Single dose of short-acting psychedelic nasal spray eased treatment-resistant depression in phase 2b trial

A single dose of a short-acting psychedelic nasal spray improved symptoms of treatment-resistant depression in a mid-stage trial published in JAMA on 26 October 2026.

The study

• Design: randomised, double-blind phase 2b trial in 193 adults whose depression had not responded to standard treatment.
• Drug: mebufotenin benzoate (a form of 5-MeO-DMT) given once as a nasal spray at 8 mg or 12 mg. It acts on the serotonin 5-HT1A and 5-HT2A receptors and has a short psychedelic effect.
• Comparator: a 0.3 mg “subperceptual” dose meant to produce no noticeable effect, instead of a pure placebo.
• Main result: on day 29, the 12 mg dose reduced the Montgomery-Åsberg Depression Rating Scale (MADRS) score by 5.3 points more than the comparator, a statistically significant difference. The authors describe it as effective and well tolerated, with rapid recovery after dosing.

Limitations

• This is a phase 2b trial with a few hundred people and a four-week primary endpoint; it does not show how long benefit lasts or how it compares with existing treatments.
• With psychedelics, participants may guess which dose they got, which can weaken blinding.
• The corresponding author is listed with an AtaiBeckley email address, indicating company involvement. Larger phase 3 trials and regulatory review would be needed before any approval. JAMA published an accompanying editorial.

People with depression should not try psychedelics on their own; talk to your doctor about treatment options.