Pfizer was investigating inhibitors of the enzyme fatty acid amide hydrolase (FAAH) as a treatment for pain. FAAH degrades the endogenous cannabinoid—anandamide (AEA), which is a CB-1 and CB-2 cannabinoid receptor agonist. Increased levels of anandamide attenuate firing of pain-sensing neurons (nociceptors). Pfizer’s clinical pharmacology team wanted to know whether the proposed doses of FAAHi PF-04457845, a potent FAAH inhibitor in development for treating pain, would test the pharmacology fully. Read this case study to learn how a quantitative systems pharmacology approach (QSP) with internal and external data was used to address this and other questions.