Evaluation Of Treatments Of Opioid And Cocaine Dependence

阿片类药物和可卡因依赖的治疗评估

• 批准号: 9339203
• 负责人: Kenzie Preston
• 金额: $ 39.97万
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9339203
• 关键词: Abstinence; Adrenergic beta-Antagonists; Affect; Amaze; Association Learning; Attenuated; Auditory; Behavioral; Buffers; Cell Line; Characteristics; Cocaine; Cocaine Dependence; Cognitive Therapy; Communities; Cues; Data; Development; Disease; Dopamine D2 Receptor; Drug usage; Ecological momentary assessment; Electronics; Emotional; Environmental Exposure; Evaluation; Event; Evidence based treatment; Experimental Models; Exposure to; Gene Expression Regulation; Genes; Genetic Polymorphism; Genetic Variation; Goals; Human; Imagery; In Vitro; Individual Differences; Intervention; Interview; Life; Measurement; Memory; Minisatellite Repeats; Moods; Movement; Neurons; Opiate Addiction; Opioid; Outpatients; Participant; Patients; Pharmaceutical Preparations; Physiological; Placebos; Pluripotent Stem Cells; Preclinical Drug Evaluation; Propranolol; Randomized; Research; Stress; Techniques; Technology; Technology Transfer; Testing; Travel; Urine; Valproic Acid; Writing; addiction; attenuation; base; cocaine use; craving; cue reactivity; design; diaries; dopamine transporter; dopaminergic neuron; improved; insight; methadone maintenance; personalized medicine; psychosocial; response; stressor; substance abuser; therapy development; treatment effect; treatment response

We evaluated whether the beta-adrenergic antagonist propranolol could attenuate or erase the learned associations, or emotional memories, that underlie craving elicited by drug-related cues, administering propranolol during the reconsolidation window shortly after the memories were reactivated by cues. Healthy outpatients who used cocaine while receiving methadone maintenance were asked to recall specific cocaine-use events and neutral events in preliminary interviews. In the intervention sessions, we administered propranolol (40 mg) or placebo before presentation of personalized auditory imagery scripts and cue sets developed from the interviews. Group assignment was randomized, and medications were matched so that neither the participants nor the research staff knew what drug was given. Participants returned to the lab twice a week for urine drug screens. Cue reactivity was assessed by craving scales and physiological responses as participants were reexposed to the script/cue sets 1 week and 5 weeks after the propranolol/placebo session. Unexpectedly, participants in the propranolol group showed greater cue reactivity than those in the placebo group. This effect was present during propranolol administration and seemed to persist (though without reaching statistical significance) during the later test sessions. These results do not support the use of propranolol for attenuation of cue/cocaine associations in opioid-maintained patients. In another study, we evaluated the effects of homework-task simplification and electronic-diary reminders on completion of written homework during cognitive-behavioral therapy (CBT) for addiction. All participants received all combinations of our two interventions in a counterbalanced Latin-square design. Neither of the interventions increased homework completion, and based on ecological momentary assessment (EMA), standard but not simplified homework seemed to buffer the craving that followed environmental exposure to drug cues in daily life. The findings demonstrated the usefulness of EMA in assessing treatment effects, but did not support the hypothesis that homework simplification would increase compliance. We are continuing to evaluate patient characteristics that may guide developments in personalized medicine. Using inducible pluripotent stem cells (iPSCs), we produced DA neurons from opioid-dependent and control participants carrying different 3 VNTR (variable number tandem repeat) polymorphisms in the gene for the dopamine transporter (DAT or SLC6A3). We found that the 3 VNTR polymorphism affected DAT expression and that treatment of the neurons with valproic acid alters the expression of several genes important for dopaminergic functioning, including DAT, Nurr1 and TH. Valproic acid also significantly increased expression of D2 receptors, especially in cell lines derived from the opioid-dependent participants. Our data suggest that human iPSC-derived DA neurons are a useful in vitro experimental model to examine the effects of genetic variation on gene regulation, to examine underlying mechanisms of addiction and other disorders, and to serve as a platform for treatment development. Finally, we continue to develop Geographical Momentary Assessment (GMA), an approach to measurement and understanding of the relationships among mood, drug use, and environmental exposure to psychosocial stressors in participants daily travels. GMA is largely a descriptive technique, but we remain committed to transforming description into intervention. For example, we have shown that electronic-diary studies can provide amazing insight into the daily lives of substance abusers during treatment and data that are sensitive to behavioral changes during even brief periods of abstinence. The technologies that enable us to collect data on drug use, craving, and stress in the field may also be used for delivery of treatment in the field, perhaps in response to the patients movement toward previously identified triggers.

