Risks of using psilocybin in treatment of treatment-resistant depression
DOI:
https://doi.org/10.12775/JEHS.2025.79.58319Keywords
psilocybin, treatment resistant depression, safety, psychedelic assisted therapy, adverse effectsAbstract
Introduction
As depression rates continue to rise globally, the need for more effective and innovative treatments has become increasingly urgent, highlighting the potential impact of psilocybin as a promising therapeutic option. However, to ensure its safe and effective integration into clinical practice, it is essential to establish robust safety parameters for its administration. This paper focuses on addressing the risks associated with psilocybin therapy. We believe this paper can help understand risks as a platform for safety based treatment.
Material and Methods
A comprehensive literature search was conducted using the PubMed and Google Scholar databases, supplemented by references cited in the initially identified articles. The search focused on studies and reviews addressing the challenges and risks associated with psilocybin use in the treatment of treatment-resistant depression (TRD).
References
1. Wasson, R Gordon, and R. Gordon Wasson. ‘Notes on the Present Status of Ololiuhqui and the Other Hallucinogens of Mexico’. Botanical Museum Leaflets, Harvard University, vol. 20, no. 6, Nov. 1963, pp. 161--193, https://doi.org/10.5962/p.168541.
2. Nichols, David E. ‘Psilocybin: From Ancient Magic to Modern Medicine’. The Journal of Antibiotics, vol. 73, no. 10, Oct. 2020, pp. 679–86. PubMed, https://doi.org/10.1038/s41429-020-0311-8.
3. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. https://www.who.int/publications/i/item/9241544228.
4. ‘DSM-IV-TR | Psychiatry Online’. DSM Library, https://psychiatryonline.org/doi/book/10.1176/appi.books.9780890420249.dsm-iv-tr.
5. Caspi, Avshalom, et al. ‘Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene’. Science (New York, N.Y.), vol. 301, no. 5631, July 2003, pp. 386–89. PubMed, https://doi.org/10.1126/science.1083968.
6. Drevets, W. C., et al. ‘PET Imaging of Serotonin 1A Receptor Binding in Depression’. Biological Psychiatry, vol. 46, no. 10, Nov. 1999, pp. 1375–87. PubMed, https://doi.org/10.1016/s0006-3223(99)00189-4.
7. Nestler, Eric J., and William A. Carlezon. ‘The Mesolimbic Dopamine Reward Circuit in Depression’. Biological Psychiatry, vol. 59, no. 12, June 2006, pp. 1151–59. PubMed, https://doi.org/10.1016/j.biopsych.2005.09.018.
8. Bekhbat, Mandakh, et al. ‘Functional Connectivity in Reward Circuitry and Symptoms of Anhedonia as Therapeutic Targets in Depression with High Inflammation: Evidence from a Dopamine Challenge Study’. Molecular Psychiatry, vol. 27, no. 10, Oct. 2022, pp. 4113–21. PubMed, https://doi.org/10.1038/s41380-022-01715-3.
9. Liu, Xinyue, et al. ‘Epidemiology of Treatment-Resistant Depression in the United States’. The Journal of Clinical Psychiatry, vol. 83, no. 1, Nov. 2021, p. 21m13964. PubMed, https://doi.org/10.4088/JCP.21m13964.
10. Stafford, Peter G. Psychedelics Encyclopedia. Ronin Pub., 1992.
11. Beliveau V, Ganz M, Feng L, Ozenne B, Højgaard L, Fisher PM, Svarer C, Greve DN, Knudsen GM. A High-Resolution In Vivo Atlas of the Human Brain's Serotonin System. J Neurosci. 2017 Jan 4;37(1):120-128. doi: 10.1523/JNEUROSCI.2830-16.2016. PMID: 28053035; PMCID: PMC5214625.
12. De Gregorio, Danilo, et al. ‘D-Lysergic Acid Diethylamide, Psilocybin, and Other Classic Hallucinogens: Mechanism of Action and Potential Therapeutic Applications in Mood Disorders’. Progress in Brain Research, edited by Tanya Calvey, vol. 242, Elsevier, 2018, pp. 69–96. ScienceDirect, https://doi.org/10.1016/bs.pbr.2018.07.008.
13. Moliner, Rafael, et al. ‘Psychedelics Promote Plasticity by Directly Binding to BDNF Receptor TrkB’. Nature Neuroscience, vol. 26, no. 6, June 2023, pp. 1032–41. www.nature.com, https://doi.org/10.1038/s41593-023-01316-5
14. Erritzoe, D., et al. ‘Effects of Psilocybin Therapy on Personality Structure’. Acta Psychiatrica Scandinavica, vol. 138, no. 5, Nov. 2018, pp. 368–78. PubMed, https://doi.org/10.1111/acps.12904.
15. Griffiths, Rr, et al. ‘Mystical-Type Experiences Occasioned by Psilocybin Mediate the Attribution of Personal Meaning and Spiritual Significance 14 Months Later’. Journal of Psychopharmacology (Oxford, England), vol. 22, no. 6, Aug. 2008, pp. 621–32. PubMed, https://doi.org/10.1177/0269881108094300.
16. Bogenschutz, Michael P., et al. ‘Psilocybin-Assisted Treatment for Alcohol Dependence: A Proof-of-Concept Study’. Journal of Psychopharmacology (Oxford, England), vol. 29, no. 3, Mar. 2015, pp. 289–99. PubMed, https://doi.org/10.1177/0269881114565144.
17. Johnson, Matthew W., et al. ‘Pilot Study of the 5-HT2AR Agonist Psilocybin in the Treatment of Tobacco Addiction’. Journal of Psychopharmacology (Oxford, England), vol. 28, no. 11, Nov. 2014, pp. 983–92. PubMed, https://doi.org/10.1177/0269881114548296.
18. Goodwin, Guy M., et al. ‘Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression’. New England Journal of Medicine, vol. 387, no. 18, Nov. 2022, pp. 1637–48. DOI.org (Crossref), https://doi.org/10.1056/NEJMoa2206443.
19. Carhart-Harris, R. L., et al. ‘Psilocybin with Psychological Support for Treatment-Resistant Depression: Six-Month Follow-Up’. Psychopharmacology, vol. 235, no. 2, Feb. 2018, pp. 399–408. Springer Link, https://doi.org/10.1007/s00213-017-4771-x.
20. Hasler, Felix, et al. ‘Acute Psychological and Physiological Effects of Psilocybin in Healthy Humans: A Double-Blind, Placebo-Controlled Dose-Effect Study’. Psychopharmacology, vol. 172, no. 2, Mar. 2004, pp. 145–56. PubMed, https://doi.org/10.1007/s00213-003-1640-6.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Michał Orzechowski, Joanna Orzechowska, Paulina Fijałek, Jan Karczmarz, Aleksandra Paprocka, Marika Gutowska, Agnieszka Kosińska, Urszula Świrk, Wiktoria Belcarz, Karolina Kalinowska
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 359
Number of citations: 0
