伏隔核胆碱能神经元在线索诱导的海洛因复吸中的作用

目的 比较不同的二醋吗啡(海洛因)戒断时间对于环境线索(CC)或条件性线索(CS)诱导的大鼠复吸行为的影响,并探讨伏隔核胆碱能神经元可能的调节作用。方法 SD大鼠进行海洛因自身给药训练,每天4 h, 连续14 d,建立海洛因自身给药模型。随后置饲养笼自然戒断,随机分为第1天CC(d 1CC)组、d 14 CC组、d 1 CC+CS组和d 14 CC+CS组。测定有效鼻触次数,免疫组化双标法检测伏隔核(NAc)壳部和NAc核部胆碱乙酰转移酶(ChAT)与c-Fos共表达的水平。结果 海洛因自身给药大鼠随着戒断时间延长,CC诱导的海洛因觅药行为的恢复,即d 14 CC组与d 1 CC组比较,有效鼻触数明显增加(P<0.05);海洛因自身给药大鼠相同时间戒断后,不同线索诱导的海洛因觅药行为的恢复,即d 1 CC+CS组与d 1 CC组比较,以及d 14 CC+CS组与d 14 CC组比较,有效鼻触数均明显增加(P<0.05)。同时,在NAc壳部,与d 1 CC组比较,d 14 CC组大鼠的ChAT, c-Fos, ChAT+c-Fos免疫阳性细胞数分别为114±9,15±6,(13±5)个,ChAT+c-Fos占ChAT百分比为(11±4)%,明显增加(P<0.05);在NAc壳部和NAc核部,与d 1 CC组比较,d 1 CC+CS组大鼠的上述表达没有差异;在NAc壳部和NAc核部,与d 14 CC组比较,d 14 CC+CS组的ChAT, ChAT+c-Fos免疫阳性细胞数均明显减少(P<0.05)。结论 随着戒断时间的延长,CC诱导的海洛因觅药行为的增加,可能与NAc壳部胆碱能神经元的激活增多有关;而CS诱导的海洛因觅药行为的增加,可能与NAc壳部和核部胆碱能神经元的激活减少有关。     

曲唑酮联合心理治疗对海洛因依赖者脱毒期的疗效观察

目的:观察曲唑酮联合心理治疗对海洛因依赖者脱毒期间的临床疗效,探讨其在改善成瘾者心理状况、防复吸等方面的作用.方法:120例接受丁丙诺非维持治疗(BMT)的海洛因依赖者随机分为对照组、曲唑酮组、心理治疗组、曲唑酮+心理治疗组,每组30例.治疗前后,采用稽延性症状评定量表、汉密顿焦虑量表(HAMA)、汉密顿抑郁量表(HAMD)、海洛因渴求评定量表、自我控制量表分别对患者进行问卷调查.结果:曲唑酮和心理治疗均能改善海洛因依赖者脱毒期间的焦虑、抑郁症状;与曲唑酮组、心理治疗组比较,曲唑酮联合心理治疗在改善焦虑、抑郁症状方面疗效更显著.心理治疗还可降低渴求、增加自我控制能力,而曲唑酮在降低渴求、增加自我控制能力方面则无明显疗效.结论:曲唑酮联合心理治疗可有效控制海洛因依赖者脱毒期间焦虑、抑郁症状,并能增加海洛因依赖者自我控制能力,降低渴求,对预防复吸具有积极作用.     

Hypothalamic-pituitary-adrenal axis and sympatho-adreno-medullary responses during stress-induced and drug cue-induced cocaine craving states

