A phase II double-blind placebo-controlled, randomized dose-ranging trial was undertaken to determine the antiemetic efficacy and toxicity of the synthetic cannabinoid levonantradol at doses of 0.5, 1.0, 1.5, and 2.0 mg. Intramuscular levonantradol was prophylactically administered in random dosing to 20 subjects with a documented history of refractory emesis due to chemotherapy in advanced cancer. The selected dose was administered prior to the chemotherapy and was serially repeated over 12 hours, and efficacy and toxicity data were evaluated for 24 hours. Significant (P less than 0.01) antiemetic activity over placebo was observed with all doses of levonantradol administered, and a dose-effect response was not observed. Doses up to 2.0 mg were well tolerated, and observed toxicity increased with increased doses and with repeated dosing. Psychomimetic effects were mild and tolerable, and the limiting side effects were somnolence and hypotension.