A single nasal dose eased stubborn depression, a promising depression treatment

If antidepressants haven’t worked for you or someone you love, there is good news in depression treatment. In a new trial, one nasal dose of a short-acting psychedelic eased symptoms for weeks, and most people were ready to go home within 2 hours.

It isn’t available yet outside research. But it shows that a new kind of help for hard-to-treat depression is taking shape, and that it can fit into a short clinic visit.

How the study worked

This was a randomized, double-blind trial at 38 sites in Australia, Europe and the US. It included 193 adults aged 18 to 75 with moderate to severe depression that had not improved after 2 to 5 antidepressants. Each person got one nasal dose of mebufotenin at 8 mg or 12 mg, or a very low 0.3 mg dose for comparison, along with psychological support, and was followed for 8 weeks. It is a phase 2b trial, so larger trials come next. It was published Oct. 26, 2026, in JAMA.

What they found

Depression was scored on a scale from 0 to 60, where higher means more severe. Four weeks after the dose (day 29), people who got 12 mg had scores that dropped by about 11 points, or 11.1 points exactly. People on the very low dose dropped about 5 and a half points (5.5). The 8 mg group dropped 12.5 points.

The gap showed up early and held. Scores were lower with the real doses than with the low dose at every check from 2 days to 57 days after the dose.

More people felt real relief, too. At day 29, 35% of the 8 mg group and 34% of the 12 mg group responded to the treatment, compared with 12% on the low dose. Remission, meaning the depression had lifted, was 26% with 8 mg, 18% with 12 mg and 8% with the low dose.

Side effects were reported in every group, including the low-dose group, and nearly all of them (99.7%) were mild or moderate.

The visit was short. About 85% of people on 8 mg and 78% on 12 mg were ready to leave within 2 hours of the dose. Psilocybin and LSD need much longer monitoring in a clinic, and the researchers point to that as the big hurdle for wider use.

What is mebufotenin?

It is a psychedelic compound, also called 5-MeO-DMT, that acts on serotonin receptors in the brain. Its effects are brief, which is why the clinic visit can be short. Researchers also see a possible edge over esketamine, another nasal option, because one dose means fewer visits.

It is experimental. It is only given in clinical trials or approved medical settings, and that is where it belongs for now.

What you can do today

Spend five minutes looking at what is being studied near you. Go to ClinicalTrials.gov and search “treatment-resistant depression” along with your state. You can also look up this trial by its number, NCT05870540, to read how it was set up. Save any study that catches your eye so you have it ready for your next appointment.