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

This review paper (2021) explored the type of psychedelics used across a number of studies and the number of dosing sessions administered that affect subjects’ depression and anxiety outcomes and adverse drug reactions. The authors conclude that psilocybin, ayahuasca & DMT all appear to be effective and safe in improving symptoms of anxiety and depression.

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 (⩽1week) and extended (>1week) 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”

Authors: Robert F. Lang & Ellen M. Unterwald

Summary of 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

Introduction

Classical psychedelics, such as ayahuasca, psilocybin and peyote, have been used in ritual practices for thousands of years and are still used today by some spiritual and religious groups. Modern Western interest in psychedelics largely arose as a result of Albert Hofmann’s discovery of lysergic acid diethylamide (LSD) in 1943, but the use of psychedelics in the domain of clinical psychiatry was largely halted following the reclassification of psychedelics as schedule I controlled substances in 1970.

Depression and anxiety disorders are a tremendous burden on patients throughout the world, with the cost of mental health disorders in the United States alone totalling $71,100,000,000 and $29,700,000,000 in 2013 respectively. Furthermore, the personal impact of mood disorders on patients is substantial.

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