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Multiple Sclerosis (MS)

Multiple Sclerosis is a chronic, progressive disease that damages the myelin sheaths that protect nerve cells in your brain and spinal cord.

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Research Summary:

Cannabinoids are highly effective for multiple sclerosis (MS) because MS is uniquely positioned at the intersection of conditions where cannabinoids are most beneficial. MS is characterized by both autoimmune dysfunction and neurodegeneration, which are the two domains where cannabinoids are most effective. In MS, the immune system attacks the myelin sheaths surrounding brain synapses, disrupting electrical signal transmission. This damage results in faulty neuron firing, ultimately leading to spasticity and neuropathic pain. MS pathology involves neuroinflammation, excessive neuron firing (excitotoxicity), demyelination, and neurodegeneration.

Because MS encompasses both autoimmune and neurodegenerative aspects, there is a substantial body of clinical, anecdotal, and preclinical evidence supporting the use of cannabinoids to alleviate MS symptoms and slow its progression. Targeting the endocannabinoid system with compounds like CBD, THC, or PEA helps reduce brain inflammation, safeguard the oligodendrocytes responsible for myelin production, and provide relief from MS-related pain and spasticity.

Best Review Articles:

Research Timeline:

  • 2022: Many patients with multiple sclerosis use cannabinoids for pain relief
    Cannabinoid use for pain relief among people with multiple sclerosis

  • 2022: This sad survey shows that for patients with multiple sclerosis, few of them talk to their doctors about how to use cannabis & instead rely on the budtender at the dispensary
    Sources of Cannabis Information and Medical Guidance for Neurologic Use: NARCOMS Survey of People Living With Multiple Sclerosis

  • 2022: In microglial cells, treatment with CBD increased levels of the mitochondrial fusion protein Mitofusin 2 that deals with inflammation – and in mice, CBD lessened the anxiety response & cognitive deficits from an inflammatory challenge as well as helping in a mouse model of multiple sclerosis
    Mitofusin 2 confers the suppression of microglial activation by cannabidiol: Insights from in vitro and in vivo models

  • 2022: In people with multiple sclerosis, THC & CBD helped with inflammation via the Toll receptors
    Botanically-Derived Δ9-Tetrahydrocannabinol and Cannabidiol, and Their 1:1 Combination, Modulate Toll-like Receptor 3 and 4 Signalling in Immune Cells from People with Multiple Sclerosis

  • 2022: In a mouse model of multiple sclerosis, activating the CB2 receptor reduced inflammation & improved symptoms
    A CB2 Receptor Agonist Reduces the Production of Inflammatory Mediators and Improves Locomotor Activity in Experimental Autoimmune Encephalomyelitis

  • 2022: A survey of multiple sclerosis patients found that a third used cannabis to alleviate symptoms
    A Survey of Cannabis Use in a Large US-Based Cohort of People with Multiple Sclerosis

  • 2021: In mice neurons, THC promotes remyelination (the essential fatty sheaths that enable synaptic transmission & whose loss underlies diseases such as MS, lupus, Lyme disease & radiation poisoning)
    Δ 9 -Tetrahydrocannabinol Promotes Functional Remyelination in the Mouse Brain

  • 2021: In a mouse model of multiple sclerosis, CBD lowered neuroinflammation, improved gut health & attenuated the strength of the disease
    Effects of Orally Administered Cannabidiol on Neuroinflammation and Intestinal Inflammation in the Attenuation of Experimental Autoimmune Encephalomyelitis

  • 2021: In a cellular model of MS, activating the CB2 receptor caused potent immunomodulation of the T-cells (immune cells that attack foreign material)
    Potent T cell mediated anti-inflammatory role of the selective CB2 agonist lenabasum in multiple sclerosis

  • 2021: In nursing home patients with MS, there’s a clear cost-benefit to giving them Sativex (1:1 THC:CBD medicine)
    Cost-effectiveness of adding Sativex® spray to spasticity care in Belgium: using bootstrapping instead of Monte Carlo simulation for probabilistic sensitivity analyses

