Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Review: Delta-9-tetrahydrocannabinol is effective in alleviating cancer chemotherapy-induced nausea

ACP J Club. 1997 Nov-Dec;127:65. doi:10.7326/ACPJC-1997-127-3-065


Source Citation

Voth EA, Schwartz RH. Medicinal applications of delta-9-tetrahydrocannabinol and marijuana. Ann Intern Med. 1997 May 15;126:791-8.


Abstract

Objective

To review the evidence regarding the use of dronabinol (delta-9-tetrahydrocannabinol) and crude Cannabis sativa preparations (marijuana) for glaucoma, cancer chemotherapy-induced nausea, appetite stimulation, and multiple sclerosis-associated spasticity.

Data sources

Studies were identified by searching MEDLINE (1975 to 1996) using the terms cannabis, cannabinoids, marijuana, marijuana smoking, therapeutic use, antiemetics, glaucoma, cachexia, appetite, multiple sclerosis, palliative care, and terminal care. Additional articles were identified by searching the personal libraries of the investigators.

Study selection

Studies were selected if they assessed the use of dronabinol or crude cannabis for 1 of the above 4 indications. Editorials; opinion statements; abstracts; studies not done on humans; unpublished manufacturer's studies; and studies of cannabidiol, levonantradol, or nabilone were excluded.

Data extraction

Data were extracted on dosage and type of study drug (dronabinol or crude cannabis), number of patients and their ages, study design, and the principal results of the study.

Main results

No formal meta-analysis was done. 13 articles that investigated the use of dronabinol as an antiemetic agent for patients with cancer receiving chemotherapy were identified. Of these, 10 were randomized controlled trials. Review of these studies indicated that oral dronabinol, 5 to 15 mg/m2, was more effective than placebo or prochlor-perazine in treating nausea associated with cancer chemotherapy if patients were pretreated and doses were repeated every 3 to 6 hours for 24 hours. Few studies were identified with objective data on the use of pure dronabinol or crude marijuana for appetite stimulation. 1 trial found that oral dronabinol, 2.5 mg twice daily, effectively stimulated appetite in patients with AIDS. Another uncontrolled trial using the same dose found that oral dronabinol improved appetite in patients with terminal cancer, but 22% withdrew because of unacceptable psychotomimetic effects. Pure dronabinol and crude marijuana have little effect on glaucoma and may have a negative effect on multiple sclerosis. Both marijuana and pure dronabinol frequently have toxic and negative effects, primarily psychotomimetic, that depend on the route of delivery, the duration of exposure, and the patient's age and immunologic status.

Conclusions

Delta-9-tetrahydrocannabinol is useful for nausea associated with cancer chemotherapy. Both marijuana and pure delta-9-tetrahydrocannabinol frequently have toxic effects.

Source of funding: No external funding.

For article reprint: Dr. E.A. Voth, The International Drug Strategy Institute, 901 Garfield, Topeka, KS 66606, USA. FAX 913-368-0713.


Commentary

Crude Cannabis sativa preparations are unwieldy pharmaceuticals because the total and relative amounts of cannabidiol, delta-9-tetrahydrocannabinol, and cannabinol vary according to cultivar genetics, growing conditions, and preparation after harvesting (1). Delta-9-tetrahydrocannabinol induces psychedelic effects, lowers intraocular pressure, and reduces gastrointestinal motility (2); cannabidiol has none of these effects. However, cannabidiol may have activity as an anti-convulsant and may inhibit the psychedelic effects of delta-9-tetrahydrocannabinol.

The article by Voth and Schwartz summarizes what we know about the use of cannabinoids for 4 clinical indications. First, scant evidence exists to support or refute the benefit of cannabinoids in multiple sclerosis-associated spasticity. Second, patients with glaucoma have little reason to use cannabinoids because of the many therapeutic alternatives. Third, there is scant evidence supporting the use of cannabinoids as appetite stimulants in patients with cancer or AIDS-associated anorexia and no evidence that they prolong or improve the quality of life. Caution should be exerted in prescribing cannabinoids for HIV-positive patients, as some cannabinoids are immunosuppressive. Fourth, evidence shows that dronabinol is effective in treating cancer chemotherapy-associated nausea. Other medications, including selective serotonin 5-HT3-receptor antagonists, are the main treatments for this indication. Severe headache (3), constipation, and elevated serum liver enzyme levels complicate the use of ondansetron, the most extensively studied of the 5-HT3-receptor antagonists. Optimal drug prophylaxis for cancer chemotherapy-associated nausea is unclear, as no clinical trials comparing dronabinol, ondansetron, or their combination have been published.

Steven M. Belknap, MD
University of Illinois College of Medicine, PeoriaPeoria, Illinois, USA

Steven M. Belknap, MD
University of Illinois College of Medicine, Peoria
Peoria, Illinois, USA


References

1. Starks M. Marijuana Chemistry: Genetics, Processing & Potency. Berkeley, CA: Ronin Publishing; 1990.

2. Shook JE, Burks TF, Wesley JW, Norman JA. J Pharmacol Exp Ther. 1989;249:444-9.

3. Veneziano M, Framarino De Malatesta M, Bandiera AF, et al. Eur J Gynaecol Oncol. 1995;16:203-7.