Category Archives: Multiple Sclerosis (MS)

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

The Endocannabinoid System: Pharmacological Targets and Therapeutic Potential in CNS Disorders

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“The endocannabinoid system (ECS) influences a wide range of brain functions, including synaptic transmission, neuroplasticity, emotion, and immune regulation within the central nervous system, with CB1 and CB2 receptors mediating various neurophysiological and pathophysiological outcomes. Thus, growing interest in its therapeutic potential has prompted extensive research into how cannabinoid receptors contribute to the pathophysiology of neurological and psychiatric disorders, particularly CB1 and CB2.

This review has integrated findings from studies published between 2015 and 2025, covering conditions, like depression, anxiety, pain, multiple sclerosis, and Parkinson’s disease. We have also examined recent advances in receptor pharmacology and experimental technologies, including cryo-EM, optogenetics, and chemogenetics.

Although ECS-targeted therapeutics hold considerable promise, some key challenges remain in establishing safe and effective dosing protocols and integrating these approaches into clinical frameworks.

This review has provided an updated perspective on the system’s role in brain health and its potential to inform future therapeutic directions. Thus, ECS-targeted strategies may become increasingly important in managing and treating central nervous system disorders.”

https://pubmed.ncbi.nlm.nih.gov/41178765/

https://www.eurekaselect.com/article/151549

Dysregulation of the endocannabinoid system – a key factor in the progression of multiple sclerosis?

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“The endocannabinoid system has been implicated in the pathophysiology of multiple sclerosis (MS), yet its role across different disease stages and under disease-modifying treatment remains incompletely understood.

This study aimed to evaluate plasma levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in patients with MS at different clinical stages, and to explore their associations with disability, cognition, and quality of life, as well as the potential influence of teriflunomide therapy.

Thirty participants were enrolled: ten healthy controls, ten newly diagnosed relapsing-remitting MS (RRMS) patients in acute relapse, and ten teriflunomide-treated RRMS patients in remission. Plasma AEA and 2-AG were measured by ELISA; clinical assessments included the Mini-Mental State Examination (MMSE) and the SF-36 quality-of-life questionnaire.

No significant group differences were observed overall in 2-AG (P > 0.05). AEA showed a non-significant overall group effect (ANOVA, P = 0.0919) with a trend toward lower AEA in newly diagnosed patients compared to healthy controls (mean difference = -5.95 ng/ml, SE = 2.66; P = 0.098). In the teriflunomide group, AEA and 2-AG were strongly positively correlated (r = 0.882, P < 0.001). Additionally, SF-36 scores were positively associated with MMSE (r = 0.706, P = 0.023). Furthermore, SF-36 total scores were significantly lower in newly diagnosed patients compared to controls (post-hoc P = 0.044).

These findings suggest possible early dysregulation of the endocannabinoid system in MS and indicate that teriflunomide treatment is associated with a strengthened AEA-2-AG relationship. Larger, longitudinal studies are warranted to confirm these observations and to assess clinical implications for disease progression and patient quality of life.”

https://pubmed.ncbi.nlm.nih.gov/41178906/

Chemical Composition and Antioxidant Activity of the Stembark Essential Oils of Two Cannabis sativa L. Cultivars from Komga, South Africa

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“Cannabis sativa L. is an aromatic medicinal plant with various biologically active classes of compounds such as cannabinoids, polyphenols, and terpenes.

Unlike the widely investigated inflorescence and leaf, the stembark of C. sativa has been overlooked regarding its medicinal potential. This study, therefore, was aimed at determining the chemical composition and antioxidant activity of the essential oils (EOs) obtained from the fresh and dried stembark of two C. sativa cultivars, Lifter and Cherrywine, grown in Komga, South Africa, with a view to ascertaining the more promising cultivar.

The chemical profiles of the hydro-distilled EOs were analyzed by gas chromatography-mass spectrometry (GC-MS), while an in vitro antioxidant activity assessment of the EOs was performed using DPPH and H2O2 spectrophotometric methods. The identified constituents from the EOs were molecularly docked against NOX2, a protein implicated in oxidative stress. The afforded EOs were colorless with a mild skunk-like odor. A total of thirty-two constituents were identified in both fresh and dry oils from the Lifter cultivar while the Cherrywine cultivar contained a total of forty-two constituents.

The EOs of both cultivars contained twenty compounds, notably Cannabidiol (0.25-85.03%), Caryophyllene oxide (1.27-19.58%), Caryophyllene (0.64-16.61%), Humulene (0.37-8.15%), Octacosane (3.37-6.55%), Humulene-1,2-epoxide (0.45-5.78%), Nerolidol (0.32-4.99%), Palmitic acid (1.45-4.45%), Tetracosane (1.75-2.91%), Dronabinol (0.86-2.86%), Cannabinol (0.54-1.64%), 7-epi-γ-eudesmol (0.53-1.00%), Guaiol (0.37-0.66%), Linoleic acid (0.22-0.60%), γ-Selinene (0.15-0.48%), β-Eudesmol (0.34-0.50%), and Linalool (0.24-0.30%).

The dried Lifter stembark oil (DLSO) gave the best antioxidant activity among the four investigated cannabis oils, exhibiting the lowest IC50 values of 21.68 ± 1.71 and 26.20 ± 1.34 µg/mL against DPPH and H2O2 radicals, respectively. The notable antioxidant activity of the DLSO may be attributed to the higher number (30) of constituents compared to the fresh Lifter stembark oil (LSO) with 11 constituents. Additionally, the DLSO showed a unique chemical profile comprising monoterpenes, oxygenated and hydrocarbon sesquiterpenes. Further in silico studies on the putative constituents in the Lifter cultivar revealed Cannabinol, Cannabidiol, and Linalool as the promising constituents based on their higher binding energy scores of -9.7, -8.5, and -6.5 kcal/mol, respectively, compared to L-Ascorbic acid (-5.7 kcal/mol).

It can be inferred from this study that the EOs from the stembark of C. sativa contain promising compounds, such as Cannabinol, Cannabidiol, and Linalool, which might be responsible for the displayed antioxidant activity of the oils. Thus, the study findings underscore the biological importance of C. sativa stembark in the management of oxidative stress-related conditions.”

https://pubmed.ncbi.nlm.nih.gov/40943472/

https://www.mdpi.com/1422-0067/26/17/8552