纳曲酮用于海洛因脱毒后预防复吸46例

海洛因依赖者脱毒治疗后，由于不能消除对毒品的精神依赖，复吸率高达８０％～９０％［１］，因此，预防复吸已成为依赖者脱毒后康复期巩固治疗的重要措施之一。国外从七十年代末开始对纳曲酮进行研究，并将其应用于临床，是目前较好的以生物学方法预防复吸的一种措施。１...     

纳曲酮对海洛因依赖戒断后的抗复吸作用

海洛因依赖者在戒断后复吸率甚高，为了解纳曲酮是否具有抗复吸作用，对１９９４年在我所戒毒者以此药治疗后的随访结果报告如下：１　对象与方法均系多次反复脱毒人员共４７例。其中男２９例，女１８例，年龄１８～３１岁，平均２３．４岁。自愿并在家属支持下使用纳曲酮。疗前肯定已无戒断症状，尿液吗啡样物质测定阴性。并肌注纳曲酮０．８ｍｇ作催瘾试验，均证实体内已无鸦片类物质存在。首日剂量为５ｍｇ／ｄ，若无不适反应，每日加倍服用，直至４０～５０ｍｇ／ｄ为度。最高量必须维持３月以上，维持巩固量不得低于２０ｍｇ／ｄ。建立…     

安非他酮缓释片治疗海洛因依赖者稽延性戒断症状的临床研究

目的对照观察安非他酮缓释片联合纳曲酮片治疗海洛因依赖者稽延性戒断症状疗效和安全性。方法将84例海洛因依赖患者随机分成两组,研究组采用安非他酮缓释片联合纳曲酮片治疗,对照组单纯使用纳曲酮片,观察疗程为8周。采用心理渴求量表(PCS)、稽延性戒断症状量表(PWSS)、和汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)评定疗效。治疗前、后分别对患者行心电图、肝功能、肾功能等检查以评价安全性。结果治疗8周末,两组PCS、PWSS、HAMA、HAMD评分均较治疗前有显著下降(P0.01),研究组PCS、PWSS、HAMA和HAMD评分较对照组下降更显著(P0.01)。研究组和对照组的血常规、心电图、肝功能、肾功能两组比较差异无统计学意义(P0.05)。结论安非他酮缓释片能有效的缓解海洛因依赖患者在预防复吸治疗过程中的焦虑、抑郁等情绪,对海洛因依赖患者脱毒后的稽延性戒断症状可以很好改善。安非他酮缓释片联合纳曲酮治疗海洛因依赖患者稽延性戒断症状是一种安全、有效的治疗方案。     

阿片受体拮抗剂在精神科的应用

本文介绍了国外近五年来阿片受体拮抗剂纳络酮、纳曲酮在精神科领域中的临床应用，特别是在酒精、药物依赖的治疗与预防，儿童孤独症、自伤行为的治疗等一些新进展。     

纳曲酮对小鼠脾淋巴细胞增殖的影响

考察阿片受体拮抗剂纳曲酮对小鼠脾淋巴细胞增殖的影响。方法 应用＾３Ｈ－ＴｄＲ掺入法检测纳曲酮对淋巴细胞和ＩＬ－２反应细胞增殖反应的作用。结果（１）纳曲酮和淋巴细胞，ＣｏｎＡ或ＩＬ－２同时反应，其对淋巴细胞增殖无明显抑制作用。（２）纳曲酮预处理淋巴细胞几小时后，对淋巴细胞增殖具有明显的抑制作用。     

阿片受体拮抗剂在精神科的应用

本文介绍了国外近五年来阿片受体拮抗剂纳络酮，纳曲酮在精神科领域中的临床应用，特别是在酒精，药物依赖的治疗与预防，儿童孤独症，自伤行为的治疗等一些新进展。     

盐酸纳曲酮对阿片类依赖脱毒后维持治疗的临床观察

目的　评价纳曲酮对阿片类依赖者脱毒后维持治疗的可行性。方法　采用二阶段法,在常规脱毒治疗后１ 周使用纳曲酮维持,疗程观察６ 个月,评价①服用纳曲酮维持率;②服用纳曲酮后再吸阿片类的体验;③对纳曲酮的总体评价。结果　４３ 例入组观察,２０ 例（４６５ ％ ） 完成６ 个月的疗程,完成疗程随访的患者对阿片类渴求程度明显下降,其评分由入组前８２３ ±３ ．４ 降至２ ．７５ ±４ ．６ 。结论　纳曲酮对阿片类依赖患者脱毒后的维持治疗疗效肯定,不良反应能耐受,安全性较好。     

