Use of morphine and 6-monoacetylmorphine in blood for the evaluation of possible risk factors for sudden death in 192 heroin users

Aims To detect risk factors for sudden death from heroin injection. Design Evaluation of data from forensic investigations of all fatal cases of suspected heroin death in a metropolitan area. Only cases with detectable morphine and 6‐monoacetylmorphine (6‐MAM) in blood were included in order to select heroin intoxication cases. Setting Stockholm, Sweden. Measurements Autopsy investigation and toxicological analysis of blood and urine; and police reports. Findings In two‐thirds of the 192 cases, death occurred in public places, and mostly without any time delay. Blood concentrations of morphine ranged from 50 to 1200 ng/g, and of 6‐MAM from 1 to 80 ng/g. Codeine was detected in 96% of the subjects. In the majority of cases the forensic investigation indicated polydrug use, the most common additional findings being alcohol and benzodiazepines. However, in one‐quarter of the cases other drug combinations were found. Previous abstinence from heroin and use of alcohol were identified as risk factors. For 6‐MAM there was also a correlation with the presence of THC and benzodiazepines. Despite a high frequency of heart abnormalities (e.g. myocarditis and focal myocardial fibrosis), these conditions did not correlate with morphine or 6‐MAM blood concentrations. Conclusions We confirm that alcohol intake and loss of tolerance are risk factors for death from heroin use, whereas no connection to heart pathology was observed. Further, prospective, studies should focus on other possible risk factors.     

The effects of methadone maintenance treatment on heroin addicts with response inhibition function impairments: Evidence from event-related potentials

Response inhibition has been a core issue in addictive behavior. Many previous studies have found that response inhibition abilities are damaged in those with drug dependence. However, whether heroin addicts who are treated with methadone maintenance have an abnormal response inhibition ability is not clear. In order to investigate the response inhibition functions in heroin addicts who were treated with methadone maintenance, electroencephalography (EEG) was used to examine 14 heroin addicts treated with methadone maintenance (HDM), 17 heroin addicts (HD), and 18 healthy controls (HC) in an equiprobability Go\NoGo task. The reaction times (RTs) for the Go stimuli in the HD group were slower than those in the HDM and HC groups. Event-related potential (ERP) measurements showed that NoGo stimuli elicited larger N2 amplitudes than Go stimuli in the HDM and HC groups. However, for the HD group, the N2 amplitudes were similar for the two conditions. In addition, the HDM and HD groups were associated with longer P3 latencies. Our results demonstrated that methadone maintenance treatment might ease the deficits in response inhibition that result from long-term drug abuse. However, compared to normal people, HDM patients have serious problems evaluating and inhibiting inappropriate behaviors.     

The Risk Environment of Heroin Use Initiation: Young Women,Intimate Partners,and “Drug Relationships”

This paper examines young women's initiation to heroin use in the context of an intimate relationship based on data from a small-scale ethno-epidemiology of heroin use in Ireland, 2007–2009. The epidemiological sample included 120 young people, and life history interviews were conducted with a sub-sample of 40 youth aged 16–25 years. A detailed analysis of the “risk environment” of young women's heroin initiation highlights a complex interplay between women's agency and intimate partner influence. It is argued that dichotomous representations of women as victims or emancipated consumers do not adequately capture the complexity of women's initiation journeys. The study's limitations are noted and implications for drug use prevention and harm reduction strategies are discussed.     

Entangled in Big Events: Rise of Heroin Use Among Children of Ex-Gurkhas in Hong Kong

Big event models have been developed to demonstrate the relationships between wars and socioeconomic political transitions, and between rise of drug use and HIV epidemic outbreaks. This ethnographic interview-based study of a Nepali, Hong Kong community, carried out between 2009 and 2011, explored increased heroin use among the children of Hong Kong's Nepali ex-Gurkhas since its political transition in 1997. Data from its 59 informants were coded and analyzed using the grounded-theory approach. Three derived themes influencing drug use among ex-Gurkha children were identified: (1) reorganization of social networks, (2) redefinition of social norms, and (3) renegotiation of self-identity. Their associated processes crossed the boundaries of time and space. These findings document that big event modeling variables can and do overlap, are interconnected in many different ways, and their relationships are dialectical and are culturally shaped even as individuals may and do influence these processes and outcomes. Study's limitations are noted.     

A Conjugate Vaccine Attenuates Morphine- and Heroin-Induced Behavior in Rats

Background:

Currently approved medications for opioid addiction have shown clinical efficacy, but undesired side effects, dependence induced by the medications themselves, and low treatment compliance necessitate the need for novel therapies.

Methods:

A novel morphine-keyhole limpet hemocyanin conjugate vaccine was synthesized with 6-glutarylmorphine as the hapten and a lengthened linker of 6 carbon atoms. The titer and specificity of the triggered antibody were assessed by enzyme-linked immunosorbent assay. The effects of the vaccine on the morphine-induced elevation of dopamine levels in the nucleus accumbens were determined by high-performance liquid chromatography. The effects of the vaccine on morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin self-administration were also assessed.

Results:

After subcutaneous administration in rats, the vaccine triggered a high antibody titer, with comparable specificity for morphine, 6-acetylmorphine, and heroin, but no interaction with dissimilar therapeutic opioid compounds, including buprenorphine, naloxone, and nalorphine, was observed. The vaccine significantly prevented the elevation of dopamine levels in the nucleus accumbens induced by a single morphine challenge. Moreover, the vaccine prevented the expression of morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin seeking, suggesting its potential for preventing relapse.

Conclusion:

These results demonstrate that active immunization with the present vaccine induces a robust morphine/heroin-specific antibody response in rats and attenuates the behavioral effects of morphine and heroin.     

