Department of Psychiatry, Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut.
Department of Psychiatry, Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut.
Biol Psychiatry. 2016 Apr 1;79(7):568-77. doi: 10.1016/j.biopsych.2015.12.011. Epub 2015 Dec 19.
Evidence has accumulated over the past several decades suggesting that both exocannabinoids and endocannabinoids play a role in the pathophysiology of schizophrenia. The current article presents evidence suggesting that one of the mechanisms whereby cannabinoids induce psychosis is through the alteration in synchronized neural oscillations. Neural oscillations, particularly in the gamma (30-80 Hz) and theta (4-7 Hz) ranges, are disrupted in schizophrenia and are involved in various areas of perceptual and cognitive function. Regarding cannabinoids, preclinical evidence from slice and local field potential recordings has shown that central cannabinoid receptor (cannabinoid receptor type 1) agonists decrease the power of neural oscillations, particularly in the gamma and theta bands. Further, the administration of cannabinoids during critical stages of neural development has been shown to disrupt the brain's ability to generate synchronized neural oscillations in adulthood. In humans, studies examining the effects of chronic cannabis use (utilizing electroencephalography) have shown abnormalities in neural oscillations in a pattern similar to those observed in schizophrenia. Finally, recent studies in humans have also shown disruptions in neural oscillations after the acute administration of delta-9-tetrahydrocannabinol, the primary psychoactive constituent in cannabis. Taken together, these data suggest that both acute and chronic cannabinoids can disrupt the ability of the brain to generate synchronized oscillations at functionally relevant frequencies. Hence, this may represent one of the primary mechanisms whereby cannabinoids induce disruptions in attention, working memory, sensory-motor integration, and many other psychosis-related behavioral effects.
在过去的几十年中,越来越多的证据表明外源性大麻素和内源性大麻素在精神分裂症的病理生理学中都发挥了作用。本文提出的证据表明,大麻素引起精神病的机制之一是通过改变同步神经振荡。神经振荡,特别是在伽马(30-80 Hz)和θ(4-7 Hz)范围内,在精神分裂症中被打乱,并且涉及到各种感知和认知功能领域。关于大麻素,切片和局部场电位记录的临床前证据表明,中枢大麻素受体(大麻素受体 1 型)激动剂降低了神经振荡的功率,特别是在伽马和θ频段。此外,在神经发育的关键阶段给予大麻素已被证明会破坏大脑在成年期产生同步神经振荡的能力。在人类中,研究慢性大麻使用(利用脑电图)的研究表明,在神经振荡中存在与在精神分裂症中观察到的类似的异常。最后,最近在人类中的研究也表明,在急性给予大麻的主要精神活性成分 delta-9-四氢大麻酚后,神经振荡也会中断。总之,这些数据表明,急性和慢性大麻素都可以破坏大脑产生同步振荡的能力,以达到功能相关的频率。因此,这可能是大麻素引起注意力、工作记忆、感觉运动整合和许多其他与精神病相关的行为效应紊乱的主要机制之一。