Source: atai Life Sciences and Beckley Psytech announcement

Single-dose results with 5-MeO-DMT have been promising, but for many people the effect fades over weeks. This small study tested whether a second dose, given soon after the first, could build on the initial response. It's Part 3 of the same four-part Phase 2a program as the SSRI study (see the March 2026 post).

The study

Design: open-label Phase 2a proof-of-concept study (NCT05660642), with 12 weeks of follow-up.
Participants: 13 adults with treatment-resistant depression who were not taking antidepressants. 12 met the criteria for the main analysis.
Dosing: an 8 mg intranasal dose of BPL-003 (Beckley Psytech's 5-MeO-DMT nasal spray), followed by a 12 mg dose two weeks later. These are the same doses used in the larger Phase 2b trial.
Measures: safety, tolerability and several standard depression rating scales, including the MADRS, at multiple timepoints.

What it found

After the first dose: depression scores fell by an average of 13.3 points by day 2 and 12.9 points by day 8.
After the second dose: one week after the 12 mg dose, the total improvement from baseline reached 19.0 points.
At 12 weeks: an average improvement of 13.7 points from baseline remained.
Remission: 25% one week after the first dose, doubling to 50% at week 8 (six weeks after the second dose), and 42% at week 12.

Safety

Side effects: all were mild or moderate, with no severe or serious drug-related events. This is consistent with other BPL-003 studies.
The second dose: it didn't appear to change the safety or tolerability profile.
Recovery: people met discharge criteria within two hours after each dose.

Limitations

Very small: 13 people, 12 in the main analysis
Open-label with no comparison group, so expectation effects can't be ruled out
Participants weren't on antidepressants, which limits how widely the results apply
Reported in a company announcement, not yet a peer-reviewed paper

What this means, and doesn't

The signal is that a second session can deepen and extend the effect of the first, with remission roughly doubling after the second dose. Combined with the larger extension study (see the November 2025 post), it's shaping how Phase 3 trials think about repeat dosing. But a study this small and unblinded generates a hypothesis rather than a conclusion.

The pattern is familiar from ceremonial practice. A first meeting with this medicine often loosens something, and a later session can allow people to go further with more trust and familiarity. That said, a second session should never be assumed or pushed, and some people feel complete after one.

A fourth part of this program, testing two 8 mg doses in people who are also taking antidepressants, was still underway at the time.

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