Comparison of Cannabinoids to Placebo in Management of Arthralgia and Myofascial Pain Disorder of the Temporomandibular Region: A Randomized Clinical Trial.

The United States National Institute of Health Survey in 2001 conducted a self-reported survey of 30,978 people and determined the overall prevalence of temporomandibular joint and muscles disorders to be 4.6%, with 6.3% women and 1.8% men [1]. Temporomandibular joint arthralgia which is often caused by inflammatory joint arthropathy [2] and is commonly seen in conjunction with myofascial pain of the masticatory region. Myofascial pain syndrome is classically characterized by focal areas of exquisite tenderness caused by trigger points. Temporomandibular joint arthralgia and myofascial pain disorder pertaining to the temporomandibular joint region will be defined according to the research diagnostic criteria below [3].

The exact mechanism of action of CBD is not fully understood and several mechanisms of action have been proposed. Studies have indicated that CBD acts on a system in humans called the endocannabinoid system comprised of the CB1 and CB2 receptors. CB receptors were found throughout the human body: CB1 receptors in the brain and CNS and CB2 receptors are found throughout the gut, spleen, liver, heart, kidneys, blood vessels, lymph cells, and reproductive organs. CB1 receptors in the CNS help maintain core functions such as motor activity, pain perception, stress response, and memory. CB2 receptors widely distributed throughout the body in peripheral organs serve as core components of the immune system, muscular system, and cardiovascular system [4]. The endocannabinoid system has physiological and pathophysiological roles in modulation of pain [5]. Petitet et al. (1998) found CBD considerably reduced the receptor activation of a potent classical CB1 receptor agonist. CBD has a very low affinity for both known cannabinoid receptors. However, CBD antagonizes CB1 and CB2 receptor agonists at doses considerably lower than those of CBD needed to activate cannabis receptors [6]. Pertwee et al. (2002) found CBD was also shown to display inverse agonism at the human CB2 receptor, which may be a rational basis for its anti-inflammatory properties [7]. Pertwee (2002) proposes that CBD also functions outside of CB1 and CB2 receptors. An endogenous cannabinoid, anandamide, produced anti-nociception through mechanisms outside of the endocannabinoid system acting on the vanilloid receptors. The vanilloid receptors may regulate the release of inflammatory molecules (substance P) following exposure to noxious stimuli playing a role in the transmission of pain signals [7]. This pathway is well studied in capsaicin (an active component of chili peppers). Capasicin can produce an analgesic effect by desensitizing the TRPV1 receptor (a vanilloid receptor) inhibiting substance P. CBD inhibits the uptake and hydrolysis of the endocannabinoid anandamide, thus increasing its concentration [8, 9]. CBD stimulates the vanilloid receptor type 1 (VR1) with a maximum effect similar in efficacy to that of capsaicin [8] without the side effect of burning sensation. Not all cannabinoid effects can be explained through the CB1 and CB2 receptors and their endogenous ligand, anandamide. Researchers investigated the mechanisms, by which CBD reduces inflammatory and neuropathic pain in animals [10]. They found that the cannabinoid-induced analgesic effect is absent in mice lacking glycine receptors and concluded that this receptor mediates suppression of chronic pain. In other mouse models, CBD binds to the GPR55 receptor, a putative cannabinoid receptor [11]. This effect is involved in the anti-inflammatory action of CBD. In human clinical trials, Blake (2005) assessed the efficacy and safety of cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Sativex consists of a blend of plant extracts which delivers approximately equal amounts of THC and CBD. Statistically significant improvements in pain on movement, pain at rest, and quality of sleep [12]. The rationale for the starting dose is somewhat arbitrary, 600mg/2FL is the most popular with retail customers. It is the highest concentration available with the CBD PURE brand oil which allows study subjects to maximize on the possible benefits of CBD. Since there are little known side effects, the risk of a higher concentration of CBD causing more adverse side effects is minimal.