Source: Feifel D, Seynaeve M, Cubała WJ, et al. Single Intranasal Administration of the Psychedelic Mebufotenin for Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA, published online October 26, 2026. doi:10.1001/jama.2026.18380. Also see JAMA's research summary.

The companies behind this trial first shared its headline results in a July 2025 press release (summary of that announcement). Now the full study has been through peer review and published in JAMA, one of the most widely read medical journals in the world. That matters: the numbers have been checked by independent reviewers, and the authors now set out the trial's weaknesses alongside its results. Mebufotenin is the clinical name for 5-MeO-DMT.

The study

Design: a randomized, double-blind Phase 2b trial with eight weeks of blinded follow-up (NCT05870540), run from September 2023 to April 2025.
Where: 38 sites in Australia, Europe and the United States.
Participants: 193 adults aged 18 to 75 (average age 41, 59% women) with moderate-to-severe depression that hadn't responded to two to five antidepressants in the current episode.
Dosing: a single spray of 5-MeO-DMT into one nostril, given by a trained clinician, with psychological support and at least four hours of observation. 73 people received 12 mg, 46 received 8 mg, and 74 received 0.3 mg, a dose too small to feel, used in place of a placebo.
Measures: depression was rated on the MADRS scale (0 to 60, higher is more severe). The main endpoint was the change at day 29 for 12 mg versus 0.3 mg. Readiness to go home was checked from 90 minutes after dosing.

What it found

Main result: at day 29, scores dropped by 11.1 points on 12 mg versus 5.5 on the comparison dose, a difference of 5.3 points (statistically significant).
The lower dose: 8 mg did at least as well, dropping 12.5 points, 6.2 more than the comparison.
Speed and staying power: both real doses did better than the comparison at every check, from day 2 through day 57.
Response and remission at day 29: 35% responded on 8 mg and 34% on 12 mg, versus 12% on the comparison. 26% reached remission on 8 mg and 18% on 12 mg, versus 8%.

Safety

Side effects: reported by 76% on 8 mg, 85% on 12 mg and 73% on the comparison dose. 99.7% of them were mild or moderate.
Recovery: most people were ready to go home within two hours: 85% on 8 mg and 78% on 12 mg.

Limitations, in the authors' own words

Blinding often broke down. Many participants could tell whether they'd had a real dose, which is hard to avoid with any psychedelic and can inflate results.
The 8 mg group was smaller, after a change to how people were assigned partway through.
Antidepressants had to be stopped first, so the results may not apply to people who stay on them.
Limited ethnic diversity among participants.
The psychological support wasn't tested on its own, so its share of the effect is unknown.
Sponsored by Beckley Psytech, now part of AtaiBeckley, the company developing the spray. The authors say Phase 3 trials are needed to confirm the results.

What changed since the announcement

The peer-reviewed numbers are very close to the July 2025 topline release. The comparison group improved slightly less than first reported (5.5 points rather than 5.8), and the 8 mg group slightly more (12.5 rather than 12.1). The paper adds the response and remission rates, and a clear list of limitations.

What this means, and doesn't

Publication in JAMA makes this the strongest evidence yet that 5-MeO-DMT can help people whose depression hasn't responded to other treatments, from a single dose and a short clinic visit. The effect is real and lasting over eight weeks, but moderate rather than miraculous: about a third of people responded, and the comparison group improved too, a reminder of how much care, attention and expectation do on their own.

The lower dose doing as well as the higher one, with more people reaching remission, echoes something careful ceremonial practice has long held: the strongest possible experience isn't the goal. Finding the right amount for each person is.

These results describe a pharmaceutical nasal spray in a clinic, not ceremony. They're promising, and they don't make 5-MeO-DMT right for everyone.

Research summaries are for education, not medical advice. Considering 5-MeO-DMT yourself?
Start with Safety & Screening.