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To compare the prevalence of mental disorders between frequent cannabis users with and without dependence and the general population.Cross-sectional comparison of interview data.Enriched community sample of frequent cannabis users and a representative sample of non-users and non-frequent users from the general population.A total of 521 young adult (aged 18–30 years) frequent cannabis users, 252 of whom were with DSM-IV cannabis dependence (D+) and 269 without DSM-IV cannabis dependence (D−), and 1072 young adults from the general population.Multinomial logistic regression was used to compare groups regarding the presence of DSM-IV mental disorders. Detailed measures of cannabis use, childhood adversity and other substance use were considered confounders.Compared with the general population, externalizing disorders were more prevalent in D− [odds ratio (OR) = 8.91, P < 0.001] and most prevalent in D+ (OR = 17.75, P < 0.001), but internalizing disorders were associated only with D+ (mood OR = 4.15, P < 0.001; anxiety OR = 2.20, P = 0.002). Associations were attenuated (and often became non-significant) after correction for childhood adversity and substance use other than cannabis. However, the prevalence of mental disorders remained higher in D+ compared with D− (OR = 2.40, P < 0.001), although cannabis use patterns were remarkably similar.Cannabis use patterns, childhood adversity and the use of other substances are similar in dependent and non-dependent frequent cannabis users. With the exception of more externalizing disorders, the mental health condition of non-dependent frequent cannabis users is similar to that of the general population, whereas it is worse in dependent frequent cannabis users.