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Amyotrophic Lateral Sclerosis
#1
AMYOTROPHIC LATERAL SCLEROSIS


Edit by Author, 1/15/2013


Some of the source links below are now dead. I was only allowed


to take one third of the original content. And leave links.


I give you permission to use one third also. Or search out the


videos first and and take them from there
.




http://www.youtube.com/watch?v=Dp4q8YNF9o4

[Image: alsnerves.gif]

What Types of Nerves Make Your Body Work Properly?
(from Living with ALS, Manual 1: What's It All About?)

The body has many kinds of nerves. There are those involved in the process of thinking, memory, and of detecting sensations (such as hot/cold, sharp/dull), and others for vision, hearing, and other bodily functions. The nerves that are affected when you have ALS are the motor neurons that provide voluntary movements and muscle power. Examples of voluntary movements are your making the effort to reach for the phone or step off a curb; these actions are controlled by the muscles in the arms and legs.

The heart and the digestive system are also made of muscle but a different kind, and their movements are not under voluntary control. When your heart beats or a meal is digested, it all happens automatically. Therefore, the heart and digestive system are not involved in ALS. Breathing also may seem to be involuntary. Remember, though, while you cannot stop your heart, you can hold your breath - so be aware that ALS may eventually have an impact on breathing.

Although the cause of ALS is not completely understood, the recent years have brought a wealth of new scientific understanding regarding the physiology of this disease.

Source





Marijuana's Potential Exciting Researchers in Treatment of ALS, Parkinson's Disease


A Legal Mood Lifter: Researchers are investigating a new antidepressant and pain reliever that works like cannabis (marijuana), without the illegal side effects.

A decade ago, when Daniele Piomelli went to scientific conferences, he was often the only researcher studying cannabinoids, the class of chemicals that give marijuana users a high. His work often drew snickers and jokes, but no more.

At the annual Society for Neuroscience conference recently, scientists here delivered almost 200 papers on the subject.

Why the attention? Many scientists believe cannabis-like drugs might be able to treat a wide range of diseases, far beyond the nausea and chronic pain typically treated with medical cannabis. Researchers here presented tantalizing evidence that cannabinoid drugs can help treat amyotrophic lateral sclerosis, known as ALS or Lou Gehrig's disease, Parkinson's disease and obesity.


Other researchers are studying whether the compounds can help victims of stroke and multiple sclerosis.

Although the chemicals work on the same area of the nervous system, the new drugs are much more refined and targeted than cannabis, with few of its side effects.

"Cannabinoids have a lot of pharmaceutical potential," said Piomelli, a neuroscientist at the University of California at Irvine.

"A lot of people are very excited"

Although the federal government opposes the use of medical marijuana, it generally doesn't restrict cannabinoid research, most of which doesn't involve the cannabis plant itself. Scientists who use Marinol, a legal but tightly regulated marijuana-like drug, do need government permission.

Because the cannabinoid system wasn't discovered until the late 1980s, decades after serotonin, dopamine and other neurotransmitters, researchers still know relatively little about how it works. Like all neurotransmitter networks, the cannabinoid system consists of a series of chemical pathways through the brain and nervous system.

Cannabis produces its effects by activating this pathway, primarily through the effects of tetrahydrocannabinol, or THC, the drug's main active ingredient.

Over the past decade, researchers have been following these abundant trails to determine their real purpose.

"You don't have them there to get stoned. So, there must be internal reasons," said Andrea Giuffrida, a neuroscientist at the University of Texas Health Sciences Center in San Antonio.

Researchers have learned that endogenous cannabinoids, internal brain chemicals that activate the system, play a role in tissue protection, immunity and inflammation, among other functions. The cannabinoid system also appears to exert wide influence, modulating the release of dopamine, serotonin and other neurotransmitters.

Giuffrida and others believe cannabinoids can treat degenerative disorders such as Parkinson's disease and ALS.

At the conference, Giuffrida announced that a cannabinoid drug wards off Parkinson's-like effects in mice.

The disorder, which afflicts more than 1 million Americans, destroys neurons in a key part of the brain, causing patients to lose control over movement.

Giuffrida, with colleagues David Price and James Roberts, injected mice with a chemical called MPTP, which mimics Parkinson's damage.

When some of the animals subsequently received a drug that blocks cannabinoid receptors, their nerve cells suffered far less damage than did the cells of the other mice.

This was the first demonstration that a cannabinoid drug can have this effect. Although he is not sure how the anti-cannabinoid compound works, Giuffrida suspects it protects neurons by reducing inflammation, a key component in Parkinson's.

