Arthritis Marijuana Treatment Research

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Arthritis Marijuana Treatment Research

Rheumatoid arthritis (RA) is an inflammatory disease of the joints characterized by pain, stiffness, and swelling, as well as an eventual loss of limb function. Rheumatoid arthritis affects about one percent of the population, primarily women.

The cannabis plant is acknowledged to possess anti-inflammatory, anti-arthritic, and anti-rheumatic properties,[1] and the endocannabinoid system has been proposed as modulator of RA.[2]

The use of cannabis to treat symptoms of RA is frequently self-reported by patients. In a 2005 anonymous questionnaire survey of medicinal cannabis patients in Australia, 25 percent reported using cannabinoids to treat RA.[3] A survey of British medical cannabis patients found that more than 20 percent of respondents reported using cannabis for symptoms of arthritis.[4] A review of state-registered medical cannabis pain patients reported that 27 percent used it to treat arthritis.[5] Nevertheless, there exists limited clinical data with respect to the use of cannabinoids on RA in the literature at this time.

In January 2006, investigators at the British Royal National Hospital for Rheumatic Disease reported successful treatment of arthritis with cannabinoids in the first-ever controlled trial assessing the efficacy of natural cannabis extracts on RA.[6] Investigators reported that the administration of cannabis extracts over a five week period produced statistically significant improvements in pain on movement, pain at rest, quality of sleep, inflammation and intensity of pain compared to placebo. No serious adverse effects were observed. Similar results had been reported in smaller trials investigating the use of orally administered cannabis extracts on symptoms of RA.[7] A randomized, placebo-controlled trial assessing the use of vaporized cannabis in osteoarthritis patients began in Canada in 2016.[8] Nonetheless, the limited number of studies and their short-term duration “allows for only limited conclusions for the effects of cannabinoids in rheumatic conditions.”[9]

Preclinical data indicates that cannabinoids moderate RA progression. Writing in the Journal of the Proceedings of the National Academy of Sciences, investigators at London’s Kennedy Institute for Rheumatology reported that cannabidiol administration suppressed the progression of arthritis in vitroand in animals.[10] Administration of CBD after the onset of clinical symptoms protected joints against severe damage and “effectively blocked [the] progression of arthritis,” investigators concluded. Daily administration of the synthetic cannabinoid agonist HU-320 has also been reported to protect joints from damage and to ameliorate arthritis in preclinical models,[11] as has the administration of the cannabinoid agonist HU-444.[12]

Summarizing the available literature in the Journal of Neuroimmunology, researchers at Tokyo’s National Institute for Neuroscience concluded, “Cannabinoid therapy of RA could provide symptomatic relief of joint pain and swelling as well as suppressing joint destruction and disease progression.”[13] More recently, experts in the field have opined that “specific activation of CB2 (receptor) may relieve RA”[14] and that “a selective CB(2) agonist could be a new therapy for RA.”[15]

 

Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis.

Centre for Analytical Bioscience, School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, UK. denise.richardson@pfizer.com

Abstract

INTRODUCTION:

Cannabis-based medicines have a number of therapeutic indications, including anti-inflammatory and analgesic effects. The endocannabinoid receptor system, including the cannabinoid receptor 1 (CB1) and receptor 2 (CB2) and the endocannabinoids, are implicated in a wide range of physiological and pathophysiological processes. Pre-clinical and clinical studies have demonstrated that cannabis-based drugs have therapeutic potential in inflammatory diseases, including rheumatoid arthritis (RA) and multiple sclerosis. The aim of this study was to determine whether the key elements of the endocannabinoid signalling system, which produces immunosuppression and analgesia, are expressed in the synovia of patients with osteoarthritis (OA) or RA.

METHODS:

Thirty-two OA and 13 RA patients undergoing total knee arthroplasty were included in this study. Clinical staging was conducted from x-rays scored according to Kellgren-Lawrence and Larsen scales, and synovitis of synovial biopsies was graded. Endocannabinoid levels were quantified in synovial fluid by liquid chromatography-mass spectrometry. The expression of CB1 and CB2 protein and RNA in synovial biopsies was investigated. Functional activity of these receptors was determined with mitogen-activated protein kinase assays. To assess the impact of OA and RA on this receptor system, levels of endocannabinoids in the synovial fluid of patients and non-inflamed healthy volunteers were compared. The activity of fatty acid amide hydrolase (FAAH), the predominant catabolic endocannabinoid enzyme, was measured in synovium.

RESULTS:

CB1 and CB2 protein and RNA were present in the synovia of OA and RA patients. Cannabinoid receptor stimulation of fibroblast-like cells from OA and RA patients produced a time-dependent phosphorylation of extracellular signal-regulated kinase (ERK)-1 and ERK-2 which was significantly blocked by the CB1 antagonist SR141716A. The endocannabinoids anandamide (AEA) and 2-arachidonyl glycerol (2-AG) were identified in the synovial fluid of OA and RA patients. However, neither AEA nor 2-AG was detected in synovial fluid from normal volunteers. FAAH was active in the synovia of OA and RA patients and was sensitive to inhibition by URB597 (3′-(aminocarbonyl) [1,1′-biphenyl]-3-yl)-cyclohexylcarbamate).

CONCLUSION:

Our data predict that the cannabinoid receptor system present in the synovium may be an important therapeutic target for the treatment of pain and inflammation associated with OA and RA.

 

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