  • 2021: In patients with MS, a nabixmol (1:1 THC:CBD medicine) did not help with depression, suicidality, or working memory/processing speed
    Effect of nabiximols cannabinoid oromucosal spray on depressive symptoms, suicidality, and cognition in persons with multiple sclerosis (PwMS)

  • 2021: In humans with MS, cannabis seems to improve their inflammatory cytokines & clinical profiles
    The Effect of Cannabis on the Clinical and Cytokine Profiles in Patients with Multiple Sclerosis

  • 2021: In young mice, THC promoted myelination & the development of oligodendrocytes (myelin producing cells) via the mTORC1 pathway
    Δ 9 -Tetrahydrocannabinol promotes oligodendrocyte development and CNS myelination in vivo

  • 2020: In humans with multiple sclerosis, about half of them gave up on nabiximols (1:1 THC:CBD medicine) because of the loss of efficacy or adverse events
    Nabiximols discontinuation rate in a large population of patients with multiple sclerosis: a 18-month multicentre study

  • 2020: In a mouse model of MS, activating the CB1 receptor can have different effects on inflammatory cytokines depending on the cell type
    The CB1 Receptor Differentially Regulates IFN-γ Production In Vitro and in Experimental Autoimmune Encephalomyelitis

  • 2020: In 15 patients, a THC/CBD spray helped with the pain & spasticity of MS
    Cannabinoids in multiple sclerosis: A neurophysiological analysis

  • 2020: In 20 patients with MS, nabiximols (THC/CBD mixtures) improved cognition and memory
    Long-term Assessment of the Cognitive Effects of Nabiximols in Patients With Multiple Sclerosis: A Pilot Study

  • 2020: In mouse model of MS, the many mechanisms by which CBD helps
    Efficacy of cannabidiol treatment in experimental MS is due to immunosuppressive activity of myeloid cells in CNS downregulating recruitment of CD4+ T cells, proinflammatory chemokines and gasdermin D expression

  • 2020: In mice with autoimmune encephalomyelitis (a model of multiple sclerosis), CBD suppressed neuroinflammation
    CBD Suppression of EAE Is Correlated with Early Inhibition of Splenic IFN-γ + CD8+ T Cells and Modest Inhibition of Neuroinflammation

  • 2020: In humans with MS, a large multicenter trial finds a spray of THC/CBD helpful
    Effects of THC/CBD oromucosal spray on spasticity-related symptoms in people with multiple sclerosis: results from a retrospective multicenter study

  • 2020: In a study of why people stopped using Sativex (the 1:1 THC:CBD formula from GW Pharma) to treat their MS, the best predictor of stopping Sativex use was for patients starting with higher physical and cognitive disabilities. Assumedly, those disabilities were exacerbated by the THC.
    Predictors of Nabiximols (Sativex®) discontinuation over long-term follow-up: a real-life study

  • 2020: In humans with MS, this cost analysis finds it to be a reasonable incremental cost for improving the lives of patients
    Cost-Effectiveness Analysis of Cannabinoid Oromucosal Spray Use for the Management of Spasticity in Subjects with Multiple Sclerosis

  • 2020: In MS patients, Sativex (1:1 THC:CBD)  relieved resistant spasticity, spasticity severity, spasticity duration & lessened pain
    Tetrahydrocannabinol and cannabidiol oromucosal spray in resistant multiple sclerosis spasticity: consistency of response across subgroups from the SAVANT randomized clinical trial

  • 2019: in glial cell model of MS, CBD protects the brain by increasing the expression of the neuroprotective BNTF-3 & IGF-1 genes
    Neuroprotective effect of cannabidiol on NTF-3 and IGF-1 genes expression

  • 2019: In humans, a survey of cannabis use for MS
    Cannabis use for symptom relief in multiple sclerosis: A cross-sectional survey of webinar attendees in the US and Canada

