Neuropsychobiology in Polysubstance Abusers during Abstinence

多物质滥用者禁欲期间的神经心理生物学

• 批准号: 9414009
• 负责人: DIETER J MEYERHOFF
• 金额: $ 53.97万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9414009
• 关键词: Abstinence; Affect; Aftercare; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohol or Other Drugs use; Alcohols; Anterior; Antioxidants; Behavior; Behavior Control; Behavior Therapy; Biological; Biology; Blood flow; Brain; Brain Injuries; Brain imaging; Brain region; Cerebrum; Chronic; Clinical Research; Cognition; Cognitive; Cognitive deficits; Communities; Comorbidity; Corpus striatum structure; Data; Decision Making; Development; Disease; Disease remission; Drug abuse; Drug usage; Energy Metabolism; Frequencies; Functional disorder; Future; General Population; Gliosis; Glutamates; Glutathione; Goals; Health behavior; Hypertrophy; Illicit Drugs; Impulsive Behavior; Individual; Inferior; Inflammatory; Informal Social Control; Injury; Knowledge; Learning; Magnetic Resonance; Measurement; Measures; Memory; Metabolic; Methamphetamine; Monitor; Morphology; National Institute of Drug Abuse; Nature; Neurobiology; Neurocognition; Neurocognitive Deficit; Neuronal Injury; Neuronal Plasticity; Neurons; Neuropsychology; Neurotransmitters; Oxidative Stress; Pattern; Perception; Perfusion; Peripheral; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacology; Pharmacotherapy; Policies; Population; Prevalence; Public Opinion; Quality of life; Recording of previous events; Recovery; Relapse; Research; Research Personnel; Resources; Risk; Risk-Taking; Sampling; Severities; Short-Term Memory; Smoking; Substance abuse problem; System; Testing; Thinness; Time; Tobacco; Tobacco use; Training; Translational Research; United States; addiction; alcohol abstinence; alcohol comorbidity; alcohol use disorder; base; brain abnormalities; cigarette smoking; clinical predictors; clinically relevant; cocaine use; cognitive control; cognitive performance; cohort; cytokine; drug abstinence; drug use vulnerability; effective therapy; functional improvement; improved; magnetic field; marijuana use disorder; multimodality; neuroadaptation; neuroimaging; novel; polysubstance abuse; pre-clinical research; processing speed; public health relevance; relapse prediction; relapse risk; response; skills; social stigma; sociodemographics; substance abuse treatment; substance misuse; targeted treatment; treatment group; white matter

 DESCRIPTION (provided by applicant): Polysubstance use disorder (PSUD) is more common among treatment seekers today than monosubstance use disorders. Chronic cigarette smoking is more prevalent among treated substance users than in the general population, and it is more prevalent in polysubstance users (PSU) than monosubstance users. Yet, very little is known about the neurobiological effects of PSUD and comorbid smoking, their potential relationships to neuro- cognition and related substance use behavior, or about effective treatment of PSUD. Extensive brain imaging and cognitive research indicate that monosubstance use is associated with abnormal brain biology and function that facilitate continued misuse; some of these brain abnormalities partially recover with abstinence. Further, smoking has clear detrimental effects on brain biology and function in monosubstance users (alcohol, methamphetamines), even in otherwise healthy controls. Notably, our preliminary studies show that brain abnormalities in PSU are different in extent, nature, and impact on cognition and behavior than in `pure' alcohol dependent samples with similar alcohol and tobacco use histories, and that both neurobiology and cognition improve in PSU over 3 months of abstinence. The ethnic and sociodemographic composition of PSU treatment cohorts is also distinctly different from that of `pure' alcohol dependent cohorts, altogether suggesting that they constitute different populations. We propose to study a well-defined and well-characterized group of PSU at 1- 3 weeks of abstinence with select brain magnetic resonance (MR), cognition, and self-regulation measures, to re-study abstinent PSU 3 months later, and to relate cross-sectional and longitudinal change measures to relapse and substance use assessed 6-9 months after baseline. Our regional focus is on fronto-striatal brain critical for achieving and maintaining long-term abstinence in addictive disorders. Our neuro-psychological focus is on traditional cognitive domains and measures of impulsive behavior and cognitive control. Our main neurobiological focus is on oxidative stress (OxS), hypothesized to underlie both PSUD and chronic smoking, and the neurobiological and systemic correlates of OxS. We further hypothesize that specific cognitive and regional MR abnormalities improve with abstinence and that longitudinal change measures during early remission predict subsequent relapse better than the corresponding cross-sectional measures. Additional MR measures will probe fronto-striatal neuronal injury, gliosis, glutamatergic and GABA-ergic effects, and perfusion deficits as they relate to cognition, self-regulation, and substance and tobacco use pre- and post-treatment. Studies will be conducted in treatment seekers with comorbid alcohol and cocaine use disorders (moderate to severe), with or without tobacco and mild cannabis use disorder. This hypotheses-driven proposal is aimed at identifying multifaceted determinants of continued substance misuse or abstinence as potential new targets for pharmacological and behavioral treatment of PSU. Showing neurobiological and functional improvements with abstinence will also help move public opinion to a mindset more helpfully described as `your brain in recovery'.