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）：物质使用障碍是美国的一个主要公共卫生问题，在美国造成的死亡、疾病和残疾比任何其他可改变的健康问题都多。长期和过度使用酒精、甲基苯丙胺、可卡因、大麻素、海洛因和烟草制品，单独使用和各种组合使用（即，多物质使用障碍（PSUD）与人类大脑生物学和认知的许多异常有关。近50%有药物滥用问题的人患有PSUD，超过一半的人也依赖尼古丁。PSUD中的共病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证据，表明吸烟对脑形态、血流、生物化学和认知产生不利影响。这些与吸烟有关的生物学发现在性质上与在药物滥用中观察到的发现相似，并且涉及中皮质边缘奖赏回路的主要组成部分，该回路与所有形式的成瘾的开始和维持有关。此外，长期吸烟会阻碍酗酒者的神经生物学和认知恢复，吸烟与治疗后更高水平的酒精和物质使用有关。关于PSUD的神经生物学和认知后果的研究很少，并且尚未考虑慢性吸烟对恢复的潜在调节作用。此外，虽然复发在PSUD中很常见，但对该人群中复发的神经生物学和认知相关性了解甚少。最近的研究越来越多地暗示奖励回路异常是所有物质使用复发的主要因素，但缺乏PSUD的相应证据。我们假设：（i）慢性吸烟对PSUD的神经生物学和认知有可测量的不良影响，特别是在中皮质边缘奖励通路的主要组成部分，（ii）吸烟与短期戒烟PSUD的认知恢复减少有关，（iii）提出的神经生物学和认知措施区分戒烟者和治疗后恢复物质使用者。我们将联合收割机最先进的磁共振方法与认知评估相结合，以测量20名吸烟和20名非吸烟多物质使用者在进入物质使用障碍治疗时PSUD和慢性吸烟的后果。基线磁共振研究将比较这些组的局部脑容量，血流量和神经元和胶质细胞活力的代谢物标志物，以及主要的神经递质系统的措施。认知测试将在戒毒后立即评估大脑功能，并在4-6周的物质戒断监测后进行评估。这项创新的研究调查了慢性吸烟对PSUD的神经生物学和认知影响。这项探索性和转化性建议的结果将为未来的PSUD和其他物质使用障碍研究提供信息，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：慢性多种物质滥用是美国的一个主要健康问题，并导致脑损伤和多种认知问题。长期吸烟也与脑损伤和认知缺陷有关，在多种物质滥用者中比在一般人群中更常见。这一探索性的建议测试的假设，即慢性吸烟的多物质滥用者与更大的区域特定的脑损伤，通过磁共振方法测量和更大的认知缺陷比多物质滥用本身。这些试点研究的结果，在更大的后续研究中得到证实时，将对吸烟和药物滥用研究、治疗结果预测、公共卫生教育和药物政策制定产生重大影响。