Heroin-dependent Patients Research Articles

Sleeping problems among Chinese heroin-dependent individuals

Background: Heroin abuse is a major public health problem with high morbidity and mortality. Treatment-seeking heroin-dependent subjects frequently report sleep-related problems that contribute to high relapse rates. Few studies have systematically studied the prevalence of sleep disorders among Chinese heroin-dependent subjects. Objectives: This study aimed to explore the prevalence of sleep disorders with a battery of self-reported questionnaires in 140 heroin-dependent subjects in China. Methods: A self-report survey design was used to gather the data, using the Pittsburgh Sleep Quality Index (PSQI), Zung's Self-Rating Anxiety Scale (SAS), and Zung's Self-Rating Depression Scale (SDS). A total of 140 drug users participated in the survey. Results: PSQI results revealed that poor sleep quality (PSQI ≥ 8) was noted in 130 (96.30%) subjects. Those who displayed depressive symptoms, smoked and drank excessively, and had long-term histories of drug use had poorer sleep quality than those who did not. No correlation was found between anxiety, quantity of drugs, and sleeping disorders. Conclusions: This study found that the majority of heroin-dependent patients reported poor sleep quality. Depression, smoking, drinking, and long-term drug use were associated with poor sleep quality in heroin-dependent individuals. Scientific significance: Despite the fact that this study collected data only using self-report measures, focused only on heroin-dependent patients, and did not include long-term follow-up study, given the potential link between poor sleep quality and relapse, factoring in this link is an important consideration as part of a comprehensive heroin-dependent treatment program.

A pilot assessment of relapse prevention for heroin addicts in a Chinese rehabilitation center

Objectives: To conduct a pilot assessment of relapse prevention (RP) group therapy for heroin-dependent patients in a drug rehabilitation center in China. Methods: A randomized case–control study was conducted to assess the efficacy of RP delivered over a 2-month period to male heroin addicts (n = 50, RP group) in the Shanghai Labor Drug Rehabilitation Center (LDRC) compared with an equal number of participants (n = 50, labor rehabilitation (LR) group) in the LDRC program receiving standard-of-care treatment. Outcomes were assessed by the Beck Depression Inventory (BDI), the Self-Rating Anxiety Scale (SAS), the Self-Efficacy Scale (SE), and the Self-Esteem Scale (SES) after completion of RP, and by the Addiction Severity Index (ASI) and abstinence rates of heroin use at 3-month follow-up post release from the LDRC for both groups. Results: Significant improvements in scores on SAS, SE, and SES were found in the RP group after completion of the 2-month RP group therapy compared with the LR group (SAS 7.85 ± 6.20 vs 1.07 ± 5.42, SE 3.88 ± 3.60 vs .08 ± 2.89, and SES 3.83 ± 3.31 vs .78 ± 2.55). At 3-month follow-up, the RP group participants had more improvements on ASI scores in most domains and had higher abstinence rates than that in the LR group (37.2% vs 16.7%). Conclusions: An RP component can be effective in increasing abstinence rates among post-program heroin-dependent individuals and may help reduce anxiety and improve self-esteem and self-efficacy during and following treatment. Scientific Significance: This study suggests RP as a potentially effective component of treatment for heroin addicts.

Influence of Treatment with Inhalable Heroin on Pulmonary Function

This study aims to asses the influence of inhalable heroin on pulmonary function in chronic heroin-dependent patients treated with inhalable heroin. Among 32 patients (all cigarette smokers), a spirometric test was conducted at baseline and after an average period of 10 months of treatment with medically prescribed heroin. Patients showed a high frequency of pulmonary dysfunction at baseline [34%, with percentage of forced expiratory volume in 1 s (%FEV₁) <80%]. However, after excluding those who started pulmonary treatment (n = 2) or who used heroin intravenously only (n = 2), no statistically significant differences in %FEV₁ between baseline and follow-up were observed (n = 28; mean %FEV₁ 86% at baseline vs. 91% at follow-up; p = 0.09). This small and relatively brief study suggests that 10 months of co-prescribed inhalable heroine base does not seem to (further) deteriorate pulmonary function in chronic, cigarette smoking treatment refractory heroin addicts. Screening for and treatment of pulmonary dysfunction is recommended for methadone patients with and without co-prescribed heroin.

