Studies on the effects of cannabis (marijuana) have led to the recent discovery of an endogenous system of ligands in humans involved in a number of physiological processes including pain and inflammation.
The main naturally occurring ligands for this system, anandamide and 2-arachidonoylglycerol (2-AG), activate a number of cannabinoid receptors, including CB1 and CB2 receptors. CB1 receptors and associated ligands are mainly localized in the brain whereas CB2 receptors are found mainly in peripheral tissues, particularly immune cells such as leukocytes and mast cells, which have been shown to be involved in pain and inflammatory responses. Cara is developing lead molecules that selectively modulate peripheral CB receptors without targeting CNS cannabinoid receptors. Peripheral CB receptor modulators will be initially developed as a novel therapeutic approach for neuropathic pain, a condition currently without consistently effective therapies. Cara’s most advanced CB compound, CR701, is in preclinical development.
CR701 has been evaluated in a rodent model of neuropathic pain that produces both hyperalgesia (sensitization of nerve endings to painful stimuli) and allodynia (painful perception of innocuous stimuli) comparable to human conditions. Administration of CR701 to animals with neuropathy resulted in significant reversal of both hyperalgesia and allodynia, as measured by responses to thermal and tactile stimuli, respectively.