Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participants.

A new intranasal formulation of 5-MeO-DMT, called BPL-003, was tested in 44 healthy people who had never used psychedelics. Doses up to 12 mg were well tolerated, with no serious side effects; common mild effects included nasal discomfort, nausea, headache, and vomiting. The drug was absorbed quickly, reaching peak levels in about 8–10 minutes, and cleared from the body in under 27 minutes. Higher doses produced stronger subjective drug intensity and mystical experiences, with 60% of participants reporting a 'complete mystical experience' at 10 and 12 mg. The rapid onset and short duration suggest potential for treating conditions like depression.

Study at a glance

Abstract

To investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of BPL-003, a novel intranasal benzoate salt formulation of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), in healthy participants. In all, 44 psychedelic-naïve participants enrolled in the double-blind, placebo-controlled single ascending dose study (1-12 mg BPL-003). Concentrations of 5-MeO-DMT and its pharmacologically active metabolite, bufotenine, were determined in plasma and urine. PD endpoints included subjective drug intensity (SDI) rating, the Mystical Experience Questionnaire (MEQ-30) and the Ego Dissolution Inventory (EDI). BPL-003 was well tolerated at doses up to 12 mg. There were no serious adverse events (AEs), and most AEs were mild; the most common being nasal discomfort, nausea, headache and vomiting. 5-MeO-DMT was rapidly absorbed and eliminated; the median time to peak plasma concentration was approximately 8-10 min and the mean terminal elimination half-life was <27 min. 5-MeO-DMT systemic exposure increased approximately dose-proportionally, while plasma bufotenine concentrations and urinary excretion of 5-MeO-DMT and bufotenine were negligible. The intensity of the SDI ratings was associated with plasma 5-MeO-DMT concentrations. MEQ-30 and EDI scores generally increased with the BPL-003 dose; 60% of participants had a 'complete mystical experience' at 10 and 12 mg doses. Profound and highly emotional consciousness-altering effects were observed with BPL-003, with a rapid onset and short-lasting duration. The novel intranasal formulation of BPL-003 was well tolerated with dose-proportional increases in PK and PD effects. The short duration of action and induction of mystical experiences suggest clinical potential, warranting further trials. NCT05347849.