Work

Catalyst for change: Psilocybin’s antidepressant mechanisms—A systematic review

Year: 2025

Type: review

Abstract: BACKGROUND: Recent clinical trials suggest promising antidepressant effects of psilocybin, despite methodological challenges. While various studies have investigated distinct mechanisms and proposed theoretical opinions, a comprehensive understanding of psilocybin's neurobiological and psychological antidepressant mechanisms is lacking. AIMS: Systematically review potential antidepressant neurobiological and psychological mechanisms of psilocybin. METHODS: Search terms were generated based on existing evidence of psilocybin's effects related to antidepressant mechanisms. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, 15 studies were systematically reviewed, exploring various therapeutic change principles such as brain dynamics, emotion regulation, cognition, self-referential processing, connectedness, and interpersonal functioning. RESULTS: Within a supportive setting, psilocybin promoted openness, cognitive and neural flexibility, and greater ability and acceptance of emotional experiences. A renewed sense of connectedness to the self, others, and the world emerged as a key experience. Imaging studies consistently found altered brain dynamics, characterized by reduced global and within default mode network connectivity, alongside increased between-network connectivity. CONCLUSIONS: Together, these changes may create a fertile yet vulnerable window for change, emphasizing the importance of a supportive set, setting, and therapeutic guidance. The results suggest that psilocybin, within a supportive context, may induce antidepressant effects by leveraging the interplay between neurobiological mechanisms and common psychotherapeutic factors. This complements the view of purely pharmacological effects, supporting a multileveled approach that reflects various relevant dimensions of therapeutic change, including neurobiological, psychological, and environmental factors.

Source: Journal of Psychopharmacology

DOI: 10.1177/02698811241312866

Authors: Joshua Liebnau, Felix Betzler, André Kerber

Institutions: Freie Universität Berlin, Humboldt-Universität zu Berlin, Charité - Universitätsmedizin Berlin

Language: English

Topic: Psychedelics and Drug Studies

Subfield: Clinical Psychology

Field: Psychology

Domain: Social Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,400