  • 2019: In tissue model of MS, CBD shown to regulate the T cells of the immune system
    Cannabidiol Regulates Gene Expression in Encephalitogenic T cells Using Histone Methylation and noncoding RNA during Experimental Autoimmune Encephalomyelitis

  • 2019: In a mouse model of MS, THC & CBD treatment caused positive changes in the microbiome that were crucial to attenuating the disease
    Combination of cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), mitigates experimental autoimmune encephalomyelitis (EAE) by altering the gut microbiome

  • 2019: a survey of MS patients found one-quarter of them used a form of cannabis
    Cannabis-based product use in a multiple sclerosis cohort

  • 2019: In humans, a genetic variant which reduces the activity of the CB2 receptor conferred a 2.7-fold higher chance of developing multiple sclerosis (200 patients in a genetic association study)
    Cannabinoid CB2 Receptor Functional Variation (Q63R) Is Associated with Multiple Sclerosis in Iranian Subjects

  • 2019: In humans with MS, a THC/CBD spray helped with spasticity & synergized with physiotherapy (297 patients in an observational multicenter study)
    The influence of physiotherapy intervention on patients with multiple sclerosis-related spasticity treated with nabiximols (THC:CBD oromucosal spray)

  • 2019: In chart review of 77 patients, MS patients taking cannabis were able to reduce intake of opioids and benzodiazepines
    Multiple Sclerosis and Use of Medical Cannabis: A Retrospective Review Evaluating Symptom Outcomes (P5.2-106)

  • 2019: in mouse model of MS, CBD extracts helped with neurological disability & behavioral assessments via TNF-α & (BDNF)
    Therapeutic impact of orally administered cannabinoid oil extracts in an experimental autoimmune encephalomyelitis animal model of multiple sclerosis

  • 2019: in humans with MS, Sativex found helpful for spasticity
    Sativex® as add-on therapy vs. further optimized first-line ANTispastics (SAVANT) in resistant multiple sclerosis spasticity: a double-blind, placebo-controlled randomised clinical trial

  • 2019: in the mouse model of MS, a combo of THC and CBD suppress neuroinflammation and slows disease development
    Combination of Cannabinoids, Δ9- Tetrahydrocannabinol and Cannabidiol, Ameliorates Experimental Multiple Sclerosis by Suppressing Neuroinflammation Through Regulation of miRNA-Mediated Signaling Pathways

  • 2018: In humans with MS, Sativex helped to improve daily functioning
    Effect of tetrahydrocannabinol:cannabidiol oromucosal spray on activities of daily living in multiple sclerosis patients with resistant spasticity: a retrospective, observational study

  • 2018: In humans with MS, a kinetic study shows that even small amounts of Sativex can make a difference (12 patients in a  pilot, single center, open, and prospective)
    Tetrahydrocannabinol/Cannabidiol Oromucosal Spray in Patients With Multiple Sclerosis: A Pilot Study on the Plasma Concentration-Effect Relationship

  • 2018: In a mouse model of MS, CBD rich extracts (from Avidekel cannabis) work as well as the common drug copaxone in suppressing symptoms
    Avidekel Cannabis extracts and cannabidiol are as efficient as Copaxone in suppressing EAE in SJL/J mice

  • 2018: in mouse model of MS, CBD caused a significant reduction in clinical scores of paralysis, decreased T cell infiltration in the CNS & reduced levels of IL-17 & IFNγ – also led to a profound increase in myeloid-derived suppressor cells (MDSCs)
    Cannabidiol Attenuates Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis Through Induction of Myeloid-Derived Suppressor Cells

  • 2017: In mouse model of MS, CBD improved the clinical signs “and reduced infiltration, demyelination and axonal damage”
    Mechanisms of action of cannabidiol in adoptively transferred experimental autoimmune encephalomyelitis

