Multiple sclerosis (MS) is an autoimmune and neuroinflammatory disorder that affects the neurological system and impairs physique functions. The pathogenesis of MS is characterized by development of auto-antibodies versus myelin peptides/sheath of nerve cells that results in nerve inflammation and impaired neurotransmission regulate between the muscles and the central nervous system.
In MS patients, impaired motor regulate leads to uncontrolled spastic movements and pain symptoms. Spasticity is characterized by overactive muscle activity along with movement disorder, pain, generalized weakness, hypertonia, and contracture – as well as associated neurological problems. The finish pathogenesis of spasticity in MS patients is not understood. However, it is believed that it occurs as a result of selective neuronal loss and alterations in the balance.
Based on the available findings, it has actually been confirmed that MS is an immune-mediated disorder, and the treatment need to target, modulate, and normalize the abnormal immune system.
Modern medical approaches involve administration of exogenous steroids, which do not achieve therapeutic success, even though these drugs are immunosuppressive in nature. Use of biologics – such as interferons – might offer symptomatic relief; albeit, along with major adverse effects. In most of cases, the MS treatment adverse effects outweigh the feasible benefits.
Recent interest in medical cannabis has trended towards the use of cannabinoids to treat the symptoms of MS including spasticity and pain. Particularly, medical cannabis takes the edge over conventional therapy as it provides a desirable therapeutic outcome along with fewer and much more tolerable adverse effects.
Let’s look in to the outcomes of clinical trial evidence and the therapeutic potential of cannabis in MS patients, as well as the pharmacology of cannabinoids.
Evidence from preclinical studies
The role of endocannabinoids in the regulation of spasticity has actually been demonstrated in several experimental surveys using MS models. As cannabinoid receptors regulate the tonic regulate of spasticity, targeting the cannabinoid receptors, medical cannabis can easily offer positive treatment outcomes. Experimental use of endocannabinoid agonists in MS models has actually shown that cannabis can easily be therapeutically used for tonic regulate of spasticity.
In preclinical MS models, cannabinoids treatment drastically reduced spasticity and tremor by influencing CB1 and CB2 receptors. In MS-induced (experimentally) animals, elevated levels of blood circulation endocannabinoid were observed in the brains and spinal cords. Administration of cannabis constituents has ameliorated the symptoms of MS by inhibiting endocannabinoid membrane transport or enzymatic hydrolysis. Although, the finish role of endocannabinoids in the pathogenesis of MS is not understood, it is clear that endocannabinoids play a essential role in MS pathogenesis and serves as a potential drug target.
In addition to anti-spasticity benefits, THC additionally possesses immunosuppressive properties that can easily be beneficial to treat MS, which is an autoimmune disorder. Experimental surveys have demonstrated the THC injections attenuated or delayed clinical signs of experimental autoimmune encephalomyelitis (MS model), and this benefit was not observed in non-treated animals. Histopathological examination of the animals’ brain showed incredible reduction of inflammation and inflammatory cells (macrophages) presence. However, no reduction of inflammatory reactions was observed in untreated animals.
Now it all of makes sense.
Cannabinoids can easily treat MS symptoms by treating/preventing spasticity and pain, as well as by protecting the nerves from inflammation in MS patients.
Human clinical trial results
Based on the outcomes of experimental studies, medical cannabis has actually been tested in humans and modest improvements of MS symptoms were reported. Although, most of the studies involved small numbers of trial subjects, Δ9-tetrahydrocannabinol has actually been shown to offer target and/or subjective relief of MS symptoms such as tremor, spasticity, pain, and nocturia. These outcomes were in accordance/concordant along with the outcomes of experimental animal studies.
Recently, Sativex – a cannabis-based medication – has actually been tested and proved to be beneficial for treatment of spasticity and neuropathic pain in MS patients. Similar outcomes were reported in other studies. In a randomized, placebo-controlled study that enrolled 667 steady MS patients, cannabinoids treatment showed target improvement in mobility and pain (as reported by trial subjects/self-reporting benefits).
In a small double-blind, cross-over, placebo-controlled study, delta-9-THC treatment significantly improved spasticity in multiple sclerosis patients. These findings were similar to the results of a double-blind, randomized, placebo-controlled study that employed cannabis-based medicinal extract (CBME) that contains THC and CBD.
An independent study to demonstrate the anti-spasticity property of CBME has shown that CBME low lesser spasm frequency and improved mobility in conventional treatment-resistant MS patients that endured persistent spasticity. The adverse effects of CBME treatment were reported to be tolerable.
