Emerging mechanisms of psilocybin-induced neuroplasticity
Sonia Sonda, Diana Pendin, Stefano Comai, Sara de Martin, Paolo L. Manfredi, Andrea Mattarei
TIPS - Trends in Pharmacological Sciences September 16, 2025 DOI: 10.1016/j.tips.2025.08.012 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Neuroplasticity Psilocybin |
| Citations | 11 |
| Key findings | Psilocybin's therapeutic and neuroplastic effects involve a complex molecular interactome beyond just 5-HT2A receptor activation, including multiple serotonin receptor subtypes and non-serotonergic targets such as TrkB. |
Abstract
Psilocybin, a serotonergic psychedelic, is gaining attention for its rapid and sustained therapeutic effects in depression and other hard-to-treat neuropsychiatric conditions, potentially through its capacity to enhance neuronal plasticity. While its neuroplastic and therapeutic effects are commonly attributed to serotonin 2A (5-HT 2A ) receptor activation, emerging evidence reveals a more nuanced pharmacological profile involving multiple serotonin receptor subtypes and nonserotonergic targets such as TrkB. This review integrates current findings on the molecular interactome of psilocin (psilocybin active metabolite), emphasizing receptor selectivity, biased agonism, and intracellular receptor localization. Together, these insights offer a refined framework for understanding psilocybin's enduring effects and guiding the development of next-generation neuroplastogens with improved specificity and safety.
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 16
- Low, non-psychedelic doses of psilocybin as a novel treatment for MASLD, obesity and type 2 diabetes via 5-HT2B receptor-dependent mechanisms Pharmacological Research December 29, 2025
- Knocking at the Doors of Perception: Relating LSD Effects on Low‐Frequency Fluctuations and Regional Homogeneity to Receptor Densities in fMRI European Journal of Neuroscience November 1, 2025
- THE IMPACT OF SELECTED PSYCHOACTIVE SUBSTANCES - COCAINE, AMPHETAMINE, PSILOCYBIN, MDMA, AND KETAMINE - ON THE BODY IN PHYSICAL AND PSYCHOLOGICAL ASPECTS AND THEIR MAIN MECHANISMS OF ACTION: A NARRATIVE REVIEW International Journal of Innovative Technologies in Social Science September 28, 2026
- Acute psilocybin or ethocybin leads to a sustained increase in Pavlovian aversion memory in male mice Frontiers in Pharmacology September 22, 2026
- Pharmacokinetics and safety of a modified‐release psilocybin formulation: A SAD Phase I trial in normal‐weight and overweight/obese participants British Journal of Clinical Pharmacology September 21, 2026
and 11 more in the library
Cites 72
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
- Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder JAMA Psychiatry August 24, 2022
and 67 more in the library