Viveros Maria-Paz, Bermúdez-Silva Francisco-Javier, Lopez-Rodriguez Ana-Belén, Wagner Edward J
Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense, Madrid 28040, Spain.
Laboratorio de Medicina Regenerativa, Fundación IMABIS, Hospital Carlos Haya, Málaga 29010, Spain.
Pharmaceuticals (Basel). 2011 Aug 10;4(8):1101-1136. doi: 10.3390/ph4081101.
The endocannabinoid system (ECS) has been implicated in many physiological functions, including the regulation of appetite, food intake and energy balance, a crucial involvement in brain reward systems and a role in psychophysiological homeostasis (anxiety and stress responses). We first introduce this important regulatory system and chronicle what is known concerning the signal transduction pathways activated upon the binding of endogenous cannabinoid ligands to the G-coupled CB1 cannabinoid receptor, as well as its interactions with other hormones and neuromodulators which can modify endocannabinoid signaling in the brain. Anorexia nervosa (AN) and bulimia nervosa (BN) are severe and disabling psychiatric disorders, characterized by profound eating and weight alterations and body image disturbances. Since endocannabinoids modulate eating behavior, it is plausible that endocannabinoid genes may contribute to the biological vulnerability to these diseases. We present and discuss data suggesting an impaired endocannabinoid signaling in these eating disorders, including association of endocannabinoid components gene polymorphisms and altered CB1-receptor expression in AN and BN. Then we discuss recent findings that may provide new avenues for the identification of therapeutic strategies based on the endocannabinod system. In relation with its implications as a reward-related system, the endocannabinoid system is not only a target for cannabis but it also shows interactions with other drugs of abuse. On the other hand, there may be also a possibility to point to the ECS as a potential target for treatment of drug-abuse and addiction. Within this framework we will focus on enzymatic machinery involved in endocannabinoid inactivation (notably fatty acid amide hydrolase or FAAH) as a particularly interesting potential target. Since a deregulated endocannabinoid system may be also related to depression, anxiety and pain symptomatology accompanying drug-withdrawal states, this is an area of relevance to also explore adjuvant treatments for improving these adverse emotional reactions.
内源性大麻素系统（ECS）与许多生理功能有关，包括食欲调节、食物摄入和能量平衡，在大脑奖赏系统中起关键作用，以及在心理生理稳态（焦虑和应激反应）中发挥作用。我们首先介绍这个重要的调节系统，并记录关于内源性大麻素配体与G蛋白偶联的CB1大麻素受体结合后激活的信号转导途径的已知情况，以及它与其他激素和神经调节剂的相互作用，这些激素和神经调节剂可以改变大脑中的内源性大麻素信号。神经性厌食症（AN）和神经性贪食症（BN）是严重的致残性精神疾病，其特征是严重的饮食和体重改变以及身体形象障碍。由于内源性大麻素调节饮食行为，内源性大麻素基因可能导致这些疾病的生物学易感性，这是合理的。我们展示并讨论数据，这些数据表明这些饮食失调中存在内源性大麻素信号受损的情况，包括内源性大麻素成分基因多态性的关联以及AN和BN中CB1受体表达的改变。然后我们讨论最近的发现，这些发现可能为基于内源性大麻素系统确定治疗策略提供新途径。鉴于其作为奖赏相关系统的影响，内源性大麻素系统不仅是大麻的作用靶点，还显示出与其他滥用药物的相互作用。另一方面，也有可能将ECS作为治疗药物滥用和成瘾的潜在靶点。在此框架内，我们将重点关注参与内源性大麻素失活的酶机制（特别是脂肪酸酰胺水解酶或FAAH），将其作为一个特别有趣的潜在靶点。由于失调的内源性大麻素系统也可能与药物戒断状态伴随的抑郁、焦虑和疼痛症状有关，这也是一个相关领域，可探索辅助治疗以改善这些不良情绪反应。
