Changes in the prevalence of new psychoactive substances before and after the introduction of the generic scheduling of synthetic cannabinoids in Japan.

To counter the spread of the many analogues of psychoactive substances, the Pharmaceutical Affairs Law in Japan was amended in 2006 to establish a new category - Designated Substances - in order to more promptly control these drugs. As of March 2013, 106 substances (including one plant, Salvia divinorum) were listed in the category of Designated Substances, and 13 of them had had their category changed from Designated Substances into the much stricter category, Narcotics. However, new analogues of controlled substances, especially synthetic cannabinoids, appeared one-by-one since the new category was introduced. To avoid a cat-and-mouse game between regulators and illicit drug manufacturers, a comprehensive system (generic scheduling) for designating naphthoylindole-type synthetic cannabinoids, with particular substituents, was introduced into the Designated Substances in 2013. Since late 2012, the naphthoylindole-type compounds have been gradually replaced by other types of synthetic cannabinoids, such as cyclopropylmethanones, cannabimimetic carboxamide derivatives, adamanthoyl indoles, and cannabimimetic quinolinyl carboxylates. After the enforcement of the generic scheduling for designating naphthoylindoles in March 2013, these naphthoylindoles have been completely replaced by other types and have rarely been detected in the products. New types of psychoactive substances, including opioid receptor agonists (e.g. AH-7921, MT-45), hallucinogenic phenethylamines (e.g. NBOMe-type compounds), and thiophene derivatives (e.g. methiopropamine, α-PVT) have also appeared. The almost infinite possibilities of altered structures of chemicals make it difficult to carry out effective and exhaustive scheduling. To prevent the widespread distribution and abuse of these new psychoactive substances, continuous and dedicated monitoring for the emergence of these substances is necessary.