Effects of Stress on Decision-Making Deficits in Formerly Heroin-Dependent Patients After Different Durations of Abstinence

Drug abuse is associated with substantial impairments in decision making. However, little is known about the time course of changes in decision-making ability after abstinence or about the effects of stress on decision making in individuals recovering from heroin dependence after different durations of abstinence. First, the authors assessed decision-making performance with the original card version of the Iowa Gambling Task in formerly heroin-dependent patients who had been abstinent for 3, 7, 15, or 30 days or 3, 6, 12, or 24 months. Second, patients who had been abstinent from heroin for 15 or 30 days or 3, 12, or 24 months were challenged with acute stress induced by the Trier Social Stress Test. Third, the β-adrenoceptor antagonist propranolol (40 mg) was administered 1 hour before stress to those who had been abstinent for 30 days or 12 or 24 months. The short-term abstinence groups (3-30 days) performed worse on the Iowa Gambling Task compared with the long-term abstinence groups (3-24 months). Psychosocial stress unmasked a latent impairment in decision making in the 24-month abstinence group, which seemed to perform identically to healthy comparison subjects in the absence of stress. Propranolol blocked the stress-induced impairment of decision making, which was seen only in the formerly heroin-dependent patients. Stress can exacerbate an already existing impairment of decision making or unmask a latent one in individuals recovering from heroin dependence. The β-adrenergic blockade reduces this effect and might hold promise for treatment of substance use disorders.

Association between heroin dependence and prodynorphin gene polymorphisms

Dynorphin peptides and k-opioid receptor are important in the rewarding effects of drugs of abuse such as heroin. This study examined potential association between heroin dependence and four single nucleotide polymorphisms (SNPs) of prodynorphin (PDYN) gene (rs35286281 in promoter region and rs1022563, rs2235749, rs910080 in 3′UTR). Participants included 304 heroin-dependent subjects and 300 healthy controls. Genotype, allele frequencies and difference between groups were analyzed by HaploView 4.0 and SPSS 11.5 software. The analysis indicated a significant higher frequency of the PDYN 68bp VNTR (rs35286281) H allele in heroin-dependent subjects than in controls ( p = 0.002 after Bonferroni correction). Strong linkage disequilibrium was observed between rs1022563, rs2235749 and rs910080 polymorphism ( D′ > 0.9). Significantly more TCT haplotypes were found in heroin-dependent patients than in the controls ( p = 0.006 after Bonferroni correction). We found significant pointwise correlation of these three variants (rs1022563, rs2235749 and rs910080) with heroin dependence. These findings support the important role of PDYN polymorphism in heroin dependence, and may guide future studies to identify genetic risk factors for heroin dependence.

P01-97 - Impulsivity and addiction severity in cocaine, cocaine and heroin and heroin dependent patients measured by BIS-11 and Europasi

ObjectivesWe aimed to study the relationship between impulsivity and the addiction severity in 3 groups of outpatients attending our clinic, through the Barrat Impulsivity Scale (BIS-11) and the standarized, semistructured interview EuropAsi.Methods174 outpatients were analized (82.6% men, 113 cocaine-dependent as main drug (mean age 32.71 y.o. (31.45–33.96)), 43 cocaine and heroin-dependent (mean age 36.68 y.o. (33.52–39.85)) and 18 heroin dependent (mean age 37.94 (32.71–41.50)). 26.3% were cannabis-dependent and 10.9% abused of Cannabis. Statistical analysis used was the Kruskal-Wallis Test.ResultsDifferences in motor impulsivity were found between the 2 groups with cocaine dependency and the only heroin-dependent (mean = 20.59, ST ± 7.7 and mean = 17.11, ST ± 7.3, respectively; W: .019). EuropASI, showed intergroup differences in the medical, use of alcohol and legal areas. In the medical area the most affected were the heroin dependent group (mean score = .40), followed by cocaine and heroin group (mean score = .27) and the cocaine-dependent (Mean = .10). In the use of alcohol area the most affected were the cocaine group (Mean = .16) followed by the cocaine and heroin-dependent (mean = .11) and heroin dependent (Mean = .06). In the legal area the most affected were the the cocaine and heroin-dependent (Mean =.22) followed by heroin-dependent (Mean = .09) and cocaine-dependent (Mean = .07).ConclusionsPatients suffering from stimulant dependency alone or together with heroin dependency show different impulsivity levels. The addiction severity varies depending on the substance of abuse. Treatment programs should be designed attending patients’ needs.

