Endocannabinoid System (ECS)

Author: Jo Frowde. Scleroderma is highly variable. See Types of Scleroderma. Read Disclaimer
Cannabidiol (CBD)
Marijuana (Cannabis sativa)
Autoimmune Diseases


ECS KaleidoscopeThe Endocannabinoid System is the name for a series of endogenous cell receptors that respond to certain kinds of agonists, known as Cannabinoid Receptor 1 (CB1), which are abundant in the central nervous system and Cannabinoid Receptor 2 (CB2), which are more often found on immune cells, in the gastrointestinal tract, and in the peripheral nervous system. Endocannabinoids are chemicals made by the body which produce a relaxing sensation similar to smoking cannabis.

The role of the endocannabinoid system in pain. Signalling through both CB1 and CB2 receptor subtypes has a role in normal nociceptive processing and also in the development resolution of acute pain states. PubMed, Handb Exp Pharmacol, 2015;227:119-43. (Also see Pain Management)

Endocannabinoids and Their Pharmacological Actions. This review describes endocannabinoids and their pharmacological actions and their interaction with CB1 and CB2 receptors. PubMed, Handb Exp Pharmacol, 2015;231:1-37.

Endocannabinoids and the Cardiovascular System in Health and Disease. In neurovascular disorders such as stroke, endocannabinoids are upregulated and protective. Although most of this evidence is from preclinical studies, it seems likely that cannabinoid–based therapies could be beneficial in a range of cardiovascular disorders. PubMed, Handb Exp Pharmacol, 2015;231:393-422. (Also see Cardiac (Heart) Involvement)

Distribution of the Endocannabinoid System in the Central Nervous System. This review will focus on the localization of the best–known components of the endocannabinoid system for which the strongest anatomical evidence exists. PubMed, Handb Exp Pharmacol, 2015;231:59-93.

ECS and the Gut

Changes in the Peripheral Endocannabinoid System as a Risk Factor for the Development of Eating Disorders. Besides their central role in controlling food behaviours, peripheral cannabinoids are also involved in regulating adipose tissue and insulin signalling as well as cell metabolism in peripheral tissues such as liver, pancreas, fatty tissue, and skeletal muscle. PubMed, Endocr Metab Immune Disord Drug Targets, 02/12/2018.

Intestinal microbiome in scleroderma (SSc): recent progress. Emerging evidence suggests that alterations in gut microbiota exist in the SSc disease state and more studies are needed to ascertain the mechanism by which these alterations perpetuate inflammation and fibrosis in SSc. PubMed, Curr Opin Rheumatol, 2017 Nov;29(6):553-560. (Also see Bowel Dysfunction)

Endocannabinoid system acts as a regulator of immune homeostasis in the gut. Our study unveils a role for the endocannabinoid system in maintaining immune homeostasis in the gut/pancreas and reveals a conversation between the nervous and immune systems using distinct receptors. PubMed, Proc Natl Acad Sci U S A, 2017 May 9;114(19):5005-5010. (Also see Bowel Dysfunction)

Endocannabinoids in the Gut This review highlights research that reveals an important role for the endocannabinoid system in the control of a variety of gastrointestinal functions. PMC, Cannabis Cannabinoid Res, 2016; 1(1): 67–77. (Also see Bowel Dysfunction)

Cannabidiol (CBD)

What is CBD? Cannabidiol (CBD) is a cannabis compound that has significant medical benefits and scientific and clinical research underscores CBD’s potential as a treatment for a wide range of conditions. Project CBD.

10 Facts About Cannabidiol (CBD) CBD, or cannabidiol, is a compound in marijuana that offers many benefits without any high. Leaf Science, 10/11/2017.

Marijuana (Cannabis sativa)

Marijuana (Cannabis sativa) The most commonly studied ingredients in marijuana are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Research has looked at these compounds both alone and in combination. Mayo Clinic.

Cannabinoids: Medical implications. Medical cannabis patients must be informed about potential adverse effects, such as acute impairment of memory, coordination and judgment, and possible chronic effects, such as cannabis use disorder, cognitive impairment, and chronic bronchitis. PubMed, Ann Med, 2016;48(3):128-41. (Also see Pain Management)

CBD for Autoimmune Diseases

Corbus Pharmaceuticals Expands Target Indications by Adding More Than 600 Compounds Focused on the Endocannabinoid System from Jenrin Discovery. Corbus Pharmaceuticals Holdings, Inc. announced today that it has licensed the exclusive worldwide rights to develop, manufacture and market drug candidates, which includes CRB-4001, a peripherally–restricted, CB1 inverse agonist targeting liver, lung, heart and kidney fibrotic diseases. Corbus Pharmaceuticals, 09/20/2018. (Also see Endocannabinoid System)

