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一个主要的公共卫生问题，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要多。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（即多物质使用障碍，PSUD）与人类大脑生物学和认知中的许多异常有关。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合并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越来越多的证据表明吸烟对脑形态、血流、生物化学和认知有不利影响。这些与吸烟相关的生物学发现在本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励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，长期吸烟阻碍酗酒者的神经生物学和认知恢复，并且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，尚未考虑长期吸烟对康复的潜在调节作用。此外，尽管PSUD复发很常见，但该人群中复发的神经生物学和认知相关因素尚不清楚。最近的研究越来越多地表明，奖赏回路异常是导致所有药物使用复发的主要因素，但在PSUD中缺乏相应的证据。我们假设：(i)长期吸烟对PSUD的神经生物学和认知有可测量的不利影响，特别是在中脑皮质边缘奖励通路的主要组成部分，（ii）吸烟与短期戒断PSUD的认知恢复减少有关，（iii）拟议的神经生物学和认知测量区分了戒断和恢复药物使用后的个体。我们将结合最先进的磁共振方法和认知评估来测量20名吸烟和20名非吸烟多物质使用者在进入药物使用障碍治疗时的PSUD和慢性吸烟的后果。基线磁共振研究将比较这些组的区域脑容量、血流量和代谢物标志物的神经元和神经胶质活力，以及主要的神经递质系统。认知测试将在戒毒后立即评估大脑功能，并在4-6周的药物戒断监测后进行。这项创新研究探讨了慢性吸烟对PSUD患者的神经生物学和认知影响。这一探索性和转化性建议的结果将为PSUD和其他物质使用障碍的未来研究提供信息，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：慢性多种药物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。长期吸烟还与脑损伤和认知缺陷有关，在多种药物滥用者中比在一般人群中更为常见。这一探索性提议验证了一种假设，即通过磁共振方法测量，多种物质滥用者的慢性吸烟与更大的区域特异性脑损伤有关，并且与多种物质滥用本身相比，更大的认知缺陷有关。这些初步研究的结果如果在更大规模的后续研究中得到证实，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。