Abnormal sensitivity of cannabinoid CB1 receptors in the striatum of mice with experimental amyotrophic lateral sclerosis.

“Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motor neurons.

The sensitivity of cannabinoid CB1 receptors controlling both glutamate and GABA transmission was remarkably potentiated in ALS mice, indicating that adaptations of the endocannabinoid system might be involved in the pathophysiology of ALS. In conclusion, our data identify possible physiological correlates of striatal dysfunction in ALS mice, and suggest that cannabinoid CB1 receptors might be potential therapeutic targets for this dramatic disease.”

http://www.ncbi.nlm.nih.gov/pubmed/19452308

Identification of receptors and enzymes for endocannabinoids in NSC-34 cells: relevance for in vitro studies with cannabinoids in motor neuron diseases.

“NSC-34 cells, a hybridoma cell line derived from the fusion of neuroblastoma cells with mice spinal cord cells, have been widely used as an in vitro model for the study of motor neuron diseases [i.e. amyotrophic lateral sclerosis (ALS)]. In the present study, they were used to characterize different elements of the cannabinoid signaling system, which have been reported to serve as targets for the neuroprotective action of different natural and synthetic cannabinoid compounds…

Assuming that glutamate toxicity is one of the major causes of neuronal damage in ALS and other motor neurons diseases, the differentiated NSC-34 cells might serve as a useful model for studying neuroprotection with cannabinoids in conditions of excitotoxic injury, mitochondrial malfunctioning and oxidative stress.”

http://www.ncbi.nlm.nih.gov/pubmed/22206832

The endocannabinoid system in the inflammatory and neurodegenerative processes of multiple sclerosis and of amyotrophic lateral sclerosis.

Abstract

“Multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are chronic diseases of the central nervous system (CNS), featured by a complex interplay between inflammation and neurodegeneration. Increasing evidence supports the involvement of the endocannabinoid system (ECS) in both inflammatory and neurodegenerative processes typical of these pathological conditions. Exogenous or endogenous cannabinoids regulate the function of immune system by limiting immune response. On the other hand, by preventing excitotoxic damage, cannabinoids protect neuronal integrity and function. Of note, the ECS not only plays a role as modulator of disease processes, but it can also be disrupted by the same diseases. Agents modulating cannabinoid receptors or endocannabinoid tone provide promising therapeutic opportunities in the treatment of inflammatory neurodegenerative disorders of the CNS.”

http://www.ncbi.nlm.nih.gov/pubmed/20353778

The (endo)cannabinoid system in multiple sclerosis and amyotrophic lateral sclerosis.

“Alterations of the endocannabinoid system (ECS) have been recently implicated in a number of neuroinflammatory and neurodegenerative conditions so that the pharmacological modulation of cannabinoid (CB) receptors and/or of the enzymes controlling synthesis, transport, and degradation of these substances has emerged as a valuable option to treat neurological diseases.

Here, we describe the current knowledge concerning the rearrangement of ECS in a primarily inflammatory disorder of the central nervous system such as multiple sclerosis (MS), and in a primarily degenerative condition such as amyotrophic lateral sclerosis (ALS).

 Furthermore, the data supporting a therapeutic role of agents modulating CB receptors or endocannabinoid tone in these disorders will also be reviewed. Complex changes of ECS take place in both diseases, influencing crucial aspects of their pathophysiology and clinical manifestations. Neuroinflammation, microglial activation, oxidative stress, and excitotoxicity are variably combined in MS and in ALS and can be modulated by endocannabinoids or by drugs targeting the ECS.”

http://www.ncbi.nlm.nih.gov/pubmed/17678961

Medical Marijuana For Multiple Sclerosis and Amyotrophic Lateral Sclerosis

“Marijuana has been classified as a Schedule 1 narcotic since the 1960’s, which means it is deemed by the federal government to have no medicinal value and heavy risk. However, there is an increasing body of research to show that marijuana can be helpful for certain debilitating conditions and 15 states have now legalized it for medicinal usage. One of those conditions research is showing marijuana’s medicinal value is multiple sclerosis (MS) and another is Amyotrophic Lateral Sclerosis (ALS). They are both diseases involving neurologic deterioration.