Rationale Environmental stimuli associated with cocaine are known to elicit drug craving and increase the likelihood of relapse. However, the psychobiological changes that occur with exposure to these stimuli and in episodes of drug craving are not well understood. This study examined the response of brain stress circuits to environmental stimuli that are known to increase cocaine craving in cocaine dependent individuals.Methods Fifty-four treatment seeking cocaine dependent individuals, who were admitted to an inpatient treatment research unit for 2–4 weeks, participated in three laboratory sessions. Subjects were exposed to a brief 5-min guided imagery procedure that involved imagining a recent personal stressful situation, a drug-related situation and a neutral-relaxing situation, one imagery per session presented in random order. Subjective ratings of craving and anxiety, cardiovascular measures, and plasma levels of adrenocorticotrophic hormone (ACTH), cortisol, prolactin, norepinephrine (NE) and epinephrine (EPI) were assessed.Results Exposure to stress and to drug cues each resulted in significant increases in cocaine craving and subjective anxiety, pulse rate, systolic blood pressure, ACTH, cortisol, prolactin and NE as compared to the response to neutral imagery. In addition, stress imagery also increased diastolic blood pressure and plasma EPI as compared to responses to the drug cue imagery and neutral-relaxing imagery.Conclusions The findings indicate a significant activation of the CRF-HPA axis and noradrenergic/sympatho-adreno-medullary (SAM) system response during stress-induced and drug cue induced cocaine craving states in cocaine dependent individuals. The role of stress system activation in cocaine craving and in cocaine use is discussed.     

Prescribing drug of choice to illicit heroin users: The experience of a U.K. community drug team

Functioning across several life domains, in the first cohort of illicit heroin users to be prescribed injectable diamorphine (pharmaceutical heroin) as an adjunct to treatment within a community drugs service, was assessed in a cross-sectional study with a 6-month follow-up. Case-control matching procedures were employed to compare outcomes in this group with an oral methadone-prescribed sample, attending different clinics within the same community service and geographical locale. The Heroin Prescribed (HP) group manifested lower levels of psychopathology and showed greater retention in treatment. Although reduced, illicit heroin misuse was not eliminated; the use of other illicit substances was comparable between groups but significantly more of the HP group were using illicit cocaine. Although no differences in current physical health were apparent, the sharing of used injecting equipment was reported only in the MP group. Criminal activity appeared significantly reduced, but not eliminated, in the HP group. Implications for prescribing practice are discussed.     

The relationship between initial route of heroin administration and speed of transition to daily heroin use

Introduction and Aims. The effect of heroin administration route on speed of transition to regular use is unknown. This paper aims to determine whether the speed of transition from initiation of heroin use to daily heroin use differs by route of administration (injecting, chasing/inhaling or snorting). Design and Methods. Privileged access interviewer survey of purposively selected sample of 395 current people who use heroin (both in and not in treatment) in London, UK (historical sample from 1991). Data on age and year of initiation, time from initiation to daily use and routes of administration were collected by means of a structured questionnaire. Generalised ordered logistic models were used to test the relationship between route of initial administration of heroin and speed of transition to daily heroin use. Analyses were adjusted for gender, ethnicity, daily use of other drug(s) at time of initiation, year of initiation and treatment status at interview. Results. After adjustment, participants whose initial administration route was injecting had a 4.71 (95% confidence interval 1.34–16.5) increase in likelihood of progressing to daily use within 1–3 weeks of initiation, compared to those whose initial administration route was non‐injecting. Discussion and Conclusions. The speed of transition from first use to daily heroin use is faster if the individual injects heroin at initiation of use. Those who initiate heroin use through injecting have a shorter time frame for intervention before drug use escalation. [Hines LA, Lynskey M, Morley KI, Griffiths P, Gossop M, Powis B, Strang J. The relationship between initial route of heroin administration and speed of transition to daily heroin use. Drug Alcohol Rev 2017;00:000‐000]     

Combined effects of law enforcement and substitution treatment on heroin mortality

