Department of Pharmacology, Addiction Science and Toxicology, College of Medicine, The University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Cannabis Cannabinoid Res. 2024 Feb;9(1):252-266. doi: 10.1089/can.2021.0234. Epub 2022 Sep 15.
Alcohol (ethanol) and cannabis are among the most widely used recreational drugs in the world. With increased efforts toward legalization of cannabis, there is an alarming trend toward the concomitant (including simultaneous) use of cannabis products with alcohol for recreational purpose. While each drug possesses a distinct effect on cerebral circulation, the consequences of their simultaneous use on cerebral artery diameter have never been studied. Thus, we set to address the effect of simultaneous application of alcohol and (-)-trans-Δ-9-tetrahydrocannabinol (THC) on cerebral artery diameter. We used Sprague-Dawley rats because rat cerebral circulation closely mimics morphology, ultrastructure, and function of cerebral circulation of humans. We focused on the middle cerebral artery (MCA) because it supplies blood to the largest brain territory when compared to any other cerebral artery stemming from the circle of Willis. Experiments were performed on pressurized MCA , and in cranial windows . Ethanol and THC were probed at physiologically relevant concentrations. Researchers were "blind" to experimental group identity during data analysis to avoid bias. In males, ethanol mixed with THC resulted in greater constriction of pressurized MCA when compared to the effects exerted by separate application of each drug. In females, THC, ethanol, or their mixture failed to elicit measurable effect. Vasoconstriction by ethanol/THC mixture was ablated by either endothelium removal or pharmacological block of calcium- and voltage-gated potassium channels of large conductance (BK type) and cannabinoid receptors. Block of prostaglandin production and of endothelin receptors also blunted constriction by ethanol/THC. In males, the constriction of MCA by ethanol/THC did not differ from ethanol alone. In females, the constriction of this artery by ethanol was significantly smaller than in males. However, artery constriction by ethanol/THC did not differ from the constriction in males. Our data point at the complex nature of the cerebrovascular effects elicited by simultaneous use of ethanol and THC. These effects include both local and systemic components.
酒精（乙醇）和大麻是世界上使用最广泛的娱乐性药物之一。随着大麻合法化的努力不断增加，同时（包括同时）将大麻产品与酒精一起用于娱乐目的的趋势令人震惊。虽然每种药物对大脑循环都有独特的影响，但它们同时使用对大脑动脉直径的影响从未被研究过。因此，我们着手研究同时应用酒精和（-）-反式-Δ-9-四氢大麻酚（THC）对大脑动脉直径的影响。我们使用 Sprague-Dawley 大鼠，因为大鼠的大脑循环在形态、超微结构和功能上与人类的大脑循环非常相似。我们专注于大脑中动脉（MCA），因为与源自 Willis 环的任何其他大脑动脉相比，它为大脑的最大区域供血。在加压 MCA 和颅窗上进行实验。以生理相关浓度探查乙醇和 THC。在数据分析过程中，研究人员对实验组成分一无所知，以避免偏见。在雄性中，与单独应用每种药物相比，乙醇与 THC 混合会导致加压 MCA 更大程度的收缩。在雌性中，THC、乙醇或它们的混合物未能引起可测量的作用。乙醇/THC 混合物引起的血管收缩通过去除内皮或药理学阻断大电导钙和电压门控钾通道（BK 型）和大麻素受体来消除。阻断前列腺素的产生和内皮素受体也会使乙醇/THC 引起的收缩减弱。在雄性中，乙醇/THC 对 MCA 的收缩与单独使用乙醇没有区别。在雌性中，乙醇对这条动脉的收缩明显小于雄性。然而，乙醇/THC 对动脉的收缩与雄性没有区别。我们的数据表明，同时使用乙醇和 THC 引起的脑血管效应具有复杂的性质。这些影响包括局部和全身成分。
