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Medicinal Uses of Cannabis

http://www.medscape.com/viewarticle/458076

July, 2003
Medscape coverage of: Canadian Pharmacists Association 91st Annual Meeting
Anisha Lakhani, BSc(Pharm), Pharm D

Cannabis (see footnote*) has both disappointed and intrigued scientific researchers for decades. "Cannabis most likely came from China and Assyria," said Dr. Orlando Hung, at the Canadian Pharmacists Association's Annual Conference. It has been used for centuries to treat waste disease, rheumatism, and injuries. Right from its early history of use to the current time, cannabis has many claims to its fame, but rigorous scientific evidence is lacking.

Dr. Orlando Hung, previously a pharmacist and now an anesthetist and researcher at Dalhousie University in Halifax, Nova Scotia, made it very clear that his interest in cannabis was purely from the medical science perspective, not political. A significant amount of interest in this compound, in both the political and scientific arenas, was sparked by extensive recreational use in the 1960s. By the late 1960s, the active compound in marijuana called delta-9-tetrahydrocannabinol (THC) (see footnote†) was discovered.

Marijuana is obtained from a plant called cannabis sativa. It is composed of dried flower tops and leaves. The fiber obtained from other parts of the plant is hemp, which is used in textiles, paper, paints, and clothing. Hemp has only a minute amount of THC. The dried and compressed secretions from the same plant are referred to as "hashish," which is rich in THC. There are more than 400 chemicals in marijuana, many of which have varying degrees of toxic effects. Scientists are hoping to develop synthetic cannabinoids that would have better properties.

The variations in the potency of marijuana and the unique physio-chemical properties of THC have posed tremendous challenges in medical research. THC is a highly lipid soluble compound that does not form into salts. THC is highly sensitive to temperature, low acidity (eg, pH < 4 of the stomach), light, and atmospheric oxygen.

In spite of the above problems, marijuana research has revealed some interesting insights. In the past decade, 2 types of cannabinoid receptors have been identified. CB1 receptors have been found to have anti-nociceptive effects in the animal studies. These receptors are found centrally (ie, in the basal ganglia, cerebellum, cortex, hippocampus, periaqueductal gray, and spinal cord), as well as in some peripheral tissues such as the heart and uterus.[1] CB2 receptors occur peripherally in spleen and macrophages, and play a role in modulating lymphocyte function. CB2 receptors may also produce anti-nociceptive effects against inflammatory pain.[1] Endogenous ligands have also been identified.

Acute adverse effects of marijuana are thought to be associated with CB1 receptor stimulation and include sedation, anxiety, and panic attacks.[2,3] Other effects include mental euphoria, impaired coordination, and impaired memory. With larger doses, dysphoria, delusion, delirium, and hallucinations can occur. Cardiovascular effects include increased heart rate, low cardiac output, bradycardia, and hypotension.[3,4] Long-term respiratory effects from inhalation of insoluble particulates and carbon monoxide load are similar to, if not greater than, the effects of cigarette smoking. Endocrine effects include immunosuppression and depression of spermatogenesis. Additionally, repeat exposure is thought to lead to tolerance and physical dependence.

There are many areas of research involving medical uses of cannabinoids. Animal studies have shown agonistic (anti-nociceptive) effects in a variety of pain tests. Although these studies do not suggest efficacy anywhere close to that of narcotics, they do suggest a possible role in the treatment of neuropathic pain, where narcotics are largely ineffective.[1]

Evidence from animal models of multiple sclerosis have shown cannabinoids to alleviate tremor and spasticity. There are many case reports of the use of cannabis in multiple sclerosis (MS) patients. In a recently published study, investigators conducted a randomized, double-blind, 2-fold, cross-over, placebo-controlled trial involving 16 patients with progressive MS.[5] Patients were given 2 daily oral capsules of 2.5 mg THC or plant extract containing THC, with dose increases after 2 weeks if tolerated. Both THC and plant extract produced several side effects; 1 patient suffered acute psychosis. Various tools such as MS specific Fatigue Severity Scale, Medical Outcomes Study Short Form 36, daily Visual Analogue Scale, and other tests were used for assessing efficacy. Unfortunately, compared with placebo, active treatments did not result in significant differences in the muscle tone. Instead, they showed a trend for deterioration. The study was inadequately powered and no conclusions could be drawn regarding the therapeutic benefit of THC or the plant extract.

Cannabinoids are known to have antiemetic effects on chemotherapy-induced nausea and vomiting. However, there are more effective agents available today. There is evidence suggesting cannabinoids render neuroprotective effects that may prove to be useful in Parkinson's disease.[3] A cannabinoid receptor agonist has been used to increase appetite in HIV patients.

"Clinical applications of cannabinoids must be based on scientific evidence," said Dr. Hung. Research has been hindered significantly due to the lack of suitable delivery systems. More development is continuing in the area of synthetic, nonpsychoactive analogues as well as novel delivery systems. There is exciting research involving cannabinoid receptors as nociceptive targets.[1] Also, newly identified modulators of endogenous cannabinoid system are targets for therapeutic research.[2] In any case, well-designed, randomized human trials are needed to provide reliable evidence for the medical purposes of cannabinoids.

* Refer to FDA Schedules of Controlled Substances.
† Toxicology device. Refer to FDA's Accredited Persons and Third Party Program.

References

  1. Wu CL, Garry MG, Zollo RA, Yang J. Gene therapy for the management of pain: part II: molecular targets. Anesthesiology. 2001;95:216-240. Abstract
  2. Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharm. 2003;42:327-360.
  3. Croxford JL. Therapeutic potential of cannabinoids in CNS disease. CNS Drugs. 2003;17:179-202. Abstract
  4. Steadman JL, Birnbach DJ. Patients on party drugs undergoing anesthesia. Curr Opin Anesthesiol. 2003;16:147-153.
  5. Killestein J, Hoogervost EJL, Reif M, et al. Safety, tolerability and efficacy of orally administered cannabinoids in MS. Neurology. 2002;58:1404-1407. Abstract


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