我们评估了-肾上腺素能拮抗剂心得安是否可以减弱或消除由药物相关线索引发的学习关联或情感记忆，在记忆被线索重新激活后不久的再巩固窗口期间给予心得安。在接受美沙酮维持期间使用可卡因的健康门诊患者在初步访谈中被要求回忆特定的可卡因使用事件和中性事件。在干预阶段，我们在提供个性化的听觉图像脚本和从访谈中开发的线索集之前，给予心得安（40毫克）或安慰剂。小组分配是随机的，药物是匹配的，所以参与者和研究人员都不知道服用的是什么药物。参与者每周两次返回实验室进行尿液药物筛查。线索反应是通过渴望量表和生理反应来评估的，当参与者在普萘洛尔/安慰剂治疗后1周和5周再次暴露于脚本/线索组时。出乎意料的是，心得安组的参与者比安慰剂组的参与者表现出更强的线索反应。这种效果在服用心得安期间存在，并且在随后的测试中似乎持续存在（尽管没有达到统计学意义）。这些结果不支持在阿片类药物维持的患者中使用心得安来减弱线索/可卡因的关联。

项目成果

Promoting abstinence from cocaine and heroin with a methadone dose increase and a novel contingency.

• DOI: 10.1016/j.drugalcdep.2008.11.006
• 发表时间: 2009-04-01
• 期刊: DRUG AND ALCOHOL DEPENDENCE
• 影响因子: 4.2
• 作者: Epstein, David H.;Schmittner, John;Umbricht, Annie;Schroeder, Jennifer R.;Moolchan, Eric T.;Preston, Kenzie L.
• 通讯作者: Preston, Kenzie L.

Psychostimulant addiction treatment.

• DOI: 10.1016/j.neuropharm.2014.04.002
• 发表时间: 2014-12
• 期刊: Neuropharmacology
• 影响因子: 4.7
• 作者: Phillips KA;Epstein DH;Preston KL
• 通讯作者: Preston KL

A meta-analysis of acupuncture combined with opioid receptor agonists for treatment of opiate-withdrawal symptoms.

• DOI: 10.1007/s10571-008-9336-4
• 发表时间: 2009-06
• 期刊: CELLULAR AND MOLECULAR NEUROBIOLOGY
• 影响因子: 4
• 作者: Liu, Ting-ting;Shi, Jie;Epstein, David H.;Bao, Yan-ping;Lu, Lin
• 通讯作者: Lu, Lin

Cigarette smoking and short-term addiction treatment outcome.

• DOI: 10.1016/j.drugalcdep.2010.08.017
• 发表时间: 2011-06-01
• 期刊: DRUG AND ALCOHOL DEPENDENCE
• 影响因子: 4.2
• 作者: Harrell, P. T.;Montoya, I. D.;Preston, K. L.;Juliano, L. M.;Gorelick, D. A.
• 通讯作者: Gorelick, D. A.

Randomized trial comparing two treatment strategies using prize-based reinforcement of abstinence in cocaine and opiate users.

随机试验比较两种使用有奖强化可卡因和阿片类药物使用者戒断的治疗策略。

• DOI: 10.1901/jaba.2008.41-551
• 发表时间: 2008
• 期刊: Journal of applied behavior analysis
• 影响因子: 2.9
• 作者: Preston,KenzieL;Ghitza,UdiE;Schmittner,JohnP;Schroeder,JenniferR;Epstein,DavidH
• 通讯作者: Epstein,DavidH