It is reported that chemotherapy-induced vomiting can be prevented in more than two-thirds of patients if antiemetics are used correctly.1 Nausea remains difficult to prevent and manage and is typically more commonly reported than emesis: 54.9% versus 45.1% at any cycle. Several treatment guidelines exist published by reliable institutions providing recommendations to optimize CINV prevention and management, yet CINV remains an issue. In a recent report, despite prophylactic antiemetics, approximately 60% of patients who received moderately and highly emetogenic chemotherapy regimens still experienced some form of CINV; delayed being more common (58% versus 34%).3 Improvements in CINV management are needed.

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Several antiemetic options exist to manage CINV. Corticosteroids, serotonin receptor antagonists (5-HT3 RAs), and neurokinin receptor antagonists (NK1 RAs) are the classes most commonly used in the prevention of CINV.

Corticosteroids have been utilized as an effective antiemetic for over 30 years, with dexamethasone being the most common agent.4 This class may be used for acute and delayed CINV and are effective when given in combination for prevention of CINV in moderately and highly emetogenic regimens. A meta-analysis of over 5,000 patients receiving highly or moderately emetogenic chemotherapy assessed the efficacy of dexamethasone as prophylaxis for CINV. In the majority of trials included, dexamethasone was given in combination with other antiemetics, such as 5-HT3 RAs, or metoclopramide. Dexamethasone was determined to be superior to placebo or no treatment in terms of complete protection (no vomiting or retching) for both acute (odds ratio: 2.22, 95% confidence interval: 1.89–2.60) and delayed (odds ratio: 2.04, 95% confidence interval: 1.63–2.56) vomiting. Corticosteroids are usually well tolerated when used as a short-term antiemetic. Moderate-to-severe insomnia (45%), gastrointestinal discomfort (27%), agitation (27%), increased appetite (19%), weight gain (16%), and acne (15%) have been reported by patients taking dexamethasone for the prevention of delayed CINV.

Selective 5-HT3 RAs have been incorporated into the management of CINV for over the last 20 years.4In the United States, the following agents are approved: dolasetron, granisetron, ondansetron, and palonosetron, with palonosetron having a significantly longer half-life, making it exceptionally useful in the prevention of delayed CINV. Various studies have shown this class of agents to be effective in the prevention of acute and delayed CINV. One meta-analysis including ten studies revealed an 8.2% absolute risk reduction compared to placebo for the development of delayed CINV. One of the more notable adverse effects of this class is the potential development of electrocardiogram abnormalities, including QT prolongation. Additional side effects reported with these medications include headache, constipation, and abdominal pain.

One of the newer classes of medications approved for the prevention of CINV is the NK1 RAs. Agents from this class should be administered in combination with dexamethasone and a 5-HT3 RA to prevent acute and delayed CINV associated with moderately and highly emetogenic chemotherapy.2 A meta-analysis including nearly 9,000 patients receiving moderately and highly emetogenic chemotherapy experienced a significant improvement in CINV in the acute, delayed, and overall phases (P<0.001) when NK1 RAs were added to 5-HT3 RAs and corticosteroids.4 Medications from this class tend to be well tolerated with minimal side effects. It is important to note the potential for drug interactions with medications metabolized through the cytochrome P450 enzyme system.

Olanzapine is the latest unique agent to be added to the treatment guidelines.2 Olanzapine works on several neurotransmitters involved in the development of CINV such as dopamine, serotonin, histamine, and acetylcholine.4 Data support its role for the prevention of acute and delayed CINV as well as for the management of breakthrough CINV. Caution should be employed when using this agent in elderly patients with dementia-related psychosis as it may place them at an increased risk of death.

There are many alternative drug classes utilized for the prevention and management of CINV such as antihistamines, benzodiazepines, anticonvulsants, cannabinoids, and dopamine receptor antagonists. Medications belonging to these classes generally have lower efficacy and are associated with more adverse effects. They are also not as well studied compared to the agents mentioned above. The remainder of this review will focus on dronabinol, a member of the cannabinoid class, and its role in CINV.


Cannabis sativa L. (also known as marijuana) contains naturally occurring delta-9-tetrahydrocannibinol (delta-9-THC). The synthetic version of delta-9-THC is the active ingredient in dronabinol that makes dronabinol an orally active cannabinoid.

There are at least two types of cannabinoid receptors, CB1 and CB2.5 CB1 receptors are located throughout the central nervous system, whereas CB2 receptors are present on the brainstem neurons but mostly concentrated in the periphery, primarily on immunocytes and mast cells.6 These receptors can be activated not only by cannabis-derived and synthetic agonists, but also by endogenous cannabinoids produced in mammalian tissues.5 The mediating effects of dronabinol and other cannabinoids occur through these cannabinoid receptors located in neural tissues.7

Dronabinol has an onset of action of approximately 0.5–1 hour, with a peak effect at 2–4 hours, lasting a total of 4–6 hours with the psychoactive effects. After a single dose of dronabinol, 90%–95% of the medication is systemically absorbed; however, only 10%–20% enters the systemic circulation due to the high lipid solubility and first-pass hepatic metabolism. Dronabinol has a large volume of distribution, approximately 10 L/kg, which allows for the metabolites to be released over a prolonged period of time at low levels. It undergoes first-pass hepatic metabolism, leading to active and inactive metabolites. The clearance for dronabinol varies greatly, with an average of 0.2 L/kg/h. Dronabinol metabolites have been detected after a single dose more than 5 weeks after administration in the urine and feces. The major route of elimination for dronabinol is through the feces, with approximately 35%–50% removed by this route; however, about 10%–15% is found in the urine.7