The therapeutic use of psychedelics continues to gain ground in psychiatry, particularly in the management of complex disorders such as treatment-resistant depression, where available options remain limited. In this context, a phase II clinical trial published in JAMA Psychiatry evaluated the efficacy and safety of GH001, an inhaled synthetic formulation of mebufotenin (5-MeO-DMT), a fast-acting psychedelic compound, in these patients. The study included Narcís Cardoner, Director of the Psychiatry Department at Hospital de Sant Pau and researcher in the Mental Health group at the Sant Pau Research Institute.
This fast-acting psychedelic compound is being investigated as a potential therapeutic alternative in psychiatric disorders, particularly due to its ability to produce rapid clinical effects after a single treatment session in patients with treatment-resistant depression. In this regard, Narcís Cardoner notes that “interest in psychedelics in mental health reflects the need to explore new therapeutic pathways in patients who do not respond to conventional treatments.”
The study included 193 patients with treatment-resistant depression who received GH001 via inhalation in a controlled clinical setting with structured psychological support. The design included the administration of repeated doses within a single session until achieving a defined therapeutic effect.
The results showed significant reductions in depressive symptoms following treatment, with a mean decrease of up to 15 points on the MADRS (Montgomery-Åsberg Depression Rating Scale), a widely used clinical tool to assess depression severity and changes after treatment. This magnitude of reduction is considered clinically meaningful in patients with treatment-resistant depression. In addition, approximately 57% of patients achieved a clinical response, and nearly 29% reached remission in the weeks following the intervention. The observed safety profile was consistent with that of other psychedelic compounds, with adverse events generally transient and manageable within the trial setting.
Based on these findings, Narcís Cardoner states that “this type of study helps consolidate interest in psychedelics as a potential therapeutic pathway in complex psychiatric disorders, although results should be interpreted with caution, as these are early-phase trials.”
The study also assessed the treatment’s safety profile, describing mostly transient adverse events that were manageable in the clinical trial context. However, these findings highlight the need for further research to determine the duration of the effect, optimal dosing, and the role of psychotherapeutic support in the observed response.
For Narcís Cardoner, beyond the specific results, the value of the study lies in its contribution to an emerging field. “Psychedelics are generating growing interest in clinical research, and studies like this help better define their potential and limitations, as well as lay the groundwork for larger and independent future trials.”
The management of treatment-resistant depression remains one of the major challenges in mental health, driving the exploration of new therapeutic strategies. In this context, research on psychedelics is consolidating as an area of growing interest, in which IR Sant Pau is strengthening its research activity with the aim of contributing to the development of new evidence-based options.
Reference Article:
Cubała WJ, Bajbouj M, Bauer M, Baune BT, Cardoner N, Devlin F, Doolin K, Dueñas Herrero RM, Elices M, Feeney A, Gałuszko-Węgielnik M, Jakuszkowiak-Wojten K, Janů L, Kelly JR, Ledden K, Maclsaac R, Madero S, McInerney SJ, Montejo AL, Nawka A, Páleníček T, Pérez Solà V, Ramaekers JG, Reif A, Ritter P, Ryan F, Svendsen CB, Sweeney C, Terwey TH, Trivedi MH, Valcheva V, Vieta E, Thase ME. GH001 vs placebo in patients with treatment-resistant depression: A randomized clinical trial. JAMA Psychiatry 2026. https://doi.org/10.1001/jamapsychiatry.2026.0096
