Category Archives: Multiple Sclerosis (MS)

Cannabidiol as a Promising Anti-Inflammatory Agent Targeting TYK2: Molecular Docking and Dynamic Simulation Approaches for Therapeutic Applications in Multiple Sclerosis

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“Introduction: Multiple sclerosis (MS) involves chronic inflammation driven by dysregulation of the JAK-STAT pathway. This study aimed to evaluate the potential interaction of natural cannabinoids with TYK2, with a focus on cannabidiol (CBD), using computational in silico approaches.

Methods: A combined molecular docking and molecular dynamics (MD) workflow was used. Cannabinoid ligands and the TYK2 structure (JH2 domain) were prepared and docked in MOE, followed by 20 ns MD simulations under NVT and NPT conditions in GROMACS. Complex stability and ligand-protein interactions were analysed.

Results: CBD showed a competitive docking score (-7.31 kcal/mol) and a refined RMSD of 0.9198 Å. MD simulations revealed a stable CBD-TYK2 complex, with RMSD fluctuations of 0.15-0.20 nm, which were lower than those observed for the reference inhibitor, deucravacitinib. RMSF analysis revealed a slight increase in local flexibility in specific regions without affecting the overall stability of the protein. The radius of gyration remained stable throughout the simulation, indicating that the protein’s compactness was preserved. Hydrogen bond analysis showed fewer but transient interactions for CBD, consistent with a binding mode dominated by hydrophobic interactions.

Discussion: These computational results suggest that CBD interacts stably with TYK2 through a distinct binding mode compared to the reference inhibitor, deucravacitinib, while maintaining the structural integrity of the protein.

Conclusion: CBD showed a stable predicted interaction with TYK2, supporting its potential as a candidate for further in vitro and in vivo studies in the context of MS-related inflammation.”

https://pubmed.ncbi.nlm.nih.gov/42576587

https://www.eurekaselect.com/article/157501

Nabiximols in Multiple Sclerosis: Beyond Spasticity-An Exploratory Systematic Review and Meta-Analysis of Symptomatic Outcomes

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“Background/Objectives: Nabiximols, a standardized extract of Cannabis sativa, has been approved as an add-on therapy for patients with moderate to severe spasticity associated with multiple sclerosis (MS). Moreover, current Italian treatment algorithms suggest that cannabis-based therapies may have further relevance in the management of MS. The aim of our systematic review and meta-analysis was to assess the effectiveness of nabiximols in relieving symptoms other than spasticity in adult MS patients. 

Methods: A systematic search was conducted in Web of Science, MEDLINE (via PubMed), Cochrane CENTRAL and Embase on September 10, 2025. Study selection was performed according to the predefined PROSPERO protocol (CRD42022329952). Data were combined into a common denominator and examined using a random-effects model with meta-regression expressed as mean difference (MD) and a 95% confidence interval (CI). Risk of bias was assessed using the Cochrane risk of bias instrument (RoB2) and the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. 

Results: Of the 49 eligible articles, 25 were included in the statistical analysis (2949 patients). Significant improvements in spasm quality (MD = -16.87; 95% CI = (-29.75)-(-3.99)), bladder function (MD = -16.38; 95% CI = (-22.18)-(-10.58)), sleep disruption (MD = -15.75; 95% CI = (-22.02)-(-9.49)) and gait function (timed walk MD(s) = -5.31; 95% CI(s) = (-9.88)-(-0.74)) were observed. Time-dependency was not significant. The subject global impression of change (SGIC) improved significantly after the first month (odds ratio (OR) = 1.69; 95% CI = (1.30)-(2.18)). 

Conclusion: Beyond spasticity, nabiximols may represent a signal of benefit for bladder function, sleep disruption, spasm quality, and gait function in MS, in line with the “spasticity-plus” concept. However, the evidence certainty was low to very low, and these findings should be considered exploratory.”

https://pubmed.ncbi.nlm.nih.gov/42506315

“Nabiximols is a well-characterized extract of Cannabis sativa (27 mg/mL tetrahydrocannabinol (THC) and 25 mg/mL cannabidiol (CBD)) that acts on the cannabinoid system. It is effective in treatment-resistant MS-related spasticity and may also improve several associated symptoms. Moreover, nabiximols has shown encouraging results in the treatment of various symptoms such as pain, gait function, sleep disruption, bladder function, fatigue, and tremors.”

https://www.mdpi.com/2076-3271/14/3/346


Cannabidiol and other non-psychotropic cannabinoids from Cannabis sativa as therapeutics for microglial-mediated neuroinflammation and neurodegeneration

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“Non-psychotropic phytocannabinoids produced by Cannabis sativa, including cannabidiol, cannabigerol, cannabichromene and their varin and acidic analogs, are emerging as promising modulators of neuroinflammation, particularly through actions on microglia, the brain’s resident immune cells.

