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Low-level alcohol consumption is commonly perceived as being inconsequential or even beneficial for overall health, with some reports suggesting that it may protect against dementia or cardiovascular risks. However, these potential benefits do not preclude the concurrent possibility of negative health outcomes related to alcohol consumption. To examine whether casual, non-heavy drinking is associated with premature brain aging, we utilized the Brain-Age Regression Analysis and Computational Utility Software package to predict brain age in a community sample of adults [n = 240, mean age 35.1 (±10.7) years, 48% male, 49% African American]. Accelerated brain aging was operationalized as the difference between predicted and chronological age ("brain age gap"). Multiple regression analysis revealed a significant association between previous 90-day alcohol consumption and brain age gap (β = 0.014, p = 0.023). We replicated these results in an independent cohort [n = 231 adults, mean age 34.3 (±11.1) years, 55% male, 28% African American: β = 0.014, p = 0.002]. Our results suggest that even low-level alcohol consumption is associated with premature brain aging. The clinical significance of these findings remains to be investigated., (Copyright © 2021. Published by Elsevier Inc.)

The deleterious effects of the drug addiction epidemic are compounded by treatment strategies that are only marginally efficacious. Memantine is a unique glutamatergic medication with proven ability to attenuate drug addiction in preclinical models. However, clinical translational studies are inconsistent. In this review, we summarize preclinical evidences and clinical trials that investigated the efficacy of memantine in treating patients with alcohol, opiate, cocaine, and nicotine use disorders and discuss the results from a mechanistic point of view. Memantine has shown efficacy in reducing alcohol and opiate craving, consumption, and withdrawal severity. However, in cocaine and nicotine use disorders, memantine did not have significant effect on cravings or consumption. Additionally, memantine was associated with increased subjective effects of alcohol, cocaine, and nicotine. We discuss possible mechanisms behind this variability. Since memantine transiently blocks NMDA receptors and protects neurons from overstimulation by excessive synaptic glutamate, its efficacy should be observed in drug phases that cause hyperglutamatergic states, while hypoglutamatergic drug use states would not resolve with blocking NMDA receptors. Second, memantine pharmacokinetic studies have been done in rodents and healthy volunteers, but not in patients with substance use disorder. Memantine, opiates, cocaine, and nicotine share the same transporter family at the blood brain barrier. This shared transport mechanism could impact brain concentrations of memantine and its effects. In conclusion, memantine remains an intriguing compound in our pharmacopeia with controversial results in treating certain aspects of drug addiction. Further studies are needed to understand the clinical and biological correlates of its efficacy., (Published by Elsevier Inc.)