Anandamide is a lipid mediator that acts as an endogenous ligand of CB1 receptors. These receptors are also the primary molecular target responsible for the pharmacological effects of Δ9-tetrahydrocannabinol, the psychoactive ingredient in Cannabis sativa. Several studies demonstrate that anandamide exerts an overall modulatory effect on the brain reward circuitry. Several reports suggest its involvement in the addiction-producing actions of other abused drugs, and it can also act as a behavioral reinforcer in animal models of drug abuse. Importantly, all these effects of anandamide appear to be potentiated by pharmacological inhibition of its metabolic degradation. Enhanced brain levels of anandamide after treatment with inhibitors of fatty acid amide hydrolase, the main enzyme responsible for its degradation, seem to affect the rewarding and reinforcing actions of many drugs of abuse. In this review, we will provide an overview from a preclinical perspective of the current state of knowledge regarding the behavioral pharmacology of anandamide, with a particular emphasis on its motivational/reinforcing properties. We will also discuss how modulation of anandamide levels through inhibition of enzymatic metabolic pathways could provide a basis for developing new pharmaco-therapeutic tools for the treatment of substance use disorders.

中文翻译：

---

anandamide 的大脑活动：一种有益的幸福？

Anandamide 是一种脂质介质，可作为 CB1 受体的内源性配体。这些受体也是负责 Δ9-四氢大麻酚（大麻中的精神活性成分）药理作用的主要分子靶标。几项研究表明，anandamide 对大脑奖励电路具有整体调节作用。一些报告表明它参与了其他滥用药物的成瘾行为，并且它也可以作为药物滥用动物模型的行为强化剂。重要的是，anandamide 的所有这些作用似乎都通过药理学抑制其代谢降解而得到增强。用脂肪酸酰胺水解酶抑制剂（负责其降解的主要酶）治疗后，脑内 anandamide 水平升高，似乎影响许多滥用药物的奖励和强化作用。在这篇综述中，我们将从临床前的角度概述有关 anandamide 行为药理学的当前知识状态，特别强调其激励/强化特性。我们还将讨论如何通过抑制酶代谢途径调节 anandamide 水平可以为开发用于治疗物质使用障碍的新药物治疗工具提供基础。