These compounds engage numerous receptors, ion channels, and intracellular signaling systems in microglia associated with neuroinflammation, and therefore are promising therapeutic candidates to treat chronic microglial inflammation-mediated neurodegenerative disorders.

Despite substantial public and scientific interest, comprehensive evaluation of their mechanistic diversity, disease-relevant potential, and translational gaps across neurodegenerative disorders remains limited. Commonly, gaps also exist between cannabis breeders’ and cultivators’ knowledge of phytocannabinoid diversity and translational scientists’ understanding of therapeutic potential.

In this review, we first provide an in-depth overview of the main non-psychotropic phytocannabinoids, their biosynthesis, and the genetics that control their production in cannabis. We then summarize the known mechanisms of action for each cannabinoid in microglial-expressed molecular targets and signaling pathways relevant to neuroinflammation.

Lastly, we review the effects of non-psychotropic phytocannabinoids in pre-clinical models and clinical trials of four neuroinflammation-associated neurodegenerative diseases: Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and Huntington’s disease.

Current evidence supports meaningful biological activity and complex cannabinoid-specific polypharmacology, yet substantial gaps persist, especially for cannabinoids other than cannabidiol; addressing these gaps in disease-relevant models will be essential for translating these compounds into future therapeutic strategies. Further, we anticipate the summarized information will foster collaboration between cannabis breeders/cultivators and applications scientists for therapeutic evaluation and development of emerging non-psychotropic phytocannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/42121212

https://link.springer.com/article/10.1186/s42238-026-00445-5

Anti-Neuroinflammatory Cannabinoid Acids as a New Therapeutic Approach for Multiple Sclerosis

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“Neuroinflammation is a hallmark of multiple sclerosis (MS). MS is marked by glial cell activation, autoreactive T cells, and the release of pro-inflammatory cytokines and free radicals. Current therapeutic strategies aim to modulate the immune response using disease-modifying therapies, to slow disease progression.

The specific aims of this study were: (a) to investigate the effect of cannabinoid acids on the release of glial neuroinflammatory mediators, (b) to examine the effect of intraperitoneally administered cannabinoid acids on symptoms of MS, and (c) to evaluate their effects on microglial and astrocyte activation and CD4+ T cell infiltration into the spinal cords of MS mice.

Exposure of BV2 microglia to cannabinoid acids attenuated lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase by 40-90% it also reduced the release of nitric oxide and interleukin-17A. Among the cannabinoid acids tested, cannabidiolic acid (CBDA) significantly increased tumor necrosis factor alpha (TNFα) secretion by up to 40% in LPS-stimulated BV2 cells. Intraperitoneal administration of CBDA also resulted in a twofold increase in TNFα secretion in splenocytes isolated from MS mice, compared to untreated MS controls.

This study provides evidence that CBDA significantly reduces neurological scores, while both cannabinoid acids attenuate microgliosis, astrogliosis, and CD4+ T cell migration in lumbar spinal cord sections of MS mice. These compounds cross the blood-brain barrier (BBB) and act directly within the central nervous system. The consistent elevation of TNFα in the presence of CBDA across three experimental models suggests a distinctive immunomodulatory role for CBDA, with potential therapeutic implications in MS.”

https://pubmed.ncbi.nlm.nih.gov/41976267

“Cannabinoid acids, including tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), are precursors of the main active cannabinoids tetrahydrocannabinol (THC) and cannabidiol (CBD), respectively. CBDA and THCA are the main cannabinoids found in cannabis and have attracted attention for their potential immunomodulatory properties.”

