Movement Disorders

Movement Disorders are a group of neurological diseases which is thought to be caused by defects in the basal ganglia, clusters of nerve cells in the brain that control muscular activity.
Injury to these regions ultimately affects the motion of muscles in the face, limbs, and trunk. The movement disorders most often discussed as candidates for marijuana based therapies are dystonias, Huntington's disease, Parkinson's disease and Tourette's syndrome. As a general consideration, it is important to note that stress and anxiety tend to worsen the symptoms of movement disorders. Thus, marijuana's calming effect could be a primary reason why some patients claim that it brings them relief.

Dystonias are a subgroup of movement disorders that share similar symptoms: slow, sustained, involuntary muscle contractions that often cause sufferers to hold their limbs, trunks, or necks in odd positions. They may be confined to one part of the body; for example, spasmodic torticollis affects only the neck, while Meige's syndrome distorts the face. These chronic, slowly progressive disorders are often painful and can cause mild to severe disability. Some dystonias are inherited, while others occur as side effects of certain drugs. Scientists have yet to discover the specific neurological malfunctions that cause dystonias.

Several different drugs are used to treat various forms of dystonia. The most commonly prescribed drugs—benzodiazepines, baclofen, Botulinum toxin, anticholinergic agents, and tetrabenazine—merely relieve the symptoms of dystonia rather than resolving the condition itself. In many cases the relief they provide is incomplete. Baclofen (Lioresal) and benzodiazepines, including diazepam (Valium) and clonazepam (Klonopin, Rivotril), act by reducing the nervous system's ability to stimulate muscle contractions. Both drugs usually make patients drowsy and may also cause a range of additional side effects, including muscle weakness and behavioral problems. Botulinum toxin—a bacterial compound that also causes food poisoning—also blocks muscle stimulation; it produces few side effects but must be injected directly into the affected muscles. Anticholinergic drugs such as trihexyphenidyl (Artane) and diphenhydramine (Benadryl) deactivate muscle contractions; they, too, cause drowsiness and other side effects that can become severe at high doses. Tetrabenazine, although not available in the United States, is a dopaminedepleting compound available in Canada and Europe that is often prescribed for the relief certain types of dystonia.

No controlled study of marijuana in patients with dystonia has yet been published. Cannabidiol, a chemical component of marijuana (see Chapter 2), was tested in a preliminary open trial in which patients knew they were receiving the experimental drug. The five participants showed only modest improvements, which increased with the amount of drug they received.1 Better results occurred in a study of an animal model for dystonia —a mutant strain of hamsters—in which researchers tested a synthetic cannabinoid that activates the same cellular receptors as THC. The hamsters exhibited a type of dystonia that produces either sudden spasms of rapid, jerky motions or slow, repetitive writhing movements, both of which decreased under the influence of the cannabinoid.2

Besides being a diagnosis in its own right, dystonia is also a symptom of other major movement disorders, including Huntington's disease. This inherited disorder usually manifests itself in middle age, continues to worsen, and ultimately leads to death within 15 years of its appearance. Symptoms include rapid, uncontrolled muscle movements (called “chorea, ” from the Greek word for dance), emotional disturbance and eventually dementia. Patients may take drugs, including reserpine or haloperidol, mainly to control their psychological symptoms. All of these medicines produce adverse side effects, so physicians often wait to prescribe them until a patient's symptoms become severe.

Since anxiety and stress appear to worsen involuntary movements in many patients with Huntington's disease and since marijuana reduces those feelings in most users, some have proposed it as an alternative to existing medications. Animal studies suggest that cannabinoids might suppress choreic movements, presumably by stimulating receptors in the basal ganglia (see Chapter 2). In a preliminary study of four people with Huntington's disease, one patient showed improvement under the influence of cannabidiol.3 Based on this limited success, researchers attempted a double-blind crossover study (see Introduction to Part II for a discussion of clinical study design) on 15 patients who were not taking medications to inhibit chorea but found that participants ' symptoms neither improved nor worsened after treatment with cannabidiol. 4 These results are perhaps to be expected, though, since cannabidiol does not bind to the predominant type of cannabinoid receptor (CB1) on neurons affected by Huntington's dis-ease. THC or other cannabinoids that readily bind CB1 receptors seem likelier candidates as medications for Huntington 's disease, but their effects on patients with the disorder remain unknown.

One of the most devastating movement disorders, Parkinson's disease, affects approximately 1 million Americans age 50 and older. Symptoms include tremor, muscular rigidity, instability, and impeded motion (both slowed movement and abrupt stopping in midmovement). The single most effective drug to treat Parkinson's disease, levodopa (L-Dopa, Larodopa, Dopar), has many drawbacks, so physicians tend to reserve it for functionally impaired patients. After several years of use, levodopa tends to wear off quickly after each dose, so patients constantly cycle through phases of mobility and disability. Additional side effects include nausea, hallucination, and confusion. Researchers also suspect that, while levodopa dramatically improves all of the signs and symptoms of Parkinson's disease, its use may accelerate the disease's progress; no clinical evidence confirms this concern.

Because they act on the same neurological pathways that Parkinson 's disease disrupts, cannabinoids could in theory be useful in treating the disorder (see Chapter 2). The IOM team found only one published account of a clinical trial of marijuana for Parkinson's disease. The study was prompted by a patient's report that smoking marijuana reduced tremor, but when researchers tested the drug on five additional patients with tremor, they found no evidence of improvement. On the other hand, conventional medications, including levodopa, successfully reduced tremor in all five patients.5

Unlike Huntington's and Parkinson's diseases, Tourette's syndrome typically appears during childhood. Patients exhibit a variety of rapid, involuntary, repetitive movements and vocalizations, collectively called tics. The causes of Tourette's syndrome are largely unknown but are thought to impair brain areas that convert a person's intent to move into actual movements. Damage to these same areas produces involuntary movement in Huntington's disease and restricts voluntary movement in Parkinson's disease.

