A single nasal spray cut depression scores in treatment-resistant depression
The full story behind my Short: Phase 2b JAMA trial (193 adults, 38 sites): one dose of mebufotenin benzoate nasal spray; day-29 remission 26% (8 mg) and 18% (12 mg) vs 8% low dose. Benefit still at day 57. Company-funded; needs phase 3.
This is phase 2b, company-funded, and not approved. Functional unblinding was common. This page is not medical advice. Talk to your mental health team.
The short version
Mebufotenin benzoate is a short-acting psychedelic given as a single nasal spray. In a phase 2b randomised, double-blind trial published in JAMA, adults with treatment-resistant depression (failed 2–5 antidepressants in the current episode) received one dose plus psychological support [1][2].
What they found
Primary end point: change in MADRS score at day 29 for 12 mg vs 0.3 mg was statistically significant (mean difference −5.3 points). The 8 mg dose also beat the low dose (−6.2). Benefit held through day 57 [1][2].
Side effects were common (about 76–85%) but nearly all mild or moderate. Most participants were ready to go home within about two hours — much shorter monitoring than older psychedelics such as psilocybin [1].
Limits and caveats
- Phase 2b. Needs confirmation in phase 3 [2].
- Company-funded. Beckley Psytech Ltd, an AtaiBeckley company [2].
- Unblinding. Functional unblinding was common, so treat the numbers carefully [2].
- Not approved. Not a licensed treatment.
- Selected patients. Moderate–severe TRD after 2–5 failed antidepressants; results may not generalise [1].
Watch the Short
Why it matters
Treatment-resistant depression is hard to treat, and existing psychedelic options can mean long clinic days. A short-acting nasal spray that still shows benefit weeks later — if confirmed in phase 3 — could matter for access.
Full narration (transcript)
A single nasal spray of a short-acting psychedelic cut depression scores in people who'd failed other antidepressants. It's mebufotenin. The phase two bee trial had 193 adults at 38 sites, published in JAMA. Everyone got one dose: 8 milligrams, 12 milligrams, or a tiny 0.3 milligram comparator, plus psychological support. At day 29, 26 percent on 8 milligrams were in remission, versus 18 percent on 12, and 8 percent on the low dose. The benefit was still there at day 57. Most people were ready to go home in about 2 hours, far shorter than older psychedelic sessions. Side effects were mostly mild or moderate. But this is phase two bee, company-funded, and it still needs phase three. It's not approved. Functional unblinding was common, so treat the numbers carefully. This isn't medical advice. Talk to your mental health team. Follow the link to the main website for much deeper information.
Sources
- [1] Feifel D, Seynaeve M et al. Single intranasal administration of the psychedelic mebufotenin for treatment-resistant depression. JAMA. Published online 26 Oct 2026. doi:10.1001/jama.2026.18380. https://media-prod.ama-assn.org/media-releases/10.1001/jama.2026.18380
- [2] JAMA Network research summary (funding: Beckley Psytech Ltd, an AtaiBeckley company). https://jamanetwork.com/journals/jama/fullarticle/2855794
Credits
Images via Wikimedia Commons (illustrative unless stated): Girl using nasal spray in indoor setting.jpg (Shixart1985, CC BY 2.0); Action photo of nasal spray on a black background.jpg (robin_24, CC BY 2.0); Sad-Mental-Illness.jpg (Fotorech, CC0). On-screen graphics: own.
AI voice note: the narration in the Short is an AI clone of my own voice (Chatterbox TTS by Resemble AI, MIT licence), used with my consent. I wrote the script and checked the figures against the sources above.
This page is general information, not medical or dental advice. Please talk to a doctor, dentist or pharmacist about your own health.