Category Archives: Multiple Sclerosis (MS)

β-Amyrin, the cannabinoid receptors agonist, abrogates mice brain microglial cells inflammation induced by lipopolysaccharide/interferon-γ and regulates Mφ1/Mφ2 balances.

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“Inflammation is a primary response to infection that can pathologically lead to various diseases including neurodegenerative diseases. The purpose of this study was to evaluate the effect of β-Amyrin, a naturally occurring pentacyclic triterpenoid compound, on inflammation induced by lipopolysaccharide (LPS) and interferone-γ (IFN-γ) in rat microglial cells.

CONCLUSION:

β-Amyrin reduces inflammation in microglial cells and can be used as a potential anti-inflammatory agent in central nervous system neurodegenerative diseases such as Alzheimer and multiple sclerosis, by affecting the inflammatory cytokine and differentiation of microglia as resident CNS macrophages.” https://www.ncbi.nlm.nih.gov/pubmed/29501766 “Amyrin and the endocannabinoid system. The canonical triterpene amyrin was recently suggested to bind to CB1 receptors and to significantly mediate cannabimimetic effects in animal models of pain.”   http://gertschgroup.com/blog/entry/3188293/amyrin-and-the-endocannabinoid-system

“The antinociceptive triterpene β-amyrin inhibits 2-arachidonoylglycerol (2-AG) hydrolysis without directly targeting CB receptors”   https://www.researchgate.net/publication/225079976_The_antinociceptive_triterpene_b-amyrin_inhibits_2-arachidonoylglycerol_2-AG_hydrolysis_without_directly_targeting_CB_receptors

“Finally, pentacyclic triterpenes such as β-amyrin and cycloartenol have been shown to possess numerous biological activities including anti-bacterial, anti-fungal, anti-inflammatory and anti-cancer properties.” https://www.linkedin.com/pulse/cannabis-has-terpenes-say-what-pure-hempnotics Image result for β-Amyrin]]>

Hypoxia mimetic activity of VCE-004.8, a cannabidiol quinone derivative: implications for multiple sclerosis therapy.

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“Multiple sclerosis (MS) is characterized by a combination of inflammatory and neurodegenerative processes variously dominant in different stages of the disease. Thus, immunosuppression is the goal standard for the inflammatory stage, and novel remyelination therapies are pursued to restore lost function.

Cannabinoids such as 9Δ-THC and CBD are multi-target compounds already introduced in the clinical practice for multiple sclerosis (MS). Semisynthetic cannabinoids are designed to improve bioactivities and druggability of their natural precursors. VCE-004.8, an aminoquinone derivative of cannabidiol (CBD), is a dual PPARγ and CB2agonist with potent anti-inflammatory activity.

Activation of the hypoxia-inducible factor (HIF) can have a beneficial role in MS by modulating the immune response and favoring neuroprotection and axonal regeneration.

We investigated the effects of VCE-004.8 on the HIF pathway in different cell types. CONCLUSIONS: This study provides new significant insights about the potential role of VCE-004.8 for MS treatment by ameliorating neuroinflammation and demyelination.” https://www.ncbi.nlm.nih.gov/pubmed/29495967 https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-018-1103-y]]>

Cannabidiol inhibits pathogenic T cells, decreases spinal microglial activation and ameliorates multiple sclerosis-like disease in C57BL/6 mice.

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“Cannabis extracts and several cannabinoids have been shown to exert broad anti-inflammatory activities in experimental models of inflammatory CNS degenerative diseases. Clinical use of many cannabinoids is limited by their psychotropic effects. However, phytocannabinoids like cannabidiol (CBD), devoid of psychoactive activity, are, potentially, safe and effective alternatives for alleviating neuroinflammation and neurodegeneration.

Treatment with CBD during disease onset ameliorated the severity of the clinical signs of EAE.

CBD, a non-psychoactive cannabinoid, ameliorates clinical signs of EAE in mice, immunized against MOG. Suppression of microglial activity and T-cell proliferation by CBD appeared to contribute to these beneficial effects.”

https://www.ncbi.nlm.nih.gov/pubmed/21449980 “In summary, we have shown that CBD administered to MOG-immunized C57BL/6 mice, at the onset of EAE disease, reduced the severity of the clinical signs of EAE. CBD treatment was accompanied by diminished axonal loss and inflammation (infiltration of T cells and microglial activation). Moreover, CBD prevented proliferation of myelin-specific T cells in vitro. These observations suggest that CBD may have potential for alleviating MS-like pathology.” http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01379.x/full

“Study Shows Cannabidiol (CBD) Improves MS-Like Symptoms”  http://www.prohealth.com/library/showarticle.cfm?libid=31211

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Effect of marijuana on Essential Tremor: A case report

