04-16-2012, 10:30 PM
Multiple Sclerosis / Muscle Spasms
A.D.A.M. Medical Encyclopedia.
Multiple sclerosis
MS; Demyelinating diseaseLast reviewed: September 26, 2011.
Multiple sclerosis is an autoimmune disease that affects the brain and spinal cord (central nervous system).
Causes, incidence, and risk factors
Multiple sclerosis (MS) affects women more than men. The disorder is most commonly diagnosed between ages 20 and 40, but can be seen at any age.
MS is caused by damage to the myelin sheath, the protective covering that surrounds nerve cells. When this nerve covering is damaged, nerve signals slow down or stop.
The nerve damage is caused by inflammation. Inflammation occurs when the body's own immune cells attack the nervous system. This can occur along any area of the brain, optic nerve, and spinal cord.
It is unknown what exactly causes this to happen. The most common thought is that a virus or gene defect, or both, are to blame. Environmental factors may play a role.
You are slightly more likely to get this condition if you have a family history of MS or live in an part of the world where MS is more common.
Symptoms
Symptoms vary, because the location and severity of each attack can be different. Episodes can last for days, weeks, or months. These episodes alternate with periods of reduced or no symptoms (remissions).
Fever, hot baths, sun exposure, and stress can trigger or worsen attacks.
It is common for the disease to return (relapse). However, the disease may continue to get worse without periods of remission.
Because nerves in any part of the brain or spinal cord may be damaged, patients with multiple sclerosis can have symptoms in many parts of the body.
Muscle symptoms:
Signs and tests
Symptoms of MS may mimic those of many other nervous system disorders. The disease is diagnosed by ruling out other conditions.
People who have a form of MS called relapsing-remitting may have a history of at least two attacks, separated by a period of reduced or no symptoms.
The health care provider may suspect MS if there are decreases in the function of two different parts of the central nervous system (such as abnormal reflexes) at two different times.
A neurological exam may show reduced nerve function in one area of the body, or spread over many parts of the body. This may include:
Is marijuana an effective treatment for spasticity disorders such as multiple sclerosis?
Movement Disorders stated in a Sep. 2004 article titled "Survey on Cannabis Use in Parkinson's Disease" by researchers from the Movement Disorders Centreat the Department of Neurology at Charles University, Prague, Czech Republic: "An anonymous questionnaire sent to all patients attending the Prague Movement Disorder Centre revealed that 25% of 339 respondents had taken cannabis and 45.9% of these described some form of benefit.... The late onset of cannabis action is noteworthy. Because most patients reported that improvement occurred approximately two months after the first use of cannabis, it is very unlikely that it could be attributed to a placebo reaction."
More Pro's and Cons
People with multiple sclerosis and other diseases that cause severe muscle spasms, spasticity and tremors have used cannabis for a very long time, and have consistently reported that it relieves their symptoms. In what is perhaps the earliest medical report on the use of cannabis to treat muscle spasms, Dr. William OShaughnessy, a British physician working in India, reported in 1842 that cannabis extracts effectively controlled the spasticity he observed in cases of tetanus, and in 1890
More
Cannabis has also been shown to be effective in relieving muscle spasms and spasticity associated with a number of other illnesses such as irritable bowel syndrome, premenstrual dysphoric disorder (PMDD) and PMS, cerebral palsy, Parkinsons Disease, amyotrophic lateral sclerosis (Lou Gehrigs disease), spinal cord injury and other nerve injuries, and may also relieve the bronchial spasms that cause asthma, though little formal research has been done on cannabis in any of these conditions.
Alan Shackelford, M.D., graduated from the University of Heidelberg School of Medicine and trained at major teaching hospitals of Harvard Medical School in internal medicine, nutritional medicine and hyperalimentation and behavioral medicine. He is principle physician for Intermedical Consulting, LLC and Amarimed of Colorado, LLC and can be contacted at Amarimed.com.