Cannabinoids might also slow down ALS, which destroys neurons that control muscles until victims become paralyzed, unable to breathe on their own.

Neuroscientist Mary Abood first became interested in cannabinoids after hearing about ALS patients who got some relief from smoking cannabis. So she began animal experiments at the California Pacific Medical Center in San Francisco.

In her study, mice with a variant of ALS were given a combination of THC and cannabidiol, another compound found in cannabis.

Both substances are cannabinoid agonists, chemicals that activate the cannabinoid system. Abood measured the course of the ailment by testing how long the mice could stand on a rod that was slowly rotating.

The treatment delayed disease progression by more than seven days and extended survival by six days.

In human terms, this would amount to about three years. That's a significant improvement over the only existing ALS drug, riluzole, which extends life by two months.

"I was very excited when I got my initial results," Abood said.

Also at the conference, researchers at the Institute of Neurology in London announced results that corroborated her findings. Cannabinoids have also helped some human ALS patients in one small trial, and Abood is trying to get funding for a larger one.

If cannabinoids can shield human neurons from harm, researchers say, they might prove useful against other neurological diseases, including mental illness.

Scientists are looking at whether cannabinoids can treat multiple sclerosis, epilepsy and Huntington's disease, while Giuffrida is beginning a study of their effect on schizophrenia.

Advocates of medical cannabis have long argued that the drug can be useful for treating many conditions, particularly chronic pain, nausea and glaucoma (in the latter, cannabis works by temporarily decreasing pressure around the eye).

Although they don't dispute this view, most researchers believe there are better, more precise ways to stimulate the cannabinoid system.

They believe cannabis has too many negatives to be a truly effective drug, with side effects that include memory problems, decreased immunity and possibly addiction. (Some researchers dispute this "addictive" claim.)

Cannabis has another drawback. From a scientific standpoint, Giuffrida says, it's "a very dirty drug." It contains more than 300 compounds, 60 of which affect the cannabinoid system. Scientists don't understand what most of these substances do or how they work together. This complexity makes it hard for researchers to pinpoint cannabis' effects.

One cannabinoid, Marinol, is available legally. The compound, which contains THC in a pill form, is usually prescribed for nausea and for appetite loss among AIDS patients. But Marinol has the same psychoactive effects as cannabis.

"So the key", Piomelli says, "is getting the effects without the side effects."

To that end, Piomelli has developed a compound called URB597, which doesn't flood the body with cannabinoids, as Marinol and cannabis do.

Instead, it slows the breakdown of the cannabinoids in the system. He thinks the drug may help treat pain, anxiety and even depression without making patients stoned and forgetful. He and others are testing it on animals.

SOURCE
http://www.illinoisn...ent/view/600/1/


http://www.youtube.com/watch?v=-qFSMXEYC3c




Survey of Cannabis Use in Patients with Amyotrophic Lateral Sclerosis

Dagmar Amtmann, PhD
Patrick Weydt, Md
Kurt L. Johnson, PhD
Mark P. Jensen, PhD
Gregory T. Carter, M.D.


Abstract

Cannabis (marijuana) has been proposed as treatment for a widening spectrum of medical condtions and has many properties that may be applicable to the management of amyotrophic lateral sclerosis (ALS). This study is the first, anonymous survey of persons with ALS regarding the use of cannabis. There were 131 respondents, 13 of whom reported using cannabis in the last 12 months. Although the small number of people with ALS that reported using cannabis limits the interpretation of the survey findings, the results indicate that cannabis may be moderately effective at reducing symptoms of appetite loss, depression, pain, spasticity, and drooling. Cannabis was reported ineffective in reducing difficulties with speech and swallowing, and sexual dysfuction. The longest relief was reported for depression (approximately two to three hours). Key words: pain, palliative care, cannabis, medicinal marijuana, amyotrophic lateral sclerosis.

