Ware et al (NNT) for complete control of nausea was 8; compared with active control (7 studies), the NNT was 6.4. Compared with placebo (4 studies) and active control (6 studies), the NNT for complete control of vomiting was 3.3 and 8, respectively. Cannabinoids were shown to be well tolerated, and analysis demonstrated a patient preference for these agents over both active controls and placebo. As well, the authors commented that “In selected patients, cannabinoids may be useful as mood enhancing adjuvants for the control of chemotherapy related sickness”, likely referring to the possible beneﬁts in patients with anticipatory nausea and vomiting (Tramér et al 2001). Since these studies were conducted, the 5-HT3 and NK receptor antagonists have been developed and incorporated into routine clinical care protocols. Studies comparing nabilone to these agents either alone or in combination have not been done to date. Dronabinol, a synthetic form of tetrahydrocannabinol (the principle psychoactive ingredi- ent in cannabis) has also been licensed as an antiemetic and has not been shown to be superior to ondansetron (Meiri et al 2007). Head-to-head comparative studies are needed to determine the possible clinical and cost beneﬁts of can- nabinoid therapy. Nabilone has recently been approved by the Food and Drug Administration (FDA) for the treatment of nausea and vomiting associated with chemotherapy in cancer patients who fail to respond adequately to conventional antiemetic treatments (Waknine 2006). Nabilone is typically given twice daily owing to its long duration of action (8–12 hours). The usual daily dosage of nabilone is 1–2 mg bid, with the ﬁrst dose given 1–3 hours before administration of chemo- therapy; the maximum recommended daily dosage is 6 mg daily divided bid or tid. Similar to several medications, there is a therapeutic window for nabilone, at which maximum beneﬁt is obtained without intolerable side effects. Thus, treatment should be initiated with the lowest starting dose, and the dose should be increased based on patient response to minimize side effects. Patients often beneﬁt from one dose the evening before chemotherapy, and another dose 1 to 3 hours pre-chemotherapy. The most commonly occurring side effects of nabilone therapy are drowsiness, vertigo, dry mouth, euphoria, ataxia, headache, and concentration difﬁculties. Generally, the side effects are mild in intensity and temporary in duration. Toler- ance to the CNS effects of nabilone, such as drowsiness and vertigo, develops rapidly. Assessing patients prior to initiat- ing therapy can assist in reducing side effects and increasing tolerability. Patients should be warned about taking nabilone 104 with alcohol, sedatives, hypnotics, or other psychoactive substances due to the potential for augmentation of CNS effects. Nabilone should be used with caution in patients with current or past history of psychiatric disorders, as well as those with a history of substance abuse. Both short- and long-term cognitive effects of cannabinoids are not well described under therapeutic conditions, but based on the well-known cognitive effects of recreational cannabis use, careful monitoring is advised. Severe cognitive impairment from therapeutic use of nabilone has not been described. The response to and tolerance of nabilone varies from individual to individual; thus, patients should remain under the supervi- sion of a responsible adult during initial use of the medica- tion. Drug–drug interactions may be a concern in cancer patients who might be taking several different medications concurrently. Nabilone does not induce cytochrome P450 3A4 isoenzymes and lacks signiﬁcant 3A4 inhibitory effect (Nahas et al 2002). Thus, interactions with drugs metabolized via this pathway, such as macrolide antibiotics, calcium chan- nel blockers, and others, are unlikely. In summary, results from early clinical trials demon- strated the efﬁcacy of nabilone in reducing the frequency of vomiting and lessening the severity of nausea in cancer patients with severe and/or refractory CINV. Importantly, nabilone was effective across the 5 days of chemotherapy in reducing both vomiting episodes and nausea severity, speciﬁc areas in which other antiemetic agents fail to provide adequate patient relief. While the incidence of side effects with nabilone therapy is higher than with active controls, the side effects generally are mild to moderate in intensity, resolve over time, and do not impact patient preference for nabilone over other medications. To minimize the risk for and severity of side effects and improve patient tolerance, it is important to “start low and go slow” in terms of initial dose and dose titration. While studies comparing nabilone to modern antiemetics are anticipated, nabilone is an additional tool in the oncologist’s efforts to control nausea and improve the tolerability of potentially life-saving chemotherapy. Potential uses of nabilone in cancer patients A better understanding of the mechanism of action of endo- cannabinoids has led to investigation of the potential beneﬁt of pharmaceutical cannabinoids for the treatment of other symptoms and side effects of therapy and diseases. Published evidence supports the possible use of nabilone and other cannabinoids in cancer patients to treat radiotherapy-induced nausea, depression and anxiety, sleep disorders, and pain, Therapeutics and Clinical Risk Management 2008:4(1)