Depression Risk

Adolescent cannabis use is associated with increased risk of depression (OR 1,37), suicidal ideation (OR 1,50) and suicide attempts (OR 3,46) in young adulthood; anxiety disorders show no statistical significance (OR 1,18).

SR of 11 studies (n=23.317 adolescents); adolescent cannabis use associated with increased risk of depression in young adulthood (OR=1.37, 95% CI 1.16-1.62, p0.001), anxiety disorders (OR=1.18, 95% CI 1.10-1.26, p0.001) and suicidality (OR=1.50, 95% CI 1.11-2.03, p0.01).

Meta-analysis shows a strong bidirectional association between major depression and cannabis use disorder (MDD prevalence in CUD: 19-22%, CUD prevalence in MDD: 4,6-28,5% depending on setting).

Meta-analysis on the bidirectional association between Major Depression (MDD) and Cannabis Use Disorder (CUD); k=55 studies, n=3.279.774 participants (454.547 with CUD, 112.328 with MDD). Current MDD prevalence in CUD patients: 19,24% (psychiatric samples) and 21,65% (community samples). Current CUD prevalence in MDD patients: 28,45% (psychiatric) vs. 4,61% (community). Strong bidirectional comorbidity across different settings; no publication bias (Egger's test).

Cannabis use was associated with worsening of the course and symptoms of both mood disorders, with more consistent associations in bipolar disorder.

CANMAT guideline based on systematic review (k=56 studies, n=2.479.640 participants total). Lifetime prevalence of cannabis use: 52-71% in bipolar disorder, 6-50% in major depressive disorder. Cannabis use associated with worse course and increased depressive symptoms in MDD (evidence less consistent than in bipolar disorder). Systematic recommendations for clinical practice formulated according to GRADE methodology.

Prevalence of substance use disorders in major depression: 25% for any SUD, 20,8% alcohol use disorder, 11,8% illicit drugs, 11,7% cannabis; men show significantly higher alcohol use disorder prevalence (36%) than women (19%).

Systematic review and meta-analysis on substance use disorders (SUDs) in major depression (MDD); k=48 articles (14 epidemiological studies, 2 national registers, 7 cohorts, 20 clinical trials), n=348.550. Prevalence of any SUD in MDD: 25,0%; highest prevalence for alcohol use disorder (20,8%), followed by illicit drugs (11,8%) and cannabis (11,7%). Pooled variance for alcohol use disorder in men with MDD 36% vs. women 19% (OR=2,63, 95% CI 2,50-2,76).

Cannabis use, especially heavy use, is associated with an increased risk of developing depressive disorders (OR 1.17 for cannabis users, OR 1.62 for heavy users).

Systematic review and meta-analysis of k=14 prospective studies (n=76.058) on the association between cannabis use and the development of depression (controlled for baseline depression). Cannabis use vs. control: OR=1.17 (95% CI 1.05-1.30); heavy cannabis use vs. non-/light use: OR=1.62 (95% CI 1.21-2.16). No significant age effect, marginal effect of follow-up duration.

Recent cannabis use was associated with higher symptomatic scores over time and worse treatment response in anxiety disorders and affective disorders.

Systematic review on cannabis in anxiety and affective disorders; k=12 prospective cohort studies (n=11.959), of which 2 on depressive disorders. In 11/12 studies current cannabis use (past 6 months) was associated with higher symptom levels over time; 10 studies showed lower symptom improvement under treatment (medication/psychotherapy) in cannabis users vs. non-users.

Chronic cannabis use predicts suicidality with moderate to strong odds ratios; for acute use sufficient evidence is still lacking.

Meta-analysis, k=17 studies (diverse suicidality outcomes); chronic cannabis use and suicide death: OR=2,56 (95% CI 1,25–5,27, k=4); cannabis use and suicidal ideation: OR=1,43 (95% CI 1,13–1,83, k=6); heavy use and suicide attempt: OR=3,20 (95% CI 1,72–5,94, k=6); acute use not a confirmed predictor of immediate suicidality risk.

Cannabis use disorder is strongly associated with major depression (OR 3,22) and generalized anxiety disorder (OR 2,99), indicating a 3-fold increased comorbidity rate.

Systematic review of k=8 nationally representative epidemiological surveys on the comorbidity of cannabis use disorder (CUD) with major depression (MD) and generalized anxiety disorder (GAD). CUD strongly associated with MD (OR=3.22; 95% CI 2.31–4.49) and with GAD (OR=2.99; 95% CI 2.14–4.16). 3-fold increased comorbidity risk confirmed.

Cannabis use is associated with increased depressive and manic symptoms as well as increased risk for major depression and bipolar disorder and is associated with an unfavourable prognosis.

Systematic review on cannabis use and affective disorders; examines associations between cannabis use and depression/anxiety, evidence synthesis across epidemiological and clinical data.

