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  • #16
    Originally posted by ActiveMSers View Post
    Brain Behav Immun. 2019 Jul 26. pii: S0889-1591(19)30647-6. doi: 10.1016/j.bbi.2019.07.028. [Epub ahead of print]

    Combination of cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), mitigates experimental autoimmune encephalomyelitis (EAE) by altering the gut microbiome.

    Al-Ghezi, et al

    Abstract

    Currently, a combination of marijuana cannabinoids including delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is used as a drug to treat muscle spasticity in patients with Multiple Sclerosis (MS). Because these cannabinoids can also suppress inflammation, it is unclear whether such patients benefit from suppression of neuroinflammation and if so, what is the mechanism through which cannabinoids act.

    In the currently study, we used a murine model of MS, experimental autoimmune encephalomyelitis (EAE), to study the role of gut microbiota in the attenuation of clinical signs of paralysis and inflammation caused by cannabinoids.

    THC+CBD treatment attenuated EAE and caused significant decrease in inflammatory cytokines such as IL-17 and IFN-γ while promoting the induction of anti-inflammatory cytokines such as IL-10 and TGF-β. Use of 16S rRNA sequencing on bacterial DNA extracted from the gut revealed that EAE mice showed high abundance of mucin degrading bacterial species, such as Akkermansia muciniphila (A.muc), which was significantly reduced after THC+CBD treatment. Fecal Material Transfer (FMT) experiments confirmed that THC+CBD-mediated changes in the microbiome play a critical role in attenuating EAE. In silico computational metabolomics revealed that LPS biosynthesis, a key component in gram-negative bacteria such as A.muc, was found to be elevated in EAE mice which was confirmed by demonstrating higher levels of LPS in the brain, while treatment with THC+CBD reversed this trend. EAE mice treated with THC+CBD also had significantly higher levels of short chain fatty acids such as butyric, isovaleric, and valeric acids compared to naïve or disease controls.

    Collectively, our data suggest that cannabinoids may attenuate EAE and suppress neuroinflammation by preventing microbial dysbiosis seen during EAE and promoting healthy gut microbiota.
    Thanks Dave for all you do for us and the information you share with us.

    Comment


    • #17
      Original Article
      Published: 25 April 2020

      Effects of THC/CBD oromucosal spray on spasticity-related symptoms in people with multiple sclerosis: results from a retrospective multicenter study

      Francesco Patti, Clara Grazia Chisari, […]on behalf of the SA.FE. group
      Neurological Sciences (2020)

      Abstract

      Introduction
      The approval of 9-δ-tetrahydocannabinol (THC)+cannabidiol (CBD) oromucosal spray (Sativex®) in Italy as an add-on medication for the management of moderate to severe spasticity in multiple sclerosis (MS) has provided a new opportunity for MS patients with drug-resistant spasticity. We aimed to investigate the improvement of MS spasticity-related symptoms in a large cohort of patients with moderate to severe spasticity in daily clinical practice.

      Materials and methods
      MS patients with drug-resistant spasticity were recruited from 30 Italian MS centers. All patients were eligible for THC:CBD treatment according to the approved label: ≥ 18 years of age, at least moderate spasticity (MS spasticity numerical rating scale [NRS] score ≥ 4) and not responding to the common antispastic drugs. Patients were evaluated at baseline (T0) and after 4 weeks of treatment (T1) with the spasticity NRS scale and were also asked about meaningful improvements in 6 key spasticity-related symptoms.

      Results
      Out of 1615 enrolled patients, 1432 reached the end of the first month trial period (T1). Of these, 1010 patients (70.5%) reached a ≥ 20% NRS score reduction compared with baseline (initial responders; IR). We found that 627 (43.8% of 1432) patients showed an improvement in at least one spasticity-related symptom (SRSr group), 543 (86.6%) of them belonging to the IR group and 84 (13.4%) to the spasticity NRS non-responders group.

      Conclusion
      Our study confirmed that the therapeutic benefit of cannabinoids may extend beyond spasticity, improving spasticity-related symptoms even in non-NRS responder patients.
      Dave Bexfield
      ActiveMSers

      Comment


      • #18
        ACTRIMS 2020 POSTER SESSION

        P0439 - Cannabis Use Among People with MS: A 2020 NARCOMS Survey (ID 1483)


        SpeakersAuthors
        Presentation Number
        P0439
        Presentation Topic
        EpidemiologyBackground
        The North American Research Committee on Multiple Sclerosis (NARCOMS) registry is a voluntary self-report registry for persons with MS. Interest has been growing over time regarding the benefits of cannabis for management of various symptoms in MS, particularly as cannabis becomes more accessible.

