Differences between men and women in the course of opiate dependence: is there a telescoping effect?

According to the so-called telescoping effect, there is a gender-specific course of alcohol dependence with women starting alcohol use later than men and having a faster development of harmful consequences. There are inconsistent data regarding a telescoping effect in opiate dependence. In each of six European centres, 100 opiate addicts were investigated by a structured interview (mainly the EuropASI and CIDI) at admission to various kinds of treatment (TREAT project). In a secondary analysis of the TREAT data, women and men were compared regarding age at onset of heroin use and the current severity of addiction. In addition, a comparison of female (n = 140) and male (n = 140) addicts matched for age and study centre were carried out. Eventually, multiple logistic and linear regressions were done with the interaction term of gender and time of regular consumption as predictor for the severity of dependence, besides, other sociodemographic variables. There was no difference between genders regarding the age at onset of regular heroin consumption. Up to 4 years of regular consumption, there are gender-specific differences in the course of opiate dependence, e.g. a faster progression of legal problems in men and social problems in women. There were no differences in the severity of dependence other than more economic problems for women. A telescoping effect could only partially be observed in this large sample of opiate addicts. A gender-specific course was limited to the first years of consumption, and included domains with a faster progression for men. It has to be assumed that opiate dependence is a rapidly developing disorder with early chronification. Afterwards, only individual courses with influences of the national treatment system were observed.     

Maintenance treatment of opiate addicts

Maintenance treatment is now the most common treatment of opiate addicts in Germany. The principle of maintenance treatment is the administration of an opioid in order to suppress withdrawal symptoms and heroin craving. In this manner, maintenance treatment successfully reduces heroin abuse and directly associated risk behaviour. Only a minority of maintenance patients became opiate abstinent (including the maintenance drug). Racemic methadone is the most extensively evaluated maintenance drug. A differential indication between medical opioids has not been scientifically established. According to the German regulations psychosocial support is an obligatory part of maintenance treatment. Most opiate addicts suffer from comorbid mental and somatic diseases. Therefore psychiatric and somatic treatment is indicated and of proven value.     

Clonidine Abuse Among Opiate Addicts

Objective: To determine if clonidine abuse among non-pregnant opiate dependent individuals is common and the reason for such use. Method: Self report of personal use or knowledge of others' use of this drug. Results: Fourteen of fifteen treatment seeking individuals with opiate dependence knew of clonidine abuse. Ten had used it personally to decrease the amount of heroin necessary to achieve a desired effect and to prolong the length of the opiate's action. Conclusion: clonidine abuse among opiate addicts may be more common than previous studies have suggested. Opiate addicts should be screened for abuse of this substance, especially in view of its widespread use for the purpose of opiate withdrawal. Further, such patients should be warned of potential health hazards attendant upon clonidine use and abrupt cessation.     

Differences in drug consumption,comorbidity and health service use of opioid addicts across six European urban regions (TREAT-project)

ObjectivesThis comparative study investigated consumption patterns, comorbidity and treatment utilization of opioid addicts in six European cities (Athens, Essen, London, Padua, Stockholm, Zurich).Subjects and methodsData were collected by structured face-to-face interviews. The representative sample comprises 599 addicts (100 patients per centre, 99 in London) at the start of a treatment episode.ResultsPatients were dependent on opioids for about 10 years. Regional differences were significant regarding the patients’ drug consumption pattern and their method of heroin administration (up to a fourth of the patients in Essen, London and Zurich usually smoke heroin). Concomitant use of benzodiazepines, cannabis and alcohol was common in all regions with the German and English samples showing the highest level of polydrug use. The prevalence of major depression was high in all regions (50%). Stockholm and London patients worry most about their physical health. Differences in the amount of needle sharing and especially in the use of public health service were prominent between the sites. Opioid addiction was a long-term disorder associated with a high burden of comorbidity and social problems in all cities.ConclusionThe results of the study show significant interregional differences of opioid addicts which might require different treatment strategies in European countries to handle the problem.     

Asthma in opiate addicts

A case-note study of 2276 opiate addicts revealed that 112(5%) had a history of asthma and that in 31(1.4%) cases there appeared to be a definite temporal relationship between heroin abuse and the onset of asthma. This rarely-reported complication of heroin dependence has a higher incidence among female addicts (3.3%) than among male addicts (0.7%).     

Is the bipolar spectrum the psychopathological substrate of suicidality in heroin addicts?