Article from Culture Magazine and republished with special permission
The question of whether marijuana (Cannabis sativa) should be used for symptom management in MS is a complex one. It is generally agreed that better therapies are needed for distressing symptoms including pain, tremor, and spasticity that may not be sufficiently relieved by available treatments. Yet there are serious uncertainties about the benefits of marijuana relative to its side effects. The fact that marijuana is an illegal drug in many states and by federal statute (see in the News) further complicates the issue.
Some people with MS report that smoking marijuana relieves several of their MS symptoms. However, for any therapy to be recognized as an effective treatment, this kind of subjective, anecdotal reporting needs to be supported by carefully gathered objective evidence of safety and benefit. Unfortunately, it has proven difficult to do carefully controlled clinical trials of marijuana. One reason for this is that marijuana is psychoactive and makes people feel "high." This means that people taking the active drug during a clinical trial usually become aware of it thus "unblinding" the study and possibly biasing results. Studies completed thus far have not provided convincing evidence that marijuana or its derivatives provide substantiated benefits for symptoms of MS.
Conflicting results of previous research, coupled with the need for additional therapies to treat symptoms of MS, make it important that more research be done on the potential of marijuana and its derivatives. The National MS Society is funding a well controlled study on the effectiveness of different forms of marijuana to treat spasticity in MS, and established a task force to examine the use of Cannabis in MS to review what is currently known about its potential. This task force had made specific recommendations on the research that still needs to be done to answer pressing questions about the potential effectiveness and safety of marijuana and its derivatives in treating MS.
Download Recommendations Regarding the Use of Cannabis in Multiple Sclerosis (.pdf)
Early Studies Showed Mixed Results and Some Side Effects
Well known for its mind-altering properties, marijuana is produced from the flowering top of the hemp plant, Cannabis sativa.
Early studies explored the role of THC (tetrahydrocannabinol an active ingredient in marijuana) or smoked marijuana in treating spasticity, tremor, and balance control in small numbers of people with MS. Most of these studies were done with THC. Because THC can be given by mouth, it is easier to control the dose. The results of these studies were mixed, and participants reported a variety of uncomfortable side effects. In addition, smoked marijuana poses health risks that are at least as significant as those associated with tobacco.
For spasticity (unusual muscle tension or stiffness)
Studies of THC for spasticity have had mixed results. While some people reported feeling "looseness" and less spasticity, this could not always be confirmed by objective testing done by physicians. Even at its best, effects lasted less than three hours. Side effects, especially at higher doses, included weakness, dry mouth, dizziness, mental clouding, short-term memory impairment, space-time distortions and lack of coordination.
For tremor (uncontrolled movements)
In a small study of THC involving eight seriously disabled individuals with significant tremor and ataxia (lack of muscle coordination), two people reported improvement in tremor that could be confirmed by an examination by a physician and another three reported improvement in tremor that could not be confirmed. All eight patients taking THC experienced a "high," and two reported feelings of discomfort and unease.
For balance
Smoked marijuana was shown to worsen control of posture and balance in 10 people with MS and 10 who did not have MS. All 20 study participants reported feeling "high."
National Academy of Sciences/ Institute of Medicine Report
A 1999 report by the National Academy of Sciences/Institute of Medicine on the medical uses of marijuana raised additional questions. While the report concluded that smoked marijuana does not have a role in the treatment of MS, there remained the possibility that specific compounds derived from marijuana might reduce some MS symptoms, particularly MS-related spasticity. Well designed and controlled studies of the therapeutic potential of marijuana compounds (called cannabinoids) were indicated, in conjunction with the development of safe, reliable drug delivery technology.
Study on Marijuana Derivatives in Mice
Investigators in the United Kingdom and United States tested the ability of two marijuana derivatives and three synthetic cannabinoids to control spasticity and tremor, symptoms of the MS-like disease, EAE, in mice. The results, published in the March 2, 2000 issue of Nature, suggested that four different cannabinoids could temporarily relieve spasticity and/or tremor. While the study suggested that similar derivatives of marijuana might be developed for human use, it was clear that the psychoactive effects of these cannabinoids would need to be reduced sufficiently to make them a safe and comfortable treatment for people with MS.
