Cannabinoids prevent the acute hyperthermia and partially protect against the 5-HT depleting effects of MDMA ("Ecstasy") in rats.
Cannabinoid-MDMA interactions were examined in male Wistar rats. MDMA (4 x 5 mg/kg or 2 x 10 mg/kg over 4 h on each of 2 days) was administered with or without Delta 9-tetrahydrocannabinol (THC) (4 x 2.5 mg/kg), the synthetic cannabinoid receptor agonist CP 55,940 (2 x 0.1 or 0.2 mg/kg) or the cannabinoid receptor antagonist SR 141716 (2 x 5 mg/kg). Co-administered Delta 9-THC and CP 55,940 but not SR 141716 prevented MDMA-induced hyperthermia, causing a powerful hypothermia. Co-administered Delta 9-THC, CP 55,940 and SR 141716 all tended to decrease MDMA-induced hyperactivity. Co-administered Delta 9-THC provided protection against the long-term increases in anxiety seen in the emergence test, but not the social interaction test, 6 weeks after MDMA treatment. Co-administered Delta 9-THC and CP 55,940, but not SR 141716, partly prevented the long-term 5-HT and 5-HIAA depletion caused by MDMA in various brain regions. SR 141716 administered with CP 55,940 and MDMA prevented the hypothermic response to the CP 55,940/MDMA combination but did not alter the CP 55,940 attenuation of MDMA-induced 5-HT depletion. These results suggest a partial protective effect of co-administered cannabinoid receptor agonists on MDMA-induced 5-HT depletion and long-term anxiety. This action appears to operate independently of cannabinoid CB1 receptors.
Morley
Kirsten C
KC
School of Psychology, University of Sydney, Sydney, NSW 2006, Australia.
Li
Kong M
KM
Hunt
Glenn E
GE
Mallet
Paul E
PE
McGregor
Iain S
IS
D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology / Q000627:therapeutic use*; D003511:Cyclohexanols / Q000494:pharmacology / Q000627:therapeutic use; D005334:Fever / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077285:Rimonabant; D012701:Serotonin / Q000378:metabolism*
D002186:Cannabinoids; D003511:Cyclohexanols; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D012701:Serotonin; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D000077285:Rimonabant