Cannabinoids In Multiple Sclerosis Research Articles

Unveiling the Potential of Cannabinoids in Multiple Sclerosis and the Dawn of Nano-Cannabinoid Medicine.

Multiple sclerosis is the predominant autoimmune disorder affecting the central nervous system in adolescents and adults. Specific treatments are categorized as disease-modifying, whereas others are symptomatic treatments to alleviate painful symptoms. Currently, no singular conventional therapy is universally effective for all patients across all stages of the illness. Nevertheless, cannabinoids exhibit significant promise in their capacity for neuroprotection, anti-inflammation, and immunosuppression. This review will examine the traditional treatment for multiple sclerosis, the increasing interest in using cannabis as a treatment method, its role in protecting the nervous system and regulating the immune system, commercially available therapeutic cannabinoids, and the emerging use of cannabis in nanomedicine. In conclusion, cannabinoids exhibit potential as a disease-modifying treatment rather than merely symptomatic relief. However, further research is necessary to unveil their role and establish the safety and advancements in nano-cannabinoid medicine, offering the potential for reduced toxicity and fewer adverse effects, thereby maximizing the benefits of cannabinoids.

Cannabinoids and Multiple Sclerosis: A Critical Analysis of Therapeutic Potentials and Safety Concerns.

Multiple sclerosis (MS) is a complicated condition in which the immune system attacks myelinated axons in the central nervous system (CNS), destroying both myelin and axons to varying degrees. Several environmental, genetic, and epigenetic factors influence the risk of developing the disease and how well it responds to treatment. Cannabinoids have recently sparked renewed interest in their therapeutic applications, with growing evidence for their role in symptom control in MS. Cannabinoids exert their roles through the endogenous cannabinoid (ECB) system, with some reports shedding light on the molecular biology of this system and lending credence to some anecdotal medical claims. The double nature of cannabinoids, which cause both positive and negative effects, comes from their actions on the same receptor. Several mechanisms have been adopted to evade this effect. However, there are still numerous limitations to using cannabinoids to treat MS patients. In this review, we will explore and discuss the molecular effect of cannabinoids on the ECB system, the various factors that affect the response to cannabinoids in the body, including the role of gene polymorphism and its relation to dosage, assessing the positive over the adverse effects of cannabinoids in MS, and finally, exploring the possible functional mechanism of cannabinoids in MS and the current and future progress of cannabinoid therapeutics.

The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews.

Pharmaceutical cannabinoids such as nabiximols, nabilone and dronabinol, and plant-based cannabinoids have been investigated for their therapeutic potential in treating multiple sclerosis (MS) symptoms. This review of reviews aimed to synthesise findings from high quality systematic reviews that examined the safety and effectiveness of cannabinoids in multiple sclerosis. We examined the outcomes of disability and disability progression, pain, spasticity, bladder function, tremor/ataxia, quality of life and adverse effects. We identified 11 eligible systematic reviews providing data from 32 studies, including 10 moderate to high quality RCTs. Five reviews concluded that there was sufficient evidence that cannabinoids may be effective for symptoms of pain and/or spasticity in MS. Few reviews reported conclusions for other symptoms. Recent high quality reviews find cannabinoids may have modest effects in MS for pain or spasticity. Future research should include studies with non-cannabinoid comparators; this is an important gap in the evidence.

Are cannabinoids effective in multiple sclerosis?

Multiple beneficial effects have been proposed lately for cannabinoids in different clinical situations. Among them, it has been postulated they would control symptoms of multiple sclerosis. However, there is no consensus about their real clinical role. To answer this question, we searched in Epistemonikos database, which is maintained by screening multiple databases. We identified 25 systematic reviews including 35 studies overall, of which 26 were randomized trials. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded cannabinoids in multiple sclerosis do not reduce spasticity or pain, and are probably associated to frequent adverse effects.