Introduction

Amyotrophic lateral sclerosis (ALS), with an incident rate of five to seven per 100,000 population, is the most common form of adult motor neuron disease.1-3 ALS is a rapidly progerssive neuromuscular disease that destroys both upper and lower motor neurons, ultimately causing death, typically from respiratory failure. The vast majority of ALS is acquired and occurs sporadically. There is not yet a known cure for ALS. 4-6

ALS patients may present with any number of clinical symptoms, including weakness, spasticity, cachexia, dysarthria and drooling, and pain secondary to immobility, among others.7-8 Previous studies have reported both direct and theoretical applications for using cannabis to manage some of these ALS symptoms.9-11 Cannabis has easily observable clinical effects with rapid onset (e.g., analgesia, muscle relaxation, dry mouth). Moreover, some components of marijuana (not inhaled smoke) have been shown in laboratory studiues to have neuroprotective properties that may help prolong neuronal cell survival over extended time.12-16

Marijuana is a complex plant, containing over 400 chemicals.17 Approximately 60 are cannabinoids, chemically classified as 21 carbon terpenes.17,18 Among the most psychoactive of these is delta-9-tetrahydrocannabinol (THC).17,18 Because of this biochemical complexity, characterizing the clinical pharmacology of marijuana is difficult. The clinical pharmacology of marijuana containing high concentrations of THC may well differ from plant material containing small amounts of THC and higher amounts of the other cannabinoids. The bioavailability and pharmacokinetics of inhaled marijuana are also substantially different from those taken by ingestion. The cannabinoids are all lipid soluble compounds and are not soluble in water.19 Besides THC, which is the active ingredient in dronabinol, varying proportions of other cannabinoids, mainly cannabidiol (CBD) and cannabinol (CBN), are also present in marijuana and may modify the pharmacology of the THC as well as have distinct effects of their own. CBD is not psychoactive but has significant anticonvulsant and sedative pharmacologic properties and may interact with THC.20-21

The concentration of THC and other cannabinoids in marijuana varies greatly depending on growing conditions, plant genetics, and processing after harvest.21 In the usual mixture of leaves and stems distributed as marijuana, concentration of THC ranges from 0.3 percent to 4 percent by weight.21,22 However, specially grown and selected marijuana can contain 15 percent or more THC. Thus, one gram of marijuana might contain as little as three milligrams of THC or more than 150 mg.21 THC is a potent psychoactive drug, and large doses may produce mental and perceptual effects similar to hallucinogenic drugs.23,24 Despite this, THC and other cannabinoids have low toxicity, and lethal doses in humans have not been described.25,26

Despite risk for bronchitis, the main advantage of smoking is rapid onset of effect and easy dose titration. When marijuana is smoked, cannabinoids in the form of an aerosol in the inhaled smoke are rapidly absorbed and delivered to the brain, as would be expected of a highly lipid-soluble drug.27,28 However, smoking anything, including marijuana, carries health risks for the lungs and airway system. A healthier option is vaporization. Because the cannabinoids are volatile, they will vaproize at a temperature much lower than actual combustion.24 Heated air can be drawn through marijuana and the active compounds will vaporize, which can then be inhaled. This delivers the substance in a rapid manner that can be easily titrated to desired effect.29 Vaporization therefore removes most of the health hazards of smoking.27

The medicinal use of cannabis is better documented in multiple sclerosis (MS) than in other clinical conditions, although evidence tends to be anecdotal, and no controlled clinical trials of medicinal marujuana use in MS have been published.30-39 With respect to pain, the concominant use of cannabis with narcotics may be beneficial, because the cannabinoid receptor system appears to be discrete from that of opioids.40-45 In that regard, the antiemetic effect of cannabis may also help with the nausea sometimes associated with narcotic medications. Untoward effects of cannabis include potentially significant psychoactive properties, which may produce a sense of well-being or euphoria but can also induce anxiety, confusion, paranoia, and lethargy.46

To date there have not yet been any empirical studies to investigate the use of cannabis for medicinal purposes in ALS. The purpose of this survey was to gather preliminary data on the extent of use of cannabis among persons with ALS (PALS) and to learn which of the symptoms experienced by PALS are reported to be alleviated by the use of cannabis.

Metohdology

Participants in this survey were recruited from the ALS Digest (the Digest), an electronic discussion list published weekly to serve the worldwide ALS community, including patients, families, caregivers, and providers. The Digest serves as a forum for discussion of issues related to ALS and is not intended to provide medical advice on individual health matters. The Digest can be viewed at www.alslinks.com. Currently there are over 5,600 subscribers in 80 countries worldwide. However, the number of subscribers with ALS is not known. The editor is not a physician and the Digest is not peer reviewed. An e-mail invitation to participate was posted to the Digest four times over two months.

