A randomized placebo-controlled trial demonstrates significant benefits of an inhaled psychedelic treatment for patients with treatment-resistant depression. GH001, also known as mebufotenin, showed rapid effectiveness with minimal side effects in a single-day treatment regimen among 81 patients.
Rapid symptom improvement with high remission rates
Among 81 patients, a single day of GH001 treatment led to a least squares mean change in Montgomery-Åsberg Depression Rating Scale score of -15.2 from baseline to day 8, compared with 0.3 with placebo (least squares mean difference -15.5, P<0.001). Day 8 remission rates reached 57.5% with GH001 versus 0% with placebo. No severe or serious adverse events were reported during the placebo-controlled period. The research is particularly significant because fewer than half of patients with major depressive disorder achieve remission with standard antidepressants, and few treatments for treatment-resistant depression—defined as non-response to two to five oral antidepressants—are currently approved in the United States.
Practical advantages over existing psychedelic treatments
The median length of psychoactive effect ranged from 9 to 14 minutes for 6-, 12-, and 18-mg doses of GH001. This short duration presents practical advantages: clinicians would not need to provide all-day monitoring as required with psilocybin, which produces effects lasting approximately 6 hours. Treatment-emergent adverse events occurred in 72.5% of patients who received GH001 versus 7.3% of those given placebo. The most common events in the active drug arm were nausea (42.5%), salivary hypersecretion (20%), paresthesia (20%), dysgeusia (7.5%), and headache (7.5%).
Study design and future directions
This 7-day double-blind phase IIb trial with a 6-month open-label extension was conducted at 16 sites in Europe from May 2023 to March 2025. Patients ages 18 to 64 with treatment-resistant depression and current episode duration of up to 2 years were eligible. In the GH001 arm, mean age was 41.6 with 60% women, and baseline characteristics were similar between groups. The researchers found no evidence of treatment-emergent worsening of suicidal ideation, psychotic symptoms, or dissociation at discharge. The authors plan to explore longer-term efficacy and safety of GH001 in future studies.
This article is an AI-assisted summary. All facts and figures are drawn from the original report: https://www.medpagetoday.com/psychiatry/depression/120489