“Our findings provide direct evidence supporting immunomodulatory effects of CBDA and THCA in both in vitro and in vivo models, highlighting their potential therapeutic relevance in MS.”

https://www.mdpi.com/1420-3049/31/7/1227

A sesquiterpene-rich essential oil from Cannabis sativa L. attenuates symptoms and neuroinflammation in experimental autoimmune encephalomyelitis model through a CB2-mediated signalling

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“Background: The efficacy of cannabinoid-based medication as analgesic and neuroprotective in multiple sclerosis (MS) has been described, but little is known on other cannabis active compounds, such as terpenes.

Purpose: To investigate the therapeutic potential and molecular mechanism of non-psychotropic Cannabis sativa L. essential oil (EO) in an animal model of MS.

Methods: Chemical composition of EO was analyzed using GC-MS and GC-FID. Mouse model of experimental autoimmune encephalomyelitis (EAE) was employed to evaluate EO efficacy on pain (hot and cold plate test, von Frey test), motor disability (clinical score, rotarod), emotional alterations (sucrose splash test, tail suspension test, open field, light-dark box test) (n = 11). Tissues and LPS-stimulated BV2 cells were analyzed by Western blot, immunofluorescence, Luxol Fast Blue (LFB), hematoxylin and eosin (H&E) staining, UHPLCHRMS analysis.

Results: β-caryophyllene, α-humulene, and caryophyllene oxide were the most abundant EO constituents. Intranasal administration of EO attenuated thermal and mechanical hypersensitivity, promoted motor function recovery, and induced antidepressant- and anxiolytic-like effects in EAE mice. EO increased LFB staining and MBP content while reducing H&E staining. In spinal cord and hippocampal tissues, EO reduced proinflammatory microglia (CD11b/IBA-1 ratio), restored the IL-17/IL-10 balance, and promoted a shift of microglia toward an anti-inflammatory phenotype by increasing CD206 and FoxP3 expression. Mechanistically, EO markedly upregulated CB2 receptor expression in both EAE mice and LPS-stimulated BV2 cells. The protective effect of EO was abolished by a CB2 antagonist (AM630) but not by CB1 blockade (AM251).

Conclusion: Intranasal EO alleviates EAE symptoms and comorbidities through a CB2-mediated attenuation of neuroinflammation and demyelination.”

https://pubmed.ncbi.nlm.nih.gov/41875735

“Studies on the use of medical cannabis in the treatment of MS suggest a reduction in pain and spasticity and most clinical trials have shown symptom improvement with cannabis-based drugs administration”

“Present findings provide the first evidence that a sesquiterpene-rich EO obtained from non-psychoactive C. sativa mitigates EAE neurological symptoms, alleviating pain hypersensitivity, motor disability and mood-related comorbidities through a CB2-mediated anti-neuroinflammatory mechanism.”

https://www.sciencedirect.com/science/article/pii/S0944711326003041?via%3Dihub

Enhancing the endocannabinoid system to treat residual disease in relapse-free multiple sclerosis

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“The recent introduction of High-Efficacy Therapies (HETs) in clinical practice has drastically reduced the frequency of acute inflammatory episodes and relapses, in patients with Multiple Sclerosis (MS), gradually shifting the interest of clinicians toward preventing disease progression and treating symptoms associated with the residual disease. This article summarizes the output of a recent meeting (June 2025, in Rome) among an Italian group of neurologists, who discussed about published evidence supporting the involvement of the endocannabinoid system (ECS) in MS spasticity and its associated symptoms. Sharing their clinical experiences about the silent progression of the disease, in patients with Relapse-Free Multiple Sclerosis (RFMS), treated with HETs, authors propose a new algorithm to treat residual disease in RFMS, by enhancing ECS with both cannabinoid agents and lifestyle interventions (diet and physical activity).”

https://pubmed.ncbi.nlm.nih.gov/41859417

“authors developed a treatment algorithm, emphasizing the importance of timely intervention both with an increase in endogenous cannabinoids, through diet and physical activity, and with the use of an exogenous cannabinoid agent such as nabiximols.”

https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2026.1747131/full

“Nabiximols (brand name Sativex) is a pharmaceutical-grade, oromucosal spray containing a 1:1 ratio of cannabinoids THC and CBD derived from Cannabis sativa.”

Unveiling Neurological Benefits: A Review of Hemp Leaf, Flower, Seed Oil Extract, and Their Phytochemical Properties in Neurological Disorders

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“Neurological disorders such as epilepsy, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis present significant global health care challenges, with complex pathophysiology and limited therapeutic options that often carry substantial side effects.

