Gut microbiota, cannabinoid system and neuroimmune interactions: New perspectives in multiple sclerosis.

Biochemical Pharmacology

“The gut microbiota plays a fundamental role on the education and function of the host immune system.

Immunological dysregulation is the cause of numerous human disorders such as autoimmune diseases and metabolic disorders frequently associated with inflammatory processes therefore is critical to explore novel mechanisms involved in maintaining the immune system homeostasis.

The cannabinoid system and related bioactive lipids participate in multiple central and peripheral physiological processes that affect metabolic, gastrointestinal and neuroimmune regulatory mechanisms displaying a modulatory role and contributing to the maintenance of the organism’s homeostasis.

In this review, we gather the knowledge on the gut microbiota-endocannabinoids interactions and their impact on autoimmune disorders such as inflammatory bowel disease, rheumatoid arthritis and particularly, multiple sclerosis (MS) as the best example of a CNS autoimmune disorder.

Furthermore, we contribute to this field with new data on changes in many elements of the cannabinoid system in a viral model of MS after gut microbiota manipulation by both antibiotics and probiotics.

Finally, we highlight new therapeutic opportunities, under an integrative view, targeting the eCBS and the commensal microbiota in the context of neuroinflammation and MS.”

https://www.ncbi.nlm.nih.gov/pubmed/30171835

https://www.sciencedirect.com/science/article/abs/pii/S0006295218303630

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Variability of Multiple Sclerosis Spasticity Symptoms in Response to THC:CBD Oromucosal Spray: Tracking Cases through Clinical Scales and Video Recordings.

Logo Case Reports in Neurology

“Multiple sclerosis (MS) is an inflammatory and neurodegenerative autoimmune demyelinating disease of the central nervous system. Patients exhibit heterogeneous patterns of disabling symptoms, including spasticity. In the majority of patients with MS spasticity, it and its associated symptoms contribute to disability, interfere with performance of everyday activities, and impair quality of life. Even under treatment with oral antispasticity drugs, about a third of patients continue to experience spasticity of moderate to severe intensity, underscoring the need for additional treatment options.

The efficacy of tetrahydrocannabinol: cannabidiol (THC:CBD) oromucosal spray as add-on therapy in patients with refractory MS spasticity has been demonstrated in clinical trials and observational studies.

To gain insight into patients’ response to treatment at the individual level, in-depth changes from baseline in various clinical scales and video-assessed parameters were evaluated in patients with resistant MS spasticity before and after 1 month of treatment with THC:CBD oromucosal spray. All 6 patients showed ≥20% improvement in the spasticity Numerical Rating Scale (i.e., were initial responders to treatment), but displayed individual variability in other spasticity-related parameters.

Improved Modified Ashworth Scale scores were observed in 5 cases, with a reduction of -2/-3 points in lower limb scores for 1 patient who also showed benefit in terms of a more stable gait but modest improvement in the timed 10-meter walk test (10MWT). Improvement in the 10MWT (or 25-foot walk test) was noted in 4 of the 6 cases. THC:CBD oromucosal spray also improved upper limb function as indicated by faster 9-Hole Peg Test results.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabidiol Attenuates Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis Through Induction of Myeloid-Derived Suppressor Cells.

Image result for frontiers in immunology

“Multiple sclerosis (MS) is a chronic debilitating autoimmune disease without a cure. While the use of marijuana cannabinoids for MS has recently been approved in some countries, the precise mechanism of action leading to attenuate neuroinflammation is not clear. We used experimental autoimmune encephalomyelitis (EAE), a murine model of MS, to explore the anti-inflammatory properties of cannabidiol (CBD), a non-psychoactive cannabinoid. Treatment with CBD caused attenuation of EAE disease paradigms as indicated by a significant reduction in clinical scores of paralysis, decreased T cell infiltration in the central nervous system, and reduced levels of IL-17 and IFNγ. Interestingly, CBD treatment led to a profound increase in myeloid-derived suppressor cells (MDSCs) in EAE mice when compared to the vehicle-treated EAE controls. These MDSCs caused robust inhibition of MOG-induced proliferation of T cells in vitro. Moreover, adoptive transfer of CBD-induced MDSCs ameliorated EAE while MDSC depletion reversed the beneficial effects of CBD treatment, thereby conclusively demonstrating that MDSCs played a crucial role in CBD-mediated attenuation of EAE. Together, these studies demonstrate for the first time that CBD treatment may ameliorate EAE through induction of immunosuppressive MDSCs.”

