THC, the principal psychoactive substituent of the marijuana plant Cannabis sativa (Gaoni and Mechoulam, 1964), acts within the endocannabinoid system to produce characteristic effects in mice [i.e., ‘cannabinoid tetrad’: suppression of activity, antinociception, hypothermia and catalepsy; (Martin et al., 1991)] and distinctive discriminative stimulus effects in rodents and nonhuman primates (Balster and Prescott, 1992; Gold et al., 1992), with the latter being a pharmacologically selective animal model of marijuana’s subjective effects (Balster and Prescott, 1992). While cannabinoid CB1 receptor activation has been shown to be mediate the discriminative stimulus effects of THC (Wiley et al., 1995), the degree to which endogenous cannabinoids contribute to THC’s psychoactive effects has received less research attention. Given that endocannabinoids also activate cannabinoid CB1 receptors, a logical “first step” in determination of the role of endocannabinoids in THC’s psychoactive effects is to investigate whether changes in the levels of one or both of the two best-characterized endocannabinoids, anandamide and 2-AG, mimic the abuse-related effects of THC. In humans, alterations in endocannabinoid concentrations may result from factors such as genetic variation in degradative enzyme levels (Sipe
