April 1998
Medication forum
Q: Are there any valid
medical uses of marijuana?
Denis Bélanger, B.Sc.Phm.
A: There has been a recent resurgence in interest in the medical uses of marijuana, following an Ontario court ruling that certain sections of the Controlled Drug and Substance Act are unconstitutional in cases where marijuana is used for medically approved purposes.1 The judge stayed charges of cultivation and possession of marijuana against a 42-year-old man with epilepsy. The judge agreed that the man’s illness was best controlled with a combination of standard prescribed medication and smoking marijuana, and that depriving him of marijuana was unconstitutional. (The man was, however, convicted of trafficking in marijuana.) In the U.S., Proposition 200 in Arizona and Proposition 215 in California allow for the use of marijuana (as a prescribed medication) for the treatment of a variety of conditions.
Crude marijuana (also referred to as pot, grass, weed, reefer, ganja, joint) is an undefined herb that contains approximately 480 substances, including 66 cannabinoid constituents.2 Delta-9-tetrahydrocannabinol (THC), one of these cannabinoid constituents, is the major active ingredient in marijuana.2 It is available commercially by prescription as dronabinol.
Several medical uses of THC and marijuana have been studied, including nausea and vomiting associated with cancer chemotherapy, cachexia in cancer and AIDS patients, multiple sclerosis, and glaucoma.2 By far, most of the medical research on the uses of oral THC and smoked marijuana has focused on the control of nausea associated with cancer chemotherapy. Oral THC has generally been found as effective or more effective for nausea than oral prochlorperazine or oral metoclopramide.3-8 The toxicity profile of oral THC, however, has been less than favourable in many studies. In two studies, adverse effects occurred in 81 per cent of patients.4,5 Nine per cent of these patients experienced hallucinosis, distortion of reality, and/or mental depression. The effectiveness of THC was usually correlated to the onset of a “high” or intoxicated feeling. In another study, the toxic effects of THC were so profound that most patients preferred nausea to THC therapy.9
In one of the few studies examining smoked marijuana, researchers found that nausea was controlled in patients in whom conventional antiemetics had failed.10 However, this study was uncontrolled, and patients themselves evaluated the results. Dosing varied because the dose was rounded to the nearest one-fourth of a marijuana cigarette. In contrast to the oral THC studies, plasma THC levels were not measured. In another study involving 20 patients, the efficacy of smoked marijuana was compared to pure oral THC in a randomized, double-blind fashion.11 Oral THC was more effective for nausea than smoked marijuana in 35 per cent of patients; 45 per cent of patients did not note any difference between the two treatments. A search of published literature did not reveal any studies that compared the antiemetic effects of smoked marijuana or oral THC to the serotonin antagonists (i.e., ondansetron, granisetron, dolasetron).
The appetite-stimulating effects of THC and marijuana may be beneficial for patients with cancer or AIDS-related wasting; however, there are very few well-designed studies which support this indication. In two studies, oral THC (2.5 mg twice daily) effectively stimulated appetite in patients with terminal cancer and patients with AIDS.12,13 Another study compared the effects on appetite stimulation of oral and rectal suppository forms of THC with those of smoked marijuana, in healthy individuals.14 Smoked marijuana was found to be no more effective than the suppository form of THC in stimulating appetite. The THC plasma levels peaked more rapidly with smoked marijuana, but also decreased more quickly than with THC suppositories.
THC has been shown to reduce intraocular pressure in laboratory animals and humans with glaucoma.15 However, intraocular pressure is only reduced if patients stay under the effects of THC almost continuously, and there is no evidence that pure THC or crude marijuana affects or arrests the underlying disease. Researchers have concluded that side effects such as hypotension, tachycardia, palpitations and altered mental status generally preclude the use of marijuana or THC in patients with glaucoma.15
Some anecdotal reports and case reports have suggested that THC may help to control the spasticity of multiple sclerosis. However, a double-blind, randomized, placebo-controlled study in patients with multiple sclerosis showed that smoking marijuana negatively affected posture and balance.16
A literature search did not reveal any published reports of the use of THC in patients with epilepsy.
Distortion of reality, euphoria, dysphoria and changes in coordination and concentration have been associated with the use of smoked and oral THC. Motor coordination, memorization, and memory retrieval can be adversely affected by the use of crude marijuana. Respiratory problems are often prevalent in patients with cancer or AIDS; smoking marijuana exposes these patients to 50 per cent higher levels of the procarcinogen benzpyrene than does smoking tobacco.17 Smoking marijuana also produces carboxyhemoglobin levels that are five times higher and tar levels that are three times higher than those produced by tobacco smoking.17 Pathogenic bacteria including Klebsiella, Enterobacter, and Group D Streptococcus have been cultured from marijuana.18 Infections with Salmonella and fungi have been associated with marijuana use; immunosuppressed patients such as cancer and AIDS patients would be at particular risk.
