Cannabinoids prevent the acute hyperthermia and partially protect against the 5-HT depleting effects of MDMA ("Ecstasy") in rats
by
Morley KC, Li KM, Hunt GE, Mallet PE, McGregor IS.
School of Psychology, University of Sydney,
Sydney, NSW 2006, Australia.
Neuropharmacology. 2004 Jun;46(7):954-65
ABSTRACTCannabinoid-MDMA interactions were examined in male Wistar rats. MDMA ( [Formula: see text] mg/kg or [Formula: see text] mg/kg over 4 h on each of 2 days) was administered with or without Delta(9)-tetrahydrocannabinol (THC) ( [Formula: see text] mg/kg), the synthetic cannabinoid receptor agonist CP 55,940 ( [Formula: see text] or 0.2 mg/kg) or the cannabinoid receptor antagonist SR 141716 ( [Formula: see text] 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.THC
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