anandamide and Osteoarthritis--Knee

Multimodal therapies comprising spa applications are widely used as non-pharmaceutical treatment options for musculoskeletal diseases. The purpose of this randomized, controlled, open pilot study was to elucidate the involvement of the endocannabinoid system in a multimodal therapy approach. Twenty-five elderly patients with knee osteoarthritis (OA) received a 2-week spa therapy with or without combination of low-dose radon therapy in the Bad Gastein radon gallery. A 10-point numerical rating scale (pain in motion and at rest), WOMAC questionnaire, and the EuroQol-5D (EQ-5D) questionnaire were recorded at baseline, and during treatment period at weeks one and two, and at 3-month and 6-month follow-ups. Plasma levels of the endocannabinoid anandamide (AEA) were determined at baseline and at 2 weeks, and serum levels of several cartilage metabolism markers at all five time-points. A significant and sustained reduction of self-reported knee pain was observed in the study population, but no further significant effect of the additional radon therapy up and above base therapy. This pain reduction was accompanied by a significant reduction of AEA plasma levels during treatment in both groups. No significant differences were seen in serum marker concentrations between the groups treated with or without radon, but a small reduction of serum cartilage degradation markers was observed during treatment in both groups. This is the first study investigating AEA levels in the context of a non-pharmacological OA treatment. Since the endocannabinoid system represents a potential target for the development of new therapeutics, further studies will have to elucidate its involvement in OA pain.

Topics: Aged; Arachidonic Acids; Combined Modality Therapy; Endocannabinoids; Humans; Osteoarthritis, Knee; Pain; Pilot Projects; Polyunsaturated Alkamides; Radon; Self Report; Treatment Outcome

Cannabis-based drugs have been shown to be effective in inflammatory diseases. A number of endocannabinoids including N- arachidonoylethanolamide (anandamide, AEA) and 2-arachidonyl glycerol (2-AG) with activity at the cannabinoid receptors (CBR) CBR1 and CBR2, have been identified. Other structurally related endogenous fatty acid compounds such as oleoylethanolamide (OEA) and palmitoyl ethanolamide (PEA) have been identified in biological tissues. These compounds do not bind to CBR but might be involved in facilitating the actions of directly acting endocannabinoids and thus are commonly termed "entourage" compounds due to their ability to modulate the endocannabinoid system. The aim of this study was to evaluate the presence of endocannabinoids and entourage compounds in the synovial fluid of dogs with osteoarthritis subjected to arthrotomy of the knee joint. Cytokines and cytology were studied as well.. AEA, 2-AG, OEA and PEA were all present in the synovial fluid of arthritic knees and in the contralateral joints; in addition, a significant increase of OEA and 2AG levels were noted in SF from OA knees when compared to the contralateral joints.. The identification and quantification of endocannabinoids and entourage compounds levels in synovial fluids from dogs with OA of the knee is reported for the first time. Our data are instrumental for future studies involving a greater number of dogs. Cannabinoids represent an emerging and innovative pharmacological tool for the treatment of OA and further studies are warranted to evaluate the effectiveness of cannabinoids in veterinary medicine.

Topics: Animals; Arachidonic Acids; Dog Diseases; Dogs; Endocannabinoids; Ethanolamines; Female; Glycerides; Male; Oleic Acids; Osteoarthritis, Knee; Palmitic Acids; Pilot Projects; Polyunsaturated Alkamides; Synovial Fluid

In rheumatoid arthritis (RA) synovial fluid, levels of the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol are elevated. Since synovial fibroblasts (SFs) possess all of the enzymes necessary for endocannabinoid synthesis, it is likely that these cells contribute significantly to elevated endocannabinoid levels. While glucocorticoids initiate endocannabinoid synthesis in neurons, this study was undertaken to test whether cortisol also regulates endocannabinoid levels in mesenchymal cells such as SFs, and whether this interferes with integrin-mediated adhesion.. Adhesion was determined in 1-minute intervals over 60 minutes using an xCELLigence system. Slopes from individual treatment groups were averaged and compared to the control. Fatty acid amide hydrolase (FAAH) and cyclooxygenase 2 (COX-2) were detected by immunocytochemistry, and AEA was detected by mass spectrometry.. Cortisol increased the adhesion of RASFs and osteoarthritis SFs with a maximum of 200% at both 10(-7) M and 10(-8) M. When cortisol was administered together with either cannabinoid receptor 1 (CB(1) ) antagonist (rimonabant; 100 nM), CB(2) antagonist (JTE907; 100 nM), transient receptor potential vanilloid channel 1 (TRPV-1) antagonist (capsazepine; 1 μM), FAAH inhibitor, or COX-2 inhibitor, adhesion was reduced below the level in controls. Concomitant inhibition of FAAH and COX-2 reversed these effects. Mass spectrometry revealed the presence of AEA in SFs.. Our findings indicate that glucocorticoid-induced adhesion is dependent on CB(1) /CB(2) /TRPV-1 activation. Since AEA is produced in SFs, this endocannabinoid is the most likely candidate to mediate these effects. Since AEA levels are regulated by COX-2 and FAAH, inhibition of both enzymes along with low-dose glucocorticoids may provide a therapeutic option to maximally boost the endocannabinoid system in RA, with possible beneficial effects.

Topics: Aged; Amidohydrolases; Arachidonic Acids; Arthritis, Rheumatoid; Cell Adhesion; Cells, Cultured; Cyclooxygenase 2; Dose-Response Relationship, Drug; Endocannabinoids; Female; Fibroblasts; Fibronectins; Humans; Hydrocortisone; Male; Middle Aged; Osteoarthritis, Knee; Polyunsaturated Alkamides; Synovial Membrane