Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies. Inhibitory cannabinoid 2 (CB2) receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB2 receptor agonist JWH133 attenuated OAinduced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that spinal administration of JWH133...

Abstract The Cannabis sativa herb contains over 100 phytocannabinoid (pCB) compounds and has been used for thousands of years for both recreational and medicinal purposes. In the past two decades, characterisation of the body's endogenous cannabinoid (CB) (endocannabinoid, eCB) system (ECS) has highlighted activation of central CB(1) receptors by the major pCB, Δ(9)-tetrahydrocannabinol (Δ(9)-THC) as the primary mediator of the psychoactive, hyperphagic and some of the potentially therapeutic properties of ingested cannabis. Whilst Δ(9)-THC is the most prevalent and widely studied pCB, it is also the predominant psychotropic component of cannabis, a property that likely limits its widespread therapeutic use as an isolated agent....

The effects of chronic exposure to cannabinoids on short-term memory in rats were assessed during repeated daily injections of an initially debilitating dose (3.75 mg/kg) of the potent CB1 cannabinoid receptor ligand, WIN 55,212-2. Delayed nonmatch to sample (DNMS) performance was assessed over a 35-day exposure period in which performance was initially disrupted during the first 21 days of exposure but recovered by day 30 and was stable at pre-drug levels for 5 days thereafter. Withdrawal was precipitated by injections of the CB1 receptor antagonist SR141716A and transiently reduced performance for 2 days but was restabilized to pre-drug levels within 3– 4 days. Concomitant...