Corbus Pharmaceuticals to Commence Phase 3 Study of Lenabasum for the Treatment of Rare Autoimmune Disease Dermatomyositis. Corbus Pharmaceuticals announced today that the Company will proceed with a Phase 3 trial evaluating the efficacy and safety of lenabasum for the treatment of dermatomyositis. Globe Newswire, 07/25/2018. (Also see Treatments for Dermatomyositis and Clinical Trials)

The relationship of endocannabinoidome lipid mediators with pain and psychological stress in women with fibromyalgia (FM)– a case control study. This study reports about elevated plasma levels of endocannabinoidome lipid mediators in FM. PubMed, J Pain, 06/06/2018. (Also see Treatments for Fibromyalgia)

Mechanisms of action of cannabidiol (CBD) in adoptively transferred experimental autoimmune encephalomyelitis (EAE). CBD markedly improved the clinical signs of at–EAE and reduced infiltration, demyelination and axonal damage. PubMed, Exp Neurol, 2017 Sep 1;298(Pt A):57-67.

Purified Cannabidiol (CBD), the main non–psychotropic component of Cannabis sativa, alone, counteracts neuronal apoptosis in experimental multiple sclerosis (MS). Purified CBD possesses an anti–apoptotic power against the neurodegenerative processes underlying MS development. PubMed, Eur Rev Med Pharmacol Sci, 2015 Dec;19(24):4906-19. (Also see Multiple Sclerosis)

Role of Endocannabinoid Activation of Peripheral CB1 Receptors in the Regulation of Autoimmune Disease. Based on the evidence presented using the endocannabinoids, we propose that the peripheral CB1 receptor is involved in the regulation and amelioration of inflammation associated with autoimmune diseases. PubMed, Int Rev Immunol, 2015;34(5):403-14.

CBD for Scleroderma

Lenabasum Safe and Effective in Diffuse Scleroderma Patients, One–year Trial Data Show. Lenabasum, by Corbus Pharmaceuticals, was shown to be safe, well-tolerated and of benefit to patients treated for one year in a long-term extension of a Phase 2 trial. Scleroderma News, 05/17/2018. (Also see Clinical Trials)

Corbus Wins Expanded U.S. Patent Coverage of Anabasum Therapy for Systemic Sclerosis. Corbus Pharmaceuticals has extended its intellectual property portfolio with a new patent for its investigative cannabinoid–derived drug candidate anabasum to treat inflammatory diseases. Scleroderma News, 11/02/2017. (Also see Clinical Trials)

Emerald Health Pharmaceuticals Granted FDA Orphan Drug Designation for Systemic Scleroderma. Emerald Health Pharmaceuticals Inc. (EHP), which is developing medications based on cannabinoid science, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for its lead molecule, EHP-101, for the treatment of systemic scleroderma. Globe Newswire, 10/20/2017.

New Cannabinoid-based Drug Slows Fibrosis, Blocks Inflammation in Early Scleroderma Study. The drug, VCE-004.8, prevented the formation of fibrosis-promoting myofibroblasts in culture and stopped fibrotic changes in a mouse model of dermal fibrosis. Findings from these pre-clinical studies, while early, are promising and may lead to a new therapy for SSc. Scleroderma News, 03/24/2016.

Expression of the endocannabinoid receptors in human fascial tissue. The endocannabinoid receptors of fascial fibroblasts can contribute to modulate the fascial fibrosis and inflammation. PubMed, Eur J Histochem, 2016 Jun 28;60(2):2643. (Also see Fibroblasts)

Cannabinoids and autoimmune diseases: A systematic review. Cannabinoids are effective as treatment for fibromyalgia and have shown to have anti–fibrotic effect in scleroderma. PubMed, Autoimmun Rev, 2016 Jun;15(6):513-28. (Also see Fibromyalgia)

Pathogenesis of Systemic Sclerosis (SSc). The roles played by other ubiquitous molecular entities in influencing the immune system, vasculature, and connective tissue cells may provide insights into new therapeutic approaches to treat SSc. PubMed, Front Immunol, 2015 Jun 8;6:272.

Warnings for CBD

In states with medical marijuana, there is product testing through the legitimate dispensaries, normally making them the best resource for actual CBD.

Warning Letters and Test Results for Cannabidiol–Related Products. Over the past several years, The US Food and Drug Administration (FDA) has issued several warning letters to firms that market unapproved new drugs that allegedly contain cannabidiol (CBD). FDA, 11/02/2017. (Also see Warnings and Voluntary Recalls on Medications and Treatments)

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