Fast Fact and Concept #093: Cannabinoids in the Treatment of Symptoms in Cancer and AIDS

2nd Edition

Author(s): L Scott Wilner; Robert M. Arnold

The healing properties of cannabis have been asserted for centuries. Popular claims notwithstanding, there are no data to support the use of marijuana in the treatment of asthma, anxiety, depression, epilepsy, glaucoma, alcohol withdrawal, or infection; and limited data to support using cannabinoids as analgesics. Recent scientific studies of cannabinoids for symptom management have focused on nausea/vomiting and appetite stimulation.

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. Nabilone is an engineered THC analog that forms the basis of the Schedule 2 drug Cesamet .

Pharmacology

Cannabinoids act on cannabinoid receptors: the CB 1 receptor in the CNS and on the CB 2 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 (~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.

Anti-emetic 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; and 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 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 to many of these effects develops over 1 to 2 weeks. D ronabinol 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/m 2 starting 2 hours before chemotherapy and every 4 hours thereafter, to a total of 4 to 6 doses daily.

OREXIGENIC: Dronabinol is started at 2.5 mg twice daily, one hour before lunch and dinner, or as a single 2.5 mg dose at night.

References

  1. Walsh D, Nelson KA, Mahmoud FA. Established and potential therapeutic applications of cannabinoids in oncology. Supportive Care in Cancer 2003; 11:137-143.
  2. Otten EJ. Marijuana. In Toxicologic Emergencies, 7 th Edition. LR Goldfrank, NE Flomenbaum, et al, Editors. McGraw-Hill, New York, NY, 2002.
  3. Tramer MR, Carroll D, Campbell FA, et al. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ. 2001; 323:16-21.
  4. Beal JE, Olson R, Laubenstein L, et al. Dronabinol as a Treatment for Anorexia with Weight Loss in Patients with AIDS. Journal of Pain and Symptom Management. 1995; 10:89-97.
  5. Jatoi A, Windschitl HE, et al. Dronabinol Versus Megestrol Acetate Versus Combination Therapy for Cancer-Associated Anorexia: A North Central Cancer Treatment Group Study. Journal of Clinical Oncology. 2002; 20:567-573.
  6. Slatkin NE. Cannabinoids in the treatment of chemotherapy-induced nausea and vomiting: beyond prevention of acute emesis. Journal of Supportive Oncology. 2007:5(Suppl 3):1-9.
  7. Davis M, Maida V, et al. The emerging role of cannabinoid neuromodulators in symptom management. Supportive Care in Cancer. 2007; 15(1):63-71.
  8. Ben Amar M. Cannabinoids in medicine: A review of their therapeutic potential. Journal of Ethnopharmacology. 2006; 105:1-25.
  9. Anonymous. Nabilone (Cesamet) for chemotherapy-induced nausea and vomiting. Medical Letter on Drugs & Therapeutics. 2006; 48(1249/1250):103-4.
  10. Nemechek PM, Polsky B, Gottlieb MS. Treatment Guidelines for HIV-associated wasting. Mayo Clinic Proceedings. 2000; 75(4): 386-94.

Fast Facts are edited by Drew A. Rosielle MD, Palliative Care Center, Medical College of Wisconsin. For comments/questions write to: drosiell@mcw.edu. The complete set of Fast Facts is available at EPERC: www.eperc.mcw.edu.

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Wilner LS, Arnold R. Fast Fact and Concept #93. Cannabinoids in the Treatment of Symptoms in Cancer and AIDS. 2 nd Edition. December 2007. End-of-Life/Palliative Education Resource Center ( www.eperc.mcw.edu).

Disclaimer: Fast Facts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in 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.

Creation Date: 1/2008

Purpose: Instructional Aid, Self-Study Guide, Teaching
Audience(s)

    

Training: Fellows, 1st/2nd Year Medical Students, 3rd/4th Year Medical Students, PGY1 (Interns), PGY2-6, Physicians in Practice

    

Specialty: Anesthesiology, Emergency Medicine, Family Medicine, General Internal Medicine, Geriatrics, Hematology/Oncology, Neurology, OB/GYN, Ophthalmology, Pulmonary/Critical Care, Pediatrics, Psychiatry, Surgery

    

Non-Physician: Lawyers, Nurses, Social Workers

ACGME Competencies: Medical Knowledge, Patient Care

Keyword(s): Non pain symptoms & syndromes; cancer

Specific Disease and Organ System Category(s): Cancer