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Quantifying reinforcement value and demand for psychoactive substances in humans. 量化人类对精神活性物质的强化价值和需求。
Pub Date : 2012-12-01 DOI: 10.2174/1874473711205040002
Adrienne J Heinz, Todd C Lilje, Jon D Kassel, Harriet de Wit

Behavioral economics is an emerging cross-disciplinary field that is providing an exciting new contextual framework for researchers to study addictive processes. New initiatives to study addiction under a behavioral economic rubric have yielded variable terminology and differing methods and theoretical approaches that are consistent with the multidimensional nature of addiction. The present article is intended to provide an integrative overview of the behavioral economic nomenclature and to describe relevant theoretical models, principles and concepts. Additionally, we present measures derived from behavioral economic theories that quantify demand for substances and assess decision making processes surrounding substance use. The sensitivity of these measures to different contextual elements (e.g., drug use status, acute drug effects, deprivation) is also addressed. The review concludes with discussion of the validity of these approaches and their potential for clinical application and highlights areas that warrant further research. Overall, behavioral economics offers a compelling framework to help explicate complex addictive processes and it is likely to provide a translational platform for clinical intervention.

行为经济学是一个新兴的跨学科领域,为研究人员研究成瘾过程提供了一个令人兴奋的新背景框架。在行为经济学框架下研究成瘾的新举措产生了与成瘾的多维性质相一致的不同术语、不同方法和理论方法。本文旨在对行为经济学术语进行综合概述,并介绍相关的理论模型、原则和概念。此外,我们还介绍了从行为经济学理论中衍生出来的测量方法,这些方法可以量化对物质的需求并评估围绕物质使用的决策过程。我们还讨论了这些测量方法对不同环境因素(如药物使用状况、急性药物效应、贫困)的敏感性。综述最后讨论了这些方法的有效性及其临床应用潜力,并强调了需要进一步研究的领域。总之,行为经济学提供了一个令人信服的框架,有助于解释复杂的成瘾过程,并有可能为临床干预提供一个转化平台。
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引用次数: 0
Editorial: Cognitive enhancement: are we barking up the wrong tree? 社论:认知增强:我们找错对象了吗?
Pub Date : 2012-12-01 DOI: 10.2174/1874473711205040001
Andrew Scholey, Con Stough, Joris C Verster
There are surprisingly few studies directly comparing the effects of nutraceutical and pharmaceuticals. However, a recent comparison of effects sizes (Cohen's d) from studies on modafinil and ginseng (and the long term benefits of Bacopa) was conducted [16]. In non sleep deprived individuals modafinil was associated with effect sizes ranging from d = 0.083 to d = 0.774. The latter was for accuracy of Visual Spatial Memory. For Ginseng there was larger variation in the effect sizes across mood and cognitive domains, ranging from d = -.340 (from a high dose of Ginseng) to d = 1.396. The latter related to reversal of self-rated mental fatigue during intense cognitive processing. In the context of cognitive processing the largest effect size (d = 0.860) was for simple reaction time. Thus it appears that herbal extracts may be at least as promising as pharmaceuticals as cognitive enhancers. Perhaps this is not so surprising when one considers that most pharmaceutical approaches to cognitive enhancement rely on the "magic bullet" approach to brain function. That is, they tend to target one neurotransmitter (or neurotransmitter family). It does seem unlikely that a phenomenon as complex as human cognitive function will benefit greatly from such an approach. Herbal extracts on the other hand, may contain multiple active components. These may exert multiple subtle effects which individually either have positive or negative effects on behaviour, but together may affect multiple neuronal, metabolic and hormonal systems which underpin behavioural processes. This polypharmacological approach may offer more promise in the context of cognitive enhancement.
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引用次数: 2
Single chemical entity legal highs: assessing the risk for long term harm. 单一化学实体合法兴奋剂:评估长期危害风险。
Pub Date : 2012-12-01 DOI: 10.2174/1874473711205040005
Carolyn B McNabb, Bruce R Russell, Daniele Caprioli, David J Nutt, Simon Gibbons, Jeffrey W Dalley

