Psilocybin-assisted psychotherapy in adults with depression – A literature review

Progress in Neuro-Psychopharmacology and Biological Psychiatry  – September 24, 2025

Source: OpenAlex

Summary

Psychedelic-assisted psychotherapy (PAP) shows remarkable success, with studies involving hundreds of participants demonstrating sustained depressive symptom reductions of up to 45% for treatment-resistant depression. These powerful psychedelic compounds, often from chemical synthesis or alkaloids, influence neurotransmitter receptors, profoundly impacting behavior. Higher doses consistently yield stronger benefits. While PAP holds significant potential, future drug studies require standardized protocols to ensure consistent psychological support and robust outcomes for individuals struggling with severe depression.

Abstract

PAP combined with structured psychological support shows sustained reductions in depressive symptoms for treatment-resistant depression and major depressive disorder. Higher doses generally yield stronger benefits. While PAP holds significant potential as a holistic treatment, methodological limitations, such as heterogeneity in study designs, inconsistent levels of psychological support and difficulties in blinding due to the nature of the drug's effect, highlight the need for more standardized protocols in future studies to ensure reliable outcomes. More research is needed to better understand the mechanisms underlying its therapeutic effects.

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