Oral delivery of delta-9-tetrahydrocannabinol provides symptom and disease modification in a mouse model of knee osteoarthritis

Purpose: Osteoarthritis (OA) is a whole joint disease that results in joint pain, cartilage degeneration, and synovitis, ultimately reducing the quality of life of those affected. Current therapies only modify pain and there are no approved OA disease-modifying drugs. Recent studies suggest that individuals with OA are self-medicating with cannabis, with some anecdotally reporting reduced joint pain. One of the most prominent cannabinoids in cannabis is delta-9-tetrahydrocannabinolic acid, which produces the psychoactive compound delta-9-tetrahydrocannabinol (THC) upon decarboxylation. THC can signal via CB1 and CB2 cannabinoid receptors altering intracellular cAMP levels. CB1 and CB2 are found on joint cells, including chondrocytes and fibroblast-like synoviocytes (FLS). Currently, there are no studies linking THC to disease modification in OA. In this study, we investigated the effects and mechanisms of action of THC on pain and disease modification in pre-clinical models of knee OA.