<div><iframe width="459" height="344" src="https://www.youtube.com/embed/qgySDmRRzxY?feature=oembed" frameborder="0" allowfullscreen="true"></iframe></div>
Received 18 August 1999;accepted 20 January 2000
References 1.
Baker, D. et al. Induction of chronic relapsing experimental allergic
encephalomyelitis in Biozzi mice. J. Neuroimmunol. 28, 261-270 (1990).
2.
Consroe, P., Musty, R., Rein, J., Tillery, W. & Pertwee, R. The perceived
effects of smoked cannabis on patients with multiple sclerosis. Eur. Neurol.
38, 44-48 (1997).
3.
Consroe, P. Cannabinoid systems as targets for the therapy of neurological
disorders. Neurobiol. Dis. 5, 534-551 (1998). Links
4.
Petro, D. J. & Ellenberger, C. Treatment of human spasticity with 9-
tetrahydrocannabinol. J. Clin. Pharmacol. 21 (suppl.), 413-416 (1981).
5.
Clifford, D. B. Tetrahydrocannabinol for tremor in multiple sclerosis. Ann.
Neurol. 13, 669-671 (1983). Links
6.
Ungerleider, J. T., Andyrsiak, T., Fairbanks, L., Ellison, G. W. & Myers, L.
W. 9-THC in the treatment of spasticity associated with multiple sclerosis.
Adv. Alcohol Substance Abuse 7, 39-50 (1987).
7.
Martyn, C. N., Illis, L. S. & Thom, J. Nabilone in the treatment of multiple
sclerosis. Lancet 345, 579 (1995). Links
8.
Pertwee, R. G. Pharmacology of cannabinoid receptor ligands. Curr. Med. Chem.
6, 635-664 (1999). Links
9.
Lyman, W. D., Sonett, J. R., Brosnan, C. F., Elkin, R. & Bornstein, M. B.
9-tetrahydrocannabinol: a novel treatment for experimental autoimmune
encephalomyelitis. J. Neuroimmunol. 23, 73-81 (1989). Links
10.
Wirguin, I. et al. Suppression of experimental autoimmune encephalomyelitis
by
cannabinoids. Immunopharmacology 28, 209-214 (1994). Links
11.
Heller, A. H. & Hallet, M. Electrophysiological studies with the spastic
mutant mouse. Brain Res. 234, 299-308 (1982). Links
12.
Chai, C. K. Hereditary spasticity in mice. J. Heredity 52, 241-243 (1961).
13.
Pertwee, R. G. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol.
Therapeut. 74, 129-180 (1997).
14.Breivogel, C. S. & Childers, S. R. The functional neuroanatomy of brain
cannabinoid receptors. Neurobiol. Dis. 5, 417-431 (1998). Links
15.
Landsman, R. S., Burkey, T. H., Consroe, P., Roeske, W. R. & Yamamura, H.
I. SR141716A is an inverse agonist at the human cannabinoid CB1 receptor.
Eur. J. Pharmacol. 334, R1-R2 (1997). Links
16.
Portier, M. et al. SR144528, an antagonist for the peripheral cannabinoid
receptor that behaves as an inverse agonist. J. Pharmacol Exp. Ther. 288,
582-589 (1999). Links
17.
Calignano, A., La Rana, G., Giuffrida, A. & Piomelli, D. Control of pain
initiation by endogenous cannabinoids. Nature 394, 277-281 (1998). Links
18.
Giuffrida, A. et al. Dopamine activation of endogenous cannabinoid signalling
in dorsal striatum. Nature Neurosci. 2, 358-363 (1999). Links
19.
