Cannabinoid Reduces Inflammatory Cytokines, Tumor Necrosis Factor-a, and Type I Interferons in Dermatomyositis In Vitro

Summary: Cannabis has been used in medicinal preparations for centuries to treat diseases such as chronic pain, neuropathy, and epilepsy. Recent research has identified antiinflammatory properties in both endocannabinoids and phytocannabinoids. Our study investigated whether the anti-inflammatory effects of a nonpsychoactive cannabinoid called ajulemic acid could target the cytokines pathogenic in cutaneous dermatomyositis. One obstacle to the use of cannabinoids as therapeutics is their psychoactive effect. It is well established that specific chemical modifications to tetrahydrocannabinol (THC) render it free of central nervous system activity. This strategy was used to design ajulemic acid. Ajulemic acid has a 65-fold higher affinity for the cannabinoid 2 receptor compared with the cannabinoid 1 receptor (Tepper et al., 2014). The cannabinoid 2 receptor is found on immune cells and plays a natural role in resolving inflammation (Bouaboula et al., 1993; Munro et al., 1993). Ajulemic acid has a low affinity for the cannabinoid 1 receptor, which is found in the nervous system and mediates THC’s psychoactive effects. Preferential binding for the cannabinoid 2 receptor enables ajulemic acid to preserve THC’s intiinflammatory properties without the psychological stimulatory effects, making it a potentially useful therapy for treating autoimmune diseases.