Plasma endocannabinoid levels in multiple sclerosis.
BACKGROUND
Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS. Therapies that affect the endocannabinoid (EC) system may have immunomodulatory, symptomatic and neuroprotective effects.


OBJECTIVE
The aim of this study was to determine how levels of EC and related compounds are altered in MS.


METHODS
Plasma and whole blood were collected from 24 MS patients (10 relapsing-remitting (RR); 8 secondary-progressive (SP); 6 primary-progressive (PP); 19 females; 25-66 years) and 17 controls (10 females; 22-62 years). Plasma EC and related compounds were quantified by liquid chromatography-tandem mass spectrometry. Fatty acid amide hydrolase (FAAH), cannabinoid receptors CB(1) and CB(2) mRNA were measured by quantitative reverse transcriptase-polymerase chain reaction.


RESULTS
Anandamide (AEA) and palmitoylethanolamide (PEA) were higher in RRMS compared to controls (p=0.001 and p=0.027). AEA, PEA and oleoylethanolamide were also increased in SPMS plasma (p=0.001, p=0.004, and p=0.005). PPMS patients had higher AEA plasma levels compared to controls (p=0.009). FAAH mRNA was decreased in SPMS (p=0.04) but not in RRMS or PPMS blood. CB(1) (p=0.012) and CB(2) mRNA (p=0.003) were increased in the PPMS.


CONCLUSIONS
The EC system is altered in MS. It may be dynamically modulated depending on the subtype of the disease, but further studies with larger subgroups are needed to confirm this.
Jean-Gilles
L
L
Division of Clinical Neurology at Queens Medical Centre, University of Nottingham, Nottingham NG7 2UH, United Kingdom.
Feng
S
S
Tench
C R
CR
Chapman
V
V
Kendall
D A
DA
Barrett
D A
DA
Constantinescu
C S
CS
D000328:Adult; D000368:Aged; D000577:Amides; D000581:Amidohydrolases / Q000235:genetics; D001095:Arachidonic Acids / Q000032:analysis / Q000097:blood; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics; D063385:Cannabinoid Receptor Modulators / Q000032:analysis / Q000097:blood*; D002186:Cannabinoids / Q000494:pharmacology / Q000627:therapeutic use; D002853:Chromatography, Liquid; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004185:Disability Evaluation; D063388:Endocannabinoids; D004983:Ethanolamines; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D009829:Oleic Acids / Q000032:analysis / Q000097:blood; D010169:Palmitic Acids / Q000032:analysis / Q000097:blood; D053284:Polyunsaturated Alkamides / Q000032:analysis / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000235:genetics; D000099252:Fatty Acid Amide Hydrolases
D000577:Amides; D000581:Amidohydrolases; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D004983:Ethanolamines; D009829:Oleic Acids; D010169:Palmitic Acids; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; D043882:Receptors, Cannabinoid; D000099252:Fatty Acid Amide Hydrolases; C488250:oleoylethanolamide; C005958:palmidrol; C078814:anandamide