海洛因依赖者唾液表皮生长因子水平与舌苔变化的相关探讨

目的 研究海洛因依赖者唾液表皮生长因子（EGF）水平与舌苔变化的关系，探讨海洛因依赖者脱毒后消化系统功能紊乱的原因。方法 应用放射免疫法测定92例海洛因依赖者唾液表皮生长因子（EGF）含量，结合临床观察相应的舌苔变化。结果 海洛因依赖者唾液EGF水平与正常对照组比较有显著降低（P〈0．01），海洛因依赖者脱毒后唾液EGF低下是其舌苔厚腻和消化系统功能紊乱的原因之一。结论 EGF水平低下是海洛因依赖者脱毒后消化系统功能紊乱的原因之一。     

Reduced thalamic resting‐state functional connectivity and impaired cognition in acute abstinent heroin users

As a critical component of cortico‐striato‐thalamo‐cortical loop in addiction, our understanding of the thalamus in impaired cognition of heroin users (HU) has been limited. Due to the complex thalamic connection with cortical and subcortical regions, thalamus was divided into prefrontal (PFC), occipital (OC), premotor, primary motor, sensory, temporal, and posterior parietal association subregions according to white matter tractography. We adopted seven subregions of bilateral thalamus as regions of interest to systematically study the implications of distinct thalamic nuclei in acute abstinent HU. The volume and resting‐state functional connectivity (RSFC) differences of the thalamus were investigated between age‐, gender‐, and alcohol‐matched 37 HU and 33 healthy controls (HCs). Trail making test‐A (TMT‐A) was adopted to assess cognitive function deficits, which were then correlated with neuroimaging findings. Although no significant different volumes were found, HU group showed decreased RSFC between left PFC_thalamus and middle temporal gyrus as well as between left OC_thalamus and inferior frontal gyrus and supplementary motor area relative to HCs. Meanwhile, the higher TMT‐A scores in HU were negatively correlated with PFC_thalamic RSFC with inferior temporal gyrus, fusiform, and precuneus. Craving scores were negatively correlated with OC_thalamic RSFC with accumbens, hippocampus, and insula. Opiate Withdrawal Scale scores were negatively correlated with left PFC/OC_thalamic RSFC with orbitofrontal cortex and medial PFC. We indicated two thalamus subregions separately involvement in cognitive control and craving to reveal the implications of thalamic subnucleus in pathology of acute abstinent HU.     

A prospective, randomized, multicenter acceptability and safety study of direct buprenorphine/naloxone induction in heroin-dependent individuals

Aims To provide controlled data on direct induction with buprenorphine/naloxone (BNX) versus indirect buprenorphine (BPN)‐to‐BNX induction. Design Phase 4, prospective, randomized, active‐drug controlled, parallel‐group trial consisting of a 2‐day, double‐blind, double‐dummy induction phase followed by 26 days of open‐label treatment with BNX. Setting Nineteen sites in 10 European countries from March 2008 to December 2009. Participants A total of 187 opioid‐dependent men and women ≥15 years of age. Measurements The primary objective was assessment of patient response to direct and indirect BNX induction [proportion of patients receiving the scheduled 16‐mg BNX dose on day 3 (i.e. first day post‐induction)]. Secondary assessments included illicit drug use, treatment retention and compliance, withdrawal scale scores, and safety. Findings Patient response to direct‐ versus indirect‐BNX induction was similar [direct 91.4% (85/93) versus indirect 90.4% (85/94); 95% confidence interval (CI): −7.3%, 9.2%]. Rapid dose induction (16 mg of BPN equivalent on day 2) was acceptable and 72% of patients completed treatment (day 28). There were no significant differences in secondary measures across groups. An average BNX maintenance dose of 15.3 mg across groups was associated with substantial reductions in illicit opioid use and no self‐reported intravenous misuse. Treatment compliance and retention rates were similar (98.5% and 81.3%, respectively). Treatment‐emergent adverse event rates were comparable: 75% versus 74% for direct‐ versus indirect‐induction groups, respectively. Conclusions Direct buprenorphine/naloxone induction was a safe and effective strategy for maintenance treatment of opioid dependence. Response to high‐dose direct buprenorphine/naloxone induction appears to be similar to indirect buprenorphine‐to‐buprenorphine/naloxone induction and was not associated with reports of intravenous buprenorphine/naloxone misuse.     

Drug use in rural China: a preliminary investigation in Hunan Province

Aims To compare characteristics and illicit drug abuse patterns among drug abusers in rural and urban areas of Hunan Province, China. Measurements and design Data collected by public security bureau on newly registered drug abusers between 2005 and 2008 in five urban and five rural areas (n = 1639) were extracted anonymously and analyzed. Setting and participants All newly registered drug users in urban (n = 812) and rural (n = 827) areas of Hunan Province were included. Findings Drug users from the rural areas were younger [31 (6.6) versus 34 (8.0) years, P < 0.001], with a higher proportion of males (86% versus 82%, P < 0.05) or married (34% versus 27%, P < 0.01). Rural drug users reported an earlier onset of drug use [27 (5.9) versus 30 (7.9) years old, P < 0.001], were more likely to report heroin as their primary drug of abuse (53% versus 47%, P < 0.001) and had a lower prevalence of criminal activities (19% versus 31%, P < 0.001). Rural drug users were less likely to report needle sharing (1.8% versus 4.3%, P < 0.01), less likely to report being human immunodeficiency virus positive (0.8% versus 2.6%, P < 0.01) and less likely to report prior drug treatment participation (2.8% versus 6.8%, P < 0.001). Conclusions Drug abuse is a substantial problem in both urban and rural areas in China. The very low proportion of newly registered drug users reporting any prior drug abuse treatment points to the importance of expanding substance abuse treatments, especially in rural areas where treatment penetration is even lower than in urban areas.