Pharmacology and toxicology of new psychoactive substances

National Institute On Drug Abuse

Investigators

Linked publications & trials

Abstract

Summary- Substantial progress was made on this project, with publication of five research articles and one scholarly review. Along with our collaborators, we have characterized the pharmacological effects of numerous synthetic cathinones, cannabinoids, and opioids found in the street drug marketplace. In one article that is relevant to the current opioid crisis, we reviewed the pharmacology and toxicology of U-47700, a novel synthetic opioid (NSO) that is associated with many overdose deaths. The recreational use of opioid drugs is a global threat to public health and safety. In particular, an epidemic of opioid overdose fatalities is being driven by illicitly manufactured fentanyl, while NSOs are appearing on recreational drug markets as standalone products, adulterants in heroin, or ingredients in counterfeit drug preparations. Trans-3,4-dichloro-N-2-(dimethylamino)cyclohexyl-N-methylbenzamide (U-47700) is a prime example of a non-fentanyl NSO that is associated with numerous intoxications and fatalities in the United States and worldwide. We reviewed the medicinal chemistry, preclinical pharmacology, clandestine availability, methods for detection, and forensic toxicology of U-47700 and its analogs. An up-to-date summary of the human cases involving U-47700 intoxication and death were described. The evidence demonstrates that U-47700 is a potent mu-opioid receptor agonist, which poses a serious risk for overdose and death. However, most newer analogs of U-47700 appear to be less potent and have been detected infrequently in forensic specimens. U-47700 represents a classic example of how chemical entities from the medicinal chemistry or patent literature can be diverted for use in recreational drug markets. Lessons learned from the experiences with U-47700 can inform scientists, clinicians, and policymakers who are involved with responding to the spread and impact of NSOs.