Inhaled 5-MeO-DMT in 10 women with postpartum depression: an open-label phase 2a trial

The question

Can a single day of inhaled mebufotenin (5-MeO-DMT), given as the formulation GH001, reduce depression symptoms in women with postpartum depression, and is it tolerated?

What they did

This was an early-stage, open-label trial, meaning everyone knew they were getting the drug and there was no placebo group. Ten women aged 18-45 with major depressive disorder that began around pregnancy or birth took part between March 2023 and August 2024. All had at least moderate-to-severe symptoms at the start, scoring 28 or higher on the Montgomery-Asberg Depression Rating Scale (MADRS), a clinician-rated depression scale. On a single day, each received an individualized regimen of up to three escalating inhaled doses (6, 12 and 18 mg). The main measure was the change in MADRS score from the start to day 8.

What they found

Average MADRS score at the start was 36.7 (standard deviation 4.8). By day 8, scores had fallen by an average of 35.4 points (standard deviation 5.5; P < .0001). All 10 patients met the criteria for response (at least a 50% drop in score) and for remission (MADRS of 10 or less) at day 8, and remission was first seen 2 hours after the final dose on day 1. No serious adverse events were reported. All side effects that occurred during treatment were mild or moderate, with headache the most common.

The fine print

With only 10 participants, no placebo group and no blinding, the large improvement cannot be attributed to the drug alone; expectation effects and natural improvement in postpartum depression can be substantial. The reported follow-up is short, ending at day 8 for the main outcome, so nothing is known here about how long the effect lasts. Participants were a selected group of women aged 18-45 with severe symptoms, which limits how widely the results apply. This summary is based on the abstract only.

What it means

This small early trial suggests inhaled 5-MeO-DMT was tolerated and was followed by rapid, large drops in depression scores in women with postpartum depression, but the design cannot show the drug caused the change. Randomized, placebo-controlled trials with longer follow-up are needed.

Evidence grade: Very low. A very small open-label trial with 10 participants, no placebo group and no comparison treatment, so improvement cannot be separated from expectation and natural recovery.

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