Alcohol Use Disorder: Neurobiology and Therapeutics.

Alcohol use disorder (AUD) encompasses the dysregulation of multiple brain circuits involved in executive function leading to excessive consumption of alcohol, despite negative health and social consequences and feelings of withdrawal when access to alcohol is prevented. Ethanol exerts its toxicity through changes to multiple neurotransmitter systems, including serotonin, dopamine, gamma-aminobutyric acid, glutamate, acetylcholine, and opioid systems. These neurotransmitter imbalances result in dysregulation of brain circuits responsible for reward, motivation, decision making, affect, and the stress response. Despite serious health and psychosocial consequences, this disorder still remains one of the leading causes of death globally. Treatment options include both psychological and pharmacological interventions, which are aimed at reducing alcohol consumption and/or promoting abstinence while also addressing dysfunctional behaviours and impaired functioning. However, stigma and social barriers to accessing care continue to impact many individuals. AUD treatment should focus not only on restoring the physiological and neurological impairment directly caused by alcohol toxicity but also on addressing psychosocial factors associated with AUD that often prevent access to treatment. This review summarizes the impact of alcohol toxicity on brain neurocircuitry in the context of AUD and discusses pharmacological and non-pharmacological therapies currently available to treat this addiction disorder.

Novel central nervous system drug delivery systems.

For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases.