Non-hallucinogenic psychedelics for mood and anxiety disorders: A systematic review
Psychiatry Research – May 08, 2025
Source: OpenAlex
Summary
Imagine treating severe mood and anxiety disorders with psychedelics, but without the intense hallucinogen experience. Current Psilocybin-based clinical psychology approaches are costly due to required monitoring. Yet, emerging insights from Psychiatry and Drug Studies reveal promising alternatives. Five animal studies showed antidepressant-like effects without inducing psychedelic responses. Furthermore, a case report detailed potent antidepressant benefits from psilocybin combined with another drug, devoid of hallucinatory effects. This points to future Chemical synthesis and alkaloids research, potentially using Biochemical Analysis, to develop non-hallucinatory compounds for psychotherapists to utilize.
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.