Rocky Mountain MS Center on medicinal cannabis
Source: Rocky Mountain MS Centre

The below content was discovered on the Rocky Mountain MS Centre web site. The above link should take one to the origional page.

Marijuana

Marijuana, also known as cannabis, is obtained from one of the oldest cultivated plants, Cannabis sativa. It has been used medicinally for thousands of years (1).

There is limited information about how common marijuana use is among people with MS, especially in the United States. In the United Kingdom, estimates of marijuana use in people with MS range from 4-8 % (2,3). Among people with a variety of medical conditions in Germany, Austria, and Switzerland, MS was the second most common medical reason for using marijuana (depression was the most common) (4).

For more than a century, there has been controversy about the use of marijuana to treat MS and other medical conditions. The divergent opinions about the medical use of marijuana are apparent in the following quotations (3,5):

"There is not a shred of scientific evidence that shows that smoked marijuana is useful or needed. This is not medicine. This is a cruel hoax."

-Gen. Barry McCaffrey, US drug czar, 1996

"The key point is that a cannabis-based medicine has not been scientifically demonstrated to be safe, efficacious, and of suitable quality."

-British Minister of Health, 1997

"Marijuana's therapeutic uses are well documented in the modern scientific literature."

-L. Zimmer and J.P. Morgan, 1997

"Multiple sclerosis represents a promising target for cannabis-based medicines."

-Leslie Iversen, British pharmacologist, 2000

Arguments favoring or opposing the medical use of marijuana may be politically driven and may not be based on a balanced view of the scientific and clinical evidence. This review provides an unbiased, fact-based assessment of our current understanding of the relevance of marijuana to MS.

Forms of Marijuana

Different forms of marijuana are available (1,6). Most commonly, the leaves and small stems of the plant are smoked. Marijuana may also be consumed in food or drink. One method of eating marijuana involves heating leaves in butter or vegetable oil and then using the butter or oil to make brownies and other baked items. One particularly potent preparation that has become popular recently is cannabis oil, which is an alcohol extract of resin ("hashish") from the cannabis plant.

Pill forms of marijuana-derived chemicals are also available (7). The predominant active ingredient in marijuana is "THC" or delta-9-tetrahydrocannabinol. In the United States, THC is available as a prescription drug known as Marinol or dronabinol. In Canada, Europe, and Australia, there is another prescription drug, Cesamet or nabilone, that is a synthetic form of THC.

It is sometimes noted that the beneficial effects of smoked marijuana are greater than those of oral forms of the drug. This is presumably due to the fact that THC is absorbed rapidly and relatively reliably when marijuana is smoked. In contrast, when it is taken by mouth, THC is absorbed slowly and unpredictably from the stomach. Also, after THC is absorbed from the stomach, it travels to the liver where much of it may be inactivated (8).

How Marijuana Produces its Effects

In marijuana, there is a class of chemicals known as "cannabinoids." THC, which is one of these cannabinoids, and appears to be the chemical that is responsible for most of the effects of marijuana (6).

Over the past decade, there have been remarkable advances in our understanding of how THC and other cannabinoids act. One of the major breakthroughs has been the identification of the mechanism by which these chemicals exert their effects. As with other drugs, THC attaches to specific cells in the body and alters the biological activity of these cells. The attachment sites on the cells are known as "receptors." Two major types of receptors for THC have been identified. These are known as "CB1" and "CB2" receptors. Interestingly, the two body systems affected by MS, the nervous system and the immune system, are the same two systems that contain the majority of the CB1 and CB2 receptors. CB1 receptors are primarily located in the nervous system, while CB2 receptors predominate in the immune system.