Huffman, J. W. et al. 3-(1,1-Dimethylbutyl)-1-deoxy-9-THC and related compounds:
synthesis of selective ligands for the CB2 receptor. Bioorg. Med. Chem. 7,
2905-2914 (1999). Links
20.
Noth, J. Trends in the pathophysiology and pharmacotherapy of spasticity. J.
Neurol. 238, 131-139 (1991). Links
Acknowledgements. The authors would like to thank the Multiple Sclerosis
Society of Great Britain and Northern Ireland, the Medical Research Council,
the National Institute on Drug Abuse and the Wellcome Trust for their
financial support.
Nature Macmillan Publishers Ltd 2000 Registered No. 785998 England.
Smoked Cannabis Reduces Some Symptoms of Multiple Sclerosis
Controlled trial shows improved spasticity, reduced pain after smoking medical marijuana
A clinical study of 30 adult patients with multiple sclerosis (MS) at the University of California, San Diego School of Medicine has shown that smoked cannabis may be an effective treatment for spasticity a common and disabling symptom of this neurological disease.
The placebo-controlled trial also resulted in reduced perception of pain, although participants also reported short-term, adverse cognitive effects and increased fatigue. The study will be published in the Canadian Medical Association Journal on May 14.
Principal investigator Jody Corey-Bloom, MD, PhD, professor of neurosciences and director of the Multiple Sclerosis Center at UC San Diego, and colleagues randomly assigned participants to either the intervention group (which smoked cannabis once daily for three days) or the control group (which smoked identical placebo cigarettes, also once a day for three days). After an 11-day interval, the participants crossed over to the other group.
We found that smoked cannabis was superior to placebo in reducing symptoms and pain in patients with treatment-resistant spasticity, or excessive muscle contractions, said Corey-Bloom.
Earlier reports suggested that the active compounds of medical marijuana were potentially effective in treating neurologic conditions, but most studies focused on orally administered cannabinoids. There were also anecdotal reports of MS patients that endorsed smoking marijuana to relieve symptoms of spasticity.
However, this trial used a more objective measurement, a modified Ashworth scale which graded the intensity of muscle tone by measuring such things as resistance in range of motion and rigidity. The secondary outcome, pain, was measured using a visual analogue scale. The researchers also looked at physical performance (using a timed walk) and cognitive function and at the end of each visit asked patients to assess their feeling of highness.
Although generally well tolerated, smoking cannabis did have mild effects on attention and concentration. The researchers noted that larger, long-terms studies are needed to confirm their findings and determine whether lower doses can result in beneficial effects with less cognitive impact.
The current study is the fifth clinical test of the possible efficacy of cannabis for clinical use reported by the University of California Center for Medicinal Cannabis Research (CMCR). Four other human studies on control of neuropathic pain also reported positive results.
The study by Corey Bloom and her colleagues adds to a growing body of evidence that cannabis has therapeutic value for selected indications, and may be an adjunct or alternative for patients whose spasticity or pain is not optimally managed, said Igor Grant, MD, director of the CMCR, which provided funding for the study.
Additional contributors include Tanya Wolfson, Anthony Gamst, PhD, Shelia Jin, MD, MPH, Thomas D. Marcotte, PhD, Heather Bentley and Ben Gouaux, all from UC San Diego School of Medicine.
Press Release From University Of California, San Diego
A.D.A.M. Medical Encyclopedia.
Multiple sclerosis
MS; Demyelinating diseaseLast reviewed: September 26, 2011.
Multiple sclerosis is an autoimmune disease that affects the brain and spinal cord (central nervous system).
Causes, incidence, and risk factors
Multiple sclerosis (MS) affects women more than men. The disorder is most commonly diagnosed between ages 20 and 40, but can be seen at any age.
MS is caused by damage to the myelin sheath, the protective covering that surrounds nerve cells. When this nerve covering is damaged, nerve signals slow down or stop.
The nerve damage is caused by inflammation. Inflammation occurs when the body's own immune cells attack the nervous system. This can occur along any area of the brain, optic nerve, and spinal cord.
