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

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• 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).• There is no information on the tolerability of an acute dose titration of a whole-plant cannabis-based medicine (CBM).• 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• This is the first controlled study assessing the tolerability of an acute dose titration of a CBM.• 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. AIMSDespite 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. METHODSPatients 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. RESULTSSeven 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 Only one patient in the CBM arm was withdrawn due to AEs.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. CONCLUSIONCompared 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.

Cannabis as a Possible Treatment for Spasticity in Multiple Sclerosis / Kanabis Kao Moguci Tretman U Lecenju Spasticnosti Kod Multiple Skleroze

“…Numerous studies, most of them carried out in the 1970s and 1980s, have demonstrated that cannabinoids are equally or more effective in treating chemotherapy-related nausea and vomiting as the standard antiemetics (15,16,17). Some studies have shown that cannabis is effective in the treatment of anorexia and cachexia in patients with human immunodeficiency virus (HIV) (18), tumours (19) and Alzheimer's disease (20), as well as in the treatment of chronic neuropathic pain and multiple sclerosis (21,22).…”

The Gastrointestinal Pharmacology of Cannabinoids: Focus on Motility

“…Conditioned retching in S. murinus and conditioned gaping in the rat induced by the context (signs of anticipatory vomiting and nausea, respectively) were also reduced by CBD [53,56]. All these data suggest that CBD might be a useful non-psychotropic CB alternative to control nausea and emesis in humans too; to our knowledge, it has not been tested on its own for this, but the effects are positive when combined with THC [40]. …”

“…Different CBs (THC and nabilone, its synthetic analogue) and CB extracts (containing both THC and CBD) have proved to be effective anti-emetics in humans [39,40]. Moreover, CBs exert antinauseant effects [41].…”

Medical Use of Marijuana

“…32 The overall observation included early (0-24 hours) and delayed (24-120 hours) phase periods. This study included a heterogeneous population in terms of type of cancer and the chemotherapeutic agents used.…”