The aforementioned experiments with SR141716A and O-2050 indicate that CB1 SCH772984 942183-80-4 receptor activation by endogenous ligands induces impulsive action as measured in the 5-CSRTT, while reducing impulsive choice in the DRT. Therefore, we next tested the effects of direct, agonist-induced CB1 receptor activation on impulsive behavior in rats. D9-THC was used as an exogenous, non-selective CB1 receptor agonist, since this compound is regularly used in clinical studies and has previously been shown to acutely affect impulsivity in healthy volunteers. This study provides evidence for an important role of the cannabinoid CB1 receptor in modulating impulsive action as well as impulsive choice and the effects of the psychostimulant drug amphetamine thereon. Previous studies showed that CB1 receptor antagonists with inverse agonistic properties increase baseline PR-171 inhibitory control in the 5-CSRTT. The current study extends these findings by showing that amphetamineinduced decreases in inhibitory control, at least as measured in the 5-CSRTT, could be attenuated with the CB1 receptor antagonist/ inverse agonist SR141716A. Moreover, SR141716A fully prevented the ameliorating effects of amphetamine on a different form of impulsivity, that is impulsive choice as measured in the DRT, while not affecting baseline behavior in the latter task. Importantly, in both behavioral paradigms, the effects of SR141716A were mimicked by the neutral CB1 receptor antagonist O-2050. The current results are therefore not compound-specific and can unlikely be attributed to inverse agonism at the CB1 receptor, but rather reflect the effects of blockade of CB1 receptor activation by endogenous cannabinoids. Furthermore, we found that, at least under the current baseline discounting curves with vehicle, direct CB1 receptor activation by administration of the CB receptor agonist D9-THC reduced impulsive choice without affecting impulsive action. Psychostimulant drugs such as amphetamine are leading prescription drugs to treat ADHD and maladaptive display of impulsivity. The acute effects of amphetamine on inhibitory control and impulsive choice have been well characterized in both humans and rodents, and are known to depend on amphetamine��s ability to robustly enhance mesocorticolimbic DA transmission. However, other neurotransmitter systems including the endogenous opioid and 5- HT systems have also been shown to regulate certain aspects of amphetamine-induced impulsivity. Here, it was found that blocking the CB1 receptor with either SR141716A or O-2050 alleviated amphetamine-induced inhibitory control deficits and completely abolished amphetamine-induced decrements in impulsive choice, indicating that the endocannabinoid system plays a critical role in the opposite effects of amphetamine on impulsive action and impulsive choice.