There are currently three cannabinoids available on the pharmaceutical market. Dronabinol and Nabilone are both synthetic tetrahydrocannabinol (THC), which the FDA has approved for the treatment of chemotherapy-induced nausea and vomiting (CINV) after the failure of a trial of first-line anti-emetics. Both are also FDA approved to treat anorexia associated with AIDS.  Recently, the FDA has also approved a cannabidiol (CBD) product to treat seizures associated with Lennox-Gastaut Syndrome and Dravel Syndrome in pediatric patients. However, there is no FDA approved indication for its use as an anti-emetic.[1] Independently produced cannabidiol extracts are being used increasingly in the general population for many non-FDA approved indications, frequently including nausea and emesis.  In states that have decriminalized marijuana, both in recreational and medicinal contexts, products with varying ratios of cannabidiol and THC are also used for their anti-emetic properties.[1]

Cannabinoids and their anti-emetic potential are still under research, and many of the intricacies behind their mechanisms are still unknown or lack universal consensus.  Cannabinoids exert their anti-emetic properties through interactions with the centrally located CB1 receptors and 5-HT3 receptors in the dorsal vagal complex (DVC), which mediates emesis.  A significant contributor to emesis appears to be via activation of 5-HT3 receptors in the DVC, specifically in the area postrema.  Studies in animal models have shown that anandamide, an endogenous cannabinoid, THC, and several synthetic cannabinoids have demonstrated allosteric inhibitor effects on the 5-HT3 receptors in the DVC, providing a mechanism through which emesis control occurs.  Animal models have also shown that cannabinoids may work on pre-synaptic CB1to decrease the release of serotonin into the synapse, thus inhibiting the nausea/emesis response.  

Animal models have also indicated CBD to have an allosteric inhibitory effect on the 5-HT3 receptor. However, this effect may be mainly through its activation of the 5-HT1A receptor. Through activation of the 5-HT1A receptor, there is ultimately a reduction in the amount of serotonin released, and thus a lower potential to trigger emesis. CBD is also thought to activate the CB1 receptors in the gastrointestinal tract, through their G-protein-coupled receptor inhibitory effect, leading to decreased gastrointestinal motility. THC and CBD were once credited with inhibiting fatty acid amide hydrolase (FAAH), leading to an increased concentration of anandamide that could exert its anti-emetic properties at a higher intensity, but recent studies into this mechanism have been equivocal.[2]

Dronabinol dosing can be via both oral pill and oral solution forms, available in doses of 2.5 mg, 5 mg, and 10 mg. In CINV, the patients should take it 1 to 3 hours before starting their chemotherapy session, with a repeat dose available 2 to 4 hours after beginning the session as needed. Nabilone is available in oral pill form, in doses of 1 mg or 2 mg. These doses can be increased or decreased based on practitioner discretion. Patients should receive instruction to take one dose the night before starting their chemotherapy session, one dose twice a day during the entirety of the chemotherapy course, and one dose twice a day after chemotherapy has concluded. CBD is sold legally throughout the entire United States without a prescription by many private entities that are not FDA regulated; there are no concrete guidelines in dosing. However, doses generally range from 10 mg to 50 mg at a time, taken either as needed or daily.  Products containing significant levels of THC are sold legally by medicinal and recreational dispensaries in several states, depending on legal status. Doses for these generally range between 5 mg and 15 mg and are typically taken as needed as opposed to daily, due to their psychotropic effects.[1][3]

Adverse effects depend on the cannabinoid administered. The most common adverse effects of formulas containing a THC component are acute intoxication, tachycardia, aboulia, and psychosis. Psychoses manifest most commonly as perceptual alteration, but also frequently include panic attacks, anxiety, paranoia, and depression.[4] Individuals using THC containing cannabinoid products chronically and at a high volume are also at risk of developing cannabis hyperemesis syndrome, which can present as intractable nausea and vomiting.[5] Cannabinoid formulas containing only a CBD component have less potential to cause behavioral side effects, although drowsiness occurs frequently. CBD is a CYP3A4 inhibitor, which can lead to drug interactions and toxicities in molecules metabolized by the CYP3A4 system.[6] In vitro studies have shown an association between CBD and reduced fertility and alterations of cell viability. Dronabinol has reported adverse effects of gastrointestinal upset, dizziness, paranoia, somnolence, and abnormal thoughts.[7] Nabilone has reported adverse effects that include acute intoxication, ataxia, headache, drowsiness, and deficits to concentration.[8]

Cannabinoids are contraindicated in individuals with a history of hypersensitivity reactions that can be related to any form of cannabinoid consumption. They should be used cautiously in patients who have experienced intolerable side effects in the past. Dronabinol is specifically contraindicated in patients with hypersensitivity to sesame oil.[7]