Activation of cannabinoid CB2 receptors reduces hyperalgesia in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis

Clinical trials investigating the analgesic efficacy of cannabinoids in multiple sclerosis have yielded mixed results, possibly due to psychotropic side effects mediated by cannabinoid CB1 receptors. We hypothesized that, a CB2-specific agonist (JWH-133) would decrease hyperalgesia in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. Four weeks after induction of experimental autoimmune encephalomyelitis, we found that intrathecal administration of JWH-133 (10–100μg) dose-dependently reduced both mechanical and cold hypersensitivity without producing signs of sedation or ataxia. The anti-hyperalgesic effects of JWH-133 could be dose-dependently prevented by intrathecal co-administration of the CB2 antagonist, AM-630 (1–3μg). Our results suggest that JWH-133 acts at CB2 receptors, most likely within the dorsal horn of the spinal cord, to suppress the hypersensitivity associated with experimental autoimmune encephalomyelitis. These are the first pre-clinical studies to directly promote CB2 as a promising target for the treatment of central pain in an animal model of multiple sclerosis.

Therapeutic Potential of Cannabinoids in Neurodegenerative Disorders: A Selective Review

The endocannabinoid system (ECS) is now recognised as an important modulator of various central nervous system processes. More recently, an increasing body of evidence has accumulated to suggest antioxidant, anti-inflammatory and neuroprotective roles of ECS. In this review we discuss the role and therapeutic potential of ECS in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease, multiple sclerosis, Huntington's disease, Tourette's syndrome, brain ischemia and amyotrophic lateral sclerosis (ALS). Elements of the ECS, such as fatty acid amide hydrolase or the cannabinoid receptors are now considered as promising pharmacological targets for some diseases. Although still preliminary, recent reports suggest that modulation of the ECS may constitute a novel approach for the treatment of AD. There are windows of opportunity in conditions caused by acute events such as trauma and ischemia as well in conditions that may involve altered functionality of the target receptors of the ECS, such as in AD. The ECS changes in Parkinson's disease could be compensatory as well as pathogenic of the illness process and needs further understanding and clinical studies are still in the preliminary stage. There is not enough evidence to support use of cannabinoids in treating Huntington's disease, tics and obsessive compulsive behaviour in Tourette's syndrome. Evidence on therapeutic use of cannabinoids in multiple sclerosis and ALS is currently limited. A major challenge for future research is the development of novel compounds with more selectivity for various components of the ECS which could target different neurotoxic pathways and be used in combination therapy.

Role of Cannabinoids in Multiple Sclerosis

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.

Increased Cannabinoid Receptor 1-Immunoreactive Nerve Fibers in Overactive and Painful Bladder Disorders and Their Correlation With Symptoms

To study the expression of cannabinoid receptor 1 (CB1) in human urinary bladder hypersensitivity and overactivity disorders, and correlate changes with symptoms. Cannabinoid receptor agonists have been shown to modulate urinary bladder contractility and reduce pain after bladder inflammation; their clinical efficacy on lower urinary tract symptoms was demonstrated in the Cannabinoids in Multiple Sclerosis study. Bladder tissue specimens were obtained from patients with painful bladder syndrome (PBS, n=13), idiopathic detrusor overactivity (IDO, n=14), and from controls with asymptomatic microscopic hematuria (n=16). The severity of symptoms was assessed using the Pelvic Pain and Urgency/Frequency Questionnaire. Pain score was also recorded on a visual analogue scale. Specimens were immunostained using specific antibodies to CB1 and to neurofilaments as a structural maker. Detrusor and suburothelial nerve fiber density was quantified with a visual grading scale. The immunohistochemistry results were correlated with "Pain, Frequency, and Urgency" scores. CB1-immunoreative nerve fibers were significantly increased in the suburothelium of PBS (P=.0123) and IDO (P=.0013) specimens, and in detrusor layer in IDO (P=.0003), as compared with controls. CB1-immunoreactive suburothelial nerve fiber density correlated significantly with pain scores (Visual Analogue Scale) in PBS (r=.6878, P=.0347) and urgency scores in IDO (r=.6623, P=.0027). Neurofilaments-immunoreactive suburothelial nerve fibers were significantly increased in PBS (P=.019) and IDO (P=.05). The results of this study suggest that increased nerve fibers, which express CB1, may be related to bladder pain in PBS and urgency in IDO. Our findings support clinical trials of CB1 agonists in bladder disorders.

