Acute Effects of Intravenous 5-MeO-DMT in Healthy Participants

This Phase I, randomised, quadruple-masked, placebo-controlled, parallel trial (n=40) will assess the acute subjective, physiological and pharmacokinetic effects of intravenous 5-MeO-DMT in healthy adult participants. The study compares single ascending infusion rates of 5-MeO-DMT (0.2, 0.4, 0.6, 0.8 mg/min administered intravenously over 30 minutes) against a saline placebo, with the primary focus on change in subjective effects over time. Participants aged 25–65 who meet eligibility criteria will attend three on-site visits over approximately two weeks (screening, study drug administration, and a follow-up about one week later). Participants are randomised to one of four active dose arms or placebo and are blinded to assignment. During the administration visit blood pressure and heart rate are monitored regularly, blood samples are collected via an intravenous catheter for pharmacokinetic analyses, and subjective effect scales are completed repeatedly from 1 hour 5 minutes before dosing to multiple time points after dosing (assessment window up to 245 minutes, including timepoints up to 180 minutes post-dosing). Key exclusions include current or past major psychiatric disorder, certain cardiovascular conditions, recent heavy hallucinogen use, pregnancy or breastfeeding, and other standard safety-related criteria.