Source: Ritter et al., poster presented at ISBD 2025 (via GH Research SEC filing) · Trial registration NCT05839509

Bipolar II disorder involves long, often stubborn episodes of depression alternating with periods of hypomania, a milder form of mania. Treatment options for the depressive episodes are limited. People with bipolar disorder are usually excluded from psychedelic trials because of the risk of triggering mania, so this small trial is unusual. It was the first time 5-MeO-DMT was given to people with bipolar II disorder in a clinical study, using GH Research's inhaled synthetic formulation, GH001.

The study

Design: Phase 2a, open-label, proof-of-concept trial (NCT05839509), run at sites in Europe.
Participants: 6 adults with bipolar II disorder in a current depressive episode. Four were women, all were White, and the average age was 44. Their illness was long-standing, averaging 14 previous depressive episodes, with the current one lasting about 21 weeks.
Screening: participants had to have very few manic symptoms at baseline and again before dosing. Antidepressants were not allowed for at least 7 days before dosing, and lithium was not allowed within the previous 6 months.
Dosing: up to three escalating inhaled doses (6, 12 and 18 mg) on a single day, one hour apart. Each further dose depended on how strongly the person had felt the previous one and how well they had tolerated it.
Setting: a clinic with medical supervision and supportive care, but no planned psychotherapy.

What it found

Depression scores (MADRS): the average baseline score of 32 fell by 16.3 points at 2 hours after dosing, 13.3 points at Day 2, and 16.8 points at Day 8, a 52.5% reduction.
Response and remission: at Day 8, 2 of the 6 participants (33.3%) met criteria for response, and 2 (33.3%) for remission.
Other measures: a bipolar-specific depression scale, an overall severity rating and a broader psychiatric symptom scale all improved in line with the main result.
Mania: scores on a mania rating scale stayed low and slightly decreased, from 2.2 to 1.0 by Day 8, with no signs of manic symptoms emerging.

Safety

Overall: 5 of 6 participants had side effects, 18 in total. Most were mild, with two moderate events and one severe episode of anxiety that settled within 24 hours.
Most common: headache (3 people), nausea (2) and anxiety (2).
Serious events: none, and no one withdrew from the trial. No flashbacks were reported.
Recovery: everyone was ready to go home the same day.

Limitations

Only 6 participants, all White
Only 8 days of follow-up, far too short to know whether mood switching might happen later
No placebo group and no blinding
Participants were carefully selected for very low manic symptoms and had recently stopped other medications
Presented as a conference poster, not yet a full peer-reviewed paper
Sponsored by GH Research, with several authors employed by or consulting for the company

What this means, and doesn't

The results are an interesting early signal: a rapid improvement in depression, and no sign of mania over the following week in this tightly selected group. Still, the improvement was smaller and less consistent than in GH001's trials in other kinds of depression, with only a third of participants responding.

It's important to be clear about what this doesn't show. Six people followed for eight days in a medical setting can't establish that 5-MeO-DMT is safe for people with bipolar disorder. The main concern, a switch into hypomania or mania, can appear weeks later, and this study wasn't designed to detect that.

For that reason, bipolar disorder remains an important contraindication in ceremonial work with 5-MeO-DMT. Anyone with bipolar disorder who is curious about this research should talk with their psychiatrist, and look to clinical trials rather than non-clinical settings.

Research summaries are for education, not medical advice. Considering 5-MeO-DMT yourself?
Start with Safety & Screening.