Inhaled 5-MeO-DMT (GH001) worked regardless of how many antidepressants had failed before

The question

Does the antidepressant effect of GH001, an inhaled synthetic form of the psychedelic mebufotenin (5-MeO-DMT), depend on how many antidepressants a person has already tried without success?

What they did

Researchers re-analyzed data from the 40 people with treatment-resistant depression who received GH001 during the double-blind part of a Phase 2b randomized trial. GH001 was given as a single-day individualized dosing regimen. They checked whether the number of prior lifetime antidepressant failures was linked to change in depression scores on the Montgomery-Asberg Depression Rating Scale (MADRS) at Day 8, and again among people who completed a 6-month open-label extension. They also compared remission rates (MADRS score of 10 or below) across groups with 2, 3, 4, or 5 or more prior failures.

What they found

There was no meaningful link between the number of prior antidepressant failures and depression score improvement at Day 8 (correlation r = -0.13; P = 0.44) or among 6-month extension completers (r = -0.10; P = 0.60). Remission rates at Day 8 were similar across subgroups, ranging from 53.9% to 63.6%, and ranged from 61.5% to 85.7% at the end-of-treatment visit or Month 6. The abstract notes the original trial found a least-squares mean difference of -15.5 points versus placebo, an effect size of -2.0, and 57.5% remission at Day 8 compared with 0% on placebo. Secondary outcome measures also showed no association with treatment history.

The fine print

This was a post hoc analysis, meaning the comparison was planned after the results were in, and the subgroups were very small within a total of 40 people who received the drug. Absence of a correlation in such a small sample is not strong proof that treatment history does not matter. The 6-month results come from an open-label extension with no placebo group and only among people who completed it, which can flatter the numbers. This summary is based on the abstract alone, which reports no safety or side effect data.

What it means

In this small early-phase trial, a single day of inhaled GH001 reduced depression scores to a similar degree whether people had failed two antidepressants or five or more, but the finding comes from an exploratory analysis and needs testing in larger, purpose-designed studies.

Evidence grade: Low. This is a post hoc (after-the-fact) analysis of a small Phase 2b trial, looking at subgroups that the trial was not designed or powered to compare.

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