Should we skip the trip? Clinical implications of psychedelic-associated subjective effects and the potential role of non-hallucinogenic alternatives.
Kush V. Bhatt, James D Asuncion, Al Alam, Sidney Zisook, Stephen M Stahl
General Hospital Psychiatry July 3, 2025 DOI: 10.1016/j.genhosppsych.2025.07.001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Neuroplasticity |
| Keywords | Psychedelics Hallucinogens Entheogens Psychoactive substances Trips Mental health Psychiatric treatment Mental well-being Healing Brain benefits Brain function Drug development Therapeutics Psychopharmacology Novel treatments Treatment options Non-hallucinogenic compounds |
| Citations | 4 |
| Key findings | The necessity of acute subjective effects in psychedelic therapy may be avoidable, and both psychedelic and nonhallucinogenic approaches warrant space in clinical psychiatry. |
Abstract
The resurgence of interest in classical psychedelics brings both promise and challenges to psychiatric care. Increasing evidence supports the therapeutic potential of psychedelics for a range of mental health conditions, and approval for clinical use appears inevitable. The psychedelic-associated acute subjective experience may mediate or enhance therapeutic outcomes, but also presents significant clinical challenges. This review explores the role of psychedelic-associated subjective effects in psychiatric treatment, including their phenomenology, therapeutic benefit, potential risks, and challenges for implementation. We also explore emerging research on nonhallucinogenic psychedelic analogues that may retain neuroplastic effects while minimizing or eliminating the acute subjective effects. We argue that a debate over the necessity of acute subjective effects of psychedelics may be avoidable and that clinical psychiatry warrants space for both perspectives. Future research should continue to explore the clinical implications of psychedelic-associated subjective experience, while also exploring alternative compounds that broaden the breadth of treatment options for patients.
Comparable studies
Other narrative reviews on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists | 2012 | Review | |
| Towards an understanding of psychedelic-induced neuroplasticity. Review of preclinical and clinical studies | 2023 | Review | |
| Buddha's Brain: Neuroplasticity and Meditation [In the Spotlight] | 2008 | Review | |
| Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics | 2021 | Review | |
| Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms | 2020 | Review |
Citations in the library
Cited by 3
- Commentary on Methods for Addressing Functional Unblinding and Mechanistic Uncertainty in Clinical Trials of Psychedelic-Assisted Treatments Current Treatment Options in Psychiatry November 11, 2025
- Not a Standalone Treatment: Considerations for Psychedelic‐Assisted Therapy Brain and Behavior April 1, 2026
- Bringing Psilocybin-Assisted Therapy to Palliative Oncology: Early Lessons from Real-World Implementation. Healthcare June 3, 2026
Cites 47
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin Journal of Psychopharmacology October 6, 2015
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic Effects. ACS Pharmacology & Translational Science December 10, 2020
- Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors Journal of Psychopharmacology October 11, 2017
and 42 more in the library