Positive Results in Phase 2b Trial of Psychedelic Agent GH001 for Treatment-Resistant Depression

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A phase 2b clinical trial of GH001, an an inhalable mebufotenin product, for treatment-resistant depression yielded positive results, according to a press release. The randomized double-blind placebo-controlled trial met primary and secondary endpoints, the company reported.

The trial included 81 participants with treatment-resistant depression who were randomized to receive GH001 (N-40) or placebo (N=41).

The study found the agent resulted in rapid effects, with a 15.2 point improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score on day 8 (p<0.0001). Moreover, there was a 57.7% remission rate for those patients receiving GH001 versus 0% in the group receiving placebo (p<0.0001).

The trial also found GH001 was well-tolerated, with only mild or moderate events reported during the double-blind portion of the trial. Importantly, vital signs such as heart rate, blood pressure, and ECG measurements remained stable, with no clinically significant changes observed. Patients did not have any sedation or dissociative symptoms at discharge following treatment. Almost all patients (97.4%) were discharge ready within an hour of receiving the last dose.

According to the press release, 54 patients completed the study, and at the 6 month visit, 77.8% of those patients were in remission (MADRS≤10). Most of these patients (60.3%) received 1-4 GH001 treatments for the duration of the 6 months.

As of late January, 9 patients are ongoing in the study. Eighteen patients discontinued the study, but only 1 discontinuation was due to an adverse event.

Professor Michael E. Thase, MD, Professor of Psychiatry, Perelman School of Medicine, University of Pennsylvania, was impressed with the stud results. "Patients treated with GH001 experienced a difference of -15.5 points in MADRS score at Day 8 compared to placebo, which is truly remarkable,” he said in a press statement. “Most TRD patients have not benefited from a number of established treatment options and this illness frequently imposes years of insurmountable mental suffering and disabling effects on social and vocational functioning. A novel treatment with such a large and rapid effect, particularly one that may require only infrequent, short 1-3 hours clinic visits, has the potential to be a practice changing treatment.”

"Today, as we share our unprecedented positive Phase 2b data, we celebrate a significant milestone in our journey to interventional psychiatry and pave the way for our future commercial success with GH001 in treatment-resistant depression," said Villy Valcheva, MD, MSc, chief executive officer of GH Research. "The ultra-rapid and profound reduction in depressive symptoms, coupled with sustained remission through infrequent, short treatment visits, positions us uniquely."

GH001 is formulated for 5‐methoxy‐N,N‐dimethyltryptamine (5-MeO-DMT) administration via a proprietary inhalation approach. As a short-acting psychedelic, it has been associated with improvements in depression and anxiety.

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References

1. GH Research Announces Primary Endpoint Met in Phase 2b Trial with GH001 in TRD Demonstrating -15.5 Point Placebo-adjusted MADRS Reduction. GH Research. Press release. February 3, 2025. Accessed February 4, 2025. https://investor.ghres.com/news-releases/news-release-details/gh-research-announces-primary-endpoint-met-phase-2b-trial-gh001

2. Puigseslloses P, Nadal-Gratacós N, Ketsela G, et al. Structure-activity relationships of serotonergic 5-MeO-DMT derivatives: insights into psychoactive and thermoregulatory properties. Mol Psychiatry. 2024;29:2346-2358.