabinoids to substitute opioids and treat opioid use disorder, the therapeutic benefits of cannabinoids remain unclear, especially when weighted against their adverse effects.. We conducted a systematic review of studies examining the association between opioid withdrawal and cannabis use or delta-9-tetrahydrocannabinol (THC) administration. We searched multiple databases from inception to July 30, 2022, and assessed study quality.. Eleven studies were identified, with a total of 5330 participants, of whom 64 % were male. Nine observational studies examined the association between cannabis use and opioid withdrawal. Two randomized, placebo-controlled clinical trials (RCTs) investigated the withdrawal-alleviating effects of dronabinol, a synthetic form of THC. Four observational studies found an association between cannabis use and the alleviation of opioid withdrawal; one reported exacerbation of opioid withdrawal symptoms; and four reported no association. RCTs reported that THC alleviated opioid withdrawal, albeit with dose-dependent increases in measures of abuse liability, dysphoria, and tachycardia. There was high heterogeneity in measurements of opioid withdrawal and the type and dose of opioid at baseline.. Although there is preliminary evidence that cannabis and its main psychoactive constituent, THC, may alleviate opioid withdrawal, these effects are likely to have a narrow therapeutic window. Further, the potential of cannabinoids to alleviate opioid withdrawal is determined by complex interactions between patient characteristics and pharmacological factors. Collectively, these findings have clinical, methodological, and mechanistic implications for treating opioid withdrawal during cannabinoid use, and for efforts to alleviate opioid withdrawal using non-opioid therapeutics.

Topics: Analgesics, Opioid; Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Dronabinol; Female; Hallucinogens; Humans; Male; Narcotics; Substance Withdrawal Syndrome

Cannabis is one of the most widely used substances across the globe and its use has a substantial heritable component. However, the heritability of cannabis use varies according to substance use phenotype, suggesting that a unique profile of gene variants may contribute to the different stages of use, such as age of use onset, lifetime use, cannabis use disorder, and withdrawal and craving during abstinence. Herein, we review a subset of genes identified by candidate gene, family-based linkage, and genome-wide association studies related to these cannabis use phenotypes. We also describe their relationships with other substances, and their functions at the neurobiological, cognitive, and behavioral levels to hypothesize the role of these genes in cannabis use risk. Delineating genetic risk factors in the various stages of cannabis use will provide insight into the biological mechanisms related to cannabis use and highlight points of intervention prior to and following the development of dependence, as well as identify targets to aid drug development for treating problematic cannabis use.

Topics: Cannabis; Craving; Endocannabinoids; Genetic Association Studies; Humans; Marijuana Abuse; Phenotype; Substance Withdrawal Syndrome

There is evidence that sex- and gender-related factors are involved in cannabis patterns of use, health effects and biological mechanisms. Women and men report different cannabis use disorder (CUD) symptoms, with women reporting worse withdrawal symptoms than men. The objective of this systematic review was to examine the effectiveness of cannabis pharmacological interventions for women and men and the uptake of sex- and gender-based analysis in the included studies. Two reviewers performed the full-paper screening, and data was extracted by one researcher. The search yielded 6098 unique records-of which, 68 were full-paper screened. Four articles met the eligibility criteria for inclusion. From the randomized clinical studies of pharmacological interventions, few studies report sex-disaggregated outcomes for women and men. Despite emergent evidence showing the influence of sex and gender factors in cannabis research, sex-disaggregated outcomes in pharmacological interventions is lacking. Sex- and gender-based analysis is incipient in the included articles. Future research should explore more comprehensive inclusion of sex- and gender-related aspects in pharmacological treatments for CUD.

Topics: Cannabis; Female; Humans; Male; Marijuana Abuse; Sex Factors; Substance Withdrawal Syndrome

Cannabis use has become increasingly common in the U.S. in recent years, with legalization for medical and recreational purposes expanding to more states. With this increase in use and access, providers should be prepared to have more conversations with patients about use. This review provides an overview of cannabis terminology, pharmacology, benefits, harms, and risk mitigation strategies to help providers engage in these discussions with their patients. Current evidence for the medical use of cannabis, cannabis-related diagnoses including cannabis use disorder (CUD) and withdrawal syndromes, and the co-use of opioids and cannabis are discussed. It is crucial that providers have the tools and information they need to deliver consistent, evidence-based assessment, treatment, prevention and harm-reduction, and we offer practical guidance in these areas.

Topics: Cannabis; Communication; Drug Administration Routes; Humans; Marijuana Abuse; Medical Marijuana; Opioid-Related Disorders; Primary Health Care; Professional-Patient Relations; Substance Withdrawal Syndrome; Synthetic Drugs; United States

Cannabis use disorder (CUD) is prevalent and demand for treatment is increasing, yet few individuals engage in formal treatment and the efficacy of established interventions for CUD is modest. Existing clinical trials evaluating psychosocial and pharmacological treatments for CUD have incorporated a wide variety of measures for assessing cannabis use outcomes, including abstinence, self-reported frequency and quantity used, withdrawal, use/dependence severity, and other psychosocial outcomes. The heterogeneity of measures and outcomes has limited quantitative analyses of the comparative effectiveness of existing interventions. The purpose of this systematic review is to: 1) identify and characterize approaches for measuring cannabis use in existing CUD intervention trials, including abstinence, frequency and quantity of use, and 2) summarize measures used to assess treatment efficacy in other outcome domains (e.g., cannabis use severity, psychosocial functioning, cannabis withdrawal), and provide a platform for future research to evaluate which outcome measures are most likely to reflect treatment efficacy and clinically significant improvement in other outcome domains.

Topics: Cannabis; Humans; Marijuana Abuse; Self Report; Substance Withdrawal Syndrome; Treatment Outcome

Cannabis use disorder (CUD) commonly occurs and carries a notable economic and functional burden at both individual and societal levels. While there are no clearly efficacious medication treatments for CUD, 20 years of committed and high-quality research in the human laboratory and clinical settings have resulted in medications with demonstrated effectiveness in the treatment of cannabis withdrawal, the ability to reduce cannabis use, and results that point to promising future work. The current state of pharmacology research for CUD highlights the need to consider particular characteristics of patients, such as gender, impulsivity, and severity of cannabis use, when selecting a medication in the off-label treatment of CUD or cannabis withdrawal. As a field, the body of work also exposes some areas in need of improvement in study design, selection of outcome measures, interpretation of results, and the overall process of evaluating candidate medications. Coming to a consensus as a field and addressing these gaps in future research will likely lend itself to further advances in improving the lives of patients with CUD.

Topics: Cannabis; Humans; Marijuana Abuse; Substance Withdrawal Syndrome

Sleep disturbance is one of the hallmarks of cannabis withdrawal. Studies have indicated that treatment of this key symptom may facilitate abstinence. In the present paper we aim to provide a systematic review of the extant literature on pharmacological management of sleep disturbance associated with cannabis withdrawal.. We conducted a systematic literature search across five electronic databases including PubMed, Psycinfo, MEDLINE, Cochrane review and Embase. Human studies using a pharmacological treatment for sleep disturbances associated with cannabis withdrawal were included. Review articles, case-series, open trials, posters, and editorials were excluded.. Seventeen publications, involving 562 participants, were included in this review. Major limitations involved small sample size, high dropout rate, methodological limitations, and heterogeneity of participants. Most of the studies were at high risk of bias, further downgrading the level of evidence. A meta-analysis was not performed due to lack of quantitative data, marked heterogeneity and low quality of the included studies.. There is not sufficient evidence for any of the reviewed treatment options. Methodological limitations in a majority of the studies rendered their findings preliminary. Of the twelve investigated pharmacological agents, Gabapentin, Lofexidine, Mirtazapine, Quetiapine, and Zolpidem showed some primary benefits for treatment of sleep difficulties associated with cannabis withdrawal; however, future prospective studies are required to confirm such results.. This review examines the current evidence for potential pharmacological options for treatment of cannabis withdrawal and associated sleep disturbance. It furthers our knowledge and provides groundwork for future research. (Am J Addict 2018;27:453-464).

Topics: Cannabis; Humans; Sleep Aids, Pharmaceutical; Sleep Wake Disorders; Substance Withdrawal Syndrome

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

Topics: Adolescent; Cannabis; Humans; Marijuana Abuse; Substance Withdrawal Syndrome

Cannabis is the world's most popular illicit drug, and around half of all Danes have tried it at least once. In this paper we review the pharmacodynamic and pharmacokinetic properties of cannabis. We also discuss the treatment of cannabis intoxication and present data from The Danish Poison Information Center.

Topics: Age Distribution; Cannabinoids; Cannabis; Denmark; Drug Interactions; Humans; Illicit Drugs; Marijuana Abuse; Poison Control Centers; Substance Withdrawal Syndrome

Cannabis can have negative effects in its users, and a range of acute and chronic health problems associated with cannabis use has been dentified. Acute cannabis consumption is rarely lethal but it is associated with an increased risk of motor vehicle accident because of longer reaction time or impaired motor coordination. Chronic effects of cannabis use include generally cardiovascular and respiratory consequences but there are also oral, gastrointestinal, cutaneous and mucous, metabolic, gynecologic and obstetrical, sexual consequences, and cancer But associated tobacco smoking or other potential confounders may explain part of those somatic consequences.

Topics: Accidents, Traffic; Cannabis; Chronic Disease; Humans; Marijuana Smoking; Substance Withdrawal Syndrome

Topics: Cannabis; Humans; Marijuana Abuse; Substance Withdrawal Syndrome

The demand for treatment for cannabis dependence has grown dramatically. The majority of the people who enter the treatment have difficulty in achieving and maintaining abstinence from cannabis. Understanding the impact of cannabis withdrawal syndrome on quit attempts is of obvious importance. Cannabis, however, has long been considered a 'soft' drug, and many continue to question whether one can truly become dependent on cannabis. Skepticism is typically focused on whether cannabis use can result in 'physiological' dependence or withdrawal, and whether withdrawal is of clinical importance.. The neurobiological basis for cannabis withdrawal has been established via discovery of an endogenous cannabinoid system, identification of cannabinoid receptors, and demonstrations of precipitated withdrawal with cannabinoid receptor antagonists. Laboratory studies have established the reliability, validity, and time course of a cannabis withdrawal syndrome and have begun to explore the effect of various medications on such withdrawal. Reports from clinical samples indicate that the syndrome is common among treatment seekers.. A clinically important withdrawal syndrome associated with cannabis dependence has been established. Additional research must determine how cannabis withdrawal affects cessation attempts and the best way to treat its symptoms.

Topics: Animals; Cannabis; Dogs; Humans; Marijuana Abuse; Mice; Rats; Substance Withdrawal Syndrome

Cannabis is one of the most frequently used substances. Cannabis and its constituent cannabinoids are known to impair several aspects of cognitive function, with the most robust effects on short-term episodic and working memory in humans. A large body of the work in this area occurred in the 1970s before the discovery of cannabinoid receptors. Recent advances in the knowledge of cannabinoid receptors' function have rekindled interest in examining effects of exogenous cannabinoids on memory and in understanding the mechanism of these effects.. The literature about the acute effects of cannabinoids on memory tasks in humans is reviewed. The limitations of the human literature including issues of dose, route of administration, small sample sizes, sample selection, effects of other drug use, tolerance and dependence to cannabinoids, and the timing and sensitivity of psychological tests are discussed. Finally, the human literature is discussed against the backdrop of preclinical findings.. Acute administration of Delta-9-THC transiently impairs immediate and delayed free recall of information presented after, but not before, drug administration in a dose- and delay-dependent manner. In particular, cannabinoids increase intrusion errors. These effects are more robust with the inhaled and intravenous route and correspond to peak drug levels.. This profile of effects suggests that cannabinoids impair all stages of memory including encoding, consolidation, and retrieval. Several mechanisms, including effects on long-term potentiation and long-term depression and the inhibition of neurotransmitter (GABA, glutamate, acetyl choline, dopamine) release, have been implicated in the amnestic effects of cannabinoids. Future research in humans is necessary to characterize the neuroanatomical and neurochemical basis of the memory impairing effects of cannabinoids, to dissect out their effects on the various stages of memory and to bridge the expanding gap between the humans and preclinical literature.

Topics: Animals; Cannabinoids; Cannabis; Drug Tolerance; Humans; Marijuana Abuse; Memory; Receptors, Cannabinoid; Substance Withdrawal Syndrome

A subset of marijuana smokers develop a cannabis use disorder and seek treatment for their marijuana use on their own initiative. A less well-known consequence of daily, repeated marijuana use is a withdrawal syndrome, characterized by a time-dependent constellation of symptoms: irritability, anxiety, marijuana craving, decreased quality and quantity of sleep, and decreased food intake. Treatment studies show that rates of continuous abstinence are low (comparable to relapse rates for other abused drugs), and more treatment options are needed. The objective of this review is to update clinicians on the current state of marijuana research and to describe features of marijuana withdrawal to facilitate the diagnosis and treatment of cannabis use disorders.

Topics: Anxiety; Cannabis; Eating; Humans; Irritable Mood; Marijuana Abuse; Sleep Wake Disorders; Substance Withdrawal Syndrome

To critically review cannabis research during the past 10 years in relation to rates of use, behavioral problems, and mental disorders in young people.. Studies published in English between 1994 and 2004 were identified through systematic searches of literature databases. The material was selectively reviewed focusing on child and adolescent data.. In the 27 years between 1976 and 2002, approximately half of all 12th graders had been exposed to cannabis in the United States. There is growing evidence that early and regular marijuana use is associated with later increases in depression, suicidal behavior, and psychotic illness and may bring forward the onset of schizophrenia. Most of the recent data reject the view that marijuana is used to self-medicate psychotic or depressive symptoms. Research on treatment is very limited.. Research on the mental health effects of cannabis has increased dramatically. Although doubts still remain about the role of cannabis in the causation of juvenile psychiatric disorder, the weight of the evidence points in the direction of early and regular cannabis use having substantial negative effects on psychosocial functioning and psychopathology.

Topics: Adolescent; Cannabis; Child; Cognition Disorders; Depression; Female; Humans; Male; Marijuana Smoking; Mental Disorders; Mental Health; Psychotic Disorders; Substance Withdrawal Syndrome; Suicide, Attempted

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.

Topics: Animals; Cannabis; Disease Models, Animal; Humans; Research Design; Substance Withdrawal Syndrome

Cannabis is commonly regarded as an innocuous drug and the prevalence of lifetime and regular use has increased in most developed countries. However, accumulative evidence highlights the risks of dependence and other adverse effects, particularly among people with pre-existing psychiatric disorders.. To re-evaluate the adverse effects of cannabis in the general population and among vulnerable individuals, including those with serious psychiatric disorders.. A wide-ranging review of the topics related to these issues. Results and conclusions An appreciable proportion of cannabis users report short-lived adverse effects, including psychotic states following heavy consumption, and regular users are at risk of dependence. People with major mental illnesses such as schizophrenia are especially vulnerable in that cannabis generally provokes relapse and aggravates existing symptoms. Health workers need to recognise, and respond to, the adverse effects of cannabis on mental health.

Topics: Affective Symptoms; Cannabis; Cognition Disorders; Female; Humans; Male; Marijuana Abuse; Psychoses, Substance-Induced; Psychotic Disorders; Psychotropic Drugs; Risk Factors; Substance Withdrawal Syndrome

The final common pathway of addiction (the dopamine hypothesis of reward) has recently been evolving, with the mesocorticolimbic dopaminergic system now seen as key to natural rewards and drug-seeking behaviour, though perhaps having less of a role in the maintenance of such behaviour. The perception of a common pathway has meant that treatments for one drug of addiction have 'crossed-over' and become possible treatments for other addictive drugs.

Topics: Alcoholism; Amphetamine-Related Disorders; Animals; Benzodiazepines; Cannabis; Cocaine-Related Disorders; Dopamine; Humans; Narcotics; Substance Withdrawal Syndrome; Substance-Related Disorders; Tobacco Use Disorder

Over 50 percent of people will use marijuana sometime in their life. While intoxication lasts two to three hours, the active ingredient in marijuana, delta-9-tetrahydro-cannabinol, can accumulate in fatty tissues, including the brain and testes. Adverse effects from marijuana use include decreased coordination, epithelial damage to the lungs, increased risk of infection, cardiovascular effects and cognitive deficits. Unexplained behavior changes, altered social relationships and poor performance at school or work can signify a drug problem. Treatment requires a combination of education, social support, drug monitoring and attention to comorbid medical and psychiatric conditions.

Topics: Cannabis; Humans; Marijuana Abuse; Patient Education as Topic; Substance Withdrawal Syndrome; Teaching Materials

Topics: Benzodiazepines; Brain; Cannabis; Central Nervous System Stimulants; Delivery of Health Care; Dopamine; Health Policy; Humans; Illicit Drugs; Narcotics; Nicotine; Nucleus Accumbens; Phencyclidine Abuse; Substance Withdrawal Syndrome; Substance-Related Disorders

The effects of cannabis on health are not easy to summarize. What little is known for certain and what can be inferred from an enormous but incomplete and imperfect literature is that cannabis under certain conditions is harmful to health. Given the breadth and complexity of the issues, this very selective review only considers health-related consequences where there was consensus by two independent scientific review groups.

Topics: Abnormalities, Drug-Induced; Animals; Behavior; Cannabis; Carcinogens; Cardiovascular System; Dronabinol; Drug Interactions; Humans; Immunity; Mental Disorders; Motivation; Mutagens; Reproduction; Respiratory System; Substance Withdrawal Syndrome

This article is a review of the principal drug-induced psychiatric symptoms that are likely to be encountered in daily clinical practice as a result of drug abuse, overdoses or side effects of drugs prescribed for treatment. Many categories of medication have the potential to produce psychiatric symptoms, but antitubercular drugs, hypotensive agents and steroids have the highest incidence in clinical practice. Additionally, the problems of alcohol are all too frequently overlooked. The variety and frequency of secondary psychiatric symptoms which may be drug-related emphasise the importance of a careful consideration of all drugs taken by a patient with psychiatric complaints, to determine causal association with symptoms.

Topics: Alcoholic Intoxication; Alcoholism; Amphetamines; Analgesics; Antihypertensive Agents; Antiparkinson Agents; Antitubercular Agents; Barbiturates; Bromides; Cannabis; Cocaine; Hallucinations; Histamine H1 Antagonists; Humans; Lysergic Acid Diethylamide; Mental Disorders; Parasympatholytics; Psychotropic Drugs; Steroids; Substance Withdrawal Syndrome

The author reviews the literature on the dependence potential of cannabis. Case studies and experiments of tolerance to cannabis as well as psychological and physical dependence on cannabis are presented in man and in laboratory animals. Some effects common to both species are also recorded. Although the addictive potential of cannabis is often compared with the addictive potential of alcohol and tobacco, the author concludes that the characteristics of cannabis tolerance are similar to those of opiate dependence.

Topics: Adolescent; Adult; Animals; Cannabis; Dronabinol; Drug Tolerance; Haplorhini; Humans; Marijuana Abuse; Rats; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Cannabis; Drug Interactions; Drug Synergism; Drug Tolerance; Ethanol; Humans; Hypnotics and Sedatives; Illicit Drugs; Pharmacology; Substance Withdrawal Syndrome; Time Factors

Topics: Animals; Behavior, Animal; Cannabis; Cognition; Dogs; Dronabinol; Drug Tolerance; Haplorhini; Humans; Mitochondria, Liver; Motor Skills; Neurons; Perception; Phytotherapy; Rats; Smoke; Structure-Activity Relationship; Substance Withdrawal Syndrome; Testosterone

Topics: Abnormalities, Drug-Induced; Animals; Behavior; Blood Pressure; Body Temperature; Cannabis; Cerebral Ventricles; Dronabinol; Drug Tolerance; Electroencephalography; Female; Heart Rate; Humans; Memory; Microsomes, Liver; Phytotherapy; Pregnancy; Psychoses, Substance-Induced; Solubility; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Administration, Oral; Brain; Cannabis; Dose-Response Relationship, Drug; Dronabinol; Drug Synergism; Drug Tolerance; Heart; Humans; Phytotherapy; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adolescent; Adult; Amphetamine; Barbiturates; Cannabis; Drug Contamination; Humans; Lysergic Acid Diethylamide; Medical History Taking; Psychoses, Substance-Induced; Solvents; Substance Withdrawal Syndrome; Substance-Related Disorders; United States

Topics: Adolescent; Adult; Black or African American; Cannabis; Female; Heroin; Humans; Hypnotics and Sedatives; Lysergic Acid Diethylamide; Male; Middle Aged; Narcotics; Pentazocine; Sex Factors; Substance Withdrawal Syndrome; Substance-Related Disorders; Tranquilizing Agents; United States

Topics: Amphetamine; Antidepressive Agents; Cannabis; Central Nervous System; Hallucinogens; Humans; Hypnotics and Sedatives; Phytotherapy; Psychophysiology; Sleep; Substance Withdrawal Syndrome; Substance-Related Disorders; Tranquilizing Agents

Conflictual evidence exists regarding the effects of cannabis use on the outcomes of opioid agonist therapy (OAT). In this exploratory analysis, we examined the effect of recent cannabis use on opioid use, craving, and withdrawal symptoms, in individuals participating in a trial comparing flexible buprenorphine/naloxone (BUP/NX) take-home dosing model to witnessed ingestion of methadone.. We analyzed data from a multi-centric, pragmatic, 24-week, open label, randomized controlled trial in individuals with prescription-type opioid use disorder (n = 272), randomly assigned to BUP/NX (n = 138) or methadone (n = 134). The study measured last week cannabis and opioid use via timeline-follow back, recorded at baseline and every two weeks during the study. Craving symptoms were measured using the Brief Substance Craving Scale at baseline, and weeks 2, 6, 10, 14, 18 and 22. The study measured opioid withdrawal symptoms via Clinical Opiate Withdrawal Scale at treatment initiation and weeks 2, 4, and 6.. The mean maximum dose taken during the study was 17.3 mg/day (range = 0.5-32 mg/day) for BUP/NX group and 67.7 mg/day (range = 10-170 mg/day) in the methadone group. Repeated measures generalized linear mixed models demonstrated that cannabis use in the last week (mean of 2.3 days) was not significantly associated with last week opioid use (aβ ± standard error (SE) = -0.06 ± 0.04; p = 0.15), craving (aβ ± SE = -0.05 ± 0.08, p = 0.49), or withdrawal symptoms (aβ ± SE = 0.09 ± 0.1, p = 0.36). Bayes factor (BF) for each of the tested models supported the null hypothesis (BF < 0.3).. The current study did not demonstrate a statistically significant effect of cannabis use on outcomes of interest in the context of a pragmatic randomized-controlled trial. These findings replicated previous results reporting no effect of cannabis use on opioid-related outcomes.

