Source: atai Life Sciences and Beckley Psytech press release

This was the largest controlled study of 5-MeO-DMT ever run, and the first blinded Phase 2 study of it to include the United States. Its results set much of the following year in motion: the FDA's Breakthrough Therapy designation, the merger that formed AtaiBeckley, and plans for Phase 3.

The study

Design: an eight-week, quadruple-masked, dose-finding Phase 2b trial (NCT05870540). Participants, the staff giving the medicine, investigators and outcome assessors were all unaware of who received which dose.
Where: 38 sites across six countries.
Participants: 193 adults with moderate-to-severe treatment-resistant depression, meaning no response to two or more treatments in the current episode.
Dosing: a single intranasal dose of BPL-003 (Beckley Psytech's 5-MeO-DMT nasal spray). 73 people received 12 mg, 46 received 8 mg, and 74 received 0.3 mg, a comparison dose too small to have much effect. Using a tiny active dose instead of a placebo helps keep the blinding intact.
Measures: blinded central raters assessed depression (MADRS) at days 2, 8, 29 and 57. The main endpoint was the change at day 29 for the 12 mg dose.

What it found

Main result: at day 29, the 12 mg group's scores had dropped by 11.1 points on average, versus 5.8 for the comparison dose, a statistically significant difference. The 8 mg group dropped 12.1 points.
Day 2: both real doses beat the comparison from the very first assessment, with drops of 8.8 (8 mg) and 8.9 (12 mg) points versus 3.9.
Day 8: improvements deepened to 11.1 (8 mg) and 10.8 (12 mg) points.
Day 57 (eight weeks): effects largely held, at 10.8 (8 mg) and 10.2 (12 mg) points, versus 5.2 for the comparison.
Dose: 8 mg worked as well as 12 mg, and was chosen to advance into Phase 3.

Safety

Side effects: over 99% were mild or moderate, with no drug-related serious adverse events and no signs of increased suicidal thoughts or behaviour.
Dose-related effects: nasal discomfort, nausea, headache, raised blood pressure and anxiety were more common at 12 mg than 8 mg.
Recovery: most people were ready to go home at the 90-minute check after dosing, and the average was within two hours.
Retention: 90% of participants completed the study.

Limitations

Reported as topline results in a company announcement, with full data still to be published
The improvement on the active doses was meaningful but moderate, roughly 5-6 points more than the comparison at day 29
A single dose, followed for only eight weeks
Sponsored by the companies developing the drug

What this means, and doesn't

A blinded trial of this size is strong evidence that 5-MeO-DMT has a real antidepressant effect beyond hope or expectation. It's also notable that the comparison group improved by about half as much, a reminder of how much expectation, attention and care contribute on their own. The effect sizes are meaningful rather than miraculous, and Phase 3 trials will give a clearer picture.

The finding that the lower dose worked as well as the higher one, with fewer side effects, is worth highlighting. It supports an approach common in careful ceremonial practice: more isn't always better, and finding the right dose for each person's nervous system matters more than reaching the strongest possible experience.

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