Another study that involved 160 MS patients have actually shown that CBME (Sativex) treatment significantly low the spasticity visual analog scale (VAS) score as evidenced by improvements in spasticity, pain, bladder problem, tremor, and spasms. These treatment benefits were not observed in the placebo group. No incredible adverse effects on mood, cognition, or intoxication was observed, and most of the reported symptoms were mild.
What we have actually is a number of small-scale clinical trials that proved the anti-spasticity benefits of cannabis in MS patients. We demand large-scale, randomized clinical trials to showcase scientifically-plausible therapeutic benefits of medical cannabis and to nail the lies of big pharma companies that go on to oppress the potential therapeutic benefits of medical cannabis. I strongly believe that such trials are not far-away.
Receptor pharmacology of Cannabis
Research evidence have shown that CB1 receptors are predominantly expressed in nerve cells present in the brain and peripheral tissues. Recent surveys have shown that endocannabinoid system and cannabinoid type 1 (CB1) receptors are involved in regulation of synaptic neurotransmission, which confirms the notion that cannabinoids can control spasticity in humans.
Unlike CB1, limited evidences are available to prove to that normal nerve tissues can easily express CB2 receptors; however, CB2 receptors are widely expressed in leucocytes.
Studies have confirmed that apparent CB2 agonist might possess anti-spastic activity, which demand not to be owing to direct activity of CB2 receptors. However, the anti-spastic activity can easily possibly occur as a result of in-vivo generation of certain cannabinoid metabolites that possess affinity for CB1 receptors, which actually mediate the therapeutic/anti-spastic effects.
Receptor pharmacological studies on the cannabinoid system and cannabis have actually shown that tetrahydrocannabinol and CB1 receptors are the predominant mediators of therapeutic benefits (anti-spasticity) as well as the side events.
To treat MS symptoms, targeting not only CB1 receptors yet CB2 is additionally beneficial to attenuate neuroinflammatory reactions. CB2 receptors are widely expressed in MS plaques by microglia, lymphocytes, and astrocytes that contribute to MS symptoms.
The pathogenesis of MS includes activation of myelin-personal CD4+ peripheral T cells which goes into the spinal cord and differentiates in to T-helper cells that elicit delayed-type hypersensitivity reactions. In this process, immune cells, as well as adjacent tissue cells, respond to the inflammatory signals that lead to progressive destruction of myelin sheath (demyelination) and motor nerve cells. This cascade of inflammatory events contributes to nerve damage, spasticity, and pain in MS patients.
Research surveys have shown that CB2 is predominantly expressed in MS plaques by astrocytes, microglia and migratory lymphocytes (inflammation causatives). In experimental animal studies, selective CB2 agonist administration improved motor function by modulating lymphocyte-mediated microglial inflammation in the spinal cord. In this context, it is clear that CB2-targeting agonists, such as cannabinoids, can easily serve as potential therapeutic agents.
The available evidence clearly demonstrate that CB2 receptor activation by cannabis constituents can easily boost autoimmune-mediated demyelination by modulating or inhibiting activation of CD4+ T cells, dendritic cells, B lymphocytes, and brain-associated macrophages (microglial and astrocyte) that involve in induction of delayed type hypersensitivity reactions. The activation of CB2 receptors by cannabis constituents can easily most likely be useful to modulate inflammatory response/reactions including neuroinflammatory processes in MS in addition to anti-spastic benefits.
Taken together, the activation of CB2 receptors by cannabis constituents such as Delta9-tetrahydrocannabinol (Delta9-THC) can easily offer neuroprotection in MS patients by cutting down inflammatory CD4+ lymphocyte infiltration, suppressing leucocyte adhesion molecules in the brain endothelium, inhibiting microglial response to inflammation along with improved neural plasticity and fewer adverse effects.
Chewing takes the edge over smoking
To stay away from feasible respiratory adverse effects, non-smoking form of marijuana, something adore chewing gum, can easily be beloved to reduce spasticity and related pain in MS patients. Chewing gum formulation has actually fewer adverse effects, and it is additionally much more socially-acceptable compared to conventional marijuana consumption routes such as smoking.
As reported by AXIM Biotechnology, a marijuana gum manufacturer, chewing gum formulation is uniquely made to release marijuana components in to the oral mucosal blood circulation that bypasses liver metabolic processes (first-pass metabolism). By this way, prolonged/sustained dose release can easily be ensured free of peaking too much.
In addition to cannabis medical benefits, chewing (mastication) has actually its own medical benefits including neurostimulation and neuroprotective effects. Available research evidences have actually shown that mastication can easily aid neurogenesis, promote oral and heart health, and reduce tension and age-related cognitive decline.