Cannabinoids, multiple sclerosis and neuroprotection

The cannabinoid signaling system participates in the control of cell homeostasis in the CNS, which explains why, in different neurodegenerative diseases including multiple sclerosis (MS), alterations in this system have been found to serve both as a pathogenic factor (malfunctioning of this system has been found at early phases of these diseases) and as a therapeutic target (the management of this system has beneficial effects). MS is an autoimmune disease that affects the CNS and it is characterized by inflammation, demyelination, remyelination, gliosis and axonal damage. Although it has been considered mainly as an inflammatory disorder, recent studies have recognized the importance of axonal loss both in the progression of the disorder and in the appearance of neurological disability, even in early stages of the disease. In recent years, several laboratories have addressed the therapeutic potential of cannabinoids in MS, given the experience reported by some MS patients who self-medicated with marijuana. Most of these studies focused on the alleviation of symptoms (spasticity, tremor, anxiety and pain) or on the inflammatory component of the disease. However, recent data also revealed the important neuroprotective action that could be exerted by cannabinoids in this disorder. The present review will be precisely centered on this neuroprotective potential, which is based mainly on antioxidant, anti-inflammatory and anti-excitotoxic properties, exerted through the activation of CB1 or CB2 receptors or other unknown mechanisms.

The effect of cannabis on urge incontinence in patients with multiple sclerosis: a multicentre, randomised placebo-controlled trial (CAMS-LUTS)

To test whether cannabinoids reduce urge incontinence episodes without affecting voiding in patients with multiple sclerosis. This was part of the multicentre trial of the Cannabinoids in Multiple Sclerosis (CAMS) study. The CAMS study randomised 630 patients to receive oral administration of cannabis extract, Delta(9)-tetrahydrocannabinol (THC) or matched placebo. For this substudy subjects completed incontinence diaries. All three groups showed a significant reduction, p<0.01, in adjusted episode rate (i.e. correcting for baseline imbalance) from baseline to the end of treatment: cannabis extract, 38%; THC, 33%; and placebo, 18%. Both active treatments showed significant effects over placebo (cannabis extract, p=0.005; THC, p=0.039). The findings are suggestive of a clinical effect of cannabis on incontinence episodes in patients with MS. This is in contrast to the negative finding of the CAMS study, where no difference was seen in the primary outcome of spasticity.

Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up

Objective: To test the effectiveness and long term safety of cannabinoids in multiple sclerosis (MS), in a follow up to the main Cannabinoids in Multiple Sclerosis (CAMS) study. Methods: In...

The use of cannabinoids in multiple sclerosis

Naturally occurring cannabinoids including Δ9-tetrahydrocannabinol and cannabidiol as well as endocannabinoids and synthetic cannabinoids may have a role in modulating experimental models of multiple sclerosis. Recent clinical studies to treat symptoms of multiple sclerosis have shown varying results, which may reflect issues relating to the way in which such studies were conducted. There is now increasing interest in the potential role of cannabinoids not only in symptom relief, but also for their possible neuroprotective actions.

Cannabinoids in multiple sclerosis: do they have a therapeutic role?

This is an exciting time for cannabinoid research. Evidence suggests that cannabis (marijuana) can alleviate symptoms like muscle spasticity and pain in patients with multiple sclerosis (MS). Interest in the field of cannabinoids has been strengthened by the identification and cloning of cannabinoid receptors located in the central nervous system and the peripheral immune organs, and by the discovery of the endogenous cannabinoid ligands. Cannabinoids are also efficacious in animal models of MS. However, there have been only ten published clinical reports on the use of cannabis in MS, involving 78 individuals worldwide, and the results have been equivocal. Researchers encounter a number of difficulties in designing clinical studies that use cannabinoids. From the studies reporting the use of cannabinoids in MS patients with spasticity, the somewhat better designed studies failed to demonstrate objective improvement. Therefore, convincing evidence that cannabinoids are effective in MS is still lacking.

Immunomodulatory effects of orally administered cannabinoids in multiple sclerosis

Cannabinoids can modulate the function of immune cells. We here present the first human in vivo study measuring immune function in 16 MS patients treated with oral cannabinoids. A modest increase of TNF-α in LPS-stimulated whole blood was found during cannabis plant-extract treatment ( p=0.037), with no change in other cytokines. In the subgroup of patients with high adverse event scores, we found an increase in plasma IL-12p40 ( p=0.002). The results suggest pro-inflammatory disease-modifying potential of cannabinoids in MS.