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“Objective: Examine the effectiveness of THC marijuana versus non-THC marijuana on handwriting in Essential Tremor. Background: Essential tremor (ET) is a chronic movement disorder which can be quite debilitating. ET is often progressive, beginning as a mild visible tremor with little or no impact on activities of daily living (ADLs) but tends to increase in severity over the course of years, often to the extent that people with ET may have extreme difficulty with task such as writing, drinking, eating, shaving, or putting on make-up. Unfortunately, a certain portion of people with ET are either intolerant or unresponsive to the currently recommended treatments. Patients occasionally report improvement in ET after marijuana use. While reports exist of THC effect on tremor in patients with Multiple Sclerosis (MS) and Parkinson’s disease (PD), the same is not true for ET. Methods: Case Report. Results: Patient JB, a retired psychologist, had long-standing severe familial tremor significantly interfering with ADLs. Standard treatments were tried. Primidone was partially effective, but resulted in erectile dysfunction and anorgasmia. Propranolol was mildly effective, but was switched to metoprolol by his cardiologist. Gabapentin was ineffective and caused GI distress. Topiramate was ineffective. Diazepam and alcohol were effective but used only occasionally due to sedating effects. While on a family vacation in a state with legalized marijuana, JB recorded his handwriting at baseline, after using an oral non-THC marijuana derivative, after using standard marijuana (oral), and after using alcohol. Handwriting was moderately improved after taking the THC preparation, as well as after taking alcohol; the improvement was roughly equivalent with these two treatments. It did not improve with the non-THC preparation. Conclusions: This case report suggests 1) handwriting in ET may be improved with the use of THC, 2) handwriting in ET may not be improved with non-THC derivatives of marijuana, and 3) the effect of THC in this case was similar to that of alcohol. While there have been several small studies and case reports addressing the efficacy of marijuana in controlling tremor in PD and MS, no such studies have been conducted regarding ET and the use of marijuana and its derivatives for control of ET is currently considered category U due to insufficient evidence. Further investigation of the potential efficacy of marijuana for ET is clearly warranted.” http://www.mdsabstracts.org/abstract/effect-of-marijuana-on-essential-tremor-a-case-report/ http://www.mdsabstracts.org/abstract/effect-of-marijuana-on-essential-tremor-a-case-report/

“Marijuana May Improve Essential Tremor and Parkinson’s”  http://parkinsonsclinic.com/1/post/2016/05/marijuana-may-improve-essential-tremor-and-parkinsons.html

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Systematic review of systematic reviews for medical cannabinoids: Pain, nausea and vomiting, spasticity, and harms.

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Image result for Can Fam Physician “To determine the effects of medical cannabinoids on pain, spasticity, and nausea and vomiting, and to identify adverse events.

Systematic reviews with 2 or more randomized controlled trials (RCTs) that focused on medical cannabinoids for pain, spasticity, or nausea and vomiting were included.

  There is reasonable evidence that cannabinoids improve nausea and vomiting after chemotherapy. They might improve spasticity (primarily in multiple sclerosis). There is some uncertainty about whether cannabinoids improve pain, but if they do, it is neuropathic pain” https://www.ncbi.nlm.nih.gov/pubmed/29449262]]>

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

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Current Neurology and Neuroscience Reports

“Pharmaceutical cannabinoids such as nabiximols, nabilone and dronabinol, and plant-based cannabinoids have been investigated for their therapeutic potential in treating multiple sclerosis (MS) symptoms.

This review of reviews aimed to synthesise findings from high quality systematic reviews that examined the safety and effectiveness of cannabinoids in multiple sclerosis. We examined the outcomes of disability and disability progression, pain, spasticity, bladder function, tremor/ataxia, quality of life and adverse effects.

We identified 11 eligible systematic reviews providing data from 32 studies, including 10 moderate to high quality RCTs. Five reviews concluded that there was sufficient evidence that cannabinoids may be effective for symptoms of pain and/or spasticity in MS. Few reviews reported conclusions for other symptoms. Recent high quality reviews find cannabinoids may have modest effects in MS for pain or spasticity. Future research should include studies with non-cannabinoid comparators; this is an important gap in the evidence.” https://www.ncbi.nlm.nih.gov/pubmed/29442178 https://link.springer.com/article/10.1007%2Fs11910-018-0814-x]]>

Perspectives on marijuana use and effectiveness: A survey of NARCOMS participants.

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Home“Interest in and use of marijuana by persons with multiple sclerosis (MS) has increased. While potential benefits have been reported, so have concerns about potential risks. Few large studies have been conducted about the perceptions and current usage of marijuana and medical cannabinoids in persons with MS.

METHODS:

Participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) registry were surveyed in 2014 regarding legality and history of marijuana usage, both before and after diagnosis with MS.

