Cannabis Coadministration Potentiates the Effects of “Ecstasy” on Heart Rate and Temperature in Humans

Abstract

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.

Effects of the α2-Adrenergic Agonist Clonidine on the Pharmacodynamics and Pharmacokinetics of 3,4-Methylenedioxymethamphetamine in Healthy Volunteers

“…Second, both clonidine and MDMA bind to ␣ 2 -adrenergic receptors (Battaglia et al, 1988;Lavelle et al, 1999), and some ␣ 2 agonistic actions in the peripheral NE system have been documented for MDMA in vitro (Lavelle et al, 1999). However, in contrast to clonidine, MDMA increased plasma NE levels and blood pressure in the present and previous studies (Dumont et al, 2009;Hysek et al, 2011), indicating that the ␣ 2 agonistic effects of MDMA are not relevant for its main action in humans or are outweighed by the transporter-mediated release of NE and other monoamines.…”

Cannabis Abusers Show Hypofrontality and Blunted Brain Responses to a Stimulant Challenge in Females but not in Males

“…The cannabinoid system is an important regulator of noradrenergic systems in part via CB1 receptors (Reyes et al, 2009;Carvalho and Van Bockstaele, 2012;Cathel et al, 2014) and downregulation of CB1 receptors in CA (Hirvonen et al, 2012) could underlie the attenuated responses to MP-induced changes in metabolism observed in these brain regions. A prior study in CA showed that co-administration of Δ-9-tetrahydrocannabinol (THC) with ecstasy, which like MP is a monoamine transporter blocker, enhanced its cardiovascular effects and the increases in epinephrine and norepinephrine in plasma (Dumont et al, 2009). This is indicative of enhanced effects to ecstasy when CB1 receptors are co-stimulated by THC.…”

The Health Effect of Psychostimulants: A Literature Review

“…Researchers in Australia did a compilation of hyperthermia case reports (n=69) from MDMA and found a clear correlation of the fatality rate and the body temperature at the arrival in the emergency room (20% for temperature < or equal to 39.5°C, 78% for temperature > 42.5°C) [148]. The temperature increase was shown to be longer if cannabis was used with MDMA and the heart rate was increased [149]. The same team searched for other acute adverse reactions to MDMA and found in total ten cases of seizures without hyperthermia, twelve cases of cerebrovascular accident, and six cases (all fatal) of cardiac events.…”