Non-hallucinogenic psychedelics for mood and anxiety disorders: A systematic review
Noah Chisamore, Lee Phan, Roger S McIntyre, Margery J.q. Chen, David C J Chen-Li, Muhammad Ishrat Husain, Joshua D. Di Vincenzo, Rodrigo B. Mansur, Danica E. Johnson, Joshua D. Rosenblat
Psychiatry Research May 8, 2025 DOI: 10.1016/j.psychres.2025.116532 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Case report Peer reviewed |
|---|---|
| Topics | Anxiety Psilocybin |
| Keywords | Hallucinogen Mood Clinical psychology Psychotherapist |
| Citations | 7 |
| Key findings | Non-hallucinatory psychedelics show antidepressant-like effects in animal studies and a case report suggests similar potential in humans without hallucinatory effects. |
Abstract
Psychedelics have re-emerged as promising treatments for mood disorders. The current model provides a moderate-to-high dose of a psychedelic agent (e.g., psilocybin) to reliably induce an altered state of consciousness. Unfortunately, the hallucinatory effects limit the treatment's potential scalability given patients' vulnerability and extensive monitoring costs, leading to growing interest in non-hallucinatory psychedelics (NHPs). This review's objective was to identify, summarize and synthesize all published pre-clinical and clinical studies evaluating NHPs for mood and anxiety disorders. We included five animal studies demonstrating antidepressant-like effects through assessments like forced swim test (FST) and open field test (OFT) without observing head-twitch response (HTR), and one case report that identified a patient who inadvertently combined trazodone and psilocybin and experienced potent antidepressant effects without psychedelic effects. These preliminary findings provide a strong impetus for further investigation in human samples with rigorously designed clinical trials that may delineate the potential antidepressant effects of psychedelics without hallucinatory effects.
Comparable studies
Other systematic reviews and meta-analyses on psilocybin for anxiety, most cited first.
Citations in the library
Cited by 7
- Psilocybin as a fast-acting and long-lasting antidepressant for adolescence: Proposing NeuroD1 as a biomarker of its long-term plasticity Biomedicine & Pharmacotherapy October 30, 2025
- Simple Analogs of the LSD D-Ring: A Consideration of Structure-Activity Relationships and Their Potential as Therapeutics. ACS Chemical Neuroscience November 5, 2025
- α2-Adrenergic receptor modulates 5-HT2A-mediated behavioral effects of MDMA and psilocybin in mice. Molecular Psychiatry July 7, 2026
- An exploratory study of breathwork-induced altered states of consciousness in experienced practitioners: the airways to alteration (A2A) trial Frontiers in Psychology June 10, 2026
- Psychedelic Therapies for Comorbid Major Depressive Disorder and Chronic Pain: A Review of Putative Mechanisms of Action. Pharmacology Research & Perspectives April 1, 2026
and 2 more in the library
Cites 33
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Journal of Psychopharmacology January 13, 2015
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
and 28 more in the library