Neurobiological and Therapeutic Potential of Psilocybin in Psychiatric Disorders
M Loganathan, A Saravanakumar, P. Parthiban, G Anandharaj, S Gobika, D Dharshana, Mohamed Ali
Journal of Pharma Insights and Research October 5, 2025 DOI: 10.69613/thv1dn30 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Psilocybin-assisted therapy |
| Topics | Default mode network Neuroplasticity Psilocybin |
| Keywords | Context archaeology Antidepressant Neurocognitive Cognition Anxiolytic Depression economics Clinical trial Partial agonist Psychotherapist Disengagement theory Mediator Pharmacology Clinical psychology |
| Key findings | Psilocybin-assisted therapy produces rapid and sustained antidepressant and anxiolytic effects, likely through acute disruption of the Default Mode Network followed by enhanced neuroplasticity. |
Abstract
Psilocybin, an indoleamine alkaloid derived from various fungal species, is the subject of renewed, rigorous investigation for its therapeutic potential in psychiatry. This compound, a prodrug for the active metabolite psilocin, functions primarily as a partial agonist at the serotonin 2A (5-HT2A) receptor. Its administration within a structured psychotherapeutic context is associated with rapid and sustained antidepressant and anxiolytic effects, particularly in populations with treatment-resistant depression and existential distress related to life-threatening illnesses. The neurobiological mechanisms are multifaceted, initiated by acute 5-HT2A-mediated disruption of key brain networks, most importantly the Default Mode Network (DMN). This network destabilization correlates with subjective experiences of ego dissolution and is hypothesized to create a state of elevated brain entropy. This acute phase is followed by a period of enhanced neuroplasticity, driven by downstream signaling pathways involving BDNF and mTOR, which promotes synaptogenesis and dendritic spine growth in cortical neurons. This "window of plasticity" may facilitate the unlearning of maladaptive cognitive patterns and the formation of new, adaptive associations. Clinical trials demonstrate significant efficacy, though psychological risks necessitate careful screening, preparation, and a supportive therapeutic environment. The translation of psilocybin-assisted therapy from research to clinical practice presents challenges related to protocol optimization, clinician training, and scalability
Comparable studies
Other narrative reviews on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| The pharmacology of psilocybin | 2002 | Review | |
| Serotonin research: contributions to understanding psychoses | 2008 | Review | |
| Psychedelics, Meditation, and Self-Consciousness | 2018 | Review | |
| The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act | 2018 | Review |