https://www.ncbi.nlm.nih.gov/pubmed/12617697: The major psychoactive constituent of Cannabis sativa, delta(9)-tetrahydrocannabinol (delta(9)-THC), and endogenous cannabinoid ligands, such as anandamide, signal through G-protein-coupled cannabinoid receptors localised to regions of the brain associated with important neurological processes. Signalling is mostly inhibitory and suggests a role for cannabinoids as therapeutic agents in CNS disease where inhibition of neurotransmitter release would be beneficial. Anecdotal evidence suggests that patients with disorders such as multiple sclerosis smoke cannabis to relieve disease-related symptoms. Cannabinoids can alleviate tremor and spasticity in animal models of multiple sclerosis, and clinical trials of the use of these compounds for these symptoms are in progress. The cannabinoid nabilone is currently licensed for use as an antiemetic agent in chemotherapy-induced emesis. Evidence suggests that cannabinoids may prove useful in Parkinson's disease by inhibiting the excitotoxic neurotransmitter glutamate and counteracting oxidative damage to dopaminergic neurons. The inhibitory effect of cannabinoids on reactive oxygen species, glutamate and tumour necrosis factor suggests that they may be potent neuroprotective agents. Dexanabinol (HU-211), a synthetic cannabinoid, is currently being assessed in clinical trials for traumatic brain injury and stroke. Animal models of mechanical, thermal and noxious pain suggest that cannabinoids may be effective analgesics. Indeed, in clinical trials of postoperative and cancer pain and pain associated with spinal cord injury, cannabinoids have proven more effective than placebo but may be less effective than existing therapies. Dronabinol, a commercially available form of delta(9)-THC, has been used successfully for increasing appetite in patients with HIV wasting disease, and cannabinoid receptor antagonists may reduce obesity. Acute adverse effects following cannabis usage include sedation and anxiety. These effects are usually transient and may be less severe than those that occur with existing therapeutic agents. The use of nonpsychoactive cannabinoids such as cannabidiol and dexanabinol may allow the dissociation of unwanted psychoactive effects from potential therapeutic benefits. The existence of other cannabinoid receptors may provide novel therapeutic targets that are independent of CB(1) receptors (at which most currently available cannabinoids act) and the development of compounds that are not associated with CB(1) receptor-mediated adverse effects. Further understanding of the most appropriate route of delivery and the pharmacokinetics of agents that act via the endocannabinoid system may also reduce adverse effects and increase the efficacy of cannabinoid treatment. This review highlights recent advances in understanding of the endocannabinoid system and indicates CNS disorders that may benefit from the therapeutic effects of cannabinoid treatment. Where applicable, reference is made to ongoing clinical trials of cannabinoids to alleviate symptoms of these disorders.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931550: In addition to potentially preventing inflammatory and excitotoxic damage in MS, cannabinoids may also have a role in promoting repair of the axonal myelin sheath. Several studies have indicated that cannabinoids, via CB1 or CB2 (or both), may regulate myelination in the developing brain (Arevalo-Martin et al., 2007), the normal adult brain (Kittler et al., 2000) and the inflamed brain in the TMEV model of MS (Arevalo-Martin et al., 2003). The increased remyelination seen in the TMEV model may reflect the ability of cannabinoids to reduce inflammatory mediators which retard remyelination processes. Alternatively, the cannabinoids may have a bona fide stimulatory effect upon myelination, by enhancing the survival (Molina-Holgado et al., 2002), migration and differentiation towards an oligodendrocyte fate (Arevalo-Martin et al., 2007) of oligodendrocyte progenitor cells in the inflamed brain. If these exciting findings of cannabinoid-mediated attenuation of inflammation, stimulation of remyelination, and behavioural and symptomatic recovery translate from model systems to humans, cannabinoids may be promising therapeutics in MS.
http://www.ncbi.nlm.nih.gov/pubmed/22583441: For many years, multiple sclerosis (MS) patients have been self-medicating with illegal street cannabis to alleviate symptoms associated with MS. Data from animal models of MS and clinical studies have supported the anecdotal data that cannabis can improve symptoms such as limb spasticity, which are commonly associated with progressive MS, by the modulation of excessive neuronal signalling. This has lead to cannabis-based medicines being approved for the treatment of pain and spasticity in MS for the first time. Experimental studies into the biology of the endocannabinoid system have revealed that cannabinoids have activity, not only in symptom relief but also potentially in neuroprotective strategies which may slow disease progression and thus delay the onset of symptoms such as spasticity. This review appraises the current knowledge of cannabinoid biology particularly as it pertains to MS and outlines potential future therapeutic strategies for the treatment of disease progression in MS.
http://www.ncbi.nlm.nih.gov/pubmed/18496477: Pain, spasticity, tremor, spasms, poor sleep quality, and bladder and bowel dysfunction, among other symptoms, contribute significantly to the disability and impaired quality of life of many patients with multiple sclerosis (MS). Motor symptoms referable to the basal ganglia, especially paroxysmal dystonia, occur rarely and contribute to the experience of distress. A substantial percentage of patients with MS report subjective benefit from what is often illicit abuse of extracts of the Cannabis sativa plant; the main cannabinoids include delta-9-tetrahydrocannabinol (delta9-THC) and cannabidiol. Clinical trials of cannabis plant extracts and synthetic delta9-THC provide support for therapeutic benefit on at least some patient self-report measures. An illustrative case is presented of a 52-year-old woman with MS, paroxysmal dystonia, complex vocal tics, and marijuana dependence. The patient was started on an empirical trial of dronabinol, an encapsulated form of synthetic delta9-THC that is usually prescribed as an adjunctive medication for patients undergoing cancer chemotherapy. The patient reported a dramatic reduction of craving and illicit use; she did not experience the "high" on the prescribed medication. She also reported an improvement in the quality of her sleep with diminished awakenings during the night, decreased vocalizations, and the tension associated with their emission, decreased anxiety and a decreased frequency of paroxysmal dystonia.
