Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects.
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 beta-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.
Strassman
R J
RJ
Department of Psychiatry, School of Medicine, University of New Mexico, Albuquerque.
Qualls
C R
CR
D000324:Adrenocorticotropic Hormone / Q000097:blood; D001341:Autonomic Nervous System / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013006:Growth Hormone / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D013287:Illicit Drugs; D007262:Infusions, Intravenous; D004130:N,N-Dimethyltryptamine / Q000008:administration & dosage / Q000494:pharmacology*; D010919:Placebos; D011388:Prolactin / Q000097:blood; D011680:Pupil / Q000187:drug effects; D019966:Substance-Related Disorders / Q000523:psychology; D001615:beta-Endorphin / Q000097:blood
D013287:Illicit Drugs; D010919:Placebos; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013006:Growth Hormone; D006854:Hydrocortisone; D004130:N,N-Dimethyltryptamine