Cannabinoid Regulation of Acute and Anticipatory Nausea

Abstract

Chemotherapy-induced nausea is one of the most distressing symptoms reported by patients undergoing treatment, and even with the introduction of newer antiemetics such as ondansetron and aprepitant, nausea remains problematic in the clinic. Indeed, when acute nausea is not properly managed, the cues of the clinic can become associated with this distressing symptom resulting in anticipatory nausea for which no effective treatments are available. Clinical trials exploring the potential of exogenous or endogenous cannabinoids to reduce chemotherapy-induced nausea are sparse; therefore, we must rely on the data from pre-clinical rat models of nausea. In this review, we explore the human and pre-clinical animal literature examining the potential for exogenous and endogenous cannabinoid treatments to regulate chemotherapy-induced nausea. The pre-clinical evidence points to a compelling need to evaluate the antinausea potential of cannabidiol, cannabidiolic acid, and treatments that boost the functioning of the endocannabinoid system in human clinical trials.

Cannabidiol (CBD) in Cancer Management

“…Parker reports that animal studies have found CBD can suppress nausea and vomiting within a limited dosage range, with the anti-nausea/emetic effects potentially mediated via indirect activation of somatodentritic 5-HT 1A receptors in the dorsal raphe nucleus which reduces release of 5-HT in terminal forebrain areas [ 40 ]. Various animal studies indicate that cannabinoid acids (cannabidiolic acid (CBDA) and tetrahydrocannabinolic acid (THCA)) can suppress nausea [ 179 , 180 , 181 , 182 ], with CBDA 1000 times more potent than CBD in decreasing acute and anticipatory nausea [ 181 ]. In addition, subthreshold doses of CBDA potentiated the anti-nausea effect of Ondansetron (see [ 182 ]).…”

Prospects for the Use of Cannabinoids in Oncology and Palliative Care Practice: A Review of the Evidence

“…The endocannabinoid system has shown an important role in the regulation of nausea in preclinical studies. Smoked or orally administered THC appeared to be effective in reducing chemotherapy-induced vomiting and nausea (CINV) in several trials [68].…”

Acute chemotherapy-induced nausea and vomiting in children with cancer: Still waiting for a common consensus on treatment

“…Some adjuvant drugs (e.g., benzodiazepines and cannabinoids) have a role in CINV control, particularly in the management of anticipatory symptoms and anxiety, 36 , 37 however, the wide spectrum of toxicity (sedation, dizziness, dysphoria, disorientation and hallucinations) limits their routine use in paediatric patients. 38 , 39…”

“…35 In 2016, MASCC/ESMO recommended acute CINV prophylaxis using a 5-HT3 antagonist for children receiving low emetogenic chemotherapy, and using a 5-HT3 antagonist AE dexamethasone AE aprepitant for children receiving highly or moderately emetogenic chemotherapy. 4 Some adjuvant drugs (e.g., benzodiazepines and cannabinoids) have a role in CINV control, particularly in the management of anticipatory symptoms and anxiety, 36,37 however, the wide spectrum of toxicity (sedation, dizziness, dysphoria, disorientation and hallucinations) limits their routine use in paediatric patients. 38,39 Finally, in CINV control and prevention, a series of complementary, non-pharmacological interventions (e.g.…”