Volume 30, Issue 176, October 2026

Psilocybin as a novel drug in the treatment of major depressive disorder: a systematic review

Jakub Magdziak^1♦, Oliwia Borowska¹, Eliza Mędrek², Paulina Zegarska³, Natalia Sałkowska⁴, Natalia Brzozowska², Karolina Zawadzka², Barbara Wardzyńska⁵, Sara Awad¹, Hanna Markowska⁶, Paulina Małyszczak¹, Katarzyna Zięba⁷

¹Independent Public Clinical Hospital CMKP, Czerniakowska 231, 00- 416 Warsaw, Poland.
²Nowodworskie Centrum Medyczne, Miodowa 2, 05-100 Nowy Dwór Mazowiecki, Poland.
³Grochowski Hospital, Grenadierów 51/59, 04-073 Warsaw, Poland.
⁴University Clinical Center of the Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland.
⁵Independent Public Healthcare Complex in Wyszków, Komisji Edukacji Narodowej 1, 07-200 Wyszków, Poland.
⁶Samodzielny Publiczny Wielospecjalistyczny Zakład Opieki Zdrowotnej Ministerstwa Spraw Wewnętrznych i Administracji w Bydgoszczy, ul. Ks. R. Markwarta 4-6, 85-015 Bydgoszcz, Poland.
⁷Health Center in Piaseczno, address: ul. Fabryczna 1, 05-500 Piaseczno, Poland.

^♦Corresponding author
Jakub Magdziak; Independent Public Clinical Hospital CMKP, Czerniakowska 231, 00- 416 Warsaw, Poland

ABSTRACT

Major depressive disorder remains one of the most common and debilitating psychiatric disorders in the global population, with a significant number of patients not responding adequately to traditional antidepressant treatments. As such, the need for new methods has prompted studies exploring the use of psychedelic medicines, such as psilocybin, which is a serotonergic psychedelic drug produced by mushrooms from the Psilocybe genus. This literature review explores the use of psilocybin as a medicine in major depressive disorder, along with the sustainability of any improvements. A literature review was undertaken on six clinical studies on the use of psilocybin therapy for different kinds of depression. The literature review entailed both randomized clinical trials and longitudinal studies. There were several aspects of the research designs that we considered when reviewing the studies, including study design and methodology. Based on existing evidence, psilocybin-assisted treatments can lead to rapid and meaningful improvements in depression, even for patients who did not respond to conventional treatments. Large-scale randomized trials have been able to prove effectiveness on resistant patients, and further follow-up trials reveal that some patients may derive longterm benefits. But the variety in the sample group, methods used, and time periods observed makes a direct comparison hard. Psilocybin is one such promising pharmaceutical treatment for depression, especially for those who do not respond to existing treatments. Still, more studies are needed to gain a better understanding of how best to administer psilocybin.

Keywords: psilocybin, major depressive disorder, treatment-resistant depression, psychedelic-assisted therapy, mystical experience

Medical Science, 2026, 30, e201ms3896

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Published: 12 October 2026