Hemp-derived compounds, particularly from Cannabis sativa seeds, leaves, and flowers, have gained attention for their potential neuroprotective properties.

This review aims to synthesize the current evidence surrounding the therapeutic benefits of hemp-derived compounds, focusing on their bioactive phytochemical profiles, mechanisms of action, and therapeutic efficacy in treating neurological disorders.

A comprehensive review of pre-clinical and clinical studies was conducted, analyzing the phytochemical composition of hemp extracts, including cannabinoids (such as cannabidiol, CBD), terpenes, flavonoids, and polyunsaturated fatty acids. We explored their mechanisms of action through interactions with the endocannabinoid system, neurotransmitter receptors, inflammatory pathways, and oxidative stress mechanisms.

The review highlights the therapeutic potential of hemp-derived extracts in mitigating various neurological conditions. Pre-clinical and clinical studies have demonstrated their efficacy in reducing seizure frequency in epilepsy, protecting dopaminergic neurons in Parkinson’s disease, alleviating neuroinflammation and oxidative stress in Alzheimer’s disease, and promoting remyelination in multiple sclerosis.

The entourage effect, where cannabinoids, terpenes, and flavonoids work synergistically, enhances these therapeutic effects. Innovations in extraction technologies have optimized yield and preserved bioactivity, further enhancing clinical relevance.

Hemp-derived compounds exhibit significant neuroprotective and therapeutic potential for managing neurological disorders. However, challenges such as product standardization, safety profiles, and regulatory frameworks must be addressed for clinical translation. Further research is essential to optimize dosing, establish safety parameters, and develop standardized formulations, which will be crucial for fully harnessing the therapeutic potential of hemp-derived products in treating neurological conditions.”

https://pubmed.ncbi.nlm.nih.gov/41468178

https://www.liebertpub.com/doi/10.1177/25785125251410822


Cannabidiol as a Neuroprotective Agent in Acrylamide-Induced Neurotoxicity: Effects on Oxidative Stress, Inflammation, and Cholinergic Function in Male Mice

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“The neuroprotective potential of cannabidiol (CBD) was assessed in a mouse model of acrylamide-induced neurotoxicity.

Acrylamide (AA), an environmental and dietary pollutant, is known to cross the blood-brain barrier and induce oxidative stress, inflammation and neurotoxic effects.

Male C57BL/6 mice were randomly assigned to four groups: Control (Con), Acrylamide (AA), Cannabidiol (CBD), and a combination treatment (AA + CBD). The AA group received acrylamide (10 mg/kg, i.p.) daily for 5 days. CBD was administered (10 mg/kg, i.p.) for 10 days in the CBD and AA + CBD groups. In the AA + CBD group, acrylamide (10 mg/kg, i.p.) was co-administered during the last 5 days of CBD treatment.

Behavioral outcomes were analyzed using the open field test, revealing that CBD mitigated anxiety-like behavior induced by acrylamide, enhancing movement and center exploration. Further, CBD treatment modulated oxidative stress responses, reducing MDA levels and partially restoring antioxidant markers (GSH, SOD, and CAT) in the hippocampus and striatum. Inflammatory markers were also assessed, revealing that acrylamide elevated pro-inflammatory cytokines TNF-α and IL-6.

Notably, CBD co-treatment reduced TNF-α levels in the hippocampus and cortex and attenuated IL-6 levels in the cortex and striatum, suggesting an anti-inflammatory effect. Additionally, CBD modulated neuroplasticity by increasing BDNF levels in the hippocampus, counteracting the reduction caused by acrylamide. CBD also influenced cholinergic activity by restoring Ach levels and altering AChE activity across brain regions.

Findings suggest that CBD exhibits neuroprotective properties by reducing oxidative stress, inflammation and cholinergic dysregulation, thereby offering a promising therapeutic approach for mitigating pollutant-induced neurotoxicity and potentially treating neurodegenerative disorders.”

https://pubmed.ncbi.nlm.nih.gov/41395773

“By improving behavioral outcomes, reducing oxidative stress, modulating inflammation, enhancing neuroplasticity and preserving cholinergic function, CBD shows promise as a potential therapeutic approach for neurotoxic and neurodegenerative conditions. “

https://onlinelibrary.wiley.com/doi/10.1002/jnr.70098

Investigating the effectiveness and adverse events of medicinal cannabis for patients with muscle spasticity or spasms

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“Appropriate treatment of muscle spasticity and spasms is important as these conditions may significantly impair patients’ quality of life. Conventional pharmacological treatments for these conditions have poor effectiveness and/or tolerability.

