Long‐lasting increased pain sensitivity in rat following exposure to heroin for the first time

Acute dependence, defined as a precipitation of somatic signs by an antagonist, may occur after a single administration of an opiate drug. Because hyperalgesia is a consistent sign of the withdrawal syndrome, we tested the effectiveness of heroin, an opiate used by addicts, to induce pain facilitation even after a first exposure to the drug. In opiate-naive rats, subcutaneous injection of heroin induced analgesia followed by allodynia, a decrease in pain threshold. This latter phenomenon was observed in the absence of noxious stimuli and lasted several days. An N-methyl-d -aspartate (NMDA) receptor antagonist, MK-801 prevented such long-lasting allodynia. These results suggest that allodynia is an early sign reflecting neural plasticity associated with the development of dependence.     

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.     

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.     

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.     

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.     

Activation of reward circuitry in human opiate addicts

The neurobiological mechanisms of opiate addictive behaviour in humans are unknown. A proposed model of addiction implicates ascending brainstem neuromodulatory systems, particularly dopamine. Using functional neuroimaging, we assessed the neural response to heroin and heroin-related cues in established opiate addicts. We show that the effect of both heroin and heroin-related visual cues are maximally expressed in the sites of origin of ascending midbrain neuromodulatory systems. These context-specific midbrain activations predict responses to salient visual cues in cortical and subcortical regions implicated in reward-related behaviour. These findings implicate common neurobiological processes underlying drug and drug-cue-related effects.     

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%).     

多巴胺2受体基因TaqIA多态性与美沙酮维持治疗海洛因依赖患者心理症状相关性研究

目的研究昆明市美沙酮维持治疗A门诊接受美沙酮维持治疗的汉族海洛因依赖者多巴胺D2受体基因TaqIA多态性与接受美沙酮维持治疗海洛因依赖患者心理症状的相关性,探讨影响病人治疗效果的遗传因素。方法对81例接受美沙酮维持治疗的海洛因依赖者实施SCL-90测试,应用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）技术,检测多巴胺D2受体基因TaqIA基因多态,比较不同基因型与SCL-90各因子的关系。结果 A1＋组（A1/A1,A1/A2）与A1-组（A2/A2）SCL-90各因子分无显著性差异。结论D2受体基因TaqIA多态性与美沙酮维持治疗海洛因依赖患者心理症状可能不存在相关性。     

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.     

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.     

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.     

Neuroleptic therapy of comorbid narcotic dependent patients in ambulatory methadone maintenance

Methadon maintenance therapy with opiate addicts who suffer from a comorbid schizophrenia in an outpatient treatment setting of a psychiatric hospital is described. We examined five patients looking for periods of inpatient treatment, drug free urine tests, social integration and illegal activities before and after neuroleptic treatment. In comparison with standard neuroleptics patients show under the therapy with atypical neuroleptics better outcome in drug urine tests especially concerning cannabis and benzodiazepines. According to these findings, the best improvements seem to occur with a combination of methadone and clozapine.     

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.     

Propoxyphene form maintenance treatment of narcotic addiction

Two studies compared propoxyphene napsylate (Darvon-N) with methadone hydrochloride as maintenance treatment for narcotic addicts. Most measures indicated that methadone was more effective than propoxyphene as a maintenance drug. Patients receiving propoxyphene reported more withdrawal-related symptoms early in treatment, tended to drop out sooner than patients receiving methadone, and were more likely to abuse heroin. Nevertheless, follow-up interviews at one and six months after treatment indicated no between-group differences in adjustment.     

长沙市芙蓉区美沙酮门诊海洛因依赖人群HIV、HCV和梅毒感染状况调查

目的 了解长沙市芙蓉区美沙酮门诊海洛因依赖人群HIV、HCV和梅毒感染情况及其危险因素.方法 对参加维持治疗的323名海洛因依赖者进行HIV、HCV梅毒血清学检测和问卷调查.结果 71％成瘾者采用静脉吸毒,6.9％的静脉吸毒者共用注射器.HIV抗体阳性率0.3％ (1/323) HCV抗体阳性率61％ (198/32...     

Metyrapone effects on beta-endorphin, ACTH and cortisol levels after chronic opiate receptor stimulation in man

The aim of this study was to evaluate beta-endorphin, ACTH, and cortisol plasma levels during metyrapone administration in man after chronic opioid receptor stimulation. Metyrapone (750 mg every 4 hr for 6 doses) was administered to ten male heroin addicts, who had been on a maintenance therapy with methadone for at least 6 months and to ten healthy sex- and age-matched volunteers. Before metyrapone administration the basal levels of cortisol and ACTH were significantly decreased in addicts as compared to normal controls, while plasma beta-endorphin was not different. The response of beta-endorphin and ACTH to metyrapone administration was significantly blunted in addicts (p less than 0.01). These results suggest that the chronic stimulation of opiate receptors can impair the function of the anterior pituitary gland.     

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.     

Twelve-month follow-up of psychotherapy for opiate dependence

To provide information on the long-debated issue of the value of psychotherapy as an addition to paraprofessional counseling services for opiate addicts receiving methadone maintenance, the authors obtained 12-month follow-up data on 93 such patients randomly assigned to a 6-month course of either paraprofessional drug counseling or counseling plus professional psychotherapy. The psychotherapy patients had a significantly better overall status at 7-month follow-up and also at 12-month follow-up, 6 months after the psychotherapy ended. The authors conclude that psychotherapy can be evaluated by using scientific methods and that it can have measurable and sustained benefits in the treatment of opiate addiction.     

Evaluation of clonidine suppression of opiate withdrawal reactions: a multidisciplinary approach

The purpose of this open, uncontrolled study in a group of confirmed heroin addicts of both sexes was to determine whether clonidine by itself suppresses opiate withdrawal reactions, its maximal effective dosage range, the time of maximal effect, duration of its effectiveness and the extent of cardiovascular side effects. After a washout phase of opium residues, clonidine was administered for eight days and its effects were closely monitored and recorded. Even during the first 24 hour period, when clonidine was administered alone in a high dosage, it suppressed the signs and symptoms of opiate withdrawal reactions. The maximum effect was attained within three days. Thereafter, it maintained improvement until natural resolution of the reactions. Side effects were limited to some small but statistically significant cardiovascular changes. Illicit drug use during the treatment period indicated that drug related behaviour is only slightly affected by clonidine. The drug is thus effective in the acute withdrawal phase but does not replace the important psychosocial management needed to achieve long term drug abstinence.