Positive allosteric modulation of CB1 suppresses pathological pain without producing tolerance or dependence

摘要

BackgroundActivation of cannabinoid CB1 receptors suppresses pathological pain but also produces unwanted central side effects. We hypothesized that a positive allosteric modulator (PAM) of CB1 signaling would suppress inflammatory and neuropathic pain without producing cannabimimetic effects or physical dependence. We also asked whether a CB1-PAM would synergize with inhibitors of endocannabinoid deactivation and/or an orthosteric cannabinoid agonist.