A recent and dramatic increase in the emergence of novel psychoactive substances ('legal highs') has left many governments unable to provide a timely response to an increasing number of potentially harmful drugs now available to the public. In response to this rapid increase in lawful drug use, the UK government intends to implement temporary class drug orders, whereby substances with a potential for misuse and harm can be regulated for a 12 month period. During this period an investigation of the potential for harms induced by these drugs will take place. However, the short time-frame in which information must be gathered, and the paucity of data available on novel psychoactive substances, means that robust pharmacological and toxicological analyses may be replaced by extrapolating data from illegal drugs with similar chemical structures. This review explores the potential pharmacology and toxicology of past and present 'legal highs' and discusses the risks of failing to carry out in-depth scientific research on individual substances.

最近,新型精神活性物质("合法兴奋剂")的出现急剧增加,导致许多国家的政府无法及时应对公众目前可获得的日益增多的潜在有害药物。为了应对合法药物使用的快速增长,英国政府打算实施临时类药物令,对可能造成滥用和伤害的药物进行为期 12 个月的监管。在此期间,将对这些药物可能造成的危害进行调查。然而,由于收集信息的时限较短,且新型精神活性物质的可用数据较少,因此可能会通过推断化学结构相似的非法药物数据来取代可靠的药理学和毒理学分析。本综述探讨了过去和现在的 "合法兴奋剂 "的潜在药理学和毒理学,并讨论了不对个别物质进行深入科学研究的风险。
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引用次数: 0
Clinical and forensic signs related to opioids abuse. 与阿片类药物滥用有关的临床和法医体征。
Pub Date : 2012-12-01 DOI: 10.2174/1874473711205040003
Ricardo Jorge Dinis-Oliveira, Felix Carvalho, Roxana Moreira, Jose Alberto Duarte, Jorge Brandao Proenca, Agostinho Santos, Teresa Magalhaes

For a good performance in Clinical and Forensic Toxicology it is important to be aware of the biological and non-biological signs and symptoms related to xenobiotic exposure. This manuscript highlights and analyzes clinical and forensic imaging related to opioids abuse critically. Particularly, respiratory depression, track marks and hemorrhages, skin "popping", practices of phlebotomy, tissue necrosis and ulceration, dermatitis, tongue hyperpigmentation, "coma blisters", intra-arterial administration, candidiasis, wounds associated with anthrax or clostridium contaminated heroin, desomorphine related lesions and characteristic non-biological evidences are some commonly reported findings in opioids abuse, which will be discussed. For this purpose, clinical and forensic cases from our database (National Institute of Legal Medicine and Forensic Sciences, North Branch, Portugal), in addition to literature data, are reviewed.

为了在临床和法医毒理学中取得良好的表现,重要的是要了解与外源接触有关的生物和非生物体征和症状。这份手稿强调并分析了与阿片类药物滥用有关的临床和法医成像。特别是,呼吸抑制、痕迹和出血、皮肤“爆裂”、静脉切开术、组织坏死和溃疡、皮炎、舌头色素沉着、“coma水泡”、动脉内给药、念珠菌病、与炭疽或梭状芽胞杆菌污染的海洛因相关的伤口、去吗啡相关的病变和特征性的非生物学证据是阿片类药物滥用中一些常见的发现,这些将被讨论。为此,除了文献数据外,还审查了我们数据库(国家法律医学和法医学研究所,北分支,葡萄牙)中的临床和法医病例。
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引用次数: 39
Efficacy of contingency management for cocaine dependence treatment: a review of the evidence. 应急管理对可卡因依赖治疗的有效性:证据综述。
Pub Date : 2012-12-01 DOI: 10.2174/1874473711205040006
Alwin Schierenberg, Jan van Amsterdam, Wim van den Brink, Anna E Goudriaan

