Low Doses of β-Caryophyllene Reduced Clinical and Paraclinical Parameters of an Autoimmune Animal Model of Multiple Sclerosis: Investigating the Role of CB2 Receptors in Inflammation by Lymphocytes and Microglial

Multiple Sclerosis (MS) is a prevalent inflammatory disease in which the immune system plays an essential role in the damage, inflammation, and demyelination of central nervous system neurons (CNS). The cannabinoid receptor type 2 (CB2) agonists possess anti-inflammatory effects against noxious stimuli and elevate the neuronal survival rate. We attempted to analyze the protective impact of low doses of β-Caryophyllene (BCP) in experimental autoimmune encephalomyelitis (EAE) mice as a chronic MS model. Immunization of female C57BL/6 mice was achieved through two subcutaneous injections into different areas of the hind flank with an emulsion that consisted of myelin Myelin oligodendrocyte glycoprotein (MOG)35–55 (150 µg) and complete Freund’s adjuvant (CFA) (400 µg) with an equal volume. Two intraperitoneal (i.p.) injections of pertussis toxin (300 ng) were performed on the animals on day zero (immunizations day) and 48 h (2nd day) after injection of MOG + CFA. The defensive effect of low doses of BCP (2.5 and 5 mg/kg/d) was investigated in the presence and absence of a CB2 receptor antagonist (1 mg/kg, AM630) in the EAE model. We also examined the pro/anti-inflammatory cytokine levels and the polarization of brain microglia and spleen lymphocytes in EAE animals. According to our findings, low doses of BCP offered protective impacts in the EAE mice treatment in a CB2 receptor-dependent way. In addition, according to results, BCP decreased the pathological and clinical defects in EAE mice via modulating adaptive (lymphocytes) and innate (microglia) immune systems from inflammatory phenotypes (M1/Th1/Th17) to anti-inflammatory (M2/Th2/Treg) phenotypes. Additionally, BCP elevated the anti-inflammatory cytokine IL-10 and reduced blood inflammatory cytokines. BCP almost targeted the systemic immune system more than the CNS immune system. Thus, a low dose of BCP can be suggested as a therapeutic effect on MS treatment with potent anti-inflammatory effects and possibly lower toxicity.

Multiple Sclerosis and Use of Medical Cannabis: A Retrospective Review of a Neurology Outpatient Population

Patients diagnosed as having multiple sclerosis (MS) experience a wide range of symptoms requiring pharmacologic management, and many do not achieve adequate symptom control. The purpose of this study was to evaluate the role of medical cannabis (MC) as part of a comprehensive treatment plan for patients with MS. A retrospective medical record review of 141 patients with MS receiving MC for symptom management was conducted. Data were collected for up to 4 follow-up appointments after initiation of MC. Outcomes included changes in MS symptoms, medication changes, adverse events, and changes in cognition and mobility.

Therapeutic Potential of Phytocannabinoid Cannabigerol for Multiple Sclerosis: Modulation of Microglial Activation In Vitro and In Vivo

Multiple sclerosis (MS) is a widespread chronic neuroinflammatory and neurodegenerative disease. Microglia play a crucial role in the pathogenesis of MS via the release of cytokines and reactive oxygen species, e.g., nitric oxide. Research involving the role of phytocannabinoids in neuroinflammation is currently receiving much attention. Cannabigerol is a main phytocannabinoid, which has attracted significant pharmacological interest due to its non-psychotropic nature. In this research, we studied the effects of cannabigerol on microglial inflammation in vitro, followed by an in vivo study. Cannabigerol attenuated the microglial production of nitric oxide in BV2 microglia and primary glial cells; concomitant treatment of the cells with cannabigerol and telmisartan (a neuroprotective angiotensin receptor blocker) decreased nitric oxide production additively. Inducible nitric oxide synthase (iNOS) expression was also reduced by cannabigerol.

Multiple Sclerosis and Use of Medical Cannabis: A Retrospective Review of a Neurology Outpatient Population

Patients diagnosed as having multiple sclerosis (MS) experience a wide range of symptoms requiring pharmacologic management, and many do not achieve adequate symptom control. The purpose of this study was to evaluate the role of medical cannabis (MC) as part of a comprehensive treatment plan for patients with MS. A retrospective medical record review of 141 patients with MS receiving MC for symptom management was conducted. Data were collected for up to 4 follow-up appointments after initiation of MC. Outcomes included changes in MS symptoms, medication changes, adverse events, and changes in cognition and mobility.

The Dynamic Role of Microglia and the Endocannabinoid System in Neuroinflammation

Microglia, the resident immune cells of the brain, can take on a range of pro- or anti-inflammatory phenotypes to maintain homeostasis. However, the sustained activation of pro-inflammatory microglia can lead to a state of chronic neuroinflammation characterized by high concentrations of neurotoxic soluble factors throughout the brain.

Cannabidiol and Other Cannabinoids in Demyelinating Diseases

A growing body of preclinical evidence indicates that certain cannabinoids, including cannabidiol (CBD) and synthetic derivatives, may play a role in the myelinating processes and are promising small molecules to be developed as drug candidates for management of demyelinating diseases such as multiple sclerosis (MS), stroke and traumatic brain injury (TBI), which are three of the most prevalent demyelinating disorders. Thanks to the properties described for CBD and its interesting profile in humans, both the phytocannabinoid and derivatives could be considered as potential candidates for clinical use. In this review we will summarize current advances in the use of CBD and other cannabinoids as future potential treatments.

Immunomodulatory Potential of Cannabidiol in Multiple Sclerosis: a Systematic Review

Authors Alessia Furgiuele, Marco Cosentino, Marco Ferrari & Franca Marino Published in Journal of Neuroimmune Pharmacology January 2021 Abstract Multiple sclerosis (MS) is the most common chronic autoimmune disease of…

Cannabis Therapeutics and the Future of Neurology

Author: Ethan B. Russo Published in: Frontiers in Integrative Neuroscience  October 2018 Abstract Introduction: Cannabis burst across the Western medicine horizon after its introduction by William O’Shaughnessy in 1838 (O’Shaughnessy, 1838–1840;…

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

Authors: Nicholas Dopkins, Kiesha Wilson, Kathryn Miranda, Prakash S Nagarkatti and Mitzi Nagarkatti Published in The Journal of Immunology May 2020   Abstract Cannabidiol (CBD) is a nonpsychoactive ingredient from…

Tetrahydrocannabinol and cannabidiol oromucosal spray in resistant multiple sclerosis spasticity: consistency of response across subgroups from the SAVANT randomized clinical trial.

Authors: Sven G. Meuth, Thomas Henze, Ute Essner, Christiane Trompke, Carlos Vila Silván Published in International Journal of Neuroscience Abstract Objective: To determine whether differences in disability status, spasticity severity,…

The influence of THC:CBD oromucosal spray on driving ability in patients with multiple sclerosis-related spasticity.

Authors: Elisabeth G. Celius, Carlos Vila
Brain and Behavior, 6 April 2018

BACKGROUND: Driving ability is a key function for the majority of patients with multiple sclerosis (MS) to help maintain daily interactions. Both physical and cognitive disability, as well as treatments, may affect the ability to drive. Spasticity is a common symptom associate…

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

Authors: Atheer Zgair, Jong Bong Lee, Jonathan C. M. Wong, Dhiaa A. Taha, Jehan Aram, et al
Scientific Reports, 6 November 2017

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 lympha…