Pattern of consecutive urinalysis results for patients on take-home buprenorphine–naloxone in India: Do patients really take it at home?

International experience suggests that buprenorphine–naloxone combination can be misused and diverted. Little is known about the non-adherence to take-home buprenorphine–nloxone in India. A retrospective pilot study of 100 consecutive urine samples of heroin-dependent patients on take-home buprenorphine–naloxone medication was carried out. Urinalysis was done by thin layer chromatography, using a modified hydrolysis method. The mean daily dose for prescribed buprenorphine was 7.93 ± 2.73 mg/day, dispensed once or twice a week. Urinalysis results revealed that 30% of samples tested negative for prescribed drug despite being on regular take-home buprenorphine–naloxone medication. Nearly half of these patients also tested positive for a non-prescribed drug. The results and trends of urinalysis results carry important clinical implications and urges for a close monitoring for non-adherence and diversion of take-home medication.

Multiple substance use among heroin-dependent patients before and during attendance at methadone maintenance treatment program, Yunnan, China

BackgroundMultiple substance use is a common problem among heroin users. This study aims to describe patterns of multiple substance use one year before and during attendance at methadone maintenance treatment (MMT) programs and associated variables of continued heroin use in MMT clinics in Yunnan, China. MethodsThe study was conducted among 168 heroin addicts who had received treatment for at least one year at two MMT clinics in Kunming city. A structured questionnaire, a medical record, and computer database were used to obtain history of substances use, significant clinical information, and treatment details, respectively. ResultsHeroin, tobacco, and alcohol were the most commonly used substances both before and during MMT. After one year in MMT, use of heroin, alcohol, tramadol, and triazolam significantly decreased whereas use of ephedrine increased. Simultaneous substance use was halved but the decrease was not statistically significant. The proportion of injecting users was reduced from 61% to 43%. History of heroin use in the preceding 6 months during MMT increased the odds of continued heroin use (OR=5.8, 95% CI=[2.9–11.3]). An average 10mg higher methadone dose increment was associated with a reduced odds of heroin use by 10%. ConclusionMMT did not reduce the number of substances used, but the number of injecting heroin users after the first year of treatment decreased. Heroin use in the preceding 6 months during MMT treatment and lower methadone dose were associated with continued heroin use in MMT.

Do methadone and buprenorphine have the same impact on psychopathological symptoms of heroin addicts?

BackgroundThe idea that the impact of opioid agonist treatment is influenced by the psychopathological profile of heroin addicts has not yet been investigated, and is based on the concept of a specific therapeutic action displayed by opioid agents on psychopathological symptoms. In the present report we compared the effects of buprenorphine and methadone on the psychopathological symptoms of 213 patients (106 on buprenorphine and 107 on methadone) in a follow-up study lasting 12 months.MethodsDrug addiction history was collected by means of the Drug Addiction History Rating Scale (DAH-RS) and psychopathological features were collected by means of the Symptom Checklist-90 (SCL-90), using a special five-factor solution. Toxicological urinalyses were carried out for each patient during the treatment period.ResultsNo statistically significant differences were detected in psychopathological symptoms, including 'worthlessness-being trapped', 'somatization', and 'panic-anxiety'. Methadone proved to be more effective on patients characterized by 'sensitivity-psychoticism', whereas buprenorphine was more effective on patients displaying a 'violence-suicide' symptomatology.ConclusionsHeroin-dependent patients with psychiatric comorbidities may benefit from opioid agonist treatment not only because it targets their addictive problem, but also, precisely due to this, because it is effective against their mental disorder too.

Evaluation of Circulating Immune Complexes and Anti-phospholipid Antibodies (anti Beta 2 Glycoprotein 1) in Heroin Addicts and their Clinical Significance

