Single Intranasal Administration of the Psychedelic Mebufotenin for Treatment-Resistant Depression

Is mebufotenin benzoate nasal spray, a 5-hydroxytryptamine 1A (5-HT_1A) and 5-HT_2A agonist with a short psychedelic duration, effective, safe, and well tolerated in patients with treatment-resistant depression? In this randomized, double-blind, phase 2b trial of single doses of 8-mg or 12-mg mebufotenin benzoate nasal spray in 193 adults with treatment-resistant depression, the primary outcome of change from baseline in the Montgomery-Åsberg Depression Rating Scale total score at day 29 between the 12-mg dose and a subperceptual low-dose comparator (0.3 mg) was statistically significant (mean difference, −5.3 points). Mebufotenin benzoate nasal spray demonstrates potential as an effective, well-tolerated therapy for treatment-resistant depression with a rapid recovery time.

Corresponding Author: Mathieu Seynaeve, MD, Beckley Park, Beckley, Oxford OX3 9SY, United Kingdom (mathieu@ataibeckley.com).

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