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      Prevalence of Cannabis Withdrawal Symptoms Among People With Regular or Dependent Use of Cannabinoids : A Systematic Review and Meta-analysis

      research-article
      , MD 1 , 2 , , 3 , , BSocSc, RP 2 , , MSc, PhD 2 , , MD, PhD 1 , 2 , 4
      JAMA Network Open
      American Medical Association

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          Key Points

          Questions

          What is the prevalence of cannabis withdrawal syndrome among individuals with regular or dependent use of cannabis, and which factors are associated with cannabis withdrawal syndrome?

          Findings

          In this meta-analysis of observational studies including 23 518 participants, the prevalence of cannabis withdrawal syndrome was found to be 47%. Factors that were associated with higher cannabis withdrawal syndrome were clinical settings (particularly inpatient and outpatient vs population settings), concurrent tobacco or other substance use, and daily cannabis use.

          Meaning

          Cannabis withdrawal syndrome appears to be common among regular users of cannabis, particularly those in outpatient and inpatient settings and individuals with substance use disorders; clinicians should be aware of the high prevalence of cannabis withdrawal syndrome to counsel patients and support individuals who are reducing their use of cannabis.

          Abstract

          Importance

          Cannabis withdrawal syndrome (CWS)—a diagnostic indicator of cannabis use disorder—commonly occurs on cessation of heavy and prolonged cannabis use. To date, the prevalence of CWS syndrome has not been well described, nor have the factors potentially associated with CWS.

          Objectives

          To estimate the prevalence of CWS among individuals with regular or dependent use of cannabinoids and identify factors associated with CWS.

          Data Sources

          A search of literature from database inception to June 19, 2019, was performed using MEDLINE, Embase, PsycINFO, Web of Science, the Cumulative Index to Nursing and Allied Health Literature, ProQuest, Allied and Complementary Medicine, and Psychiatry online, supplemented by manual searches of reference lists of included articles.

          Study Selection

          Articles were included if they (1) were published in English, (2) reported on individuals with regular use of cannabinoids or cannabis use disorder as a primary study group, (3) reported on the prevalence of CWS or CWS symptoms using a validated instrument, (4) reported the prevalence of CWS, and (5) used an observational study design (eg, cohort or cross-sectional).

          Data Extraction and Synthesis

          All abstracts, full-text articles, and other sources were reviewed, with data extracted in duplicate. Cannabis withdrawal syndrome prevalence was estimated using a random-effects meta-analysis model, alongside stratification and meta-regression to characterize heterogeneity.

          Main Outcomes and Measures

          Cannabis withdrawal syndrome prevalence was reported as a percentage with 95% CIs.

          Results

          Of 3848 unique abstracts, 86 were selected for full-text review, and 47 studies, representing 23 518 participants, met all inclusion criteria. Of 23 518 participants included in the analysis, 16 839 were white (72%) and 14 387 were men (69%); median (SD) age was 29.9 (9.0) years. The overall pooled prevalence of CWS was 47% (6469 of 23 518) (95% CI, 41%-52%), with significant heterogeneity between estimates ( I 2 = 99.2%). When stratified by source, the prevalence of CWS was 17% (95% CI, 13%-21%) in population-based samples, 54% in outpatient samples (95% CI, 48%-59%), and 87% in inpatient samples (95% CI, 79%-94%), which were significantly different ( P < .001). Concurrent cannabis (β = 0.005, P < .001), tobacco (β = 0.002, P = .02), and other substance use disorders (β = 0.003, P = .05) were associated with a higher CWS prevalence, as was daily cannabis use (β = 0.004, P < .001).

          Conclusions and Relevance

          These findings suggest that cannabis withdrawal syndrome appears to be prevalent among regular users of cannabis. Clinicians should be aware of the prevalence of CWS in order to counsel patients and support individuals who are reducing their use of cannabis.

          Abstract

          This systematic review and meta-analysis examines the prevalence of cannabis withdrawal syndrome in individuals who use cannabinoids regularly.

          Related collections

          Most cited references94

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          The global burden of disease attributable to alcohol and drug use in 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

