Wyrofsky Ryan, McGonigle Paul, Van Bockstaele Elisabeth J
Drexel University, Department of Pharmacology and Physiology , Mail Stop 400, New College Building, 245 N. 15th Street, Philadelphia, PA 19102 , USA
Expert Opin Drug Discov. 2015 Jan;10(1):17-36. doi: 10.1517/17460441.2014.966680. Epub 2014 Dec 9.
The endocannabinoid (eCB) system plays an important role in the control of mood, and its dysregulation has been implicated in several psychiatric disorders. Targeting the eCB system appears to represent an attractive and novel approach to the treatment of depression and other mood disorders. However, several failed clinical trials have diminished enthusiasm for the continued development of eCB-targeted therapeutics for psychiatric disorders, despite the encouraging preclinical data and promising preliminary results obtained with the synthetic cannabinoid nabilone for treating post-traumatic stress disorder.
This review describes the eCB system's role in modulating cell signaling within the brain. There is a specific focus on eCB's regulation of monoamine neurotransmission and the stress axis, as well as how dysfunction of this interaction can contribute to the development of psychiatric disorders. Additionally, the review provides discussion on compounds and drugs that target this system and might prove to be successful for the treatment of mood-related psychiatric disorders.
The discovery of increasingly selective modulators of CB receptors should enable the identification of optimal therapeutic strategies. It should also maximize the likelihood of developing safe and effective treatments for debilitating psychiatric disorders.
内源性大麻素（eCB）系统在情绪调控中发挥着重要作用，其功能失调与多种精神疾病有关。针对eCB系统似乎是治疗抑郁症和其他情绪障碍的一种有吸引力的新方法。然而，尽管临床前数据令人鼓舞，且合成大麻素纳布隆治疗创伤后应激障碍取得了有前景的初步结果，但多项临床试验的失败削弱了人们对继续开发针对精神疾病的eCB靶向疗法的热情。
本综述描述了eCB系统在调节大脑内细胞信号传导中的作用。特别关注eCB对单胺神经传递和应激轴的调节，以及这种相互作用的功能障碍如何导致精神疾病的发生。此外，本综述还讨论了靶向该系统且可能被证明对治疗与情绪相关的精神疾病有效的化合物和药物。
越来越多选择性CB受体调节剂的发现应有助于确定最佳治疗策略。这也应能最大限度地提高开发针对使人衰弱的精神疾病的安全有效治疗方法的可能性。
