Department of Psychosis Studies, King's College London, Institute of Psychiatry, 6th Floor, Main Building, PO Box 067, De Crespigny Park, SE5 8AF, London, UK.
Curr Pharm Des. 2012;18(32):5045-54. doi: 10.2174/138161212802884636.
Pharmacological challenge in conjunction with neuroimaging techniques has been employed for over two decades now to understand the neural basis of the cognitive, emotional and symptomatic effects of the main ingredients of cannabis, the most widely used illicit drug in the world. This selective critical review focuses on the human neuroimaging studies investigating the effects of delta-9- tetrahydrocannabinol (THC) and cannabidiol (CBD), the two main cannabinoids of interest present in the extract of the cannabis plant. These studies suggest that consistent with the polymorphic and heterogeneous nature of the effects of cannabis, THC and CBD have distinct and often opposing effects on widely distributed neural networks that include medial temporal and prefrontal cortex and striatum, brain regions that are rich in cannabinoid receptors and implicated in the pathophysiology of psychosis. They help elucidate the neurocognitive mechanisms underlying the acute induction of psychotic symptoms by cannabis and provide mechanistic understanding underlying the potential role of CBD as an anxiolytic and antipsychotic. Although there are ethical and methodological caveats, pharmacological neuroimaging studies such as those reviewed here may not only help model different aspects of the psychopathology of mental disorders such as schizophrenia and offer insights into their underlying mechanisms, but may suggest potentially new therapeutic targets for drug discovery.
药理学挑战与神经影像学技术相结合，已经被应用了二十多年，以了解大麻主要成分（世界上使用最广泛的非法药物）的认知、情感和症状效应的神经基础。本选择性批判性综述重点关注研究 delta-9-四氢大麻酚（THC）和大麻二酚（CBD）影响的人类神经影像学研究，这两种主要大麻素存在于大麻植物提取物中。这些研究表明，与大麻效应的多态性和异质性一致，THC 和 CBD 对广泛分布的神经网络具有明显且常常相反的影响，包括内侧颞叶和前额叶皮层和纹状体，这些大脑区域富含大麻素受体，并与精神病的病理生理学有关。它们有助于阐明大麻急性诱导精神病症状的神经认知机制，并为 CBD 作为抗焦虑药和抗精神病药的潜在作用提供机制理解。尽管存在伦理和方法上的注意事项，但药理学神经影像学研究，如本文所综述的研究，不仅可能有助于模拟精神障碍（如精神分裂症）的精神病理学的不同方面，并为其潜在机制提供见解，而且可能为药物发现提供潜在的新治疗靶点。