It is unknown what exactly causes this to happen. The most common thought is that a virus or gene defect, or both, are to blame. Environmental factors may play a role.
You are slightly more likely to get this condition if you have a family history of MS or live in an part of the world where MS is more common.
Symptoms
Symptoms vary, because the location and severity of each attack can be different. Episodes can last for days, weeks, or months. These episodes alternate with periods of reduced or no symptoms (remissions).
Fever, hot baths, sun exposure, and stress can trigger or worsen attacks.
It is common for the disease to return (relapse). However, the disease may continue to get worse without periods of remission.
Because nerves in any part of the brain or spinal cord may be damaged, patients with multiple sclerosis can have symptoms in many parts of the body.
Muscle symptoms:
- Loss of balance
- Muscle spasms
- Numbness or abnormal sensation in any area
- Problems moving arms or legs
- Problems walking
- Problems with coordination and making small movements
- Tremor in one or more arms or legs
- Weakness in one or more arms or legs
- Constipation and stool leakage
- Difficulty beginning to urinate
- Frequent need to urinate
- Strong urge to urinate
- Urine leakage (incontinence)
- Double vision
- Eye discomfort
- Uncontrollable rapid eye movements
- Vision loss (usually affects one eye at a time)
- Facial pain
- Painful muscle spasms
- Tingling, crawling, or burning feeling in the arms and legs
- Decreased attention span, poor judgment, and memory loss
- Difficulty reasoning and solving problems
- Depression or feelings of sadness
- Dizziness and balance problems
- Hearing loss
- Problems with erections
- Problems with vaginal lubrication
- Slurred or difficult-to-understand speech
- Trouble chewing and swallowing
Signs and tests
Symptoms of MS may mimic those of many other nervous system disorders. The disease is diagnosed by ruling out other conditions.
People who have a form of MS called relapsing-remitting may have a history of at least two attacks, separated by a period of reduced or no symptoms.
The health care provider may suspect MS if there are decreases in the function of two different parts of the central nervous system (such as abnormal reflexes) at two different times.
A neurological exam may show reduced nerve function in one area of the body, or spread over many parts of the body. This may include:
- Abnormal nerve reflexes
- Decreased ability to move a part of the body
- Decreased or abnormal sensation
- Other loss of nervous system functions
- Abnormal pupil responses
- Changes in the visual fields or eye movements
- Decreased visual acuity
- Problems with the inside parts of the eye
- Rapid eye movements triggered when the eye moves
- Lumbar puncture (spinal tap) for cerebrospinal fluid tests, including CSF oligoclonal banding
- MRI scan of the brain and MRI scan of the spine are important to help diagnose and follow MS
- Nerve function study (evoked potential test)
Is marijuana an effective treatment for spasticity disorders such as multiple sclerosis?
Movement Disorders stated in a Sep. 2004 article titled "Survey on Cannabis Use in Parkinson's Disease" by researchers from the Movement Disorders Centreat the Department of Neurology at Charles University, Prague, Czech Republic: "An anonymous questionnaire sent to all patients attending the Prague Movement Disorder Centre revealed that 25% of 339 respondents had taken cannabis and 45.9% of these described some form of benefit.... The late onset of cannabis action is noteworthy. Because most patients reported that improvement occurred approximately two months after the first use of cannabis, it is very unlikely that it could be attributed to a placebo reaction."
More Pro's and Cons
People with multiple sclerosis and other diseases that cause severe muscle spasms, spasticity and tremors have used cannabis for a very long time, and have consistently reported that it relieves their symptoms. In what is perhaps the earliest medical report on the use of cannabis to treat muscle spasms, Dr. William OShaughnessy, a British physician working in India, reported in 1842 that cannabis extracts effectively controlled the spasticity he observed in cases of tetanus, and in 1890
More
Cannabis has also been shown to be effective in relieving muscle spasms and spasticity associated with a number of other illnesses such as irritable bowel syndrome, premenstrual dysphoric disorder (PMDD) and PMS, cerebral palsy, Parkinsons Disease, amyotrophic lateral sclerosis (Lou Gehrigs disease), spinal cord injury and other nerve injuries, and may also relieve the bronchial spasms that cause asthma, though little formal research has been done on cannabis in any of these conditions.
