Unique Pharmacology, Brain Dysfunction, and Therapeutic Advancements for Fentanyl Misuse and Abuse
Ying Han1 • Lu Cao3 • Kai Yuan2 • Jie Shi1 • Wei Yan2 • Lin Lu2,31 National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing 100191, China
2 Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing 100191, China
3 Peking-Tsinghua Center for Life Sciences and PKU-IDG/ McGovern Institute for Brain Research, Peking University, Beijing 100871, China
Abstract
Fentanyl is a fully synthetic opioid with analgesic and anesthetic properties. It has become a primary driver of the deadliest opioid crisis in the United States and elsewhere, consequently imposing devastating social, economic, and health burdens worldwide. However, the neural mechanisms that underlie the behavioral effects of fentanyl and its analogs are largely unknown, and approaches to prevent fentanyl abuse and fentanyl-related overdose deaths are scarce. This review presents the abuse potential and unique pharmacology of fentanyl and elucidates its potential mechanisms of action, including neural circuit dysfunction and neuroinflammation. We discuss recent progress in the development of pharmacological interventions, anti-fentanyl vaccines, anti-fentanyl/heroin conjugate vaccines, and monoclonal antibodies to attenuate fentanyl-seeking and prevent fentanyl-induced respiratory depression. However, translational studies and clinical trials are still lacking. Considering the present opioid crisis, the development of effective pharmacological and immunological strategies to prevent fentanyl abuse and overdose are urgently needed.
Keywords
Fentanyl abuse; Neural mechanisms; Pharmacological interventions; Fentanyl vaccines
