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Pharmacol Biochem Behav. 2013 Oct;111:120-7. doi: 10.1016/j.pbb.2013.08.013. Epub 2013 Sep 5.

Transdermal delivery of cannabidiol attenuates binge alcohol-induced neurodegeneration in a rodent model of an alcohol use disorder.

Author information

1
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 S. Limestone St., Lexington, KY 40536, USA. Electronic address: dlipu2@uky.edu.

Erratum in

  • Pharmacol Biochem Behav. 2014 Nov;126:187-8.

Abstract

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.

KEYWORDS:

Alcoholism; Cannabidiol; Ethanol; Neuroprotection; Neurotoxicity; Transdermal

PMID:
24012796
PMCID:
PMC4096899
DOI:
10.1016/j.pbb.2013.08.013
[Indexed for MEDLINE]
Free PMC Article

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