Topics: Analgesics, Opioid; Bayes Theorem; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cannabis; Humans; Methadone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Withdrawal Syndrome

Cannabis use disorder (CUD) is widespread, and there is no pharmacotherapy to facilitate its treatment. AEF0117, the first of a new pharmacological class, is a signaling-specific inhibitor of the cannabinoid receptor 1 (CB

Topics: Animals; Cannabis; Double-Blind Method; Dronabinol; Hallucinogens; Marijuana Abuse; Mice; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome

Withdrawal from cannabis use is associated with sleep disturbances, often leading to resumption of use. Less is known about the impact of abstinence on sleep in adolescence, a developmental window associated with high rates of sleep disturbance. This study investigated effects of sustained abstinence on self-reported sleep quality and disturbance in adolescents reporting frequent cannabis use.. Non-treatment seeking adolescents, recruited from school screening surveys and the community, with frequent cannabis use (M. Participants in CB-Abst reported higher overall PSQI scores than those in CB-Mon (M=1.06, p=0.01) indicating worse sleep during the four-week trial. Sleep disruptions in CB-Abst increased during Week 1 of abstinence (d=0.34, p=0.04), decreased during Week 2 (d=0.36, p=0.04), and remained constant for the rest of the trial. At Week 4, sleep was comparable to baseline levels for those in CB-Abst (p=0.87). Withdrawal-associated sleep disruption in the CB-Abst group was circumscribed to increases in sleep latency (b=0.35; p=0.05).. Cannabis abstinence in adolescents was associated with transient delayed onset of sleep initiation falling asleep during the first week of abstinence. Findings highlight withdrawal-associated changes in sleep latency as an intervention target for supporting adolescents attempting abstinence. Future research should use objective measures of sleep and focus on elucidating mechanisms underlying sleep disturbances with cannabis use and withdrawal.

Topics: Adolescent; Behavior Therapy; Cannabis; Female; Humans; Male; Marijuana Abuse; Sleep; Sleep Latency; Substance Withdrawal Syndrome

Attenuating enzymatic degradation of endocannabinoids (eCBs) by fatty acid amide hydrolase (FAAH) reduces cannabis withdrawal symptoms in preclinical and clinical studies. In mice, blocking cyclooxygenase-2 (COX-2) activity increases central eCB levels by inhibiting fatty acid degradation. This placebo-controlled study examined the effects of the FDA-approved COX-2 selective inhibitor, celecoxib, on cannabis withdrawal, 'relapse', and circulating eCBs in a human laboratory model of cannabis use disorder. Daily, nontreatment-seeking cannabis smokers (12M, 3F) completed a crossover study comprising two 11-day study phases (separated by >14 days for medication clearance). In each phase, the effects of daily BID placebo (0 mg) or celecoxib (200 mg) on cannabis (5.3% THC) intoxication, withdrawal symptoms (4 days of inactive cannabis self-administration) and 'relapse' (3 days of active cannabis self-administration following abstinence) were assessed. Outcome measures included mood, cannabis self-administration, sleep, food intake, cognitive performance, tobacco cigarette use and circulating eCBs and related lipids. Under placebo maintenance, cannabis abstinence produced characteristic withdrawal symptoms (negative mood, anorexia and dreaming) relative to cannabis administration and was associated with increased OEA (a substrate of FAAH) and oleic acid (metabolite of OEA), with no change in eCB levels. Compared to placebo, celecoxib improved subjective (but not objective) measures of sleep and did not affect mood or plasma levels of eCBs or associated lipids and increased cannabis craving. The overall absence of effects on cannabis withdrawal symptoms, self-administration or circulating eCBs relative to placebo, combined with an increase in cannabis craving, suggests celecoxib does not show promise as a potential pharmacotherapy for CUD.

Topics: Cannabinoid Receptor Agonists; Cannabis; Celecoxib; Cross-Over Studies; Cyclooxygenase 2; Dronabinol; Endocannabinoids; Humans; Marijuana Abuse; Recurrence; Smokers; Substance Withdrawal Syndrome

Sleep disturbance is a common symptom encountered by cannabis-dependent individuals abstaining from cannabis use. In the present study, we investigated the effect of daily aerobic cycling exercise versus control stretching on sleep quality during inpatient cannabis withdrawal in treatment-seeking dependent cannabis users. The protocol incorporated three consecutive phases: a 4-Day (4-Night) (at-home) 'Baseline' phase, a 6-Day (5-Night) 'Treatment' phase (within a 7-Day inpatient hospital stay) and a 3-Day (4-Night) (at-home) 'Post-Treatment' phase. Participants performed 35 min of monitored activity per day during the Treatment phase. The intervention group (n = 19) cycled at ~60% aerobic capacity (VO

Topics: Adult; Cannabis; Exercise; Female; Humans; Inpatients; Male; Substance Withdrawal Syndrome; Surveys and Questionnaires

Pharmacotherapy for cannabis use disorder (CUD) is an important unmet public health need.. In a 12-week randomized double-blind placebo-controlled trial, the efficacy of quetiapine (300 mg nightly) for the treatment of CUD was tested in 130 outpatients. Weekly cannabis use was categorized into three groups: heavy use (5-7 days), moderate use (2-4 days) and light use (0-1 days).. At baseline both groups were considered heavy users (using days per week: median = 7.0; interquartile range (IQR): 6.5-7.0; daily dollar value: median = $121.4; IQR: 73.8-206.3). The week-by-treatment interaction was marginally significant (χ. The use of quetiapine to treat CUD was associated with an increased likelihood of heavy frequency use transitioning to moderate use, but not light use. The clinical significance of reductions in cannabis use, short of abstinence warrants further study.

Topics: Adult; Antipsychotic Agents; Cannabis; Double-Blind Method; Female; Hallucinogens; Humans; Male; Marijuana Abuse; Marijuana Smoking; Middle Aged; Outpatients; Quetiapine Fumarate; Substance Withdrawal Syndrome; Treatment Outcome

Cannabis is one of the most widely used drugs worldwide. Cannabis use disorder is characterised by recurrent use of cannabis that causes significant clinical and functional impairment. There are no approved pharmacological treatments for cannabis use disorder. One approach is to potentiate endocannabinoid signalling by inhibiting fatty acid amide hydrolase (FAAH), the enzyme that degrades the endocannabinoid anandamide. We aimed to test the efficacy and safety of the FAAH-inhibitor PF-04457845 in reduction of cannabis withdrawal and cannabis use in men who were daily cannabis users.. We did a double-blind, placebo-controlled, parallel group phase 2a trial at one site in men aged 18-55 years with cannabis dependence according to DSM-IV criteria (equivalent to cannabis use disorder in DSM-5). After baseline assessments, participants were randomly assigned (2:1) to receive PF-04457845 (4 mg per day) or placebo using a fixed block size of six participants, stratified by severity of cannabis use and desire to quit. Participants were admitted to hospital for 5 days (maximum 8 days) to achieve abstinence and precipitate cannabis withdrawal, after which they were discharged to continue the remaining 3 weeks of treatment as outpatients. The primary endpoints were treatment-related differences in cannabis withdrawal symptoms during hospital admission, and week 4 (end of treatment) self-reported cannabis use and urine THC-COOH concentrations in the intention-to-treat population. The study is registered at ClinicalTrials.gov, number NCT01618656.. PF-04457845, a novel FAAH inhibitor, reduced cannabis withdrawal symptoms and cannabis use in men, and might represent an effective and safe approach for the treatment of cannabis use disorder.. United States National Institute of Drug Abuse (NIDA).

Topics: Adolescent; Adult; Amidohydrolases; Cannabis; Double-Blind Method; Humans; Male; Marijuana Abuse; Marijuana Smoking; Middle Aged; Pyridazines; Substance Withdrawal Syndrome; Treatment Outcome; Urea; Young Adult

Sex differences in cannabis use disorder (CUD) and its treatment have been identified. Women report more severe withdrawal and have shown worse treatment outcomes. Ovarian hormones are implicated in these differences and research suggests that exogenous progesterone may be an effective pharmacotherapy.. The current randomized, placebo-controlled, feasibility trial tested a novel multimodal methodology for administering exogenous progesterone during acute cannabis withdrawal. Eight heavy cannabis using women received micronized progesterone (200 mg bid) (n = 3) or matching placebo (n = 5) during the early follicular phase of their menstrual cycle over a 5-day study period while abstaining from cannabis. Laboratory visits (days 1 and 5) included biological and self-report assessments, while home-based procedures (days 2-4) included ambulatory assessments, video data capture and tele-drug testing, and biological assessments. Primary outcomes were medication adherence and salivary hormone levels, and the exploratory outcome was cannabis withdrawal severity.. Medication adherence rates were high as assessed via self-report (100.0%) and video data capture (98.0%). Salivary progesterone levels differed between groups over time (p < 0.027) and the progesterone group achieved levels within the normal range during the luteal phase in healthy adults. All tele-drug tests were negative confirming cannabis abstinence and there was an indication (p = 0.07) of reduced cannabis craving among participants receiving progesterone.. More effective and sex-based treatments for cannabis use disorder are needed. The current study provides a novel multimodal methodology with low participant burden for investigating new medications for cannabis withdrawal. Clinical trials of progesterone for cannabis withdrawal may be warranted.

Topics: Adolescent; Adult; Cannabis; Feasibility Studies; Female; Humans; Middle Aged; Placebos; Progesterone; Substance Withdrawal Syndrome; Young Adult

Despite the high prevalence of blunt smoking among cannabis users, very few studies examine the clinical profile of blunt smokers relative to those using more common methods of cannabis use, such as joints.. The current study uses baseline data from the ACCENT (Achieving Cannabis Cessation-Evaluating N-acetylcysteine Treatment) study, a multi-site randomized pharmacotherapy clinical trial within the National Drug Abuse Treatment Clinical Trials Network, to predict the association between blunt and joint use frequency and cannabis use characteristics (e.g., grams of cannabis used) and consequences (e.g., withdrawal) among past-month cannabis users (N = 377) who were screened for study participation.. After controlling for race, age, gender, other forms of cannabis use (including joint use) and nicotine dependence, multivariable linear regression models indicated that the number of days of blunt use in the past month was a significant predictor of the average amount of cannabis per using day (t = 3.04, p <  .01), the estimated average cost of cannabis (t = 2.28, p <  .05) and Cannabis Withdrawal Scale scores (t = 1.94, p <  .05). Frequency of joint use did not significantly predict any of the cannabis use characteristics or consequences.. Blunt smokers may present to treatment with greater amounts of cannabis smoked and more intense withdrawal symptoms, which may adversely impact their likelihood of successful abstinence. Cannabis-dependent blunt smokers may be more likely to benefit from treatment that targets physiological and mood-related withdrawal symptoms.

Topics: Adolescent; Adult; Cannabis; Female; Humans; Linear Models; Male; Marijuana Smoking; Middle Aged; Patient Acceptance of Health Care; Prevalence; Smoking; Substance Withdrawal Syndrome; Tobacco Use Disorder

One of the most commonly cited reasons for chronic cannabis use is to cope with stress. Consistent with this, cannabis users have shown reduced emotional arousal and dampened stress reactivity in response to negative imagery.. To our knowledge, the present study represents the first to examine the effects of an acute stress manipulation on subjective stress and salivary cortisol in chronic cannabis users compared to non-users.. Forty cannabis users and 42 non-users were randomly assigned to complete either the stress or no stress conditions of the Maastricht Acute Stress Test (MAST). The stress condition of the MAST manipulates both physiological (placing hand in ice bath) and psychosocial stress (performing math under conditions of social evaluation). Participants gave baseline subjective stress ratings before, during, and after the stress manipulation. Cortisol was measured from saliva samples obtained before and after the stress manipulation. Further, cannabis cravings and symptoms of withdrawal were measured.. Subjective stress ratings and cortisol levels were significantly higher in non-users in the stress condition relative to non-users in the no stress condition. In contrast, cannabis users demonstrated blunted stress reactivity; specifically, they showed no increase in cortisol and a significantly smaller increase in subjective stress ratings. The stress manipulation had no impact on cannabis users' self-reported cravings or withdrawal symptoms.. Chronic cannabis use is associated with blunted stress reactivity. Future research is needed to determine whether this helps to confer resiliency or vulnerability to stress-related psychopathology as well as the mechanisms underlying this effect.

Topics: Adaptation, Psychological; Adult; Cannabis; Emotions; Female; Humans; Hydrocortisone; Male; Marijuana Smoking; Middle Aged; Saliva; Self Report; Stress, Psychological; Substance Withdrawal Syndrome

There is currently no pharmacological treatment approved for cannabis dependence. In this proof of concept study, we assessed the feasibility/effects of fixed and self-titrated dosages of Sativex (1:1, Δ(9)-tetrahydrocannabinol (THC)/cannabidiol (CBD)) on craving and withdrawal from cannabis among nine community-recruited cannabis-dependent subjects.. Participants underwent an 8-week double-blind placebo-controlled trial (an ABACADAE design), with four smoke as usual conditions (SAU) (A) separated by four cannabis abstinence conditions (B-E), with administration of either self-titrated/fixed doses of placebo or Sativex (up to 108 mg THC/100 mg CBD). The order of medication administration during abstinence conditions was randomized and counterbalanced. Withdrawal symptoms and craving were assessed using the Cannabis Withdrawal Scale (CWS), Marijuana Withdrawal Checklist (MWC) and Marijuana Craving Questionnaire (MCQ). Medication use was assessed during the study by means of self-reports, vial weight control, toxicology and metabolite analysis. Cannabis use was assessed by means of self-reports.. High fixed doses of Sativex were well tolerated and significantly reduced cannabis withdrawal during abstinence, but not craving, as compared to placebo. Self-titrated doses were lower and showed limited efficacy as compared to high fixed doses. Participants reported a significantly lower "high" following Sativex or placebo as compared to SAU conditions. Cannabis/medication use along the study, as per self-reports, suggests compliance with the study conditions.. The results found in this proof of concept study warrant further systematic exploration of Sativex as a treatment option for cannabis withdrawal and dependence.

Topics: Adult; Cannabidiol; Cannabis; Craving; Double-Blind Method; Dronabinol; Drug Combinations; Female; Humans; Male; Marijuana Abuse; Marijuana Smoking; Middle Aged; Plant Extracts; Substance Withdrawal Syndrome; Substance-Related Disorders; Treatment Outcome; Young Adult

Sleep disturbance is a hallmark feature of cannabis withdrawal. In this study we explored the effects of lithium treatment supplemented with nitrazepam on objective and subjective measures of sleep quality during inpatient cannabis withdrawal.. Treatment-seeking cannabis-dependent adults (n = 38) were admitted for 8 days to an inpatient withdrawal unit and randomized to either oral lithium (500 mg) or placebo, twice daily in a double-blind RCT. Restricted nitrazepam (10 mg) was available on demand (in response to poor sleep) on any 3 of the 7 nights. Dependent outcome measures for analysis included repeated daily objective actigraphy and subjective sleep measures throughout the 8 day detox, subjective cannabis withdrawal ratings, and detoxification completion rates.. Based on actigraphy, lithium resulted in less fragmented sleep compared to placebo (p = 0.04), but no other objective measures were improved by lithium. Of the subjective measures, only nightmares were suppressed by lithium (p = 0.04). Lithium did not have a significant impact on the use of nitrazepam. Sleep bout length (p < 0.0001), sleep efficiency (p < 0.0001), and sleep fragmentation (p = 0.05) were improved on nights in which nitrazepam was used. In contrast, only night sweats improved with nitrazepam from the subjective measures (p = 0.04). A Cox regression with daily repeated measures of sleep efficiency averaged across all people in the study a predictor suggests that a one-unit increase in sleep efficiency (the ratio of total sleep time to the total time in bed expressed as a percentage) resulted in a 14.6% increase in retention in treatment (p = 0.008, Exp(B) = 0.854, 95% CI = 0.759-0.960). None of the other sleep measures, nor use of lithium or nitrazepam were significantly associated with retention in treatment.. Lithium seems to have only limited efficacy on sleep disturbance in cannabis withdrawal. However the nitrazepam improved several actigraphy measures of sleep disturbance, warranting further investigation. Discord between objective and subjective sleep indices suggest caution in evaluating treatment interventions with self-report sleep data only.

Topics: Adult; Cannabis; Double-Blind Method; Enzyme Inhibitors; Female; Humans; Hypnotics and Sedatives; Lithium Carbonate; Male; Nitrazepam; Sleep; Sleep Initiation and Maintenance Disorders; Substance Withdrawal Syndrome; Treatment Outcome

Preclinical studies suggest that lithium carbonate (lithium) can reduce precipitated cannabinoid withdrawal in rats by stimulating release of the neuropeptide oxytocin, while two open-label studies indicate lithium may ameliorate cannabis withdrawal symptoms in humans.. This study was conducted to examine the efficacy and safety of lithium in the inpatient management of cannabis withdrawal and to determine whether lithium affects plasma oxytocin and the rate of elimination of plasma cannabinoids during abstinence.. Treatment-seeking cannabis-dependent adults (n = 38) were admitted for 8 days to an inpatient withdrawal unit and randomized to either oral lithium (500 mg) or placebo given twice a day under double-blind randomized controlled trial (RCT) conditions. Primary outcomes included withdrawal severity [cannabis withdrawal scale (CWS)], rates of detoxification completion, and adverse events. Plasma cannabinoids, plasma oxytocin and serum lithium levels were measured repeatedly over admission. Follow-up research interviews were conducted at 14, 30, and 90 days postdischarge.. Lithium did not significantly affect total CWS scores relative to placebo, although it significantly reduced individual symptoms of "loss of appetite," "stomach aches," and "nightmares/strange dreams." No significant group differences were found in treatment retention or adverse events. Lithium did not increase plasma oxytocin levels nor influence the rate of elimination of cannabinoids. Both placebo- and lithium-treated participants showed reduced levels of cannabis use (verified by urinalysis) and improved health and psychosocial outcomes at 30- and 90-day follow-up relative to pretreatment baselines.. Despite the strong rationale for the present study, the efficacy of lithium over placebo in the management of cannabis withdrawal was not demonstrated.

Topics: Adult; Antipsychotic Agents; Appetite; Cannabinoids; Cannabis; Double-Blind Method; Female; Humans; Inpatients; Lithium Carbonate; Male; Marijuana Smoking; Middle Aged; Oxytocin; Substance Withdrawal Syndrome; Treatment Outcome

Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders.. Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked five puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad libitum cannabis use.. Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120mg doses.. Dronabinol's ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg/day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted.

Topics: Adolescent; Adult; Cannabis; Cross-Over Studies; Dose-Response Relationship, Drug; Dronabinol; Drug Administration Schedule; Eating; Female; Heart Rate; Humans; Male; Marijuana Abuse; Middle Aged; Sleep; Substance Withdrawal Syndrome

There are no FDA-approved pharmacotherapies for cannabis dependence. Cannabis is the most widely used illicit drug in the world, and patients seeking treatment for primary cannabis dependence represent 25% of all substance use admissions. We conducted a phase IIa proof-of-concept pilot study to examine the safety and efficacy of a calcium channel/GABA modulating drug, gabapentin, for the treatment of cannabis dependence. A 12-week, randomized, double-blind, placebo-controlled clinical trial was conducted in 50 unpaid treatment-seeking male and female outpatients, aged 18-65 years, diagnosed with current cannabis dependence. Subjects received either gabapentin (1200 mg/day) or matched placebo. Manual-guided, abstinence-oriented individual counseling was provided weekly to all participants. Cannabis use was measured by weekly urine toxicology and by self-report using the Timeline Followback Interview. Cannabis withdrawal symptoms were assessed using the Marijuana Withdrawal Checklist. Executive function was measured using subtests from the Delis-Kaplan Executive Function System. Relative to placebo, gabapentin significantly reduced cannabis use as measured both by urine toxicology (p=0.001) and by the Timeline Followback Interview (p=0.004), and significantly decreased withdrawal symptoms as measured by the Marijuana Withdrawal Checklist (p<0.001). Gabapentin was also associated with significantly greater improvement in overall performance on tests of executive function (p=0.029). This POC pilot study provides preliminary support for the safety and efficacy of gabapentin for treatment of cannabis dependence that merits further study, and provides an alternative conceptual framework for treatment of addiction aimed at restoring homeostasis in brain stress systems that are dysregulated in drug dependence and withdrawal.

