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Endocannabinoid pathways and their role in multiple sclerosis-related muscular dysfunction.
Expert Rev Neurother. 2011 Apr; 11(4 Suppl):9-14.ER

Abstract

Endocannabinoids are endogenous agonists of the mammalian cannabinoid receptors CB(1) and CB(2), and they appear to be produced in tissues as an adaptive reaction to re-establish normal homeostasis when this is acutely altered. However, the production of endocannabinoids can be altered pathologically. The two most widely studied endocannabinoids are anandamide and 2-arachidonoyl glycerol. The levels of these endogenous modulators are regulated in different and sometimes opposing ways, and alterations in cerebrospinal fluid and/or spinal cord levels have been documented in animal models of neurodegenerative diseases and in samples from patients with multiple sclerosis (MS). Modulation of the endocannabinoid system has been shown to have therapeutic potential in a number of disease states. Sativex(®) (nabiximols, USAN name) contains the two main phytocannabinoids from Cannabis sativa, tetrahydrocannabinol and cannabidiol in a 1:1 ratio, and it acts as an endocannabinoid system modulator. In an experimental mouse model of MS-related spasticity, Sativex dose-dependently improved hind limb flexion/stiffness and a dosage of 10 mg/kg was shown to be as effective as the most widely established anti-spasticity treatment baclofen (5 mg/kg). These findings with Sativex are very promising and offer encouragement for MS patients, the majority of whom will develop spasticity-related disabling and recalcitrant symptoms. Furthermore, research into the endocannabinoid system may offer potential in other neurodegenerative, inflammatory and pain disorders.

Authors+Show Affiliations

Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Naples, Italy. vdimarzo@icmib.na.cnr.it.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

21449854

Citation

Di Marzo, Vincenzo. "Endocannabinoid Pathways and Their Role in Multiple Sclerosis-related Muscular Dysfunction." Expert Review of Neurotherapeutics, vol. 11, no. 4 Suppl, 2011, pp. 9-14.
Di Marzo V. Endocannabinoid pathways and their role in multiple sclerosis-related muscular dysfunction. Expert Rev Neurother. 2011;11(4 Suppl):9-14.
Di Marzo, V. (2011). Endocannabinoid pathways and their role in multiple sclerosis-related muscular dysfunction. Expert Review of Neurotherapeutics, 11(4 Suppl), 9-14.
Di Marzo V. Endocannabinoid Pathways and Their Role in Multiple Sclerosis-related Muscular Dysfunction. Expert Rev Neurother. 2011;11(4 Suppl):9-14. PubMed PMID: 21449854.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endocannabinoid pathways and their role in multiple sclerosis-related muscular dysfunction. A1 - Di Marzo,Vincenzo, PY - 2011/4/1/entrez PY - 2011/4/1/pubmed PY - 2014/7/11/medline SP - 9 EP - 14 JF - Expert review of neurotherapeutics JO - Expert Rev Neurother VL - 11 IS - 4 Suppl N2 - Endocannabinoids are endogenous agonists of the mammalian cannabinoid receptors CB(1) and CB(2), and they appear to be produced in tissues as an adaptive reaction to re-establish normal homeostasis when this is acutely altered. However, the production of endocannabinoids can be altered pathologically. The two most widely studied endocannabinoids are anandamide and 2-arachidonoyl glycerol. The levels of these endogenous modulators are regulated in different and sometimes opposing ways, and alterations in cerebrospinal fluid and/or spinal cord levels have been documented in animal models of neurodegenerative diseases and in samples from patients with multiple sclerosis (MS). Modulation of the endocannabinoid system has been shown to have therapeutic potential in a number of disease states. Sativex(®) (nabiximols, USAN name) contains the two main phytocannabinoids from Cannabis sativa, tetrahydrocannabinol and cannabidiol in a 1:1 ratio, and it acts as an endocannabinoid system modulator. In an experimental mouse model of MS-related spasticity, Sativex dose-dependently improved hind limb flexion/stiffness and a dosage of 10 mg/kg was shown to be as effective as the most widely established anti-spasticity treatment baclofen (5 mg/kg). These findings with Sativex are very promising and offer encouragement for MS patients, the majority of whom will develop spasticity-related disabling and recalcitrant symptoms. Furthermore, research into the endocannabinoid system may offer potential in other neurodegenerative, inflammatory and pain disorders. SN - 1744-8360 UR - https://www.unboundmedicine.com/medline/citation/21449854/Endocannabinoid_pathways_and_their_role_in_multiple_sclerosis_related_muscular_dysfunction_ L2 - http://www.tandfonline.com/doi/full/10.1586/ern.11.26 DB - PRIME DP - Unbound Medicine ER -