Alan Shackelford, M.D., graduated from the University of Heidelberg School of Medicine and trained at major teaching hospitals of Harvard Medical School in internal medicine, nutritional medicine and hyperalimentation and behavioral medicine. He is principle physician for Intermedical Consulting, LLC and Amarimed of Colorado, LLC and can be contacted at Amarimed.com.
Article from Culture Magazine and republished with special permission
The question of whether marijuana (Cannabis sativa) should be used for symptom management in MS is a complex one. It is generally agreed that better therapies are needed for distressing symptoms including pain, tremor, and spasticity that may not be sufficiently relieved by available treatments. Yet there are serious uncertainties about the benefits of marijuana relative to its side effects. The fact that marijuana is an illegal drug in many states and by federal statute (see in the News) further complicates the issue.
Some people with MS report that smoking marijuana relieves several of their MS symptoms. However, for any therapy to be recognized as an effective treatment, this kind of subjective, anecdotal reporting needs to be supported by carefully gathered objective evidence of safety and benefit. Unfortunately, it has proven difficult to do carefully controlled clinical trials of marijuana. One reason for this is that marijuana is psychoactive and makes people feel "high." This means that people taking the active drug during a clinical trial usually become aware of it thus "unblinding" the study and possibly biasing results. Studies completed thus far have not provided convincing evidence that marijuana or its derivatives provide substantiated benefits for symptoms of MS.
Conflicting results of previous research, coupled with the need for additional therapies to treat symptoms of MS, make it important that more research be done on the potential of marijuana and its derivatives. The National MS Society is funding a well controlled study on the effectiveness of different forms of marijuana to treat spasticity in MS, and established a task force to examine the use of Cannabis in MS to review what is currently known about its potential. This task force had made specific recommendations on the research that still needs to be done to answer pressing questions about the potential effectiveness and safety of marijuana and its derivatives in treating MS.
Download Recommendations Regarding the Use of Cannabis in Multiple Sclerosis (.pdf)
Early Studies Showed Mixed Results and Some Side Effects
Well known for its mind-altering properties, marijuana is produced from the flowering top of the hemp plant, Cannabis sativa.
Early studies explored the role of THC (tetrahydrocannabinol an active ingredient in marijuana) or smoked marijuana in treating spasticity, tremor, and balance control in small numbers of people with MS. Most of these studies were done with THC. Because THC can be given by mouth, it is easier to control the dose. The results of these studies were mixed, and participants reported a variety of uncomfortable side effects. In addition, smoked marijuana poses health risks that are at least as significant as those associated with tobacco.
For spasticity (unusual muscle tension or stiffness)
Studies of THC for spasticity have had mixed results. While some people reported feeling "looseness" and less spasticity, this could not always be confirmed by objective testing done by physicians. Even at its best, effects lasted less than three hours. Side effects, especially at higher doses, included weakness, dry mouth, dizziness, mental clouding, short-term memory impairment, space-time distortions and lack of coordination.
For tremor (uncontrolled movements)
In a small study of THC involving eight seriously disabled individuals with significant tremor and ataxia (lack of muscle coordination), two people reported improvement in tremor that could be confirmed by an examination by a physician and another three reported improvement in tremor that could not be confirmed. All eight patients taking THC experienced a "high," and two reported feelings of discomfort and unease.
For balance
Smoked marijuana was shown to worsen control of posture and balance in 10 people with MS and 10 who did not have MS. All 20 study participants reported feeling "high."