纳曲酮对小鼠脾淋巴细胞增值的影响

目的考察阿片受体拮抗剂纳曲酮（naltrexone）对小鼠脾淋巴细胞增殖的影响。方法应用3H-TdR掺入法检测纳曲酮对淋巴细胞和IL-2反应细胞（ConA活化的脾细胞）增殖反应的作用。结果（1）纳曲酮（10-4mol／L）和淋巴细胞、ConA或IL-2同时反应，其对淋巴细胞增殖无明显抑制作用（P＞0．05）。（2）纳曲酮（10(-4)mol／L）预处理淋巴细胞几小时后，对淋巴细胞增殖具有明显的抑制作用（P＜0．01）。3）纳曲酮的浓度变化对两种细胞的抑制作用不同；对淋巴细胞的抑制作用随浓度（10(-6)～10(-4)mol／L）的增加而增强（P＜0．05，P＜0．01），低浓度（＜10(-7)mol／L）时抑制作用消失；对IL-2反应细胞，在本组实验药物的所有浓度下（10(-8)～10(-4)）均有抑制作用（P＜0．01）。结论阿片受体拮抗剂纳曲酮对小鼠脾淋巴细胞的增殖有明显的抑制作用，而且这种抑制作用较为缓慢、强烈而持久。     

盐酸纳曲酮治疗酒依赖患者复饮

酒依赖的防复饮治疗是目前医学上的难题，盐酸纳曲酮是为数不多的酒依赖防复饮药物之一，本文综述了纳曲酮在酒依赖治疗方面的疗效、安全性、作用机制及不良反应等，以期为酒依赖患者彻底解除酒瘾提供有力的帮助。     

长效纳曲酮缓释剂植入治疗阿片依赖渴求的线索诱发事件相关电位评价**☆

目的：在前期成功研制出长效纳曲酮缓释剂植入剂型的基础上，应用线索诱发事件相关电位观察长效纳曲酮缓释剂植入治疗阿片依赖者心理渴求的神经心理学作用。 方法：①对象和分组：阿片依赖综合征患者自湖北、湖南和广东等地，包括两个不同戒毒方式的组，即长效纳曲酮缓释剂治疗组和强制戒毒组，同时设计一个未戒毒的阿片依赖对照组和一个健康对照组。②方法：采用事件相关电位记录被试由图片的情绪内涵激发的脑内电活动，无需被试对所观察的图片作出外显反应，现场采集记录其观看药物相关情景线索图片和中性图片时产生的脑电事件相关电位波形。 结果：①长效纳曲酮缓释剂治疗组各波形的潜伏期和波幅已接近健康对照组（P > 0.05）；而强制戒毒组和阿片依赖对照组的P200潜伏期与健康对照组差异非常显著（P < 0.01）；而且，与未治疗的阿片依赖对照组比较，强制戒毒组没有表现出显著的P200正常化的效应。②源定位分布表明，观察药物相关线索图片P200的源发生点健康对照组在中脑导水管周围灰质，长效纳曲酮缓释剂治疗组在扣带回后部，强制戒毒者在内侧前额叶皮质，阿片依赖对照组在大脑前额叶皮质。 结论：①与强制戒毒比较，长效纳曲酮缓释剂植入能降低心理渴求，使患者的心理状况更好。②长效纳曲酮缓释剂治疗能有效改善阿片药物依赖者的神经系统功能，抑制其心理渴求的高级神经活动。     

立体定向毁损术治疗海洛因心理依赖(18个月随访分析)

目的探讨立体定向毁损治疗海洛因心理依赖手术疗效及安全性。方法应用立体定向手术治疗海洛因心理依赖58例,并于术后3个月、18个月进行随访,采用上门家访或电话随访。随访内容包括复吸与否、生活工作情况、有无神经精神功能障碍。上门家访时进行了渴求量表、欲望量表、记忆、智商、人格等精神心理测验。结果未复吸36例,复吸16例,失访6例,操守率为62.06%。记忆、智商、性欲比术前提高,无人格、行为等精神障碍。结论立体定向手术治疗海洛因心理依赖疗效明显优于常规药物戒毒治疗,是消除吸毒者心理依赖、摆脱毒瘾的有效方法,且对智力、欲望、思维、人格无明显负面影响。     

立体定向术治疗海洛因成瘾临床随访观察

目的:了解立体定向术治疗海洛因成瘾者后3年的复吸率和不良反应。方法:对接受脑立体定向术治疗的海洛因成瘾者215例,运用门诊随访、信访、电话随访和登门拜访的方式,采取统一随访表、家属问卷和心理卫生调查表进行随访,了解患者出院后的病情信息。结果:术后3年有75例患者复吸,未复吸者107例,失随访32例,1例在手术3年后车祸去世。未复吸者中64例参加工作,出院后结婚20例,生子女24例,不吸烟者7例,目前存在睡眠障碍16例,情绪不稳、行为幼稚者4例,记忆力下降12例,自感性功能下降1例。结论:立体定向手术治疗海洛因成瘾是有效的,不良反应较小,有进一步研究的价值。     

