Ware et al Figure 2a Nabilone reduces frequency of vomiting on chemotherapy days 1 through 5. Reproduced with permission from Einhorn LH, Nagy C, Furnas B,Williams SD. 1981. Nabilone:An effective antiemetic in patients receiving cancer chemotherapy. J Clin Pharmacol, 21(suppl):64–69. Copyright © 1981 SAGE Publications. in vast quantities in the CNS, exceeding levels of nearly all neurotransmitter receptors, and in nearly every brain region, including those involved in the pathophysiology of CINV (Martin and Wiley 2004). CB1 receptors are therefore valid targets for antiemetic effects in patients with CINV. Anticipatory nausea and vomiting is a learned response to chemotherapy that develops only after poor initial control of CINV. Studies have shown that anticipatory nausea and vom- iting follows the theory of a Pavlovian conditioned reﬂex; the thought of chemotherapy or other elements associated with it is the stimulus (Stockhorst et al 1993). The risk of developing this problem increases with the number of cycles received and may persist for some time after the completion of therapy (Aapro et al 2005). Anxiety may play a role in this condition (Morrow et al 1998), and two randomized trials have shown efﬁcacy using benzodiazepines when added to psychological support programs (Razavi et al 1993; Malik et al 1995). Inter- estingly, the synthetic cannabinoid nabilone has been found to be effective in anxiety (Fabre and McLendon 1981). An animal model of anticipatory nausea and vomiting has been developed for the testing of cannabinoids (Parker and Kemp 2001; Limebeer et al 2006), which has shown cannabinoids to be effective in anticipatory nausea, signiﬁcantly better than both placebo and ondansetron (Parker and Kemp 2006). Efﬁcacy and safety of nabilone Nabilone is a synthetic cannabinoid developed in the 1970’s (Lemberger and Rowe 1975) which is a potent CB1 agonist. Results from early clinical studies demonstrated the efﬁcacy, safety, and tolerability of nabilone in reducing the frequency 102 of vomiting and lessening the severity of nausea in cancer patients with CINV (Herman et al 1977, 1979; Einhorn et al 1981). In patients (n = 13) with CINV unrelieved by prochlorperazine, nabilone reduced vomiting frequency and nausea severity in 77%; more than half of the patients experi- enced “excellent response” to therapy or complete resolution of CINV (Herman et al 1977). In this study, patients were given either 1 mg or 2 mg nabilone every 8 hours. A more potent antiemetic effect was observed with the higher dose. Generally, the commonly occurring side effects – sedation, dry mouth, dizziness, and some decrease in coordination – as well as those that occurred less often, were mild or moderate in severity. More than one half of the patients reported an increase in appetite and food intake. A second paper by the same authors reported on two double-blind, crossover trials conducted in a total of 113 evaluable patients with severe CINV (Herman et al 1979). During chemotherapy cycle 1, patients received either 2 mg nabilone or 10 mg prochlorperazine every 8 hours. The patients crossed over to the second drug regimen during the second cycle. All patients received 2 doses of antiemetic medication before chemotherapy for both cycles. Nabilone was more effective for providing complete relief of nausea and vomiting than was prochlorperazine (8% vs 0%), and signiﬁcantly (p 0.01) more effective for providing a partial response (72% vs 32%). The number of partial and com- plete responses occurring with nabilone was signiﬁcantly (p 0.001) greater than that with prochlorperazine (80% vs 32%). The response to nabilone in terms of reduced vomiting was greater on all 5 days of therapy when compared with Therapeutics and Clinical Risk Management 2008:4(1)