From molecules to meaning: unpacking the antidepressant mechanisms of psychedelic drugs.
Victor Pablo Acero, Taylor A Flatt, Peter M. Gooch, Skylar J. Gaughan, Adam W. Levin, Alan K. Davis
Expert Review of Clinical Pharmacology June 11, 2025 DOI: 10.1080/17512433.2025.2515866 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Philosophy of mind Psychedelic-assisted therapy |
| Keywords | Psychedelic pharmacology Psychedelic transdiagnostic mechanisms Psychedelics for depression Psychopharmacology Depression treatment Neuroscience research |
| Key findings | Psychedelics likely exert antidepressant effects through complex, interwoven biological, psychological, and experiential processes that cannot be reduced to single mechanisms. |
Abstract
Psychedelic compounds are emerging treatments for depression, capable of producing rapid and lasting symptom reduction after 1-2 administrations in the context of psychotherapy - a stark contrast to traditional antidepressants. Despite promising outcomes, the mechanisms underlying psychedelics' reported antidepressant effects remain poorly understood and are often framed in fragmented ways. Clarifying these mechanisms is crucial for guiding future research and clinical innovation with psychedelics. This review critically examines current evidence on the mechanisms by which psychedelics may exert antidepressant effects. We highlight key mechanisms of action within biological, psychological, social, and spiritual domains that we believe are among the most compelling and deserving of further investigation. Throughout, we compare these mechanisms to those proposed for traditional antidepressants, identifying points of overlap and divergence. Although mechanistic research is valuable, an overemphasis on identifying discrete pathways may limit psychedelic science. Psychedelics likely work through complex, interwoven biological, psychological, and experiential processes that cannot be fully reduced to single mechanisms. Future research should move beyond frameworks and metrics used to validate conventional antidepressants to explore how suprapharmacological factors - set, setting, therapy modality, and integration - shape outcomes. Embracing this complexity is essential to realizing psychedelics' full therapeutic potential for depression.
Comparable studies
Other narrative reviews on psychedelic-assisted therapy, most cited first.
Citations in the library
Cites 144
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and 139 more in the library