Earlier studies have reported that heroin might cause the structural and antigen changes on numerous tissues, organs and subsequent development of autoimmune reactions (production of antibodies and creation of immune complexes) as a result the immunotoxic effect of heroin. The aims of our study were to: a) Evaluate CIC and antibeta2GP1 in heroin addicts; b) Correlate between the values of the obtained CIC and antibeta2GP1 (stratified by the duration and route of heroin application); c) Compare the CIC and antibeta2GP1 in heroin addicts and the control group and d) Assess the clinical importance of CIC and antibeta2GP1 in heroin addicts. This was a cross-sectional study performed at the University Clinic of Toxicology and the Institute of Transfusiology, Skopje, Republic of Macedonia. Patients referred to the Clinic for clinical examinations who met the inclusion criteria were analyzed. Protocol for work was the following: 1.) detailed anamnestic data, 2.) a whole set of laboratory biochemical blood and urine analyses, 3.) examination with the Schiller's twelve-channel ECG; 4.) toxicological analyses for opioids in a urine sample; circulating immune complexes and 5.) antiphospholipid antibodies (antibeta2GP1, fractions: IgA, IgG, IgM). The obtained results were statistically analyzed. We included 37 heroin addicts and a control group of 27 healthy subjects. Male abusers predominated over female in--28 (76%) subjects; mean age being 26 +/- 5.06. The results which refer to the increased values of circulating immune complexes have shown a high statistically significant dominance of heroin addicts, in comparison with the control group (p < 0.01) and increased values above the reference ones of IgG antibeta2GP1, alone in the group of intravenous heroin abusers (p < 0.025). The mean duration of the heroin use in intravenous abusers was 6.21 +/- 3.25 years, whereas in those snorting heroin was 5.15 +/- 2.26 years. Duration of heroin application was in a positive correlation with IgG antibeta2GP1 (p = 0.35). Our data showed that heroin-dependent patients in our study had increased values of circulating immune complexes and changes in IgG and IgM antibeta2GP1 with significantly increased values of IgG antibeta2GP1 in the intravenous heroin abusers. The duration of heroin application is in direct proportional relationship with IgG antibeta2GP1. Heroin addicts had significantly higher values of circulating immune complexes and statistically significant difference in IgG antibeta2GP1, in comparison with the control group. Changes in the fractions of antibeta2GP1 and CIC suggest a possible relation with the somatic changes found in heroin addicts (i.e. thrombocytopenia, reduced renal clearance, etc).

Can Ropinirole Modulate Reinforcing Subjective Effects of Cocaine in Humans?

In this study we evaluated, by means of the “cocaine rush visual analog scale,” the impact of ropinirole on the expected rush induced by cocaine in a group of heroin addicts abusing cocaine; the self-reported reaction to the rush blockade (if any) on cocaine consumption, and the correlations between this self-reported reaction and individual, clinical, and therapeutic parameters. Nineteen cocaine abuser heroin-dependent patients entered the study. Their experienced cocaine rush was 61.31 ± 32.1% of the maximum effect previously experienced. Compared with their previous rush intensity 16 patients experienced significantly lower intensity, 3 the same intensity, and none a higher intensity. In particular, two patients experienced a complete blockade of rush and reported a reduced use of cocaine. Fourteen patients experienced a partial blockade of cocaine rush; of these, nine reported they had reduced their use of cocaine. Ropinirole does diminish the subjective intensity of an expected cocaine rush, so interfering with the dynamics of reward, while supporting its possible use in the treatment of cocaine dependence.

Inhibition of Anti-HIV MicroRNA Expression: A Mechanism for Opioid-Mediated Enhancement of HIV Infection of Monocytes

Inhibition of Anti-HIV MicroRNA Expression: A Mechanism for Opioid-Mediated Enhancement of HIV Infection of Monocytes

Heroin reduces startle and cortisol response in opioid-maintained heroin-dependent patients

Heroin dependence (HD) is a chronic relapsing brain disorder characterized by a compulsion to seek and use heroin. Stress is seen as a key factor for heroin use. Methadone maintenance and the prescription of pharmaceutical heroin [diacetylmorphine (DAM)] are established treatments for HD in several countries. The present study examined whether DAM-maintained patients and methadone-maintained patients differ from healthy controls in startle reflex and cortisol levels. Fifty-seven participants, 19 of each group matched for age, sex and smoking status, completed a startle session which included the presentation of 24 bursts of white noise while eye-blink responses to startling noises were recorded. Salivary cortisol was collected three times after awakening, before, during and after the startle session. DAM was administered before the experiment, while methadone was administered afterwards. Both heroin-dependent patient groups exhibited significantly smaller startle responses than healthy controls (P < 0.05). Whereas the cortisol levels after awakening did not differ across the three groups, the experimental cortisol levels were significantly lower in DAM-maintained patients, who received their opioid before the experiment, than in methadone-maintained patients and healthy controls (P < 0.0001). Opioid maintenance treatment for HD is associated with reduced startle responses. Acute DAM administration may suppress cortisol levels, and DAM maintenance treatment may represent an effective alternative to methadone in stress-sensitive, heroin-dependent patients.