        Objectives
        To evaluate the contemporary prevalence of cannabis use among persons with MS, and demographic factors associated with cannabis use for MS symptom management.

        Methods
        Active US NARCOMS participants were invited to complete an online, supplemental survey regarding cannabis use (excluding hemp CBD and products labeled as CBD only) for their MS symptoms. Demographic and clinical characteristics captured included age, sex, race, state of residence, age at MS symptom onset, and disability level measured using the Patient Determined Disease Steps (PDDS). Participant-reported symptoms of spasticity, pain, and sleep problems were captured using a numeric rating scale (NRS) with scores ranging from 0 (no problems) to 10 (worst possible problems). For the analysis we categorized NRS scores as 0 (normal), 1-3 (mild), 4–6 (moderate), and 7–10 (severe). We summarized the findings using descriptive statistics.

        Results
        Of the 6934 participants invited, 3249 (46.9%) responded. Most respondents were female (78.5%), Caucasian (88.5%), and had a mean (SD) age of 61.2 (10.2) years. The respondents had a mean age at symptom onset of 31.2 (10.3) years, and a median (25th, 75th) PDDS level of 3 [Gait Disability] (1 [Mild Disability], 6 [Bilateral Support]). Over 60% of respondents reported moderate to severe spasticity, pain, or sleep problems. Thirty-one percent of respondents (n=1012) indicated they had used cannabis for their MS symptoms at least once; of these respondents, 50.5% had used cannabis to treat spasticity, 43.6% had used cannabis for pain, and 38.4% had used cannabis for sleep. There were 636 (19.6%) respondents who reported current use of cannabis for their MS, while 376 (11.6%) reported past use but not current use. Current users were comparable to past users except current users were more likely to be male (p=0.001) and on average slightly younger (p=0.009).

        Conclusions
        In this US registry-based sample, 31% of participants reported ever using cannabis for MS symptoms, and 20% reported current use within the prior 30 days.
        Dave Bexfield
        ActiveMSers

        Comment


        • #19
          Molecules
          2020 Oct 25;25(21):E4930.
          A Critical Review of the Role of the Cannabinoid Compounds Δ 9-Tetrahydrocannabinol (Δ 9-THC) and Cannabidiol (CBD) and their Combination in Multiple Sclerosis Treatment

          Éamon Jones 1, Styliani Vlachou 1
          Affiliations expandAbstract

          Many people with MS (pwMS) use unregulated cannabis or cannabis products to treat the symptoms associated with the disease. In line with this, Sativex, a synthetic combination of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) has been approved to treat symptoms of spasticity. In animals, CBD is effective in reducing the amounts of T-cell infiltrates in the spinal cord, suggesting CBD has anti-inflammatory properties. By doing this, CBD has shown to delay symptom onset in animal models of multiple sclerosis and slow disease progression. Importantly, combinations of CBD and Δ9-THC appear more effective in treating animal models of multiple sclerosis. While CBD reduces the amounts of cell infiltrates in the spinal cord, Δ9-THC reduces scores of spasticity. In human studies, the results are less encouraging and conflict with the findings in animals.

          Drugs which deliver a combination of Δ9-THC and CBD in a 1:1 ratio appear to be only moderately effective in reducing spasticity scores, but appear to be almost as effective as current front-line treatments and cause less severe side effects than other treatments, such as baclofen (a GABA-B receptor agonist) and tizanidine (an α2 adrenergic receptor agonist). The findings of the studies reviewed suggest that cannabinoids may help treat neuropathic pain in pwMS as an add-on therapy to already established pain treatments. It is important to note that treatment with cannabinoid compounds may cause significant cognitive dysfunction. Long term double-blind placebo studies are greatly needed to further our understanding of the role of cannabinoids in multiple sclerosis treatment.
          Dave Bexfield
          ActiveMSers

          Comment


          • #20
            Interesting, I thought it was just CBD that helped MS spasticity and pain...this article suggests it works in combo with the THC. Article also opines it is better to start with this treatment over baclofen and tizadine, which have significant negative side effects. Nevertheless, this finding is of no use to me or other MSers with pain and spasticity in states where medical marijuana it is illegal. Maybe the fact that it is a synthetic drug that can be regulated (and measured dose) will lead to it being legally allowed to all in the future. Sigh. Idk, why is baclofen ok to be prescribed over salivex??? Baclofen gave me relief but i did not like.. it made me rubbery and would kick my butt with a strong rebound effect. So I just suffer. So glad another treatment may be on horizon.

            Comment


            • #21
              Also interesting, the authors apparently do not consider "significant cognitive disfunction" a serious side effect but since essentially all drugs have side effects, it does come down to what the user considers too serious to warrant symptom relief.

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