Outsmarting generic legislation: 4 years into the cat-and-mouse game of the synthetic cannabinoid receptor agonist market since the Chinese ban in 2021.

Abstract

The enactment of the generic ban on synthetic cannabinoid receptor agonists (SCRAs) in China in 2021 has significantly altered the international SCRA landscape, both in size and diversity. To circumvent the new legislation, covering 7 common SCRA scaffolds, manufacturers have employed various ban-evading strategies during the past 4 years, yielding numerous novel compounds with distinct properties and challenges. These strategies include introducing alternative core moieties, such as a oxoindolins ("OXIZIDs"), an oxopyridone (CH-FUBBMPDORA) and a 4-methyl benzoate (NMDMSB), as well as replacing the carboxamide linker with an acetamide (e.g., seen in ADB-FUBIATA). Additional approaches involve modifying conventional core structures by switching tail group positions (e.g., pyrazoles 5F-3,5-AB-PFUPPYCA and 3,5-ADB-4en-PFUPPYCA), or removing/adding substitutions (e.g., tail-less SCRAs like ADB-INACA and brominated SCRAs like ADB-5'Br-BUTINACA, respectively). Furthermore, a concerning 'do-it-yourself' synthesis approach has emerged, enabling users or intermediate suppliers to easily generate banned, potent SCRAs themselves from ban-evading tail-less precursors, thereby obtaining renewed access to previously scheduled and potentially dangerous compounds. In addition to the proliferation of structurally novel, unknown substances, new ways to market readily existing (highly potent) SCRAs, continue to complicate analytical detection and risk assessment. This review explores the ban-evading strategies that have been observed between mid-2021 and mid-2025, along with a discussion on strategies for detection, identification, metabolic profiling, and pharmacological characterization of the SCRAs that have emerged as a result of this ban. Additionally, for some compounds that have not been pharmacologically characterized in literature, the first published data are presented here.