          Summary Background Alcohol and drug use can have negative consequences on the health, economy, productivity, and social aspects of communities. We aimed to use data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 to calculate global and regional estimates of the prevalence of alcohol, amphetamine, cannabis, cocaine, and opioid dependence, and to estimate global disease burden attributable to alcohol and drug use between 1990 and 2016, and for 195 countries and territories within 21 regions, and within seven super-regions. We also aimed to examine the association between disease burden and Socio-demographic Index (SDI) quintiles. Methods We searched PubMed, EMBASE, and PsycINFO databases for original epidemiological studies on alcohol and drug use published between Jan 1, 1980, and Sept 7, 2016, with out language restrictions, and used DisMod-MR 2.1, a Bayesian meta-regression tool, to estimate population-level prevalence of substance use disorders. We combined these estimates with disability weights to calculate years of life lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 1990–2016. We also used a comparative assessment approach to estimate burden attributable to alcohol and drug use as risk factors for other health outcomes. Findings Globally, alcohol use disorders were the most prevalent of all substance use disorders, with 100·4 million estimated cases in 2016 (age-standardised prevalence 1320·8 cases per 100 000 people, 95% uncertainty interval [95% UI] 1181·2–1468·0). The most common drug use disorders were cannabis dependence (22·1 million cases; age-standardised prevalence 289·7 cases per 100 000 people, 95% UI 248·9–339·1) and opioid dependence (26·8 million cases; age-standardised prevalence 353·0 cases per 100 000 people, 309·9–405·9). Globally, in 2016, 99·2 million DALYs (95% UI 88·3–111·2) and 4·2% of all DALYs (3·7–4·6) were attributable to alcohol use, and 31·8 million DALYs (27·4–36·6) and 1·3% of all DALYs (1·2–1·5) were attributable to drug use as a risk factor. The burden of disease attributable to alcohol and drug use varied substantially across geographical locations, and much of this burden was due to the effect of substance use on other health outcomes. Contrasting patterns were observed for the association between total alcohol and drug-attributable burden and SDI: alcohol-attributable burden was highest in countries with a low SDI and middle-high middle SDI, whereas the burden due to drugs increased with higher S DI level. Interpretation Alcohol and drug use are important contributors to global disease burden. Effective interventions should be scaled up to prevent and reduce substance use disease burden. Funding Bill & Melinda Gates Foundation and Australian National Health and Medical Research Council.
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            Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers.

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

              This review provides an overview of the changing US epidemiology of cannabis use and associated problems. Adults and adolescents increasingly view cannabis as harmless, and some can use cannabis without harm. However, potential problems include harms from prenatal exposure and unintentional childhood exposure; decline in educational or occupational functioning after early adolescent use, and in adulthood, impaired driving and vehicle crashes; cannabis use disorders (CUD), cannabis withdrawal, and psychiatric comorbidity. Evidence suggests national increases in cannabis potency, prenatal and unintentional childhood exposure; and in adults, increased use, CUD, cannabis-related emergency room visits, and fatal vehicle crashes. Twenty-nine states have medical marijuana laws (MMLs) and of these, 8 have recreational marijuana laws (RMLs). Many studies indicate that MMLs or their specific provisions did not increase adolescent cannabis use. However, the more limited literature suggests that MMLs have led to increased cannabis potency, unintentional childhood exposures, adult cannabis use, and adult CUD. Ecological-level studies suggest that MMLs have led to substitution of cannabis for opioids, and also possibly for psychiatric medications. Much remains to be determined about cannabis trends and the role of MMLs and RMLs in these trends. The public, health professionals, and policy makers would benefit from education about the risks of cannabis use, the increases in such risks, and the role of marijuana laws in these increases.
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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                9 April 2020
                April 2020
                9 April 2020
                : 3
                : 4
                : e202370
                Affiliations
                [1 ]Department of Public Health Sciences, Queen’s University, Kingston, Ontario, Canada
                [2 ]Department of Psychiatry, Queen’s University, Kingston, Ontario, Canada
                [3 ]Queen’s University School of Kinesiology and Health Studies, Kingston, Ontario, Canada
                [4 ]Cumming School of Medicine, Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada
                Author notes
                Article Information
                Accepted for Publication: February 10, 2020.
                Published: April 9, 2020. doi:10.1001/jamanetworkopen.2020.2370
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Bahji A et al. JAMA Network Open.
                Corresponding Author: Anees Bahji, MD, Department of Psychiatry, Department of Public Health Sciences, Queen’s University, 21 Arch St, Abramsky Hall, Rm 328, Kingston, Ontario K7L 3N6, Canada ( 0ab104@ 123456queensu.ca ).
                Author Contributions: Dr Bahji and Mr Stephenson had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Bahji, Stephenson, Hawken, Seitz.
                Acquisition, analysis, or interpretation of data: Bahji, Stephenson, Tyo, Seitz.
                Drafting of the manuscript: Bahji, Stephenson, Tyo.
                Critical revision of the manuscript for important intellectual content: Bahji, Stephenson, Hawken, Seitz.
                Statistical analysis: Bahji, Stephenson, Seitz.
                Obtained funding: Seitz.
                Administrative, technical, or material support: Bahji, Seitz.
                Supervision: Hawken, Seitz.
                Conflict of Interest Disclosures: Dr Bahji reported receiving a Canadian Institutes of Health Research Master's Student scholarship during the time the manuscript was drafted. Dr Seitz reported participating as a site investigator for a clinical trial sponsored by Hoffmann La Roche. No other disclosures were reported.
                Additional Contributions: Karen Gagnon, BSc, MLIS (Providence Care Hospital, affiliated with Queen’s University), assisted in development of the literature search strategy; there was no financial compensation outside of salary.
                Article
                zoi200122
                10.1001/jamanetworkopen.2020.2370
                7146100
                32271390
                876ea66d-7f61-4e65-8aa4-3cabaa60ae0f
                Copyright 2020 Bahji A et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 25 October 2019
                : 10 February 2020
                Categories
                Research
                Original Investigation
                Online Only
                Substance Use and Addiction

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