Introduction and Aims. To explore the combined effects of street‐level law enforcement and substitution treatment programs on drug‐related mortality, taking into account prevalence of heroin use and changes in injecting behaviour. Design and Methods. Time trend analysis using annual police reports and case register data of opioid substitution treatments in Switzerland, 1975–2007. Results. Drug‐related mortality increased during times of more intense street‐level law enforcement [odds ratio (OR) 1.32, 95% confidence interval (95% CI) 1.15–1.51], and the number of drug‐related deaths predicted the number of heroin possession offences 2 years later (r = 0.97, P < 0.001). Substitution treatment had a protective effect on drug‐related mortality (OR 0.23, 95% CI 0.18–0.30). Surprisingly, the number of drug‐related deaths was substantially biased by an oscillation period of 14 years (OR 1.24, 95% CI 1.17–1.32). Discussion and Conclusions. Our analysis revealed that the amount of police resources allocated to law enforcement was determined rationally, however, on biased grounds and with untoward consequences. Substitution treatment of heroin users reduced drug‐related mortality in the long run, but different factors masked its impact for several years. Therefore, the introduction—or the expansion—of opioid substitution treatment programs should not be promoted with the argument of an immediate reduction of drug‐related deaths in a country.[Nordt C, Stohler R. Combined effects of law enforcement and substitution treatment on heroin mortality. Drug Alcohol Rev 2010]     

Australian reports into drug use and the possibility of heroin maintenance

Official Australian reports into drug use reveal a high level of agreement over the nature of drug use and the problems associated with drug use. We examine the lines of argument which make up the shared approach of past reports into drugs, and assess to what degree the connections between these lines of argument are changing. This assessment reflects on the possibility of arguing that heroin should be made available for the treatment (including maintenance) of heroin-dependent users. This paper is derived from a report prepared for a feasibility study which examined whether or not heroin should be made available in the Australian Capital Territory in a controlled manner. After a close reading of a number of official reports, we conclude that it is possible to argue that heroin should become available.     

Changes in the initiation of heroin use after a reduction in heroin supply

Increasing heroin use in Australia over the past 30 years has been associated with a decline in the age of initiation to heroin use. The 2001 Australian heroin shortage was used to assess the effects of a reduction in heroin supply on age of initiation into heroin injecting. Data collected from regular injecting drug users (IDU) over the period 1996 - 2004 as part of the Australian Illicit Drug Reporting System were examined for changes in self-reported age of first heroin use after the onset of the heroin shortage. Estimates were also made of the number of young people who may not have commenced injecting heroin during the heroin shortage. The proportion of IDU interviewed in the IDRS who were aged ≤24 years decreased from 46% in 1996 to 12% in 2004, with the most marked drop in 2001, the year in which there was an abrupt and marked reduction in heroin availability. Of those who reported first injecting between 1993 and 2000, similar proportions reported heroin and amphetamine as the first drug injected. After 2000, methamphetamine was the drug most often reported as being the first injected. Estimates suggested that between 2745 and 10 560 young people may not have begun to inject heroin in 2001 as a result of reduced heroin supply. If around one in four of these young users had progressed to regular or dependent heroin use, then there may have been a reduction of between 700 and 2500 dependent heroin users. There was an increase in amphetamine injecting but it is unclear to what extent any reduction in heroin injecting has been offset by increased amphetamine injecting. Reduced heroin availability probably resulted in a reduction in the number of new heroin injectors in Australia. Efforts need to be made to reduce the chances that young people who have initiated methamphetamine injecting do not move to heroin injecting when the heroin supply returns. [Day C, Degenhardt L, Hall W. Changes in the initiation of heroin use after a reduction in heroin supply. Drug Alcohol Rev 2006;25:307 - 313]     

An exploration of alcohol use severity and route of drug administration among persons that use heroin and cocaine

ABSTRACT

Background: Alcohol use is prevalent among populations of persons that use illicit drugs. Problematic alcohol use among persons that use heroin and cocaine has been associated with poor treatment adherence, abstinence maintenance, and mental health concerns. Fully exploring how alcohol use severity interacts with route of administration (ROA) may be of notable importance in development of treatment protocols for persons that use heroin and cocaine. Methods: Data from a neurological and sociobehavioral assessment of risk factors among injection and noninjection drug users known as the NEURO-HIV Epidemiologic Study was used in the analyses. Participants (N = 551) included those who reported their level of past-30-day alcohol use and past-6-month heroin and cocaine use. Results: Multiple logistic regression analyses found that both problematic and moderate alcohol users were significantly less likely than abstainers to report injecting heroin and cocaine. Both problematic and moderate alcohol users were significantly more likely than abstainers to snort substances. Conclusions: Alcohol use may play a role in promoting or impeding the use of substances through certain ROAs. Treatment protocols that transition persons that use injection heroin and cocaine to noninjection use of these substances may be used in conjunction with treatments that reduce alcohol consumption as a means to reduce noninjection drug use.     

