ABSTRACT: OBJECTIVE:Although cannabis is the most widely abused illicit drug, little is known about the prevalence of cannabis withdrawal and its factor structure, clinical validity, and psychiatric correlates in the general population. METHOD:National Epidemiologic Survey on Alcohol and Related Conditions participants were assessed, in 2001-2002, with structured in-person interviews covering substance history, DSM-IV Axis I and II disorders, and withdrawal symptoms after cessation of use. Of these, 2613 had been frequent cannabis users (> or = 3 times/week), and a "cannabis-only" subset (N = 1119) never binge-drank or used other drugs > or = 3 times/week. RESULTS:In the full sample and subset, 44.3% (SE = 1.19) and 44.2% (SE = 1.75), respectively, experienced > or = 2 cannabis withdrawal symptoms, while 34.4% (SE = 1.21) and 34.1% (SE = 1.76), respectively, experienced > or = 3 symptoms. The symptoms formed 2 factors, one characterized by weakness, hypersomnia, and psychomotor retardation and the second by anxiety, restlessness, depression, and insomnia. Both symptom types were associated with significant distress/impairment (p < .01), substance use to relieve/avoid cannabis withdrawal symptoms (p <.01), and quantity of cannabis use (among the cannabis-only users p < .05). Panic (p < .01) and personality (p > .01) disorders were associated with anxiety symptoms in both samples, family history of drug problems was associated with weakness symptoms in the subset (p = .01), and depression was associated with both sets of symptoms in the subset (p < or = .05). CONCLUSION:Cannabis withdrawal was prevalent and clinically significant among a representative sample of frequent cannabis users. Similar results in the subset without polysubstance abuse confirmed the specificity of symptoms to cannabis. Cannabis withdrawal should be added to DSM-V, and the etiology and treatment implications of cannabis withdrawal symptoms should be investigated.