Multiple sclerosis (MS) is an autoimmune and neuroinflammatory disorder that affects the neurological system and impairs body functions. The pathogenesis of MS is characterized by development of auto-antibodies against myelin peptides/sheath of nerve cells that results in nerve inflammation and impaired neurotransmission control between the muscles and the central nervous system.
In MS patients, impaired motor control leads to uncontrolled spastic movements and pain symptoms.
Spasticity is characterized by overactive muscle activity with movement disorder, pain, generalized weakness, hypertonia, and contracture – as well as associated neurological problems. The complete 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 been confirmed that MS is an immune-mediated disorder, and the treatment should target, modulate, and normalize the abnormal immune system.
Modern medical approaches involve administration of exogenous steroids, which do not achieve therapeutic success, although these drugs are immunosuppressive in nature. Use of biologics – such as interferons – may provide symptomatic relief; albeit, with serious side effects. In most of cases, the MS treatment side effects outweigh the possible 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 with fewer and more tolerable side effects.
Let’s look into the results 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 been demonstrated in several experimental studies using MS models. As cannabinoid receptors regulate the tonic control of spasticity, targeting the cannabinoid receptors, medical cannabis can provide positive treatment outcomes. Experimental use of endocannabinoid agonists in MS models has shown that cannabis can be therapeutically used for tonic control 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 circulatory 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 complete role of endocannabinoids in the pathogenesis of MS is not understood, it is clear that endocannabinoids play a key role in MS pathogenesis and serves as a potential drug target.
In addition to anti-spasticity benefits, THC also possesses immunosuppressive properties that can be useful to treat MS, which is an autoimmune disorder. Experimental studies 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 remarkable reduction of inflammation and inflammatory cells (macrophages) presence. However, no reduction of inflammatory reactions was observed in untreated animals.
Now it all makes sense.
Cannabinoids can 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 results of experimental studies, medical cannabis has 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 been shown to provide objective and/or subjective relief of MS symptoms such as tremor, spasticity, pain, and nocturia. These results were in accordance/concordant with the results of experimental animal studies.
Recently, Sativex – a cannabis-based medication – has been tested and proved to be useful for treatment of spasticity and neuropathic pain in MS patients. Similar results were reported in other studies. In a randomized, placebo-controlled study that enrolled 667 stable MS patients, cannabinoids treatment showed objective 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 reduced lower spasm frequency and improved mobility in conventional treatment-resistant MS patients who suffered persistent spasticity. The side effects of CBME treatment were reported to be tolerable.
Another study that involved 160 MS patients have shown that CBME (Sativex) treatment significantly reduced 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 remarkable side effects on mood, cognition, or intoxication was observed, and most of the reported symptoms were mild.
What we have is a number of small-scale clinical trials that proved the anti-spasticity benefits of cannabis in MS patients. We need large-scale, randomized clinical trials to showcase scientifically-plausible therapeutic benefits of medical cannabis and to nail the lies of big pharma companies that continue 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 studies 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 show that normal nerve tissues can express CB2 receptors; however, CB2 receptors are widely expressed in leucocytes.
Studies have confirmed that apparent CB2 agonist may possess anti-spastic activity, which need not to be owing to direct activity of CB2 receptors. However, the anti-spastic activity can 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 shown that tetrahydrocannabinol and CB1 receptors are the predominant mediators of therapeutic benefits (anti-spasticity) as well as the adverse events.
To treat MS symptoms, targeting not only CB1 receptors but CB2 is also useful 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 involves activation of myelin-specific CD4+ peripheral T cells which enters the spinal cord and differentiates into 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 studies 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 serve as potential therapeutic agents.
The available evidence clearly demonstrate that CB2 receptor activation by cannabis constituents can improve 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 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 provide neuroprotection in MS patients by reducing inflammatory CD4+ lymphocyte infiltration, suppressing leucocyte adhesion molecules in the brain endothelium, inhibiting microglial response to inflammation with improved neural plasticity and fewer side effects.
Chewing takes the edge over smoking
To avoid possible respiratory side effects, non-smoking form of marijuana, something like chewing gum, can be preferred to reduce spasticity and related pain in MS patients. Chewing gum formulation has fewer side effects, and it is also more socially-acceptable than conventional marijuana consumption routes such as smoking.
As reported by AXIM Biotechnology, a marijuana gum manufacturer, chewing gum formulation is uniquely designed to release marijuana components into the oral mucosal blood circulation that bypasses liver metabolic processes (first-pass metabolism). By this way, prolonged/sustained dose release can be ensured without peaking too much.
In addition to cannabis medical benefits, chewing (mastication) has its own medical benefits including neurostimulation and neuroprotective effects. Available research evidences have shown that mastication can aid neurogenesis, promote oral and heart health, and reduce stress and age-related cognitive decline.
No comments:
Post a Comment