Polysubstance Use and Chronic Smoking: Neuroimaging and Cognition

多种物质使用和长期吸烟：神经影像学和认知

• 批准号: 7737533
• 负责人: DIETER J MEYERHOFF
• 金额: $ 23.25万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7737533
• 关键词: AODD relapse; Abstinence; Adverse effects; Affect; Aftercare; Alcohol consumption; Alcohol dependence; Alcohol or Other Drugs use; Alcohols; Aminobutyric Acids; Arts; Biochemistry; Biological; Biology; Blood flow; Brain; Brain Injuries; Cannabinoids; Cerebrovascular Circulation; Cessation of life; Chronic; Clinical; Cocaine; Cognition; Cognitive; Cognitive deficits; Dependence; Development; Disease; Drug Metabolic Detoxication; Drug abuse; Follow-Up Studies; Foundations; Future; General Population; Glutamates; Health; Heroin; Human; Impaired cognition; Individual; Injury; Link; Location; Magnetic Resonance; Maintenance; Measurable; Measures; Methamphetamine; Methodology; Methods; Monitor; Mood Disorders; Morbidity - disease rate; Nature; Neurobiology; Neurocognition; Neurocognitive; Neurons; Neurotransmitters; Nicotine; Oxidative Stress; Pathway interactions; Pharmaceutical Preparations; Phenotype; Pilot Projects; Policies; Policy Making; Population; Prevalence; Public Health; Public Health Education; Recovery; Relapse; Research; Rewards; Severities; Smoke; Smoking; Societies; Structure; Substance Use Disorder; Substance abuse problem; Surrogate Markers; System; Testing; Time; Tobacco; Treatment outcome; United States; Veterans; Wood material; addiction; alcohol measurement; brain morphology; brain volume; cerebrovascular; cigarette smoking; cognitive recovery; cost; disability; executive function; follow-up; innovation; mortality; neurocognitive test; neuroimaging; neuropsychological; non-smoking; novel; polysubstance abuse; problem drinker; public health relevance; reward circuitry; treatment response

DESCRIPTION (provided by applicant): Substance use disorders are a major public health concern in the USA and cause more deaths, illness and disabilities than any other modifiable health problem in the USA. Chronic and excessive use of alcohol, methamphetamines, cocaine, cannabinoids, heroin, and tobacco products individually and in various combinations (i.e., polysubstance use disorder, PSUD), have been linked to numerous abnormalities in human brain biology and cognition. Nearly 50% of all individuals with substance abuse problems have PSUD and more than half are also nicotine dependent. Comorbid chronic cigarette smoking in PSUD may be of considerable clinical and functional relevance, as recent research provides converging lines of evidence that cigarette smoking adversely affects brain morphology, blood flow, biochemistry, and cognition. These smoking- related biological findings are similar in nature to those observed in substance abuse and involve major components of the mesocorticolimbic reward circuitry, which is implicated in the initiation and maintenance of all forms of addiction. Furthermore, chronic smoking hinders neurobiological and cognitive recovery in alcoholics, and smoking is related to higher levels of alcohol and substance use after treatment. Research on the neurobiological and cognitive consequences of PSUD is sparse and has not yet considered the potential modulating effects of chronic smoking on recovery. Additionally, although relapse is common in PSUD, the neurobiological and cognitive correlates of relapse in this population are poorly understood. Recent research increasingly implicates abnormalities of the reward circuitry as a major contributing factor to relapse in all substance use, but corresponding evidence in PSUD is lacking. We hypothesize that (i) chronic cigarette smoking has measurable adverse effects on neurobiology and cognition in PSUD, especially in major components of the mesocorticolimbic reward pathway, (ii) smoking is associated with diminished cognitive recovery in short-term abstinent PSUD, and (iii) the proposed neurobiological and cognitive measures distinguish individuals who abstain from those who resume substance use after treatment. We will combine state-of-the-art magnetic resonance methods with cognitive assessment to measure consequences of PSUD and chronic cigarette smoking in 20 smoking and 20 non-smoking polysubstance users at entry into treatment for substance use disorders. Baseline magnetic resonance studies will compare these groups on measures of regional brain volumes, blood flow and metabolites markers of neuronal and glial viability, as well as major neurotransmitter systems. Cognitive testing will assess brain function immediately after detoxification and after 4-6 weeks of monitored abstinence from substances. This innovative research investigates neurobiological and cognitive effects of chronic smoking in PSUD. Results from this exploratory and translational proposal will inform future research in PSUD and other substance use disorders, may help to predict treatment outcome, and will have major implications for public health education and policy making. PUBLIC HEALTH RELEVANCE: Chronic polysubstance abuse is a major health problem in the US and leads to brain injury and multiple cognitive problems. Chronic cigarette smoking is also associated with brain injury and cognitive deficits and is much more common in polysubstance abusers than in the general population. This exploratory proposal tests the hypothesis that chronic smoking in polysubstance abusers is associated with greater region-specific brain injury as measured by magnetic resonance methods and with greater cognitive deficits than polysubstance abuse by itself. The results of these pilot studies, when confirmed in larger follow-up studies, will have major implications for smoking and drug abuse research, for prediction of treatment outcome, for public health education, and for drug policy making.

