The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges.
Mauro Scala, Chiara Fabbri, Paolo Fusar‐poli, Giorgio Di Lorenzo, Maria Ferrara, Andrea Amerio, Laura Fusar‐poli, Anna Pichiecchio, Carlo Asteggiano, Marco Menchetti, Diana De Ronchi, Giuseppe Fanelli, Alessandro Serretti
CNS Spectrums December 1, 2024 DOI: 10.1017/s1092852924002268 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Critical review Peer reviewed |
|---|---|
| Topics | Addiction Anxiety Neuroplasticity Psilocybin |
| Keywords | Psychedelics magic mushrooms Psychological treatment Cognitive flexibility Personality Pharmacotherapy Rapid-acting antidepressants Mental health depression Neuroscience brain plasticity Hallucinogens |
| Citations | 8 |
| Key findings | Psilocybin holds promise for treating several psychiatric conditions, but larger, more rigorous studies are needed to address gaps in efficacy, safety, and practical implementation. |
Abstract
The revival of psilocybin in psychopharmacological research heralds a potential paradigm shift for treating mood and anxiety disorders, and other psychiatric conditions beyond the psychotic spectrum. This critical review evaluates current evidence on psilocybin's efficacy, juxtaposing potential benefits with the practical aspects of psychedelic-assisted psychotherapy (PAP) and the methodological constraints of existing research.An electronic literature search was conducted using PubMed/MEDLINE, selecting studies published up to December 2023 that explored the clinical use of psilocybin in mood and anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, and substance use disorder. Despite promising preliminary results suggesting psilocybin's efficacy in alleviating depression and anxiety, as well as obsessions, compulsions, and addictive behaviors, significant evidence gaps persist. These include evaluating the efficacy of psilocybin compared to standard antidepressants or anxiolytic molecules and identifying patient subpopulations that might benefit most from PAP. Concerns about psilocybin's safety, long-term efficacy, and optimal dosage remain unclear due to previous trials' limitations. Real-world implementation faces challenges, including infrastructural requirements, personnel training, and unresolved legal and ethical issues. This paper argues for further research to substantiate the evidence base, emphasizing the need for larger studies that overcome current methodological limitations and explore psilocybin's full therapeutic potential. While psilocybin holds promise for psychiatry, its successful translation from research to clinical practice demands more robust evidence on efficacy, safety, and methodological rigor. In addition, other factors, such as cultural stigma and legal/ethical issues, need to be successfully addressed to facilitate psilocybin's implementation in healthcare systems.
Comparable studies
Other narrative reviews on psilocybin for addiction, 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 | |
| Psychedelics as anti-inflammatory agents Animal models and cellular studies | 2018 | Review | |
| Psychedelic Drugs in Biomedicine | 2017 | Review | |
| DARK Classics in Chemical Neuroscience: Psilocybin | 2018 | Review | |
| Psilocybin for treating substance use disorders? | 2016 | Narrative review |
Citations in the library
Cited by 6
- Anhedonia: Current and future treatments Psychiatry and Clinical Neurosciences Reports March 1, 2025
- Ethical issues with psychedelic-assisted treatments in psychiatry: A systematic scoping review Psychological Medicine 2025
- Psychedelics and autism spectrum disorder: Mechanistic insights, translational evidence and ethical challenges Journal of Psychiatric Research June 23, 2026
- Psychedelics in Psychiatry: New Treatment Paradigms or Addictive Treatment Strategies? A Narrative Review Pharmaceutical Science December 9, 2025
- Exploring psilocybin's role in mental health and palliative medicine: a path to improved well-being. Expert Opinion on Emerging Drugs June 1, 2025
and 1 more in the library
Cites 74
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- 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 can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
and 69 more in the library