Authors:
Liput DJ, Hammell DC, Stinchcomb AL, Nixon K.
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.