Objective We assessed controlled non-interventional studies and randomized clinical trials (RCTs) evaluating THC-containing cannabis’ safety and effectiveness for anxiety. Methods We searched PubMed, Embase, APA PsychInfo, and Cochrane databases in February 2023 for clinical studies that reported patient-level controlled quantitative assessments of anxiety outcomes following cannabis treatment. Exclusion criteria included: publication before 2000, in non-English language, assessment of topical treatment or containing <0.3% tetrahydrocannabinol, and FDA-approved products. We assessed risk of bias via RoB2/ROBINS-I, and rated evidence quality using the GRADE approach. PROSPERO:CRD42023411999 Results From 6453 search records, 4 RCTs and 1 observational study met inclusion criteria. All studies involved patients with severe comorbid medical conditions, with anxiety assessed as a secondary outcome, limiting generalizability to primary anxiety disorders. Interventions included THC-rich cannabis oil for fibromyalgia, cannabinoids for obsessive-compulsive disorder (OCD), cannabidiol (CBD)-enriched extracts for Parkinson’s disease, nabiximols (THC:CBD 1:1) for multiple sclerosis (MS), and cannabis for chronic non-cancer pain. Anxiety was measured via self-reported scales. Due to heterogeneity in anxiety measures, results were synthesized narratively. Compared with placebo, the OCD RCT showed significant anxiety worsening 4.31 (1.70, 6.92); the Parkinson’s disease RCT non-significant improvement -0.82 (-1.97, 0.33), and the fibromyalgia and MS RCTs show no significant effects 0.38 (-2.91, 3.67); -2.00 (-7.51, 3.51). The pain observational study reported no initial significant effect on anxiety -0.30 (-1.53, 0.93). Quality of life (QoL) worsened with THC in Parkinson’s -0.14 (-0.23, -0.04) and showed non-significant improvement in MS 0.35 (-1.09, 1.79). The evidence quality was rated low to moderate. Conclusions Evidence on THC-containing cannabis’ effects on anxiety is limited and inconsistent, with heterogeneous measures and mixed findings preventing meaningful quantitative synthesis. Across studies, no consistent evidence of benefit was observed. Higher-quality studies with standardized outcomes are needed to clarify their impact on anxiety and quality of life. Evidence quality was rated as low to moderate, driven by small sample sizes, short durations, and limited generalizability.
Kotecha et al. (Mon,) studied this question.