After controlling for predisposing factors, frequent cannabis use was shown to be associated with an increased risk for major depressive disorder (MDD) and suicidal ideation, according to a recent twin study published in Lancet Psychiatry.

In this retrospective analysis, same-sex twin pairs (n=13,896; 6181 monozygotic and 7805 dizygotic) from the Australian Twin Registry were evaluated for associations between cannabis use patterns and MDD, suicidal ideation, and suicide plans or attempts. Samples were broken down into 1992 through 1993 (sample 1), 1996 through 2000 (sample 2), and 2005 through 2009 (sample 3). Association analyses were done in the full sample as well as in pairs of twins discordant for cannabis use at a single time point.

Cannabis use was highest in sample 3 (69.0%, n=2275/3299) followed by sample 2 (59.8%, n=3741/6255) and sample 1 (30.4%, n=1345/4432). Among cannabis users, early use (prior to 18 years for sample 1 and prior to 17 years for samples 2 and 3) and frequent use (100 times) were found in 21.3% and 15.9% of sample 1, 23.1% and 27.9% of sample 2, and 37.7% and 21.9% of sample 3.

Suicidal ideation was noted in 24.9% of sample 1, 26.3% of sample 2, and 26.2% of sample 3. MDD was found in 20.3% of sample 1, 28.3% of sample 2, and 24.7% of sample 3. After adjusting for covariates including sex, age, early alcohol or nicotine use, early dysphoric or anhedonic mood, conduct disorder, and childhood sexual abuse, monozygotic twins who used cannabis frequently had a higher risk for MDD (odds ratio [OR]: 1.98, 95% confidence interval [CI]: 1.11-3.53) and suicidal ideation (OR: 2.47, CI: 1.19-5.10) compared with the monozygotic twins who used cannabis less frequently.

After adjustment, early cannabis use was not significantly associated with MDD or suicidal thoughts and behaviors within monozygotic twins (OR: 1.17-2.00) but was within dizygotic twins (OR: 2.23-6.50). According to study authors, this may be indicative of shared genetic factors contributing to the association.

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The study authors concluded that they were “unable to exclude the possibility that frequent cannabis use might increase risks for MDD and suicidal ideation, independent of shared predisposing influences.” They noted the importance of understanding this potential susceptibility, particularly “against the backdrop of evidence supporting a role of the endocannabinoid system in mood regulation.”


Agrawal A, Nelson EC, Bucholz KK, et al. Major depressive disorder, suicidal thoughts and behaviours, and cannabis involvement in discordant twins: a retrospective cohort study. Lancet Psychiatry. 2017;4:706-714.