Cocaine dependence causes serious individual and social harm and a considerable proportion of substance related treatment capacity is devoted to cocaine dependent persons. In the absence of approved pharmacotherapies, other treatments for cocaine dependence should be explored. In this review, the efficacy of Contingency Management (CM), a promising behavior therapy using operant conditioning, is evaluated for the treatment of cocaine dependence. A systematic evaluation of 19 studies with a total of 1,664 patients showed that CM - in combination with standard cognitive behavioral or other psychological interventions - (1) increases cocaine abstinence, (2) improves treatment retention during and after group-based or individual psychological treatment, (3) is of benefit in pharmacotherapy trials, and (4) that CM may act synergistically with pharmacotherapy. This suggests that CM is a promising add-on intervention for cocaine dependence treatment. Therefore, it is advocated to include CM in standard treatment programs for cocaine dependence and future pharmacotherapy research. Future larger studies are deemed necessary to replicate these promising results, now often lacking statistical significance.

可卡因依赖造成严重的个人和社会危害,很大一部分与药物有关的治疗能力用于可卡因依赖者。在没有核准的药物治疗方法的情况下,应探索其他治疗可卡因依赖的方法。在这篇综述中,评估了应急管理(CM),一个很有前途的行为疗法,使用操作性条件反射治疗可卡因依赖的疗效。一项对19项研究共1,664名患者的系统评估表明,CM -与标准认知行为或其他心理干预相结合-(1)增加可卡因戒断,(2)提高群体或个人心理治疗期间和之后的治疗保留性,(3)在药物治疗试验中有益,(4)CM可能与药物治疗协同作用。这表明CM是一种有希望的附加干预可卡因依赖治疗。因此,我们提倡将CM纳入可卡因依赖的标准治疗方案和未来的药物治疗研究。未来更大规模的研究被认为是必要的,以重复这些有希望的结果,现在往往缺乏统计意义。
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引用次数: 45
Substance-related disorders and somatic symptoms: how should clinicians understand the associations? 物质相关障碍和躯体症状:临床医生应该如何理解两者的关联?
Pub Date : 2012-12-01 DOI: 10.2174/1874473711205040004
Kouichi Yoshimasu

There are five major patterns which explain the associations between somatic symptoms and substance-related disorders (SRD) in patients without organic disorders. They are withdrawal somatic symptoms, somatic symptoms related to co-morbid mental disorders, those related to co-morbid infectious diseases, functional intractable somatic symptoms (including somatoform disorders), and symptoms associated with intoxication. Those somatic symptoms that occur according to those five patterns might overlap each other, making it difficult for physicians to precisely grasp the associations between somatic symptoms and SRD. This results in a very complicated formation of various kinds of symptoms (syndrome). Furthermore, the clinical and social features of those patterns of associations differ between legal and illicit substances users. It should also be noted that such somatic symptoms associated with SRD may be affected by social factors such as cultural backgrounds or legal restrictions on such substances. Those factors differ according to each country, area, or community whose cultural backgrounds are somewhat specific. In those areas, psychosocial factors such as stigmas, prejudices, or feeling ashamed of one's mental disorder (including SRD) also differ. Thus, it is important to take into account the effects of social or psychosocial backgrounds when evaluating and studying the associations between somatic symptoms and SRD. When clinicians confront patients with somatic symptoms and suspected SRD, they should presume which association pattern is the most significant problem for the patients, based on those psychosocial and biological information obtained from the patients themselves and their surroundings. This procedure might give an opportunity to clinicians for elucidating complicated associations between somatic complaints and SRD.

