2026 年 51 巻 2 号 p. 131-139
Over-the-counter (OTC) medicines are available without a prescription and are key to the promotion of self-medication. However, they also pose the risks of misuse, overdose, addiction, and abuse. These risks have recently emerged as global public health concerns. An important aspect of OTC drugs in Japan is that they are often combined with drugs with different effects. Although it has been noted that interactions between depressants and stimulants of the central nervous system (CNS) may promote drug dependence, the details remain unclear due to a lack of basic evidence. Therefore, an assessment was conducted to determine the interaction between CNS depressants, including dextromethorphan, diphenhydramine, and bromovalerylurea, and the CNS stimulant caffeine, by employing a conditioned place preference test in mice. Even at low doses, long-term administration of dextromethorphan and diphenhydramine induced place preference. Long-term administration of high-dose bromovalerylurea also induced this effect. The period required for dextromethorphan, diphenhydramine, bromovalerylurea, and morphine to acquire place preference was shortened by co-administration with caffeine, demonstrating that CNS stimulation enhances the preference of these sedatives in mice. Moreover, the preference for these drugs was suppressed by the dopamine D1 receptor antagonist SCH23390, and by the dopamine D2 receptor antagonist sulpiride, suggesting that dopamine is involved in the enhancing effect. These findings underscore the need to reconsider the active ingredients and distribution practices of OTC products, as the prolonged or inappropriate use of OTC medications and polypharmacy increases the risk of dependence.