Cannabis users show an increased risk of depression (OR 1,29, 95% CI 1,13-1,46).

Systematic review and meta-analysis of k=22 longitudinal studies (update to Lev-Ran et al.); cannabis use associated with increased risk of depression (OR=1.29, 95% CI: 1.13–1.46, p<0.001). Studies controlled for depression at baseline to establish temporal relationship. Medium risk of bias, no evidence of publication bias (Egger test).

Recreational use of cannabis shows a positive association with suicidal ideation and suicide attempts in the general population and specific patient groups, while therapeutic cannabinoid use is considered safe.

Umbrella review on cannabis and suicidality; k=25 systematic reviews (24 on recreational use, 1 on therapeutic use). Positive association between cannabis use and suicidal ideation/attempts in the general population and in bipolar/depressed patients; bidirectional causal link reported. Therapeutic cannabis assessed as safe.

CUD is associated with markedly increased risk of affective disorders – in particular psychotic bipolar disorder.

Prospective Danish register study (n=6.651.765, 119,5 million person-years, 1995–2021): Cannabis use disorder (CUD) associated with increased risk of unipolar depression HR=1,84 (95% CI 1,78–1,90), psychotic depression HR=1,97 (95% CI 1,73–2,25). CUD → bipolar disorder men HR=2,96 (95% CI 2,73–3,21), women HR=2,54 (95% CI 2,31–2,80); psychotic bipolar disorder HR=4,05 (95% CI 3,52–4,65). Adjusted for alcohol/substance use disorders, parental history and further covariates.

Cannabis use moderately to markedly increases the risk of first-onset depression and bipolar disorder, but not of anxiety disorders.

n=3.881 adults (18-64 y.) without lifetime diagnosis of affective disorders at baseline (NEMESIS study, Netherlands); cannabis use increased the risk of first-onset major depression (OR 1,62; 95% CI 1,06-2,48) and of bipolar disorder (OR 4,98; 95% CI 1,80-13,81) after adjustment for strong confounders; no significant association with anxiety disorders after adjustment.

After adjustment, no increased risk of depression from cannabis use, but strongly increased risk of schizoaffective disorder with heavy use.

n=45.087 Swedish men, cannabis use at age 18–20 years, 35-year follow-up; highest level of consumption: crude HR 1,5 (95%-CI 1,0–2,2) for depression, but after confounder adjustment no longer a significant association; no increased risk of depression from cannabis use confirmed after full adjustment.

Substance use disorders and major depression show consistently significant comorbidity in the US general population, with variation by substance, diagnosis type and demographic subgroups.

n=42.862 adults (US national study NLAES 1992); comorbidity between DSM-IV drug use disorders (including cannabis) and major depression: all OR significant >1; drug dependence shows a stronger association than abuse; OR gender-specific (stronger for dependence in men). Cannabis use disorder significantly associated with major depression (OR>1, p-value not explicitly stated).

Cannabis use disorders in Australia are concentrated among young men, frequently comorbid with alcohol and affective disorders, and are rarely treated.

Australian national study (n=8.841, 16–85 years); 12-month cannabis use disorder prevalence 1%; strong association between current cannabis use disorder and affective disorders (OR=3,0) as well as alcohol use disorders (OR=3,6); younger users OR=4,6 for cannabis use disorder; only 36,2% with current cannabis use disorder sought treatment.

After full confounder adjustment there was no significant longitudinal association between cannabis use and depression or anxiety disorders in either direction.

n=8.598 Swedish adults (20–64 years), 3-year follow-up; cannabis use at baseline → depression: RR=1,22 [95% CI 1,06–1,42] unadjusted, no longer significant after full adjustment (alcohol, drugs, education, family tension) RR=0,99 [95% CI 0,82–1,17]; → anxiety: RR=1,38 [95% CI 1,26–1,50] unadjusted, adjusted RR=1,09 [95% CI 0,98–1,20] (NS). No longitudinal association between cannabis use and new onset depression or anxiety after full confounder control.

Cannabis use is moderately associated with an increased MDE risk, though the strength of the association is at best small.

National Comorbidity Survey (n=6.792, age 15–45 yrs); cannabis use → increased cumulative risk for Major Depressive Episode (MDE); non-dependent cannabis users had a 1,6-fold higher MDE risk vs. non-users (95%-CI 1,1–2,2) after adjustment for sex, birth cohort, alcohol dependence, and daily smoking.

Cannabis use shows only weak association with depression after adjustment; association with anxiety disappears after confounder control.

ALSPAC cohort study (n=4.561); cannabis use at 16 years → increased odds for depression at 18 years (unadjusted OR=1.50, 95%-CI 1.26–1.80); after full adjustment for confounders weak association persisted (OR=1.30, 95%-CI 0.98–1.72). No significant association with anxiety after confounder adjustment.