BACKGROUND: To describe the prevalence and the risk factors of suicidal ideation in a cohort of Italian opioid addicts presenting for treatment. METHOD: Systematic cross-sectional clinical data on suicidal ideation, socio-demographic variables, psychiatric status, social adjustment, status and history of addiction in 616 patients were gathered. RESULTS: Suicidal thoughts during the past week were reported by 29.1%. Suicidal thoughts were more frequent in patients with bipolar spectrum diagnoses (OR = 1.42) and in patients with depressive and aggressive symptoms (multiple R = 0.47). The odds of having suicidal thoughts were also higher for subjects receiving public welfare benefits (OR = 1.69), unemployed patients (OR = 1.37), those with early onset of heroin dependence (OR = 1.36), living alone (OR = 1.33), and experiencing problems in organizing social contacts and leisure time (OR = 1.28). CONCLUSION: Current suicidal ideation was a common feature of patients with opioid addiction. Depression and hostility as part of the bipolar spectrum - in the context of early-onset drug dependence, work and social/leisure problems - appear independently associated with suicidal ideation. Given the elevated rates of completed suicide in heroin addiction, these data have implications for preventing suicide in patients with this type of addiction. Prospective data are needed to further address this important clinical and public health agenda.     

A 33-year follow-up of narcotics addicts

BACKGROUND: This study examined longitudinal patterns of heroin use, other substance use, health, mental health, employment, criminal involvement, and mortality among heroin addicts. METHODS: The sample was composed of 581 male heroin addicts admitted to the California Civil Addict Program (CAP) during the years 1962 through 1964; CAP was a compulsory drug treatment program for heroin-dependent criminal offenders. This 33-year follow-up study updates information previously obtained from admission records and 2 face-to-face interviews conducted in 1974-1975 and 1985-1986; in 1996-1997, at the latest follow-up, 284 were dead and 242 were interviewed. RESULTS: In 1996-1997, the mean age of the 242 interviewed subjects was 57.4 years. Age, disability, years since first heroin use, and heavy alcohol use were significant correlates of mortality. Of the 242 interviewed subjects, 20.7% tested positive for heroin (with additional 9.5% urine refusal and 14.0% incarceration, for whom urinalyses were unavailable), 66.9% reported tobacco use, 22.1% were daily alcohol drinkers, and many reported illicit drug use (eg, past-year heroin use was 40.5%; marijuana, 35.5%; cocaine, 19.4%; crack, 10.3%; amphetamine, 11.6%). The group also reported high rates of health problems, mental health problems, and criminal justice system involvement. Long-term heroin abstinence was associated with less criminality, morbidity, psychological distress, and higher employment. CONCLUSIONS: While the number of deaths increased steadily over time, heroin use patterns were remarkably stable for the group as a whole. For some, heroin addiction has been a lifelong condition associated with severe health and social consequences.     

Effect of clonidine on the secretion of anterior pituitary hormones in heroin addicts and normal volunteers

Neuroendocrine effects of intravenous injections of clonidine, 0.15 mg, were investigated in 13 heroin addicts and 14 normal control subjects. The study was designed to determine whether continuous opiate administration leads to the development of hypersensitive alpha 2-adrenergic receptors. The peak increments in levels of plasma growth hormone (GH) and beta-endorphin induced by clonidine did not differ between heroin addicts and normal control subjects. At no time interval could the clonidine-induced rise in GH levels in addicts be differentiated from that induced by placebo. Clonidine failed to alter plasma prolactin, gonadotropin, or thyrotropin levels in either heroin addicts or controls. Since clonidine's neuroendocrine effects are reportedly due to the activation of postsynaptic alpha 2-adrenoceptors, it appears that (1) continuous opiate use does not lead to the development of hypersensitive alpha 2-adrenergic receptors involved in neuroendocrine mechanisms and (2) brain norepinephrine does not play a role in the regulation of tonic prolactin, gonadotropin, and thyrotropin secretion in man.     

Is premature termination of opiate detoxification due to intensive withdrawal or craving?

Opiate addicts terminate inpatient detoxification prematurely in about 50% of treatment episodes. Premature termination of treatment is often considered to be motivated by intensive withdrawal symptoms. Therefore, the relation between discontinuing treatment and the intensity of withdrawal symptoms and heroin craving is investigated. 130 opiate addicts consecutively admitted to a detoxification ward daily assessed the intensity of withdrawal symptoms on the Short Opiate Withdrawal Scale (SOWS) as well as the intensity of heroin craving on a visual analogue scale. Withdrawal symptoms were treated by stepwise reduction of methadone and symptom-oriented medication. 66 patients (50.8%) terminated treatment prematurely. However, during the days preceding treatment termination, these patients did not differ from regularly detoxified patients assessed on corresponding days with respect to craving, and reported even less intensity of withdrawal symptoms. In conclusion, neither the intensity of withdrawal symptoms nor the intensity of heroin craving constitutes the primary reason for premature termination of detoxification.     