In Canada, Cannabis sativa, as well as its preparations, derivatives and similar synthetic preparations, are governed by the Narcotic Control Act.19 Unlawful possession is a criminal offence. Upon summary conviction for a first offence, the penalty is a fine of up to $1,000 and/or six months’ imprisonment; for subsequent offences $2,000 and/or one year; upon conviction by indictment, the penalty is up to seven years’ imprisonment.19 Importing and exporting marijuana is punishable by a sentence of not less than seven years, up to life imprisonment.19 Cultivation of marijuana is punishable by up to seven years’ imprisonment.19
In summary, the literature suggests that oral THC may be useful for nausea associated with chemotherapy, and it may have a role in stimulating appetite in patients with AIDS. The literature does not suggest, however, that smoked marijuana is any better than oral THC for any of the indications studied to date. Since oral THC is already available as a prescription medication and several alternate effective antiemetics also exist, there does not appear to be a need to smoke crude marijuana for medicinal purposes.
References
1. Judge rules marijuana laws unconstitutional. America Online Canada News. Posted 12/10/97. Website address: http://www. rights.org/deathnet/Potnews-9712.html
2. Ross SA, Elsohly MA. Constituents of Cannabis sativa. A review of the natural constituents. J Pharm Sci 1995;4:1-10.
3. Sallan SE, Zinberg NE, Frei E. Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. N Engl J Med 1975;293:795-7.
4. Sallan SE, Cronin C, Zelen M, et al. Antiemetics in patients receiving chemotherapy for cancer: a randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine. N Engl J Med 1979; 302:135-8.
5. Chan AE, Shiling DJ, Stillman RC, et al. Delta-9-tetrahydrocannabinol as an antiemetic in cancer patients receiving high-dose methotrexate. Ann Intern Med 1979;91:819-24.
6. Frytak S, Moertel CG, O’Fallon JR, et al. Delta-9-tetrahydrocannabinol as an antiemetic for patients receiving cancer chemotherapy. Ann Intern Med 1979;91:825-30.
7. Ekert H, Waters KD, Jurk IH, et al. Amelioration of cancer chemotherapy-induced nausea and vomiting by delta-9-tetrahydrocannabinol. Med J Aust 1979;2:657-9.
8. Underleider JT, Andrysiak T, Fairbanks L, et al. Cannabis and cancer chemotherapy: a comparison of oral delta-9-tetrahydrocannabinol and prochlorperazine. Cancer 1982;50:636-45.
9. Kluin-Neleman JC, Neleman FA, Meuwissen OJ, et al. Delta-9-tetrahydrocannabinol as an antiemetic in patients treated with cancer chemotherapy. Vet Hum Toxicol 1979;21:338-40.
10. Vinciguerra V, Moore T, Brennan D. Inhalation marijuana as an antiemetic for cancer chemotherapy. NY State J Med 1988; 88:525-7.
11. Levitt M, Faiman C, Hawks R, et al. Randomized double-blind comparison of delta-9-tetrahydrocannabinol and marijuana as chemotherapy antiemetics. Proceedings of the Annual Meeting of the American Society of Clinical Oncology, Toronto, 6-8 May 1984;3:91.
12. Nelson K, Walsh D, Deeter P, et al. A phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia. J Palliat Care 1994;10:14-8.
13. Beal JE, Olson R, Laubenstein L, et al. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage 1995;10:89-97.
14. Mattes RD, Engelman K, Shaw LM, et al. Cannabinoids and appetite stimulation. Pharmacol Biochem Behav 1994;49:187-95.
15. Merritt JC, Crawford WJ, Alexander PC, et al. Effect of marijuana on intraocular and blood pressure in glaucoma. Ophthalmology 1980;87:222-8.
16. Greenberg HS, Werness AS, Pugh JE, et al. Short-term effects of smoking marijuana on balance in patients with multiple sclerosis and normal volunteers. Clin Pharmacol Ther 1994;55: 324-8.
17. Wu TC, Tashkin DP, Djahed B, et al. Pulmonary hazards of smoking marijuana as compared with tobacco. N Engl J Med 1988;318:347-51.
18. Ungerleider JT, Andrysiak T, Tashkin DP, et al. Contamination of marijuana cigarettes with pathogenic bacteria. Cancer Treat Rep 1982;66:589-90.
19. Straight facts about drugs and drug abuse. Ottawa: Health Canada. Website address: http://www.hwc.ca/links/english.html
Denis Bélanger, B.Sc.Phm., is a drug information specialist at the Ottawa Valley Regional Drug Information Service at Ottawa General Hospital, Ottawa, Ontario. Throughout the year, he will be sharing this space with contributor Glen Schoepp.