Hur Kwang-Hyun, Ma Shi-Xun, Lee Bo-Ram, Ko Yong-Hyun, Seo Jee-Yeon, Ryu Hye Won, Kim Hye Jin, Yoon Seolmin, Lee Yong-Sup, Lee Seok-Yong, Jang Choon-Gon
Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Medicinal Chemistry Laboratory, Department of Pharmacy & Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea.
Biomol Ther (Seoul). 2021 Jul 1;29(4):384-391. doi: 10.4062/biomolther.2020.212.
Currently, the expanding recreational use of synthetic cannabinoids (SCBs) threatens public health. SCBs produce psychoactive effects similar to those of tetrahydrocannabinol, the main component of cannabis, and additionally induce unexpected pharmacological side effects. SCBs are falsely advertised as legal and safe, but in reality, SCB abuse has been reported to cause acute intoxication and addictive disorders. However, because of the lack of scientific evidence to elucidate their dangerous pharmacological effects, SCBs are weakly regulated and continue to circulate in illegal drug markets. In the present study, the intravenous self-administration (IVSA) paradigm was used to evaluate the abuse potential of three SCBs (AM-1248, CB-13, and PB-22) in rats. All three SCBs maintained IVSA with a large number of infusions and active lever presses, demonstrating their reinforcing effects. The increase of active lever presses was particularly significant during the early IVSA sessions, indicating the reinforcementenhancing effects of the SCBs (AM-1248 and CB-13). The number of inactive lever presses was significantly higher in the SCB groups (AM-1248 and CB-13) than that in the vehicle group, indicating their impulsive effects. In summary, these results demonstrated that SCBs have distinct pharmacological properties and abuse potential.
目前,合成大麻素(SCBs)在娱乐用途上的不断扩张对公众健康构成威胁。SCBs产生的精神活性作用与大麻的主要成分四氢大麻酚相似,此外还会引发意想不到的药理副作用。SCBs被虚假宣传为合法且安全,但实际上,据报道滥用SCBs会导致急性中毒和成瘾性障碍。然而,由于缺乏科学证据来阐明其危险的药理作用,SCBs受到的监管较为宽松,仍在非法毒品市场流通。在本研究中,采用静脉自我给药(IVSA)范式评估了三种SCBs(AM - 1248、CB - 13和PB - 22)在大鼠中的滥用潜力。所有三种SCBs都通过大量输注和主动杠杆按压维持IVSA,证明了它们的强化作用。在早期IVSA实验阶段,主动杠杆按压的增加尤为显著,表明SCBs(AM - 1248和CB - 13)具有增强强化的作用。SCB组(AM - 1248和CB - 13)的非主动杠杆按压次数显著高于溶剂对照组,表明它们具有冲动效应。总之,这些结果表明SCBs具有独特的药理特性和滥用潜力。