Neuroimaging & Brain MeasuresHealthy VolunteersMedicinal Chemistry & Drug DevelopmentDMT

A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience

This methodological paper (2016) outlines the development of a target-controlled intravenous infusion protocol for administering DMT within the context of neuroimaging research. Whereas a single dose does not exert effects beyond 20 minutes, this method maintains a stable brain concentration that enables the investigation of a stable and prolonged DMT experience over an indefinite period.

Authors

  • Rick Strassman

Published

Frontiers in Pharmacology
individual Study

Abstract

Introduction

The state of consciousness induced by N,N-dimethyltryptamine (DMT) is one of the most extraordinary of any naturally-occurring psychedelic substance. Users consistently report the complete replacement of normal subjective experience with a novel “alternate universe,” often densely populated with a variety of strange objects and other highly complex visual content, including what appear to be sentient “beings.” The phenomenology of the DMT state is of great interest to psychology and calls for rigorous academic enquiry. The extremely short duration of DMT effects-less than 20 min-militates against single dose administration as the ideal model for such enquiry.

Methods

Using pharmacokinetic modeling and DMT blood sampling data, we demonstrate that the unique pharmacological characteristics of DMT, which also include a rapid onset and lack of acute tolerance to its subjective effects, make it amenable to administration by target-controlled intravenous infusion.

Results

This is a technology developed to maintain a stable brain concentration of anesthetic drugs during surgery.

Discussion

Simulations of our model demonstrate that this approach will allow research subjects to be induced into a stable and prolonged DMT experience, making it possible to carefully observe its psychological contents, and provide more extensive accounts for subsequent analyses. This model would also be valuable in performing functional neuroimaging, where subjects are required to remain under the influence of the drug for extended periods. Finally, target-controlled intravenous infusion of DMT may aid the development of unique psychotherapeutic applications of this psychedelic agent.

Available with Blossom Pro

Research Summary of 'A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience'

Introduction

N,N-dimethyltryptamine (DMT) produces rapid, profound and highly reproducible alterations of consciousness, commonly described as the replacement of ordinary awareness by an ‘‘alternate universe’’ populated by complex visual objects and apparent sentient ‘‘beings.’’ The compound is endogenously produced in humans, crosses the blood–brain barrier in animals, and is metabolised rapidly by monoamine oxidase (MAO) enzymes; these pharmacological features, together with the striking phenomenology, make DMT of considerable interest for psychology and neuroscience. Despite this, detailed phenomenological characterisation has been limited in part because the effects of inhaled or intravenous bolus DMT are very brief, typically resolving within 20–30 min, which hampers prolonged observation and functional neuroimaging during the state. Gallimore and Strassman set out to determine whether target-controlled intravenous infusion—a methodology from anaesthesia used to achieve and maintain a stable brain concentration of drug—could be applied to DMT. Using time-series plasma DMT data from prior human dosing sessions, the investigators developed and simulated pharmacokinetic (PK) and effect-site models to test whether a controlled infusion protocol could produce a sustained, stable DMT effect-site concentration, and to derive candidate infusion parameters for research use.

Expert Research Summaries

Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.

Full Text PDF

Full Paper PDF

Pro members can view the original manuscript directly in the browser.

Study Details

References (23)

Papers cited by this study that are also in Blossom

A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans: 1955-2010

Barker, S., McIlhenny, E. H., Strassman, R. J. · Drug Testing and Analysis (2012)

Antidepressant effects of ketamine in depressed patients

Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)

Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study

Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A. et al. · Journal of Psychopharmacology (2015)

Pharmacokinetics of Hoasca alkaloids in healthy humans

Callaway, J. C., Mckenna, D. J., Grob, C. S. et al. · Journal of Ethnopharmacology (1999)

285 cited
Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin

Carhart-Harris, R. L., Erritzoe, D., Williams, T. et al. · PNAS (2012)

Neural correlates of the LSD experience revealed by multimodal neuroimaging

Carhart-Harris, R. L., Muthukumaraswamy, S., Roseman, L. et al. · PNAS (2016)

Psychological effects of (S)-ketamine and N,N-dimethyltryptamine (DMT): a double-blind, cross-over study in healthy volunteers

Gouzoulis-Mayfrank, E., Heekeren, K., Neukirch, A. et al. · Pharmacopsychiatry (2005)

187 cited
Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer

Grob, C. S., Danforth, A. L., Chopra, G. S. et al. · JAMA Psychiatry (2011)

Show all 23 references
LSD-assisted psychotherapy in patients with terminal cancer

Grof, S., Goodman, L. E., Richards, W. A. · Pharmacopsychiatry (1973)

Hallucinogen use predicts reduced recidivism among substance-involved offenders under community corrections supervision

Hendricks, P. S., Clark, B., Johnson, M. W. et al. · Journal of Psychopharmacology (2014)

89 cited
Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials

Krebs, T. S., Johansen, P. Ø. · Journal of Psychopharmacology (2012)

Psychedelics

Nichols, D. E. · Pharmacological Reviews (2016)

The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers

Roseman, L., Leech, R., Feilding, A. et al. · Frontiers in Human Neuroscience (2014)

229 cited
113 cited
118 cited
Dose-response study of N,N-dimethyltryptamine in humans: subjective effects and preliminary results of a new rating scale

Strassman, R. J., Qualls, C. R., Uhlenhuth, E. H. et al. · JAMA Psychiatry (1994)

Cited By (11)

Papers in Blossom that reference this study

Novel extended-release transdermal formulations of the psychedelic N,N-dimethyltryptamine (DMT)

Witowski, C. G., Hess, M. R., Jones, N. T. et al. · European Journal of Pharmacology (2024)

Psychological and physiological effects of extended DMT

Luan, L. X., Eckernäs, E., Ashton, M. et al. · Journal of Psychopharmacology (2023)

Optimized infusion rates for N,N-dimethyltryptamine to achieve a target psychedelic intensity based on a modeling and simulation framework

Eckernäs, E., Koomen, J., Timmermann, |. C. et al. · Pharmacometrics and Systems Pharmacology (2023)

19 cited
Psychedelics and virtual reality: parallels and applications

Aday, J. S., Davoli, C. C., Bloesch, E. K. · Therapeutic Advances in Psychopharmacology (2020)

Psychedelic use and intimate partner violence

Walsh, Z., Bird, B. M., Lafrance, A. et al. · Journal of Psychopharmacology (2018)

N,N-dimethyltryptamine and the pineal gland: Separating fact from myth

Nichols, D. E. · Journal of Psychopharmacology (2017)

Show all 11 papers
Pharmacokinetics and pharmacodynamics of lysergic acid diethylamide in healthy subjects

Dolder, P. C., Schmid, Y., Steuer, A. E. et al. · Clinical Pharmacokinetics (2017)

Your Personal Research Library

Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.