阳泉市3年海洛因非法使用情况研究

目的了解阳泉市海洛因滥用情况,并探讨了相应的措施。方法统计2003年1月-2005年12月期间由于海洛因的非法使用而被阳泉市公安局禁毒处拘留、并强制戒毒3个月~6个月的犯罪人员的案宗,内容包括海洛因非法使用者的年龄、性别、职业、文化程度。用EXCEL对数据进行统计分析并进行t检验。结果阳泉市海洛因非法使用以男性为主体,占83.3%。平均年龄(29±6)岁。20~29岁与30~39岁年龄段为其好发年龄。多为初中文化程度,达91.4%。多为无业人员,达到91.7%。复吸总人数占总样本人数的13.4%。女性复吸人员平均年龄小于总样本女性平均年龄。结论阳泉市海洛因非法使用以中青年男性、低学历、无业者为主。女性复吸低龄化。禁毒工作重在预防。     

Imaging stress- and cue-induced drug and alcohol craving: association with relapse and clinical implications

Stress- and drug-related cues are major factors contributing to high rates of relapse in addictive disorders. Brain imaging studies have begun to identify neural correlates of stress and drug cue-induced craving states. Findings indicate considerable overlap in neural circuits involved in processing stress and drug cues with activity in the corticostriatal limbic circuitry underlying both affective and reward processing. More recent efforts have begun to identify the relationships between neural activity during stress and drug cue exposure and drug relapse outcomes. Findings suggest medial prefrontal, anterior and posterior cingulate, striatal and posterior insula regions to be associated with relapse outcomes. Altered function in these brain regions is associated with stress-induced and drug cue-induced craving states and an increased susceptibility to relapse. Such alterations can serve as markers to identify relapse propensity and a more severe course of addiction. Efficacy of pharmacological and behavioral treatments that specifically target stress and cue-induced craving and arousal responses may also be assessed via alterations in these brain correlates. [Sinha R, Li C-SR. Imaging stress- and cue-induced drug and alcohol craving: association with relapse and clinical implications. Drug Alcohol Rev 2007;26:25 - 31]     

Changes in patterns of drug use among injecting drug users following changes in the availability of heroin in New South Wales, Australia

The aim of this study was to examine changes in drug use patterns among groups of injecting drug users (IDU) who remained in the drug market during a period of reduced heroin availability in NSW, Australia. Cross-sectional data collected from regular IDU interviewed as part of the NSW Illicit Drug Reporting System (IDRS) between 1996 - 2003 were analysed. Drug use patterns, reported drug availability and price were assessed. There was a marked decrease in the frequency of heroin use during the period of reduced availability in 2001, with some increase in 2002 and 2003. Heroin availability and frequency of use have not returned to levels reported prior to 2001; however; even at the peak of the reduction in supply, users continued to access heroin. There was a significant shift among IDU from heroin to cocaine during 2001, which subsequently reversed. The availability of cocaine has fluctuated in recent years, but the price has remained stable. The price of heroin appeared to be more responsive to market fluctuations, and co-varied with heroin availability. IDU used cocaine when heroin was less available; however, patterns of cocaine use were not maintained. The frequency of heroin use remained lower, which may be indicative of a less consistent supply, increased price or increased numbers of IDU entering treatment. The reduced supply of heroin in 2001 highlighted the adaptable nature of IDU patterns of use, indicative of the need for a commensurate treatment response. It also highlighted the importance of the ongoing monitoring of drug trends in Australia. [Roxburgh A, Degenhardt L, Breen C. Changes in patterns of drug use among injecting drug users following changes in the availability of heroin in New South Wales, Australia. Drug Alcohol Rev 2004;23:287-294]     