Topics: Adolescent; Adult; Amines; Calcium Channel Blockers; Cannabis; Counseling; Cyclohexanecarboxylic Acids; Double-Blind Method; Executive Function; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Male; Marijuana Abuse; Middle Aged; Substance Withdrawal Syndrome; Treatment Outcome

Sleep difficulty is a common symptom of cannabis withdrawal, but little research has objectively measured sleep or explored the effects of hypnotic medication on sleep during cannabis withdrawal.. Twenty daily cannabis users completed a within-subject crossover study. Participants alternated between periods of ad libitum cannabis use and short-term cannabis abstinence (3 days). Placebo was administered at bedtime during one abstinence period (withdrawal test) and extended-release zolpidem, a non-benzodiazepine GABA(A) receptor agonist, was administered during the other. Polysomnographic (PSG) sleep architecture measures, subjective ratings, and cognitive performance effects were assessed each day.. During the placebo-abstinence period, participants had decreased sleep efficiency, total sleep time, percent time spent in Stage 1 and Stage 2 sleep, REM latency and subjective sleep quality, as well as increased sleep latency and time spent in REM sleep compared with when they were using cannabis. Zolpidem attenuated the effects of abstinence on sleep architecture and normalized sleep efficiency scores, but had no effect on sleep latency. Zolpidem was not associated with any significant side effects or next-day cognitive performance impairments.. These data extend prior research that indicates abrupt abstinence from cannabis can lead to clinically significant sleep disruption in daily users. The findings also indicate that sleep disruption associated with cannabis withdrawal can be attenuated by zolpidem, suggesting that hypnotic medications might be useful adjunct pharmacotherapies in the treatment of cannabis use disorders.

Topics: Adult; Cannabinoids; Cannabis; Control Groups; Cross-Over Studies; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Placebos; Polysomnography; Pyridines; Sleep; Sleep Initiation and Maintenance Disorders; Sleep, REM; Substance Withdrawal Syndrome; Young Adult; Zolpidem

The present study investigated the potential efficacy of buspirone for treating marijuana dependence. Participants received either buspirone (maximum 60mg/day) (n=23) or matching placebo (n=27) for 12 weeks, each in conjunction with motivational interviewing. In the modified intention-to-treat analysis, the percentage of negative UDS results in the buspirone-treatment group was 18 percentage points higher than the placebo-treatment group (95% CI: -2% to 37%, p=0.071). On self-report, participants receiving buspirone reported not using marijuana 45.2% of days and participants receiving placebo reported not using 51.4% of days (p=0.55). An analysis of participants that completed the 12-week trial showed a significant difference in the percentage negative UDS (95% CI: 7-63%, p=0.014) and a trend for participants randomized to the buspirone-treatment group who completed treatment to achieve the first negative UDS result sooner than those participants treated with placebo (p=0.054). Further study with buspirone in this population may be warranted; however, strategies to enhance study retention and improve outcome measurement should be considered in future trials.

Topics: Adult; Anti-Anxiety Agents; Anxiety; Buspirone; Cannabinoids; Cannabis; Double-Blind Method; Female; Humans; Male; Marijuana Abuse; Motivation; Psychiatric Status Rating Scales; Sample Size; Substance Withdrawal Syndrome; Surveys and Questionnaires; Treatment Outcome

This article reports the first single-blind study using psychotropic analgesic nitrous oxide (PAN) for treating acute withdrawal states following the abuse of methaqualone combined and smoked with cannabis. Smoked methaqualone combined with cannabis is called "white pipe" (WP). South Africa is the only country in the world where WP is a major form of substance abuse. This article demonstrates in 101 consecutively treated patients given placebo (100% oxygen) followed by PAN that this therapy produced a measurable therapeutic effect (more than 50% improvement) in 87 patients. This study confirms that WP is a form of substance abuse confined mainly to young adult male subjects.

Topics: Adult; Cannabis; Female; Humans; Hypnotics and Sedatives; Male; Methaqualone; Middle Aged; Nitrous Oxide; Outcome Assessment, Health Care; Psychotropic Drugs; Single-Blind Method; Substance Withdrawal Syndrome

Persistent dose-related cognitive decrements have been reported in 28-day abstinent heavy marijuana (MJ) users. However, the neural substrates of these decrements in cognitive performance are not known. This study aimed to determine if 25-day abstinent MJ users show persistent dose-related alterations in performance and brain activity using PET H(2)(15)O during the Iowa Gambling Task-IGT (a decision-making task). Eleven heavy MJ users and 11 non-drug users participated. The MJ group resided in an inpatient research unit at the NIH/NIDA-IRP for 25 days prior to testing to ensure abstinence. A dose-related association was found between increased MJ use and lower IGT performance and alterations in brain activity. The MJ group showed greater activation in the left cerebellum and less activation in the right lateral orbitofrontal cortex (OFC) and the right dorsolateral prefrontal cortex (DLPFC) than the Control group. When the MJ group was divided into Moderate (8-35 joints/week) and Heavy users (53-84 joints/week), the Heavy MJ group showed less activation in the left medial OFC and greater activation in the left cerebellum than the Moderate group. However, brain activity and task performance were similar between the Moderate MJ users and the Control group, suggesting a "threshold effect". These preliminary findings indicate that very heavy users of MJ have persistent decision-making deficits and alterations in brain activity. Specifically, the Heavy MJ users may focus on only the immediate reinforcing aspects of a situation (i.e., getting high) while ignoring the negative consequences. Thus, faulty decision-making could make an individual more prone to addictive behavior and more resistant to treatment. Finally, it is unclear if these neurologic findings will become progressively worse with continued heavy MJ use or if they will resolve with abstinence from MJ use.

Topics: Adult; Brain; Cannabis; Cerebrovascular Circulation; Data Interpretation, Statistical; Decision Making; Dose-Response Relationship, Drug; Gambling; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Marijuana Smoking; Positron-Emission Tomography; Substance Withdrawal Syndrome

Abstinence following daily marijuana use can produce a withdrawal syndrome characterized by negative mood (eg irritability, anxiety, misery), muscle pain, chills, and decreased food intake. Two placebo-controlled, within-subject studies investigated the effects of a cannabinoid agonist, delta-9-tetrahydrocannabinol (THC: Study 1), and a mood stabilizer, divalproex (Study 2), on symptoms of marijuana withdrawal. Participants (n=7/study), who were not seeking treatment for their marijuana use, reported smoking 6-10 marijuana cigarettes/day, 6-7 days/week. Study 1 was a 15-day in-patient, 5-day outpatient, 15-day in-patient design. During the in-patient phases, participants took oral THC capsules (0, 10 mg) five times/day, 1 h prior to smoking marijuana (0.00, 3.04% THC). Active and placebo marijuana were smoked on in-patient days 1-8, while only placebo marijuana was smoked on days 9-14, that is, marijuana abstinence. Placebo THC was administered each day, except during one of the abstinence phases (days 9-14), when active THC was given. Mood, psychomotor task performance, food intake, and sleep were measured. Oral THC administered during marijuana abstinence decreased ratings of 'anxious', 'miserable', 'trouble sleeping', 'chills', and marijuana craving, and reversed large decreases in food intake as compared to placebo, while producing no intoxication. Study 2 was a 58-day, outpatient/in-patient design. Participants were maintained on each divalproex dose (0, 1500 mg/day) for 29 days each. Each maintenance condition began with a 14-day outpatient phase for medication induction or clearance and continued with a 15-day in-patient phase. Divalproex decreased marijuana craving during abstinence, yet increased ratings of 'anxious', 'irritable', 'bad effect', and 'tired.' Divalproex worsened performance on psychomotor tasks, and increased food intake regardless of marijuana condition. Thus, oral THC decreased marijuana craving and withdrawal symptoms at a dose that was subjectively indistinguishable from placebo. Divalproex worsened mood and cognitive performance during marijuana abstinence. These data suggest that oral THC, but not divalproex, may be useful in the treatment of marijuana dependence.

Topics: Adult; Affect; Analysis of Variance; Anticonvulsants; Body Weight; Cannabis; Double-Blind Method; Dronabinol; Eating; Humans; Male; Neuropsychological Tests; Psychomotor Performance; Psychotropic Drugs; Sleep; Smoking; Social Behavior; Substance Withdrawal Syndrome; Surveys and Questionnaires; Time Factors; Valproic Acid

Symptoms of withdrawal after daily marijuana smoking include increased ratings of irritability and depression. Similar mood symptoms are reported by cigarette smokers during nicotine abstinence.. Given the successful use of sustained-release bupropion in treating nicotine dependence, this study investigated how maintenance on bupropion influenced symptoms of marijuana withdrawal compared to maintenance on placebo.. Marijuana smokers (n=10) were maintained outpatient on active (300 mg/day) or placebo (0 mg/day) bupropion for 11 days, and were then maintained inpatient on the same bupropion dose for 17 days. For the first 4 inpatient days, participants smoked active marijuana [2.8% delta9-tetrahydrocannabinol (THC)] 5 times/day. For the remaining inpatient days, participants smoked placebo marijuana (0.0% THC) 5 times/day. Participants were then maintained outpatient on the alternate dose of bupropion for 11 days, followed by a second inpatient residential stay, paralleling the first. Medication administration was double-blind. Mood, psychomotor task performance, food intake, and sleep were measured daily during each inpatient phase. The order of active and placebo bupropion maintenance was counterbalanced between groups.. Bupropion had few behavioral effects when participants smoked active marijuana. During placebo marijuana smoking, i.e., active marijuana withdrawal, ratings of irritability, restlessness, depression, and trouble sleeping were increased by bupropion compared to placebo maintenance.. These data suggest that bupropion does not show promise as a potential treatment medication for marijuana dependence.

Topics: Adult; Affect; Antidepressive Agents, Second-Generation; Bupropion; Cannabis; Eating; Female; Humans; Male; Psychomotor Performance; Sleep; Smoking; Social Behavior; Substance Withdrawal Syndrome

Symptoms of withdrawal after oral delta9-tetrahydrocannabinol (THC) administration have been reported, yet little is known about the development of dependence on smoked marijuana in humans. In a 21-day residential study, marijuana smokers (n = 12) worked on five psychomotor tasks during the day (0915-1700 hours), and in the evening engaged in recreational activities (1700-2330 hours); subjective-effects measures were completed 10 times/day. Food and beverages were available ad libitum from 0830 to 2330 hours. Marijuana cigarettes (0.0, 1.8, 3.1% THC) were smoked at 1000, 1400, 1800, and 2200 hours. Placebo marijuana was administered on days 1-4 . One of the active marijuana doses was administered on days 5-8, followed by 4 days of placebo marijuana (days 9-12). The other concentration of active marijuana cigarettes was administered on days 13-16, followed by 4 days of placebo marijuana (days 17-20); the order in which the high and low THC-concentration marijuana cigarettes were administered was counter-balanced between groups. Both active doses of marijuana increased ratings of "High," and "Good Drug Effect," and increased food intake, while decreasing verbal interaction compared to the placebo baseline (days 1-4). Abstinence from active marijuana increased ratings such as "Anxious," "Irritable," and "Stomach pain," and significantly decreased food intake compared to baseline. This empirical demonstration of withdrawal from smoked marijuana may suggest that daily marijuana use may be maintained, at least in part, by the alleviation of abstinence symptoms.

Topics: Adult; Affect; Appetite; Cannabis; Eating; Humans; Male; Memory; Psychomotor Performance; Sleep; Smoking; Social Behavior; Substance Withdrawal Syndrome; Substance-Related Disorders; Surveys and Questionnaires

Topics: Adult; Cannabis; Clinical Trials as Topic; Dronabinol; Drug Administration Schedule; Drug Tolerance; Electroencephalography; Humans; Male; Psychopharmacology; Substance Withdrawal Syndrome; Substance-Related Disorders; Surveys and Questionnaires; Time Factors

Topics: Amphetamine; Analgesics; Barbiturates; Cannabis; Clinical Trials as Topic; Cocaine; Cyclazocine; Drug Tolerance; Euphoria; Humans; Morphine; Nalorphine; Narcotic Antagonists; Pupil; Substance Withdrawal Syndrome; Substance-Related Disorders

While cannabis use in women is increasing worldwide, research into gender differences in cannabis use disorder (CUD) symptomology is lacking. In response to limited effectiveness of addiction treatment, research focus has been shifting from clinical diagnoses towards interactions between symptoms, as patterns of symptoms and their interactions could be crucial in understanding etiological mechanisms in addiction. The aim of this study was to evaluate the CUD symptom network and assess whether there are gender differences therein.. A total of 1257 Dutch individuals reporting weekly cannabis use, including 745 men and 512 women, completed online questionnaires assessing DSM-5 CUD symptoms and additional items on plans to quit or reduce use, cigarette use, and the presence of psychological diagnoses. Gender differences were assessed for all variables and an Ising model estimation method was used to estimate CUD symptom networks in men and women using network comparison tests to assess differences.. There were gender differences in the prevalence of 6 of the 11 symptoms, but symptom networks did not differ between men and women. Cigarette use appeared to only be connected to the network through withdrawal, indicating a potential role of cigarette smoking in enhancing cannabis withdrawal symptoms. Furthermore, there were gender differences in the network associations of mood and anxiety disorders with CUD symptoms.. The association between smoking and withdrawal as well as gender differences in the role of comorbidities in the CUD network highlight the value of using network models to understand CUD and how symptom interactions might affect treatment.

Topics: Anxiety Disorders; Cannabis; Female; Hallucinogens; Humans; Male; Marijuana Abuse; Sex Factors; Substance Withdrawal Syndrome

Rates of cannabis use disorder (CUD) are higher in people with schizophrenia than in the general population. Irrespective of psychiatric diagnosis, tobacco co-use is prevalent in those with CUD and leads to poor cannabis cessation outcomes. The cannabis withdrawal syndrome is well-established and increases cannabis relapse risk. We investigated whether cannabis withdrawal severity differed as a function of high versus no/low tobacco dependence and psychiatric diagnosis in individuals with CUD.. Men with CUD (N = 55) were parsed into four groups according to schizophrenia diagnosis and tobacco dependence severity using the Fagerstrom Test for Nicotine Dependence (FTND): men with schizophrenia with high tobacco dependence (SCT+, n = 13; FTND ≥ 5) and no/low tobacco dependence (SCT-, n = 22; FTND ≤ 4), and nonpsychiatric controls with high (CCT+, n = 7; FTND ≥ 5) and no/low (CCT-, n = 13; FTND ≤ 4) tobacco dependence. Participants completed the Marijuana Withdrawal Checklist following 12-h of cannabis abstinence.. There was a significant main effect of tobacco dependence on cannabis withdrawal severity (p < .001). Individuals with high tobacco dependence had significantly greater cannabis withdrawal severity (M = 13.85 [6.8]) compared to individuals with no/low tobacco dependence (M = 6.49, [4.9]). Psychiatric diagnosis and the interaction effects were not significant. Lastly, cannabis withdrawal severity positively correlated with FTND (r = .41, p = .002).. Among individuals with CUD and high tobacco dependence, cannabis withdrawal severity was elevated twofold, irrespective of diagnosis, relative to individuals with CUD and no/low tobacco dependence. Findings from this study emphasize the importance of addressing tobacco co-use when treating CUD.

Topics: Cannabis; Humans; Male; Marijuana Abuse; Schizophrenia; Substance Withdrawal Syndrome; Substance-Related Disorders; Tobacco Use Disorder

The objectives of this study were to characterize the detailed cannabis use patterns (eg, frequency, mode, and product) and determine the differences in the whole-blood cannabinoid profiles during symptomatic versus asymptomatic periods of participants with suspected cannabinoid hyperemesis syndrome recruited from the emergency department (ED) during a symptomatic episode.. This is a prospective observational cohort study of participants with symptomatic cyclic vomiting onset after chronic cannabis use. Standardized assessments were conducted to evaluate for lifetime and recent cannabis use, cannabis use disorder, and cannabis withdrawal symptoms. Quantitative whole-blood cannabinoid testing was performed at 2 times, first when symptomatic (ie, baseline) and at least 2 weeks after the ED visit when asymptomatic. The differences in cannabinoid concentrations were compared between symptomatic and asymptomatic testing. The study was conducted from September 2021 to August 2022.. There was a difference observed between delta-9-tetrahydrocannabinol metabolites, but not the parent compound during symptomatic episodes and asymptomatic periods. Most participants (84%) reported using cannabis > once per day (median 3 times per day on weekdays, 4 times per day on weekends). Hazardous cannabis use was universal among participants; the mean cannabis withdrawal discomfort score was 13, indicating clinically significant rates of cannabis withdrawal symptoms with cessation of use. Most participants (79%) previously tried to stop cannabis use, but a few (13%) of them had sought treatment.. Patients presenting to the ED with cannabinoid hyperemesis syndrome have high cannabis use disorder scores. Further studies are needed to better understand the influence of THC metabolism and concentrations on symptomatic cyclic vomiting.

Topics: Cannabinoids; Cannabis; Cohort Studies; Emergency Service, Hospital; Humans; Marijuana Abuse; Substance Withdrawal Syndrome; Vomiting

Cannabis use disorder (CUD) presents differently in men and women, particularly in symptoms of cannabis withdrawal. Novel pharmacotherapeutic interventions for CUD, such as those that target the endocannabinoid (eCB) system, must be developed in a manner consistent with these sex differences. The present pilot study sought to prospectively assess sex differences in cannabis withdrawal in a small sample of adults with moderate-to-severe CUD and to determine if withdrawal was associated with peripheral eCB and eCB congener tone. Men and women (n = 5/sex) completed 2 weeks of study participation separated by 1 month; in the latter week, participants abstained from cannabis use. Each week, participants attended in-person laboratory visits during which blood was drawn repeatedly to assess plasma eCB and eCB congener tone. Participants also completed multiple daily ambulatory assessments to assess cannabis use and withdrawal symptoms. As anticipated, women reported a greater increase in withdrawal symptoms during the abstinent week [Δ = 9.4 (SE = 1.1); p < 0.001] than men [Δ = 1.2 (SE = 1.2); p = 0.35]. Sex differences in levels of the eCB N-arachidonoylethanolamide (AEA), as well as the eCB congeners stearoylethanolamide (SEA) and linoleylethanolamide (LEA), were evident during abstinence at the morning time point only (p's < 0.05). LEA was associated with withdrawal symptom expression in both sexes [β = 0.16 (SE = 0.09)] and palmitoylethanolamide (PEA) [β = 0.22 (SE = 0.13)] and 2-arachidonoylglycerol (2-AG) [β = 0.32 (SE = 0.15)] were associated with withdrawal symptoms in women only. Pharmacotherapeutic development for CUD should consider evident sex differences in eCB and eCB congener tone during abstinence and their associations with cannabis withdrawal, as eCB-based interventions may produce differential effects by sex.

Topics: Adult; Caffeine; Cannabinoid Receptor Agonists; Cannabis; Endocannabinoids; Female; Humans; Male; Marijuana Abuse; Pilot Projects; Sex Characteristics; Substance Withdrawal Syndrome; Substance-Related Disorders

Synthetic cannabinoid receptor agonists (SCRAs) may be used as an alternative to natural cannabis; however, they may carry a greater risk of problematic use and withdrawal. This study aimed to characterise the withdrawal symptom profile of SCRAs and compare their profile of effect with high-potency herbal cannabis. Global Drug Survey data (2015 and 2016) were used to access a clinically relevant sample of people reporting use of SCRAs >10 times in the past 12-months, a previous SCRA quit attempt, and lifetime use of high-potency herbal cannabis. Participants completed an 11-item SCRA withdrawal symptom checklist and compared SCRAs and high-potency herbal cannabis on their onset and duration of effects, speed of the development of tolerance, severity of withdrawal, and difficulty with dose titration. Participants (n = 284) reported experiencing a mean of 4.4 (95% CI: 4.1, 4.8) withdrawal symptoms after not using SCRAs for >1 day; most frequently reported were sleep issues (59.2%), irritability (55.6%), and low mood (54.2%). Withdrawal symptoms were significantly associated with frequency (>51 vs. 11-50 times per year: IRR = 1.43, 95% CI: 1.16, 1.77, p = 0.005) and quantity (grams per session: IRR = 1.13, 95% CI: 1.05, 1.22, p = 0.001) of SCRA use. Compared to high-potency herbal cannabis, SCRAs were rated as having a faster onset and shorter duration of effects, faster development of tolerance, and more severe withdrawal (p's < 0.001). In conclusion, SCRA withdrawal symptoms are more likely to occur after greater SCRA exposure. The effects of SCRA indicate a more severe withdrawal syndrome and a greater risk of problematic use than natural cannabis.

Topics: Analgesics; Cannabinoid Receptor Agonists; Cannabis; Hallucinogens; Humans; Substance Withdrawal Syndrome

Topics: Adolescent; Cannabinoid Receptor Agonists; Cannabis; Cotinine; Cross-Sectional Studies; Hallucinogens; Humans; Marijuana Abuse; Sleep; Sleep Initiation and Maintenance Disorders; Substance Withdrawal Syndrome; Young Adult

Cannabis withdrawal symptoms contribute to relapse, but the underlying mechanism remains unclear. We hypothesize that cannabis withdrawal may be associated with a reset of regional γ-amino butyric acid (GABA) and glutamate concentrations secondary to changes in the endocannabinoid system during abstinence and conducted a study on this issue. We used magnetic resonance spectroscopy (MRS) to detect the associated changes of these neurochemicals in twenty-six frequent, recreational cannabis users and eleven age-matched non-using controls. Twenty users (8F/12M) and ten control (5F/5M) participants completed a verified 21-day abstinence period. Striatal GABA and glutamine concentrations were measured at baseline and on abstinence days 7 and 21 in conjunction with measures of cannabis withdrawal symptoms and mood state. Cannabis users reported increased self-reported ratings of cannabis-withdrawal-symptoms on abstinence day 7 relative to controls. Striatal glutamate + glutamine (Glx) group concentrations were elevated in cannabis users at baseline and abstinence days 7 and 21 (F = 7.16, p = 0.012), and changes in GABA concentration and withdrawal symptoms between baseline and abstinence day 7 were positively correlated (r = 0.550, p = 0.010). In addition, baseline striatal GABA concentrations were negatively correlated with withdrawal symptoms on abstinence day 7 (r = -0.680, p = 0.003). Our data demonstrate that striatal Glx was elevated in cannabis users and baseline striatal GABA correlated with withdrawal during the abstinence. In addition, striatal GABA may temporally correlate with self-reported withdrawal symptoms during the initial days of abrupt cannabis abstinence. These findings provide preliminary evidence that striatal GABA and Glx are associated with the severity of cannabis withdrawal.

