Unraveling the neurobiology of impulsivity may allow the development of novel pharmacotherapies to treat maladaptive impulsivity and is therefore of utmost importance. Traditionally, studies on impulsivity have primarily focused on the role of monoamine neurotransmission. Interestingly, other neurotransmitters have also been implicated in impulsivity, including endogenous cannabinoids. The endogenous cannabinoid system, named after the fact that it is activated by D9-Tetrahydrocannabinol, the principle active component of herbal cannabis sativa, includes at least two G-protein coupled receptors, CB1 and CB2 receptors, and several endogenous ligands including N-arachidonoylethanolamide and 2-arachidonyl glycerolanandamide. CB1 receptors are the predominant cannabinoid receptors in the central nervous system with a particular abundance in brain regions comprising the mesocorticolimbic system. In the brain the endogenous cannabinoid system functions to modulate synaptic activity by controlling release of virtually all other neurotransmitters, including GABA, glutamate, and dopamine. Considering its abundance and cellular function in the brain, it is not surprising that the CB1 receptor has been implicated in regulating many different behaviors, including higher-order cognitive or executive functions such as attentional processing, behavioral flexibility, and impulsivity. With respect to the latter, it has been shown that both chronic and acute use of D9-THC can affect impulsive behavior in humans. Moreover, two recent preclinical studies found evidence for a role for CB1 receptors in modulating specific aspects of impulsivity, as it was found that the CB1 receptor antagonists/inverse agonists SR141716A and SLV330 increased inhibitory control in rats. In addition, it is noteworthy that polymorphisms in the CB1 receptor gene have been linked to impulsivity and the development of ADHD, and that ADHD patients were recently found to have decreased anandamide degradation as compared to healthy control subjects. Currently, the most widely prescribed drugs to treat ADHD and maladaptive impulsivity are the psychostimulants methylphenidate and amphetamine, which enhance monoamine neurotransmission. Somewhat paradoxically, acute challenges with amphetamine decrease inhibitory control in humans and rodents, i.e. increase impulsive action, at least when operationalized as the inability to restrain PD325901 inappropriate behavior, while reducing impulsive R428 choice, measured as an intolerance to delayed gratification or delay aversion. These opposite effects of amphetamine are well-known to depend on enhanced DA transmission. Nonetheless, interactions with other neurotransmitter systems including the endogenous opioid and 5-HT systems have also been implicated.