Plasma endocannabinoid levels in multiple sclerosis

Jean-Gilles, Lucie; Feng, Shile; Tench, Christopher R.; Chapman, Victoria; Kendall, David A.; Barrett, David A.; Constantinescu, Cris S.

doi:10.1016/j.jns.2009.07.021

Cited by 97 publications

(78 citation statements)

References 33 publications

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“…Such changes in eCB levels have been detected in plasma from patients with multiple sclerosis 78 , as well as in patients with disorders ranging from Parkinson’s disease and Huntington’s disease to amyotrophic lateral sclerosis, and/or in tissues from the corresponding animal models 79 . These changes are likely to be influenced also by age-related alterations in the composition of the eCB signalling system.…”

Section: Endocannabinoids and Neuroinflammationmentioning

confidence: 96%

Endocannabinoid signalling and the deteriorating brain

2014

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Ageing is characterized by the progressive impairment of physiological functions and increased risk of developing debilitating disorders, including chronic inflammation and neurodegenerative diseases. These disorders have common molecular mechanisms that can be targeted therapeutically. In the wake of the approval of the first cannabinoid-based drug for the symptomatic treatment of multiple sclerosis, we examine how endocannabinoid (eCB) signalling controls — and is affected by — normal ageing and neuroinflammatory and neurodegenerative disorders. We propose a conceptual framework linking eCB signalling to the control of the cellular and molecular hallmarks of these processes, and categorize the key components of endocannabinoid signalling that may serve as targets for novel therapeutics.

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Section: Endocannabinoids and Neuroinflammationmentioning

confidence: 96%

Endocannabinoid signalling and the deteriorating brain

2014

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“…(De Marchi, De Petrocellis et al 2003, Hill, Miller et al 2009, Koppel, Bradshaw et al 2009, Caraceni, Viola et al 2010, Matias, Gatta-Cherifi et al 2012) Little is known about eCBs in MS and previously published data on serum eCBs levels in individuals with MS were inconclusive. (Jean-Gilles, Feng et al 2009) Our results suggest that AEA levels may be increased in individuals with MS. A change in eCB signaling is not apparently sufficient to affect disease process in MS, but may participate in MS progression. (Pryce 2012) Specifically, since AEA has been suggested to be neuro-protective and have an anti-inflammatory profile in CNS parenchyma (Correa, Mestre et al 2009) (Eljaschewitsch, Witting et al 2006), eCB changes likely influence both immune response and resulting cell damage in brain tissue.…”

Section: Discussionmentioning

confidence: 56%

Cannabis use by individuals with multiple sclerosis: effects on specific immune parameters

et al. 2014

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Cannabinoids affect immune responses in ways that may be beneficial for autoimmune diseases. We sought to determine whether chronic Cannabis use differentially modulates a select number of immune parameters in healthy controls and individuals with multiple sclerosis (MS cases). Subjects were enrolled and consented to a single blood draw, matched for age and BMI. We measured monocyte migration isolated from each subject, as well as plasma levels of endocannabinoids and cytokines. Cases met definition of MS by international diagnostic criteria. Monocyte cell migration measured in control subjects and individuals with MS were similarly inhibited by a set ratio of phytocannabinoids. The plasma levels of CCL2 and IL17 were reduced in non-naïve cannabis users irrespective of the cohorts. We detected a significant increase in the endocannabinoid arachidonoylethanolamine (AEA) in serum from individuals with MS compared to control subjects, and no significant difference in levels of other endocannabinoids and signaling lipids irrespective of Cannabis use. Chronic Cannabis use may affect the immune response to similar extent in individuals with MS and control subjects through the ability of phytocannabinoids to reduce both monocyte migration and cytokine levels in serum. From a panel of signaling lipids, only the levels of AEA are increased in individuals with MS, irrespective from Cannabis use or not. Our results suggest that both MS cases and controls respond similarly to chronic Cannabis use with respect to the immune parameters measured in this study.

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“…MS is an autoimmune disease which causes chronic inflammation in the central nervous system, due to infiltration of Th17 and Th1 cells as well as macrophage activation [51]. Together, the T cell infiltration and macrophage activation can cause oligodendrocyte death, demyelination, and damage to axons [52].…”

Section: Introductionmentioning

confidence: 99%

“…In a study of both RRMS and SPMS patients, EC levels were analyzed in plasma (nanomolar) during a time when no immunomodulatory drugs were given and the RRMS patients were in clinical remission [51]. Jean-Gilles et al found that AEA and PEA levels were significantly increased in both RRMS and SPMS patients compared to healthy controls, and neither RRMS or SPMS patients exhibited increased levels of 2-AG in blood plasma [51].…”

Section: Introductionmentioning

confidence: 99%

“…Jean-Gilles et al found that AEA and PEA levels were significantly increased in both RRMS and SPMS patients compared to healthy controls, and neither RRMS or SPMS patients exhibited increased levels of 2-AG in blood plasma [51]. It was also found that SPMS patients had significantly increased levels of AEA and PEA compared to RRMS patients, and also had significantly less FAAH present in whole blood samples possibly due to pro-inflammatory cytokines such as IFN- γ and IL-12 [51]. A cytokine-mediated reduction in FAAH could be affecting the EC levels seen in MS patients [71].…”

Section: Introductionmentioning

confidence: 99%

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Role of Endocannabinoid Activation of Peripheral CB1 Receptors in the Regulation of Autoimmune Disease

Sido

Nagarkatti

2014

International Reviews of Immunology

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The impact of the endogenous cannabinoids (AEA, 2-AG, PEA, and virodamine) on the immune cell expressed cannabinoid receptors (CB1, CB2, TRPV-1, and GPR55) and consequent regulation of immune function is an exciting area of research with potential implications in the prevention and treatment of inflammatory and autoimmune diseases. Despite significant advances in understanding the mechanisms through which cannabinoids regulate immune functions, not much is known about the role of endocannabinoids in the pathogenesis or prevention of autoimmune diseases. Inasmuch as CB2 expression on immune cells and its role has been widely reported, the importance of CB1 in immunological disorders has often been overlooked especially because it is not highly expressed on naive immune cells. Therefore, the current review aims at delineating the effect of endocannabinoids on CB1 receptors in T cell driven autoimmune diseases. This review will also highlight some autoimmune diseases in which there is evidence indicating a role for endocannabinoids in the regulation of autoimmune pathogenesis. Overall, based on the evidence presented using the endocannabinoids, specifically AEA, we propose that the peripheral CB1 receptor is involved in the regulation and amelioration of inflammation associated with autoimmune diseases.

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Plasma endocannabinoid levels in multiple sclerosis

Cited by 97 publications

References 33 publications

Endocannabinoid signalling and the deteriorating brain

Endocannabinoid signalling and the deteriorating brain

Cannabis use by individuals with multiple sclerosis: effects on specific immune parameters

Role of Endocannabinoid Activation of Peripheral CB1 Receptors in the Regulation of Autoimmune Disease

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