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Federal government websites often end in. Before sharing sensitive information, make sure you're on a federal government site. The site is secure. NCBI Bookshelf. Mack A, Joy J. Marijuana as Medicine? The Science Beyond the Controversy. Coping with stiff, aching, cramping muscles is a way of life for most of the 2. 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 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 survey of regular marijuana users with multiple sclerosis replied that the drug lessened both pain and spasticity. 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. 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. 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. 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. 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. Perhaps not surprisingly, most of the patients—or in one case the investigators who examined them—reported that treatment with THC improved their symptoms see Figure 7. The drug was not effective for all patients, however, and frequently caused unpleasant side effects. Effect of THC on tremor caused by multiple sclerosis. In this experiment, a 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. 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. Effect of nabilone on multiple sclerosis symptoms. This chart shows the results of a trial in which a 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. 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. Two factors complicate the design of such trials. 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. Second, human trials should rule out any masking or enhancing effect of anxiety reduction due to THC, since anxiety worsens spasticity in many patients. If THC or a related compound does prove to relieve spasticity, it would make sense for some patients to take the drug orally. In this way patients could take advantage of THC's ability to remain active in the body for several hours. People with spinal cord injury, whose symptoms vary little throughout the day, could get extended relief from a pill taken at bedtime or in the morning. On the other hand, MS patients might find more use for an inhaled form of THC to relieve their more intermittent symptoms. Unlike pills, this delivery method would allow patients to feel the drug's effects quickly and with a minimum of sedation. At nighttime MS patients might actually prefer pills that cause drowsiness as well as relieve spasticity. People with MS may soon be able to test a cannabinoid inhaler if the previously described British clinical trials receive funding. Additional trials may take place in Canada, where in July the government issued a request for research proposals to study medical uses of marijuana. While the official announcement did not prescribe specific research topics, it mentioned multiple sclerosis as a possible subject for a clinical trial. Clifford DB. Turn recording back on. Help Accessibility Careers. Show details Mack A, Joy J. Search term. Footnotes 1. Copyright by the National Academy of Sciences. All rights reserved. In this Page. Recent Activity. Clear Turn Off Turn On. Follow NCBI.
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PTX causes marked molecular and cellular damage, mainly in the peripheral nervous system, including sensory neurons in the dorsal root ganglia DRG. Several studies have shown the therapeutic potential of cannabinoids, including cannabidiol CBD , the major non-psychotomimetic compound found in the Cannabis plant, to treat peripheral neuropathies. PECS did not alter motor coordination, produce tolerance, or show abuse potential. Publication types Research Support, Non-U.
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