An overview of psilocybin, LSD, MDMA, and ketamine in revitalizing psychedelic-assisted therapy: Insights, limitations and future directions.
Kiana Askariyan, Mohammad Taghi Joghataei, Samaneh Dehghan, Shabnam Nohesara, Leila Riahi Pour, Mohammad Hossein Mohammadi, Nooshin Ahmadirad
Progress in neuro-psychopharmacology & biological psychiatry July 25, 2025 DOI: 10.1016/j.pnpbp.2025.111461 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Peer reviewed |
|---|---|
| Interventions | Psilocybin LSD MDMA ketamine |
| Topics | Ketamine LSD MDMA Psilocybin Psychedelic-assisted therapy PTSD |
| Keywords | Psychedelic compounds: compounds Agents |
| Citations | 9 |
| Key findings | Psychedelic-assisted psychotherapy, through compounds like psilocybin, LSD, MDMA, and ketamine, offers therapeutic potential for depression, PTSD, and addiction by modulating serotonin receptors and brain network connectivity, though challenges remain in methodology, regulation, and ethics. |
Abstract
The resurgence of psychedelic-assisted psychotherapy marks a pivotal evolution in mental health treatment, challenging traditional paradigms by integrating compounds such as psilocybin, LSD, MDMA, and ketamine into clinical practice. Historically marginalized due to regulatory and societal concerns, these agents are now gaining recognition for their unique neurobiological mechanisms and therapeutic potential in addressing complex conditions like depression, PTSD, and addiction. Unlike conventional treatments, psychedelics exert their effects primarily through modulation of serotonin receptors and brain network connectivity, with each substance demonstrating distinct pharmacological profiles and clinical applications. Notably, psilocybin and LSD share serotonergic pathways but differ in receptor specificity and subjective effects, while MDMA's empathogenic properties and ketamine's rapid antidepressant action offer alternative therapeutic avenues. Recent FDA breakthrough therapy designations for psilocybin and MDMA underscore a shift toward evidence-based acceptance, yet the field remains challenged by methodological limitations, regulatory barriers, and ethical considerations. This narrative review synthesizes historical developments, mechanistic insights, and clinical outcomes, emphasizing the need for rigorous research, diverse patient cohorts, and thoughtful integration of psychedelics with psychotherapeutic modalities to realize their full therapeutic promise.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Psychedelic-assisted psychotherapy, through compounds like psilocybin, LSD, MDMA, and ketamine, offers therapeutic potential for depression, PTSD, and addiction by modulating serotonin receptors and brain network connectivity, though challenges remain in methodology, regulation, and ethics.
Synthesized
Comparable studies
Other narrative reviews on psilocybin for PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA. | 2016 | Review | |
| Registered clinical studies investigating psychedelic drugs for psychiatric disorders. Registered clinical trials on clinicaltrials.gov evaluating psychedelics for... | 2021 | Review | n = 70 |
| The Psychedelic Future of Post-Traumatic Stress Disorder Treatment | 2024 | Comprehensive review | |
| Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation. | 2022 | Review | |
| Is it now time to prepare psychiatry for a psychedelic future? | 2024 | Review |