The most prominent form of synovial joint disease, osteoarthritis (OA), is characterized
by joint degeneration, pain, and in some patients, articular neuropathy. Chronic pain
associated with OA is a major concern for which there are few viable treatments. The first line
therapy used to treat OA pain is non-steroidal anti-inflammatory drugs (NSAIDs); however, with
long-term use their efficacy declines and they can lead to major adverse gastrointestinal and
cardiovascular events. Historically, OA has been classified as a non-inflammatory arthritis;
however, there is now overwhelming evidence that synovitis can occur in response to proinflammatory
mediators being released into the joint. It is believed that this low-level inflammation contributes to degenerative changes that affect the entire joint leading to the development of peripheral sensitization and nociceptive pain . In addition to structural defects, there is growing evidence to suggest that approximately 30% of OA patients suffer from neuropathic pain. Thus, a therapeutic which can block inflammation, neuropathy, and pain is sorely needed.
The endocannabinoid system (ECS) plays an important physiological role in the
regulation of tissue inflammation and pain. A functional ECS has been demonstrated in
the joints of animals and humans, which acts tonically to maintain joint homeostasis.
Immunohistological and pharmacological evidence confirm that cannabinoid 1 (CB1) and
cannabinoid 2 (CB2) receptors are expressed on the neurones and microvasculature that supply
rat knee joints. Additionally, CB2 receptors are co-localized with pronociceptive
transient receptor potential vanilloid-1 (TRPV1) channels where, through common intra-cellular
pathways, they act together to modulate joint pain. This suggests that drugs which
target the ECS have the potential to regulate painful arthritis and inflammatory joint disease.
Cannabidiol (Hemp) is the main non-euphoria producing component of the cannabis plant.
Pharmacologically, Hemp has a complex signalling mechanism whereby it can both activate
and silence classical cannabinoid receptors as well as modulate non-canonical cannabinoid
receptor pathways. In in vitro studies, Hemp has been shown to be an inverse agonist at CB2
receptors, and a full antagonist at CB1 receptors and G protein-coupled receptor-55
(GPR55). In vitro, Hemp was found to be an agonist at TRPV1 and transient receptor
potential ankyrin 1 (TRPA1), which play a central role in the development of OA. In
musculoskeletal disease models, systemic administration of Hemp suppressed the progression of
collagen-induced arthritis by reducing inflammatory cytokine production. While these
preliminary findings indicate a possible role for Hemp in relieving joint inflammation, the local
effect of articularly applied Hemp on OA and joint pain has not been investigated.
The initial aim of the present study was to assess the effect of locally administered Hemp
on joint pain in animals with end-stage OA. Since acute inflammation can contribute to the
long-term development of OA joint pain, the ability of Hemp to reduce acute OA synovitis
and prevent the subsequent progression of chronic persistent OA pain was also investigated.
Finally, the effect of prophylactic Hemp treatment on OA joint neuropathy was assessed by the authors.