Adolescent cannabis use presumably has causal negative effects on educational performance and socioeconomic outcomes, but not on mental health or cognitive abilities in adulthood.

Longitudinal twin study (n=3.762) on cannabis use in adolescence and outcomes in young adulthood: Univariately higher psychopathology with heavier use, but monozygotic co-twin control analyses showed NO causal signal for mental health (including depression) in adulthood — only socioeconomic outcomes remained (education, income, occupational status). Confounding by shared genetic/environmental factors explains the association.

Early onset and frequent cannabis use are associated, independently of other influencing factors, with a significantly increased risk of anxiety and depression in young adulthood.

Prospective cohort n=3.239 Australian young adults (birth to age 21); early cannabis use before age 15 combined with frequent use at age 21 associated with >3-fold increased risk of anxiety/depression (OR=3,4; 95% CI 1,9–6,1), independent of other drug use.

Cannabis use is associated with later suicidal ideation and attempts, but not with depression.

Population-based 13-year longitudinal study (n=2.033 Norwegians, adolescence to late twenties): Cannabis exposure in early adolescence NOT associated with later depression. In adulthood (twenties) significant association with suicide attempts at intensive use (≥11×/12 months): OR=2,9 (95% CI 1,3-6,1) after adjustment for confounders. Finding: cannabis does not per se lead to depression, but is associated with later suicidal ideation/attempts.

Frequent cannabis use during adolescence significantly increases the risk of depression and anxiety disorders in young adulthood, especially with daily use in girls.

Prospective 7-wave cohort study (n=1601, age 14–20 years, Victoria/Australia): Daily cannabis use in young women: OR=5,6 (95%-KI 2,6–12,0) for depression and anxiety disorder in adulthood after adjustment for other substance use. Weekly or more frequent use in adolescence: approximately 2-fold increased risk of later depression+anxiety (OR≈1,9; 95%-KI 1,1–3,3). Reverse causation not confirmed: prior depression/anxiety did not predict later cannabis use.

Cannabis problems in adolescence did not significantly increase the risk of depression in young adulthood in either women or men.

n=1.494 adolescents (55% female), cohort age 6–21 years (1985–2002), repeated measurements, propensity score adjustment; estimated risk of depression in young adulthood associated with adolescent cannabis problems: OR women=0,7 (95% CI 0,2–2,3), OR men=1,7 (95% CI 0,8–3,6) — both not significant; no statistical evidence of a causal association between adolescent cannabis problems and young adult depression.

Affective and anxiety disorders are significantly associated with cannabis use and CUD even after controlling for externalizing disorders, though anxiety disorders less consistently so.

10-year longitudinal study (n=1.395, age 14–17 years baseline); cumulative cannabis use incidence 54.3%, CUD incidence 13.7% over 10 years; depressive and bipolar disorders significantly associated with CU and CUD also after controlling for externalizing disorders (p<0.05); CUD baseline prevalence 2.6%, CU baseline 19.3%.

Regular cannabis use is associated with increased rates of psychosocial adjustment problems, strongest among school-age adolescents.

21-year prospective birth cohort (N=1.265, New Zealand, age 14–21). Frequency of cannabis use remained significantly associated with depression after controlling for time-dynamic and fixed confounders (p<0.05). No age effect for the cannabis-depression association (in contrast to crime/suicide). Temporal direction consistent with cannabis as a risk factor.

Chronic cannabis use in adolescence increases the risk of cannabis and alcohol use disorders in young adulthood, but not of depressive or anxiety disorders.

Longitudinal cohort n=1.205 adolescents (4 measurement time points), 5 cannabis use trajectories (Abstainer, Experimental, Decreaser, Increaser, High Chronic) followed into young adulthood (mean 23,5 years); trajectory membership significantly associated with cannabis and alcohol use disorders — NOT with major depression or anxiety disorders. Negative finding for depression risk from adolescent cannabis use patterns.

Cannabis abuse increases the risk of later depressive symptoms (OR ~4), not vice versa.

Prospective ECA cohort study (total N=1.920; analysis subcohort without baseline depression n=849). Cannabis abuse at baseline → 4-fold increased risk of depressive symptoms at 14-year follow-up, after adjustment for age, sex, antisocial symptoms (OR approx. 4). Increased suicidal ideation and anhedonia. Reverse direction not significant (p>0.05): baseline depression did not predict cannabis abuse.

Adolescent cannabis use significantly increases the risk of depression and suicidality in adulthood, but not the risk of anxiety disorders.

