Departments of Cell Biology and Anatomy & Psychiatry, Cumming School of Medicine, Hotchkiss Brain Institute and The Mathison Centre for Mental Health Research and Education, University of Calgary, Calgary, Canada.
Department of Psychiatry, New York State Psychiatric Institute and Columbia University Irving Medical Center, New York, USA.
Psychol Med. 2023 Nov;53(15):7006-7024. doi: 10.1017/S0033291723002465. Epub 2023 Sep 6.
Cannabis is well established to impact affective states, emotion and perceptual processing, primarily through its interactions with the endocannabinoid system. While cannabis use is quite prevalent in many individuals afflicted with psychiatric illnesses, there is considerable controversy as to whether cannabis may worsen these conditions or provide some form of therapeutic benefit. The development of pharmacological agents which interact with components of the endocannabinoid system in more localized and discrete ways then via phytocannabinoids found in cannabis, has allowed the investigation if direct targeting of the endocannabinoid system itself may represent a novel approach to treat psychiatric illness without the potential untoward side effects associated with cannabis. Herein we review the current body of literature regarding the various pharmacological tools that have been developed to target the endocannabinoid system, their impact in preclinical models of psychiatric illness and the recent data emerging of their utilization in clinical trials for psychiatric illnesses, with a specific focus on substance use disorders, trauma-related disorders, and autism. We highlight several candidate drugs which target endocannabinoid function, particularly inhibitors of endocannabinoid metabolism or modulators of cannabinoid receptor signaling, which have emerged as potential candidates for the treatment of psychiatric conditions, particularly substance use disorder, anxiety and trauma-related disorders and autism spectrum disorders. Although there needs to be ongoing clinical work to establish the potential utility of endocannabinoid-based drugs for the treatment of psychiatric illnesses, the current data available is quite promising and shows indications of several potential candidate diseases which may benefit from this approach.
大麻已被证实可通过与内源性大麻素系统相互作用，主要影响情绪状态、情感和感知处理。虽然在许多患有精神疾病的个体中，大麻的使用相当普遍，但对于大麻是否会加重这些疾病或提供某种形式的治疗益处，仍存在相当大的争议。与植物大麻素相比，通过与内源性大麻素系统的成分以更局部和离散的方式相互作用的药理学制剂的发展，使得人们可以研究直接针对内源性大麻素系统本身是否可能成为一种治疗精神疾病的新方法，而不会产生与大麻相关的潜在不良副作用。本文综述了目前关于各种已开发的靶向内源性大麻素系统的药理学工具的文献，它们在精神疾病的临床前模型中的作用，以及最近在精神疾病临床试验中使用这些工具的数据，特别关注物质使用障碍、与创伤相关的障碍和自闭症。我们强调了几种靶向内源性大麻素功能的候选药物，特别是内源性大麻素代谢抑制剂或大麻素受体信号调节剂，它们已成为治疗精神疾病的潜在候选药物，特别是物质使用障碍、焦虑和与创伤相关的障碍以及自闭症谱系障碍。尽管需要进行持续的临床工作来确定基于内源性大麻素的药物治疗精神疾病的潜在效用，但目前可用的数据非常有希望，并表明有几种潜在的候选疾病可能受益于这种方法。