National Academy of Sciences/ Institute of Medicine Report
A 1999 report by the National Academy of Sciences/Institute of Medicine on the medical uses of marijuana raised additional questions. While the report concluded that smoked marijuana does not have a role in the treatment of MS, there remained the possibility that specific compounds derived from marijuana might reduce some MS symptoms, particularly MS-related spasticity. Well designed and controlled studies of the therapeutic potential of marijuana compounds (called cannabinoids) were indicated, in conjunction with the development of safe, reliable drug delivery technology.
Study on Marijuana Derivatives in Mice
Investigators in the United Kingdom and United States tested the ability of two marijuana derivatives and three synthetic cannabinoids to control spasticity and tremor, symptoms of the MS-like disease, EAE, in mice. The results, published in the March 2, 2000 issue of Nature, suggested that four different cannabinoids could temporarily relieve spasticity and/or tremor. While the study suggested that similar derivatives of marijuana might be developed for human use, it was clear that the psychoactive effects of these cannabinoids would need to be reduced sufficiently to make them a safe and comfortable treatment for people with MS.
<div><iframe width="459" height="344" src="https://www.youtube.com/embed/qgySDmRRzxY?feature=oembed" frameborder="0" allowfullscreen="true"></iframe></div>
Received 18 August 1999;accepted 20 January 2000
References 1.
Baker, D. et al. Induction of chronic relapsing experimental allergic
encephalomyelitis in Biozzi mice. J. Neuroimmunol. 28, 261-270 (1990).
2.
Consroe, P., Musty, R., Rein, J., Tillery, W. & Pertwee, R. The perceived
effects of smoked cannabis on patients with multiple sclerosis. Eur. Neurol.
38, 44-48 (1997).
3.
Consroe, P. Cannabinoid systems as targets for the therapy of neurological
disorders. Neurobiol. Dis. 5, 534-551 (1998). Links
4.
Petro, D. J. & Ellenberger, C. Treatment of human spasticity with 9-
tetrahydrocannabinol. J. Clin. Pharmacol. 21 (suppl.), 413-416 (1981).
5.
Clifford, D. B. Tetrahydrocannabinol for tremor in multiple sclerosis. Ann.
Neurol. 13, 669-671 (1983). Links
6.
Ungerleider, J. T., Andyrsiak, T., Fairbanks, L., Ellison, G. W. & Myers, L.
W. 9-THC in the treatment of spasticity associated with multiple sclerosis.
Adv. Alcohol Substance Abuse 7, 39-50 (1987).
7.
Martyn, C. N., Illis, L. S. & Thom, J. Nabilone in the treatment of multiple
sclerosis. Lancet 345, 579 (1995). Links
8.
Pertwee, R. G. Pharmacology of cannabinoid receptor ligands. Curr. Med. Chem.
6, 635-664 (1999). Links
9.
Lyman, W. D., Sonett, J. R., Brosnan, C. F., Elkin, R. & Bornstein, M. B.
9-tetrahydrocannabinol: a novel treatment for experimental autoimmune
encephalomyelitis. J. Neuroimmunol. 23, 73-81 (1989). Links
10.
Wirguin, I. et al. Suppression of experimental autoimmune encephalomyelitis
by
cannabinoids. Immunopharmacology 28, 209-214 (1994). Links
11.
Heller, A. H. & Hallet, M. Electrophysiological studies with the spastic
mutant mouse. Brain Res. 234, 299-308 (1982). Links
12.
Chai, C. K. Hereditary spasticity in mice. J. Heredity 52, 241-243 (1961).
13.
Pertwee, R. G. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol.
Therapeut. 74, 129-180 (1997).
14.Breivogel, C. S. & Childers, S. R. The functional neuroanatomy of brain
cannabinoid receptors. Neurobiol. Dis. 5, 417-431 (1998). Links
15.
Landsman, R. S., Burkey, T. H., Consroe, P., Roeske, W. R. & Yamamura, H.
I. SR141716A is an inverse agonist at the human cannabinoid CB1 receptor.
Eur. J. Pharmacol. 334, R1-R2 (1997). Links
16.