  • 2017: in mouse model of MS, injections of CBD downregulated PI3K/Akt/mTOR pathway. Increased BDNF & reduced pro-inflammatory cytokines like IFN-γ and IL-17 together with an up-regulation of PPARγ – CBD was found to promote neuronal survival by inhibiting JNK and p38 MAP kinases
    Target regulation of PI3K/Akt/mTOR pathway by cannabidiol in treatment of experimental multiple sclerosis

  • 2016: in T-cell culture model of MS, CBD cause antiinflammation & “exerts its immunoregulatory effects in activated memory TMOG cells via (a) suppressing proinflammatory Th17-related transcription, (b) by promoting T cell exhaustion/tolerance, (c) enhancing IFN-dependent anti-proliferative program, (d) hampering antigen presentation, and (d) inducing antioxidant milieu resolving inflammation”
    Pathways and gene networks mediating the regulatory effects of cannabidiol, a nonpsychoactive cannabinoid, in autoimmune T cells

  • 2016: in mouse model of MS, CBD largely attenuated the CD3+ and CD4+ T cell-mediated inflammatory response and injury, myocardial fibrosis and cardiac dysfunction
    Cannabidiol Limits T Cell-Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation

  • 2016: In humans, Sativex helped with MS symptoms
    Tetrahydrocannabinol:Cannabidiol Oromucosal Spray for Multiple Sclerosis-Related Resistant Spasticity in Daily Practice

  • 2015: in mouse model of MS, treatment with PEA or CBD reduced disease severity with diminished inflammation, demyelination, axonal damage and inflammatory cytokine expression – but they did not work as well togtether
    Interaction between the protective effects of cannabidiol and palmitoylethanolamide in experimental model of multiple sclerosis in C57BL/6 mice

  • 2015: In mouse model of MS, CBD “possesses an anti-apoptotic power against the neurodegenerative processes underlying MS development”
    Purified Cannabidiol, the main non-psychotropic component of Cannabis sativa, alone, counteracts neuronal apoptosis in experimental multiple sclerosis

  • 2015: in mouse model of MS, synthetic CBD slows disease progress, possibly by voltage-gated sodium channels – THC also slowed disease progression
    Neuroprotection in Experimental Autoimmune Encephalomyelitis and Progressive Multiple Sclerosis by Cannabis-Based Cannabinoids

  • 2015: in mouse model of MS, CB2 activation required for the benefits of ABHD6 inhibition
    Activation of CB2 receptor is required for the therapeutic effect of ABHD6 inhibition in experimental autoimmune encephalomyelitis

  • 2015: in T cell model of MS, CBD’s immunoregulatory effects rely on a strong up-regulation of inhibitory molecules
    Cannabidiol, a non-psychoactive cannabinoid, leads to EGR2-dependent anergy in activated encephalitogenic T cells

  • 2015: in mouse model of MS, 1% CBD cream protected against clinical disease progression
    A new formulation of cannabidiol in cream shows therapeutic effects in a mouse model of experimental autoimmune encephalomyelitis

  • 2014: In model of MS, activating CB2 slows disease progression
    Selective CB2 receptor activation ameliorates EAE by reducing Th17 differentiation and immune cell accumulation in the CNS

  • 2013: in humans with MS, Sativex helpful for the neuropathic pain
    A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis

  • 2013: In viral model of MS, the role of the adenosine receptors in why CBD protects: decreases microglia activation – effects blocked by A2A antagonist
    Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: a role for A2A receptors

  • 2012: in humans, cannabis extract found to help with muscle stiffness
    Multiple sclerosis and extract of cannabis: results of the MUSEC trial

  • 2012: in oligodendrocyte progenitor cells (OPCs), mechanisms of how CBD protects and helps them differentiate into myelinating cells (might be helpful for MS & depression) – reduces cell death and free radical production
    Cannabidiol protects oligodendrocyte progenitor cells from inflammation-induced apoptosis by attenuating endoplasmic reticulum stress

