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.