Decreased immunodensities of micro-opioid receptors, receptor kinases GRK 2/6 and beta-arrestin-2 in postmortem brains of opiate addicts

The homologous regulation of opioid receptors, through G protein-coupled receptor kinases (GRKs) and beta-arrestins, is an initial step in the complex molecular mechanisms leading to opiate tolerance and dependence. This study was designed to evaluate in parallel the contents of immunolabeled micro-opioid receptors (glycosylated proteins), two representative GRKs (GRK 2 and GRK 6) and beta-arrestin-2 in brains of opiate addicts who had died of an opiate overdose (heroin or methadone). The immunodensities of micro-opioid receptors were decreased (66 kDa protein: 24%, n=24, P<0.0001; 85 kDa protein: 16%, n=24, P<0.05) in the prefrontal cortex of opiate addicts compared with sex-, age-, and PMD-matched controls. This down-regulation of brain micro-opioid receptors was more pronounced in opiate addicts dying of a heroin overdose (27-30%, n=13) than in those who died of a methadone overdose (5-16%, n=11). In the same brains, significant decreases in the immunodensities of GRK 2 (19%, n=24, P<0.05), GRK 6 (25%, n=24, P<0.002) and beta-arrestin-2 (22%, n=24, P< 0.0005) were also quantitated. In contrast, the content of alpha-internexin (a neuronal marker used as a negative control) was not changed in brains of opiate addicts. In these subjects, there was a significant correlation between the densities of GRK 6 and beta-arrestin-2 (r=0.63, n=24, P=0.001), suggesting that both proteins are regulated in a coordinated manner by opiate drugs in the brain. The results indicate that opiate addiction in humans (tolerant state) is associated with down-regulation of brain micro-opioid receptors and regulatory GRK 2/6 and beta-arrestin-2 proteins. These molecular adaptations may be relevant mechanisms for the induction of opiate tolerance in brains of opiate addicts.     

Untreated opiate addicts. How do they differ from those seeking treatment?

Treatment-seeking opiate addicts were compared with an untreated, community sample identified through the chain-referral technique. Community and treatment-seeking addicts were found to be comparable in duration and severity of opiate use and in current engagement in risky, illegal activities connected with procurement of drugs. However, community addicts reported more adequate social functioning, fewer drug-related legal problems, and lower rates of depressive disorders. Despite the comparatively less severe problems in current functioning, community addicts were found to be a substantially impaired group whose failure to seek help appeared more related to misunderstanding of the severity of their drug use and of treatment opportunities than to the lack of need for help.     

美沙酮联用丁丙诺啡对海洛因依赖重度药瘾戒毒治疗临床研究

目的　探索对海洛因依赖重度药瘾较理想的戒毒治疗方法。　　方法　采用美沙酮与丁丙诺啡联合用药方案 ,对海洛因依赖重度药瘾 41例行戒毒治疗 ,1 2天为一疗程 ,并与单用美沙酮组 2 0例进行比较。　　结果　联合用药组控制症状较彻底 ,鸦片类药物戒断症状量表 (OWS)总分平稳下降 ,症状波动小 ,减药顺利 ,两药替换平稳 ,戒毒成功率 73 2 %。　　结论　我们认为美沙酮联用丁丙诺啡是一种值得推荐的戒毒治疗方法。     

Experience of social discrimination correlates with neurometabolism: a pilot study in heroin addicts

Experimental social neuroscience has shown that being socially excluded is processed in the anterior cingulate cortex (ACC). We hypothesize that a chronic form of social exclusion resembling one aspect of social stigmatization is associated with altered neural plasticity reflected by neurometabolic alterations in the ACC. To test this hypothesis, a highly stigmatized patient group of heroin addicts (N = 15) during opiate maintenance therapy rated a questionnaire about being stigmatized, and neurometabolic markers in the ACC were determined using ¹H MR spectroscopy. We found a negative correlation between discrimination experience and N-acetylaspartate (NAA), indicating attenuated neuron functioning in the anterior cingulate cortex in those patients reporting high discrimination experience. Furthermore, perceived stigmatization showed an association with anxiety that was mediated by NAA. Although the correlative analysis cannot give evidence for a causal relationship, the relation of NAA in the ACC and discrimination experience indicates a malfunction of the neural system involved in cognitive control over emotionally relevant social stimuli in discrimination reporting heroin addicts. Further research is needed to elucidate factors associated with chronic stigmatization.     