Affective reactivity in heroin-dependent patients with antisocial personality disorder

The Antisocial personality disorder (ASPD), one of the most common co-morbid psychiatric disorders in heroin-dependent patients, is associated with a lack of affective modulation. The present study aimed to compare the affect-modulated startle responses of opioid-maintained heroin-dependent patients with and without ASPD relative to those of healthy controls. Sixty participants (20 heroin-dependent patients with ASPD, 20 heroin-dependent patients without ASPD, 20 healthy controls) were investigated in an affect-modulated startle experiment. Participants viewed neutral, pleasant, unpleasant, and drug-related stimuli while eye-blink responses to randomly delivered startling noises were recorded continuously. Both groups of heroin-dependent patients exhibited significantly smaller startle responses (raw values) than healthy controls. However, they showed a normal affective modulation: higher startle responses to unpleasant, lower startle responses to pleasant stimuli and no difference to drug-related stimuli compared to neutral stimuli. These findings indicate a normally modulated affective reactivity in heroin-dependent patients with ASPD.

Patients on injectable diacetylmorphine maintenance have low bone mass

Risk factors for osteoporosis are prevalent in chronic heroin users who often start using opiates in their late teens. This study was the first to evaluate bone mineral density (BMD) in relatively young heroin-dependent patients on injectable heroin maintenance. Using cross-sectional design, BMD was assessed in a convenience sample of 19 patients (mean age ± SD = 33.9 ± 5.4; 13 men) prescribed injectable diacetylmorphine for heroin dependence. BMD of the lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry. Substance use and menstrual history, psychopathology and risk factors for low BMD were assessed by questionnaire-based interviews. According to World Health Organisation criteria almost three-quarters (74%) of the sample had osteopenia (n = 11) or osteoporosis (n = 3) at one or more sites of measurement. All patients showed multiple risk factors for bone loss, with pack-years of tobacco use and years of heroin use reaching marginally significant associations with spine Z-scores. Moreover, BMD Z-scores correlated significantly negatively with increasing age at all sites, indicating that the older the patient, the greater the BMD deviation from an age-controlled population. Prolonged heroin dependence appears to be associated with lower-than-normal bone mass already at early age and these individuals might be at greater risk for fracture with advancing age. The negative correlation of age-adjusted Z-scores with increasing age suggests factors other than age for low BMD in this population (e.g. smoking, heroin use). Prospective studies are warranted to determine the necessity for diagnostic and preventive measures.

Neither single‐marker nor haplotype analyses support an association between the dopamine transporter gene and heroin dependence in Han Chinese

Much evidence suggests that dysfunction of dopamine transporter-mediated dopamine transmission may be involved in the pathophysiology of substance abuse and dependence. The aim of this study was to examine whether the dopamine transporter gene (DAT1; SLC6A3) is associated with the development of heroin dependence (HD) and whether DAT1 influences personality traits in patients with HD. Polymorphisms of DAT1 were analyzed in a case-control study of 1046 Han Chinese (615 patients and 431 controls). All participants were screened using a Chinese version of the modified Schedule of Affective Disorder and Schizophrenia-Lifetime and all patients met the criteria for HD. Furthermore, a Chinese version of the Tridimensional Personality Questionnaire (TPQ) was used to assess personality traits in the patient group and examine the association between their personality traits and DAT1 polymorphisms. Of the patient group, 271 completed the TPQ. No statistically significant differences in allele or genotype frequencies of all investigated variants between HD patients and controls were observed. In haplotype analyses, four haplotype blocks of DAT1 were not associated with the development of HD. These DAT1 polymorphisms did not influence novelty seeking and harm avoidance scores in HD patients. This study suggests that the DAT1 gene may not contribute to the risk of HD and specific personality traits in HD among the Han Chinese population.

Risk Factors for Attempting Suicide in Heroin Addicts

In order to examine risk factors for attempting suicide in heroin dependent patients, a group of 527 abstinent opiate dependent patients had a psychiatric interview and completed the Childhood Trauma Questionnaire. Patients who had or had never attempted suicide were compared on putative suicide risk factors. It was found that 207 of the 527 heroin abusers (39.3%) had attempted suicide. Attempters were younger; more were female, reported childhood trauma, a family history of suicidal behavior, a history of aggression, treatment with antidepressant medication, and alcohol and cocaine dependence. Logistic regression revealed that a family history of suicidal behavior, alcohol dependence, cocaine dependence, and treatment with antidepressant medication were significant predictors of attempting suicide. These results suggest that attempting suicide is common among opiate dependent patients and that both distal and proximal risk factors may play a role.

