24.5: Chemotherapy-Induced Nausea and Vomiting: Cannabinoids

Tetrahydrocannabinol (THC) is a phytocannabinoid that primarily interacts with the CB₁ receptor, a type of G protein-coupled receptor (GPCR) predominantly in and around the chemoreceptor trigger zone (CTZ) and emetic center. THC also blocks the serotonin receptor activity in the dorsal vagal complex (DVC) by inhibiting serotonin release. THC exerts its anti-emetic effects through these interactions, which are beneficial for patients undergoing chemotherapy.

Two synthetic agonists of THC, Dronabinol (Marinol) and Nabilone (Cesamet), are FDA-approved for treating chemotherapy-induced nausea and vomiting (CINV). Dronabinol is the primary psychoactive compound of marijuana. It's a highly lipid-soluble compound that is rapidly absorbed after oral administration. It should be administered 1-3 hours before chemotherapy, with an optional repeat dose 2-4 hours after the session begins if needed. However, it undergoes extensive first-pass hepatic metabolism, which can limit its bioavailability. Nabilone comes in oral pill form only. It is recommended the night before, during, and after chemotherapy. However, these cannabinoids have adverse effects such as acute intoxication, tachycardia, psychosis, anxiety, dizziness, dry mouth, and euphoria.

Vomiting, a protective reflex to expel toxins from the gut, can become a distressing side effect of regular chemotherapy.

Neurons near the chemoreceptor trigger zone and emetic center contain cannabinoid or CB₁ receptors. When activated by tetrahydrocannabinol or THC, these receptors inhibit the release of neurotransmitters such as serotonin, halting the neurotransmission of vomiting stimuli. This makes the CB₁ receptor an attractive drug target.

Several agonist drugs like dronabinol or nabilone enhance CB₁ receptor activity, mitigating vomiting reflex.

Both agonists are given orally and act rapidly within an hour of ingestion to prevent chemotherapy-induced nausea and vomiting.

Dronabinol, a marijuana plant extract, undergoes extensive first-pass hepatic metabolism, decreasing its bioavailability. Its regimen typically involves one dose before chemotherapy and subsequent doses every 2-4 hours after.

They can cause adverse effects such as dizziness, dry mouth, euphoria, anxiety, postural hypotension, and tachycardia.