http://www.ncbi.nlm.nih.gov/pubmed/18781983: Multiple sclerosis (MS) is a neurodegenerative disease that is characterised by repeated inflammatory/demyelinating events within the central nervous system (CNS). In addition to relapsing-remitting neurological insults, leading to loss of function, patients are often left with residual, troublesome symptoms such as spasticity and pain. These greatly diminish "quality of life" and have prompted some patients to self-medicate with and perceive benefit from cannabis. Recent advances in cannabinoid biology are beginning to support these anecdotal observations, notably the demonstration that spasticity is tonically regulated by the endogenous cannabinoid system. Recent clinical trials may indeed suggest that cannabis has some potential to relieve, pain, spasms and spasticity in MS. However, because the CB(1) cannabinoid receptor mediates both the positive and adverse effects of cannabis, therapy will invariably be associated with some unwanted, psychoactive effects. In an experimental model of MS, and in MS tissue, there are local perturbations of the endocannabinoid system in lesional areas. Stimulation of endocannabinoid activity in these areas either through increase of synthesis or inhibition of endocannabinoid degradation offers the positive therapeutic potential of the cannabinoid system whilst limiting adverse events by locally targeting the lesion. In addition, CB(1) and CB(2) cannabinoid receptor stimulation may also have anti-inflammatory and neuroprotective potential as the endocannabinoid system controls the level of neurodegeneration that occurs as a result of the inflammatory insults. Therefore cannabinoids may not only offer symptom control but may also slow the neurodegenerative disease progression that ultimately leads to the accumulation of disability.
http://www.ncbi.nlm.nih.gov/pubmed/21323391: Although extracts from the cannabis plant have been used medicinally for thousands of years, it is only within the last 2 decades that our understanding of cannabinoid physiology and the provision of evidence for therapeutic benefit of cannabinoids has begun to accumulate. This review provides a background to advances in our understanding of cannabinoid receptors and the endocannabinoid system, and then considers how cannabinoids may help in the management of multiple sclerosis (MS). The relative paucity of treatments for MS-related symptoms has led to experimentation by patients with MS in a number of areas including the use of cannabis extracts. An increasing amount of evidence is now emerging to confirm anecdotal reports of symptomatic improvement, particularly for muscle stiffness and spasms, neuropathic pain and sleep and bladder disturbance, in patients with MS treated with cannabinoids. Trials evaluating a role in treating other symptoms such as tremor and nystagmus have not demonstrated any beneficial effects of cannabinoids. Safety profiles of cannabinoids seem acceptable, although a slow prolonged period of titration improves tolerability. No serious safety concerns have emerged. Methodological issues in trial design and treatment delivery are now being addressed. In addition, recent experimental evidence is beginning to suggest an effect of cannabinoids on more fundamental processes important in MS, with evidence of anti-inflammation, encouragement of remyelination and neuroprotection. Trials are currently under way to test whether cannabinoids may have a longer term role in reducing disability and progression in MS, in addition to symptom amelioration, where indications are being established.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3628147: The medical community has provided studies proving the efficacy of marijuana in treatment of patients who have not responded to other treatments. Specifically, these studies have shown the therapeutic value of marijuana in controlling pain, alleviating nausea and vomiting, as well as alleviating symptoms of multiple sclerosis (MS) and AIDS. In 2011, a randomized controlled trial of cannabinoids’ treatment of chronic non-cancer pain also demonstrated positive outcomes . Significant analgesic effects were seen in treating neuropathic pain, fibromyalgia, and rheumatoid arthritis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430692: Multiple sclerosis (MS) is a life-long chronic disease in which nerve cells are attacked by the immune system, originating painful muscle spasms and many other problems, including neuropathic pain. There are about 1.1 million worldwide sufferers of MS. Clinical trials have tested the potential medical applications of cannabis for the treatment of MS symptoms, although some of them present a small number of patients ; and there are also data from responses to questionnaires (Tables (Tables33--4)4) [68, 117]. Smoking cannabis not only has helped to stop spasms, but has halted the progression of multiple sclerosis. Although smoking cannabis is illegal in some countries, estimates suggest that 10% to 30% of MS patients in Europe smoke cannabis to ease the painful and disabling symptoms of the disease. Medications prepared from whole plant cannabis extract, containing known amounts of THC and CBD as the principal components have been prepared to be administered by oral spray to relieve MS symptoms, as well as for the treatment of other disorders with severe neuropathic pain. This product has undergone phase III placebo-controlled trials, which show that it reduces neuropathic pain, spasticity, and sleep disturbances. Its use has been approved only in Canada so far. Furthermore, animal model of multiple sclerosis, have found other advantage of cannabinoid receptor agonists, since they appear to exert CB1 receptor-mediated neuroprotective effects that would be benefitial for the neurodegeneration occurring in MS .
Cannabis -vs- Multiple Sclerosis