Another recent research advance has been the discovery of chemicals in the body that act in the same way as THC. In other words, our bodies make chemicals that produce effects similar to those of marijuana. These chemicals are known as "endocannabinoids." Since there are receptors for THC, it makes sense that our bodies make chemicals to interact with these receptors. Presumably, these receptors must exist for some reason other than to interact with THC if one happens to smoke marijuana. The receptors provide, on an ongoing basis, a way for these naturally occurring compounds (endocannabinoids) to communicate with cells in the body. This situation with endocannabinoids is similar to that of the opium-like compounds in the body, known as endorphins, that produce pain-relieving effects.

On the basis of these recent research findings, it has been hypothesized that MS may involve some abnormality in the THC-like chemicals in the body (9,10). Since cannabinoids act on both the nervous system and immune system, it is possible that an abnormality in the cannabinoid system could have widespread effects on both the nervous system and immune system, which is what is observed in MS. Further research is needed to determine if there is any validity to this hypothesis.

The Nervous System, Marijuana, and MS

In spite of a clear scientific rationale for using marijuana to treat MS symptoms and multiple reports of marijuana's beneficial effects in MS, there is a paucity of published clinical research in this area. Furthermore, none of the published studies have been large, well-designed clinical trials, and, consequently, definitive conclusions cannot be made. In some of the limited studies that have been reported, suggestive positive results have been obtained. These studies have used smoked marijuana as well as the pill forms, dronabinol (Marinol) and nabilone (Cesamet).

Promising results have been obtained in studies of spasticity, a type of muscle stiffness that occurs in MS. The muscle relaxant effects of marijuana were actually noted in the mid-nineteenth century in a medical report published by an Irish physician, Dr. William O'Shaughnessy (12). More recently, multiple studies indicate that marijuana and other cannabinoids may be effective in decreasing MS-related spasticity (3,13,14). The studies of marijuana and spasticity have not compared the effectiveness of marijuana to that of prescription medications for spasticity. A recent objective review of marijuana by the National Academy of Sciences/Institute of Medicine (NAS/IOM) concluded that marijuana may improve MS-associated spasticity (15).

Another symptom that may be relieved by marijuana is pain. Although there are no clinical studies that have specifically evaluated the effects of cannabinoids for MS-related pain, there are theoretical reasons why cannabinoids could relieve nerve-related pain. Also, limited studies of pain in people with other conditions and in experimental animals indicate that cannabinoids may have pain-relieving properties (13,16-19).

Variable results have been obtained in studies of other MS symptoms. Limited studies suggest possible improvement in tremor and bladder problems (3,13,14). In a study of one person with MS with jerky eye movements known as "nystagmus," marijuana produced beneficial effects on three occasions while nabilone (Cesamet) and cannabis oil pills were not effective (20). Other MS symptoms have not shown a clear benefit in human studies. Importantly, marijuana may actually worsen walking unsteadiness (21).

In addition to this limited clinical research, two other types of studies have contributed information in this area. First, studies have evaluated the effects of cannabinoids on an experimental form of MS in research animals. Cannabinoids significantly decrease both tremor and spasticity in these animals (22). Second, to assess possible beneficial effects and patterns of use of marijuana in people with MS, a large survey was conducted in the late 1990's in the United Kingdom and in the United States (23). In this study, 112 responses were obtained from questionnaires that were sent to 255 people with MS who used marijuana. More than 90% of the respondents felt that marijuana improved spasticity, pain, tremor, and depression. Improvement was noted by 70-90% for anxiety, tingling, numbness, weight loss, and leg weakness. On average, people had smoked marijuana for nearly six years, and marijuana was used almost three times daily for five-six days each week. There are significant limitations of this survey; it involved self-reporting of information, more than half of the questionnaires were not returned, and it was given to people who were already using marijuana.

The Immune System, Marijuana, and MS

As noted, cannabinoids interact with specific cells in the immune system (9-11,24). This interaction leads to decreased immune system activity. Since MS is characterized by excessive immune system activity, it is possible that the effects of cannabinoids could help slow down the disease process in MS. Indeed, in an experimental form of MS, multiple studies indicate that animals treated with cannabinoids have less brain inflammation and less severe disease symptoms (25,26). There have not been any human studies of the effect of marijuana or cannabinoids on the course of MS.