Assessing the Role of Corticothalamic and Thalamo-Accumbens Projections in the Augmentation of Heroin Seeking in Chronically Food-Restricted Rats

Drug addiction is a chronic disorder characterized by compulsive drug seeking, and involves repetitive cycles of compulsive drug use, abstinence, and relapse. In both human and animal models of addiction, chronic food restriction increases rates of relapse. Our laboratory has reported a robust increase in drug seeking following a period of withdrawal in chronically food-restricted rats compared with sated controls. Recently, we reported that activation of the paraventricular nucleus of the thalamus (PVT) abolished heroin seeking in chronically food-restricted rats. However, the precise inputs and outputs of the PVT that mediate this effect remain elusive. The goal of the current study was to determine the role of corticothalamic and thalamo-accumbens projections in the augmentation of heroin seeking induced by chronic food restriction. Male Long–Evans rats were trained to self-administer heroin for 10 d. Next, rats were removed from the self-administration chambers and were subjected to a 14 d withdrawal period while sated (unlimited access to food) or mildly food-restricted (FDR). On day 14, rats were returned to the self-administration context for a 3 h heroin-seeking test under extinction conditions during which corticothalamic and thalamo-accumbens neural activity was altered using chemogenetics. Surprisingly, chemogenetic activation or inhibition of corticothalamic projections did not alter heroin-seeking behavior. Chemogenetic activation of thalamo-accumbens shell, but not core, projectors attenuated heroin seeking in FDR rats. The results indicate an important role for the PVT to nucleus accumbens shell projections in the augmentation of heroin seeking induced by chronic food restriction.SIGNIFICANCE STATEMENT Relapse to heroin use is one of the major obstacles in the treatment of opiate addiction. Triggers for relapse are modulated by environmental challenges such as caloric restriction. Elucidating the brain mechanisms that underlie relapse is critical for evidence-based treatment development. Here we demonstrate a critical role for the input from the paraventricular thalamus (PVT), a hub for cortical, sensory, and limbic information, to the nucleus accumbens shell (an area known to be important for reward and motivation) in the augmentation of heroin seeking in food-restricted rats. Our findings highlight a previously unknown role for the PVT in heroin seeking following a period of abstinence.     

Developing a vaccine against multiple psychoactive targets: a case study of heroin

Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. Currently approved heroin addiction medications include drugs that bind at the same receptors (e.g. opioid receptors) occupied by heroin and/or its metabolites in the brain, but undesired side effects of these treatments, maintenance dependence and relapse to drug taking remains problematic. A vaccine capable of blocking heroin's effects could provide an economical, long-lasting and sustainable adjunct to heroin addiction therapy without the side effects associated with available treatment options. Heroin, however, presents a particularly challenging vaccine target as it is metabolized to multiple psychoactive molecules of differing lipophilicity, with differing abilities to cross the blood brain barrier. In this review, we discuss the opiate scaffolding and hapten design considerations to confer immunogenicity as well as the specificity of the immune response towards structurally similar opiates. In addition, we detail different strategies employed in the design of immunoconjugates for a vaccine-based therapy for heroin addiction treatment.     

双侧扣带回毁损术治疗海洛因精神依赖

目的探讨双侧扣带回毁损术治疗海洛因精神依赖的临床疗效和可能的作用机制。方法对4例海洛因成瘾病人术前行美沙酮脱毒治疗;之后采用MRI定位立体定向扣带回毁损术,在双侧扣带回前中1/3交界处射频制造毁损灶;术后进行康复治疗和帮助其回归社会。结果均顺利接受了治疗全过程,无明显并发症。随访半年,2例病人无复吸;1例术后1个月内偶有复吸,其后无复吸;另1例病人术后4个月起复吸。操守较好者焦虑、抑郁等精神症状明显缓解,海洛因渴求程度明显减轻。结论双侧扣带回毁损术治疗海洛因精神依赖,安全、近期有效;可能与精神症状的缓解有关,长期效果有待随访。     

Anticraving medications for relapse prevention: a possible new class of psychoactive medications

Psychiatrists have gradually developed a list of medications that are effective in the treatment of addictive disorders. Although alcoholism has received the most attention, nicotine, heroin, and cocaine have all been shown to be influenced by heredity. Of course, the immediate goal is the reduction of drug craving and the prevention of relapse to compulsive drug taking. A medication that can aid in the maintenance of the opiate-free state is naltrexone, a specific opiate antagonist. Naltrexone is also a good example of an anticraving medication used in the treatment of alcoholism. Clinicians currently have two types of medication to aid in the treatment of tobacco use disorder, arguably the most important addiction. Bupropion and nicotine replacement can be given in a coordinated fashion to provide the best available results. At present, no medication is approved by the Food and Drug Administration for the indication of cocaine addiction. Recently, however, five different medications, already approved for other purposes, have been found to be effective among cocaine addicts. Despite clinical trials that show benefit, anticraving medications are not well known and are underused by clinicians. Addiction is a heterogeneous condition, with variability in reactivity to the drug of abuse and to the medications available to treat it. Recent developments in pharmacogenetics may result in improved selection of medications based on genotype.     

