1. ¹Department of Psychiatry, Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
2. ²Department of Pharmacology–Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
3. ³Department of Chemical Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
4. ⁴Clinical Pharmaceutical and Toxicological Laboratory, Department of Pharmacy, The Hague Hospitals, The Hague, The Netherlands
5. ⁵Centre for Human Drug Research, Leiden, The Netherlands

Correspondence: GJ Dumont, (g.j.h.dumont@psy.umcn.nl)

Received 30 January 2009; Accepted 30 March 2009; Published online 13 May 2009.

Abstract

This study assessed the acute physiologic effects over time of (co)administration of 9-tetrahydrocannabinol (9-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 (CB₁) 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.