Other Possible Therapeutic Effects of Marijuana

The 1999 report from the National Academy of Sciences/Institute of Medicine (NAS/IOM) stated that marijuana or THC may be effective in the treatment of some forms of pain, nausea associated with chemotherapy, and weight loss associated with AIDS and cancer (15). Dronabinol (Marinol), the prescription form of THC, is medically indicated for chemotherapy-induced nausea and for AIDS-associated weight loss (27). Some studies also indicate that it may decrease pressure within the eye in people with glaucoma (28).

One moving account of marijuana's effects on nausea has been given by Stephen Jay Gould, the well-known Harvard biologist and author, who experienced severe nausea when he was treated with cancer chemotherapy in the early 1980's. He writes:

"I had surgery, followed by a month of radiation, chemotherapy, more surgery, and a subsequent year of additional chemotherapy. . . when I started intravenous chemotherapy (Adriamycin), absolutely nothing in the available arsenal of antiemetics worked at all. I was miserable and came to dread the frequent treatments with an almost perverse intensity. . . marijuana worked like a charm. I disliked the 'side effect' of mental blurring (the 'main effect' for recreational users), but the sheer bliss of not experiencing nausea-and then not having to fear it for all the days intervening between treatments-was the greatest boost I received in all my year of treatment, and surely had a most important effect upon my eventual cure."(29)

Risks and Drug Interactions

Although THC itself has low short- and long-term toxicity, this does not appear to be the case for smoked marijuana (30). Smoked marijuana poses a variety of significant health risks, one of the most concerning of which is cancer. Marijuana smoke, like tobacco smoke, contains cancer-causing chemicals known as carcinogens. These toxic chemicals are present in the "tar" of marijuana smoke. By some estimates, marijuana smoke contains 50% more carcinogens than does tobacco smoke. There are anecdotal reports of marijuana smokers who have developed cancer of the lung or head and neck region at relatively young ages (31,32). Limited studies suggest that marijuana use may also increase the riskof other forms of cancer (33).

Various methods have been proposed to decrease the risk of cancer with marijuana smoking (30). An inhaled aerosol spray form has been developed and is currently being studied (19). "Vaporizers" are available, but there is little information about the relative amounts of THC and tar produced by these devices. It has been proposed that it might be possible to decrease the cancer risk by developing low-tar strains of cannabis plants or using specially designed filters (30).

Until safer methods are actually developed and are readily available, one technique that may be helpful for regular users is to smoke marijuana that contains a high concentration of THC. By using this type of marijuana, adequate blood concentrations of THC may be obtained with fewer puffs and thus less exposure to the potentially harmful smoke (30).

There are other risks related to marijuana smoking (6,30,34). Marijuana use has been associated with impaired lung function and increased risk of heart attack (35). Neurologically, marijuana may increase the risk of seizures and may produce memory difficulties, confusion, incoordination, and walking unsteadiness(21). Importantly, marijuana may decrease reaction time and thereby impair driving ability for up to eight hours after use. Although marijuana is not often thought of as an addictive drug, it is becoming increasingly apparent that regular marijuana users may indeed become dependent on it. Significant psychiatric conditions, such as schizophrenia, may be worsened by marijuana. Marijuana may lead to poor outcomes during pregnancy; since THC is excreted in breast milk, marijuana use should also be avoided during breast-feeding.

There is little information about how marijuana interacts with other drugs, particularly those that are used frequently in MS. Marijuana may increase the sedating effects of medications or alcohol. Also, there is one case of mania, a state of excessive arousal and excitability, that occurred when marijuana was taken in combination with fluoxetine (Prozac) (6).

Given all of marijuana's possible adverse effects, how could it possibly be considered for legalization or for medical use? It is sometimes argued that society should be more tolerant of marijuana since it is already tolerant of alcohol and tobacco, two recreational drugs that carry health risks that are similar to or greater than those of marijuana (30).