描述（由申请人提供）：与美国其他任何可修改的健康问题相比，在美国，药物使用障碍是美国的主要公共卫生问题，造成更多的死亡，疾病和残疾。慢性和过度使用酒精，甲基苯丙胺，可卡因，大麻素，海洛因和烟草产物单独和各种组合（即多刺甲苯使用障碍，PSUD）与人脑生物学和认知的许多异常有关。在所有患有药物滥用问题的人中，近50％的人患有PSUD，一半以上也依赖于尼古丁。 psud中合并的慢性吸烟可能具有相当大的临床和功能相关性，因为最近的研究提供了融合的证据，表明吸烟对脑形态，血液流动，生物化学和认知的不利影响。这些与吸烟相关的生物学发现本质上类似于在药物滥用中观察到的生物学发现，涉及中皮质胶质奖励回路的主要组成部分，这与所有形式的成瘾形式的启动和维持有关。此外，慢性吸烟会阻碍酒精中毒的神经生物学和认知恢复，并且吸烟与治疗后的酒精和药物使用水平较高有关。对PSUD的神经生物学和认知后果的研究很少，尚未考虑长期吸烟对恢复的潜在调节作用。此外，尽管复发在PSUD中很常见，但该人群中复发的神经生物学和认知相关性知之甚少。最近的研究越来越多地暗示奖励电路的异常是所有物质使用中复发的主要因素，但是缺乏相应的证据。我们假设（I）（i）长期吸烟对PSUD的神经生物学和认知具有可测量的不良影响，尤其是在中皮质胶质奖励途径的主要组成部分中，（ii）吸烟与短期戒烟的认知恢复相关，以及（III）的使用，以及（iii），以及（iii）的使用，以及（iii），这些次数与这些人（III）相关的次数与其他人的态度相关，以确保对这些人的反复无常的措施，以此与这些人的反射性相关，以供介绍这些人，以供介绍这些人，以供介绍这些人，以指示这些人与拟议中的人相关的人，以供这些人与拟议中的人相处。 治疗。我们将将最新的磁共振方法与认知评估相结合，以衡量20种吸烟中的PSUD和慢性吸烟的后果，以及20种非吸烟的多刺激使用者，用于进入药物使用障碍治疗。基线磁共振研究将在神经元和神经胶质生存力以及主要神经递质系统的区域脑体积，血流和代谢物标记方面进行比较。认知测试将在解毒后立即评估大脑功能，并在受到监测的物质戒酒后4-6周后。这项创新的研究研究了慢性吸烟在PSUD中的神经生物学和认知作用。该探索性和翻译建议的结果将为PSUD和其他物质使用障碍的未来研究提供依据，可能有助于预测治疗结果，并将对公共卫生教育和政策制定产生重大影响。公共卫生相关性：在美国，慢性多核心滥用是一个主要的健康问题，导致脑损伤和多重认知问题。慢性吸烟还与脑损伤和认知缺陷有关，在多义滥用者中比普通人群更为普遍。该探索性提案检验了以下假设：通过磁共振方法衡量的多进化滥用者中的慢性吸烟与更大的区域特异性脑损伤有关，并且与自身的polysubstance滥用相比，认知缺陷更大。这些试点研究的结果在大型后续研究中得到证实，将对吸烟和滥用药物研究，预测治疗结果，公共卫生教育和药物政策制定具有重大影响。