Opioid maintenance therapy restores CD4+ T cell function by normalizing CD4+CD25(high) regulatory T cell frequencies in heroin user

There is an increasing body of evidence that heroin addiction is associated with severe alterations in immune function, which might contribute to an increased risk to contract infectious diseases like hepatitis B and C or HIV. However, the impact of heroin consumption on the CD4(+) T cell compartment is not well understood. Therefore, we analyzed the frequency and functional phenotype of CD4(+) T cells as well as immune-suppressive CD4(+)CD25(high) regulatory T cells (Tregs) isolated from the peripheral blood of opiate addicts currently abusing heroin (n=27) in comparison to healthy controls (n=25) and opiate addicts currently in opioid maintenance treatment (OMT; n=27). Interestingly, we detected a significant increase in the percentage of CD4(+)CD25(high) Tregs in the peripheral blood of heroin addicted patients in contrast to patients in OMT. The proliferative response of CD4(+) T cells upon stimulation with anti-CD3 and anti-CD28 antibodies was significantly decreased in heroin users, but could be restored by depletion of CD25(high) regulatory T cells from CD4(+) T cells to similar values as observed from healthy controls and patients in OMT. These results suggest that impaired immune responses observed in heroin users are related to the expansion of CD4(+)CD25(high) Tregs and more importantly, can be restored by OMT.     

Heroin vs alcohol addiction--quantifiable psychosocial similarities and differences

A pilot study of 50 heroin addicts and 66 alcohol addicts utilizing the recently developed quantitative methods for measuring life change and seriousness of illness. Alcohol addicts were found to have significant attenuation of perception of life change and seriousness of illness as compared to heroin addicts and current “normative” data. The heroin addicts were found to have a mild but significant augmentation of perception of life change and seriousness of illness as compared to the “normative” data. In addition both the heroin addicts and alcohol addicts were found to maintain very high levels of life change. The documented differences in perception and the maintenance of high levels of life change were felt to have potential significance in the treatment and evaluation of both groups of addicts.     

Opiate use and sexual function

Although opiate addicts often equate the drug experience with sexual orgasm, diminished libido and impaired sexual performance are common sequelae of chronic use. Early clinical studies suggested that opiates may interfere with sex hormone secretion. The authors carried out three sequential studies which demonstrated that heroin use in man results in acute suppression of luteinizing hormone (LH) release from the pituitary followed by a secondary drop in plasma testosterone levels. The time course of these neuroendocrine events correlates well with the tension-reducing effects of heroin and suggests that drive reduction is an important component of opiate reinforcement.     

Predicting Outcome in Public Addiction Services Using Data Collected During Routinely Assessment Procedures

The study examined the ability of several baseline variables to predict retention and treatment outcome in a cohort study that included 137 participants with heroin and cocaine addiction attending a public addiction service in Italy. Predictors included past drug use, intravenous use, initial urine drug screen results, cocaine and heroin craving and self-reported psychiatric symptoms. Severe depression and, in a lesser extent, anxiety symptoms, predicted lower retention. Only intravenous use was a significant predictor of cocaine use in the whole sample. Positive urine for cocaine and intravenous use predicted worse outcome among heroin addicts. Three Symptoms Checklist-90 (SCL-90) scales scores were associated with lower cocaine and heroin use. Multiple logistic regression showed that cocaine positivity and more structured psychosocial treatment predicted successful outcome. Results highlight the prognostic value of carefully assessing patterns of cocaine use and co-use, routes of administration and psychiatric symptoms at the beginning of treatment, especially in heroin addicts.     

康复训练对男性海洛因依赖者应对方式和社会支持的影响

目的探索康复训练对男性海洛因依赖者的影响。方法对50名海洛因依赖者进行了至少4个月的康复训练,康复训练以海洛因依赖者的需求、所处的康复阶段及接受能力为中心,包括强化戒毒治疗动机、减少吸毒造成的危害、复吸预防等各种技能训练。康复训练前后测量应对方式和社会支持。结果康复训练后海洛因依赖者幻想、退避、自责等不成熟型应对方式分值下降,而求助的分值增加,社会支持增加。结论康复训练改善男性海洛因依赖者的社会支持和应对方式。