A nationwide survey of American alcohol and drug craving assessment and treatment practices

A four-page paper survey was mailed to 500 randomly-selected substance abuse treatment agencies listed in a national directory to evaluate how often specific methods are employed to assess and treat craving in American substance abuse agencies. Of 426 eligible agencies, 149 (35%), located in 41 states, returned 152 usable replies. Although counselors regularly assessed craving during intake evaluations, they rarely used published self-report questionnaires. Almost one-half of respondents made craving a target of treatment with at least a majority (and sometimes all) of their clients, and only 5% of respondents reported never making craving a target of treatment. A variety of interventions are employed to address craving, including coping skills training, encouraging clients to avoid/leave situations where craving occurs, and providing clients with education about craving. We recommend additional professional education and training to familiarize counselors with standardized craving instruments and exposure interventions that hold promise to ameliorate craving.     

大鼠丘脑和下丘脑在线索诱导的海洛因复吸中的作用

目的研究丘脑室旁核(PVT)和下丘脑外侧区(LH)在环境线索(CC)或条件性线索(CS)诱导的大鼠海洛因复吸中的作用。方法 SD大鼠进行生理盐水(对照组)或海洛因的自身给药训练,随后自然戒断,海洛因戒断大鼠随机分成模型组、CC组和CC+CS组;在戒断d 14,对照组和CC组均以环境线索诱导、CC+CS组以环境线索联合条件性线索诱导测定海洛因觅药行为的恢复,模型组不测定;利用免疫组化法检测所有组别大鼠PVT和LH脑区c-Fos蛋白的表达。结果环境线索或条件性线索均能够诱导大鼠海洛因觅药行为的恢复;环境线索诱导大鼠海洛因觅药恢复时PVT脑区c-Fos免疫阳性表达明显增加(P<0.01);而LH脑区c-Fos免疫阳性表达在环境线索或条件性线索诱导大鼠海洛因觅药恢复时均明显增加(P<0.01)。结论 PVT参与环境线索诱导的大鼠海洛因复吸过程,而LH同时参与环境线索或条件性线索诱导的大鼠海洛因复吸。     

Identifying viable theoretical frameworks with essential parameters for real-time and real world alcohol craving research: a systematic review of craving models

Background: Substance use is known to be episodic, dynamic, complex, and highly influenced by the environment, therefore a situational and momentary focus to alcohol craving research is appropriate. Current advances in mobile and wearable technology provide novel opportunities for craving research. However, the lack of consensus within craving theory impedes the identification and prioritization of parameters to be monitored. The aim of this study is to critically review current craving models in order to determine viable theoretical frameworks of alcohol craving and its essential parameters.

Methods: Eighteen models of craving were reviewed by applying a literature search with a five-step strategy that accounted for the momentary nature of craving and included a snowballing search and a key term extraction algorithm. Based on this review, multiple decision criteria were defined upon which to evaluate the models.

Results: Six models for alcohol craving were supported by sufficient empirical research to be eligible. The inferences drawn on these six models resulted in three decision criteria: the model should (1) incorporate negative affect as a predictor of relapse; (2) explain that dependent drinkers have a higher attentional bias towards alcohol cues than nondependent drinkers; (3) incorporate increased risk of relapse with heightened stress levels.

Conclusions: The affective processing model of negative reinforcement, the cognitive processing model, the incentive sensitization theory of addiction and the theory of neural opponent motivation are classified as viable theoretical frameworks, resulting in negative affect and stress as relevant parameters to include in real-time craving monitoring research.     

