Effect of THC on tremor caused by multiple sclerosis. In this experiment, a 30-year-old man with multiple sclerosis who suffered from a disabling tremor was treated with 5 milligrams of THC. Researchers compared the man's handwriting and head movement (more. ) Objective measurements of patients' symptoms in these studies were often at odds with their subjective reports. In one study researchers measured muscle tremor with a mechanical device, which showed detectable change in only two of eight patients, seven of whom had reported improved symptoms.
5 In another study standardized physician's measures showed that treatment with THC had not produced any changes in spasticity despite reports of reduced spasticity by 11 of 13 patients. 6 It may be that the measuring techniques used in both studies were not sensitive enough to detect subtle improvements. It is also possible that patients' reports of symptom improvement were influenced by placebo effects or by effects of THC, such as anxiety reduction, that are only indirectly related to spasticity. Neither possibility can be ruled out due to the small size of these studies. In addition to these experiments on THC, a single patient who tested the THC analog nabilone—a synthetic compound that activates the same cellular receptors as THC—also reported an improvement in spasticity as well as in other MS symptoms (see Figure 7.2). This chart shows the results of a trial in which a 45-year-old man with MS received treatments with the THC analog nabilone, alternating with a placebo. While the results suggest that THC might relieve (more.
) These clinical results are considerably less dramatic than survey and anecdotal reports of marijuana's effectiveness in relieving muscle spasms. It is possible, however, that a series of larger, better-designed clinical trials would produce stronger evidence in favor of marijuana-based medicines for MS. At this writing such studies are in the planning stages in Britain, where a large proportion of medical marijuana users are people with MS. For example, researchers have proposed a clinical trial to compare the effectiveness of three types of treatment for MS: marijuana extract, delivered by inhaler; dronabinol (Marinol); and placebo. Clinical trials usually require preliminary experiments on animal models of a disease, which enable researchers to predict its effects on humans. With that knowledge scientists can then design trials that accurately measure the ability of the drug to relieve patients' symptoms. Existing animal models mimic some MS symptoms, but so far none have succeeded in duplicating spasticity. But researchers can use the best-available indicator of the condition, known as the pendulum test, to study the effectiveness of antispasticity drugs in human subjects. Participants in this test lie on an examining table with their legs extending over the edge. They let their legs fall, and a video camera records the resulting motion, which is affected by muscle resistance. Computer analysis of the recording enables researchers to determine the degree to which spasticity impeded each patient's movement. Since THC is mildly sedating it is important to distinguish this effect from any actual decrease in spasticity produced by the drug. Researchers could make such a distinction by using the pendulum test to compare THC's effects with those of other mild sedatives, such as benzodiazepines. If an antispasmodic drug is developed from THC, its sedative effect could prove beneficial to MS patients whose muscle spasms interrupt their sleep. Drowsiness at bedtime might be welcome, and any mood-altering side effects might be less of a problem than when the patient was awake. It is also possible, however, that THC might disrupt normal sleep patterns in some people. While the same physiological process causes spasticity in both MS and spinal cord injury, it produces quite different symptoms in the two diseases. People with MS tend to experience occasional “attacks” of intense pain, stiffness, or muscle spasms at unpredictable intervals, while people with spinal cord injuries experience only minor fluctuations and persistent discomfort. Nevertheless, it is very likely that the same drugs could be adapted to treat the two groups of patients. People with MS and those with spinal cord injury alike would benefit from medications that relieve pain, stiffness, and spasms without muscle weakening, which occurs with the best currently available treatments. Because of the harms associated with long-term marijuana smoking, it should be discouraged as a means of treating chronic conditions such as spinal cord injury or MS. Whether marijuana could yield useful medicines for spasticity remains to be determined, for the clinical evidence to date is too sparse to accept. But the few positive reports of the ability of THC and nabilone to reduce spasticity, together with numerous anecdotal accounts from marijuana users with MS and spinal cord injuries, suggest that carefully designed clinical trials testing the effects of cannabinoids on muscle spasticity would be worthwhile.
First, while MS patients report that marijuana relieves spasticity, it negatively affects their ability to balance, exacerbating another symptom of the disorder. It may be that patients would become tolerant to the balance-impairing effects of cannabinoids relatively quickly yet continue to get relief from spasticity.
It might also be possible to separate these effects by creating chemical variants of natural cannabinoids.