The survey was available online from January 6 through March 2, 2003, approximately eight consecutive weeks. Any subscriber with ALS was invited to participate on a voluntary and anonymous basis. The sponsoring institution human subjects review board approved the study protocol. A Web-based survey tool developed by the University of Washignton was used to collect responses. The tool uses SSL encryption for transferred data, and all identifying information was stored in a code translation table separate from the actual data to protect the privacy of respondents. The University of Washington human subjects review board has approved this tool for research purposes.

PALS who wanted to participate were given a Web site address that introduced the survey and provided a link to the survey site. The invitation to participate did not mention cannabis or marijuana, in order to discourage participation by individuals who do not have ALS but might otherwise be interested in promoting legalization of marijuana. The sruvey was titled "A survey of ALS Patients Who Use Alternative Therapies to Treat Symptoms."

It was presumed by the investigatiors that the diagnostic information provided by the survey participants was accurate (i.e., no medical records were reviewed to confirm their diagnosis). In addition to a series of questions related to the ALS symptoms, the use of cannabis, and its effectiveness in alleviating the symptoms of ALS, participants were also asked to provide demographic and diagnostic information. The survey was anonymous and it is therefore impossible to conclusively determine whether all respondents were individuals with ALS. However, the first six questions of the survey asked about how and when the respondent was diagnosed with ALS and specifically asked those who were not diagnosed with ALS by a physician to not fill out the survey. The authors carefully studied the demographic and diagnostic information provided by each respondent for completeness, consistency, and plausiblity. Records with the diagnostic information missing were excluded from the analysis. Many participants offered extensive information about other alternative therapies they use, and the general comments appeared to reflect experiences of individuals living with ALS.

Results

A total of 137 responses were received. Four responses were excluded because of duplicate submission (i.e. the same person inadvertently submitting more than one survey by hitting the submit key more than once) and two because of failure to complete most of the questions of the survey. Eletronic logs of all submissions were inspected for repeated entries from the same Internet protocol (IP) address. None were found. A total of 131 responses were retained for analysis.

The demographics of the sample are shown in Table 1. Seventy-five percent of the respondents were male and 90 percent were caucasian. The average age of participants was 54 years [standard deviation(sd)=11], with no significant difference between the genders [Mean(M) mean(m)=54 for=for males,=males, sd=12.5 m=53 females,=females,]. Eighty-four percent of the respondents were married or living with a significant other, 17 percent were employed (full time or part-time), 64 percent were unemployed or retired due to disability, and 18 percent were retired due to age. Respondents reported high levels of education, with only 13 percent with high school education or less and 62 percent with college education or higher. The time since ALS diagnosis ranged from one month to 24 years. The median time since diagnosis (i.e., duration) was three years, the mean duration was approximately four years (M=4.4, SD=4.0). About a half of the sample reported they used a wheelchair usually or always, and about 20 percent reported no restrictions in mobility. Eighty-one percent of the respondents filled out the survey independently while 19 percent reported that they required assistance from others. One-half of the participants were taking Riluzole. The majority of participants (69 percent) reported that they live in the Unted States, 8 percent in Canada, and 5 percent in Australia. Six percent of the participants live in Europe, while the rest (12 percent) of the respondents reported that they were from Africa, India, Israel, Brazil, Ecuador, Guatemala, or Argentina. Fifty-three participants (41 percent) reported drinking alcohol, 14 (11 percent) reported that they use tobacco, and four (3 percent) reported consuming both alcohol and tobacco.

Use of cannabis

Seventy-seven respondents (60 percent) reported that they never used cannabis, and 41 (31 percent) used cannabis in teenage or college years only. Thirteen respondents (10 percent) reported using cannabis in the last 12 months, and their demographics are outlined in Table 2.

Those who reported using cannabis in the last 12 months were all male and all lived in the US. Ten of those who reported using cannabis in the last 12 months also responded affirmatively to the question that asked about the use of cannabis during the teenage, college, and adult years. All of those who reported using cannabis in the last 12 months also reported that they used cannabis at some point in their lives before they were diagnosed with ALS. Six of the cannabis users reported that they lived in a state where medical cannabis is legal, and four lived in a state where medical cannabis is illegal. The remaining three respondents were not sure whteher medical cannabis was legal in their state. There were no statistcally significant differences between the cannabis users and non-users (see Table 2) on any demographic variable (age, marital status, employment status, education level, time since diagnosis, mobility status).

None of those who reported using cannabis in the past 12 months reported tobacco use, but all reported drinking alcohol.

Eight cannabis users reported smoking cannabis in the last three months. Two respondents reported smoking cannabis infrequently (less often than once a month), one reported smoking one to two times a week, and three reported daily use.