Topics: Cannabis; gamma-Aminobutyric Acid; Glutamic Acid; Glutamine; Hallucinogens; Humans; Substance Withdrawal Syndrome

A growing body of research has reported on the potential opioid-sparing effects of cannabis and cannabinoids, but less is known about specific mechanisms. The present research examines cannabis-related posts in two large online communities on the Reddit platform ("subreddits") to compare mentions of naturalistic cannabis use by persons self-identifying as actively using opioids versus persons in recovery. We extracted all posts mentioning cannabis-related keywords (e.g., "weed", "cannabis", "marijuana") from December 2015 through August 2019 from an opioid use subreddit and an opioid recovery subreddit. To investigate how cannabis is discussed at-scale, we identified and compared the most frequent phrases in cannabis-related posts in each subreddit using term-frequency-inverse document frequency (TF-IDF) weighting. To contextualize these findings, we also conducted a qualitative content analysis of 200 random posts (100 from each subreddit). Cannabis-related posts were about twice as prevalent in the recovery subreddit (n = 908; 5.4% of 16,791 posts) than in the active opioid use subreddit (n = 4,224; 2.6% of 159,994 posts, p < .001). The most frequent phrases from the recovery subreddit referred to time without using opioids and the possibility of using cannabis as a "treatment." The most frequent phrases from the opioid subreddit referred to concurrent use of cannabis and opioids. The most common motivations for using cannabis were to manage opioid withdrawal symptoms in the recovery subreddit, often in conjunction with anti-anxiety and GI-distress "comfort meds," and to enhance the "high" when used in combination with opioids in the opioid subreddit. Despite limitations in generalizability from pseudonymous online posts, this examination of reports of naturalistic cannabis use in relation to opioid use identified withdrawal symptom management as a common motivation. Future research is warranted with more structured assessments that examines the role of cannabis and cannabinoids in addressing both somatic and affective symptoms of opioid withdrawal.

Topics: Analgesics, Opioid; Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Humans; Marijuana Abuse; Marijuana Smoking; Medical Marijuana; Narcotics; Opioid-Related Disorders; Social Media; Social Support; Substance Withdrawal Syndrome

Glutamate plays an important role in continued use of and relapse to abused substances. However, its involvement in cannabis withdrawal is still unclear. We hypothesize that regional glutamate is associated with the cannabis withdrawal syndrome and recently examined possible association of glutamate with cannabis withdrawal, using magnetic resonance spectroscopy (MRS), in non-treatment-seeking cannabis users. We recruited 26 frequent cannabis users and 11 age-matched non-using controls. Of the 37, 20 users (8f/12m) and 10 controls (5f/5m) completed a verified 21-day abstinence protocol. Dorsal anterior cingulate cortex (dACC) glutamate and γ-amino butyric acid (GABA) were measured with proton MRS at baseline and on abstinent days 7 and 21 in conjunction with measures of cannabis withdrawal and craving (MCQ), sleep difficulties (PSQI) and mood state. We used ANOVA to examine group differences in glutamate and GABA from baseline through day 21 and used linear regression to evaluate correlations between intra-individual glutamate and withdrawal symptoms. We found that self-reported anxiety severity (HAMA) was correlated with urinary THC/Cr ratios at baseline (r = 0.768, p = 0.000076) and abstinent day 7 (r = 0.5636, p = 0.0097), dACC glutamate was significantly lower in the users compared with the controls from baseline through day 21 (F = 5.90, p = 0.022), changes in glutamate between baseline and abstinent day 21 had a significantly negative correlation with corresponding changes in craving (r = -0.72, p = 0.005) after adjusting for age, consumption of alcohol/cigarettes, sleep difficulties, and urinary THC levels. These findings provide preliminary evidence that dACC glutamate is associated with the cannabis withdrawal syndrome.

Topics: Cannabinoid Receptor Agonists; Cannabis; Dronabinol; gamma-Aminobutyric Acid; Glutamic Acid; Gyrus Cinguli; Hallucinogens; Humans; Protons; Sleep Initiation and Maintenance Disorders; Substance Withdrawal Syndrome

African American/Black individuals experience significant health disparities, particularly as it relates to cannabis use. As such, there is a need to identify intrapersonal factors related to more severe patterns of use among this subpopulation. Worry about quitting or reducing cannabis as a result of the anticipated anxiety-related states during deprivation (i.e., abstinence phobia) is one factor that is theoretically important in the context of cannabis-related disparities.. Cannabis abstinence phobia was associated with greater severity of cannabis use problems, more perceived barriers for quitting cannabis use, and more severe cannabis withdrawal symptoms.. Abstinence phobia may represent an underrecognized intervention target for addressing cannabis use problems and quit success.

Topics: Adult; Analgesics; Black or African American; Cannabis; Cross-Sectional Studies; Female; Hallucinogens; Humans; Male; Marijuana Abuse; Phobic Disorders; Substance Withdrawal Syndrome

Topics: Adolescent; Cannabis; Hallucinogens; Humans; Marijuana Abuse; Marijuana Smoking; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Analgesics; Cannabinoid Receptor Agonists; Cannabis; Hallucinogens; Humans; Substance Withdrawal Syndrome; Young Adult

Anxiety sensitivity (AS) is a promising intervention target due to its relevance to negative health behaviors broadly, and substance use specifically. The aim of the current study was to evaluate the direct and indirect pathways through which elevated AS could relate to recent substance use among a national adolescent sample recruited via social-media. As predicted, AS was indirectly associated with greater likelihood of using alcohol, cigarettes, and electronic nicotine delivery systems in the past-month through anxiety symptoms. Regarding cannabis, AS was directly related to increased likelihood of past-month cannabis use; however, the indirect relation between AS and likelihood of past-month use via anxiety symptoms was not significant. Through chained indirect effects, AS was related positively to past-month alcohol and cannabis use via anxiety symptoms and coping-related motives, and through withdrawal symptoms and coping-related motives. Study findings can be used to generate hypotheses on potential pathways through which AS could prospectively relate to substance use among youth.

Topics: Adaptation, Psychological; Adolescent; Alcohol Drinking; Anxiety; Cannabis; Humans; Motivation; Nicotine; Substance Withdrawal Syndrome

In many countries, liberalisation of the legislation regulating the use of cannabis has outpaced rigorous scientific studies, and a growing number of patients presenting for surgery consume cannabis regularly. Research to date suggests that cannabis can impact perioperative outcomes. We present recommendations obtained using a modified Delphi method for the perioperative care of cannabis-using patients. A steering committee was formed and a review of medical literature with respect to perioperative cannabis use was conducted. This was followed by the recruitment of a panel of 17 experts on the care of cannabis-consuming patients. Panellists were blinded to each other's participation and were provided with rater forms exploring the appropriateness of specific perioperative care elements. The completed rater forms were analysed for consensus. The expert panel was then unblinded and met to discuss the rater form analyses. Draft recommendations were then created and returned to the expert panel for further comment. The draft recommendations were also sent to four independent reviewers (a surgeon, a nurse practitioner, and two patients). The collected feedback was used to finalise the recommendations. The major recommendations obtained included emphasising the importance of eliciting a history of cannabis use, quantifying it, and ensuring contact with a cannabis authoriser (if one exists). Recommendations also included the consideration of perioperative cannabis weaning, additional postoperative nausea and vomiting prophylaxis, and additional attention to monitoring and maintaining anaesthetic depth. Postoperative recommendations included anticipating increased postoperative analgesic requirements and maintaining vigilance for cannabis withdrawal syndrome.

Topics: Cannabinoids; Cannabis; Consensus; Delphi Technique; Humans; Intraoperative Complications; Marijuana Use; Perioperative Care; Postoperative Complications; Substance Withdrawal Syndrome

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.. 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).. Baseline, 12-month and 24-month assessments of withdrawal symptoms using the Marijuana Withdrawal Checklist-revised.. 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.. 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.

Topics: Adult; Cannabis; Chronic Pain; Hallucinogens; Humans; Medical Marijuana; Middle Aged; Substance Withdrawal Syndrome

Topics: Canada; Cannabinoids; Cannabis; Humans; Substance Withdrawal Syndrome

In psychiatry, routine EEGs are often abnormal and not very specific, raising questions about the clinical relevance and consequences of potential anomalies. One such question is whether the administration of anticonvulsants would be useful if epileptic discharges are detected in patients without any clinical correlates. With regard to this question, we present a case study in which abnormal EEG patterns were observed in a patient with chronic migraine and cannabis addiction. The patient was a 34-year-old woman with a 14-year history of cannabis abuse who, during withdrawal, showed epileptic spikes, without any corresponding clinical symptoms, and migraine attacks of increasing intensity and frequency. This case study is in line with the new

Topics: Adult; Anticonvulsants; Brain; Cannabis; Electroencephalography; Epilepsy; Female; Humans; Migraine Disorders; Substance Withdrawal Syndrome

Four states have legalized medical cannabis for the purpose of treating opioid use disorder. It is unclear whether cannabinoids improve or exacerbate opioid withdrawal. A more thorough examination of cannabis and its impact on specific symptoms of opioid withdrawal is warranted.. Two hundred individuals recruited through Amazon Mechanical Turk with past month opioid and cannabis use and experience of opioid withdrawal completed the survey. Participants indicated which opioid withdrawal symptoms improved or worsened with cannabis use and indicated the severity of their opioid withdrawal on days with and without cannabis.. 62.5% (n = 125) of 200 participants had used cannabis to treat withdrawal. Participants most frequently indicated that cannabis improved: anxiety, tremors, and trouble sleeping. A minority of participants (6.0%, n = 12) indicated cannabis worsened opioid withdrawal, specifically symptoms of yawning, teary eyes, and runny nose. Across all symptoms, more participants indicated that symptoms improved with cannabis compared to those that indicated symptoms worsened with cannabis. Women reported greater relief from withdrawal with cannabis use than men.. These results show that cannabis may improve opioid withdrawal symptoms and that the size of the effect is clinically meaningful. It is important to note that symptoms are exacerbated with cannabis in only a minority of individuals. Prospectively designed studies examining the impact of cannabis and cannabinoids on opioid withdrawal are warranted.

Topics: Analgesics, Opioid; Cannabis; Female; Humans; Male; Marijuana Abuse; Narcotics; Self Report; Substance Withdrawal Syndrome

Topics: Aggression; Cannabis; Carcinogenesis; Central Nervous System Depressants; Cognitive Dysfunction; Dangerous Behavior; Ethanol; Fetal Alcohol Spectrum Disorders; Harm Reduction; Health Status Indicators; Humans; Illicit Drugs; Marketing; New Zealand; Safety; Substance Withdrawal Syndrome

Cannabis addiction is worldwide one of the most prevalent addictions, without any effective pharmacotherapeutic options. Nabiximols spray, consisting of 2.7 mg tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD), could serve as an effective substitution therapy for cannabis addiction. Researchers reported that patients who were treated for 12 weeks with nabiximols significantly reduced the number of days on which they used cannabis (18.6 days less compared to placebo users; 95% CI: 3.5-33.7). There was no difference between groups regarding general health, the use of other substances, cannabis craving, withdrawal symptoms or achieving abstinence.

Topics: Analgesics; Cannabidiol; Cannabis; Clinical Trials as Topic; Dronabinol; Drug Combinations; Female; Humans; Male; Marijuana Abuse; Nasal Sprays; Substance Withdrawal Syndrome

The α2a-adrenergic agonist, lofexidine, reduced cannabis withdrawal-related sleep disruption in the laboratory, but side effects (e.g. fatigue, hypotension) limit its utility as a treatment for cannabis use disorder. This study tested the potential efficacy and tolerability of a daily bedtime administration of the FDA-approved α2a-adrenergic agonist, guanfacine, in a human laboratory model of cannabis use disorder. Daily, nontreatment-seeking cannabis smokers (13M, 2F) completed a within-subject study comprising two 9-day inpatient study phases. Each phase tested the effects of daily placebo or immediate-release guanfacine (2 mg) on cannabis intoxication (5.6 percent THC; 2 days), withdrawal (4 days of abstinence) and subsequent 'relapse' (3 days of cannabis self-administration). Ratings of mood, sleep, cardiovascular effects, food intake, psychomotor performance and cannabis self-administration were assessed. An outpatient phase preceded each inpatient phase for medication clearance or dose induction. Under placebo medication conditions, cannabis abstinence produced significant withdrawal, including irritability, sleep disruption and anorexia. Guanfacine reduced ratings of irritability and improved objective measures of sleep during cannabis withdrawal relative to placebo but did not reduce cannabis self-administration. Guanfacine was well tolerated with little evidence of fatigue and only small decreases in blood pressure: no dose was held due to hypotension. Thus, a single daily administration of guanfacine at bedtime improved sleep and mood during cannabis withdrawal relative to placebo. This positive signal supports further studies varying the guanfacine dose, formulation or frequency of administration, or combining it with other medications to increase the likelihood of having an impact on cannabis use.

Topics: Adrenergic alpha-2 Receptor Agonists; Adult; Affect; Anorexia; Blood Pressure; Cannabis; Feeding Behavior; Female; Guanfacine; Humans; Irritable Mood; Male; Marijuana Abuse; Psychomotor Performance; Self Administration; Sleep; Substance Withdrawal Syndrome; Young Adult

Cannabis withdrawal syndrome (CWS) was newly added to the Diagnostic and Statistical Manual of Mental Disorders in its most recent edition, DSM-5. With cannabis use increasing among U.S. adults, information is needed about the prevalence and correlates of DSM-5 CWS in the general population. This study presents nationally representative findings on the prevalence, sociodemographic and clinical correlates of DSM-5 CWS among U.S. adults.. Participants ≥18 years were interviewed in the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III) in 2012-2013. Among the sub-sample of frequent cannabis users in the prior 12 months (≥3 times a week; N = 1527), the prevalence and demographic and clinical correlates of DSM-5 CWS were examined.. In frequent cannabis users, the prevalence of CWS was 12.1%. The most common withdrawal symptoms among those with CWS were nervousness/anxiety (76.3%), hostility (71.9%), sleep difficulty (68.2%) and depressed mood (58.9%). CWS was associated with significant disability (p < 0.001), and with mood disorders (adjusted odds ratios [aOR] = 1.9-2.6), anxiety disorders (aOR = 2.4-2.5), personality disorders (aOR = 1.7-2.2) and family history of depression (aOR = 2.5) but not personal history of other substance use disorders or family history of substance use problems.. CWS is highly comorbid and disabling. Its shared symptoms with depressive and anxiety disorders call for clinician awareness of CWS and the factors associated with it to promote more effective treatment among frequent cannabis users.

Topics: Adolescent; Adult; Aged; Anxiety Disorders; Cannabis; Comorbidity; Diagnostic and Statistical Manual of Mental Disorders; Female; Health Surveys; Humans; Male; Marijuana Abuse; Marijuana Smoking; Middle Aged; Personality Disorders; Substance Withdrawal Syndrome; United States; Young Adult

There is a rapidly evolving legal and medical culture around cannabis, with corresponding changes in the demographics of users. For instance, the percentage of the aging population accessing cannabis is growing substantially, outpacing other age groups. The goals of this study were to describe the acute effects of cannabis, subjective experiences of withdrawal, and beliefs around the addictiveness of cannabis, as well as to determine whether these effects differ as a function of age or reason for use (medical vs. recreational use). It was hypothesized that medical users and younger users would report fewer adverse effects.. Survey responses from 2905 cannabis users were analyzed.. Hierarchical logistic regression analyses were used to compare group percentages after statistically controlling for confounding differences in their demographic and cannabis use characteristics. The most commonly endorsed acute effects were improved sleep, more calm/peaceful, desire to eat, more creative, and dry mouth; while the most commonly endorsed withdrawal symptoms were irritability, insomnia, and anxiety. Relative to recreational users, medical users were less likely to report undesirable acute effects but were more likely to report undesirable withdrawal symptoms. Older (50+) individuals reported fewer undesirable acute effects and withdrawal symptoms compared with younger users (18-29). Only 17% of the total sample reported believing that cannabis is addictive, and this did not vary as a function of reason for use.. Older people and medical users appear to experience acute and withdrawal effects of cannabis differently than recreational and younger users, perhaps because these groups benefit more from the medicinal properties of cannabis. These data can provide descriptive information to help inform health care providers and potential consumers about effects of cannabis use.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Behavior; Cannabis; Cognition; Cross-Sectional Studies; Female; Humans; Male; Marijuana Use; Medical Marijuana; Middle Aged; Plant Extracts; Substance Withdrawal Syndrome; Young Adult

Rates of cannabis use and related problems continue to rise, ranking as the third most common substance use disorder in the United States, behind tobacco and alcohol use. Past work suggests that perceived distress tolerance is related to several clinically significant features of cannabis use (e.g., coping-oriented use). However, there has been little exploration of the mechanisms that may underlie relations between perceived distress tolerance and cannabis use problems, withdrawal severity, and self-efficacy for quitting. The current study sought to examine the experience of pain, which frequently co-occurs with cannabis use (Ashrafioun, Bohnert, Jannausch, & Ilgen, 2015), as an underlying factor in the relation between perceived distress tolerance and cannabis related problems among 203 current cannabis-using adults (29.2% female, M = 37.7 years, SD = 10.2, 63% African American). Results indicated that perceived distress tolerance via pain related affective distress significantly predicted the severity of cannabis use problems (Pm = 0.60), degree of cannabis withdrawal (Pm = 0.39), and lower self-efficacy for quitting cannabis (Pm = 0.36). Future work may usefully explore the role of pain-related affective distress as a mechanistic factor in the context of perceived distress tolerance-cannabis relations.

Topics: Adaptation, Psychological; Adult; Affect; Cannabis; Female; Humans; Male; Marijuana Abuse; Middle Aged; Pain; Self Efficacy; Stress, Psychological; Substance Withdrawal Syndrome

Cannabis use disorders and psychiatric comorbidities. Psychiatric disorders and personality disorders are common among patients with cannabis use disorders. Symptoms of cannabis intoxication or withdrawal need to be disentangled from symptoms of psychiatric disorders. Cannabis use disorders and psychiatric disorders worsen each other. Cannabis use disorders could induce psychiatric disorders, in particular depressive disorders and anxiety disorders. Cannabis withdrawal anxiety typically begins after cannabis use has been stopped or reduced. Patients with cannabis use disorder experience, on a daily basis, subthreshold withdrawal anxiety symptoms, characterized by irritability associated with craving for cannabis. By contrast, individuals with primary anxiety disorders have different features. Integrated approaches to treatment for patients presenting with co-occurring cannabis use disorders and psychiatric disorders are recommended, including simultaneous treatments.. Consommation de cannabis et comorbidités psychiatriques. La fréquence des troubles psychiatriques et des troubles de la personnalité est élevée chez les consommateurs réguliers de cannabis. La symptomatologie des troubles anxieux ou dépressifs primaires et celle des troubles anxieux ou dépressifs induits par la consommation de cannabis sont intriquées. Ils s’aggravent mutuellement avec le temps. La symptomatologie anxieuse ou dépressive liée au manque ou au sevrage chez les sujets dépendants au cannabis est intermittente. Elle survient après une période d’abstinence, notamment au réveil. Elle est caractérisée par l’irritabilité ou la nervosité, l’existence de craving pour le cannabis et cède à la reprise de la consommation. La prise en charge optimale des patients à double diagnostic est une prise en charge dite « intégrée », combinant simultanément les approches thérapeutiques, addictologiques et psychiatriques.

Topics: Anxiety Disorders; Cannabis; Comorbidity; Humans; Marijuana Abuse; Mental Disorders; Substance Withdrawal Syndrome

Cannabis sativa withdrawal syndrome is characterized mainly by psychological symptoms. By using computational tools, the aim of this study was to propose drug candidates for treating withdrawal syndrome based on the natural ligands of the cannabinoid type 1 receptor (CB1). One compound in particular, 2-n-butyl-5-n-pentylbenzene-1,3-diol (ZINC1730183, also known as stemphol), showed positive predictions as a human CB1 ligand and for facile synthetic accessibility. Therefore, ZINC1730183 is a favorable candidate scaffold for further research into pharmacotherapeutic alternatives to treat C. sativa withdrawal syndrome.

Topics: Animals; Blood-Brain Barrier; Caco-2 Cells; Cannabis; Cell Membrane Permeability; Drug Design; Half-Life; Humans; Ligands; Mice; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Resorcinols; Substance Withdrawal Syndrome

To determine whether maternal and infant outcomes are associated with exposure to marijuana during the third trimester in a population of opioid dependent pregnant women maintained on buprenorphine.. This retrospective cohort study of 191 maternal-infant dyads exposed to buprenorphine during pregnancy examines a variety of variables including gestational age, birthweight, method of delivery, Apgar scores at one and five minutes, duration of infant hospital stay, peak neonatal abstinence syndrome (NAS) score, duration of NAS and incidence of pharmacologic treatment of NAS in infants exposed to marijuana during the third trimester as compared to infants not exposed to marijuana during the third trimester.. Analyses failed to support any significant relationship between marijuana use in the third trimester and a variety of maternal and infant outcomes. Two important variables - the likelihood of requiring pharmacologic treatment for NAS (27.6% in marijuana exposed infants vs. 15.7% in non-marijuana exposed infants, p=0.066) and the duration of infant hospital stay (7.7days in marijuana exposed infants vs. 6.6days in non-exposed infants, p=0.053) trended toward significance.. Preliminary results indicate that marijuana exposure in the third trimester does not complicate the pregnancy or the delivery process. However, the severity of the infant withdrawal syndrome in the immediate postnatal period may be impacted by marijuana exposure. Because previous study of prenatal marijuana exposure has yielded mixed results, further analysis is needed to determine whether these findings are indeed significant.