Approximately 200 individuals per week are diagnosed with MS, with the usual onset between 20 and 40 years of age. The disease has no known cure and involves a neuro-degeneration in which the brain and spinal cord nerves undergo a gradual destruction of its protective tissue called myelin.

Myelin covers these regions in what’s called a Myelin sheath, and as the sheath degenerates symptoms include painful muscle spasms, numbness, impaired vision, loss of coordination, tremors, weakness, and imbalance (ataxia). The disease is progressive and can become incapacitating and lead to death.

MS patients may find that marijuana relieves symptoms of spasticity, tremors, imbalance, depression, and fatigue. Numerous studies have looked at Sativex, which is an oral cannabis spray developed in the UK. It has been shown to relieve pain, spasticity, depression, fatigue, and incontinence.

THC appears to have some immunosuppressive or immunomodulatory effects. This may be beneficial to MS patients. Long term studies need to be completed to see if this is for real and a disease modifying effect is real.

Lou Gehrig’s disease, also called Amyotrophic Lateral Sclerosis, involves the ongoing loss of the brain’s motor neurons. It is rapidly progressive, and usually fatal. There is no known cause. The usual age of onset is 40 to 60 years, and men are more commonly affected.

The most well known person with ALS is Stephen Hawking, a physicist who has lived for over 40 years after being diagnosed. He is the exception, the unfortunate usual prognosis is grim, with about half of patients dying with 2.5 years of onset.

The cannabinoids in medical marijuana may protect against glutamate toxicity. This may be very helpful because ALS involves excessive glutamate in the brain tissue, spinal fluid, and serum of those suffering.

By lowering the chance of glutamate toxicity, there is a chance that marijuana may have a neuroprotective effect. In addition, patients describe alleviation of pain and spasms, improvement of appetite, and less drooling issues which is a common problem with ALS.”

By David L. Greene

 

Medical Marijuana Use: Miracle Medicine Good for Dozens of Diseases

“When the State of Oregon first legalized Medical Marijuana I disbelieved and was astonished at the diverse medical conditions that State DHS said were acceptable conditions for a permit to use: Cancer, Glaucoma, HIV/AIDS, Alzheimer’s, Cachexia/Anorexia, Severe pain, Severe nausea, Seizures and Muscle spasms.

I found out soon after I started seeing patients for marijuana permits that the DHS was far too modest about this surprisingly effective medicine. As I continued to see more than 4000 patients I was truly amazed at the diversity of diseases for which marijuana was helpful and more so than standard medicine.”-

Dr. Phil Leveque

Read more: http://www.salem-news.com/articles/may262009/marijuana_treatments_pl_5-26-09.php

Marijuana-Like Compounds May Aid Array Of Debiliatiing Conditions Ranging From Parkinson’s Disease To Pain

“Oct. 27, 2004 — No longer a pipe dream, new animal research now indicates that marijuana-like compounds can aid a bevy of debilitating conditions, ranging from brain disorders such as amyotrophic lateral sclerosis (ALS) and Parkinson’s disease, to pain and obesity.

Research from California Pacific Medical Center in San Francisco points to the promise of marijuana-like treatments for those with the fatal brain disorder ALS, also known as Lou Gehrig’s disease.

“Our research indicates that select marijuana compounds, including THC, significantly slow the disease process and extend the life of mice with ALS,” says study author Mary Abood, PhD.

The study extends earlier work from Abood’s group that found that THC also can alleviate some ALS symptoms, like muscle spasms, in patients.

ALS wreaks its havoc by harming nerve cells that control muscles. As a consequence of the damage, an estimated 5,000 Americans afflicted annually experience progressive muscle weakness that can hinder movement, speech, even swallowing and breathing. New treatments for ALS are desperately needed…

“For the first time, our research shows the neuroprotective value of marijuana-like compounds in a well-established animal model of Parkinson’s disease,” says study author Andrea Giuffrida, PhD, of the University of Texas Health Science Center in San Antonio.

Parkinson’s afflicts some 1 million Americans. Symptoms include slowness of movement, muscle stiffness, and shaky tremors, which can harm a person’s ability to walk, talk, write, and eat. This havoc results from the death or injury of brain cells that produce the chemical dopamine.