Cannabis is being explored as a treatment.

This was a longitudinal study of patient use of different cannabis products. Data was collected from patient surveys, clinic records, and changes in Patient Reported Outcome Measures Information System 29-Item scores over time. Patient-reported responses on health-related quality of life adverse events (n = 150) and outcomes (n = 78) from treatment for spasticity or spasms were analyzed. No improvements in physical functioning were observed for either group of patients across all product types. However, patients with spasticity who were using cannabidiol-only products experienced an improvement in sleep disturbance, fatigue, pain interference, and pain intensity.

Patients with spasms who were using balanced, cannabidiol-dominant, or tetrahydrocannabinol-dominant products also experienced improvements in these 4 outcomes. Commonly reported adverse events were dry mouth, drowsiness, fatigue, dizziness, and nausea. Despite no observation of improvement in physical functioning, the results suggest that cannabis may help relieve some of the secondary complications associated with these conditions, such as poor sleep and pain.

SIGNIFICANCE STATEMENT: This longitudinal study highlights differential benefits across cannabis product types, with cannabidiol-only formulations aiding spasticity-related symptoms and tetrahydrocannabinol- or cannabidiol-dominant products benefiting those with spasms.

These findings support the potential of cannabis as a potential therapy to improve health-related quality of life in patients with limited options from conventional pharmacological treatments.”

https://pubmed.ncbi.nlm.nih.gov/41386046

https://jpet.aspetjournals.org/article/S0022-3565(25)40293-6/abstract


UK Medical Cannabis Registry: An Updated Analysis of Cannabis-Based Medicinal Products for Multiple Sclerosis

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“Introduction: Multiple sclerosis (MS) is a neurodegenerative disease presenting with a wide range of motor, sensory, and psychiatric symptoms. Although nabiximols is licensed for MS-induced spasticity, cannabis-based medicinal products (CBMPs) have also displayed promising therapeutic potential for managing pain, sleep, and anxiety. Therefore, further evaluation of CBMP treatment for MS is warranted. This study aimed to assess the efficacy and tolerability of CBMP treatment in patients with MS by investigating changes in MS-specific and general health-related patient-reported outcome measures and adverse events.

Methods: This was a prospective case series including patients with MS enrolled on the UK Medical Cannabis Registry. Changes in MS Quality of Life-54 (MSQOL-54), Generalised Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L scores were assessed from baseline up to 24 months. The prevalence and severity of all adverse events were also assessed.

Results: This study included 203 patients, of whom 47.29% (n = 96) were female and 80.79% (n = 164) had prior cannabis exposure. Improvements in the MSQOL-54 subscales: change in health, energy, health distress, pain, physical function, and physical role limitations, along with improvements in SQS and EQ-5D-5L scores, were seen at all follow-up times compared to baseline (p < 0.050). A total of 278 adverse events were reported by 26 patients (12.81%). Most adverse events were mild (n = 91, 32.73%) or moderate (n = 138, 49.64%) in severity, with fatigue (n = 27, 13.30%) and spasticity (n = 17, 8.37%) being the most common.

Conclusion: CBMP treatment over 24 months was associated with improvements in health-related quality of life and was well tolerated in patients with MS. Future randomised controlled trials with more representative study populations are needed to establish causal relationships.”

https://pubmed.ncbi.nlm.nih.gov/41357430

“There is increasing evidence for the involvement of the endocannabinoid system (ECS) in modulating inflammatory and neurodegenerative processes.”

“Through interactions with the ECS, THC and CBD have displayed analgesic, muscle relaxant, neuroprotective, and anti-inflammatory properties in preclinical and clinical studies.”

“Therefore, cannabis-based medicinal products (CBMPs) containing these phytocannabinoids show promise for managing MS symptoms.”

“In conclusion, this observational study found CBMP treatment was associated with improvements in many HRQoL measures, including pain and sleep in patients with MS. Also, CBMP use over 2 years was generally well tolerated.”

https://karger.com/mca/article/8/1/201/938322/UK-Medical-Cannabis-Registry-An-Updated-Analysis