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Placebo Effects in the Treatment of Depression-Implications for the Psychedelic Renaissance.

Mina Ansari, Sophie I Elliott, Sophie E Holmes, Gerard Sanacora

Neurologic clinics February 1, 2026 DOI: 10.1016/j.ncl.2025.08.009 via PubMed

Summary

AI-generated from the abstract

Placebo effects in depression treatment trials are substantial and can obscure the true efficacy of new drugs, especially for psychedelic-like compounds. Expectancy, the therapeutic setting, and trial design all interact to shape patient outcomes. This review examines these factors and discusses emerging methods to mitigate, measure, or harness placebo effects in future research on rapid-acting antidepressants and psychedelic therapies.

Study at a glance

Characteristics Review Peer reviewed
Population Individuals with mental illness (depression, PTSD)
Topics Ketamine MDMA Psilocybin Psychedelic-assisted therapy
Keywords Antidepressant Masking
Citations 1
Key finding Placebo effects in depression trials are influenced by expectancy, therapeutic setting, and trial design, and these factors are particularly relevant for evaluating psychedelic-like compounds.

Abstract

The development of novel, rapid-acting treatments and the resurgence of interest in the therapeutic potential of psychedelic-like compounds has stimulated excitement and enthusiasm within the pharmaceutical industry, and provided new hope for millions of individuals suffering with mental illness such as major depressive disorder and post-traumatic stress disorder. This review summarizes the scope and mechanisms of placebo related effects in depression treatment trials, with a particular focus on their implications for psychedelic-like compounds. We examine how expectancy, therapeutic setting, and trial design interact to shape outcomes and consider emerging approaches for mitigating, measuring, or even harnessing placebo-effects in future research.

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