  • 2012: in mouse model of MS, deep study on the positive effects from treatment with a CB1/CB2 agonist 
    Cannabinoids ameliorate disease progression in a model of multiple sclerosis in mice, acting preferentially through CB1 receptor-mediated anti-inflammatory effects

  • 2011: in mouse model of MS, anandamide downregulated gene expression of IL-12p70 and IL-23 – levels of IL-17A decreased while IL-10 increased – partially mediated by CB2
    The endocannabinoid anandamide downregulates IL-23 and IL-12 subunits in a viral model of multiple sclerosis: evidence for a cross-talk between IL-12p70/IL-23 axis and IL-10 in microglial cells

  • 2011: in a mouse model of MS, CBD treatment reduced severity of the disease including less axonal damage & inflammation & less microglial activation & T-cell recruitment – effect not mediated by CB1 & CB2
    Cannabidiol inhibits pathogenic T cells, decreases spinal microglial activation and ameliorates multiple sclerosis-like disease in C57BL/6 mice

  • 2011: in humans with MS, double-blind study shows Sativex helps with spasticity
    A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex(®) ), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis

  • 2011: In mouse model of MS, the mechanisms of how CBD helps
    Cannabidiol inhibits pathogenic T cells, decreases spinal microglial activation and ameliorates multiple sclerosis‐like disease in C57BL/6 mice

  • 2011: in mouse model of MS, confusingly, injections of THC helped, CBD didn’t, they didn’t work well together, while the cannabinoid-free extract did help
    Acute and chronic cannabinoid extracts administration affects motor function in a CREAE model of multiple sclerosis

  • 2011: in humans, a certain CB1 genetic variant with more severe MS
    The (AAT)n repeat of the cannabinoid CB1 receptor gene influences disease progression in relapsing multiple sclerosis

  • 2010: in humans with MS, effect of Sativex on overactive bladder
    Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis

  • 2010: in humans with MS, Sativex study saw help for spasticity
    A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis

  • 2010: in animal models of MS, ECS tone causes less excitotoxicity in cells
    An endocannabinoid tone limits excitotoxicity in vitro and in a model of multiple sclerosis

  • 2010: in human genetics, certain CB1 variants associated with MS
    The cannabinoid receptor 1 gene (CNR1) and multiple sclerosis: an association study in two case-control groups from Spain

  • 2009: in humans, study of the cognitive effects of cannabis in MS patients found no harms at therapeutic levels
    Psychopathological and cognitive effects of therapeutic cannabinoids in multiple sclerosis: a double-blind, placebo controlled, crossover study

  • 2009: in humans, map of endocannabinoid levels in various stages of MS
    Plasma endocannabinoid levels in multiple sclerosis

  • 2008: in mouse model of MS, CB2 was upregulated as was 2-AG & PEA – but not AEA – PEA applied exogenously reduced disability and lowered inflammation
    Study of the Regulation of the Endocannabinoid System in a Virus Model of Multiple Sclerosis Reveals a Therapeutic Effect of Palmitoylethanolamide

  • 2007: in humans, map of endocannabinoid machinery levels across brain regions
    Cannabinoid CB1 and CB2 receptors and fatty acid amide hydrolase are specific markers of plaque cell subtypes in human multiple sclerosis

  • 2007: in mouse model of MS, CB1 knockout mice demonstrate that the CB1 receptor – not CB2 – is responsible for the help for spasticity
    Control of spasticity in a multiple sclerosis model is mediated by CB1, not CB2, cannabinoid receptors

  • 2007: in mouse model of MS, CB1 work via the neurons while the CB2’s worked on the T cells to control inflammation
    Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells

  • 2007: in mouse model of MS, cannabinoid agonist reduced damage and excitotoxicity from MS
    Excitotoxicity in a chronic model of multiple sclerosis: Neuroprotective effects of cannabinoids through CB1 and CB2 receptor activation

  • 2007: In humans with MS, THC/CBD spray found helpful for 66 patient’s neuropathic pain from MS with no tolerance after 2 years
    Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial

