“Cannabinoids possess immunomodulatory activity, are neuroprotective in vivo and in vitro and can modify the production of inflammatory mediators… Cannabinoid-induced immunosuppression may have implications for the treatment of neurological disorders that are associated with excess immunological activity, such as multiple sclerosis and Alzheimer’s disease. There is anecdotal evidence that cannabis use improves the symptoms of multiple sclerosis, and studies with animal models are beginning to provide evidence for the mechanism of such effects. The development of nonpsychotropic cannabinoid analogues and modulators of the metabolism of endogenous cannabinoid ligands may lead to novel approaches to the treatment of neurodegenerative disorders.”
Category Archives: Multiple Sclerosis (MS)
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.”
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.”
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
Cannabinoid receptor agonist protects cultured dopaminergic neurons from the death by the proteasomal dysfunction.
“Cannabinoids (CBs) from the Cannabis sativa L. plant, including tetrahydrocannabinol, the principal psychoactive component of marijuana, produce euphoria and relaxation and also impair motor coordination, perception of time, and short-term memory. The principal actions of CBs are mediated by activation of their cognate receptors on presynaptic nerve ends. Various types of cannabinoid receptors, including the orphan G-protein coupled receptors CB1 and CB2, are found in blood vessels, the central nervous system, and immune cells. While CB1 is expressed abundantly in several areas in the brain as well as in peripheral tissues, CB2 is primarily expressed in the immune system, although it was recently detected at low levels in peripheral nerve endings, microglial cells, and astrocytes, as well as in the cerebellum and brain stem. CB1 receptor activation is involved in the control of neural cell fate and mediates neuroprotectivity in different in vivo models of brain injury, including excitotoxicity and ischemia.
In recent years, the capacity of CBs to effect neuroprotection and neurotoxicity has received increasing attention. Evidence of possible neuroprotective effects has accumulated in vitro from models of neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases and multiple sclerosis, as well as from in vivo clinical trial data. These compounds are also able to decrease inflammation by acting on glial cells that influence neuronal survival. The molecular mechanisms underlying cannabinoid-mediated neuroprotection are still poorly understood, but may include the direct activation of neuronal survival signaling pathways through cannabinoid receptors or indirect effects mediated by microglial CB2-receptor stimulation.
Here, we investigated the neuroprotective function of a synthetic cannabinoid-receptor agonist (WIN55.212.2)… These results indicate that WIN55.212.2 may be a candidate for treatment of neurodegenerative diseases, including Parkinson’s disease.”
Latest advances in cannabinoid receptor agonists.
“Since the discovery of cannabinoid receptors and their endogenous ligands in early 1990s, the endocannabinoid system has been shown to play a vital role in several pathophysiological processes. It has been targeted for the treatment of several diseases including neurodegenerative diseases (Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and MS), cancer, obesity, inflammatory bowel disease, neuropathic and inflammatory pain. The last decade has witnessed remarkable advances in the development of cannabinergic ligands displaying high selectivity and potency towards two subtypes of cannabinoid receptors, namely CB1 and CB2.”
“…we highlight the latest advances made in the development of cannabinoid agonists and summarize recently disclosed, novel chemical scaffolds as CB-selective agonists…”
“CONCLUSIONS:
Our analysis reveals prolific patenting activity mainly in the CB2 selective agonist area. Limiting the BBB penetrability, thereby, leading to peripherally restricted CB1/CB2 agonists and enhancing CB2-selectivity emerge as likely prerequisites for avoidance of adverse central CB1 mediated side effects.”
Multiple sclerosis and extract of cannabis: results of the MUSEC trial.
“Multiple sclerosis (MS) is associated with chronic symptoms, including muscle stiffness, spasms, pain and insomnia. Here we report the results of the Multiple Sclerosis and Extract of Cannabis (MUSEC) study that aimed to substantiate the patient based findings of previous studies.”
“CONCLUSION:
The study met its primary objective to demonstrate the superiority of cannabis extract (CE) over placebo in the treatment of muscle stiffness in MS. This was supported by results for secondary efficacy variables. Adverse events in participants treated with CE were consistent with the known side effects of cannabinoids. No new safety concerns were observed.”
Cannabis eases multiple sclerosis (MS) stiffness: study
“Use of cannabis extract helps ease painful muscle stiffness among patients with multiple sclerosis (MS), according to a large trial published on Tuesday in the Journal of Neurology, Neurosurgery and Psychiatry.
The “Phase III” test — the final stage in a process to vet a new drug or medical process — took place among 22 centres in Britain.
Over 12 weeks, 144 patients were given daily tablets of tetrahydrocannabinol, which is the active ingredient in cannabis, and 135 were given a dummy pill, also called a placebo…
…They also reported improvement in sleep quality. Side effects were nervous system disorders and gut problems, but none was severe…
The trial, led by John Peter Zajicek of Britain’s Clinical Neurology Research Group, says standardized doses of cannabis extract can be useful in easing pain and spasms in this disease.
Previous Phase III trials on cannabis and MS have thrown up conflicting results, partly because of the scale by which users report any change in their symptoms, the MUSEC researchers said.”
http://articles.nydailynews.com/2012-10-10/news/34367509_1_multiple-sclerosis-cannabis-nerve-cells
Smoking Cannabis May Reduce Symptoms in Multiple Sclerosis Patients – ABC News
“Smoking marijuana may reduce certain symptoms in patients with multiple sclerosis, according to a new small study published Monday in the Canadian Medical Association Journal.
Researchers from the University of California at San Diego School of Medicine conducted a double blind, controlled clinical trial that included 30 participants who had multiple sclerosis. The scientists hoped to understand whether smoked cannabis reduces symptoms of spasticity, a common symptom of the disease that refers to stiffness and involuntary muscle spasms.
While most past trials have focused on the effects of a pill-form of cannabis, researchers wanted to see specifically whether a smoked form of the drug has a beneficial effect.
“Smoking cannabis was indeed superior to the placebo in reducing spasticity and pain…”
Read More: http://abcnews.go.com/Health/marijuana-reduce-symptoms-multiple-sclerosis-patients/story?id=16328805
Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial.
“Spasticity is a common and disabling symptom that remains a substantial problem for many patients with multiple sclerosis. Some patients have adverse effects from conventional antispasticity medications; for others, spasticity persists despite treatment. A report from the Institute of Medicine in the United States concluded that the active compounds of cannabis (marijuana) are potentially effective in treating neurologic conditions and “should be tested rigorously in clinical trials.” There is evidence that the cannabinoid receptors CB1 and CB2 may be involved in the control of spasticity in multiple sclerosis2 and that the endogenous ligand of CB1, anandamide, is itself an effective antispasticity agent.3 CB1 receptors are primarily presynaptic; their activation inhibits calcium influx and glutamate release, and reduces neuronal excitability by activating somatic and dendritic potassium channels.“
“Although many patients with multiple sclerosis endorse smoking cannabis as therapy, evidence that it relieves spasticity is largely anecdotal, as most trials focus on orally administered cannabinoids. We sought to assess the safety and efficacy of smoked cannabis versus placebo in patients with multiple sclerosis who have treatment-resistant spasticity.”
“Smoked cannabis was superior to placebo in symptom and pain reduction in participants with treatment-resistant spasticity. Future studies should examine whether different doses can result in similar beneficial effects with less cognitive impact.”
“No serious adverse events occurred during the trial.”