Introduction
SD, anxiety
N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic that induces a rapid and transient altered state of consciousness when inhaled or injected via bolus administration. Its marked and novel subjective effects make DMT a powerful tool for the neuroscientific study of consciousness and preliminary results show its potential role in treating mental health conditions. In a within-subjects, placebo-controlled study, we investigated a novel method of DMT administration involving a bolus injection paired with a constant-rate infusion, with the goal of extending the DMT experience. Pharmacokinetic parameters of DMT estimated from plasma data of a previous study of bolus intravenous DMT were used to derive dose regimens necessary to keep subjects in steady levels of immersion into the DMT experience over an extended period of 30 min, and four dose regimens consisting of a bolus loading dose and a slow-rate infusion were tested in eleven healthy volunteers (seven male, four female, mean age ± SD = 37.09 ± 8.93 years). The present method is effective for extending the DMT experience in a stable and tolerable fashion. While subjective effects were maintained over the period of active infusion, anxiety ratings remained low and heart rate habituated within 15 min, indicating psychological and physiological safety of extended DMT. Plasma DMT concentrations increased consistently starting 10 min into DMT administration, whereas psychological effects plateaued into the desired steady state, suggesting the development of acute psychological tolerance to DMT. Taken together, these findings demonstrate the safety and effectiveness of continuous IV DMT administration, laying the groundwork for the further development of this method of administration for basic and clinical research.N,N-Dimethyltryptamine (DMT) is a naturally occurring psychedelic with a mechanism of action linked to agonism at the 5-HT2A receptor (When ingested orally, DMT is rapidly metabolized in the gastrointestinal system by monoamine oxidase (MAO) (The development of a prolonged DMT experience would be an important step towards allowing for a closer study of its phenomenology and neurobiological effects, and would make it possible to control the length, intensity, and dynamics of the DMT experience, with the potential for real-time adjustment. This could make extended DMT a valuable tool in conjunction with therapy, to tailor the psychedelic effects to the individual needs of each patient and their clinical condition, as well as for consciousness research, whereby the intensity of the DMT experience can be adjusted according to specific hypotheses and research questions. In a previous study, continuous infusions of DMT were safely administered for up to 90 min (The present study developed the first systematic protocol for the continuous IV infusion of DMT and tested its effectiveness in healthy volunteers. The main goal of the study was to provide first steps towards establishing infusion parameters for maintaining a steady state of DMT effects for a chosen length of time.