Role of nabilone in CINV cannabinoids, and others (Andrews et al 1998; Lynch 2005). Antagonism of serotonin, dopamine, and substance P recep- tors (5-HT3 , D2, and NK , respectively) produces clinically 1 meaningful antiemetic effects. In contrast, it is the agonism of CB1 receptors, such as that produced by cannabinoid compounds, which results in antiemetic effects. CB agonist drugs circumvent the multi-step process of the endogenous system (Figure 1) (Croxford 2003; Navari 2003; Freund et al 2003; Piomelli 2003; Diana and Mart 2004). In addition to modulatory effects on CB receptors, the CB1 agonist nabi- lone may also indirectly and partially manipulate 5-HT3 and D2 receptors (Ward and Holmes 1985; Nahas et al 2002). Speciﬁc areas of the brain are involved in emesis and nausea, including the dorsal vagal complex, particularly the nucleus of the solitary tract (NTS) within this complex. Neurons in the area postrema, which is often referred to as the chemoreceptor trigger zone, transmit messages regarding such blood-borne emetics as cytotoxic drugs to the NTS. The NTS also receives messages regarding abdominal irritants through vagal afferents. In turn, NTS neurons transmit these messages to the brainstem, which directs emetic behavior (Hornby 2001). Other areas of the brain involved in CINV are the higher cortical and limbic regions, where the senses of taste, smell, sight, and memory are modulated. Through descending connections with the brainstem emetic center, these regions can inﬂuence stimulation or suppression of nau- sea and vomiting, including anticipatory nausea and vomiting (Grunberg 1989; Fride et al 2005). CB1 receptors are present Figure 1The mechanism of action of cannabinoids.The innate cannabinoid system inhibits release of neurotransmitters via a multi-step retrograde signaling pathway.Nabilone mimics the action of endocannabinoids via direct activation of CB1 receptors (derived from Croxford 2003; Freund et al 2003; Navari 2003; Piomelli 2003; Diana and Mart 2004). Abbreviations: THC, tetrahydrocannabinol. Therapeutics and Clinical Risk Management 2008:4(1) 101