February 1994

Dose-Response Study of N,N-Dimethyltryptamine in HumansI. Neuroendocrine, Autonomic, and Cardiovascular Effects

Author Affiliations

From the Departments of Psychiatry (Dr Strassman) and Medicine (Dr Qualls), School of Medicine, and the Department of Mathematics and Statistics (Dr Qualls), University of New Mexico, Albuquerque.

Arch Gen Psychiatry. 1994;51(2):85-97. doi:10.1001/archpsyc.1994.03950020009001

Background:  To begin applying basic neuropharmacological hypotheses of hallucinogenic drug actions to humans, we generated dose-response data for intravenously administered dimethyltryptamine fumarate's (DMT) neuroendocrine, cardiovascular, autonomic, and subjective effects in a group of experienced hallucinogen users.

Methods:  Dimethyltryptamine, an endogenous mammalian hallucinogen and drug of abuse, was administered intravenously at 0.05,0.1,0.2, and 0.4 mg/kg to 11 experienced hallucinogen users, in a double-blind, saline placebo—controlled, randomized design. Treatments were separated by at least 1 week.

Results:  Peak DMT blood levels and subjective effects were seen within 2 minutes after drug administration, and were negligible at 30 minutes. Dimethyltryptamine dose dependently elevated blood pressure, heart rate, pupil diameter, and rectal temperature, in addition to elevating blood concentrations of β-endorphin, corticotropin, cortisol, and prolactin. Growth hormone blood levels rose equally in response to all doses of DMT, and melatonin levels were unaffected. Threshold doses for significant effects relative to placebo were also hallucinogenic (0.2 mg/kg and higher). Subjects with five or more exposures to 3,4-methylenedioxymethamphetamine demonstrated less robust pupil diameter effects than those with two or fewer exposures.

Conclusions:  Dimethyltryptamine can be administered safely to experienced hallucinogen users and dose-response data generated for several measures hypothesized under serotonergic modulatory control. Additional studies characterizing the specific mechanisms mediating DMT's biological effects may prove useful in psychopharmacological investigations of drug-induced and endogenous alterations in brain function.