Prospective cohort study over 30 years (n=591, Zurich). Cannabis use in adolescence (24%) associated with depression in adulthood (aOR=1.70, 95%-CI=1.24-2.32) and suicidality (aOR=1.65, 95%-CI=1.11-2.47). Early first use (≤15/16 years) and frequent use in adolescence additionally increased depression risk. No significant effect on anxiety disorders (aOR=1.10, 95%-CI=0.82-1.48). Associations independent of cannabis abuse and other substances in adulthood.

Both light and heavy cannabis use are epidemiologically associated with an increased risk of anxiety and mood disorders.

n=14.531 adults (Ontario, CAMH Monitor 2001–2006); frequent cannabis use (almost daily) associated with increased risk of anxiety and mood disorders (AMD): prevalence 18.1% vs. 8.7% among abstinent; OR=2.04 for daily users, OR=1.43 for occasional users (each vs. abstinent); effects preserved after controlling for demographics and alcohol problems.

Cannabis use was associated with more depressive symptoms, however this effect was largely no longer detectable after adjustment for confounders.

n=2348 individuals with baseline MDD (NESARC), longitudinal; cannabis use was significantly associated with more depressive symptoms at follow-up (particularly anhedonia, weight changes, sleep disturbances, psychomotor problems); after adjustment for confounders no significant association with suicidality, functioning or quality of life; result suggests confounding by sociodemographic/clinical factors.

Cannabis use and depression/anxiety symptoms show small bidirectional associations, with distinctly stronger associations in LGB adolescents in the sense of possible self-medication.

Longitudinal cohort study (n=1.430 adolescents, Quebec Longitudinal Study) examined bidirectional associations between cannabis use and depression/anxiety symptoms at age 13–17 years via cross-lagged models. Total sample: cannabis at 13 years → anxiety symptoms at 15 years (significant after controlling for alcohol/cigarettes/other drugs); depression symptoms at 15 years → cannabis at 17 years (significant). The initial effect cannabis 13→depression 15 was explained by other drug use. LGB minorities showed a substantially stronger association depression 15→cannabis 17 (p<0.05 after controlling for covariates). Effect sizes overall small; bidirectional relationship in adolescence demonstrated.

Decrease in cannabis use is accompanied by fewer psychotic experiences, increase by more positive symptoms, but not by negative or depressive symptoms.

Longitudinal study (N=705, age 18–27 years, follow-up 6 months to 5 years): Increase in cannabis use was NOT significantly associated with an increase in depressive symptom scores (β not significant). Decrease in use was significantly associated with a decrease in overall psychotic experiences (β=−0,096; p=0,01). No evidence for cannabis as a risk factor for depressive symptoms in this age group.

Cannabis use increases depressive symptoms only in genetically vulnerable adolescents (5-HTTLPR short allele), not in all.

Longitudinal cohort study (n=310 adolescents, 4 years) on cannabis use and depressive symptoms. Parallel growth model: cannabis use increases the risk of an increase in depressive symptoms over time, but exclusively in carriers of the short allele of the 5-HTTLPR genotype (p<0.05 after covariate control). Effect confirmed in sibling replication sample. No evidence for reverse causality (depression → cannabis).

Persistent cannabis use was associated with lower school performance and more externalizing, but not internalizing, symptoms, with the effects no longer significant after controlling for alcohol and tobacco use.

Prospective cohort study (n=254) of upper-middle-class adolescents over 4 high school years; persistent cannabis use showed NO significant association with internalizing symptoms (β=0.04, p=0.53) — no increased depression risk after adjustment. However, externalizing symptoms (behavioral problems) were significantly increased (β=0.29, p<0.001). Effects became non-significant after controlling for concurrent alcohol and tobacco use.

Monthly cannabis use was associated with increased odds for suicidal ideation (OR 1,59) and depressive episode (OR 1,55); association strengthened from 2002 to 2012.

Pooled cross-sectional data from the Canadian Community Health Survey 2002 and 2012 (n=43.466, age 15-60 years). At least monthly cannabis use associated with increased odds for major depressive episode (MDE) and suicidal ideation. Association strengthened in 2012 vs. 2002: OR=1.59 (95% CI 1.11-2.27) for suicidal ideation, OR=1.55 (95% CI 1.12-2.13) for MDE. Effect persisted after controlling for other substance use.

Individuals with depression had significantly higher odds for cannabis use (1,90x for any cannabis use, 2,29x for daily use), and this association increased markedly from 2005 to 2016.

n=16.830 US adults 20-59 years (NHANES 2005-2016), depression associated with past-month cannabis use (adjusted OR=1.51, 95% CI 1.04-2.18, p0.05), cross-sectional design limits interpretation of causality.

Early cannabis use predicted an increased risk for later depression, alcohol dependence and substance use disorders in the longitudinal cohort.

n=736 cohort over 20 years, cannabis use associated with increased risk for major depression (OR=2.1, 95% CI 1.4-3.2), alcohol dependence and substance disorders; long-term epidemiological data on psychiatric risks.