While most conventional medications reach the public only after an extensive process of development and testing (see Chapter 10), medical knowledge concerning marijuana's potential benefits and risks has accumulated largely through its widespread use. As mentioned in the previous chapter, a recent poll indicates that approximately one in three Americans over age 12 have tried marijuana or hashish at least once, although only about one in 20 currently use these drugs.
Medical scientists know far more about marijuana's adverse effects than about its ability to relieve specific symptoms, mainly because of the difficulties of conducting clinical research on marijuana. In addition to securing financial support for their research, medical scientists who study marijuana must demonstrate their compliance with a multitude of federal and state regulations before carrying out their investigations (see Chapter 11). Thus, despite recent discoveries highlighted in Chapter 2, substantial clinical studies on the medicinal properties of marijuana remain scarce.
Yet clinical experiments must be undertaken to determine whether marijuana-based medicines live up to their promising performance in numerous basic science studies. Before any medication can be approved for sale by the U.S. Food and Drug Administration, it must pass a series of clinical trials to assure that it is both safe and effective. The trials, which are conducted on healthy volunteers and qualified patients, allow scientists to predict how drugs will perform in the general population.
In a well-designed clinical trial, patients are assigned to treatment groups in such a way that any possible biases in outcome are removed. For example, to compare two medications for nausea, the group of patients being treated with each drug should contain people of equivalent age, gender, and health status. Another approach to providing matched samples is the use of a “crossover” design in which all patients receive both the experimental drug and a placebo in random order.
Clinical trials should also be designed to eliminate the effects of both the patients' and the researchers' expectations concerning the results of the trial. Consider the patient who tries an experimental antinausea drug with the expectation that it will work.
She is far more likely to feel relief after taking the medicine than a patient who does not know if the pill she swallowed contains an active compound, a phenomenon known as the placebo effect. Similarly, knowing whether a patient received the drug or a placebo would likely influence a researcher's evaluation of that patient. For these reasons many clinical studies are designed to be double blind, that is, neither the patient or the researcher knows what treatment the patient has received.
In addition to well-matched treatment groups and double blinding, a good-quality clinical trial also incorporates controls for other factors unrelated to the drug being tested but that nonetheless may influence the treatment outcome. For example, THC reduces anxiety in some people to the extent that they mistakenly believe their symptoms have improved. Although anxiety reduction may be a valuable form of treatment for some patients, it also interferes with attempts to determine whether THC relieves specific symptoms. Successful clinical trials must therefore eliminate this influence—for example, by comparing the effect of THC on a particular symptom with that of a drug known to reduce anxiety but not the specific symptom being studied.
While double-blind, randomized, controlled clinical trials are the best way to evaluate a drug's effectiveness, such trials are not always feasible. For example, children, women of childbearing age, and the elderly are often excluded from experimental drug trials for safety reasons, yet patients in all of these groups take prescription medications. To get around this problem, medical scientists sometimes conduct single-patient trials in which individuals—including patients from vulnerable populations—are treated sequentially with several different medications or are given alternating doses of an experimental drug and a placebo. Although limited in scope, single-patient trials can permit objective comparisons between treatments.
The next six chapters describe scientists' initial attempts to test the safety and effectiveness of marijuana and cannabinoid drugs in the treatment of human patients. The discussion is limited to research on conditions that marijuana has been most often claimed to help, such as pain, AIDS, cancer, and muscular spasticity. Other sources, particularly recent books by Grinspoon and Bakalar and Mathre,1 discuss indications for marijuana beyond
those described here. Most of these less common uses of medical marijuana, such as in patients with Crohn's disease and asthma, are based on a few anecdotal reports. However, since many different disorders share symptoms such as pain, nausea, and muscle spasms, it is possible that a wide variety of patients may be helped by medicines derived from marijuana.
All of the clinical trials we discuss share a common characteristic: they are intended to test whether marijuana or cannabinoids can improve specific symptoms, not whether marijuana-based medicines can cure disease. Although marijuana 's potential usefulness appears to be limited entirely to relieving discomfort, preliminary evidence indicates that it can provide relief to at least some patients.
Taken as a whole, the results of both basic research and clinical research on marijuana and cannabinoids suggest a variety of potential applications for marijuana-based medicines. Cannabinoids appear to be especially strong candidates for use in pain relievers, antinausea drugs, and appetite stimulants—or perhaps in broad-spectrum medications designed to treat all of these symptoms simultaneously, as they occur in AIDS patients and people undergoing chemotherapy for cancer. Most encouraging marijuana-related clinical studies reflect the therapeutic potential of a single cannabinoid: THC, the primary psychoactive ingredient in marijuana.
Weaker but still favorable scientific evidence supports the use of cannabinoids to treat muscle spasticity in patients with multiple sclerosis or spinal cord injury. The least promising indications discussed here include movement disorders, epilepsy, and glaucoma; nevertheless, animal experiments on movement disorders appear favorable enough to warrant continued exploration in the clinic.
1. Grinspoon L, Bakalar JB. 1997. Marijuana: The Forbidden Medicine. New Haven, CT: Yale University Press; Mathre ML, ed. 1997. Cannabis in Medical Practice. Jefferson, NC: McFarland.