Effects of Different Cannabinoid Formulations on Anxiety-Related Disorders, and Tourette Syndrome: A Systematic Review and Meta-Analysis.

Introduction: Cannabinoid formulations have been increasingly proposed as therapeutic potential options for anxiety disorders (ADs). Several countries have expanded regulatory frameworks facilitating access to these compounds due to their alleged therapeutic benefits, including their application in ADs. Given its public health significance, we evaluated existing evidence regarding the efficacy of different medical cannabinoids as interventions for ADs and related mental conditions. Methods: A comprehensive search was conducted in PubMed, Embase, PsycInfo, Web of Science, Scielo, and Lilacs databases. We included randomized controlled trials (RTCs) assessing the effects of various cannabinoid formulations on patients with ADs and related conditions. Distinct meta-analyses were performed for cannabinoid subtypes. Analyses were conducted using Jamovi software, relying on standardized mean difference (SMD) calculations of pre/post-intervention score changes for both intervention and control groups. Results: We incorporated 21 placebo-controlled RCTs, examining cannabinoid interventions in social anxiety disorder (SAD = 5), generalized anxiety disorder (GAD = 1), post-traumatic stress disorder (PTSD = 7), obsessive-compulsive disorder (OCD = 1), and Tourette syndrome (TS = 7). Data extraction indicated considerable heterogeneity across outcomes, including clinical symptoms, neuroimaging findings, well-being, psychosocial functioning, safety, and tolerability. In studies utilizing pure or enriched CBD, the meta-analytic measure indicated a nonsignificant difference (SMD = -0.40; 95% CI: -0.84/0.03). However, a subgroup analysis of pure CBD compounds yielded a moderate, statistically significant effect size (SMD: -0.61, 95% CI: -1.15/-0.07). For studies investigating pure or enriched delta-9-tetrahydrocannabinol (Δ9-THC), the meta-analytic measure was -0.65 (95% CI: -1.06/-0.24), suggesting a moderate, significant effect favoring Δ9-THC-dominant compounds. In meta-analyses of studies with Δ9-THC and cannabidiol (CBD) mixtures, the effects were not significant (SMD = -0.73, 95% CI: -2.00/0.55). Although suggesting a potential superior efficacy of pharmaceutically pure formulations of Δ9-THC and CBD over alternative versions, these results must be interpreted with caution due to heterogeneous study designs and small sample sizes. Discussion: The current evidence is limited. Low-quality evidence suggests that pharmaceutical-grade CBD may have limited efficacy for SAD and GAD. In addition, low-quality evidence supports Δ9-THC's efficacy for the reduction of nightmares in PTSD and tic severity in TS. Further double-blind, randomized, placebo-controlled trials with larger and heterogeneous samples are required to investigate the clinical outcomes of pharmaceutical-grade cannabinoids and standardized cannabis extracts in the treatment of ADs.