Efficacy of cannabinoids for the prophylaxis of chemotherapy-induced nausea and vomiting-a systematic review and meta-analysis

Background: Cannabinoids have potential efficacy as prophylaxis for chemotherapy-induced nausea and vomiting (CINV), but no recent meta-analysis has reported on their relative efficacy compared to other antiemetics. The aim of this meta-analysis is to examine the relative efficacy of cannabinoids for prophylaxis of CINV.

Methods: A literature search was conducted in OVID Medline, EMBASE, and Cochrane Central Register of Controlled Trials from inception up until March 2024. Articles were included if they reported on complete response, no nausea, no vomiting or no use of rescue medications, and were randomized controlled trials with cannabinoids in one arm. Meta-analysis was conducted for each endpoint and for a composite endpoint amalgamating existing endpoints. Subgroup analyses by medication used in control arm and by study design were conducted. Cumulative and leave-one-out analysis was also conducted. Type I error was set at 0.05.

Results: A total of 26 studies were included in this meta-analysis, of which 23 were published before the 2000s. Nearly half of the included studies had some concern for bias. Cannabinoid had superior overall CINV control compared to placebo (RR 2.65, 95% CI 1.70-4.12, I² = 0.00%). However, there was no difference between cannabinoid and active treatment alternatives (most using dated single-agent regimens) for any outcomes. A recent phase II/III trial demonstrated superior efficacy of THC:CBD for secondary prevention of CINV when used as adjunctive therapy alongside modern antiemetic regimens, albeit mostly without olanzapine.

Conclusions: There is scant evidence for efficacy of cannabinoids for CINV in the era of triple and quadruple antiemetics. Although THC:CBD showed promised in a recent trial, further trials should examine its safety and efficacy in the context of regimens containing olanzapine.