Topics: Analgesics, Opioid; Birth Weight; Buprenorphine; Cannabis; Female; Gestational Age; Humans; Infant; Infant, Newborn; Length of Stay; Marijuana Smoking; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Retrospective Studies; Substance Withdrawal Syndrome

To examine the prevalence and correlates of sleep problems in a sample of medical cannabis patients.. Adults ages 21 and older (N=801,M age=45.8) who were seeking medical cannabis certification (either for the first time or as a renewal) for chronic pain at medical cannabis clinics in southern Michigan completed baseline measures of cannabis use, sleep, pain, and other related constructs.. Over half of the sample (59%) met criteria for past 1-month sleep disturbance, defined as at least one sleep problem occurring on 15 or more nights in the past month. Most participants (86%) reported that sleep problems were due to their current pain. Approximately 80% of participants reported using cannabis in the past 6 months to improve sleep and, among these participants, cannabis was rated as helpful for improving sleep. Sleep-related cannabis side effects were rare (35%), but sleep-related cannabis withdrawal symptoms were relatively common (65%). Statistically significant correlates of past 1-month sleep disturbance included a) being female, b) being white, c) being on disability, d) not having a medical cannabis card, and e) frequency of using cannabis to help sleep.. Sleep problems are highly prevalent and frequent in medical cannabis patients and are closely tied to pain. Sleep-related cannabis withdrawal symptoms are relatively common but their clinical relevance is unknown. The association between frequency of cannabis use to help sleep with higher odds of sleep problems will need to be clarified by longitudinal studies.

Topics: Adult; Cannabis; Chronic Pain; Humans; Medical Marijuana; Michigan; Prevalence; Sleep Wake Disorders; Substance Withdrawal Syndrome; Substance-Related Disorders

We report a case of mild cannabinoid poisoning in a preschool child, after 3-week ingestion of hemp seed oil prescribed by his pediatrician to strengthen his immune system. The patient presented neurological symptoms that disappeared after intravenous hydration. A possible mild withdrawal syndrome was reported after discharge. The main metabolite of Δ-tetrahydrocannabinol was detected in urine, and very low concentration of Δ-tetrahydrocannabinol was detected in the ingested product. This is, as far as we know, the first report of cannabinoid poisoning after medical prescription of hemp seed oil in a preschool child.

Topics: Cannabinoids; Cannabis; Child, Preschool; Cytochrome P-450 CYP2C9; Cytochrome P-450 CYP3A; Dronabinol; Humans; Infusions, Intravenous; Male; Plant Oils; Poisoning; Seeds; Substance Withdrawal Syndrome; Treatment Outcome

Young adults with psychiatric illnesses are more likely to use cannabis and experience problems from use. It is not known whether those with a lifetime psychiatric illness experience a prolonged cannabis withdrawal syndrome with abstinence. Participants were fifty young adults, aged 18-25, recruited from the Boston-area in 2015-2016, who used cannabis at least weekly, completed the Structured Clinical Interview for DSM-IV to identify Axis I psychiatric diagnoses (PD+ vs PD-), and attained cannabis abstinence with a four-week contingency management protocol. Withdrawal symptom severity was assessed at baseline and at four weekly abstinent visits using the Cannabis Withdrawal Scale. Cannabis dependence, age of initiation, and rate of abstinence were similar in PD+ and PD- groups. There was a diagnostic group by abstinent week interaction, suggesting a difference in time course for resolution of withdrawal symptoms by group, F(4,46)=3.8, p=0.009, controlling for sex, baseline depressive and anxiety symptoms, and frequency of cannabis use in the prior 90days. In post hoc analyses, there was a difference in time-course of cannabis withdrawal. PD- had significantly reduced withdrawal symptom severity in abstinent week one [t(46)=-2.2, p=0.03], while PD+ did not report improved withdrawal symptoms until the second abstinent week [t(46)=-4.1, p=0.0002]. Cannabis withdrawal symptoms improved over four weeks in young people with and without a lifetime psychiatric diagnosis. However, those with a psychiatric illness reported one week delayed improvement in withdrawal symptom severity. Longer duration of cannabis withdrawal may be a risk factor for cannabis dependence and difficulty quitting.

Topics: Boston; Cannabis; Female; Humans; Male; Marijuana Abuse; Mental Disorders; Substance Withdrawal Syndrome; Time Factors; Young Adult

Topics: Administration, Intravenous; Cannabis; Delirium; Dexmedetomidine; Female; Humans; Hypnotics and Sedatives; Male; Marijuana Abuse; Marijuana Smoking; Substance Withdrawal Syndrome; Young Adult

Long-term cannabis use may confer cognitive deficits and increased risk of psychosis. However, the relationship between cannabis use and schizophrenia is complex. In particular, little is known about the effects of chronic cannabis use on the attention-related electric brain response in schizophrenia. We investigated auditory novelty and oddball P300 evoked potentials in a mixed sample of first-episode and chronic schizophrenic patients and healthy controls with (SZCA, n = 20; COCA, n = 20, abstinence ≥28 days) or without (SZ, n = 20; CO, n = 20) chronic cannabis use. Duration of regular cannabis use was 8.3 ± 5.6 (SZCA) and 9.1 ± 7.1 (COCA) years. In general, schizophrenic patients showed reduced P300 amplitudes. Cannabis use was associated with both a reduced early and late left-hemispheric novelty P300. There was a significant 'diagnosis × cannabis' interaction for the left-hemispheric late novelty P300 in that cannabis use was associated with a reduced amplitude in the otherwise healthy but not in the schizophrenic group compared with their relative control groups (corrected p < 0.02; p > 0.9, respectively). The left-hemispheric late novelty P300 in the otherwise healthy cannabis group correlated inversely with amount and duration of cannabis use (r = -0.50, p = 0.024; r = -0.57, p = 0.009, respectively). Our study confirms attentional deficits with chronic cannabis use. However, cannabis use may lead to different cognitive sequelae in patients with schizophrenia and in healthy controls, possibly reflecting preexisting alterations in the endocannabinoid system in schizophrenia.

Topics: Adolescent; Adult; Analysis of Variance; Attention Deficit Disorder with Hyperactivity; Cannabis; Electroencephalography; Event-Related Potentials, P300; Female; Humans; Male; Marijuana Abuse; Middle Aged; Psychiatric Status Rating Scales; Schizophrenia; Substance Withdrawal Syndrome; Young Adult

Adolescents who regularly use marijuana may be at heightened risk of developing subclinical and clinical psychotic symptoms. However, this association could be explained by reverse causation or other factors. To address these limitations, the current study examined whether adolescents who engage in regular marijuana use exhibit a systematic increase in subclinical psychotic symptoms that persists during periods of sustained abstinence.. The sample comprised 1,009 boys who were recruited in 1st and 7th grades. Self-reported frequency of marijuana use, subclinical psychotic symptoms, and several time-varying confounds (e.g., other substance use, internalizing/externalizing problems) were recorded annually from age 13 to 18. Fixed-effects (within-individual change) models examined whether adolescents exhibited an increase in their subclinical psychotic symptoms as a function of their recent and/or cumulative history of regular marijuana use and whether these effects were sustained following abstinence. Models controlled for all time-stable factors (default) and several time-varying covariates as potential confounds.. For each year adolescent boys engaged in regular marijuana use, their expected level of subsequent subclinical psychotic symptoms rose by 21% and their expected odds of experiencing subsequent subclinical paranoia or hallucinations rose by 133% and 92%, respectively. The effect of prior regular marijuana use on subsequent subclinical psychotic symptoms persisted even when adolescents stopped using marijuana for a year. These effects were after controlling for all time-stable and several time-varying confounds. No support was found for reverse causation.. These results suggest that regular marijuana use may significantly increase the risk that an adolescent will experience persistent subclinical psychotic symptoms.

Topics: Adolescent; Cannabis; Child; Cohort Studies; Comorbidity; Humans; Illicit Drugs; Internal-External Control; Longitudinal Studies; Male; Marijuana Abuse; Pennsylvania; Psychoses, Substance-Induced; Risk Factors; Substance Withdrawal Syndrome; Substance-Related Disorders

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

Topics: Adult; Brain; Brain Mapping; Cannabis; Craving; Cross-Sectional Studies; Cues; Female; Food Preferences; Humans; Magnetic Resonance Imaging; Male; Marijuana Abuse; Motivation; Neuropsychological Tests; Reward; Substance Withdrawal Syndrome; Visual Perception

Cannabis is clearly the most popular illicit drug in North America, Europe and in other parts of the world. Evidence is accumulating for the involvement of the endocannabinoid system in emotional processing. However, only few studies examined emotional processing in chronic, heavy cannabis users and these studies were performed in cannabis dependent patients who were abstinent for 12-48 hours. The aim of this study was to investigate facial emotion identification and discrimination abilities in patients with cannabis dependence who were abstinent for at least 1 month.. The study included 30 males with cannabis dependency according to DSM-IV criteria and who had been abstinent for at least 1 month and 30 healthy controls. All the subjects were evaluated with Facial Emotion Identification Test (FEIT) and Facial Emotion Discrimination Test (FEDT).. The main finding of this study was the presence of deficits in both identification and discrimination of facial emotions in cannabis dependent patients during abstinence. In addition, when we examined negative and positive emotions separately, we found out that abstinent cannabis dependent patients performed significantly worse than controls in the identification of negative emotions but not positive emotions.. Our findings indicate that facial emotion recognition deficits which have previously been observed in current cannabis users are still detectable in abstinent cannabis dependent patients and do not improve quickly with abstinence (an average of 3.2 months).

Topics: Adult; Cannabis; Diagnostic and Statistical Manual of Mental Disorders; Discrimination, Psychological; Emotions; Facial Expression; Female; Humans; Male; Marijuana Abuse; Neuropsychological Tests; Recognition, Psychology; Substance Withdrawal Syndrome

Amygdala volume abnormalities have been reported in relation to craving in substance-dependent adults, but it remains unclear if these effects are seen in adolescent marijuana (MJ) users, particularly following abstinence.. The aim of this study was to examine the relationship between amygdala volume and craving during 28 days of abstinence in adolescent MJ users.. MJ-using adolescents (n = 22) aged 16-19 were recruited as part of a larger study on brain function in teen drug users. Craving measures were collected twice per week throughout a 28-day abstinence period. High-resolution anatomical magnetic resonance imaging data were collected at the end of the 28 days of confirmed abstinence. Left and right amygdala volumes were traced by hand (ICC > 0.86). Composite scores for self-reported craving and withdrawal symptoms throughout the 28-day abstinence period were calculated to provide four composite measures of total craving, mood, sleep, and somatic complaints.. Results revealed that greater craving during abstinence was significantly associated with smaller left and right amygdala volumes, after controlling for age and gender. Other measures of withdrawal, including mood, somatic complaints and sleep problems, were not related to amygdala morphometry.. These results are consistent with previous findings in adult alcohol- and cocaine-dependent individuals, who demonstrated a relationship between reduced amygdala volumes and increased craving. Future studies are needed to determine if these brain-behavior relationships are attributable to MJ use or predate the onset of substance use.

Topics: Adolescent; Amygdala; Cannabis; Craving; Female; Humans; Magnetic Resonance Imaging; Male; Marijuana Smoking; Organ Size; Substance Withdrawal Syndrome; Young Adult

To investigate the impact of inpatient detoxification treatment on psychiatric symptoms of chronic cannabis addicts and to analyze the influence of serum cannabinoid levels on the severity of these symptoms.. Thirty five treatment-seeking, not active co-morbid chronic cannabis dependents (ICD-10) were studied on admission and on abstinence days 8 and 16, using several observational and self-report scales, such as Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Young Mania Rating Scale (YMRS) and Brief Psychiatric Rating Scale (BPRS), and the Symptom Checklist-90-Revised (SCL-90-R). Simultaneously obtained serum was analyzed with regard to levels of delta-9-tetrahydrocannabinol (THC) and its main metabolites 11-hydroxy-delta-9-tetrahydrocannabinol (THC-OH) and 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH).. At admission, nearly 90% of the patients were not, or only mildly, affected by depression, anxiety or manic symptoms. In contrast, patients' self-description indicated a strong psychiatric burden in approximately 60% of the cases. All patients improved significantly within 16 days of the treatment. Effect sizes ranged from 0.7 to 1.4. (Cohen's d) for the respective scales. Serum THC-levels were positively associated with impairment of cognition in HAMA and motor retardation in BPRS. All other test results were not significantly related to the serum levels of the measured cannabinoids.. Effects of the cannabis withdrawal syndrome and executive dysfunctions might explain the discrepancy between the observer ratings and self-reported psychiatric burden.. Inpatient cannabis detoxification treatment significantly improved psychiatric symptoms. Serum THC-levels were not associated with affective symptoms and anxiety but predicted cognitive impairment and motor retardation.

Topics: Cannabis; Comorbidity; Dronabinol; Female; Humans; Inpatients; Male; Marijuana Abuse; Mental Disorders; Prospective Studies; Psychiatric Status Rating Scales; Substance Withdrawal Syndrome

Over 300,000 individuals enter treatment for cannabis-use disorders (CUDs) in the United States annually. Cannabis withdrawal is associated with poor CUD-treatment outcomes, but no prior studies have examined sex differences in withdrawal among treatment-seeking cannabis users. Treatment-seeking cannabis users (45 women and 91 men) completed a Marijuana Withdrawal Checklist (Budney, Novy, & Hughes, 1999, Budney, Moore, Vandrey, & Hughes, 2003) at treatment intake to retrospectively characterize withdrawal symptoms experienced during their most recent quit attempt. Scores from the 14-item Composite Withdrawal Discomfort Scale (WDS), a subset of the Marijuana Withdrawal Checklist that corresponds to valid cannabis withdrawal symptoms described in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; APA, 2013) were calculated. Demographic and substance-use characteristics, overall WDS scores, and scores on individual WDS symptoms were compared between women and men. Women had higher overall WDS scores than men, and women had higher scores than men on 6 individual symptoms in 2 domains, mood symptoms (i.e., irritability, restlessness, increased anger, violent outbursts), and gastrointestinal symptoms (i.e., nausea, stomach pain). Follow-up analyses isolating the incidence and severity of WDS symptoms demonstrated that women generally reported a higher number of individual withdrawal symptoms than men, and that they reported experiencing some symptoms as more severe. This is the first report to demonstrate that women seeking treatment for CUDs may experience more withdrawal then men during quit attempts. Prospective studies of sex differences in cannabis withdrawal are warranted.

Topics: Adult; Cannabis; Female; Humans; Incidence; Irritable Mood; Male; Marijuana Abuse; Marijuana Smoking; Middle Aged; Retrospective Studies; Severity of Illness Index; Sex Characteristics; Substance Withdrawal Syndrome; Young Adult

Although previously thought to have no withdrawal symptoms, there is now convergent evidence for a cannabis withdrawal syndrome (CWS), criteria for its diagnosis, and evidence of its impact in the adolescent population. Cannabis withdrawal syndrome represents an important and under-recognized consideration in adolescents with disordered eating. We describe three clinical cases of adolescents presenting to an eating disorders program with primary complaints of gastrointestinal symptoms, food avoidance, and associated weight loss. They did not meet the criteria for an eating disorder, but did fulfill the DSM-5 criteria for CWS. This report emphasizes the importance of considering the impact of heavy cannabis use in adolescents presenting with gastrointestinal complaints, and eating disorder symptoms, including weight loss.

Topics: Adolescent; Cannabinoids; Cannabis; Feeding and Eating Disorders; Female; Humans; Marijuana Abuse; Substance Withdrawal Syndrome

Cannabis is one of the most commonly used recreational drugs worldwide. Psychoactive properties of the principal compound, δ-9-tetrahydrocannabinol include euphoria, a sense of relaxation and increased appetite. Chronic cannabis use has been associated with the development of a withdrawal syndrome on abrupt discontinuation. Withdrawal symptoms typically begin within 24 h of abstinence and manifest as irritability, nervousness, sleep disturbances and decreased appetite. There is growing evidence that supports the use of plant-derived and synthetic cannabinoids for the treatment of cannabis withdrawal. In this case report, we present 20-year-old woman who developed protracted nausea and vomiting secondary to cannabis withdrawal and was successfully treated with nabilone. Nausea and vomiting is not listed in the Diagnostic and Statistical Manual-5 diagnostic criteria for cannabis withdrawal syndrome and is an uncommon symptom presentation.

Topics: Cannabinoids; Cannabis; Diagnosis, Differential; Dronabinol; Female; Humans; Nausea; Substance Withdrawal Syndrome; Vomiting; Young Adult

Topics: Australia; Cannabis; Female; Humans; Male; Marijuana Abuse; Native Hawaiian or Other Pacific Islander; Substance Withdrawal Syndrome

Evidence is accumulating that a cannabis withdrawal syndrome is common, of clinical significance, and has a clear time course. Up till now, very limited data exist on the cannabis withdrawal symptoms in patients with co-morbid substance use disorders, other than cannabis use and tobacco use.. Symptoms of withdrawal were assessed through patient self-reports during detoxification in Danish residential rehabilitation centers. Patients (n = 90) completed booklets three times during their first month at the treatment centre. Self-reported withdrawal symptoms was rated using the DSM-5 Withdrawal Symptom Check List with withdrawal symptoms from all classes of substances, with no indication that the described symptoms should be attributed to withdrawal. Self-reported time since last use of cannabis was used as a predictor of cannabis withdrawal severity.. With the exception of loss of appetite, time since last use of cannabis was associated with all types of withdrawal symptoms listed in the DSM-5. Only four of 19 symptoms intended to measure withdrawal from other substances were related to time since last use of cannabis, including vivid, unpleasant dreams.. The findings yield strong support to the notion of a cannabis withdrawal syndrome, and gives further evidence for the inclusion of the criterion of vivid, unpleasant dreams. Further, the findings speak against the significance of demand characteristics in determining the course of the symptoms of cannabis withdrawal.

Topics: Adult; Cannabis; Diagnostic and Statistical Manual of Mental Disorders; Drug Users; Female; Humans; Irritable Mood; Male; Severity of Illness Index; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Cannabis use is widespread among patients with schizophrenia despite its negative impact on the course of the disease. Craving is a considerable predictor for relapse in people with substance use disorders. Our investigation aimed to gain insight into the intensity and dimensions of cravings in patients with schizophrenia and cannabis use disorders (CUDs), compared with otherwise healthy people with CUDs (control subjects).. We examined 51 patients with schizophrenia and CUDs and 51 control subjects by means of the Cannabis-Craving Screening questionnaire.. We found greater overall intensity of craving and greater relief craving in patients with schizophrenia and CUDs. Reward craving was greater in the CUDs group. Relief craving was associated with symptoms of schizophrenia in patients with schizophrenia and CUDs.. Our findings are in line with the view that aspects of self-medication or affect regulation may account (at least in part) for cannabis use in people with schizophrenia. A better understanding of the dimensions of craving may help to improve targeted therapeutic interventions that aim to reduce drug consumption in this difficult-to-treat patient group.

Topics: Adult; Cannabis; Case-Control Studies; Female; Humans; Male; Marijuana Abuse; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Substance Withdrawal Syndrome; Young Adult

  Cannabis withdrawal in heavy users is commonly followed by increased anxiety, insomnia, loss of appetite, migraine, irritability, restlessness and other physical and psychological signs. Tolerance to cannabis and cannabis withdrawal symptoms are believed to be the result of the desensitization of CB1 receptors by THC..   This report describes the case of a 19-year-old woman with cannabis withdrawal syndrome treated with cannabidiol (CBD) for 10 days. Daily symptom assessments demonstrated the absence of significant withdrawal, anxiety and dissociative symptoms during the treatment..   CBD can be effective for the treatment of cannabis withdrawal syndrome.

Topics: Adult; Cannabidiol; Cannabis; Female; Humans; Substance Withdrawal Syndrome; Young Adult

Various studies support the inclusion of cannabis withdrawal in the diagnosis of cannabis use disorder (CUD) in the upcoming DSM-5. The aims of the current study were to (1) estimate the prevalence of DSM-5 cannabis withdrawal (criterion B), (2) estimate the role of genetic and environmental influences on individual differences in cannabis withdrawal and (3) determine the extent to which genetic and environmental influences on cannabis withdrawal overlap with those on DSM-IV-defined abuse/dependence.. The sample included 2276 lifetime cannabis-using adult Australian twins. Cannabis withdrawal was defined in accordance with criterion B of the proposed DSM-5 revisions. Cannabis abuse/dependence was defined as endorsing one or more DSM-IV criteria of abuse or three or more dependence criteria. The classical twin model was used to estimate the genetic and environmental influences on variation in cannabis withdrawal, along with its covariation with abuse/dependence.. Of all the cannabis users, 11.9% met criteria for cannabis withdrawal. Around 50% of between-individual variation in withdrawal could be attributed to additive genetic variation, and the rest of the variation was mostly due to non-shared environmental influences. Importantly, the genetic influences on cannabis withdrawal almost completely (99%) overlapped with those on abuse/dependence.. We have shown that cannabis withdrawal symptoms exist among cannabis users, and that cannabis withdrawal is moderately heritable. Genetic influences on cannabis withdrawal are the same as those affecting abuse/dependence. These results add to the wealth of literature that recommends the addition of cannabis withdrawal to the diagnosis of DSM-5 CUD.