https://www.ncbi.nlm.nih.gov/pubmed/30123217

“In conclusion, we have demonstrated that the mitigation of EAE with CBD comes from its ability to target a range of anti-inflammatory pathways, including (i) induction of anti-inflammatory MDSCs and (ii) decrease in pro-inflammatory and induction of anti-inflammatory cytokines. Because CBD is non-psychoactive, our studies suggest that CBD may constitute an excellent candidate for the treatment of MS and other autoimmune diseases. Our studies provide further evidence of the importance of MDSCs and that manipulation of such cells may constitute novel therapeutic modality to treat MS and other autoimmune diseases.”

https://www.frontiersin.org/articles/10.3389/fimmu.2018.01782/full

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Traditional Uses of Cannabinoids and New Perspectives in the Treatment of Multiple Sclerosis.

medicines-logo

“Recent findings highlight the emerging role of the endocannabinoid system in the control of symptoms and disease progression in multiple sclerosis (MS). MS is a chronic, immune-mediated, demyelinating disorder of the central nervous system with no cure so far. It is widely reported in the literature that cannabinoids might be used to control MS symptoms and that they also might exert neuroprotective effects and slow down disease progression. This review aims to give an overview of the principal cannabinoids(synthetic and endogenous) used for the symptomatic amelioration of MS and their beneficial outcomes, providing new potentially possible perspectives for the treatment of this disease.”

https://www.ncbi.nlm.nih.gov/pubmed/30111755

http://www.mdpi.com/2305-6320/5/3/91

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Emerging strategies targeting cb2 cannabinoid receptor: biased agonism and allosterism.

Biochemical Pharmacology

“During these last years, the CB2 cannabinoid receptor has emerged as a potential anti-inflammatory target in diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease, ischemic stroke, autoimmune diseases, osteoporosis, and cancer. However, the development of clinically useful CB2 agonists reveals to be very challenging. Allosterism and biased-signaling mechanisms at CB2 receptor may offer new avenues for the development of improved CB2 receptor-targeted therapies. Although there has been some exploration of CB1 receptor activation by new CB1 allosteric or biased-signaling ligands, the CB2 receptor is still at initial stages in this domain. In an effort to understand the molecular basis behind these pharmacological approaches, we have analyzed and summarized the structural data reported so far at CB2 receptor.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Therapeutic applications of cannabinoids.

Chemico-Biological Interactions

“The psychoactive properties of cannabinoids are well known and there has been a continuous controversy regarding the usage of these compounds for therapeutic purposes all over the world. Their use for medical and research purposes are restricted in various countries. However, their utility as medications should not be overshadowed by their negative physiological activities.

This review article is focused on the therapeutic potential and applications of phytocannabinoids and endocannabinoids. It highlights their mode of action, overall effects on physiology, various in vitro and in vivo studies that have been done so far and the extent to which these compounds can be useful in different disease conditions such as cancer, Alzheimer’s disease, multiple sclerosis, pain, inflammation, glaucoma and many others.

Thus, this work is an attempt to make the readers understand the positive implications of these compounds and indicates the significant developments that can occur upon utilizing cannabinoids as therapeutic agents.”  https://www.ncbi.nlm.nih.gov/pubmed/30040916

“Cannabinoids can be used as therapeutic agents.”   https://www.sciencedirect.com/science/article/pii/S0009279718307373?via%3Dihub
Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Tetrahydrocannabinol/Cannabidiol Oromucosal Spray in Patients With Multiple Sclerosis: A Pilot Study on the Plasma Concentration-Effect Relationship.

 Image result for ovid journal

“We aimed to assess the potential relationship between intrasubject 9-tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray plasma profiles and clinical effects elicited by subacute dosing in chronically treated patients with multiple sclerosis (MS).

METHODS:

The study design was pilot, single center, open, and prospective. The patients were challenged with a morning test dose of 2 THC/CBD sprays at a 15-minute interval. Venous blood samples were collected before the first spray administration and every 30 minutes after the second spray, until 240 minutes postdosing. Patients rated their spasticity by the Numerical Rating Scale (NRS) simultaneously with blood drawings. Postural and motor tests were performed before the first spray and 90 and 180 minutes thereafter.

RESULTS:

Twelve patients were recruited. Peak plasma concentrations of THC/CBD largely varied among patients, from 0.60 to 13.29 ng/mL for THC and 0.55 to 11.93 ng/mL for CBD. Time to peak plasma concentrations ranged from 150 to 240 minutes for THC and 90 to 240 minutes for CBD. Patients’ NRS serial scores decreased after dosing, from a median value of 6 to 3.5 (P < 0.001). A significant inverse correlation was observed between median intrasubject repeated NRS scores and corresponding median values of both THC (P < 0.01) and CBD (P < 0.002) plasma concentrations. No significant effect of cannabinoids dosing could be appreciated according to posturographic and motor tests.

