Comparison of Cannabinoids to Placebo in Management of TMJ Pain and Myofascial Pain in the TMJ Region
Condition: TMJ Disorder; Myofacial Pain; TMD
MeSH terms: Temporomandibular Joint Disorders; Facial Pain
Study type: Interventional

Summary: 
      The aim of this study is to determine whether the cannabinoids taken orally in the form of
      cannabidiol (CBD oil-a major non-psychoactive component of marijuana) vs placebo (hemp oil)
      will provide pain relief and improved jaw function in those who suffer from either myofascial
      pain disorder and/or arthralgia of the temporomandibular region.

        1. Primary Objectives To determine if the consumption of CBD oil is superior to placebo for
           the improvement in jaw pain.

        2. Secondary Objectives To determine if the consumption of CBD oil is superior to placebo
           for the improvement in function of the temporomandibular joint.

        3. Exploratory Objectives To determine if there are any adverse effects that result from
           the consumption of CBD oil or placebo.
    

Detailed description: 
      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.
    

Intervention name(s): CBD Oil; Hemp Oil
Intervention type(s): Other; Other
Intervention description(s): CBD PURE CBD OIL 20mg/1ml concentration; CBD PURE HEMP OIL
Other intervention name(s): Cannabinoids
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: CBD; TMJ; TMD