Carroll, F. I., Lewin, A. H., Mascarella, S. W., Seltzman, H. H., & Reddy, P. A. (2021). Designer drugs: A medicinal chemistry perspective (II). In Annals of the New York Academy of Sciences (1 ed., Vol. 1489, pp. 48-77) Advance online publication. https://doi.org/10.1111/nyas.14349
During 2012-2018, the clandestine manufacture of new psychoactive substances (NPS) designed to circumvent substance control regulations increased exponentially worldwide, with concomitant increase in fatalities. This review focuses on three compound classes identified as synthetic opioids, synthetic amphetamines, and synthetic cannabinoids and highlights the medicinal chemistry precedents utilized by clandestine laboratories to develop new NPS with increased brain penetration, longer duration of action, and greater potency. Chemical approaches to illicit drug abuse treatment options, particularly for opioid use disorder, are also discussed.