Division of Analytical Psychopharmacology, New York State Psychiatric Institute, New York, NY, USA.
Department of Psychiatry, College of Physicians & Surgeons, Columbia University, New York, NY, USA.
Adv Exp Med Biol. 2019;1162:89-127. doi: 10.1007/978-3-030-21737-2_6.
Δ-tetrahydrocannabinol (Δ-THC), the primary active component in Cannabis sativa preparations such as hashish and marijuana, signals by binding to cell surface receptors. Two types of receptors have been cloned and characterized as cannabinoid (CB) receptors. CB1 receptors (CB1R) are ubiquitously present in the central nervous system (CNS) and are present in both inhibitory interneurons and excitatory neurons at the presynaptic terminal. CB2 receptors (CB2R) are demonstrated in microglial cells, astrocytes, and several neuron subpopulations and are present in both pre- and postsynaptic terminals. The majority of studies on these receptors have been conducted in the past two and half decades after the identification of the molecular constituents of the endocannabinoid (eCB) system that started with the characterization of CB1R. Subsequently, the seminal discovery was made, which suggested that alcohol (ethanol) alters the eCB system, thus establishing the contribution of the eCB system in the motivation to consume ethanol. Several preclinical studies have provided evidence that CB1R significantly contributes to the motivational and reinforcing properties of ethanol and that the chronic consumption of ethanol alters eCB transmitters and CB1R expression in the brain nuclei associated with addiction pathways. Additionally, recent seminal studies have further established the role of the eCB system in the development of ethanol-induced developmental disorders, such as fetal alcohol spectrum disorders (FASD). These results are augmented by in vitro and ex vivo studies, showing that acute and chronic treatment with ethanol produces physiologically relevant alterations in the function of the eCB system during development and in the adult stage. This chapter provides a current and comprehensive review of the literature concerning the role of the eCB system in alcohol abuse disorders (AUD).
Δ-四氢大麻酚（Δ-THC）是大麻植物制剂（如大麻脂和大麻）中的主要活性成分，通过与细胞表面受体结合来传递信号。两种类型的受体已被克隆和表征为大麻素（CB）受体。CB1 受体（CB1R）在中枢神经系统（CNS）中普遍存在，存在于兴奋性神经元和抑制性中间神经元的突触前末梢。CB2 受体（CB2R）存在于小胶质细胞、星形胶质细胞和几种神经元亚群中，存在于突触前和突触后末梢。这些受体的大多数研究都是在过去的二十五年中进行的，在此期间，内源性大麻素（eCB）系统的分子成分得到了鉴定，这始于 CB1R 的特征描述。随后，一项开创性的发现表明，酒精（乙醇）改变了 eCB 系统，从而确立了 eCB 系统在乙醇消费动机中的作用。几项临床前研究提供了证据，表明 CB1R 显著促进了乙醇的动机和强化作用，慢性乙醇消费改变了与成瘾途径相关的大脑核团中的 eCB 递质和 CB1R 表达。此外，最近的开创性研究进一步确立了 eCB 系统在乙醇诱导的发育障碍（如胎儿酒精谱系障碍（FASD））发展中的作用。这些结果得到了体外和离体研究的补充，表明急性和慢性乙醇处理会在发育过程中和成年阶段对 eCB 系统的功能产生生理相关的改变。这一章提供了关于 eCB 系统在酒精滥用障碍（AUD）中的作用的文献的最新和全面的综述。
