Acute cannabidiol (CBD), tetrahydrocannabinol (THC) and their mixture (THC:CBD) exert differential effects on brain activity and blood flow in rats: A translational neuroimaging study.

IF 5.5 3区 医学 Q1 CLINICAL NEUROLOGY
Eilidh MacNicol, Michelle Kokkinou, Maria Elisa Serrano Navacerrada, Donna-Michelle Smith, Jennifer Li, Camilla Simmons, Eugene Kim, Michel Mesquita, Loreto Rojo Gonzalez, Tierney Andrews, Sally Loomis, Royston A Gray, Volker Knappertz, Benjamin J Whalley, Andrew C McCreary, Steven Cr Williams, David Virley, Diana Cash
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引用次数: 0

Abstract

Background: Cannabis constituents, including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), show distinct pharmacological profiles with therapeutic relevance for neurological and psychiatric conditions. THC exerts euphoric effects primarily via CB1 receptor activation, while CBD displays non-euphoric properties affecting various pathways.

Aims: This study evaluated the effects of THC, CBD, and their combination on brain functional connectivity (FC) and cerebral blood flow (CBF) using multimodal neuroimaging.

Methods: Adult male Sprague Dawley rats received intraperitoneal doses of 10 mg/kg THC, 150 mg/kg CBD, 10.8:10 mg/kg THC:CBD, or vehicle. Resting-state blood oxygenation level dependent magnetic resonance imaging and arterial spin labelling assessed FC and CBF, approximately 2 h after drug administration. Graph-theory metrics and seed-based analyses identified connectivity and perfusion alterations, while plasma analyses determined cannabinoid concentrations.

Results: THC increased whole-brain FC and clustering coefficient, with elevated CBF in cortical and subcortical regions. CBD decreased FC metrics without affecting CBF, while THC:CBD induced moderate increases in both. Seed-based analysis revealed THC-driven increases in cortical-hippocampal and cortical-striatal connectivity, attenuated in the THC:CBD group. A multivariate combined analysis of FC and CBF revealed a divergent pattern of changes induced by each drug.

Conclusions: In conclusion, we show that THC and CBD induce distinct neurophysiological profiles in rats, with THC increasing both connectivity and perfusion, moderated by CBD when combined. These findings corroborate existing knowledge about the effects of cannabinoids on the brain, while also supporting the potential of preclinical functional neuroimaging to delineate cannabinoid-induced endophenotypes, offering insights for therapeutic development.

急性大麻二酚(CBD)、四氢大麻酚(THC)及其混合物(THC:CBD)对大鼠脑活动和血流的不同影响:一项转化神经影像学研究。
背景:大麻成分,包括Δ9-tetrahydrocannabinol (THC)和大麻二酚(CBD),显示出不同的药理学特征与神经和精神疾病的治疗相关性。四氢大麻酚主要通过CB1受体激活发挥欣快作用,而CBD则表现出影响多种途径的非欣快特性。目的:本研究利用多模态神经成像技术评估四氢大麻酚(THC)、CBD及其组合对脑功能连通性(FC)和脑血流量(CBF)的影响。方法:成年雄性Sprague Dawley大鼠分别腹腔注射10 mg/kg THC、150 mg/kg CBD、10.8:10 mg/kg THC:CBD或载药。静息状态血氧水平依赖于磁共振成像和动脉自旋标记,在给药后约2小时评估FC和CBF。图论指标和基于种子的分析确定了连通性和灌注改变,而血浆分析确定了大麻素浓度。结果:四氢大麻酚增加全脑FC和聚类系数,皮质和皮质下区CBF升高。CBD降低FC指标而不影响CBF,而THC:CBD诱导两者适度增加。基于种子的分析显示,THC驱动的皮质-海马和皮质-纹状体连通性增加,在THC:CBD组中减弱。对FC和CBF的多变量联合分析显示,每种药物引起的变化模式不同。结论:总之,我们发现四氢大麻酚和CBD在大鼠中诱导了不同的神经生理特征,四氢大麻酚增加了大鼠的连通性和灌注,而CBD在联合使用时则起到了调节作用。这些发现证实了关于大麻素对大脑影响的现有知识,同时也支持临床前功能神经影像学描述大麻素诱导的内表型的潜力,为治疗开发提供见解。
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来源期刊
Journal of Psychopharmacology
Journal of Psychopharmacology 医学-精神病学
CiteScore
8.60
自引率
4.90%
发文量
126
审稿时长
3-8 weeks
期刊介绍: The Journal of Psychopharmacology is a fully peer-reviewed, international journal that publishes original research and review articles on preclinical and clinical aspects of psychopharmacology. The journal provides an essential forum for researchers and practicing clinicians on the effects of drugs on animal and human behavior, and the mechanisms underlying these effects. The Journal of Psychopharmacology is truly international in scope and readership.
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