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

Sep 14, 2021Journal of psychopharmacology (Oxford, England)

How different methods affect psychedelic treatment results for anxiety and depression: A systematic review and meta-analysis

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Abstract

Meta-analysis of nine clinical trials indicated significant, large positive effects on anxiety (Cohen's = 1.26) and depression (Cohen's = 1.38).

Psychedelics such as psilocybin, ayahuasca, and LSD are associated with rapid and sustained improvements in anxiety and depression.
Positive effects on mood were significant at both acute (⩽1 week) and extended (>1 week) time points.
No significant differences in outcomes were found between different types of psychedelic agents.
Trials administering multiple dosing sessions showed greater efficacy compared to single-session trials.
No serious adverse drug reactions were reported in the included studies.

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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 = 1.26) and depression (Cohen's = 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. d d

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.

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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

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