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Best reviews

2022: This review of 28 studies lists the benefits of cannabinoids for multiple sclerosis

Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination

2022: A review of using cannabinoids to treat multiple sclerosis

Cannabinoid and endocannabinoid system: a promising therapeutic intervention for multiple sclerosis

2021: In humans with multiple sclerosis, this review of Sativex (a 1:1 THC:CBD spray) found it helpful for spasticity

Review of available data for the efficacy and effectiveness of nabiximols oromucosal spray (SativexÒ) in multiple sclerosis patients with moderate to severe spasticity

2021: A review of using the cannabinoids to treat the pain of MS

Efficacy, tolerability and safety of cannabinoids for management of pain in adult patients with multiple sclerosis: A systematic review and meta-analysis

2020: Cannabis & MS

Perspectives on Cannabis-Based Therapy of Multiple Sclerosis: A Mini-Review

2020: In MS, this review highlights the power of targeting the endocannabinoid system

Targeting Endocannabinoid Metabolism: an Arrow with Multiple Tips Against Multiple Sclerosis

2020: A review of using full-spectrum cannabis in the treatment of the neuropathic pain of MS

The anti-inflammatory and analgesic effects of formulated full-spectrum cannabis extract in the treatment of neuropathic pain associated with multiple sclerosis

2019: This meta-review of 14 studies found Sativex helpful for MS

Daily Practice Managing Resistant Multiple Sclerosis Spasticity With Delta-9-Tetrahydrocannabinol: Cannabidiol Oromucosal Spray: A Systematic Review of Observational Studies

2018: Excellent review of the ECS & MS

The endocannabinoid system and its therapeutic exploitation in multiple sclerosis: Clues for other neuroinflammatory diseases

2018: Review of cannabinoids for MS

Cannabinoids for Treatment of MS Symptoms: State of the Evidence

2018: A review of reviews for using cannabinoids for the symptoms of MS

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

2015: A review by Dr. Pertwee

Endocannabinoids in Multiple Sclerosis and Amyotrophic Lateral Sclerosis

2014: Sativex & MS

THC:CBD spray and MS spasticity symptoms: data from latest studies

2008: The ECS & MS

The endocannabinoid system and multiple sclerosis

2007: A literature review of 7 RCTs finds cannabinoids helpful for the neuropathic pain of MS

Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain

Timeline of Research

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 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

2020: This team created a new drug that activates both CB1 & CB2 - and then found it effective in an animal model of MS & neuropathic pain

The endocannabinoid system dual-target ligand N-cycloheptyl-1,2-dihydro-5-bromo-1-(4-fluorobenzyl)-6-methyl-2-oxo-pyridine-3-carboxamide improves disease severity in a mouse model of multiple sclerosis

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 a 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 AEA (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 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 a 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 a 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 a 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 a 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 a 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 a 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 a 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 a 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 a 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 rats, MAGL inhibitor for MS & pain

Development and Pharmacological Characterization of Selective Blockers of 2-Arachidonoyl Glycerol Degradation with Efficacy in Rodent Models of Multiple Sclerosis and Pain

2016: In humans, Sativex helped with MS symptoms

Tetrahydrocannabinol:Cannabidiol Oromucosal Spray for Multiple Sclerosis-Related Resistant Spasticity in Daily Practice

2015: In a 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 a 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 a 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 a 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 a 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 a 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

2015: In humans with MS, MRI scans show structural changes in the brain (39 patients)

Multiple sclerosis, cannabis, and cognition: A structural MRI study

2014: In a 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

2014: In mice, MAGL inhibitor for MS

A reversible and selective inhibitor of monoacylglycerol lipase ameliorates multiple sclerosis

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 a 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 a 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 a 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 a 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 a 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 an animal model 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, a 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 a 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 a 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 a 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 a 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 a 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-immunoreactivities 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 a mouse model of MS, using two inhibitors of the putative cannabinoid transporters (OMDM1 & OMDM2) provides an effective therapy

Pharmacological modulation of the endocannabinoid system in a viral model of multiple sclerosis

2005: In a 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 a rat 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 a 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 on 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 a mouse model of MS, endocannabinoid system found to be protective

Cannabinoids inhibit neurodegeneration in models of multiple sclerosis

2003: In a 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 a 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

1989: In an 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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