  • 2007: in humans and rodents, MS and its experimental animal model (EAE) show dysregulation of the ECS
    The endocannabinoid system is dysregulated in multiple sclerosis and in experimental autoimmune encephalomyelitis

  • 2006: in humans, Sativex found helpful for MS – interesting list of adverse events
    Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis

  • 2006: in humans, cannabis extract helped with incontinence in MS patients
    The effect of cannabis on urge incontinence in patients with multiple sclerosis: a multicentre, randomised placebo-controlled trial (CAMS-LUTS)

  • 2006: in mouse model of MS, mapped the changes in CB1 receptors across the brain
    Changes in CB1 receptors in motor-related brain structures of chronic relapsing experimental allergic encephalomyelitis mice

  • 2006: in human spinal cords, the glial cells activated in MS & ALS show more COX2, P2X7 & CB2 – agonists suggested as therapeutic
    COX-2, CB2 and P2X7-immunoreactivties are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord

  • 2005: in humans with MS, followup of the 2003 CAMS study: “Overall, patients felt that these drugs were helpful in treating their disease.”
    Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up

  • 2005: in humans, a Sativex type drug helped with pain and sleep in MS
    Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis

  • 2005: in mouse model of MS, using two inhibitors of the putative cannabinoid transporters (OMDM1 & OMDM2) provides an effective therapy P
    harmacological modulation of the endocannabinoid system in a viral model of multiple sclerosis

  • 2005: in mouse model of MS, finds CB2 upregulated as microglia activated
    Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli

  • 2005: in rats with model of MS, AEA and 2AG decreased – suggested vanilloid activation to reduce impairment
    Decreased endocannabinoid levels in the brain and beneficial effects of agents activating cannabinoid and/or vanilloid receptors in a rat model of multiple sclerosis

  • 2004: in humans with MS, cannabis extracts helped with bladder dysfunction and other symptoms
    An open-label pilot study of cannabis-based extracts for bladder dysfunction in advanced multiple sclerosis

  • 2004: in humans, CBD/THC combo can lower spasm frequency and increase mobility
    Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study

  • 2004: in survey of MS patients, “The symptoms reported by medical cannabis users to be most effectively relieved were stress, sleep, mood, stiffness, spasm, and pain.”
    Patterns of cannabis use among patients with multiple sclerosis

  • 2004: in humans with MS, double-blind clinical study of cannabis finds it helpful
    Do cannabis-based medicinal extracts have general or specific effects n symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients

  • 2004: in humans with MS, synthetic THC found helpful for the pain
    Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial

  • 2003: in mouse model of MS, endocannabinoid system found to be protective
    Cannabinoids inhibit neurodegeneration in models of multiple sclerosis

  • 2003: in mouse model of MS, CB1 agonists caused ‘recovery of motor function and diminution of inflammation [with] paralleled extensive remyelination’
    Therapeutic action of cannabinoids in a murine model of multiple sclerosis

  • 2003: In humans with MS, multi-center clinical study saw no help for spasticity but did improve pain & mobility
    Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial

  • 2000: in mouse MS model, CB1 agonist reduced both tremor and spasticity
    Cannabinoids control spasticity and tremor in a multiple sclerosis model

  • 1997: in a survey of MS patients, it’s the first questionnaire on cannabis use & MS and it reported many improved symptoms
    The perceived effects of smoked cannabis on patients with multiple sclerosis
    “the subjects reported cannabis improved (in descending rank order): spasticity, chronic pain of extremities, acute paroxysmal phenomenon, tremor, emotional dysfunction, anorexia/weight loss, fatigue states, double vision, sexual dysfunction, bowel and bladder dysfunctions, vision dimness, dysfunctions of walking and balance, and memory loss”

  • 1989: in animal model of MS, early work shows strong results from THC
    Delta 9-tetrahydrocannabinol: a novel treatment for experimental autoimmune encephalomyelitis

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