Portier, M. et al. SR144528, an antagonist for the peripheral cannabinoid
receptor that behaves as an inverse agonist. J. Pharmacol Exp. Ther. 288,
582-589 (1999). Links
17.
Calignano, A., La Rana, G., Giuffrida, A. & Piomelli, D. Control of pain
initiation by endogenous cannabinoids. Nature 394, 277-281 (1998). Links
18.
Giuffrida, A. et al. Dopamine activation of endogenous cannabinoid signalling
in dorsal striatum. Nature Neurosci. 2, 358-363 (1999). Links
19.
Huffman, J. W. et al. 3-(1,1-Dimethylbutyl)-1-deoxy-9-THC and related compounds:
synthesis of selective ligands for the CB2 receptor. Bioorg. Med. Chem. 7,
2905-2914 (1999). Links
20.
Noth, J. Trends in the pathophysiology and pharmacotherapy of spasticity. J.
Neurol. 238, 131-139 (1991). Links
Acknowledgements. The authors would like to thank the Multiple Sclerosis
Society of Great Britain and Northern Ireland, the Medical Research Council,
the National Institute on Drug Abuse and the Wellcome Trust for their
financial support.
Nature Macmillan Publishers Ltd 2000 Registered No. 785998 England.
Smoked Cannabis Reduces Some Symptoms of Multiple Sclerosis
Controlled trial shows improved spasticity, reduced pain after smoking medical marijuana
A clinical study of 30 adult patients with multiple sclerosis (MS) at the University of California, San Diego School of Medicine has shown that smoked cannabis may be an effective treatment for spasticity a common and disabling symptom of this neurological disease.
The placebo-controlled trial also resulted in reduced perception of pain, although participants also reported short-term, adverse cognitive effects and increased fatigue. The study will be published in the Canadian Medical Association Journal on May 14.
Principal investigator Jody Corey-Bloom, MD, PhD, professor of neurosciences and director of the Multiple Sclerosis Center at UC San Diego, and colleagues randomly assigned participants to either the intervention group (which smoked cannabis once daily for three days) or the control group (which smoked identical placebo cigarettes, also once a day for three days). After an 11-day interval, the participants crossed over to the other group.
We found that smoked cannabis was superior to placebo in reducing symptoms and pain in patients with treatment-resistant spasticity, or excessive muscle contractions, said Corey-Bloom.
Earlier reports suggested that the active compounds of medical marijuana were potentially effective in treating neurologic conditions, but most studies focused on orally administered cannabinoids. There were also anecdotal reports of MS patients that endorsed smoking marijuana to relieve symptoms of spasticity.
However, this trial used a more objective measurement, a modified Ashworth scale which graded the intensity of muscle tone by measuring such things as resistance in range of motion and rigidity. The secondary outcome, pain, was measured using a visual analogue scale. The researchers also looked at physical performance (using a timed walk) and cognitive function and at the end of each visit asked patients to assess their feeling of highness.
Although generally well tolerated, smoking cannabis did have mild effects on attention and concentration. The researchers noted that larger, long-terms studies are needed to confirm their findings and determine whether lower doses can result in beneficial effects with less cognitive impact.
The current study is the fifth clinical test of the possible efficacy of cannabis for clinical use reported by the University of California Center for Medicinal Cannabis Research (CMCR). Four other human studies on control of neuropathic pain also reported positive results.
The study by Corey Bloom and her colleagues adds to a growing body of evidence that cannabis has therapeutic value for selected indications, and may be an adjunct or alternative for patients whose spasticity or pain is not optimally managed, said Igor Grant, MD, director of the CMCR, which provided funding for the study.
Additional contributors include Tanya Wolfson, Anthony Gamst, PhD, Shelia Jin, MD, MPH, Thomas D. Marcotte, PhD, Heather Bentley and Ben Gouaux, all from UC San Diego School of Medicine.
Press Release From University Of California, San Diego