Preclinical models for evaluating psychedelics in the treatment of major depressive disorder.
Laith Alexander, Dasha Anderson, Luke Baxter, Matthew D. B. Claydon, James Rucker, Emma Robinson
British Journal of Pharmacology October 28, 2024 DOI: 10.1111/bph.17370 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression |
| Keywords | Antidepressant Behaviour Hallucinogenic Neuropsychology Translation |
| Citations | 11 |
| Key findings | Behavioral approaches in animal models are central to understanding whether antidepressant and psychedelic effects of psychedelic drugs involve related or independent mechanisms, but methodological issues, dose relevance, and sex differences must be addressed. |
Abstract
Psychedelic drugs have seen a resurgence in interest as a next generation of psychiatric medicines with potential as rapid-acting antidepressants (RAADs). Despite promising early clinical trials, the mechanisms which underlie the effects of psychedelics are poorly understood. For example, key questions such as whether antidepressant and psychedelic effects involve related or independent mechanisms are unresolved. Preclinical studies in relevant animal models are key to understanding the pharmacology of psychedelics and translating these findings to explain efficacy and safety in patients. Understanding the mechanisms of action associated with the behavioural effects of psychedelic drugs can also support the identification of novel drug targets and more effective treatments. Here we review the behavioural approaches currently used to quantify the psychedelic and antidepressant effects of psychedelic drugs. We discuss conceptual and methodological issues, the importance of using clinically relevant doses and the need to consider possible sex differences in preclinical psychedelic studies.
Comparable studies
Other narrative reviews on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synaptic Dysfunction in Depression: Potential Therapeutic Targets | 2012 | Review | |
| Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse | 2003 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines | 2005 | Review |
Citations in the library
Cited by 9
- Cross-Species Evidence for Psilocin-Induced Visual Distortions: Apparent Motion Is Perceived by Both Humans and Rats. Biological Psychiatry Global Open Science September 1, 2025
- Narrating the psychoneuroimmunomodulatory properties of serotonin 5-HT2A receptor psychedelics from a transdiagnostic perspective. Acta Neuropsychiatrica July 25, 2025
- Psychedelics as pharmacotherapeutics for substance use disorders: A scoping review on clinical trials and perspectives on underlying neurobiology British Journal of Pharmacology September 2, 2025
- Cognitive and affective models of psychedelics in rodents. International review of neurobiology 2025
- Psychedelics in treatment-resistant depression: a comprehensive review of mechanisms, clinical evidence, and recommendations. Neuropsychiatrie June 30, 2026
and 4 more in the library
Cites 79
- 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 with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
and 74 more in the library