Reinstatement of cocaine seeking in 129X1/SvJ mice: effects of cocaine priming,cocaine cues and food deprivation

RATIONALE AND OBJECTIVES: The mechanisms underlying relapse to cocaine seeking induced by exposure to priming cocaine injections, cues associated with cocaine self-administration and environmental stressors have been studied in rats. Here we describe a reinstatement method for studying relapse to cocaine seeking in mice, a suitable species for studying the effect of genetic manipulations such as gene knockout or gene over-expression on compulsive drug use.METHODS: Male mice of the 129X1/SvJ strain were trained for 14-16 days to self-administer cocaine (0.75 mg/kg/infusion; 4 h/day; fixed-ratio-1 schedule of reinforcement; infusions were paired with a light-tone compound cue). Next, the lever-pressing behavior was extinguished by removing the cocaine syringes in the presence (Exps. 1 and 3) or absence (Exp. 2) of the cocaine cue. Subsequently, tests for reinstatement were conducted after exposure to priming injections of cocaine (0, 1.5, 3.0 and 6.0 mg/kg, IV; Exp. 1), response-contingent presentations of the cocaine-associated cue (Exp. 2), or food deprivation stress (1 and 22 h; Exp. 3).RESULTS: The effect of cocaine priming on reinstatement was modest and was only observed at the highest dose tested. On the other hand, reinstatement of cocaine seeking was observed following exposure to the cocaine-associated cue and food deprivation stress.CONCLUSIONS: The present data suggest that factors contributing to relapse to drugs can be studied in the reinstatement model using the common 129X1/SvJ mouse inbred strain.     

海洛因瘾康复期使用纳曲酮防止复吸100例

目的：观察盐酸纳曲酮防止海洛因依赖者戒毒后复吸疗效。方法：ｍｏ１～２每日口服纳曲酮片１５～２０ｍｇ，ｍｏ３～４服１０～１５ｍｇ，ｍｏ５～６服５～１０ｍｇ，６ｍｏ为一个疗程。结果：３ｍｏ复吸率为４２％，６ｍｏ复吸率为７２％，显效率为４５％，有效率为７４％。结论：服药后可明显减轻海洛因依赖者对毒品渴求感和焦虑症状，降低复吸率。纳曲酮本身无依赖性，副作用轻微。     

Gender related effects of heroin abuse on the simple reaction time task

Accumulated studies have demonstrated that there are serious negative consequences of drug abuse, especially the impairment of central nervous system (CNS) function. The simple reaction time (SRT) is the simplest model of measuring the function of the CNS. The purpose of the present study is to examine whether the SRT is affected by heroin abuse and whether such drug effect, if exists, is gender related. We found significant slowing of the SRT in both male and female heroin dependent patients at 1-3 months from withdrawal. However, the SRT slowing remitted after 3 months of abstinence in heroin dependent males but not in females. Our results suggested that the SRT is slowed by heroin abuse and such slowing is gender related.     

Carbon and nitrogen isotopic analysis of morphine from opium and heroin samples originating in the four major heroin producing regions

The forensic analysis of stable isotopes is a valuable tool to geo-source natural or semisynthetic drugs such as cocaine and heroin. The present study describes a novel methodology to isolate morphine from opium for isotopic analysis. Furthermore, this isotopic data from regional sources is corroborated with morphine data obtained from seized heroin (deacetylated to morphine) from the same regions. All five primary alkaloids of opium, namely, morphine, codeine, thebaine, noscapine, and papaverine, were quantified using high performance liquid chromatography with photodiode array (PDA) detector before the preparative experiment to gather a complete major alkaloidal profile. Morphine fractions of authentic opium submissions from Mexico, South America, Southwest Asia, and Southeast Asia were isolated and collected using preparative high performance liquid chromatography, and the collected morphine samples were subsequently analyzed by isotope ratio mass spectrometry. Carbon and nitrogen isotope data are presented. The data demonstrate that nitrogen ratios are capable of differentiating samples from Mexico and South America while carbon ratios are able to distinguish Southwest Asian samples from other source regions. Analogous results have routinely been observed (as part of Heroin Signature Program analysis) for morphine obtained from deacetylated authentic heroin samples from the same source regions. The results suggest that the poppy growing region has a greater influence on the carbon and nitrogen isotope values than the heroin manufacturing processes employed. When utilized in conjunction with existing signature methodologies, carbon and nitrogen isotope ratio data can enhance the ability to geo-source heroin.