Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting

center dot Orally administered synthetic cannabinoids (nabilone and dronabinol) have been shown to be superior to dopamine receptor antagonists in preventing chemotherapy-induced nausea and vomiting (CINV). center dot There is no information on the tolerability of an acute dose titration of a whole-plant cannabis-based medicine (CBM). center dot The efficacy of cannibidiol with tetrahydrocannabinol added to the current standard therapy in the control of CINV after moderately emetic cancer chemotherapy (MEC) administration has not been established. WHAT THIS STUDY ADDS center dot This is the first controlled study assessing the tolerability of an acute dose titration of a CBM. center dot The results suggest that rapid titration of a CBM appeared to be well tolerated by most patients and efficacious in reducing the incidence of delayed CINV. AIMS Despite progress in anti-emetic treatment, many patients still suffer from chemotherapy-induced nausea and vomiting (CINV). This is a pilot, randomized, double-blind, placebo-controlled phase II clinical trial designed to evaluate the tolerability, preliminary efficacy, and pharmacokinetics of an acute dose titration of a whole-plant cannabis-based medicine (CBM) containing delta-9-tetrahydrocannabinol and cannabidiol, taken in conjunction with standard therapies in the control of CINV. METHODS Patients suffering from CINV despite prophylaxis with standard anti-emetic treatment were randomized to CBM or placebo, during the 120 h post-chemotherapy period, added to standard anti-emetic treatment. Tolerability was measured as the number of withdrawals from the study during the titration period because of adverse events (AEs). The endpoint for the preliminary efficacy analysis was the proportion of patients showing complete or partial response. RESULTS Seven patients were randomized to CBM and nine to placebo. Only one patient in the CBM arm was withdrawn due to AEs. A higher proportion of patients in the CBM group experienced a complete response during the overall observation period [5/7 (71.4%) with CMB vs. 2/9 (22.2%) with placebo, the difference being 49.2% (95% CI 1%, 75%)], due to the delayed period. The incidence of AEs was higher in the CBM group (86% vs. 67%). No serious AEs were reported. The mean daily dose was 4.8 sprays in both groups. CONCLUSION Compared with placebo, CBM added to standard antiemetic therapy was well tolerated and provided better protection against delayed CINV. These results should be confirmed in a phase III clinical trial.