Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA.
Pharmacol Ther. 2011 Dec;132(3):215-41. doi: 10.1016/j.pharmthera.2011.06.005. Epub 2011 Jul 18.
The endogenous cannabinoid system is an important regulatory system involved in physiological homeostasis. Endocannabinoid signaling is known to modulate neural development, immune function, metabolism, synaptic plasticity and emotional state. Accumulating evidence also implicates brain endocannabinoid signaling in the etiology of drug addiction which is characterized by compulsive drug seeking, loss of control in limiting drug intake, emergence of a negative emotional state in the absence of drug use and a persistent vulnerability toward relapse to drug use during protracted abstinence. In this review we discuss the effects of drug intake on brain endocannabinoid signaling, evidence implicating the endocannabinoid system in the motivation for drug consumption, and drug-induced alterations in endocannabinoid function that may contribute to various aspects of addiction including dysregulated synaptic plasticity, increased stress responsivity, negative affective states, drug craving and relapse to drug taking. Current knowledge of genetic variants in endocannabinoid signaling associated with addiction is also discussed.
内源性大麻素系统是参与生理内稳态的重要调节系统。内源性大麻素信号已知可调节神经发育、免疫功能、代谢、突触可塑性和情绪状态。越来越多的证据表明，大脑内源性大麻素信号在药物成瘾的发病机制中起作用，其特征是强迫性觅药、无法控制限制药物摄入、在没有药物使用的情况下出现负性情绪状态以及在长期禁欲期间对重新使用药物的持续易感性。在这篇综述中，我们讨论了药物摄入对大脑内源性大麻素信号的影响，以及内源性大麻素系统在药物消费动机中的作用，以及药物引起的内源性大麻素功能改变，这些改变可能与成瘾的各个方面有关，包括失调的突触可塑性、应激反应性增加、负性情绪状态、药物渴望和重新开始药物滥用。还讨论了与成瘾相关的内源性大麻素信号遗传变异的现有知识。