In its objective evaluation of the medical and scientific literature, the 1999 report by the National Academy of Sciences/Institute of Medicine (NAS/IOM) strongly cautioned against the long-term use of smoked marijuana, advised that prescription medications are available for many of the conditions treated with marijuana, and proposed that non-smoking methods be developed for using marijuana (15). The report concluded:

"Marijuana is not a completely benign substance. It is a powerful drug with a variety of effects. However, except for the harms associated with smoking, the adverse effects of marijuana use are within the range of effects tolerated for other medications."

Unfortunately, the long-term health concerns associated with smoked marijuana significantly limit its use for treating a chronic disease like MS. This is a significant obstacle. The long-term effects of marijuana are less significant for some other medical conditions. For example, with cancer chemotherapy, marijuana may be used on a short-term basis and thus long-term risks are not an issue. Similarly, for advanced AIDS and cancer, marijuana's long-term effects may not be relevant because of limited life expectancy and other more imminent medical issues.

Current Studies of Marijuana and MS

Due to the promising effects of marijuana on some MS symptoms and the lack of well-designed studies to date, large clinical studies have recently been undertaken in the United Kingdom (36,37). One study, which is supported by the United Nations and the Royal Pharmaceutical Society, is evaluating the effects of cannabis oil and dronabinol (Marinol) on MS-related spasticity. Unlike the past studies of marijuana, this study is a large well-designed clinical trial that will involve 300-400 people with MS. Another large recent study in the United Kingdom is evaluating the effects of cannabis oil and dronabinol (Marinol) on several types of pain, including MS-related pain. It is hoped that these clinical studies will provide more definitive answers about the effects of marijuana on MS-related spasticity and pain.

"Medical Marijuana" Laws

In the United States, there is a movement for states to legalize marijuana use for specific medical purposes (38,39). In 1996, California and Arizona passed "medical marijuana" laws. Subsequently, similar laws were passed by the District of Columbia and several other states (Alaska, Colorado, Hawaii, Maine, Nevada, Oregon, and Washington). However, many issues regarding these state laws remain unresolved, especially after the recent Supreme Court decision issued on May 14, 2001, United States v. Oakland Cannabis Buyers' Cooperative. (To see the actual text of the opinion click here). In that case, the Court held that there was no medical necessity exception to the federal laws that prohibit the manufacture or distribution of marijuana. Thus, despite various state laws authorizing the medical use of marijuana, it continues to be a federal crime to manufacture, distribute, or dispense of marijuana for any reason. Other legal issues remain unresolved for both people with MS and for physicians, who are sometimes required to document that a person may benefit from the use of marijuana.

In Canada, similar issues are being debated (40). At the federal level, tolerance for medical marijuana appears to be higher in Canada than in the United States. In the last few years, more than 250 Canadians have been given government permission to smoke marijuana for medical reasons. Also, the government is now in the final stages of developing regulations that will lead to the licensing of marijuana growers.

Conclusion

Consideration of the use of marijuana for MS and other medical conditions is complex. It is an error to be dogmatic in this area. In attempts to make strong "pro" or "con" arguments, there is frequent misuse of the results of scientific and clinical studies. Policies and opinions must consider inconclusive medical information within the context of legal standards, societal values, and individual freedom.

Limited research studies suggest that marijuana may improve MS-associated spasticity, pain, and other symptoms. At the same time, however, it must be recognized that these clinical findings are not definitive and that smoked marijuana may cause significant side effects. Further scientific and clinical research on marijuana and marijuana-related chemicals is needed. In the United States, important legal issues have yet to be resolved at the state and federal level.

If marijuana is used, this use should be discussed with a physician and the user should be aware that there are prescription medications for many MS symptoms and that marijuana use for any purpose is illegal in most states and many other countries.

References

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