RESULTS:

A total of 5,481 participants responded, with 78.2% female, 90% relapsing disease at onset, and a current mean age of 55.5 (10.2) years. Sixty-four percent had tried marijuana prior to their MS diagnosis, 47% have considered using for their MS, 26% have used for their MS, 20% have spoken with their physician about use, and 16% are currently using marijuana. Ninety-one percent think marijuana should be legal in some form. Men, those with higher disability, current and past nicotine smokers, and younger age were associated with a higher likelihood of current use.

CONCLUSIONS:

The majority of responders favor legalization and report high interest in the use of marijuana for treatment of MS symptoms, but may be reluctant to discuss this with health care providers. Health care providers should systematically inquire about use of marijuana.”

https://www.ncbi.nlm.nih.gov/pubmed/29185555

 http://cp.neurology.org/content/7/4/333

Targeting Cannabinoid Signaling in the Immune System: “High”-ly Exciting Questions, Possibilities, and Challenges.

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“It is well known that certain active ingredients of the plants of Cannabis genus, i.e., the “phytocannabinoids” [pCBs; e.g., (-)-trans-Δ9-tetrahydrocannabinol (THC), (-)-cannabidiol, etc.] can influence a wide array of biological processes, and the human body is able to produce endogenous analogs of these substances [“endocannabinoids” (eCB), e.g., arachidonoylethanolamine (anandamide, AEA), 2-arachidonoylglycerol (2-AG), etc.].

These ligands, together with multiple receptors (e.g., CB1 and CB2 cannabinoid receptors, etc.), and a complex enzyme and transporter apparatus involved in the synthesis and degradation of the ligands constitute the endocannabinoid system (ECS), a recently emerging regulator of several physiological processes.

The ECS is widely expressed in the human body, including several members of the innate and adaptive immune system, where eCBs, as well as several pCBs were shown to deeply influence immune functions thereby regulating inflammation, autoimmunity, antitumor, as well as antipathogen immune responses, etc.

Based on this knowledge, many in vitro and in vivo studies aimed at exploiting the putative therapeutic potential of cannabinoid signaling in inflammation-accompanied diseases (e.g., multiple sclerosis) or in organ transplantation, and to dissect the complex immunological effects of medical and “recreational” marijuana consumption.

Thus, the objective of the current article is (i) to summarize the most recent findings of the field; (ii) to highlight the putative therapeutic potential of targeting cannabinoid signaling; (iii) to identify open questions and key challenges; and (iv) to suggest promising future directions for cannabinoid-based drug development.”   https://www.ncbi.nlm.nih.gov/pubmed/29176975

“Although, many open questions await to be answered, pharmacological modulation of the (endo)cannabinoid signaling, and restoration of the homeostatic eCB tone of the tissues augur to be very promising future directions in the management of several pathological inflammation-accompanied diseases.”   https://www.frontiersin.org/articles/10.3389/fimmu.2017.01487/full

Multiple sclerosis symptoms and spasticity management: new data.

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“Spasticity, perceived by patients as muscle rigidity and spasms, is a common symptom in multiple sclerosis (MS). It is associated with functional impairment that can exacerbate other MS symptoms and reduce quality of life.

Pharmacological treatment options are limited and frequently ineffective. Treatment adherence is a key issue to address in these patients.

The efficacy and safety of 9-delta-tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray for treatment of MS spasticity were demonstrated in four Phase III trials.

Observational studies and registry data subsequently confirmed the effectiveness and tolerability of THC:CBD oromucosal spray under everyday practice conditions.

Among patients who respond to treatment, THC:CBD oromucosal spray has been shown to produce positive improvements in gait parameters and to normalize muscle fibers.”

https://www.ncbi.nlm.nih.gov/pubmed/29143581
https://www.futuremedicine.com/doi/10.2217/nmt-2017-0034

Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation.

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“Cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC) have well documented immunomodulatory effects in vitro, but not following oral administration in humans. Here we show that oral co-administration of cannabinoids with lipids can substantially increase their intestinal lymphatic transport in rats. Moreover, immune cells from MS patients were more susceptible to the immunosuppressive effects of cannabinoids than those from healthy volunteers or cancer patients. Therefore, administering cannabinoids with a high-fat meal or in lipid-based formulations has the potential to be a therapeutic approach to improve the treatment of MS, or indeed other autoimmune disorders.”  https://www.ncbi.nlm.nih.gov/pubmed/29109461

“Cannabis sativa has a very long history of medical use. In summary, it has been demonstrated in this work that oral co-administration of cannabis or cannabis-based medicines with lipids results in extremely high levels of lipophilic cannabinoids in the intestinal lymphatic system and prominent immunomodulatory effects. Therefore, administering cannabinoids with a high-fat meal, as cannabis-containing food, or in lipid-based formulations has the potential to be a therapeutic approach to improve the treatment of MS, or indeed other autoimmune disorders.”  https://www.nature.com/articles/s41598-017-15026-z