The Use of Classic Psychedelics for Depressive and Anxiety-Spectrum Disorders: A Comprehensive Review.

Classic psychedelics, which act on serotonin receptors, show promise for treating depression and anxiety disorders according to clinical trials published since 2020. These compounds have been tested for major depressive disorder, treatment-resistant depression, bipolar II, and anxiety-spectrum disorders. However, the evidence is limited by short follow-up periods, nonstandard dosing, and study designs. Many findings come from post hoc analyses of a few parent studies. The review calls for more original research with larger, diverse samples, standardized methods including blinding, and long-term follow-up to assess benefits and adverse effects. Psychological support and the therapeutic alliance are also important considerations.

Study at a glance

Abstract

Following a decades-long decline in psychedelic research resulting from social, political, and legislative factors, there has been greatly renewed interest in these compounds' ability to treat psychiatric disorders. Classic psychedelics, encompassing both natural and synthetic psychoactive compounds, are characterized by their action as agonists or partial agonists of serotonin 5-hydroxytryptamine 2A receptors. In this comprehensive review, we summarize the latest clinical trials of classic psychedelics on depression and anxiety, attending to the patient demographics and methodology of each study. Overall, studies published since 2020 affirm the potential for classic psychedelics to treat major depressive disorder, treatment-resistant depression, bipolar II, and anxiety-spectrum disorders. However, findings are limited by short follow-up durations and nonstandard dosing and study designs. Given that many of the studies identified were post hoc analyses or follow-up studies from a select few parent studies, it is recommended that more original research be undertaken, with more diverse and larger sample sizes, standardized methodologies including blinding assessment, and long-term follow-up to identify duration of benefits and adverse reactions. It is also important to consider the role of psychological support and the therapeutic alliance in the psychedelic treatment of psychiatric disorders.