Single dose of intranasal 5-MeO-DMT in 12 people with treatment-resistant depression

The question

Is a single intranasal dose of BPL-003, a formulation of the short-acting psychedelic 5-MeO-DMT, safe in people with depression that has not responded to previous treatments, and does it change their depression scores?

What they did

Twelve adults with moderate-to-severe major depressive disorder that had resisted earlier treatments took part in a 12-week, open-label phase 2a trial, meaning everyone knew they were receiving the drug and there was no placebo group. Each person received one 10 mg intranasal dose of BPL-003. Researchers tracked side effects, how long people needed to stay before being judged ready for discharge, and depression scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) on days 2, 8, 29, 57 and 85 after dosing.

What they found

All 12 participants (2 women, 10 men, aged 31-55) completed the trial. Nine participants (75.0%) had a total of 18 treatment-related side effects: 8 mild, 9 moderate and 1 severe (raised blood pressure, which returned to baseline during the observation period); nausea and nasal discomfort were most common. Ten participants were judged ready for discharge at the first check about 90 minutes after dosing, and the median time to discharge readiness was 98 minutes (range 95-167). Average MADRS scores fell by 12.2 to 13.0 points from baseline across all timepoints from day 2 to day 85; 10 of 11 participants were classed as responders and 7 were in remission at one or more timepoints after dosing.

The fine print

This was a very small study of 12 people with no placebo or comparison group and no blinding, so the drop in depression scores cannot be attributed to the drug itself. The group was mostly male and follow-up ended at 12 weeks. Response and remission counts are reported out of 11 rather than 12, which the abstract does not explain. This summary is based on the abstract alone.

What it means

A single intranasal dose of 5-MeO-DMT was tolerated by this small group, with mostly mild to moderate side effects, and depression scores fell over 12 weeks. Only larger randomized trials with a control group can show whether the drug is responsible for that change.

Evidence grade: Very low. A very small open-label trial with only 12 participants, no control group and no blinding, so improvements cannot be separated from expectation or natural change.

This summary is based on the study’s published abstract.