| Publication Abstract Display |
| Type: Published Manuscript |
| Title: Cannabidiol mitigates alcohol dependence and withdrawal
with neuroprotective effects in the basolateral amygdala and
striatum. |
| Authors: Dirik S, Doyle MR, Wood CP, Campo P, Martinez AR, Fannon M, Balaguer MG, Seely S, Montoya BA, Cook GMR, Palermo GM, Lin J, Sist MD, Naghshineh PK, Lan Z, Rahman SRMU, Suhandynata R, Schweitzer P, Kallupi M, de Gugliemo G |
| Year: 2025 |
| Publication: Neuropsychopharmacology |
| Volume: Epub Jul 10 Issue: Pages: |
| Abstract:Alcohol use disorder (AUD) remains a pervasive public health issue with limited effective treatments. Cannabidiol (CBD), a non-
psychotropic constituent of cannabis, shows promise in modulating addictive behaviors. This study investigated the effects of
chronic CBD administration on alcohol dependence, withdrawal symptoms, and neurodegeneration using two complementary
rodent models: chronic intermittent ethanol (CIE) exposure, which models established alcohol dependence, and ethanol vapor self-
administration (EVSA), which captures the volitional aspects of alcohol intake. In the CIE model, CBD reduced alcohol self-
administration during acute withdrawal without affecting alcohol metabolism or locomotor activity. CBD decreased motivation for
alcohol, somatic withdrawal signs, withdrawal-induced anxiety-like behaviors, and mechanical sensitivity. During extinction, CBD
attenuated alcohol-seeking behavior and stress-induced reinstatement. Electrophysiological recordings revealed that CBD reversed
alcohol-induced decreases in neuronal excitability in the basolateral amygdala, suggesting a mechanism involving normalization of
neural function. In the EVSA model, CBD reduced voluntary alcohol intake during the escalation phase, impacting voluntary alcohol
intake. This effect was speci c to alcohol-related behaviors, as it did not affect saccharin self-administration. Immunohistochemical
analyses showed that CBD prevented alcohol-induced neurodegeneration in the nucleus accumbens shell and dorsomedial
striatum, regions implicated in the volitional control of alcohol consumption. These ndings indicate that chronic CBD
administration attenuates both behavioral and neurobiological facets of alcohol dependence by modulating neuronal excitability
and preventing neurodegeneration, supporting its therapeutic potential for AUD and providing mechanistic insights for future
research. |