Recent observational cohort studies report that 46%-57% of chemotherapy patients experience significant nausea, and 9%-37% experience vomiting. Chemotherapy-induced nausea and vomiting (CINV) is triggered by a multitude of receptors for neurotransmitters including serotonin, dopamine, substance P, and potentially the cannabinoid CB1 receptor. Limited evidence suggests that medicinal cannabis in the form of tetrahydrocannabinol (THC) may reduce CINV, and addition of cannabidiol (CBD) may improve efficacy and tolerance. Cannabis extracts containing both THC and CBD offer key advantages over alternate cannabinoids, as CBD can counteract the negative effects of THC on the central nervous system, and has inherent anxiolytic properties.
A multicentre, randomised, double-blinded, placebo-controlled, phase II/III trial was recently conducted to evaluate an oral THC:CBD cannabis extract for prevention of refractory CINV. 81 patients who experienced CINV during intravenous chemotherapy despite the administration of anti-emetic drugs. Study treatment consisted of one cycle of 1-4 self-titrated capsules of oral THC 2.5 mg/CBD 2.5 mg (TN-TC11M) three times daily, from days 1 to 5, and 1 cycle of matching placebo in a crossover design, then blinded patient preference for a third cycle. The primary end point was the proportion of participants with complete response during 0-120 h from chemotherapy.
72 completing two cycles were included in the efficacy analyses and 78 not withdrawing consent were included in safety analyses. Complete response (meaning no vomiting or use of rescue medications) was improved with the use THC:CBD from 14% to 25% with similar effects on absence of emesis, use of rescue medications, absence of significant nausea, and summary scores for the Functional Living Index-Emesis (FLIE). Thirty-one percent experienced moderate or severe cannabinoid-related adverse events such as sedation, dizziness, or disorientation, but 83% of participants preferred cannabis to placebo. No serious adverse events were attributed to THC:CBD.
The addition of oral THC:CBD to standard antiemetics was associated with less nausea and vomiting but additional side-effects. Most participants preferred THC:CBD to placebo. More studies are needed to substantiate these results.
Reference:
Grimison, P., Mersiades, A., Kirby, A., Lintzeris, N., Morton, R., Haber, P., Olver, I., Walsh, A., McGregor, I., Cheung, Y., Tognela, A., Hahn, C., Briscoe, K., Aghmesheh, M., Fox, P., Abdi, E., Clarke, S., Della-Fiorentina, S., Shannon, J., Gedye, C., … Stockler, M. (2020). Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial. Annals of oncology : official journal of the European Society for Medical Oncology, 31(11), 1553–1560. https://doi.org/10.1016/j.annonc.2020.07.020
