Assessing the effects of methodological differences on outcomes in the use of psychedelics in the treatment of anxiety and depressive disorders: A systematic review and meta-analysis

Classical psychedelics such as psilocybin, ayahuasca, and LSD appear to be effective and relatively safe for rapidly and enduringly improving anxiety and depression. A meta-analysis of nine clinical trials found large positive effects on anxiety (Cohen's d = 1.26) and depression (Cohen's d = 1.38) overall, with benefits persisting beyond one week. No serious adverse drug reactions were reported. No significant differences in effectiveness emerged between the three psychedelic agents, but trials that used multiple dosing sessions showed significantly better outcomes than those using a single session.

Study at a glance

Abstract

Background: Classical psychedelics are a group of drugs which act as agonists on the serotonin-2A (5-HT2A) receptor. Evidence suggests they may have a uniquely rapid and enduring positive effect on mood. However, marked heterogeneity between methodological designs in this emerging field remains a significant concern. Aims: To determine how differences in the type of psychedelic agent used and the number of dosing sessions administered affect subjects’ depression and anxiety outcomes and adverse drug reactions (ADR). Methods: This review collected and screened 1591 records from the MEDLINE and Web of Science databases for clinical trials reporting objective data on mood for subjects with a known anxiety or depression. Results: After screening, nine clinical trials met inclusion criteria. Meta-analysis of these studies showed significant, large positive effect sizes for measures of anxiety (Cohen’s d = 1.26) and depression (Cohen’s d = 1.38) overall. These positive effects were also significant at acute (⩽1 week) and extended (>1 week) time points. No significant differences were observed between trials using different psychedelic agents (psilocybin, ayahuasca or lysergic acid diethylamide (LSD)), however, a significant difference was observed in favour of trials with multiple dosing sessions. No serious ADR were reported. Conclusion: Psilocybin, ayahuasca and LSD all appear to be effective and relatively safe agents capable of producing rapid and sustained improvements in anxiety and depression. Moreover, the findings of the present analysis suggest that they may show a greater efficacy when given to patients over multiple sessions as compared to the more common single session used in many of the existing trials.