Psychological and physiological effects of extended DMT

Abstract

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.

Keywords: Psychedelics; ayahuasca; consciousness; dimethyltryptamine; serotonin.

Figure 1.

Experience sampling of subjective effects induced by continuous infusions of placebo and different doses of DMT. The bolus IV injection was administered at time 0. The constant-rate infusion started at min 1 and was maintained until minute 30. (a) Peak effects of DMT were successfully extended via continuous infusion. A significant dose-response relationship for Intensity was found for minutes 1–40 (assessed using a 0–10 scale with 0 = ‘no effects’ and 10 = ‘most intense effects imaginable’). (b) Anxiety ratings were given on a scale from 0 to 10, with 0 = ‘no anxiety’ and 10 = ‘most intense anxiety imaginable’. The data are expressed as the mean ± SEM.

Figure 2.

Retrospective assessment of subjective effects induced by continuous infusions of placebo and different doses of DMT. LMM analysis revealed: (a) a significant increase for all doses compared with placebo in ‘Oceanic boundlessness’ and ‘Visual restructuralization’, for Dose 2, 3 and 4 compared with placebo in ‘Dread of ego-dissolution’, and for Dose 2 and 3 compared with placebo in ‘Auditory alterations’, (b) significant increases for all doses compared with placebo in ‘Unity’, ‘Meaning’, ‘Spiritual experience’ ‘Blissful state’, ‘Insightfulness’, ‘Complex imagery’, and ‘Elementary imagery’, for Dose 3 compared with placebo in ‘Disembodiment’, and for Dose 2 and 3 compared with placebo in ‘Impaired cognition’, and (c) a significant increase for all doses versus placebo on the MEQ-30 total and all subscales. Summary statistics can be found in Supplemental Tables S4–S6. Scores are scaled between 0–1 and expressed as the mean.

Figure 3.

Retrospective assessment of ‘Immersion’, ‘Entity encounters’, ‘Ego dissolution’ and ‘Visual imagery’ over continuous infusions of placebo and different doses of DMT (minutes 0–30). DMT infusions induced sustained effects of ‘Immersion’, ‘Entity encounters’ and ‘Visual imagery’, while ‘Ego-dissolution’ remained low across doses. The data are expressed as the mean ± SEM. Additional results can be found in Supplemental Figures S1–S8.

Figure 4.

Acute changes in HR following continuous infusions of placebo and different doses of DMT (minutes 0–30). While the initial period of DMT administration is associated with an elevated HR, this then returns to baseline levels and stabilises. Values are expressed as average differences in beats per minute (bpm) from baseline HR, defined as the average HR between minutes -8 and 0, ± SEM.

Figure 5.

DMT plasma concentrations after administration of DMT fumarate IV bolus dose followed by constant-rate infusion at four dose levels (minutes 0–30). Plasma concentrations peak after bolus IV injection and before the end of the continuous IV infusion. There was a significant dose-effect relationship for all doses, for all measured timepoints until minute 50. The data are expressed as the mean ± SEM.