Topics: Adult; Australia; Cannabis; Diagnostic and Statistical Manual of Mental Disorders; Diseases in Twins; Female; Genetic Predisposition to Disease; Humans; Male; Marijuana Abuse; Prevalence; Registries; Substance Withdrawal Syndrome; Young Adult

Cannabis withdrawal occurs in frequent users who quit, but there are no accepted diagnostic criteria for a cannabis withdrawal syndrome (CWS). This study evaluated diagnostic criteria for CWS proposed in DSM-V and two earlier proposals.. A convenience sample of 384 adult, non-treatment-seeking lifetime cannabis smokers provided retrospective self-report data on their "most difficult" quit attempt without formal treatment, which was used in this secondary analysis. Prevalence, time of onset, and peak intensity (5-point Likert scale) for 39 withdrawal symptoms (drawn from the literature) were assessed via computer-administered questionnaire. Subject groups were compared using chi-square or ANOVA. Symptom clustering was evaluated with principal components analysis.. 40.9% of subjects met the DSM-V criterion of ≥3 symptoms from a list of 7. There were no associations with sex, race, or type of cannabis preparation used. There were significant positive associations between duration or frequency of cannabis use prior to the quit attempt and experiencing CWS. Subjects with CWS had a significantly shorter duration of abstinence. Alternative syndromal criteria (dropping physical symptoms from DSM-V list; requiring ≥2 or ≥4 symptoms from a list of 11) yielded a similar prevalence of CWS and similar associations with prior cannabis use and relapse. The PCA yielded 12 factors, including some symptom clusters not included in DSM-V.. Findings support the concurrent and predictive validity of the proposed DSM-V CWS, but suggest that the list of withdrawal symptoms and number required for diagnosis warrant further evaluation.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Cannabis; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Male; Marijuana Abuse; Middle Aged; Retrospective Studies; Socioeconomic Factors; Substance Withdrawal Syndrome; Surveys and Questionnaires; Young Adult

The main characteristics of cannabis dependence are craving, persistent desire or unsuccessful efforts to cut down or control cannabis use and important social, occupational, or recreational activities given up or reduced because of cannabis use. Withdrawal symptoms include insomnia, irritability, anger, restlessness, depression, mood swings and cravings. Regular cannabis use induces cognitive impairment, especially of attention, episodic memory and working memory. Alcohol and other substances abuse or dependence are frequently found in patients with cannabis dependence. Psychiatric comorbidities are frequent in patients with cannabis dependence, in particular anxiety disorders, mood disorders, and personality disorders. The treatment of cannabis dependence includes behavioral psychotherapy, especially motivational interviewing and cognitive-behavioral therapy, alongside treatment of co-occurring mental health and substance use conditions. There are currently no available pharmacological treatment interventions for cannabis dependence. The treatment of cannabis dependence and withdrawal remains nonspecific.

Topics: Cannabis; Humans; Marijuana Abuse; Substance Withdrawal Syndrome

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

Topics: Adolescent; Adult; Cannabis; Female; Humans; Male; Marijuana Abuse; Middle Aged; Recurrence; Research Design; Severity of Illness Index; Substance Withdrawal Syndrome

While animal models of epilepsy suggest that exogenous cannabinoids may have anticonvulsant properties, scant evidence exists for these compounds' efficacy in humans. Here, we report on two patients whose focal epilepsy was nearly controlled through regular outpatient marijuana use. Both stopped marijuana upon admission to our epilepsy monitoring unit (EMU) and developed a dramatic increase in seizure frequency documented by video-EEG telemetry. These seizures occurred in the absence of other provocative procedures, including changes to anticonvulsant medications. We review these cases and discuss mechanisms for the potentially anticonvulsant properties of cannabis, based on a review of the literature.

Topics: Adult; Brain; Cannabis; Electroencephalography; Epilepsies, Partial; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Phytotherapy; Seizures; Substance Withdrawal Syndrome; Tomography, Emission-Computed, Single-Photon

Despite an emerging consensus that the DSM-IV diagnostic criteria for cannabis abuse and dependence are best represented by a single underlying liability, it remains unknown if latent class or hybrid models can better explain the data.. Using structured interviews, 7316 adult male and female twins provided complete data on DSM-IV symptoms of cannabis abuse and dependence. Our aim was to derive a parsimonious, best-fitting cannabis use disorder (CUD) phenotype based on DSM-III-R/IV criteria by comparing an array of psychometric models (latent factor analysis, latent class analysis and factor mixture modeling) using full information maximum likelihood ordinal data methods in Mx.. We found little evidence to support population heterogeneity since neither latent class nor hybrid factor mixture models provided a consistently good fit to the data. When conditioned on initiation and cannabis use, the endorsement patterns of the abuse, dependence and withdrawal criteria were best explained by two latent factors for males and females. The first was a general CUD factor for which genetic effects explained 53-54% of the variance. A less interpretable second factor included a mix of cross-loading dependence and withdrawal symptoms.. This is the first study to compare competing measurement models to derive an empirically determined CUD phenotype. Commensurate with proposed changes to substance use disorders in the DSM-V, our results support an emerging consensus that a single CUD latent factor can more optimally assess the risk or liability underpinning correlated measures of use, abuse, dependence and withdrawal criterion.

Topics: Adult; Cannabis; Female; Humans; Interviews as Topic; Male; Marijuana Abuse; Middle Aged; Models, Psychological; Psychometrics; Reproducibility of Results; Substance Withdrawal Syndrome

Rates of treatment seeking for cannabis are increasing, and relapse is common. Management of cannabis withdrawal is an important intervention point. No psychometrically sound measure for cannabis withdrawal exists, and as a result treatment developments cannot be optimally targeted. The aim is to develop and test the psychometrics of the Cannabis Withdrawal Scale and use it to explore predictors of cannabis withdrawal.. A volunteer sample of 49 dependent cannabis users provided daily scores on the Cannabis Withdrawal Scale during a baseline week and 2 weeks of abstinence.. Internal reliability (Cronbach's alpha=0.91), test-retest stability (average intra-class correlation=0.95) and content validity analysis show that the Cannabis Withdrawal Scale has excellent psychometric properties. Nightmares and/or strange dreams was the most valid item (Wald χ²=105.6, P<0.0001), but caused relatively little associated distress (Wald χ²=25.11, P=0.03). Angry outbursts were considered intense (Wald χ²=73.69, P<0.0001) and caused much associated distress (Wald χ²=45.54, P<0.0001). Trouble getting to sleep was also an intense withdrawal symptom (Wald χ²=42.31, P<0.0001) and caused significant associated distress (Wald χ²=47.76, P<0.0001). Scores on the Severity of Dependence Scale predicted cannabis withdrawal.. The Cannabis Withdrawal Scale can be used as a diagnostic instrument in clinical and research settings where regular monitoring of withdrawal symptoms is required.

Topics: Adult; Cannabis; Dronabinol; Female; Forecasting; Humans; Male; Marijuana Abuse; Middle Aged; Psychiatric Status Rating Scales; Psychometrics; Psychotropic Drugs; Reproducibility of Results; Substance Withdrawal Syndrome; Surveys and Questionnaires

Despite an increased understanding of the pharmacology and long-term cognitive effects of cannabis in humans, there has been no research to date examining its chronic effects upon reward processing in the brain. Motivational theories regarding long-term drug use posit contrasting predictions with respect to how drug users are likely to process non-drug incentives. The reward deficiency syndrome (RDS) of addiction posits that there are deficits in dopamine (DA) motivational circuitry for non-drug rewards, such that only drugs of abuse are capable of normalizing DA in the ventral striatum (VS). Alternatively, the opponent process theory (OPT) holds that in individuals prone to drug use, there exists some form of mesolimbic hyperactivity, in which there is a bias towards reward-centred behaviour concomitant with impulsivity. The current study examined BOLD responses during reward and loss anticipation and their outcome deliveries in 14 chronic cannabis users and 14 drug-naive controls during a monetary incentive delay (MID) task. Despite no significant behavioural differences between the two groups, cannabis users had significantly more right VS BOLD activity during reward anticipation. Correlation analyses demonstrated that this right VS BOLD response was significantly correlated with life-time use and reported life-time cannabis joints consumed. No correlations between cannabis abstinence and BOLD responses were observed. We also observed a number of group differences following outcome deliveries, most notably hypoactivity in the left insula cortex in response to loss and loss avoidance outcome notifications in the cannabis group. These results may suggest hypersensitivity during instrumental response anticipation for non-drug rewards and a hyposensitivity to loss outcomes in chronic cannabis users; the implications of which are discussed with respect to the potentially sensitizing effects of cannabis for other rewards.

Topics: Adult; Cannabis; Cues; Dopamine; Female; Humans; Image Processing, Computer-Assisted; Limbic System; Magnetic Resonance Imaging; Male; Marijuana Abuse; Motivation; Neostriatum; Oxygen; Putamen; Reward; Substance Withdrawal Syndrome; Young Adult

Topics: Adult; Cannabis; Female; Humans; Male; Marijuana Abuse; Opioid-Related Disorders; Outpatients; Prevalence; Sleep Wake Disorders; Substance Withdrawal Syndrome; Surveys and Questionnaires

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

Topics: Adult; Cannabis; Chi-Square Distribution; Diagnostic Self Evaluation; Female; Humans; Interviews as Topic; Male; Marijuana Abuse; Patient Acceptance of Health Care; Recurrence; Severity of Illness Index; Substance Withdrawal Syndrome; Surveys and Questionnaires

Cognitive deficits that persist up to a month have been detected among adult marijuana users, but decrements and their pattern of recovery are less known in adolescent users. Previously, we reported cognitive deficits among adolescent marijuana users after one month of abstinence (Medina, Hanson, Schweinsburg, Cohen-Zion, Nagel, & Tapert, 2007). In this longitudinal study, we characterized neurocognitive changes among marijuana-using adolescents across the first three weeks of abstinence.. Participants were adolescent marijuana users with limited alcohol and other drug use (n=19) and demographically similar non-using controls (n=21) ages 15-19. Participants completed a brief neuropsychological battery on three occasions, after 3days, 2weeks, and 3weeks of stopping substance use. Abstinence was ascertained by decreasing tetrahydrocannabinol metabolite values on serial urine drug screens. Verbal learning, verbal working memory, attention and vigilance, and time estimation were evaluated.. Marijuana users demonstrated poorer verbal learning (p<.01), verbal working memory (p<.05), and attention accuracy (p<.01) compared to controls. Improvements in users were seen on word list learning after 2weeks of abstinence and on verbal working memory after 3weeks. While attention processing speed was similar between groups, attention accuracy remained deficient in users throughout the 3-week abstinence period.. This preliminary study detected poorer verbal learning and verbal working memory among adolescent marijuana users that improved during three weeks of abstinence, while attention deficits persisted. These results implicate possible hippocampal, subcortical, and prefrontal cortex abnormalities.

Topics: Adolescent; Attention; Cannabis; Case-Control Studies; Cognition; Dronabinol; Female; Humans; Learning; Learning Disabilities; Longitudinal Studies; Male; Marijuana Abuse; Memory, Short-Term; Neuropsychological Tests; Substance Withdrawal Syndrome; Young Adult

The present investigation examined the role of anxiety symptoms immediately following substance abuse treatment in the relation between frequency of pre-treatment marijuana use and relapse to marijuana use at 12-months post-treatment among 1288 male patients who used marijuana within the 3 months prior to admission to treatment. Consistent with expectation, more frequent marijuana use at intake predicted more anxiety symptoms at discharge. Anxiety symptoms at discharge predicted relapse to marijuana use at 12-month follow-up, but did not mediate the relation between intake marijuana use and relapse. Results are discussed in relation to better understanding the role of increased anxiety during discontinuation of regular marijuana use in the prediction of relapse to marijuana.

Topics: Adult; Anxiety; Cannabis; Follow-Up Studies; Humans; Male; Marijuana Abuse; Middle Aged; Psychiatric Status Rating Scales; Recurrence; Substance Withdrawal Syndrome

Adult human studies suggest frontal dysfunction associated with chronic marijuana (MJ) use, but due to continued neuromaturation, adult studies may not generalize to adolescents. This study characterized prefrontal cortex (PFC) morphometry in chronic MJ-using adolescents following 1 month of monitored abstinence. Data were collected from MJ users (n = 16) and controls (n = 16) aged 16-18. Extensive exclusionary criteria included co-morbid psychiatric and neurologic disorders. Substance use and anatomical measures were collected after 28 days of monitored abstinence. PFC volumes were ascertained from manual tracing by reliable raters on high-resolution magnetic resonance images. After controlling for lifetime alcohol use, gender and intracranial volume, MJ users did not differ from controls in PFC volume. However, marginal group-by-gender interactions were observed (P < 0.09): female MJ users demonstrated comparatively larger PFC volumes while male MJ users had smaller volumes compared with same-gender controls. Further, group status and total PFC volume interacted in predicting executive functioning (P < 0.05). Among MJ users, smaller PFC total volume was associated with better executive functioning while the opposite pattern was seen among the controls. These preliminary results indicate that gender may moderate the relationship between MJ use and PFC morphometry. Given the relationship between larger PFC total volumes and poorer executive functioning among MJ users, female MJ users may be at increased risk for neurocognitive consequences. Future research will measure PFC gray and white matter separately and follow boys and girls over adolescence to examine the influence of MJ use on neurodevelopment.

Topics: Adolescent; Cannabis; Cognition Disorders; Executive Function; Female; Humans; Magnetic Resonance Imaging; Male; Marijuana Abuse; Neuropsychological Tests; Prefrontal Cortex; Prevalence; Severity of Illness Index; Sex Factors; Substance Withdrawal Syndrome

A cannabis withdrawal syndrome has been characterized, but its clinical significance remains uncertain. One method of assessing the significance of cannabis withdrawal is to compare it directly to an established withdrawal syndrome. The present study was a within-subject comparison of cannabis, tobacco, and combined cannabis and tobacco withdrawal among users of both substances. Participants (N=12) completed three 5-day periods of abstinence in a randomized order, separated by 9-day periods of usual substance use. Overall withdrawal severity associated with cannabis alone and tobacco alone was of a similar magnitude. Withdrawal during simultaneous cessation of both substances was more severe than for each substance alone, but these differences were of short duration and substantial individual differences were noted. These results are consistent with other evidence suggesting cannabis withdrawal is clinically important and warrants detailed description in the DSM-V and ICD-11. Additional research is needed to replicate these findings and to further investigate the effects of abstaining from multiple drugs simultaneously.

Topics: Adolescent; Adult; Aggression; Alcohol Drinking; Analysis of Variance; Anger; Attention; Cannabinoids; Cannabis; Cotinine; Drug Interactions; Female; Humans; Irritable Mood; Male; Nicotiana; Psychiatric Status Rating Scales; Sleep; Substance Withdrawal Syndrome; Surveys and Questionnaires

Controversy exists regarding the inclusion of cannabis withdrawal as an indicator of dependence in the next revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD). This study contrasted the concurrent and predictive validity of three operational definitions of cannabis withdrawal in a sample of treated adolescents.. Prospective study of treated adolescents with 1-year follow-up.. Adolescents (n=214) were recruited from intensive out-patient treatment programs for substance abuse, and followed at 1 year (92% retention). Youth who were included in the analyses reported regular cannabis use.. The number of DSM-IV cannabis abuse and dependence symptoms at baseline and 1-year follow-up, past year frequency of cannabis use at baseline and follow-up, and periods of abstinence at 1-year follow-up. Cannabis withdrawal was defined based on (i) the presence of two or more cannabis withdrawal symptoms; (ii) a definition proposed by Budney and colleagues (2006) that requires four or more withdrawal symptoms (four-symptom definition); and (iii) the use of latent class analysis to identify subgroups with similar cannabis withdrawal symptom profiles.. All three definitions of cannabis withdrawal demonstrated some concurrent validity. Only the four-symptom and latent class-derived definitions of withdrawal predicted severity of cannabis-related problems at 1-year follow-up. No cannabis withdrawal definition predicted frequency of use at follow-up. Further research is needed to determine the clinical utility and validity of the four-symptom definition, as well as alternative definitions of cannabis withdrawal, to inform revisions leading to DSM-V and ICD-11.

Topics: Adolescent; Cannabis; Female; Follow-Up Studies; Humans; Male; Marijuana Abuse; Predictive Value of Tests; Prospective Studies; Severity of Illness Index; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome

This study assessed whether oral administration of delta-9-tetrahydrocannbinol (THC) effectively suppressed cannabis withdrawal in an outpatient environment. The primary aims were to establish the pharmacological specificity of the withdrawal syndrome and to obtain information relevant to determining the potential use of THC to assist in the treatment of cannabis dependence.. Eight adult, daily cannabis users who were not seeking treatment participated in a 40-day, within-subject ABACAD study. Participants administered daily doses of placebo, 30 mg (10 mg/tid), or 90 mg (30 mg/tid) oral THC during three, 5-day periods of abstinence from cannabis use separated by 7-9 periods of smoking cannabis as usual.. Comparison of withdrawal symptoms across conditions indicated that (1) the lower dose of THC reduced withdrawal discomfort, and (2) the higher dose produced additional suppression in withdrawal symptoms such that symptom ratings did not differ from the smoking-as-usual conditions. Minimal adverse effects were associated with either active dose of THC.. This demonstration of dose-responsivity replicates and extends prior findings of the pharmacological specificity of the cannabis withdrawal syndrome. The efficacy of these doses for suppressing cannabis withdrawal suggests oral THC might be used as an intervention to aid cannabis cessation attempts.

Topics: Administration, Oral; Adult; Cannabis; Dose-Response Relationship, Drug; Dronabinol; Female; Hallucinogens; Humans; Male; Marijuana Abuse; Middle Aged; Severity of Illness Index; Substance Withdrawal Syndrome; Surveys and Questionnaires

The present investigation examined the relation between anxiety sensitivity (AS) and marijuana withdrawal severity among 84 (47 female) young adult marijuana smokers. As expected, after covarying for the theoretically-relevant variables of frequency of past 30-day marijuana use, number of cigarettes smoked per day, volume of alcohol consumed, and anxious arousal as well as anhedonic depressive symptoms, both the global AS factor and the AS-mental incapacitation concerns factor were significantly related to the severity of retrospectively reported marijuana withdrawal symptoms. Results are discussed in relation to better understanding cognitive-emotional variables related to the marijuana withdrawal.

Topics: Adolescent; Adult; Anxiety Disorders; Cannabis; Female; Humans; Male; Prevalence; Retrospective Studies; Severity of Illness Index; Substance Withdrawal Syndrome; Surveys and Questionnaires

Although marijuana dependence is prevalent, most individuals with marijuana dependence do not seek treatment. There are few data characterizing treatment seeking marijuana-dependent patients compared to patients presenting for treatment of other drugs regarding the severity of illness and motivation for treatment. Forty-two marijuana-dependent individuals were compared to 58 cocaine-dependent individuals seeking treatment. Compared to cocaine-dependent patients, those with marijuana dependence were younger and less likely to be dependent on alcohol or other drugs. Both groups had similar rates of comorbid anxiety and affective disorders. Marijuana-dependent individuals had lower total number of dependence symptoms but had a higher percentage of individuals endorsing withdrawal symptoms. Although marijuana-dependent individuals had less outpatient treatment exposure, the difference between the two groups was not significant and motivation for change, based on the University of Rhode Island Change Assessment, was similar for both groups of treatment seekers. However, the Circumstances, Motivation, Readiness for Treatment Scale suggested that cocaine-dependent individuals were more motivated for treatment. Taken together, these data suggest that treatment seeking marijuana-dependent individuals have substantial withdrawal dependence symptomatology although it is less clear if they are as motivated to seek out treatment as cocaine-dependent treatment seekers.

Topics: Adult; Age Factors; Anxiety; Cannabis; Cocaine; Cocaine-Related Disorders; Comorbidity; Female; Humans; Male; Marijuana Abuse; Mood Disorders; Motivation; Patient Acceptance of Health Care; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome

Repeated marijuana use is known to lead to physical dependence in humans; however, its dependence liability has yet to be adequately assessed in laboratory animals. The goals of the present study were to: assess whether the CB(1) antagonist SR 141716 (rimonabant) precipitates withdrawal in mice that had been repeatedly exposed to marijuana smoke, and to compare these precipitated withdrawal effects to those elicited following intravenous administration of its chief psychoactive component Delta(9)-tetrahydrocannabinol (Delta(9)-THC). SR 141716 elicited a significant increase in paw tremors in mice that were repeatedly dosed with either marijuana or Delta(9)-THC. Unexpectedly, the blood and brain concentrations of Delta(9)-THC following marijuana exposure were considerably lower than those found following Delta(9)-THC injection when comparing an equivalent magnitude of paw tremors in both conditions. Finally, Delta(9)-THC dose-dependently alleviated SR 141716-induced paw tremors in marijuana-dependent mice, but marijuana itself failed to reverse the precipitated withdrawal effect. It is likely that marijuana exposure generated insufficient Delta(9)-THC brain levels (i.e., 203+/-19 ng/g) to reverse the withdrawal signs compared with the brain levels following intravenous injection (i.e., 1862+/-82 ng/g). These findings taken together indicate that mice exposed repeatedly to marijuana smoke exhibit similar precipitated withdrawal effects as Delta(9)-THC-injected mice.

Topics: Animals; Cannabis; Male; Mice; Mice, Inbred ICR; Piperidines; Pyrazoles; Rimonabant; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Brain; Cannabis; Chronic Disease; Cognition Disorders; Drug Administration Schedule; Humans; Marijuana Abuse; Neuropsychological Tests; Substance Withdrawal Syndrome; Time

To determine possible effects of prolonged marijuana use on the cerebrovascular system during a month of monitored abstinence and to assess how the intensity of current use might have influenced cerebrovascular perfusion in these marijuana users.. The authors recorded blood flow velocity in the anterior and middle cerebral arteries using transcranial Doppler sonography in three groups of marijuana users who differed in the intensity of recent use (light: n = 11; moderate: n = 23; and heavy: n = 20) and in control subjects (n = 18) to assess the nature and duration of any potential abnormalities. Blood flow velocity was recorded within 3 days of admission and 28 to 30 days of monitored abstinence on an inpatient research unit in order to evaluate subacute effects of the drug and any abstinence-generated changes.. Pulsatility index, a measure of cerebrovascular resistance, and systolic velocity were significantly increased in the marijuana users vs control subjects. These increases persisted in the heavy marijuana users after a month of monitored abstinence.. Chronic marijuana use is associated with increased cerebrovascular resistance through changes mediated, in part, in blood vessels or in the brain parenchyma. These findings might provide a partial explanation for the cognitive deficits observed in a similar group of marijuana users.