Two widely used medications for Tourette's syndrome, pimozide (Orap) and haloperidol (Haldol) inhibit the effects ofthe neurotransmitter dopamine. Cannabinoids, by contrast, increase dopamine release, so one might predict that cannabinoids would actually exacerbate the symptoms of Tourette's syndrome. Yet four clinical case histories indicate that marijuana use can reduce tics in Tourette 's patients. In three of the four cases, however, the investigators suggest that marijuana's anxiety-reducing properties—rather than any specific effect on the neural pathway that produces tics—caused the patients' symptoms to improve.6

In summary, while persuasive basic evidence exists for the role of cannabinoids in movement, clinical evidence for their usefulness in relieving the symptoms of movement disorders is lacking. The few existing studies were performed on small numbers of patients and without consideration that marijuana's antianxiety effects might reduce the symptoms in question. Moreover, while there are a few isolated anecdotal reports that marijuana helps patients with these disorders, there are no surveys to suggest that these patients' experiences are at all representative.

Thus, with the possible exception of spasticity in multiple sclerosis, there is little reason to recommend additional clinical trials of marijuana or cannabinoids for movement disorders, the IOM study team concluded. That is not to say that more extensive animal studies will never provide stronger evidence in favor of human trials. But until reliable animal models exist for most movement disorders, such evidence is unlikely to be forthcoming. In the meantime the IOM team recommends conducting double-blind, placebo-controlled clinical trials of individual cannabinoids such as THC—but not smoked marijuana—for the treatment of movement disorders.

The IOM team further specified that these trials should test the effects of cannabinoids on movement alone—that is, the experiments should distinguish cannabinoids' effects on movement from their effects on anxiety or mood. For if cannabinoids merely provide a psychological boost to people with multiple sclerosis, their use would probably not warrant the risk of short-term memory loss, cognitive impairment, and other known side effects. But if cannabinoids directly improve spasticity and other movement-related symptoms, as well as mood, they would offer a uniquely useful treatment. Cannabinoids therefore represent an

Dystonia and Cannabis

Dystonia is a neurological movement disorder characterized by sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning (e.g., lead poisoning) or reaction to pharmaceutical drugs, particularly neuroleptics.

It is the third most common movement disorder after Parkinson's disease and tremor, affecting more than 300,000 people in North America.Treatment is difficult and has been limited to minimizing the symptoms of the disorder, since there is no cure available.

Symptoms vary according to the kind of dystonia involved. In most cases, dystonia tends to lead to abnormal posturing, particularly on movement. Many sufferers have continuous pain, cramping and relentless muscle spasms due to involuntary muscle movements. Other motor symptoms are possible including lip smacking.

Early symptoms may include loss of precision muscle coordination (sometimes first manifested in declining penmanship, frequent small injuries to the hands, and dropped items), cramping pain with sustained use and trembling. Significant muscle pain and cramping may result from very minor exertions like holding a book and turning pages. It may become difficult to find a comfortable position for arms and legs with even the minor exertions associated with holding arms crossed causing significant pain similar to restless leg syndrome.

Affected persons may notice trembling in the diaphragm while breathing, or the need to place hands in pockets, under legs while sitting or under pillows while sleeping to keep them still and to reduce pain. Trembling in the jaw may be felt and heard while lying down, and the constant movement to avoid pain may result in the grinding and wearing down of teeth, or symptoms similar to TMD. The voice may crack frequently or become harsh, triggering frequent throat clearing. Swallowing can become difficult and accompanied by painful cramping.

Treatment has been limited to minimizing the symptoms of the disorder as there is yet no successful treatment for its cause. Reducing the types of movements that trigger or worsen dystonic symptoms provides some relief, as does reducing stress, getting plenty of rest, moderate exercise, and relaxation techniques. Various treatments focus on sedating brain functions or blocking nerve communications with the muscles via drugs, neuro-suppression or denervation. All current treatments have negative side effects and risks.

A small number of case reports and preclinical studies investigating the use of cannabis and cannabinoids for symptoms of dystonia are referenced in the recent scientific literature. A 2002 case study published in the July issue of the The Journal of Pain and Symptom Management reported improved symptoms of dystonia after smoking cannabis in a 42-year-old chronic pain patient.

Investigators reported that subject’s subjective pain score fell from 9 to zero (on a zero-to-10 visual analog scale) following cannabis inhalation, and that the subject did not require any additional analgesic medication for the following 48 hours. "No other treatment intervention to date had resulted in such dramatic overall improvement in [the patient's] condition," investigators concluded.

Also in 2004, a German research team at the Hannover Medical School reported successful treatment of musician’s dystonia in a 38-year-old professional pianist following administration of 5 mg of THC in a placebo-controlled single-dose trial. Investigators reported “clear improvement of motor control” in the subject’s affected hand, and noted, “[Two] hours after THC intake, the patient was able to play technically demanding literature, which had not been possible before treatment.”

Prior to cannabinoid treatment, the subject had been unresponsive to standard medications and was no longer performing publicly. “The results provide evidence that … THC intake … significantly improves [symptoms of] … focal dystonia,” investigators concluded.

At least one recent preclinical trial indicates that both synthetic cannabinoids as well as high doses of the natural non-psychoactive cannabinoid cannabidiol (CBD) could moderate the disease progression of dystonia in animals. Limited references regarding the use of cannabinoids for dystonia in humans and animals in the 1980s and the 1990s also appear in the scientific literature. It would appear that additional, larger clinical trials are warranted to investigate the use of cannabis and cannabinoids for this indication.