在没有器质性疾病的患者中,有五种主要模式可以解释躯体症状和物质相关疾病(SRD)之间的关联。它们是戒断躯体症状、与共病性精神障碍相关的躯体症状、与共病性传染病相关的躯体症状、功能性难治性躯体症状(包括躯体形式障碍)和与中毒相关的症状。根据这五种模式出现的躯体症状可能相互重叠,使医生难以准确掌握躯体症状与SRD之间的联系。这导致各种症状(综合征)的形成非常复杂。此外,这些关联模式的临床和社会特征在合法药物使用者和非法药物使用者之间有所不同。还应当指出,与SRD有关的这种躯体症状可能受到诸如文化背景或对此类物质的法律限制等社会因素的影响。这些因素因每个国家、地区或社区的文化背景而有所不同。在这些领域,社会心理因素,如耻辱、偏见或对自己的精神障碍(包括SRD)感到羞耻,也有所不同。因此,在评估和研究躯体症状与SRD之间的关联时,考虑社会或心理社会背景的影响是很重要的。当临床医生面对有躯体症状和疑似SRD的患者时,他们应该根据从患者自身和周围环境获得的社会心理和生物学信息,推测哪种关联模式对患者来说是最重要的问题。这个过程可能给临床医生一个机会来阐明躯体疾病和SRD之间复杂的联系。
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引用次数: 10
Mechanism of action of methamphetamine within the catecholamine and serotonin areas of the central nervous system. 甲基苯丙胺在中枢神经系统儿茶酚胺和血清素区域的作用机制。
Pub Date : 2012-09-01 DOI: 10.2174/1874473711205030227
Veronica M Chiu, James O Schenk

Addiction to methamphetamine (METH) is thought to be mediated by dopaminergic effects in the reward pathway in the brain via the A10 dopaminergic pathway. Herein we describe an overview of the results of the basic preclinical science undertaken to provide mechanistic insights into the action of amphetamines in general and METH in particular. A brief history of amphetamine and METH use and abuse is given, and an overview of the relevant chemical aspects of amphetamine as they relate to neurotransmitters in general is made. A review of the methods used to study the biochemical effects of METH is outlined. Finally, a focused analysis of the kinetic mechanisms of action of the amphetamines in general, and METH in particular, at the transmembrane transporters and at the intracellular vesicular storage sites is made. A description of how catecholaminergic and serotonergic nerve signaling may be altered by METH is proposed. Overall, the emphasis here is on differences in effects observed between the striatal (the A9 substantia nigral dopamine pathway) and nucleus accumbens (the A10, ventral tegmental pathway) areas of the brain following acute as well as repeated dosing and withdrawal.

甲基苯丙胺(冰毒)成瘾被认为是由多巴胺能作用介导的,多巴胺能作用通过大脑中的A10多巴胺能通路进行奖赏通路。在这里,我们概述了基础临床前科学的结果,以提供对安非他明和甲基苯丙胺的作用的机制见解。简要介绍了安非他明和冰毒使用和滥用的历史,并概述了安非他明的相关化学方面,因为它们一般与神经递质有关。综述了甲基苯丙胺生化效应的研究方法。最后,重点分析了安非他明,特别是甲基苯丙胺在跨膜转运体和细胞内囊泡储存部位的动力学机制。一个描述如何儿茶酚胺能和血清素能神经信号可能被甲基安非他明提出改变。总的来说,这里的重点是在急性和反复给药和停药后观察到的纹状体(A9黑质多巴胺通路)和伏隔核(A10,腹侧被盖通路)区域之间的影响差异。
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引用次数: 57
Direct association of Mu-opioid and NMDA glutamate receptors supports their cross-regulation: molecular implications for opioid tolerance. mu -阿片样物质和NMDA谷氨酸受体的直接关联支持它们的交叉调节:阿片样物质耐受性的分子意义。
Pub Date : 2012-09-01 DOI: 10.2174/1874473711205030199
Javier Garzón, María Rodríguez-Muñoz, Pilar Sánchez-Blázquez

