Δ9-Tetrahydrocannabinol attenuates MDMA-induced hyperthermia in rhesus monkeys.
Cannabis is commonly consumed by Ecstasy (3,4-methylenedioxymethamphetamine MDMA) users, including as an intentional strategy to manipulate the drug experience. The most active psychoactive constituent in cannabis, Δ(9)-tetrahydrocannabinol (THC), and other drugs with partial or full agonist activity at the CB(1) receptor, produces a reduction of body temperature in rodents. Reports show that administration of THC can attenuate temperature increases caused by MDMA in mice or rats however, a recent study in humans shows that THC potentiates MDMA-induced temperature elevations. Relatively little scientific evidence on the thermoregulatory effects of THC in monkeys is available. The body temperature of male rhesus macaques was recorded after challenge with THC (0.1-0.3 mgkg, i.m.) or combined challenge of THC with the CB(1) receptor antagonist SR141716 (Rimonabant 0.3 mgkg, i.m.) or combined challenge of THC (0.1, 0.3 mgkg, i.m.) with MDMA (1.78 mgkg p.o.) using minimally-invasive, implanted radiotelemetry techniques. THC reduced the body temperature of monkeys in a dose-dependent manner with the nadir observed 3-5 h post-injection however, an attenuation of normal circadian cooling was also produced overnight following dosing. Hypothermia induced by THC (0.3 mgkg, i.m.) was prevented by Rimonabant (0.3 mgkg, i.m.). Finally, 0.3 mgkg THC (i.m.) attenuated the elevation of body temperature produced by MDMA for about 4 h after oral dosing. As with rodents THC produces a robust and lasting decrement in the body temperature of rhesus monkeys this effect is mediated by the CB(1) receptor. THC also protects against the immediate hyperthermic effects of MDMA in monkeys in a dose-dependent manner. Nevertheless, a paradoxical attenuation of circadian cooling overnight after the THCMDMA combination cautions that longer-term effects may be critical in assessing risks for the recreational user of cannabis in combination with MDMA.