Since their isolation in the early 19th century, certain compounds, such as cocaine and morphine, were used as psychoactive medications to treat pain and coughing (Drake & Scott, 2018; Musto, 1991; Way, 1982). Although medical professionals initially viewed these early psychoactive substances as harmless, they began to discover their addictive properties with a high potential for abuse (Fryer, Heaton, Levitt, & Murphy, 2013). Due to their addictive properties, public perception of these drugs declined during the late 19th century. A prohibition on recreational opiate use implemented by Congress in 1905 allowed its medicinal use (Brook, Bennett, & Desai, 2017). However, the abuse of psychoactive substances continued to persist, as one to four million people were reportedly addicted to morphine and cocaine in 1920 (Walma, 2018). Drug abuse is still a prevalent global issue that continues to impact individuals. Marijuana, or Cannabis sativa, is one of the most pervasive drugs in the world due to its popularity in both medicinal and recreational use, with a significant increase in consumption reported in the United States during the 21st century (Hasin et al., 2015). The United Nations Office of Drug Control, 2020 reports that in 2020 there were 275 million people related to drug abuse and an estimated 11% rise in substance users annually until 2030 (Sacks et al., 2018). The Centers for Disease Control and Prevention reported a rise in drug overdose deaths from 71,130 in 2019 to 107,521 in 2021 (National Center for Health Statistics, 2022).

New psychoactive substances (NPSs) are synthetic recreational drugs that mimic the psychoactive effects of conventional recreational drugs such as cannabis, cocaine, 3,4-methylenedioxymethamphetamine, and lysergic acid diethylamide (Graddy, Buresh, & Rastegar, 2018; Helander & Bäckberg, 2017). NPSs include synthetic cannabinoids, synthetic cathinones, phenethylamines, and piperazines; as of January 2020, there are reportedly >950 NPSs. While some NPSs have medicinal benefits, their recreational use has expanded rapidly, especially among adolescents, because they are inexpensive, readily available, and difficult to detect. 7,8,15 NPSs are on the market as being natural and safe to consumers; however, they are neither and can cause serious adverse effects, including seizures, nephrotoxicity, and death (Kasper et al., 2019; Lapoint et al., 2011; Law et al., 2015). Indeed, adverse reactions to NPSs have increased alongside their growing popularity (Connors, 2018).

One of the most globally spread NPSs is synthetic cannabinoids, which are substances designed to mimic the main psychoactive ingredient in marijuana, Δ9-tetrahydrocannabinol (Δ9-THC) (D'Souza et al., 2004). The waves of the synthetic cannabinoid exposure-related calls to poison control has increased. The number of calls rose from 53 in 2009 to 6971 in 2011 and from 2667 in 2013 to 7795 in 2015. >10% of U.S. high school seniors reported using synthetic cannabinoids, and the abuse has spread to even 8th- and 9th-graders (Keyes, Rutherford, Hamilton, & Palamar, 2016; Palamar & Acosta, 2015). Nearly 90% of patients admitted to an emergency room for reported SCB use were between 12 and 24 years of age, and many of them are adolescents (Bush & Woodwell, 2014), whose brain development is vulnerable to harmful environmental influences (Konrad, Firk, & Uhlhaas, 2013). Emergency care for synthetic cannabinoid toxicity has not been adequately provided compared to control substances (Li et al., 2022). The use of NPSs, including synthetic cannabinoids, is associated with higher risks of unplanned sexual intercourse and pregnancy. Indeed, as many as 4 in 100 women seeking treatment for substance abuse are pregnant or nursing (Martin, Longinaker, & Terplan, 2015). However, there is a scarce amount of informtion known about the potential impact of maternal NPS abuse on neonates.

In the present article, we will introduce the chemical, physical, pharmacokinetic, and toxicological properties as well as epidemiology of NPSs, emphasizing synthetic cannabinoids. We will apply an established prediction model to identify synthetic cannabinoids and their highly accumulative metabolites in breast milk.