Intranasal 5-MeO-DMT Concomitant with SSRI for Treatment-Resistant Depression: A Proof-of-Concept Trial

In this open-label, proof-of-concept (early-stage clinical study), 12 participants with treatment-resistant depression (TRD) already taking SSRIs were administered a single dose of intranasal 5-MeO-DMT (BPL-003) given alongside ongoing SSRI treatment

In the research letter the researchers highlight the following:

“A total of 12 participants, 6 in each of the two dose cohorts, were treated with intranasal 5-MeO-DMT between 22 February 2024 and 02 January 2025. Participants were aged 31–55 years, seven were female (5–10 mg, 2–12 mg), five were male (1–10 mg, 4–12 mg), the majority were white (11/12), and one was mixed race (White and asian).

The mean time to MDD diagnosis was over 15 years in both dose cohorts, and the mean duration of the current episode was 227.8 (176.1) months in the 10 mg group and 123.7 (117.1) months in the 12 mg group. All participants had been on SSRI treatment for at least 5 months before being dosed with 5-MeO-DMT.

The results of this first phase 2a clinical trial of intranasal 5-MeO-DMT administered adjunctively to SSRIs demonstrated acceptable safety and tolerability with promising improvements in depressive symptoms. The safety findings are in line with those reported in trials of intranasal 5-MeO-DMT administered to healthy volunteers and as monotherapy to participants with TRD. The dose range evaluated does not indicate attenuation of efficacy when dosed adjunctively to SSRI.

In conclusion, the results of this first phase 2a study of intranasal 5-MeO-DMT administered concomitantly with SSRIs in participants with TRD demonstrated a single dose of 10 mg or 12 mg was well tolerated and indicate encouraging exploratory evidence for a sustained improvement in depression. Additional data are needed, supporting the case for controlled clinical trials in this population.”

A single intranasal dose of 5-MeO-DMT, given without stopping SSRIs, was associated with rapid, large, and sustained reductions in depression symptoms, with good short-term safety. However this is preliminary evidence. Strong conclusions about efficacy require randomized controlled trials

Seynaeve, M., Dunbar, F., Hindocha, C. et al. Intranasal 5-MeO-DMT Concomitant with SSRI for Treatment-Resistant Depression: A Proof-of-Concept Trial. CNS Drugs (2026). Read Paper

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