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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Individuals with mental illness (depression, PTSD) |
| Topics | Ketamine MDMA Psilocybin Psychedelic-assisted therapy Depression |
| Keywords | Antidepressant Masking Unblinding Placebo effect Clinical trial design Depression treatment |
| Citations | 1 |
| Key findings | 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.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Argues that expectancy, therapeutic setting, and trial design shape placebo effects in depression trials, and that these factors are particularly relevant for evaluating psychedelic-like compounds.
Synthesized
Comparable studies
Other narrative reviews on MDMA for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Registered clinical studies investigating psychedelic drugs for psychiatric disorders. Registered clinical trials on clinicaltrials.gov evaluating psychedelics for... | 2021 | Review | n = 70 |
| Top Ten Tips Palliative Care Clinicians Should Know About Psychedelic-Assisted Therapy in the Context of Serious Illness. Palliative care clinicians and patients | 2022 | Review | |
| MDMA and MDMA-Assisted Therapy. | 2025 | Review | |
| Role of Psychedelics in Treatment-Resistant Depression. | 2023 | Review | |
| Is it now time to prepare psychiatry for a psychedelic future? | 2024 | Review |