Background N,N-dimethyltryptamine (DMT) is unique among classical serotonergic psychedelics because of its short-lasting effects when administered intravenously. In recent years, several studies have tested the administration of either an intravenous bolus dose alone [1, 2] or combined with a subsequent continuous infusion [3-5]. However, the very quick and overwhelming rise of psychedelic effects produced by a bolus dose can cause bad drug effects and anxiety [3].

Hypothesis We hypothesized that a continuous infusion alone will be sufficient to induce rapidly rising and stable drug effects of DMT. 

Methods We conducted a double-blind, randomized, placebo-controlled crossover trial with 24 healthy participants. DMT was administered as a continuous infusion over 120 minutes in four different dose rates. In an additional, non-randomized study session, the participants could modify the DMT dose according to their preference and well-being. Outcomes included subjective effect measures, adverse effects, pharmacokinetics and neuroendocrine markers.

Main Findings DMT infusions induced dose-dependent psychedelic effects that reached a plateau after 20 – 30 minutes. At the high and very high dose rate (1.8 and 2.4 mg/min), psychedelic effects emerged very quickly within the first 2.5 – 5 minutes after the start of the infusion. Overall, the DMT infusions were very well tolerated. The highest dose rate (2.4 mg/min) produced substantial bad drug effects and anxiety in a minority of participants. In the self-guided titration session, participants opted for intermediate to very high doses from 1.2 – 2.4 mg/min. 

Conclusion Continuous DMT infusions dose-dependently induced rapidly rising and stable drug effects that were well tolerated.