CONCLUSIONS:

Our kinetic dynamic findings from THC/CBD oromucosal spray are the first obtained in real MS patients. Although preliminary, they suggest that subacute dosing might elicit a subjective clinically significant effect on MS-related spasticity, paralleling cannabinoids measurable plasma concentrations.”

https://www.ncbi.nlm.nih.gov/pubmed/30024443

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

The Management of Lower Urinary Tract Dysfunction in Multiple Sclerosis.

Current Neurology and Neuroscience Reports

“Multiple sclerosis (MS) is the most frequent neuroinflammatory disease of the central nervous system and is commonly associated with lower urinary tract (LUT) dysfunction. As a consequence, health-related quality of life is often impaired and the upper urinary tract might be at risk for damage. The aim of this review is to give an overview of current treatment options for LUT dysfunction in patients with MS.

RECENT FINDINGS:

The treatment is tailored to the type of dysfunction-storage or voiding dysfunction-beginning with conservative treatment options and ending with invasive therapies and surgery. Additionally, alternative options, e.g., different intravesical therapies or cannabinoids, have been evaluated in recent years with promising results. Current available therapies offer different possible treatments for LUT dysfunction in patients with MS. They address either voiding or storage dysfunction and therefore ameliorate LUT symptoms improve quality of life and protect the upper urinary tract.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Evidence for the use of “medical marijuana” in psychiatric and neurologic disorders.

College of Psychiatric and Neurologic Pharmacists

“Cannabis is listed as a Schedule I substance under the Controlled Substances Act of 1970, meaning the US federal government defines it as an illegal drug that has high potential for abuse and no established medical use; however, half of the states in the nation have enacted “medical marijuana” (MM) laws. Clinicians must be aware of the evidence for and against the use of MM in their patients who may consider using this substance.

RESULTS:

Publications were identified that included patients with dementia, multiple sclerosis, Parkinson disease, Huntington disease, schizophrenia, social anxiety disorder, depression, tobacco use disorder, and neuropathic pain.

DISCUSSION:

There is great variety concerning which medical conditions are approved for treatment with MM for either palliative or therapeutic benefit, depending on the state law. It is important to keep an evidence-based approach in mind, even with substances considered to be illegal under US federal law. Clinicians must weigh risks and benefits of the use of MM in their patients and should ensure that patients have tried other treatment modalities with higher levels of evidence for use when available and appropriate.”

https://www.ncbi.nlm.nih.gov/pubmed/29955495

““Medical marijuana” encompasses everything from whole-plant cannabis to synthetic cannabinoids available for commercial use approved by regulatory agencies. In determining whether MM is of clinical utility to our patients, it is important to keep in mind chemical constituents, dose, delivery, and indication. Selection of the patient appropriate for MM must be carefully considered because clinical guidelines and treatment options with stronger levels of evidence should be exhausted first in most cases. There seems to be strongest evidence for the use of MM in patients with MS and in patients with neuropathic pain; moderate evidence exists to support further research in social anxiety disorder, schizophrenia, PD, and tobacco use disorder; evidence is limited for use in patients with dementia, Huntington disease, depression, and anorexia.”

http://mhc.cpnp.org/doi/10.9740/mhc.2017.01.029?code=cpnp-site

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Structure-Activity Relationship of Cannabis Derived Compounds for the Treatment of Neuronal Activity-Related Diseases.

molecules-logo

“Cannabis sativa active compounds are extensively studied for their therapeutic effects, beyond the well-known psychotropic activity. C. Sativa is used to treat different medical indications, such as multiple sclerosis, spasticity, epilepsy, ulcerative colitis and pain. Simultaneously, basic research is discovering new constituents of cannabis-derived compounds and their receptors capable of neuroprotection and neuronal activity modulation. The function of the various phytochemicals in different therapeutic processes is not fully understood, but their significant role is starting to emerge and be appreciated. In this review, we will consider the structure-activity relationship (SAR) of cannabinoid compounds able to bind to cannabinoid receptors and act as therapeutic agents in neuronal diseases, e.g., Parkinson’s disease.”

https://www.ncbi.nlm.nih.gov/pubmed/29941830

http://www.mdpi.com/1420-3049/23/7/1526

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous