Prevalence of Cannabis Withdrawal Symptoms Among People With Regular or Dependent Use of Cannabinoids. A Systematic Review and Meta-analysis, Anees Bahji et al., 2020

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

Anees Bahji, MD; Callum Stephenson; Richard Tyo, BSocSc, RP; Emily R. Hawken, MSc, PhD; Dallas P. Seitz, MD, PhD

JAMA Network Open, 2020, 3, (4), e202370.

doi : 10.1001/jamanetworkopen.2020.2370



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 (I2 = 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.


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.



Cannabinoids are the most commonly used group of illicit drugs, and cannabis use and dependence are estimated to have increased over the past 2 decades.1 Despite common perceptions that cannabis is relatively harmless, there is substantial evidence to support an association between cannabis use and several medical, neurocognitive, functional, and psychosocial sequalae.2 The known short-term risks of cannabinoid use include impaired short-term memory and motor coordination, altered judgment, paranoia, and psychosis.3 Similarly, long-term effects of cannabinoid use include addiction, altered brain development, poor educational outcomes, cognitive impairment, diminished quality of life, increased risk of chronic respiratory tract and psychotic disorders, injuries, motor vehicle collisions, and suicide.3,4

In parallel with other substance withdrawal syndromes, a cannabis withdrawal syndrome (CWS) originally proposed by Budney and colleagues5-8 —has received recognition in recent years. Cannabis withdrawal syndrome symptoms occur reliably following a specific time course with cessation of cannabis use, were transient, could be ameliorated by readministration of cannabis, and were clinically significant. Cannabis withdrawal syndrome was recognized by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition,9 and requires the presence of at least 3 of the following symptoms developing within 7 days of reduced cannabis use: (1) irritability, anger, or aggression; (2) nervousness or anxiety; (3) sleep disturbance; (4) appetite or weight disturbance; (5) restlessness; (6) depressed mood; and (7) somatic symptoms, such as headaches, sweating, nausea, vomiting, or abdominal pain.

Several studies using varied approaches have characterized CWS, and resulting prevalence estimates have ranged from 11.1%to 94.2%.8,10-12 Hence, although there is concern about the risks associated with cannabinoid use and CWS, to our knowledge, there currently exists no comprehensive quantitative synthesis of the magnitude of risk and how elevated that risk might be relative to the general population among people with regular or problematic cannabinoid use. The primary aim of this systematic review and meta-analysis was to estimate the prevalence of CWS and identify contributors to heterogeneity in reported results.We sought to produce age-specific and sex estimates of CWS prevalence where possible.