Depression

Moderate evidence for chronic pain and spasticity, low evidence for nausea/vomiting, weight gain and sleep disorders; increased risk of side effects.

Comprehensive SR across 79 RCTs (n=6.462) on medical cannabis. NO specific data on depression as a primary indication identified. Moderate evidence for chronic pain/MS spasticity, but depression not evaluated as a robust outcome. Mentions psychiatric adverse events (anxiety/psychosis).

Cannabinoids show hardly any evidence for improving depression, anxiety disorders, ADHD, Tourette syndrome, PTSD or psychosis; only very weak evidence for small improvement of anxiety symptoms in other conditions, but increased side effects.

Systematic review of cannabinoids (THC and CBD) in mental disorders; finds almost no evidence for therapeutic benefit in depression, anxiety, PTSD, ADHD, Tourette syndrome or psychosis.

Non-medical cannabis use was associated with higher suicidal ideation, poorer mental functioning, fewer psychiatric visits and less improvement in depressive symptoms over time.

Prospective cohort study in n=307 outpatient depression patients over 12 months; 40% cannabis use (71,7% non-medical, 28,2% medical). Non-medical use associated with higher suicidality at baseline (B=1,08, p=0,002), poorer mental functioning (B=-3,79, p=0,015) and fewer psychiatric visits (B=-0,69, p=0,009). Over time less improvement in depressive symptoms (B=1,49, p=0,026) and suicidality (B=1,08, p=0,003) vs. non-users.

Medical cannabis card led to improved self-reported insomnia symptoms, but to higher incidence and severity of cannabis use disorder and no significant improvement in pain, anxiety or depressive symptoms.

n=269 adults with medical cannabis card (Massachusetts), 12-month follow-up showed no significant improvement in affective disorder symptoms (depression/anxiety, measured with PROMIS), moderate improvements in pain and sleep (p0.001), but affect unchanged.

Venlafaxine showed no benefit in reducing depressive symptoms (63% vs. 69% improvement) and led to significantly worse cannabis abstinence (11,8% vs. 36,5%) compared with placebo.

n=103 cannabis-dependent patients with comorbid major depression/dysthymia, 12-week RCT venlafaxine-XR (up to 375 mg) vs. placebo + CBT. Clinically significant depression improvement (≥50% HAM-D reduction) high in both groups: VEN-XR 63%, placebo 69% (p=0.49, no difference). Cannabis abstinence lower under VEN-XR (11.8%) vs. placebo (36.5%, p<0.01, OR=4.51 [95% CI: 1.53–13.3]). Mood improvement correlated with cannabis reduction only in the placebo group (p<0.01), not under VEN-XR.

Medical cannabis led to a statistically significant but clinically non-meaningful reduction in PHQ-9 scores of on average 0,20 points; 95,1% of patients showed no clinically relevant change.

Prospective cohort study in n=5.103 medically authorized cannabis patients (50% with depression at baseline), median follow-up 196 days (IQR 77-451). Mean PHQ-9 change -0,20 points (95% CI -0,26 to -0,14, p<0,0001); 95,1% without clinically relevant change, 3,4% improvement, 1,5% worsening. No clinically meaningful overall effect on depressive symptomatology.

Initiation of medical cannabis was associated with significantly reduced anxiety and depression symptoms.

Observational trial on antidepressant and anxiolytic effects of medical cannabis; exploratory, real-world setting with self-reported outcomes, no placebo control.