Cannabis coadministration potentiates the effects of "ecstasy" on heart rate and temperature in humans.
This study assessed the acute physiologic effects over time of (co)administration of Delta9-tetrahydrocannabinol (Delta9-THC) (the main psychoactive compound of cannabis) and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") in 16 healthy volunteers. Pharmacokinetics and cardiovascular, temperature, and catecholamine responses were assessed over time. Both single-drug conditions robustly increased heart rate, and coadministration showed additive effects. MDMA increased epinephrine and norepinephrine concentrations, whereas THC did not affect the catecholamine response. Coadministration of MDMA and THC attenuated the increase of norepinephrine concentrations relative to administration of MDMA alone. These results show that THC mediates heart rate increase independent of sympathetic (catecholaminergic) activity, probably through direct cannabinoid receptor type 1 (CB(1)) agonism in cardiac tissue. Furthermore, THC coadministration did not prevent MDMA-induced temperature increase, but it delayed the onset and prolonged the duration of temperature elevation. These effects may be of particular relevance for the cardiovascular safety of ecstasy users who participate in energetic dancing in nightclubs with high ambient temperature.
Dumont
G J
GJ
Department of Psychiatry, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. g.j.h.dumont@psy.umcn.nl
Kramers
C
C
Sweep
F C
FC
Touw
D J
DJ
van Hasselt
J G
JG
de Kam
M
M
van Gerven
J M
JM
Buitelaar
J K
JK
Verkes
R J
RJ
D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D000328:Adult; D001831:Body Temperature / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D013759:Dronabinol / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D004357:Drug Synergism; D004837:Epinephrine / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D009638:Norepinephrine / Q000097:blood; D011619:Psychotropic Drugs / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics
D018759:Adrenergic Uptake Inhibitors; D011619:Psychotropic Drugs; D013759:Dronabinol; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009638:Norepinephrine; D004837:Epinephrine