Topics: Adolescent; Adult; Alcohol Drinking; Antisocial Personality Disorder; Blood Flow Velocity; Cannabis; Cerebral Arteries; Cerebrovascular Circulation; Female; Hemodynamics; Humans; Inpatients; Male; Marijuana Abuse; Marijuana Smoking; Severity of Illness Index; Smoking; Substance Withdrawal Syndrome; Time Factors; Tobacco Use Disorder; Ultrasonography, Doppler, Transcranial; Vascular Resistance

A valid cannabis withdrawal syndrome has been demonstrated in controlled studies with adult marijuana abusers, yet few published reports have examined cannabis withdrawal among adolescents. Adolescents presenting for outpatient substance abuse treatment, whose primary substance of abuse was cannabis, completed a questionnaire reporting the presence and severity of withdrawal symptoms during past periods of cannabis abstinence. Nearly two-thirds of the sample indicated that they had experienced four or more symptoms, and over one-third reported four or more symptoms that occurred at a moderate or greater severity. The magnitude of withdrawal severity was positively correlated with current emotional and behavioral symptoms and self-reported problems with cannabis use. These findings are consistent with previous studies, though the prevalence and magnitude of withdrawal symptoms were lower than that observed in a similar study with adult treatment seekers [Budney, A.J., Novy, P., Hughes, J.R., 1999. Marijuana withdrawal among adults seeking treatment for marijuana dependence. Addiction 94, 1311-1322]. Further research is needed to elucidate associations between cannabis withdrawal effects, the initiation of cessation attempts, and relapse.

Topics: Adolescent; Cannabis; Female; Humans; Male; Marijuana Abuse; Mood Disorders; Patient Acceptance of Health Care; Retrospective Studies; Sleep Wake Disorders; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome; Vermont

Topics: Adult; Antipsychotic Agents; Cannabis; Drug Administration Schedule; Female; Humans; Lithium Carbonate; Male; Substance Withdrawal Syndrome

In this paper the dependence syndrome on cannabis as it is defined in International Classification Systems (e.g., DSM-IV) will be examined from a theoretical and a technical point of view. Therefore, both the conceptualization and the operationalization of the dependence syndrome are the focus of interest. It is shown that dependence on cannabis should deal with only psychic dependence. Analyzing criteria of psychic dependence via DSM-IV points to the need of conceptual reformulation. Deficiencies concerning variable validity and measurement conditions are pointed out. It is suggested, that the dependence syndrome on cannabis via international classification systems (e.g. DSM-IV) should be revised.

Topics: Cannabis; Diagnostic and Statistical Manual of Mental Disorders; Humans; Marijuana Abuse; Substance Withdrawal Syndrome; Substance-Related Disorders; Terminology as Topic

Topics: Brain; Cannabis; Cerebrovascular Circulation; Cerebrovascular Disorders; Clinical Trials as Topic; Cognition Disorders; Dose-Response Relationship, Drug; Humans; Marijuana Abuse; Plant Preparations; Reproducibility of Results; Substance Withdrawal Syndrome

This paper describes the process evaluation of an out-patient detoxification service (ODS) established by Drug Health Services (DHS) to increase the supervised withdrawal options for substance users in a Sydney metropolitan Area Health Service. The ODS aimed to provide a safe and effective supervised withdrawal to substance users who were at low risk of severe withdrawal, engage those with severe dependence in further treatment and increase the involvement of general practitioners (GPs) in the medical care of ODS clients. During its first 10 months of operation, the ODS received 199 inquiries, assessed 82 individuals and admitted 76 clients for detoxification. Withdrawal treatment proceeded without complications and within the expected time frames. Fifty-four clients completed withdrawal, 10 ceased treatment, 10 remained in treatment without completing withdrawal and two were transferred elsewhere. Clients who injected substances (mainly heroin) daily at admission, compared to others, were less likely to complete withdrawal and more likely to use a range of non-prescribed substances during withdrawal. One-fifth of clients went on to further treatment with DHS, attending at least once. Overall, the ODS met its goals, providing a safe and effective supervised withdrawal to local residents, especially women, young people and those withdrawing from benzodiazepines who had significant substance dependence, impairment and previous alcohol and other drug (AOD) treatment. Non-injecting substance users benefited most from the ODS in terms of withdrawal completion and ongoing treatment. The level of GP involvement in the conjoint care of ODS clients remained constant over time. The development and expansion of the ODS are discussed.

Topics: Adolescent; Adult; Anxiety; Benzodiazepines; Cannabis; Depression; Ethanol; Evaluation Studies as Topic; Female; Heroin; Humans; Male; Middle Aged; New South Wales; Outpatients; Stress, Physiological; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Amphetamines; Benzodiazepines; Cannabis; Clinical Protocols; Ethanol; Humans; Records; Substance Withdrawal Syndrome

Despite extensive research on the effects of cannabis on cognitive and motor performance, studies administering computerised cognitive batteries and pencil-and-paper tests have not provided consistent results. Contributing factors are the broad range of tests used, together with a lack of sensitivity for assessing specific cognitive processes. This study for the first time assesses a very early cognitive process, information processing, that is sufficiently fundamental as to be immune from higher cognitive, motivational, and social processes. Information processes are thought to represent the basic building blocks of higher order cognitive processes. The inspection time (IT) task was used to investigate the effects of acute and subacute cannabis use on information processing in 22 heavy users, compared to 22 noncannabis-using controls. Findings indicate that users in the subacute state display significantly slowed information-processing speeds (longer ITs) compared to controls. Paradoxically, this deficit appears to be normalised whilst users are in the acute state. These results may be explained as a withdrawal effect, but may also be due to tolerance development as a result of long-term cannabis use. Furthermore, these results may assist in providing an explanation for the development of dependence with chronic cannabis users.

Topics: Acute Disease; Adult; Cannabis; Cognition Disorders; Female; Humans; Male; Marijuana Abuse; Neuropsychological Tests; Reaction Time; Substance Withdrawal Syndrome

The aim of this study was the assessment of disorders after chronic intake of psychoactive drugs, like marijuana, amphetamine, ecstasy, cocaine and opiates. In 2002 in the Department of Clinical Toxicology detoxification unit were treated 117 chronic drug abusers. The 76 of them use the opiates predominantly, the next 41 persons (35 men, 6 women), were heavy abusers of psychostimulant drugs. In opiate abusers typical withdrawal signs and symptoms were observed. In the group of psychostimulants users, the mean time of marijuana use was 6 years, amphetamine--5 years. The cocaine was used rarely. Among 25 persons (61%) from these group the withdrawal syndrome were established. The excitation of neurovegetative system, depression, or psychomotor effects were observed. We concluded the necessity of estimation of neurobiological changes after using of psychostimulants and that more controlled research might uncover a clinically diagnosable withdrawal syndrome in human psychostimulants users.

Topics: Adolescent; Adult; Amphetamine; Amphetamine-Related Disorders; Cannabis; Cocaine; Cocaine-Related Disorders; Female; Hospitalization; Humans; Male; Marijuana Abuse; Middle Aged; N-Methyl-3,4-methylenedioxyamphetamine; Narcotics; Opioid-Related Disorders; Poland; Psychotropic Drugs; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome

Cognitive, cerebrovascular, and psychiatric impairments have been documented with chronic marijuana users. To better understand the nature and duration of these neurocognitive changes in marijuana abusers, we recorded the resting EEG of 29 abstinent chronic marijuana abusers and 21 control subjects. The marijuana abusers were tested twice: the first evaluation occurred within 72 hours of admission to the inpatient research unit; the second evaluation occurred after 28 to 30 days of monitored abstinence. A three-minute period of EEG was recorded during resting eyes-closed conditions from eight electrodes (F(3), C(3), P(3), O(1), F(4), C(4), P(4), and O(2)). The artifacted EEG was converted to six frequency bands (delta, theta, alpha(1), alpha(2), beta(1), and beta(2)) using a fast Fourier transform. During early abstinence, absolute power was significantly lower (p < 0.05) for the marijuana abusers than for the control subjects for the theta and alpha(1) bands. These reductions in theta and alpha(1) power persisted for 28 days of monitored abstinence. These EEG changes, together with cerebral blood flow deficits, might underlie the cognitive alterations observed in marijuana abusers. Additional research is needed to determine how long these deficits persist during abstinence and if treatment with neuroprotective agents may reverse them.

Topics: Adult; Cannabis; Cerebrovascular Circulation; Electroencephalography; Humans; Male; Marijuana Abuse; Substance Withdrawal Syndrome

Withdrawal symptoms following cessation of heavy cannabis (marijuana) use have been reported, yet their time course and clinical importance have not been established. A 50-day outpatient study assessed 18 marijuana users during a 5-day smoking-as-usual phase followed by a 45-day abstinence phase. Parallel assessment of 12 ex-users was obtained. A withdrawal pattern was observed for aggression, anger, anxiety, decreased appetite, decreased body weight, irritability, restlessness, shakiness, sleep problems, and stomach pain. Onset typically occurred between Days 1-3, peak effects between Days 2-6, and most effects lasted 4-14 days. The magnitude and time course of these effects appeared comparable to tobacco and other withdrawal syndromes. These effects likely contribute to the development of dependence and difficulty stopping use. Criteria for cannabis withdrawal are proposed.

Topics: Adult; Cannabis; Female; Health Status; Humans; Male; Substance Withdrawal Syndrome; Time Factors

Cannabis use is widespread in our community. Dependence on cannabis may be associated with significant mental and physical harms.. This article aims to give an overview of the adverse effects of cannabis use and guidelines for management of cannabis dependence.. General practitioners can manage cannabis dependence from a harm minimisation framework using motivational interviewing and other counselling measures. Occasionally, pharmacologic approaches may be used with the caveat that they should be brief and carefully monitored.

Topics: Adult; Australia; Cannabis; Family Practice; Female; Humans; Male; Marijuana Smoking; Practice Guidelines as Topic; Substance Withdrawal Syndrome

Topics: Cannabis; Drug and Narcotic Control; Humans; Marijuana Smoking; Substance Withdrawal Syndrome

Topics: Cannabis; Humans; Marijuana Abuse; Substance Withdrawal Syndrome

Topics: Adaptation, Physiological; Cannabis; Humans; Substance Withdrawal Syndrome

Symptoms of dependence and withdrawal after the frequent administration of high doses (210 mg/day) of oral delta9-tetrahydrocannabinol (THC) have been reported, yet little is known about dependence on lower oral THC doses, more relevant to levels attained by smoking marijuana. In a 20-day residential study, male (n = 6) and female (n = 6) marijuana smokers worked on five psychomotor tasks during the day (0915-1700 hours), and in the evening engaged in private or social recreational activities (1700-2330 hours); subjective-effects measures were completed 10 times/day, and a sleep questionnaire was completed each morning. Food and beverages were available ad libitum from 0830 to 2330 hours. Capsules were administered at 1000, 1400, 1800, and 2200 hours. Placebo THC was administered on days 1-3, 8-11, and 16-19. Active THC was administered on days 4-7 (20 mg qid) and on days 12-15 (30 mg qid). Both active doses of THC increased ratings of "High," "Good Drug Effect," and "Willingness to Take Dose Again" compared to baseline (days 1-3). THC also increased food intake by 35-45%, and decreased verbal interaction among participants compared to placebo baseline. Tolerance developed to the subjective effects of THC but not to its effects on food intake or social behavior. Abstinence from THC increased ratings of "Anxious," "Depressed," and "Irritable," decreased the reported quantity and quality of sleep, and decreased food intake by 20-30% compared to baseline. These behavioral changes indicate that dependence develops following exposure to lower daily doses of THC than have been previously studied, suggesting that the alleviation of abstinence symptoms may contribute to the maintenance of daily marijuana use.

Topics: Administration, Oral; Adult; Appetite; Appetite Stimulants; Cannabis; Dronabinol; Drug Tolerance; Eating; Female; Humans; Male; Psychomotor Performance; Social Behavior; Substance Withdrawal Syndrome; Substance-Related Disorders; Surveys and Questionnaires

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: > or = one dependence diagnoses and > or = 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.

Topics: Adolescent; Adult; Age of Onset; Cannabis; Chi-Square Distribution; Conduct Disorder; Disease Progression; Female; Humans; Interview, Psychological; Juvenile Delinquency; Male; Marijuana Abuse; Marijuana Smoking; Multivariate Analysis; Prevalence; Reward; Sampling Studies; Severity of Illness Index; Substance Withdrawal Syndrome; Substance-Related Disorders

Establishment of residual cognitive and psychotic effects (effects present at the time that all active cannabinoids are eliminated from the body) putatively produced by prolonged heavy cannabis use is difficult, because of many confounding variables like slow elimination of active cannabinoids, lack of supervision during abstinence, poor use of well-matched control groups and the presence of withdrawal symptoms. Residual cognitive effects were observed in some but not in all tests after prolonged heavy cannabis use. The effects were mostly mild. The relationship of cannabis use, psychotic effects and schizophrenia was unclear; the cannabis conceivably gave relief, but it also appeared that cannabis caused schizophrenia in young people and (or) enhanced the symptoms, especially in young people poorly able to cope with stress or in whom the antipsychotic therapy was unsuccessful.

Topics: Adolescent; Cannabinoids; Cannabis; Chronic Disease; Cognition; Cognition Disorders; Confounding Factors, Epidemiologic; Diagnosis, Differential; Drug Residues; Female; Humans; Male; Psychoses, Substance-Induced; Schizophrenia; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Amygdala; Animals; Brain; Cannabis; Corticotropin-Releasing Hormone; Dopamine; Dronabinol; Humans; Naloxone; Nucleus Accumbens; Rats; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Animals; Cannabis; Dopamine; Dronabinol; Humans; Nucleus Accumbens; Rats; Reward; Substance Withdrawal Syndrome; Substance-Related Disorders

Morphine (10 mg/kg), ethanol (8% w/v, 2 ml/kg), nicotine (0.1 mg/kg), cannabis extract (200 mg/kg), lorazepam (10 mg/kg) and ondansetron (0.1 mg/kg) were each administered to rats twice daily i.p. for 14 days and the anxiogenic response following their withdrawal was monitored by the elevated plus-maze test 24 h later. Brains were removed and endogenous monoamine oxidase (MAO) A and B inhibitory activity (tribulin) levels measured on day 14 and 24 h after drug withdrawal in different groups of animals. Morphine, ethanol, lorazepam and nicotine withdrawal was associated with significant anxiety and corresponding increase in brain tribulin activity, particularly its MAO A inhibitory component. Cannabis and ondansetron withdrawal were neither associated with anxiety or change in tribulin levels. The investigation supports the postulated role of tribulin as an endogenous correlate of anxiety, its MAO A inhibitory component accounting for a major part of this effect.

Topics: Animals; Anxiety; Brain; Brain Chemistry; Cannabis; Ethanol; Isatin; Isoenzymes; Lorazepam; Male; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Morphine; Nicotine; Ondansetron; Rats; Rats, Wistar; Substance Withdrawal Syndrome

In 31 patients with tranquilizer-and 13 patients with drug abuse the character and extent of changes in EEG during withdrawal period were studied and the influence of additional abuse of alcohol or barbiturates was investigated. The EEG showed pathological results in 22 patients (50%). Generalised spike activity was dominant, which was found more often in patients with tranquilizer abuse (35%) than in patients with drug abuse (15%). In patients with abuse of tranquilizers and additional alcoholism pathological EEGs were found more often (65%) than in the remaining patients (36%). Also in patients with additional abuse of barbiturates pathological EEGs (67%) were found more often. In patients with drug abuse with or without additional abuse of alcohol or barbiturates there was no difference between the number of normal and pathological EEGs. In patients with longer persistence of the tranquilizer abuse the number of pathological EEGs increased. Controls of the EEG revealed with increasing time interval an increasing number of normalised EEGs especially in patients without alcoholism of barbiturate abuse. Therefore the EEG revealed functional disturbances in the withdrawal period after abuse of tranquilizers or drugs which were more pronounced in patients with additional abuse or alcohol or barbiturates.

Topics: Adolescent; Adult; Aged; Barbiturates; Brain; Cannabis; Electroencephalography; Ethanol; Heroin; Humans; Middle Aged; Substance Withdrawal Syndrome; Tranquilizing Agents

Drug abuse is a prevalent problem in society and often occurs as abuse of multiple substances. The authors present a model for understanding the clinical symptomatology and course of substance-induced organic mental disorders and present a hypothesis that explains how various factors might interact to produce the disorder. A clinical case is used to illustrate the use of this approach and suggestions are made for the diagnosis and treatment of these disorders.

Topics: Adult; Alcoholic Intoxication; Cannabis; Cocaine; Drug Interactions; Humans; Lysergic Acid Diethylamide; Male; Methaqualone; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Alcoholism; Cannabis; Cocaine; Female; Fetal Alcohol Spectrum Disorders; Humans; Infant, Newborn; Narcotics; Pregnancy; Pregnancy Complications; Prenatal Care; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adult; Cannabis; Dementia; Humans; Male; Marijuana Abuse; Psychoses, Substance-Induced; Substance Withdrawal Syndrome; Syndrome

Although neonatal withdrawal syndrome is often noted in infants of narcotics addicts, ethanol withdrawal has been reported only among neonates with fetal alcohol syndrome. To examine the possibility that ethanol withdrawal occurs more widely and to identify its characteristics, the behavior of eight neonates born to women who drank a mean of 21 ounces of absolute alcohol per week during gestation was compared with that of two contrast groups: 15 infants whose mothers drank an equivalent amount but stopped in the second trimester, and 29 infants whose mothers never drank. None of the 52 infants had fetal alcohol syndrome, and all were in good health. Neurobehavioral evaluation 3 days postnatally compared the groups for the occurrence of characteristic signs of withdrawal from central nervous system depressants. Whereas there was no difference in the frequency of withdrawal symptoms among infants of mothers who never drank (mean 1.4) or of mothers who stopped drinking (mean 1.8), infants of mothers who continued to drink (mean 4.7) had significantly more tremors, hypertonia, restlessness, excessive mouthing movements, unconsolable crying, and reflex abnormalities. By interfering with state control and interactive behaviors, withdrawal could affect mother-infant bonding as well as the conditions that foster cognitive and social development.

Topics: Alcohol Drinking; Cannabis; Ethanol; Female; Fetal Alcohol Spectrum Disorders; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Pregnancy; Substance Withdrawal Syndrome

Topics: Amphetamines; Analgesics; Bromates; Cannabis; Hallucinogens; Heroin Dependence; Humans; Hypnotics and Sedatives; Narcotics; Substance Withdrawal Syndrome; Substance-Related Disorders; Tranquilizing Agents

Topics: Amphetamines; Barbiturates; Cannabis; Cocaine; Female; Fetal Alcohol Spectrum Disorders; Heroin Dependence; Humans; Infant, Newborn; Infant, Newborn, Diseases; Lysergic Acid Diethylamide; Methadone; Narcotics; Pregnancy; Substance Withdrawal Syndrome; Substance-Related Disorders; Tranquilizing Agents

Topics: Adult; Anxiety; Cannabis; Dronabinol; Humans; Male; MMPI; Personality; Social Adjustment; Substance Withdrawal Syndrome; Substance-Related Disorders

In this paper the results of a multidisciplinary long term and controlled study on chronic cannabis use are critically reviewed. The first part of the study consisted of: (a) standardization of methods and identification of the experimental sample of chronic cannabis users and matched controls; (b) comparison of the two groups on a number of variables following administration of a battery of medical, psychiatric, neurophysiologic, and psychologic tests; (c) acute cannabis inhalation experiments during which the effect of cannabis preparations of various strengths and of THC-delta-9 were studied in relation to behavioral, psychologic, neurophysiologic, and psychophysiologic responses; (d) identificaiton of possible withdrawal symptoms during a 3-day abstinence period and reintroduction of hashish use. The second part of the study consisted of: (a) a controlled histochemical and electron-microscopic investigation of blood cells and sperm, aimed at revealing changes produced by cannabis at the molecular level, particularly in the cell-nuclear area; (b) a biochemical investigation of changes in biogenic amines and substances related to their metabolism and function during cannabis pre-smoking and postsmoking periods. Our findings from the first part of the study failed to distinguish users from nonusers on most of the investigated parameters. However, they provided useful information on a variety of controversial issues and revealed methodological limitations which should guide future research. Our findings from the second part of the study, although still preliminary, clearly indicate that cannabis use affects cell-nuclear metabolism and produces changes on the molecular level potentially significant for man's biologic functioning. Furthermore findings from this part of this study indicated that cannabis' acute effects in man are correlated with changes in metabolism directly related to biogenic amine biosynthesis and function. It is concluded that despite advances in recent years cannabis research has still a long way to go before providing the definitive answers to the very important questions arising from its habitual use by man.

Topics: Adolescent; Adult; Blood Pressure; Brain; Cannabis; Cell Nucleus; Dronabinol; Electroencephalography; Female; Heart Rate; Histones; Humans; Lymphocytes; Male; Middle Aged; Motivation; Neurotransmitter Agents; Neutrophils; Psychological Tests; Psychoses, Substance-Induced; Spermatozoa; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Amphetamines; Cannabis; Heroin Dependence; Humans; Infant, Newborn; Infant, Newborn, Diseases; Lysergic Acid Diethylamide; Personality; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Aftercare; Amphetamines; Cannabis; Drug and Narcotic Control; Heroin Dependence; Humans; Hypnotics and Sedatives; Japan; Lysergic Acid Diethylamide; Psychotherapy; Substance Withdrawal Syndrome; Substance-Related Disorders; Tranquilizing Agents

Legal control of drugs available in Australia varies according to the nature of the drug. This article considers the question whether the different degrees of legal control can be justified on the basis of the pharmacological effects of the drugs or on the basis of their correlation with violent behaviour.

