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 Background Chronic neuropathic pain affects 1%–2% of the adult population and is often refractory to standard pharmacologic treatment. Patients with chronic pain have reported using smoked cannabis to relieve pain, improve sleep and improve mood. Methods Adults with post-traumatic or postsurgical neuropathic pain were randomly assigned to receive cannabis at four potencies (0%, 2.5%, 6% and 9.4% tetrahydrocannabinol) over four 14-day periods in a crossover trial. Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle, followed by a nine-day washout period. Daily average pain intensity was measured using an 11-point numeric rating...

Abstract Activation of both cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptors reduces nociceptive processing in acute and chronic animal models of pain. In addition, nociceptive processing is tonically modulated by endogenous cannabinoids (endocannabinoids, ECs). This review examines the role of cannabinoids and ECs in the brain stem–spinal pathway of pain inhibition. Preclinical studies evaluating cannabinoids in neuropathic pain management are also reviewed. Pharmacological tools modulating the interaction of cannabinoids with its receptors and the treatment of pain by the augmentation of EC levels, specifically anandamide, are discussed. Particular attention is attributed to neuropathic pain in which pharmacological manipulation resulting in EC accumulation can...

Objectives—To identify the types and frequencies of pain treatments used by individuals with cerebral palsy (CP); examine the perceived effectiveness of these treatments; and identify the types of healthcare providers that were accessed for pain-related services. Design—A cross-sectional survey design was employed. 83 adults (mean age=40.3 years, SD=13.6) with CP indicated their pain location and intensity during the past 3 months. Next, they indicated their use of 24 different pain treatments and the effectiveness of each. Finally, participants indicated the frequency of pain-related healthcare visits to specific providers over the past 6 months. Results—63% of participants reported experiencing chronic pain and rated their pain...

Cannabinoids and opioids share several pharmacologic properties and may act synergistically. The potential pharmacokinetics and the safety of the combination in humans are unknown. We therefore undertook a study to answer these questions. Twenty-one individuals with chronic pain, on a regimen of twice-daily doses of sustainedrelease morphine or oxycodone were enrolled in the study and admitted for a 5-day inpatient stay. Participants were asked to inhale vaporized cannabis in the evening of day 1, three times a day on days 2–4, and in the morning of day 5. Blood sampling was performed at 12-h intervals on days 1 and 5. The extent of chronic...

Evidence for an analgesic interaction between delta-9-tetrahydrocannabinol (Δ9 -THC) and morphine was sought using an experimental pain model applied to normal volunteers. The study incorporated a double blinded, four treatment, four period, four sequence, crossover design. Subjects received Δ9 -THC 5 mg orally or placebo and 90 min later morphine 0.02 mg/kg intravenously or placebo. Fifteen minutes later subjects rated the pain associated with the application of thermal stimuli to skin using two visual analog scales, one for the sensory and one for the affective aspects of pain. Among sensory responses, neither morphine nor Δ9 -THC had a significant effect at the doses used,...

Up to 8%5 of the European population and approximately 3.8 million individuals in the United States6 are affected by Neuropathic pain (NP). NP is generally chronic and disabling and challenging to treat with only 40-60% of patients achieving partial relief7 . Neuropathic pain may arise as a consequence of a lesion or disease affecting the somatosensory system and could be CNS or PNS related8 . The management of patients with chronic NP is complex and response to existing treatments often inadequate9 . Common therapeutics include antidepressants, antiepileptic, opioids and tramadol. The therapeutic potential of cannabinoids has recently been investigated following the discovery of the...

The endocannabinoid system consists of the cannabinoid (CB) receptors, CB1 and CB2, the endogenous ligands anandamide (AEA, arachidonoylethanolamide) and 2-arachidonoylglycerol (2-AG), and their synthetic and metabolic machinery. The use of cannabis has been described in classical and recent literature for the treatment of pain, but the potential for psychotropic effects as a result of the activation of central CB1 receptors places a limitation upon its use. There are, however, a number of modern approaches being undertaken to circumvent this problem, and this review represents a concise summary of these approaches, with a particular emphasis upon CB2 receptor agonists. Selective CB2 agonists and peripherally restricted...

Abstract Treatment options for neuropathic pain have limited efficacy and use is fraught with dose-limiting adverse effects. The endocannabinoid system has been elucidated over the last several years, demonstrating a significant interface with pain homeostasis. Exogenous cannabinoids have been demonstrated to be effective in a range of experimental neuropathic pain models, and there is mounting evidence for therapeutic use in human neuropathic pain conditions. This article reviews the history, pharmacologic development, clinical trials results, and the future potential of nonsmoked, orally bioavailable, nonpsychoactive cannabinoids in the management of neuropathic pain.

Abstract Although Δ(9)-tetrahydrocannabinol (THC) and other mixed CB(1)/CB(2) receptor agonists are well established to elicit antinociceptive effects, their psychomimetic actions and potential for abuse have dampened enthusiasm for their therapeutic development. Conversely, CB(2) receptor-selective agonists have been shown to reduce pain and inflammation, without eliciting apparent cannabinoid behavioral effects. In the present study, we developed a novel ethyl sulfonamide THC analog, O-3223, and compared its pharmacological effects to those of the potent, mixed CB(1)/CB(2) receptor agonist, CP55,940, in a battery of preclinical pain models. Competitive cannabinoid receptor binding experiments revealed that O-3223 was approximately 80-fold more selective for CB(2) than CB(1) receptors. Additionally, O-3223...