Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 S. Limestone St., Lexington, KY 40536, USA.
Pharmacol Biochem Behav. 2013 Oct;111:120-7. doi: 10.1016/j.pbb.2013.08.013. Epub 2013 Sep 5.
Excessive alcohol consumption, characteristic of alcohol use disorders, results in neurodegeneration and behavioral and cognitive impairments that are hypothesized to contribute to the chronic and relapsing nature of alcoholism. Therefore, the current study aimed to advance the preclinical development of transdermal delivery of cannabidiol (CBD) for the treatment of alcohol-induced neurodegeneration. In Experiment 1, 1.0%, 2.5% and 5.0% CBD gels were evaluated for neuroprotection. The 5.0% CBD gel resulted in a 48.8% reduction in neurodegeneration in the entorhinal cortex assessed by Fluoro-Jade B (FJB), which trended to statistical significance (p=0.069). Treatment with the 5.0% CBD gel resulted in day 3 CBD plasma concentrations of ~100.0 ng/mL so this level was used as a target concentration for development of an optimized gel formulation. Experiment 2 tested a next generation 2.5% CBD gel formulation, which was compared to CBD administration by intraperitoneal injection (IP; 40.0 mg/kg/day). This experiment found similar magnitudes of neuroprotection following both routes of administration; transdermal CBD decreased FJB+ cells in the entorhinal cortex by 56.1% (p<0.05), while IP CBD resulted in a 50.6% (p<0.05) reduction in FJB+ cells. These results demonstrate the feasibility of using CBD transdermal delivery systems for the treatment of alcohol-induced neurodegeneration.
过量饮酒是酒精使用障碍的特征，会导致神经退行性变以及行为和认知障碍，据推测这些会导致酒精成瘾的慢性和复发性。因此，本研究旨在推进大麻二酚（CBD）经皮给药治疗酒精引起的神经退行性变的临床前开发。在实验 1 中，评估了 1.0%、2.5%和 5.0% CBD 凝胶的神经保护作用。Fluoro-Jade B（FJB）评估的内嗅皮质神经退行性变，5.0% CBD 凝胶使神经退行性变减少了 48.8%，有统计学意义（p=0.069）。用 5.0% CBD 凝胶治疗导致第 3 天 CBD 血浆浓度达到约 100.0ng/ml，因此该水平被用作开发优化凝胶配方的目标浓度。实验 2 测试了下一代 2.5% CBD 凝胶配方，与腹腔注射（IP；40.0mg/kg/天）的 CBD 给药进行了比较。该实验发现两种给药途径的神经保护作用相当；经皮 CBD 使内嗅皮质的 FJB+细胞减少了 56.1%（p<0.05），而 IP CBD 使 FJB+细胞减少了 50.6%（p<0.05）。这些结果表明，使用 CBD 经皮给药系统治疗酒精引起的神经退行性变是可行的。
