Source: Journal of Psychopharmacology, 2026 (PubMed 41761045) · DOI: 10.1177/02698811261420087

This was the first group of patients ever given BPL-003, Beckley Psytech's intranasal 5-MeO-DMT, as a treatment for depression. It's Part 1 of the same four-part Phase 2a program as the SSRI study and the two-dose study. It laid the groundwork for everything that followed, including the large Phase 2b trial.

The study

Design: Phase 2a, open-label, single-group study (NCT05660642, Cohort 1) with 12 weeks of follow-up. The analysis was exploratory and descriptive, with no formal statistical testing.
Where and when: King's College London and Hammersmith Medicines Research in London, from February 2023 to February 2024.
Participants: 12 adults (10 men and 2 women, aged 31-55) with moderate-to-severe treatment-resistant depression. On average they had tried about three antidepressants in their current episode, and they tapered off antidepressants over up to six weeks before dosing.
Screening: people with heart risks sensitive to blood pressure spikes, psychotic or bipolar disorder, or a recent substance use disorder were excluded, as were people who hadn't responded to ketamine, esketamine or electroconvulsive therapy.
Dose: a single 10 mg dose of BPL-003, one spray into one nostril.
Support: three preparation sessions in the two weeks before dosing, a supervised dosing session, and three integration sessions on Days 2, 8 and 15, all following a standardized, non-directive approach. Participants stayed on site for at least four hours after dosing.

What it found

Results are for the 11 participants in the main analysis.

Depression scores (MADRS): the average score fell from 27.5 at baseline to 14.8 on Day 2, and was 14.5 at Day 85. The improvement held at roughly 12-13 points throughout the 12 weeks.
Day 2: 6 of 11 participants (54.5%) had their score cut at least in half, and 4 (36.4%) were in remission.
Over 12 weeks: 10 of 11 met criteria for response at one or more points, and 7 (63.6%) reached remission at least once.
Other measures: clinician-rated severity dropped from 4.3 to 2.5 by Day 2, self-rated depression roughly halved by Day 8, and day-to-day disability fell by about half. At Day 85, 9 of 10 who answered said they had improved, and half described themselves as much or very much improved.
Pleasure and enjoyment: scores on a scale measuring anhedonia, the loss of pleasure in life, fell from 8.4 to 1.5 by Day 85, below the threshold for anhedonia.
The experience: 3 of 12 participants (25%) had a complete mystical experience.

Safety

Overall: 10 of 12 participants had 26 side effects: 12 mild, 13 moderate and 1 severe. Most drug-related effects began and resolved on dosing day. There were no serious adverse events and no withdrawals.
Most common: nausea and nasal discomfort (4 people each) and vomiting (3).
Blood pressure: blood pressure and heart rate rose briefly, peaking around 10 minutes after dosing and returning close to baseline by 60 minutes. The one severe event was a participant whose blood pressure was already elevated before dosing and reached a systolic reading of 226. They had no symptoms, and it resolved during observation without treatment.
Suicidal thoughts: 2 participants, both with a prior history of suicidal thoughts, reported suicidal thoughts during the study. Investigators considered these clinically significant but unlikely to be caused by the medicine.
Other: one person had brief auditory pseudo-hallucinations, hearing sounds they knew weren't real, on Day 2, lasting about a day.
Recovery: most participants were ready to go home at about 90 minutes, with a median of about 98 minutes.

Limitations

Only 12 participants
No placebo or comparison group, no blinding, and participants started with positive expectations
The medicine's effect can't be separated from the psychological support and setting
Mostly middle-aged white men, so results may not reflect everyone with depression
Exploratory, with no formal statistical testing
The average score at 12 weeks (14.5) still sits in the mild depression range, so many participants improved without fully recovering
Sponsored by Beckley Psytech, with several authors employed by the company

What this means, and doesn't

As a first look, the results are encouraging. A single, short experience, held inside weeks of preparation and integration, was followed by a fast drop in depression that largely held for three months. The improvement in anhedonia is especially interesting, since a flat, joyless quality is one of the hardest parts of depression to shift.

The safety findings are just as instructive. The highest blood pressure reading came from someone whose pressure was already high before dosing, which shows why checking how a person is arriving matters on the day itself. And the suicidal thoughts reported by two participants with a prior history are a reminder that careful screening and real follow-up after a session aren't optional extras.

Still, this study is very small and uncontrolled, so it can't separate the medicine's effect from expectation, support and natural change. Its main value is historical: it was the first signal that justified the larger, blinded trial of 193 people that followed, which found a real but more modest effect.

This is also a pharmaceutical product given in a clinic to people with a diagnosed condition. It doesn't describe ceremonial work, and it isn't a reason to stop any current treatment.

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