Topics: Adult; Alcoholism; Australia; Barbiturates; Cannabis; Crime; Heroin Dependence; Humans; Legislation, Drug; Middle Aged; Substance Withdrawal Syndrome; Substance-Related Disorders; Violence

A group of experiments is described in which chimpanzees and orangutans are utilized as subjects in research projects designed to evaluate the effects of stimulant and depressant drugs on learning and performance. Efficiency of performance on a task which measures spaced responding was impaired when subjects smoked cigarettes containing delta9-tetrahydrocannabinol prior to testing. In a sequential learning task, these subjects also demonstrated reduced performance when stimulatn drugs were orally administered before testing. Depressant drugs did not produce comparable decrements in sequential learning performance. Physical and behavioral tolerance and dependence on ethanol were investigated in rhesus monkey subjects using a variety of experimental procedures, including forced oral acceptance, intragastric intubation, intravenous infusion, and conditioned voluntary oral acceptance.

Topics: Animals; Behavior, Animal; Cannabis; Discrimination Learning; Dronabinol; Drug Tolerance; Ethanol; Haplorhini; Hominidae; Humans; Macaca; Macaca mulatta; Memory; Reinforcement, Psychology; Substance Withdrawal Syndrome; Substance-Related Disorders

Tolerance at all levels of complexity in the brain involves "learning" in the sense of the acquisition of compensatory adaptations to the consequences of the presence of a drug-produced disturbance in function. Depending on the function, species, and dose of cannabis, "tissue tolerance," behaviorally augmented (to provide the presence of the disturbed function) or not, develops at different rates or not all (e.g., to impairment of the logical sequence of thoughts, to which no tolerance has yet been demonstrated). "Dispositional tolerance" (increased rate of metabolism of delta 9-THC due to enzyme induction) may play a role in the development of tolerance or "reverse tolerance" to cannabis in man. There is evidence that for the label "high," placebo effects may account for the "reverse tolerance" seen in experienced users on smoking (but not on ingestion of delta 9-THC or placebo) along with evidence of residual tolerance to other not-so-labeled effects of the drug. Dependence on cannabis, in the sense of abstinence phenomena on abrupt withdrawal of delta 9-THC, has been demonstrated in monkeys made tolerant to delta 9-THC given four times daily for about 1 month. In man, physiologic marijuana abstinence signs have not been demonstrated, but behavioral (and some physiologic) abstinence phenomena have been reported in heavy users of hashish or ganja. The between-dose hyperirritability and dysphoria reported to occur in experimental studies on chronic marijuana intoxication may actually be early and short-lived abstinence changes. In the West, where marijuana with relatively low delta 9-THC content is widely smoked, dependence in the sense of drug-seeking behavior appears to be less a function of any pharmacologic reinforcing properties the drug may have than of secondary (conditioned) reinforcement derived from the social milieu in which the marijuana is smoked. In cultures where marijuana of higher delta 9-THC content, hashish, or ganja is used, pharmacologic reinforcement (through suppression of abstinence changes) may play a greater role in maintaining drug-seeking behavior.

Topics: Animals; Behavior, Animal; Cannabis; Chickens; Columbidae; Cricetinae; Dogs; Dronabinol; Drug Tolerance; Female; Haplorhini; Humans; Learning; Male; Pan troglodytes; Rabbits; Rats; Substance Withdrawal Syndrome; Substance-Related Disorders

The effects of various doses of 1-trans-delta9-tetrahydrocannabinol (delta9-THC) on naloxone-induced withdrawal were studied in mice rendered dependent on morphine by the pellet implantation procedure. When administered i.p., 30 min prior to naloxone, delta9-THC, inhibited the naloxone-induced withdrawal jumping response. Two other signs of morphine withdrawal (defecation and rearing behavior) were also suppressed by deltapTHC. It is suggested that delta9-THC or some of its derivatives may have potential use in narcotic detoxification.

Topics: Animals; Cannabis; Dose-Response Relationship, Drug; Dronabinol; Humans; Male; Mice; Morphine Dependence; Naloxone; Substance Withdrawal Syndrome

Topics: Animals; Cannabis; Dronabinol; Humans; Hypnotics and Sedatives; Methadone; Rats; Research Design; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Animals; Cannabis; Humans; Male; Mental Disorders; Neurocognitive Disorders; Substance Withdrawal Syndrome; Wounds and Injuries

Delta-THC (10 mg/kg, i.p.) administered to mice immediately after withdrawal from a 3-day exposure to ethanol vapor was found to intensify withdrawal reactions. No effect was seen when delta-THC was administered chronically during the exposure to ethanol.

Topics: Alcoholism; Animals; Cannabis; Dronabinol; Ethanol; Humans; Male; Mice; Pyrazoles; Substance Withdrawal Syndrome

Illnesses related to both the pharmacologic properties of abused substances and their methods of administration often bring the teenager to medical attention and may provide sufficient motivation for the adolescent to seek help beyond the acute problem. Successful treatment of an overdose reaction, an abstinence syndrome, or any other medical complication of drug abuse may give the physician a unique opportunity to begine further evalution for future care.

Topics: Adolescent; Aerosols; Alcohol Drinking; Amphetamines; Bacterial Infections; Cannabis; Embolism; Female; Hallucinogens; Hepatitis A; Humans; Hypnotics and Sedatives; Malaria; Male; Opium; Pharmaceutical Preparations; Poisoning; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adult; Analysis of Variance; Behavior; Cannabis; Drug Administration Schedule; Greece; Humans; Male; Placebos; Substance Withdrawal Syndrome; Substance-Related Disorders

An acute brain syndrome in a cannabis-dependent patient, who sustained multiple injuries, is described. Points of difference between this syndrome and delirium tremens are discussed. Recommendations are made regarding the treatment of this complication, which may follow multiple injuries or operative procedures.

Topics: Acute Disease; Adult; Alcohol Withdrawal Delirium; Cannabis; Diagnosis, Differential; Fractures, Bone; Humans; Male; Postoperative Complications; Substance Withdrawal Syndrome

Widespread use of certain drugs (amphetamines, L.S.D., hypnotics) in France, allowed us to observe more than 200 cases of acute or chronic psychoses among addicts. Sometimes these are transitory outburst but the occurrence of a delusional psychosis with long range evolution raises a difficult diagnosis problem in relation to functional psychoses. The emphasis should be put on respective roles of the drug and of a predisposed mental state. Circumstances of beginning, apparently direct relationship between drug taking and pathological symptoms, therapy efficiency, absence of earlier pathological traits (as in many of our patients) and relapse when intoxication starts again, are in favour of a pharmacological origin of the troubles.

Topics: Amphetamine; Atropine Derivatives; Cannabis; Cocaine; Delusions; Ether; Humans; Hypnotics and Sedatives; Lysergic Acid Diethylamide; Opium; Paranoid Disorders; Personality Disorders; Psychoses, Substance-Induced; Substance Withdrawal Syndrome; Substance-Related Disorders

From all US Army enlistees leaving Vietnam in September 1971, a random sample of 943 men was selected. Of these, 470 represented a "general" sample of all enlistees returning at that time, and 495 represented a "drug positive" sample whose urine samples had been positive for opiates at the time of departure. We attempted to locate and personally interview all of the men in the samples. Results indicate that before arrival, hard drug use was largely casual, and less than 1% had ever been addicted to narcotics. In Vietnam, almost half of the general sample tried narcotics and 20% reported opiate addiction. After return, usage and addiction essentially decreased to pre-Vietnam levels. We discuss the use of nonnarcotic drugs, predictors and correlates of drug use in the samples, and the relationship of drugs to post-Vietnam social adjustment.

Topics: Age Factors; Alcohol Drinking; Amphetamine; Barbiturates; Cannabis; Heroin; Humans; Injections, Intravenous; Male; Military Psychiatry; Narcotics; Opium; Socioeconomic Factors; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors; United States; Veterans; Vietnam

Male rats were implanted subcutaneously with a pellet containg 75 milligrams of morphine base or placebo, and naloxone hydrochloride (4 milligrams per kilogram of body weight) was administered 72 hours later. Treatment with delta-9-tetrahydrocannabinol (2, 5, or 10 milligrams per kilogram) 1 hour before maloxone administration significantly reduced the intensity of abstinence; the two higher doses blocked the appearance of wet shakes and escapes, diarrhea, and increased defecation. delta-9-Tetrahydrocannabinol did not induce abstinence itself, and prior treatment with cannabidiol was ineffective in reducing naloxoneprecipitated abstinence in animals with morphine pellets. These data suggest that delta-9-tetrahydrocannabinol may be of value in facilitating narcotic detoxification.

Topics: Animals; Cannabis; Dose-Response Relationship, Drug; Dronabinol; Humans; Male; Morphine Dependence; Naloxone; Phytotherapy; Placebos; Rats; Substance Withdrawal Syndrome

Topics: Animals; Behavior; Cannabis; Dopamine; Dronabinol; Haloperidol; Humans; Male; Morphine Dependence; Naloxone; Promethazine; Rats; Stereotyped Behavior; Substance Withdrawal Syndrome; Time Factors

The same dose of cannabinol (CBN) or cannabidiol (CBD) further increased the attenuation of precipitated abstinence signs observed in morphine-dependent rats that also received an acute dose of delta 9-THC. By contrast, rotational behavior (turning), which is observed concomitantly in THC-treated rats during morphine abstinence, was not increased by CBN, but was potentiated by CBD. These data illustrate differences between psychoinactive cannabinoids in their interaction with delta 9-THC that might be relevant to possible clinical use of Cannabis in narcotic detoxification.

Topics: Animals; Cannabidiol; Cannabis; Depression, Chemical; Dronabinol; Drug Synergism; Humans; Male; Morphine Dependence; Rats; Stereotyped Behavior; Substance Withdrawal Syndrome

Topics: Animals; Cannabis; Dose-Response Relationship, Drug; Dronabinol; Humans; Morphine Dependence; Phytotherapy; Rats; Substance Withdrawal Syndrome

Topics: Animals; Cannabidiol; Cannabis; Dronabinol; Drug Synergism; Herb-Drug Interactions; Humans; Male; Morphine; Phytotherapy; Rats; Substance Withdrawal Syndrome

The effects of feeding cannabis at a level of 0.4% in the diet has been studied by an ethological analysis of encounters between male mice. Administration of cannabis to dominant males resulted in a reduction of non-social activity and an increase in flight and in social and sexual investigation when compared with untreated controls, but the behaviour of subordinate males was not significantly altered by cannabis. One week after withdrawal of cannabis, the behaviour of diminant males showed a rebound effect with increase in aggression. Nevertheless, by a preference feeding test it was demonstrated that the treated mice were not dependent on the cannabis-containing diet but consumed the control diet in preference.

Topics: Aggression; Animals; Behavior, Animal; Body Weight; Cannabis; Dominance-Subordination; Escape Reaction; Ethology; Humans; Male; Mice; Mice, Inbred Strains; Sexual Behavior, Animal; Social Behavior; Substance Withdrawal Syndrome

Racemic methadone hydrochloride was administered to male rats in daily subcutaneous injections of 10-30 mg/kg. Dependence, when assessed by naloxone challenge after 26 days, was quantitatively and qualitatively similar to that previously reported by us for rats implanted with a 75 mg morphine pellet for 72 hours. Abstinence scores in animals pretreated acutely with 10 mg/kg delta 9-THC one hour before naloxone were significantly less than those of a vehicle control group, and wet shakes and gastrointestinal signs of abstinence were blocked. These results extend previous observations of morphine abstinence attenuating properties of delta 9-THC to effects on animals dependent on methadone.

Topics: Animals; Behavior, Animal; Cannabis; Dronabinol; Drug Tolerance; Humans; Male; Methadone; Morphine Dependence; Naloxone; Phytotherapy; Rats; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adolescent; Adult; Amphetamine; Cannabis; Community Psychiatry; Drug and Narcotic Control; England; Follow-Up Studies; Forensic Psychiatry; Humans; Hypnotics and Sedatives; Jurisprudence; Legislation, Drug; Lysergic Acid Diethylamide; Opium; Punishment; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Alcoholism; Animals; Cannabis; Central Nervous System Stimulants; Cocaine; Dogs; Haplorhini; Humans; Hypnotics and Sedatives; Lysergic Acid Diethylamide; Mescaline; Morphine Dependence; Rats; Substance Withdrawal Syndrome; Substance-Related Disorders; Tranquilizing Agents

Topics: Adult; Alcoholism; Barbiturates; Cannabis; Diazepam; Drug Combinations; Drug Therapy, Combination; Female; Germany, West; Hospitals, General; Humans; Male; Methadone; Morphinans; Opium; Promethazine; Psychotherapy; Substance Withdrawal Syndrome; Substance-Related Disorders; Thiazines

Topics: Adrenal Glands; Animals; Barbiturates; Behavior, Animal; Body Weight; Brain; Cannabis; Drinking Behavior; Drug Hypersensitivity; Extinction, Psychological; Female; Heart; Humans; Kidney; Organ Size; Pentylenetetrazole; Plant Extracts; Rats; Seizures; Substance Withdrawal Syndrome; Time Factors

Topics: Adolescent; Age Factors; Alcoholism; Cannabis; Child; Family Characteristics; Female; Germany, West; Humans; Lysergic Acid Diethylamide; Male; Personality Disorders; Smoking; Social Problems; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Cannabis; Hallucinogens; Humans; Schizophrenia; Schizophrenic Psychology; Substance Withdrawal Syndrome; Tranquilizing Agents

Topics: Attitude to Health; Cannabis; Heroin Dependence; Humans; Lysergic Acid Diethylamide; Methadone; Parent-Child Relations; Physician-Patient Relations; Psychology; Substance Withdrawal Syndrome; Substance-Related Disorders; Tranquilizing Agents

Topics: Animals; Body Weight; Cannabis; Dronabinol; Drug Interactions; Drug Tolerance; Ethanol; Humans; Male; Mice; Pentylenetetrazole; Seizures; Substance Withdrawal Syndrome; Water Deprivation

Topics: Animals; Cannabis; Discrimination Learning; Discrimination, Psychological; Dronabinol; Drug Antagonism; Drug Tolerance; Humans; Male; Morphine; Naloxone; Phytotherapy; Rats; Reinforcement, Psychology; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Amphetamine; Antipsychotic Agents; Barbiturates; Cannabis; Child Welfare; Chlorpromazine; Diazepam; Female; Heroin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Lysergic Acid Diethylamide; Maternal-Fetal Exchange; Pregnancy; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adult; Cannabis; Electroencephalography; Electrooculography; Humans; Male; Sleep; Sleep, REM; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Amitriptyline; Animals; Atropine; Cannabis; Chlordiazepoxide; Chlorpromazine; Diazepam; Humans; Imipramine; Male; Mephenesin; Methamphetamine; Mice; Morphine Dependence; Naloxone; Pentobarbital; Perphenazine; Phenytoin; Reserpine; Substance Withdrawal Syndrome

Topics: Abnormalities, Drug-Induced; Administration, Oral; Animals; Atrophy; Brain; Cannabis; Cardiovascular System; Dose-Response Relationship, Drug; Dronabinol; Drug Interactions; Female; Humans; Injections, Intraperitoneal; Injections, Subcutaneous; Liver; Lung; Male; Pregnancy; Psychoses, Substance-Induced; Rabbits; Rats; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Alcoholic Intoxication; Amphetamine; Atropa belladonna; Atropine; Barbiturates; Cannabis; Diagnosis, Differential; Ethanol; Heroin Dependence; Humans; Hypnotics and Sedatives; Lysergic Acid Diethylamide; Mescaline; Methadone; Morphine Dependence; Plants, Medicinal; Plants, Toxic; Scopolamine; Substance Withdrawal Syndrome; Substance-Related Disorders; Tranquilizing Agents

Topics: Aggression; Automobile Driving; Cannabis; Compulsive Behavior; Drug Tolerance; Female; Hallucinations; Humans; Male; Paranoid Disorders; Perception; Sexual Behavior; South Africa; Speech; Substance Withdrawal Syndrome; United Kingdom; United States

Topics: Adolescent; Adult; Age Factors; Aged; Black or African American; Black People; Cannabis; Crime; Female; Heroin; Heroin Dependence; Humans; Legislation, Drug; Male; Methadone; Methods; Middle Aged; Opium; Sex Factors; Substance Withdrawal Syndrome; Substance-Related Disorders; United Kingdom; United States; White People

Topics: Adult; California; Cannabis; Counseling; Female; Heroin Dependence; Humans; Male; Methaqualone; Pentobarbital; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Amphetamine; Cannabis; Emergencies; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Lysergic Acid Diethylamide; Mental Disorders; Methadone; Opium; Pregnancy; Pregnancy Complications; Psychotic Disorders; Puerperal Disorders; Substance Withdrawal Syndrome; Substance-Related Disorders; Tranquilizing Agents

Topics: Cannabis; Humans; Sleep; Sleep Stages; Sleep, REM; Substance Withdrawal Syndrome

Topics: Adolescent; Adult; Amphetamine; Barbiturates; Cannabis; Cocaine; Cognition Disorders; Factor Analysis, Statistical; Hallucinogens; Humans; Male; Morphinans; Perceptual Disorders; Psychological Tests; Socioeconomic Factors; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Cannabis; Humans; Sleep; Substance Withdrawal Syndrome

Topics: Adolescent; Adult; Amphetamine; California; Cannabis; Child; Community Health Services; Female; Heroin; Humans; Male; Medical Records; Methadone; Middle Aged; Morphine Dependence; Self Medication; Socioeconomic Factors; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Alcohol Drinking; Alcoholism; Cannabis; Delayed-Action Preparations; Disulfiram; Heroin; Humans; Methadone; Morphine Dependence; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Amphetamine; Barbiturates; Cannabis; Chlormethiazole; Cocaine; Diazepam; Emergencies; Humans; Lysergic Acid Diethylamide; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adolescent; Adult; Antidotes; Cannabis; Female; Hallucinogens; Heroin; Humans; Lysergic Acid Diethylamide; Male; Mescaline; Morphine; Morphine Dependence; Poisoning; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Abdomen, Acute; Adult; Blood Pressure; Cannabis; Female; Humans; Male; Muscular Diseases; Nausea; Pulse; Substance Withdrawal Syndrome

Topics: Cannabis; Drug and Narcotic Control; Humans; Substance Withdrawal Syndrome; Substance-Related Disorders; United States

Topics: Adolescent; Adult; Age Factors; Cannabis; Delusions; Depth Perception; Female; Homosexuality; Hospitalization; Humans; Learning Disabilities; Male; Pregnancy; Psychological Tests; Psychoses, Substance-Induced; Speech Disorders; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Topics: Amphetamine; Barbiturates; Cannabis; Central Nervous System; Cocaine; Ethanol; Hallucinogens; Heroin; Humans; Morphine; Nicotine; Pharmacology; Substance Withdrawal Syndrome; Substance-Related Disorders; Synaptic Transmission

Topics: Adolescent; Adult; Age Factors; Alcohol Drinking; Alkaloids; Austria; Cannabis; Cognition Disorders; Criminal Psychology; Depressive Disorder, Major; Epilepsy, Tonic-Clonic; Histrionic Personality Disorder; Humans; Hypnotics and Sedatives; Intelligence; Juvenile Delinquency; Personality; Psychoses, Substance-Induced; Psychotherapy; Social Class; Socioeconomic Factors; Substance Withdrawal Syndrome; Substance-Related Disorders; Unconscious, Psychology

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Adult; Amphetamine; Barbiturates; Cannabis; Female; Heroin; Humans; Infant, Newborn; Lysergic Acid Diethylamide; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Acute Kidney Injury; Administration, Oral; Adolescent; Alkaline Phosphatase; Amenorrhea; Amphetamine; Barbiturates; Cannabis; Child; Cocaine; Eosinophilia; False Positive Reactions; Female; Hepatic Encephalopathy; Hepatitis B; Heroin; Humans; Injections, Intravenous; Injections, Subcutaneous; Juvenile Delinquency; Lysergic Acid Diethylamide; Peptic Ulcer; Pneumonia; Pseudotumor Cerebri; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Amphetamine; Animals; Barbiturates; Brain; Cannabis; Central Nervous System; Cocaine; Drug Tolerance; Guinea Pigs; Heroin; Humans; Hypothalamus; Ileum; Lysergic Acid Diethylamide; Morphine; Morphine Dependence; Nerve Endings; Opium; Psychoses, Substance-Induced; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Adolescent; Cannabis; Drug Prescriptions; Germany, West; Humans; Lysergic Acid Diethylamide; Psychology, Social; Social Problems; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Amphetamine; Barbiturates; Cannabis; Child Behavior Disorders; Crime; Depression; Humans; Hyperkinesis; Legislation, Drug; Lysergic Acid Diethylamide; Narcolepsy; Paranoid Disorders; Psychology, Adolescent; Psychoses, Substance-Induced; Psychotherapy; Schizophrenia; Social Behavior; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Analgesics; Antidepressive Agents; Antitussive Agents; Austria; Barbiturates; Cannabis; Chlordiazepoxide; Diazepam; Female; Hallucinogens; Hospitals, Psychiatric; Humans; Hypnotics and Sedatives; Male; Meprobamate; Morphine; Psychopharmacology; Sex Factors; Substance Withdrawal Syndrome; Substance-Related Disorders; Tranquilizing Agents

Topics: Amphetamine; Barbiturates; Cannabis; Drug and Narcotic Control; Female; Heroin; Humans; Legislation, Drug; Male; Methadone; Morphine; Nalorphine; Pregnancy; Substance Withdrawal Syndrome; Substance-Related Disorders; United States

Topics: Cannabis; Humans; Smoking; Substance Withdrawal Syndrome; Zimbabwe

Topics: Adolescent; Adult; Amphetamine; Barbiturates; Cannabis; Cocaine; Dextroamphetamine; Ethanol; Female; Follow-Up Studies; Heroin; Hospitalization; Hospitals, Psychiatric; Humans; Injections, Intravenous; Male; Methadone; Morphine; Substance Withdrawal Syndrome; Substance-Related Disorders; United Kingdom; United States

Topics: Alcoholism; Benzopyrans; Cannabis; Humans; Mental Health Services; North Carolina; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Cannabinoids; Cannabis; Humans; Pharmaceutical Preparations; Substance Withdrawal Syndrome