Coping with stiff, aching, cramping muscles is a way of life for most of the 2.5 million people in the world who have multiple sclerosis. Many of the 15 million people with spinal cord injuries also suffer from the same symptoms, which cause pain, limit movement, and rob people of needed sleep. Although several conventional medications can reduce these patients' discomfort, taking them rarely provides complete relief. Often the drugs cause weakness, drowsiness, and other side effects that some patients find intolerable.
Given this outlook, it is not hard to understand why some people with multiple sclerosis and spinal cord injuries have sought relief through marijuana. Several such patients told the IOM team that their muscle spasms decreased after smoking marijuana (see Chapter 2). Some also said they valued the drug because it relieved nausea or helped them sleep. Likewise, in a 1982 survey of people with spinal cord injuries, 21 of 43 respondents reported that marijuana reduced muscle spasticity 1 (a condition in which muscles tense reflexively and resist stretching), while nearly every participant in a 1997 survey of 112 regular marijuana users with multiple sclerosis replied that the drug lessened both pain and spasticity. 2 This is not to say that most people with multiple sclerosis find relief with marijuana but only that the marijuana users among them do. Animal research, too, suggests that marijuana calms muscle spasticity. Spasms are thought to originate in areas of the brain that control movement, including several sites with abundant cannabinoid receptors.
In one experiment, researchers found that rodents became more animated under the influence of small amounts of cannabinoids but less active when they received larger doses. Many marijuana users also note that the drug affects movement, making their bodies sway and their hands unsteady. The exact mechanism(s) by which cannabinoids exert these effects remains unknown. Despite these suggestive findings and the depth of anecdotal evidence, marijuana's antispasmodic properties remain largely untested in the clinic. The few existing reports are extremely limited in scope; for example, none of the studies discussed in this chapter included more than 13 patients, and some were conducted on a single patient. Also, in several cases the patients' subjective evaluations of improvement contrasted with objective measures of their physical performance. Still, the lack of good universally effective medicine for muscle spasticity is a compelling reason to continue exploring cannabinoid drugs in the clinic. Multiple sclerosis (or MS) is a progressive disease of the nervous system with no known cure. It appears to result from a malfunction of the immune system, which inflames nerves in the brain, brain stem, and spinal cord. Specifically, the disease destroys the protective coating called myelin that sheaths the neural fibers like insulation on electrical wire. Without an intact myelin layer, nerve cells lose some or all of their ability to transmit impulses. This situation produces an array of symptoms, including fatigue, depression, vertigo, blindness, incontinence, and loss of voluntary muscle control, as well as muscle spasticity. MS is characterized by scarring—“sclerosis”—that occurs in the white matter of the central nervous system after nerves and myelin are lost. Approximately 90 percent of MS patients develop spasticity. Some people experience this condition merely as muscle stiffness; others endure constant ache, cramps, or involuntary muscle contractions (spasms) that are both painful and debilitating. These spasms often affect the legs and can disrupt sleep. Most people with MS experience intermittent “attacks” of spasticity that become increasingly disabling the longer they have the disease. In the worst cases, patients become partially or even completely paralyzed. The drugs most commonly prescribed to treat the symptoms of MS include baclofen (Lioresal) and tizanidine (Zanaflex) which relieve both spasticity and muscle spasms but often only partially and sometimes not at all. Both are sedatives, so they cause drowsiness; additional side effects include dry mouth and muscle weakness. The latter is especially problematic for people with MS, whose muscles get weaker as the disease progresses. Both marijuana and THC have been tested for their ability to relieve spasticity in small but rigorous clinical studies. One double-blind experiment (see Introduction to Part II for an explanation of double-blind methods) included both MS patients and unaffected individuals. 3 Before and after smoking a single marijuana cigarette that contained approximately 15 milligrams of THC—enough to make most people feel “high” and to impair their motor control—patients were videotaped as they stood on a platform that slid back and forth at unpredictable times.
The researchers then measured participants' shoulder movements as an index for how well they kept their balance. Participants with MS often thought that their symptoms had improved after smoking marijuana. But while their spasticity may indeed have decreased (it was not measured), their posture and balance were actually impaired; this was also the case with the 10 participants who did not have MS. The MS patients had greater difficulty maintaining their balance before smoking and were more negatively affected by marijuana than the healthy participants. While the fact that every MS patient in the previous study experienced relief is intriguing, it does not constitute strong evidence that marijuana relieves spasticity because marijuana-induced euphoria or pain relief might decrease patients' perceptions of muscle stiffness or spasticity. The same is true of respondents to the surveys described earlier. Moreover, surveys cannot measure the degree to which respondents feel better simply because they expect to do so. Such placebo effects are signifi cant; for example, in controlled trials of pain medications, as many as 30 percent of the participants who received a placebo reported feeling relief.
This does not mean that placebo effects are not “real.” It is possible that the psychological effects of taking a placebo drug cause physiological changes in the brain. But it does mean that the effects are not directly due to the medication being tested. THC's effects on spasticity were tested in three separate clinical studies, which together enrolled a total of 30 MS patients. 4 All three were open trials in which participants knew they would be receiving THC.