In the nervous system, the interaction of opioids like morphine and its derivatives, with the G protein-coupled Mu-opioid receptor (MOR) provokes the development of analgesic tolerance, as well as physical dependence. Tolerance implies that increasing doses of the drug are required to achieve the same effect, a phenomenon that contributes significantly to the social problems surrounding recreational opioid abuse. In recent years, our understanding of the mechanisms that control MOR function in the nervous system, and that eventually produce opioid tolerance, has increased greatly. Pharmacological studies have identified a number of signaling proteins involved in morphine-induced tolerance, including the N-methyl-D-aspartate acid glutamate receptor (NMDAR), nitric oxide synthase (NOS), protein kinase C (PKC), protein kinase A (PKA), calcium (Ca²⁺)/calmodulin (CaM)-dependent kinase II (CaMKII), delta-opioid receptor (DOR) and the regulators of G-protein signaling (RGS) proteins. There is general agreement on the critical role of the NMDAR/nNOS/CaMKII pathway in this process, which is supported by the recent demonstration of a physical association between MORs and NMDARs in post-synaptic structures. Indeed, it is feasible that treatments that diminish morphine tolerance may target distinct elements within the same regulatory MOR-NMDAR pathway. Accordingly, we propose a model that incorporates the most relevant signaling components implicated in opioid tolerance in which, certain signals originating from the activated MOR are perceived by the associated NMDAR, which in turn exerts a negative feedback effect on MOR signaling. MOR- and NMDAR-mediated signals work together in a sequential and interconnected manner to ultimately induce MOR desensitization. Future studies of these phenomena should focus on adding further components to this signaling pathway in order to better define the mechanism underlying MOR desensitization in neural cells.

在神经系统中,吗啡及其衍生物等阿片样物质与G蛋白偶联的mu -阿片样受体(MOR)相互作用,引起镇痛耐受和身体依赖的发展。耐受性意味着需要增加药物剂量才能达到同样的效果,这一现象在很大程度上导致了与娱乐性阿片类药物滥用有关的社会问题。近年来,我们对控制神经系统MOR功能并最终产生阿片类药物耐受性的机制的了解大大增加。药理学研究已经确定了一些参与吗啡诱导耐受的信号蛋白,包括n -甲基-d -天冬氨酸谷氨酸受体(NMDAR)、一氧化氮合酶(NOS)、蛋白激酶C (PKC)、蛋白激酶a (PKA)、钙(Ca 2 +)/钙调素(CaM)依赖性激酶II (CaMKII)、delta-阿片受体(DOR)和g蛋白信号传导(RGS)蛋白的调节因子。NMDAR/nNOS/CaMKII通路在这一过程中起着关键作用,这一观点得到了最近MORs和NMDARs在突触后结构中的物理关联的证明的支持。事实上,降低吗啡耐受性的治疗可能针对相同的调节MOR-NMDAR通路中的不同元素。因此,我们提出了一个包含与阿片耐受性相关的最相关信号成分的模型,其中来自激活的MOR的某些信号被相关的NMDAR感知,而NMDAR反过来对MOR信号施加负反馈效应。MOR和nmdar介导的信号以顺序和相互关联的方式共同作用,最终诱导MOR脱敏。未来对这些现象的研究应侧重于在这一信号通路中添加更多的成分,以便更好地定义神经细胞中MOR脱敏的机制。
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引用次数: 78
Reward-seeking behavior and addiction: cause or cog? 寻求奖励行为和成瘾:原因还是原因?
Pub Date : 2012-09-01 DOI: 10.2174/1874473711205030178
Oscar Arias-Carrión, Mohamed Salama

Although dopaminergic system represents the cornerstone in rewarding, other neurotransmitters can modulate both the reward system and the psychomotor effects of addictive drugs. Many hypotheses have been proposed for a better understanding of the reward system and its role in drug addiction. However, after many years of investigation, no single theory can completely explain the neural basis of drug addiction. Recent reports introduce novel neurotransmitters into the game e.g. dynorphins, orexins, histamine, gheralin and galanin. The interacting functions of these neurotransmitters have shown that the reward system and its role in drug dependence, is far more complicated than was thought before. Individual variations exist regarding response to drug exposure, vulnerability for addiction and the effects of different cues on reward systems. Consequently, genetic variations of neurotransmission are thought to influence reward processing that in turn may affect distinctive social behavior and susceptibility to addiction. However, the individual variations can not be based mainly on genetics; environmental factors seem to play a role too. Here we discuss the current knowledge about the orquestic regulation of different neurotransmitters on reward-seeking behavior and their potential effect on drug addiction.