Long-Acting Injectable Versus Oral Naltrexone Maintenance Therapy With Psychosocial Intervention for Heroin Dependence

To conduct a quasi-experimental comparison of early clinical outcomes between injectable, sustained-release, depot naltrexone formulation versus oral naltrexone maintenance therapy in individuals with opiate dependence. Early retention in treatment and urine-confirmed opiate use in the first 8 weeks postdetoxification were compared between patients (diagnosed as opiate-dependent according to DSM-IV criteria) participating in 2 concurrently run randomized clinical trials of oral (n = 69; patients treated from September 1999 to May 2002) and long-acting injectable (n = 42; patients treated from November 2000 to June 2003) naltrexone maintenance therapy with psychosocial therapy. Long-acting injectable naltrexone produced significantly better outcome than oral naltrexone on days retained in treatment (F(1,106) = 6.49, P = .012) and for 1 measure of opiate use (F(1,106) = 5.26, P = .024); other measures were not significantly different, but differences were in the same direction. In subanalyses, there were interaction effects between baseline heroin use severity and type of treatment. In subanalyses, heroin users with more severe baseline use showed better retention with oral naltrexone maintenance therapy combined with intensive psychotherapy (behavioral naltrexone therapy) as compared to retention shown by severe heroin users treated with long-acting naltrexone injections combined with standard cognitive-behavioral therapy (χ²(1)= 9.31, P = .002); less severe heroin users evidenced better outcomes when treated with long-acting injectable naltrexone. This quasi-experimental analysis provides tentative indications of superior outcomes for heroin-dependent patients treated with long-acting injectable naltrexone compared to oral naltrexone. The finding that heroin users with more severe baseline use achieved better outcomes with oral naltrexone is most probably attributable to the intensive nature of the psychosocial treatments provided and points to the opportunity for continued research in augmenting injectable naltrexone with psychosocial strategies to further improve outcome, especially in individuals with more severe use. The results should be considered exploratory given the quasi-experimental nature of the study.

Temporal changes of smoking status and motivation among Chinese heroin-dependent, methadone-maintained smokers

Introduction The rates of cigarette smoking remain extremely high in active heroin users and methadone-maintained patients. It remains undetermined whether smoking status and motivation would be differentially affected by heroin and methadone administration. Methods Heroin-dependent, methadone-maintained patients were recruited in the present studies. A battery of self-report questionnaires was used in the current study, in order to assess smoking status and motivations before first heroin use, during active heroin use and after Methadone Maintenance Treatment (MMT) admission. Results An extremely high portion of participants started smoking before first heroin use. The highest level of cigarette smoking was found during the period of active heroin use, and cigarette consumption was reported to decrease after MMT admission. A wide range of smoking motivations were found before first heroin use. Moreover, “maintaining heroin pleasure” was the primary motivation for the increase in cigarette consumption during the period of active heroin use and 1 h after heroin administration, while “habitual smoking” was the primary smoking motivation before first heroin use and after MMT admission respectively. Conclusions The present study first demonstrated that the prolonged rewarding effect of heroin following cigarette smoking may account for the increase of nicotine consumption found in the heroin-dependent patients. It appears that heroin and methadone differentially influenced smoking status and motivation among heroin-dependent, methadone-maintained patients.

Heroin-assisted treatment in the Netherlands: History, findings, and international context

This monograph describes the history, findings and international context of heroin-assisted treatment (HAT) in the Netherlands. The monograph consists of (1) a short introduction and seven paragraphs describing the following aspects of HAT in the Netherlands: (2) history of HAT studies and implementation of routine HAT in the Netherlands; (3) main findings on efficacy, safety and cost-effectiveness from the two randomized controlled HAT trials in the Netherlands; (4) new findings from a large cohort study on the effectiveness of HAT in routine clinical practice in the Netherlands; (5) unique data on the patient's perspective of HAT; (6) data on the pharmacological and pharmaceutical basis for HAT in the Netherlands; (7) description of the registration process; and (8) account of the international context of HAT. Together, these data show that HAT can now be considered a safe and proven-effective intervention for the treatment of chronic, treatment-resistant heroin dependent patients.