Can one day of an inhaled psychedelic lift treatment-resistant depression?

In a phase 2b trial across 16 European sites, 81 adults with treatment-resistant depression received up to three escalating inhaled doses of mebufotenin (GH001) or placebo on a single day. One week later, 57.5% of the drug group (23 of 40) were in remission, compared with 0% of the 41 placebo patients.

Most people with treatment-resistant depression have already tried several antidepressants without much relief, so researchers keep looking for something that works faster and differently. This trial tested GH001, a synthetic inhaled form of mebufotenin (also known as 5-MeO-DMT, a short-acting psychedelic). Eighty-one adults aged 18 to 64 who had not responded to two to five previous antidepressants were randomly assigned, double-blind, to receive either GH001 or a matching placebo. Everything happened on a single day: participants got an individualized regimen of up to three escalating doses (6, 12, and 18 mg), then were followed for a week. On the standard depression rating scale, the GH001 group improved by about 15.5 points more than placebo, an unusually large effect. By day 8, 23 of 40 GH001 patients met the threshold for remission, while none of the 41 placebo patients did. No severe or serious adverse events were reported during the placebo-controlled period. The honest limitation: this is a small, one-week trial, and a drug that produces a vivid psychedelic experience is very hard to blind, so participants likely guessed which group they were in. The trial was also funded by the company developing the drug, and several authors are employees or shareholders. Longer, larger trials will decide whether the effect holds up.