Evaluation of cannabimimetic discriminative stimulus effects of anandamide and methylated fluoroanandamide in rhesus monkeys.

Abstract

In previous research arachidonylethanolamide (anandamide) has been shown to produce behavioral effects in mice characteristic of psychoactive cannabinoids, including antinociception, catalepsy, hypothermia, and hypomotility. However, differences have also been found between anandamide and delta9-tetrahydrocannabinol (delta9-THC), with anandamide having lower potency, a more rapid onset, and shorter duration of action than delta9-THC. Although it can produce delta9-THC like discriminative stimulus effects in rats, anandamide also produces concomitant response rate decreasing effects, whereas with delta9-THC there is a better separation of these two behavioral effects. The present study was designed to examine the discriminative stimulus effects of anandamide in rhesus monkeys trained to discriminate delta9-THC from vehicle. While anandamide failed to produce reliable substitution for delta9-THC and did not reduce response rates at doses up to 10 mg/kg, 2-methylarachidonyl-2'-fluoroethylamide (methylated fluoroanandamide), a putative stable analog of anandamide, produced full dose-dependent substitution for delta9-THC at doses that caused no significant changes in response rates. These results suggest that systemically administered anandamide may be metabolized in monkeys before behaviorally active concentrations could reach the brain and further suggest that the metabolically more stable analog of anandamide, methylated fluoroanandamide, may aid in the discovery of functional properties of the endogenous cannabinoid system.