No respondents reported only breathing vaporized cannabis, although one participant reported using vaporized cannabis in addition to smoking and using medicinal cannabis. Two participants reported eating cannabis, one in addition to smoking it. Three respondents used medicinal cannabinoids (i.e., Dronabinol). Of the three respondents who used medicinal cannabinoids, one reported using only medicinal cannabinoids, one also smoked cannabis, and one both smoked as well as breathed vaporized cannabis.

Symptoms

The intensity of ALS-related symptoms was quantified by asking respondents to rate how much they experience each of the symptoms on a five-point scale ranging from "not at all" (0) to "very much" (4). The most frequent sympotm was weakness, followed by speech difficulties, drooling and swalowing difficulties. The intnesity of symptoms reported by respondents who did not use cannabis was not statistically significantly idfferent from the symptom intensity reported by the cannabis users [F(10, 120)=120) 1.07,=1.07, p=.39]. A summary of symptoms and their intensity is listed in Table 3.

The ammount of relief attributed to cannabis use was assessed by asking the respondents to rate the degree to which cannabis alleviates each symptom on a five-point scale ranging from "not at all" (0) to "completely relieves the symptom" (4). Respondents reported that the use of cannabis helped moderately for depression, appetite loss, spasticity, drooling, and pain. All cannabis users who reported symptoms of appetite loss and depression also reported that cannabis reduced these symptoms. None of the cannabis users reported any reduction in difficulties with swallowing and speech or sexual dysfunction.

The duration of symptom relief was measured on a scale from 0 (no relief) to 6 (more than nine hours). Respondents reported the most lasting relief (on average two to three hours) for depression. The loss of appetite, drooling, shortness of breath, spasticity, and pain were reported to be relieved on average for approximately one hour or less. Table 4 provides a summary of symptoms reported by the cannabis users. Level of relief was reported on a five-point scale ranging from "not at all" (0) to "completely relieves the symptom" (4). The duration of sumptom relief was measured on a scale from "no relief" (0), "less than one hour" (1), "two to three hours" (2), "four to five hours" (3), "six to seven hours" (4), "eight to nine hours" (5), "more than nine hours" (6).

Discussion

There is an increasing amount of research concerning the medicinal effects of cannabinoids. For example, cannabinoids have been reported to reduce chemotherapy-induced nausea and vomiting, lower intraocular pressure in patients with glaucoma, reduce anorexia in patients with cancer and AIDS-associated weight loss, and reduce pain and spasticity in MS.30-39 Cannabinoids, the active ingredients in marijuana, may also have properties that may be applicable to the management of ALS.9,10 However, to date no empirical studies of use and effectiveness of cannabis for symptom management by PALS have been published.

Approximately 10 percent of the survey respondents reported using cannabis. This is a lower rate than the frequency of use reported by other patient populations, including MS, AIDS, and cancer patients.10,30,31 However, the pattern of symptom relief reported by the small number of PALS who reported using cannabis for symptom management by people with other conditions, including MS.30,35,36 Cannabis users reported that cannabis smoking was most effective at reducing depression, appetite loss, pain, spasticity, drooling, and weakness. The factor that most predicted current use of cannabis by PALS was reported previous use (presumably recreational).

The survey had a number of limitations. First, the survey results reported here are based on a relatively small number of respondents (131) and on reports of 13 cannabis users, and may not be representative of the patterns of cannabis use in the ALS population by people with ALS in general. Second, 75 percent of the respondents were male, 25 percent were female. Men appear to be about 1.5 times more likely to be affected with ALS than women,7,8 so the percentage of female participants is slightly lower than expected in the general ALS population (about 33 percent). Published studies of Internet use consistently report that females are less likely to use the Internet for reasons that may be independent of income and estimate that only about one-third of Internet users are women.47,48 This may account for the lower than expected participation by women with ALS.

A third limitation of the study is that a disproportionate number of the survey respondents were white (90 percent) and all cannabis users were white. There is some evidence that whites may be at higher risk for ALS though most researchers agree that ALS equally affects people of all races.49,50 Racial discrepancies in rates of ALS may be due to poorer access to healthcare for minority populations in the US, particularly access to tertiary referral centers, where the ALS diagnosis is often made. Published studies report that over 80 percent of Internet users are white;48 this is the most likely explanation for the disproportionate perticipation by Caucasians in this survey.

