Abstract
Introduction
Terminology
Cannabis sativa is the Indian hemp plant. Marijuana is a psychoactive substance derived from the plant. Cannabinoids are the biologically active compounds in the plant. THC is delta-9-tetrahydrocannabinol, the major cannabinoid. Dronabinol is synthetic THC and the main ingredient in the schedule 3 drug Marinol® (Unimed Pharmaceuticals, Inc., A Solvay Pharmaceuticals, Inc. Company, Marietta, GA). Nabilone is an engineered THC analogue that forms the basis of the schedule 2 drug Cesamet® (Meda Pharmaceuticals, Somerset, NJ).
Pharmacology
Cannabinoids act on cannabinoid receptors: the CB1 receptor in the central nervous system (CNS) and on the CB2 receptor localized primarily to immune cells. Dronabinol and nabilone are well absorbed orally, but first pass metabolism and protein binding limit bioavailability. Dronabinol has a faster onset of action (approximately 30 minutes), while nabilone has a longer duration of action (typically 8–12 hours, but potentially as long as 24 hours in some patients). Alternative delivery systems—including inhalers, suppositories, and transdermal patches—are being evaluated.
Antiemetic Use
Dronabinol and nabilone are FDA approved for the treatment of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond to conventional antiemetics. Cannabinoids in this context have two limitations. First, studies show that these agents, while efficacious in—and preferred by—many patients, have potent side effects and a variably narrow therapeutic window. Second, newer types of antiemetic therapy, including the 5-HT3 receptor antagonists and a neurokinin-1 receptor antagonist, have since been developed that appear to be both extremely effective and generally well tolerated. There are no published studies comparing dronabinol and nabilone to these newer generation agents, or to each other.
Orexigenic Use (Appetite Stimulation)
Dronabinol is FDA approved for the treatment of anorexia associated with weight loss in patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). Early studies of dronabinol in this population showed promising increases in caloric intake and stabilization or gains in weight. However, later analysis showed that the effect sometimes represented accumulation of water or fat instead of the preferred lean body mass. Nabilone is not approved as an appetite stimulant. There is no strong evidence supporting either cannabinoid for cancer-associated anorexia.
Side Effects
Side effects are both physiologic (hypotension with reflex tachycardia, gastroparesis, ataxia, somnolence, dry mouth) and psychologic (euphoria, poor concentration, and—at high doses—anxiety, delusions, and hallucinations). Symptoms are typically dose-related, vary among patients, and are worse in the elderly. Tolerance of many of these effects develops over 1 to 2 weeks. Dronabinol contains sesame oil and poses a risk of anaphylaxis to those with a hypersensitivity to sesame seeds or nuts. Relative contraindications include a history of seizures, and concurrent use of alcohol, sedatives, hypnotics, or other psychoactive agents. Patients taking cannabinoids should be advised not to drive.
Prescribing Guidelines
Antiemetic
Dronabinol is dosed 5 mg/m2 starting 2 hours before chemotherapy and every 4 hours thereafter, to a total of 4 to 6 doses daily. It can be titrated by 2.5 mg/m2, to a per-dose maximum of 15 mg/m2. Nabilone is dosed 1 mg twice daily, starting 3 hours before chemotherapy. It can be increased to 2 mg per dose, with a maximum of 6 mg/d in 3 divided doses. Nabilone is typically less expensive.
Orexigenic
Dronabinol is started at 2.5 mg twice daily, 1 hour before lunch and dinner, or as a single 2.5-mg dose at night. It can be increased gradually to a maximum of 20 mg/d, in divided doses.
Footnotes
Fast Facts and Concepts are edited by Drew A. Rosielle M.D., Palliative Care Program, University of Minnesota Medical Center–Fairview Health Services, and are published by the End of Life/Palliative Education Resource Center at the Medical College of Wisconsin. For more information write to: 
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Version History: This Fast Fact was originally edited by David E. Weissman M.D. The second edition was edited by Drew A. Rosielle and published December 2007. Current version re-copy–edited April 2009.
Disclaimer: Fast Facts and Concepts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Facts cite the use of a product in a dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.