Cannabinoids in the Treatment of Symptoms in Cancer and AIDS

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

Terminology
Cannabis sativa is the scientific name of the Indian hemp plant; Cannabinoids are the biologically active compounds in the plant. Marijuana is derived from the flowers, buds, and stems of the plant. THC is??-9-tetrahydrocannabinol, the key active ingredient in marijuana. Dronabinol is synthetic THC, available under the brand name Marinol.

Pharmacology
The effects of THC are mediated through cannabinoid receptors - CB1 in neural tissue and CB2, in non-neural tissues. 90-95% of ingested dronabinol is absorbed; first-pass hepatic metabolism reduces the effective circulating dose by 80-90 percent. To improve uptake, THC inhalers and suppositories have been studied but are not yet commercially available.

Antiemetic Use
Dronabinol is FDA approved for nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond to conventional antiemetics. Dronabinol has been shown to be superior to placebo, prochlorperazine (Compazine), and metoclopramide (Reglan), for mild/mod emetogenic chemotherapy (e.g. cyclophosphamide). For highly emetogenic chemotherapy (e.g. cisplatin) it is less effective than standard antiemetics. There is no data on the use of dronabinol for non-chemotherapy nausea.

Appetite Stimulant
Dronabinol is FDA approved for anorexia associated with weight loss in patients with AIDS. In cancer patients, this drug may improve appetite and possibly lead to weight gain. A recent randomized controlled trial found it to be inferior to megestrol acetate (Megace) for cancer associated anorexia.

Side Effects
Dronabinol is contraindicated in patients with known hypersensitivity to cannabinoids or sesame oil (component of the capsule). THC effects are both physiological (tachycardia, hypotension, delayed gastric emptying, decreased muscle strength) and psychological (drowsiness, difficulty concentrating, and at higher doses anxiety, delusions, and hallucinations). These symptoms are typically dose related, show considerable inter-patient variability, and are worse in the elderly. Tolerance to many of the effects of THC develops over the course of 10 to 12 days, but the orexigenic properties of the drug appear sustainable over study periods of up to 6 months.

Dosing Guidelines
Appetite stimulation: start 2.5 mg twice daily, one hour before lunch and dinner; increase gradually as tolerated to a maximum of 20 mg/day, given in divided doses. Antiemetic: give 5/m2 2 hours before chemotherapy and continue every 2-4 hours, for a total of 4 to 6 does daily. The dose can be titrated, by increments of 2.5 mg/m2, to a per-dose maximum of 15 mg/m2. Note: above 7 mg/m2, side effects become more pronounced. Dronabinol is a Schedule II drug; Marijuana is a Schedule I substance not approved for medical use by the DEA or FDA.

References
Walsh D, Nelson KA, Mahmoud FA. Established and potential therapeutic applications of cannabinoids in oncology. Supportive Care in Cancer 2003; 11:137-143.
Otten EJ. Marijuana. In Toxicologic Emergencies, 7th Edition, LR Goldfrank, NE Flomenbaum, et al, Editors. McGraw-Hill, New York, NY, Copyright 2002.
Tramer MR, Carroll D, Campbell FA, et al. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ, Volume 323, 7 July 2001.
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, Volume 10, 2 February 1995.
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, Volume 20, Number 2, 2002; 567-573.

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Citation for referencing. Wilner LS and Arnold R. Fast Facts and Concepts #93 CANNABINOIDS IN THE TREATMENT OF SYMPTOMS IN CANCER AND AIDS June 2003. End-of-Life Physician 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: 7/2003