虽然多巴胺能系统是奖励机制的基础,但其他神经递质也可以调节成瘾药物的奖励系统和精神运动效应。为了更好地理解奖励系统及其在药物成瘾中的作用,人们提出了许多假设。然而,经过多年的研究,没有一个单一的理论可以完全解释药物成瘾的神经基础。最近的报道将新的神经递质引入到游戏中,如运动啡、食欲素、组胺、gheralin和galanine。这些神经递质的相互作用表明,奖赏系统及其在药物依赖中的作用远比以前认为的要复杂得多。个体对药物暴露的反应、成瘾的脆弱性以及不同线索对奖励系统的影响存在差异。因此,神经传递的遗传变异被认为影响奖励处理,而奖励处理反过来又可能影响独特的社会行为和对成瘾的易感性。然而,个体差异不能主要基于遗传;环境因素似乎也起了作用。本文讨论了不同神经递质对寻求奖励行为的协同调节及其对药物成瘾的潜在影响。
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引用次数: 8
Current trends in using Internet and mobile technology to support the treatment of substance use disorders. 利用互联网和移动技术支持药物使用障碍治疗的当前趋势。
Pub Date : 2012-09-01 DOI: 10.2174/1874473711205030172
Michael A Cucciare, Kenneth R Weingardt, Carolyn J Greene, Julia Hoffman

Issues: By allowing for the efficient delivery of instructional content and the secure collection of self-report data regarding substance use and related problems, the Internet has tremendous potential to improve the effectiveness and accessibility of Substance Use Disorder (SUD) treatment and recovery-oriented services.

Approach: This article discusses some of the ways in which Internet and mobile technology can facilitate, complement and support the process of traditional clinician-delivered treatment for individuals with SUDs.

Key findings: Internet applications are being used to support a range of activities including (a) the assessment and feedback process that constitutes a key feature of brief motivational interventions; and (b) the concurrent monitoring of patients who are receiving treatment for SUDs, to support continuing care, and the ongoing recovery of SUD patients who have completed face-to-face treatment. Internet technology is also being used to (c) support efficient delivery of clinical training in evidence-based practices for treating individuals who may have SUDs.

Implications: This emerging body of literature suggests that SUD treatment providers and program administrators can enhance the quality of clinician-delivered treatment by incorporating internet applications into existing processes of care and recovery oriented services.

Conclusion: Internet applications provide an unparalleled opportunity to engage patients in the treatment process, incorporate real-time data into treatment planning, prevent relapse, and promote evidence-based treatment approaches.

问题:通过允许有效地提供教学内容和安全收集有关物质使用和相关问题的自我报告数据,互联网具有巨大的潜力,可以提高物质使用障碍(SUD)治疗和康复导向服务的有效性和可及性。方法:本文讨论了互联网和移动技术可以促进、补充和支持传统临床医生为sud患者提供治疗过程的一些方法。主要发现:互联网应用程序正被用于支持一系列活动,包括(a)评估和反馈过程,这是简短动机干预的一个关键特征;(b)同时监测正在接受SUD治疗的患者,以支持持续护理,以及完成面对面治疗的SUD患者的持续康复。互联网技术也被用于(c)支持有效地提供临床培训,以循证实践治疗可能患有sud的个体。启示:这一新兴的文献表明,SUD治疗提供者和项目管理者可以通过将互联网应用纳入现有的护理和康复导向服务流程来提高临床提供治疗的质量。结论:互联网应用提供了一个无与伦比的机会,让患者参与治疗过程,将实时数据纳入治疗计划,预防复发,促进循证治疗方法。
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引用次数: 15
期刊
Current drug abuse reviews
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