Fourth, Internet users tend to be highly educated. Almost 60 percent repoert having at least one degree.48 Those with higher education are more likely to own computer equipment and to use it to connect to the Internet.51 The results of the survey we report here provide further evidence for this trend, with only 13 respondents (10 percent) reported having high school education or less.

Finally, none of the participants from the countries where cannabis use is prevalent (India) or legal for medical uses (Australia, Canada) reported using cannabis. The most likely explanation for this finding is the small number of perticipants from these countries; only one respondent was from India, six from Australia, and eleven from Canada.

In general, professionals with university degrees living in households with disposable incomes sufficient to purchase technology tools are likely to be over-represented in Internet surveys. Women, minorities, the elderly, those who liveon social assistance disability payments, or who earn minimum wages, are much less likely to participate.48,51

Privacy is a major issue associated with Web-based methodology. When the Internet is used for research, especially for research on sensitive issues (such as using substances that are illegal under federal law and most state laws), protecting the privacy of the participants is paramount. By making the survey anonymous, the authors protected the privacy of the respondents but gave up the ability to verify respondent' diagnoses or prevent repeated or malicious submittals. Although the records showed that no two responses were submitted from the same IP address, the IP address identifies the computer, not the user. Therefore, it cannot be conclusively determined that one respondent did not submit more than one response using different computers.

The low response rate might be explained by many factors. First, we do not know how many participants in the electronic discussion list that was used to recruit participants have ALS. It is possible, even likely, that a large majority of the participants are family members, service providers, and advocates. Second, the respondents who do not use alternative therapies may have been less likely to respond. It is unclear what percentage of people with ALS use alternative therapies. A recent survey from Germany suggests that about half of the ALS patients there use complementary and alternative medicine.52 Some respondents who do not use alternative therapies such as vitamins and supplements, but do use cannabis to manage their symptoms may not have considered cannabis to be an "alternative therapy" and decided not to participate. Many respondents provided information on vitamins, supplements, and other alternative therapies in the write-in spaces of the survey even though they were nto asked about these therapies directly, probably because the respondents had anticipated the survey would gather informationon those topics. Third, even though the invitation as well as the introduction to the survey clearly stated that the survey was anonymous and there was no way for the researchers to associate a specific response with a specific respondent, many may have been individuals who are generally suspicious of providing information via the Internet and may have decided not to participate for this reason.

Despite the limitations of this study noted above, these preliminary findings support the need for further research into the potential benefits of cannabis use for the clinical management of some ALS symptoms. These include pain, which was one of the symptoms identified in a recent study as not being sufficiently addressed in ALS.53 Further research is needed to see if the current findings can be confirmed using non-Internet-based survey methodology with a defined sample. It would also be informative to inquire about cannabis use within the context of subject beliefs about the efficacy of various alternative and complimentary approaches and their engagement and satisfaction with those approaches.

Acknowledgements

Funding for this research was provided by grants from the National Institute on Disability and Rehabilitation Research, Washington, DC and from the National Institutes of Health

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source: http://www.cannabism...rts/carter4.php

Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid.
Raman C, McAllister SD, Rizvi G, Patel SG, Moore DH, Abood ME.

Forbes Norris MDA/ALS Research Center, 2351 Clay Street, Suite 416, California Pacific Medical Center, San Francisco, CA 94115, USA.

Effective treatment for amyotrophic lateral sclerosis (ALS) remains elusive. Two of the primary hypotheses underlying motor neuron vulnerability are susceptibility to excitotoxicity and oxidative damage. There is rapidly emerging evidence that the cannabinoid receptor system has the potential to reduce both excitotoxic and oxidative cell damage. Here we report that treatment with Delta(9)-tetrahydrocannabinol (Delta(9)-THC) was effective if administered either before or after onset of signs in the ALS mouse model (hSOD(G93A) transgenic mice). Administration at the onset of tremors delayed motor impairment and prolonged survival in Delta(9)-THC treated mice when compared to vehicle controls. In addition, we present an improved method for the analysis of disease progression in the ALS mouse model. This logistic model provides an estimate of the age at which muscle endurance has declined by 50% with much greater accuracy than could be attained for any other measure of decline. In vitro, Delta(9)-THC was extremely effective at reducing oxidative damage in spinal cord cultures. Additionally, Delta(9)-THC is anti-excitotoxic in vitro. These cellular mechanisms may underlie the presumed neuroprotective effect in ALS. As Delta(9)-THC is well tolerated, it and other cannabinoids may prove to be novel therapeutic targets for the treatment of ALS.

source: http://www.ncbi.nlm....Pubmed_RVDocSum


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