“There are therapies that can help replenish depleted levels of dopamine and provide symptomatic relief, but none can reverse, prevent, or delay the progression of Parkinson’s disease,” says Giuffrida. “Our research shows that marijuana-like compounds may be able to answer this need.””

Read more: http://www.sciencedaily.com/releases/2004/10/041027102621.htm

 

Neuroprotection by Δ9-Tetrahydrocannabinol, the Main Active Compound in Marijuana, against Ouabain-Induced In Vivo Excitotoxicity

“These results provide evidence that the cannabinoid system can serve to protect the brain against neurodegeneration.”

“In summary, we have shown that in an in vivo model of neurodegeneration Δ9-THC reduces neuronal damage via a CB1-receptor-mediated mechanism. This holds in both the acute and late phase after induction of excitotoxicity. Δ9-THC inhibits astrogliosis via a non-CB1-receptor-controlled mechanism. The results strengthen the concept that the endogenous cannabinoid system may serve to establish a defense system for the brain. This system may be functional in several neurodegenerative diseases in which excitotoxicity is thought to play a role, such as amyotrophic lateral sclerosis, Huntington’s and Parkinson’s diseases, and also in acute neuronal damage as found in stroke and traumatic brain injury. It is conceivable that the endogenous cannabinoid system can be exploited for therapeutic interventions in these types of primarily incurable diseases.”

http://www.jneurosci.org/content/21/17/6475.long

From cannabis to the endocannabinoid system: refocussing attention on potential clinical benefits.

Image result for West Indian Med J

“Cannabis sativa is one of the oldest herbal remedies known to man. Over the past four thousand years, it has been used for the treatment of numerous diseases but due to its psychoactive properties, its current medicinal usage is highly restricted. In this review, we seek to highlight advances made over the last forty years in the understanding of the mechanisms responsible for the effects of cannabis on the human body and how these can potentially be utilized in clinical practice. During this time, the primary active ingredients in cannabis have been isolated, specific cannabinoid receptors have been discovered and at least five endogenous cannabinoid neurotransmitters (endocannabinoids) have been identified. Together, these form the framework of a complex endocannabinoid signalling system that has widespread distribution in the body and plays a role in regulating numerous physiological processes within the body. Cannabinoid ligands are therefore thought to display considerable therapeutic potential and the drive to develop compounds that can be targeted to specific neuronal systems at low enough doses so as to eliminate cognitive side effects remains the ‘holy grail’ of endocannabinoid research.”

http://www.ncbi.nlm.nih.gov/pubmed/23155985

Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities.

Philosophical Transactions of the Royal Society B: Biological Sciences: 367 (1607)

“Human tissues express cannabinoid CB(1) and CB(2) receptors that can be activated by endogenously released ‘endocannabinoids’ or exogenously administered compounds in a manner that reduces the symptoms or opposes the underlying causes of several disorders in need of effective therapy. Three medicines that activate cannabinoid CB(1)/CB(2) receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol; Δ(9)-tetrahydrocannabinol (Δ(9)-THC)) and Sativex (Δ(9)-THC with cannabidiol). These can be prescribed for the amelioration of chemotherapy-induced nausea and vomiting (Cesamet and Marinol), stimulation of appetite (Marinol) and symptomatic relief of cancer pain and/or management of neuropathic pain and spasticity in adults with multiple sclerosis (Sativex). This review mentions several possible additional therapeutic targets for cannabinoid receptor agonists. These include other kinds of pain, epilepsy, anxiety, depression, Parkinson’s and Huntington’s diseases, amyotrophic lateral sclerosis, stroke, cancer, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders. It also describes potential strategies for improving the efficacy and/or benefit-to-risk ratio of these agonists in the clinic. These are strategies that involve (i) targeting cannabinoid receptors located outside the blood-brain barrier, (ii) targeting cannabinoid receptors expressed by a particular tissue, (iii) targeting upregulated cannabinoid receptors, (iv) selectively targeting cannabinoid CB(2) receptors, and/or (v) adjunctive ‘multi-targeting’.”  https://www.ncbi.nlm.nih.gov/pubmed/23108552

“Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities”  http://rstb.royalsocietypublishing.org/content/367/1607/3353.long