New clinical targets for alcohol use disorders: evaluation using a laboratory paradigm

admin isbra esbra

Petrakis IL1,2 & Sofuoglu M1,2

1 Yale University School of Medicine, Department of Psychiatry, New Haven, CT USA
2 VA Connecticut Health Care System, West Haven, CT USA

Current approved medications to treat alcohol use disorders (AUD) are limited by their modest efficacy, suggesting a need for new therapeutic targets. A growing body of evidence has highlighted the importance of the interplay between alcohol’s action and the neuroimmune pathways. Microglial cells are present throughout the CNS, and they have an important role in synaptic structure, function and connectivity. Microglia activation releases pro-inflammatory cytokines and chemokines, which regulate and influence the immune response. Medications that inhibit microglia activation may have utility as potential treatments for AUD. One such medication is minocycline, a tetracycline derivative antibiotic that also inhibits microglia activation and the release of pro-inflammatory cytokines, chemokines, and nitric oxide (NO) production. Previous animal studies suggest that minocycline may attenuate the reinforcing effects of alcohol. These findings are supported by human studies in other addictive disorders. In a recent study, we examined the effects of minocycline treatment on the acute physiological, behavioral and subjective responses to dextroamphetamine in healthy volunteers. . Minocycline treatment, 200mg/day for 5 days, compared to placebo attenuated subjective –rewarding effects and attenuated the amphetamine-induced cortisol increases in plasma and speeded reaction times on a Go No-Go task. In an ongoing study, we are evaluating the effects of minocycline (100 or 200 mg/day) or placebo pretreatment for 10 days. On days 8 and 10 of treatment, subjects have 2 laboratory sessions where alcohol or placebo will be administered intravenously using a clamp procedure. Alcohol administration will use a breath alcohol concentration (BrAc) method, targeting 100 mg %. The outcome measures including subjective, motor, cognitive measurement and plasma cytokine levels. On day 10, the participant will receive whichever dose (placebo or 0mg%) or alcohol (100mg%) that they did not receive on day 8. Currently 6 subjects have been randomized. Results from these studies will be presented.