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A study published in JAMA Psychiatry looks at inhaled mebufotenin for the symptoms of treatment resistant depression.
From our colleagues at SMC Spain:
Dr Gerard Anmella, a psychiatrist and researcher at the Unit for Depressive and Bipolar Disorders at Hospital Clínic in Barcelona, said:
“This is a study evaluating the effect of mebufotenine (5-MeO-DMT), a fast-acting psychoactive molecule (peak effect within a few minutes and duration <1 hour), as a treatment for treatment-resistant depression (no response to >2 antidepressants).
“The study is a randomised clinical trial involving 40 patients who received mebufotenine and 41 who received a placebo.
“The results show high treatment efficacy (>15-point reduction on a 60-point scale compared with placebo) as early as two hours after administration. The effect persisted one week later.
“Furthermore, nearly 60% of patients achieved remission from depression (minimal symptoms) in the treatment group, compared with 0% in the placebo group.
“No serious adverse effects were observed; those recorded were mild to moderate and transient.
Limitations
“Mebufotenine is administered by inhalation, requires supervision and produces a psychedelic effect that may be overwhelming for many people; therefore, prior preparation and supervision by a professional are necessary.
“Participation in the study requires discontinuation of antidepressant treatment for ≥2 weeks, which may lead to clinical worsening and potentially amplify the observed effect of the treatment.
“The response persists for one week following a single administration (it is not a daily treatment). However, in the medium- to long-term follow-up (six months), patients experience depressive relapses, most of which resolve with re-administration (87% remain in remission following further doses; these results will be published in a separate article).
“Blinding effect: although the study is randomised, the psychedelic effect is difficult to conceal. The placebo does not produce perceptual alterations (sensory, ego-related or mystical experiences), so blinding is limited.
“Selection bias: participants know they may receive a psychedelic, which may introduce an expectation bias (greater placebo effect).
Conclusions
“This is an effective, rapid treatment with no serious adverse effects.
“It has a profile clearly distinct from that of classic antidepressants: rapid onset, no need for daily administration, and efficacy within hours rather than weeks.
“The main limitation is the induction of transient psychedelic effects, which necessitates administration supervised by trained professionals, making home use unfeasible.
“Psychotherapy was not administered in this study, which could enhance the treatment’s effectiveness.
“The use of psychedelics opens up a highly promising therapeutic avenue for treatment-resistant depression”.
‘GH001 vs Placebo in Patients With Treatment-Resistant Depression A Randomized Clinical Trial’ by Wiesław J. Cubała et al. was published in JAMA Psychiatry at 15:00 UK time on Wednesday 25 March.
DOI: 10.1001/jamapsychiatry.2026.0096
Declared interests
Dr Gerard Anmella: Gerard Anmella has received fees for continuing medical education (CME) activities or consultancy services from Abartis Pharma, Adamed, Abbott, Angelini, Casen Recordati, Esteve, Johnson & Johnson, Lundbeck, Lundbeck/Otsuka, Rovi and Viatris; however, there is no financial or other relationship relevant to the subject of this article.