The effects of heroin administration and drug cues on impulsivity

Drug addiction is a chronic relapsing disorder characterized by compulsive drug seeking and continued use despite negative consequences. Behavioral impulsivity is a strong predictor of the initiation and maintenance of drug addiction. Preclinical data suggest that heroin may exacerbate impulsive characteristics in an individual but this has yet to be assessed in clinical samples. The current secondary data analysis sought to investigate the effects of heroin on impulsivity along with the effects of exposure to drug cues. Using the current data set, we also tentatively assessed the etiological relationship between impulsivity and heroin abuse. Sixteen heroin-dependent participants were recruited to complete Immediate Memory Task/Delayed Memory Task (IMT/DMT) and GoStop tasks following repeated heroin administration, following acute heroin administration, and following a drug cue exposure session. Four preceding days of active heroin availability, compared to four preceding days of placebo drug availability, increased impulsivity assessed using the IMT and DMT. Presentation of drug cues similarly acted to increase impulsivity assessments on all three tasks. It also appears that heavier users were more susceptible to the influence of drug cues on impulsivity. The present study represents a step toward a more comprehensive understanding of the interaction between opioid abuse and impulsivity. A better understanding of these factors could provide critical insight into the maintenance of heroin use and relapse.     

Relapse Risk Factors in Heroin Addicts Treated with Naltrexone and Naltrexone-Behavioural Psychotherapy

To construct a successful treatment model for heroin addiction, it is important to define factors that contribute to relapse. In this translational ambidirectional cohort study, we evaluated 2 groups of heroin addicts that underwent the same therapeutic procedures with different outcomes (133 abstainers and 56 relapsers). The study found a new variable, “relapse marker”, defined by the synergy of the following factors: (a) non-use of tramadol before treatment (p < 0.0005), (b) absence of sense of loss of control over behaviour as a motive for treatment initiation (p = 0.048), (c) use of benzodiazepines in recovery (p < 0.0005), (d) substituting heroin addiction with gambling (p < 0.009), e) younger age (p = 0.012), and (f) explicit parental demand as a treatment motive (p = 0.040). This study reports a mathematical model that predicts relapse and inability to sustain stable abstinence as an outcome of heroin addiction treatment.     

Chronic naltrexone suppresses platelet aggregation induced by adrenaline and 5-hydroxytryptamine in former heroin addicts

Summary Naltrexone, an opioid receptor antagonist, is used as an adjunct in the treatment of opiate addiction. In former heroin addicts, long-term treatment with naltrexone (350 mg/week for 5 months) resulted in suppression of adrenaline and 5-hydroxytryptamine (5-HT)-induced platelet aggregation. The results demonstrate that sustained blockade of opioid receptors can impair the functional expression of ₂-adrenoceptors and 5-HT₂ receptors in human platelets. These findings may have negative clinical implications in the treatment of opiate addiction with naltrexone.     

男女海洛因依赖者成瘾严重程度的比较

目的：了解男女海洛因依赖者成瘾严重程度的差异,为针对不同性别海洛因依赖者制定干预措施提供依据。方法：采用自制个案调查表和成瘾行为严重度指数量表（addiction severity index,ASI）对199例男性和239例女性海洛因依赖者进行评估,比较不同性别海洛因依赖者ASI量表中各维度分值的差异。结果：女性依赖者ASI中因子4（药物使用）评分平均为（0.52±0.28）分和因子7（精神健康状况）平均（0.15±0.24）分显著高于男性的（0.43±0.34）分和（0.08±0.19）分（P〈0.05或P〈0.01）;男性依赖者因子5（法律状况）评分平均（0.07±0.13）分高于女性的（0.03±0.10）分（P〈0.01）。将年龄、首次吸毒年龄及吸毒时间与ASI分量表进行偏相关分析发现,年龄（r=-0.182）、吸毒时间（r=0.158）与因子4（药物使用）分数存在显著相关;进一步相关分析发现,年龄与吸毒时间存在显著相关（r=0.364,P〈0.01）。结论：男女海洛因依赖者在成瘾行为严重程度方面存在差异,临床治疗与康复过程中应针对不同性别特征制定个体化的治疗方案以满足不同性别患者的需求。