Frontal and cingulate gray matter volume reduction in heroin dependence: Optimized voxel-based morphometry

Aims: Repeated exposure to heroin, a typical opiate, causes neuronal adaptation and may result in anatomical changes in specific brain regions, particularly the frontal and limbic cortices. The volume changes of gray matter (GM) of these brain regions, ho

The contribution of research to Australian policy responses to heroin dependence 1990-2001: a personal retrospection

Periodic public concern about heroin use has been a major driver of Australian drug policy in the four decades since heroin use was first reported. The number of heroin-dependent people in Australia has increased from several hundreds in the late 1960s to around 100000 by the end of the 1990s. In this paper I do the following: (1) describe collaborative research on heroin dependence that was undertaken between 1991 and 2001 by researchers at the National Drug and Alcohol Research Centre: (2) discuss the contribution that this research may have made to the formulation of policies towards the treatment of heroin dependence during a period when the policy debate crystallized around the issue of whether or not Australia should conduct a controlled trial of heroin prescription; and (3) reflect on the relationships between research and policy-making in the addictions field, specifically on the roles of investigator-initiated and commissioned research, the interface between researchers, funders and policymakers: and the need to be realistic about the likely impact of research on policy and practice.

Acute effects of intravenous heroin on the hypothalamic-pituitary-adrenal axis response: a controlled trial

Heroin dependence is associated with a stressful environment and with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. The present study examined the acute effects of intravenous heroin versus placebo on the HPA axis response in heroin-dependent patients. Twenty-eight heroin-dependent patients in heroin-assisted treatment and 20 age- and sex-matched healthy participants were included in a controlled trial in which patients were twice administered heroin or saline in a crossover design, and healthy controls were only administered saline. The HPA axis response was measured by adrenocorticotropic hormone (ACTH) levels and by cortisol levels in serum and saliva before and 20 and 60 minutes after substance administration. Craving, withdrawal, and anxiety levels were measured before and 60 minutes after substance application. Plasma concentrations of heroin and its main metabolites were assessed using high-performance liquid chromatography. Heroin administration reduces craving, withdrawal, and anxiety levels and leads to significant decreases in ACTH and cortisol concentrations (P < 0.01). After heroin administration, cortisol concentrations did not differ from healthy controls, and ACTH levels were significantly lower (P < 0.01). In contrast, when patients receive saline, all hormone levels were significantly higher in patients than in healthy controls (P < 0.01). Heroin-dependent patients showed a normalized HPA axis response compared to healthy controls when they receive their regular heroin dose. These findings indicate that regular opioid administration protects addicts from stress and underscore the clinical significance of heroin-assisted treatment for heroin-dependent patients.

Epidemiology of heroin : 1964-1984.

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Serious adverse events in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD)

Aims The study estimated serious adverse event (SAE) rates among entrants to pharmacotherapies for opioid dependence, during treatment and after leaving treatment. Design A longitudinal study based on data from 12 trials included in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD). Participants and settings A total of 1.244 heroin users and methadone patients treated in hospital, community and GP settings. Intervention Six trials included detoxification; all included treatment with methadone, buprenorphine, levo-alpha-acetyl-methadol (LAAM) or naltrexone. Findings During 394 person-years of observation, 79 SAEs of 28 types were recorded. Naltrexone participants experienced 39 overdoses per 100 person-years after leaving treatment (44% occurred within 2 weeks after stopping naltrexone). This was eight times the rate recorded among participants who left agonist treatment. Rates of all other SAEs were similar during treatment versus out of treatment, for both naltrexone-treated and agonist-treated participants. Five deaths occurred, all among participants who had left treatment, at a rate of six per 100 person-years. Total SAE rates during naltrexone and agonist treatments were similar (20, 14 per 100 person-years, respectively). Total SAE and death rates observed among participants who had left treatment were three and 19 times the corresponding rates during treatment. Conclusions Individuals who leave pharmacotherapies for opioid dependence experience higher overdose and death rates compared with those in treatment. This may be due partly to a participant self-selection effect rather than entirely to pharmacotherapy being protective. Clinicians should alert naltrexone treatment patients in particular about heroin overdose risks. Duty of care may extend beyond cessation of dosing.

A cost-effectiveness analysis of buprenorphine-assisted heroin withdrawal

The purpose of this study was to conduct a cost - effectiveness analysis of detoxification from heroin using buprenorphine in a specialist clinic versus a shared care setting. A randomized controlled trial was conducted with a total of 115 heroin-dependent patients receiving a 5-day treatment regime of buprenorphine. The specialist clinic was a community-based treatment agency in inner-city Sydney. Shared care involved treatment by a general practitioner supplemented by weekend dispensing and some concurrent counselling at the specialist clinic. Quanti. cation of resource use was limited to inputs for treatment provision. The primary outcome measure used in the economic analysis was the proportion of each group that completed detoxification and achieved an initial 7-day period of abstinence. Buprenorphine detoxification in the shared care setting was estimated to be $24 more expensive per patient than treatment at the clinic, which had an average treatment cost of $332 per patient. Twenty-three per cent of the shared care patients and 22% of the clinic patients reported no opiate use during the withdrawal period. These results suggest that the provision of buprenorphine treatment for heroin dependence in shared care and clinic appear to be equally cost - effective.

The impact of a reduction in drug supply on demand for and compliance with treatment for drug dependence

Background: In early 2001, Australia experienced a sudden, dramatic and;sustained decrease in heroin availability that was accompanied by sharp increases in price and decreases in street level purity-the so-called heroin shortage. These unprecedented changes occurred in a context of widespread treatment availability, which made it possible for the first time to examine the impact of a sharp reduction in heroin supply in New South Wales (NSW) on entry to and adherence with treatment for heroin dependence. Given the evidence of drug substitution by some users. the current paper also examines the effects of the shortage on entry to treatment for other forms of drug dependence. Methods: Interrupted time-series analysis of the number of persons entering opioid pharmacotherapy and other treatment modalities in NSW for heroin dependence and for the treatment for other types of drug dependence. Findings: The heroin shortage was associated with a reduction in the number of younger persons entering opioid pharmacotherapy. There was a dramatic decrease in the number of persons entering heroin withdrawal or assessment only treatment episodes. There appear to have been small improvements in adherence to and retention in heroin treatment after the reduction in heroin supply. Relatively small increases were observed in numbers being treated for cocaine dependence. Conclusions: In the context of good treatment provision, a reduction in heroin supply appeared to produce modest improvements in intermediate outcomes. Supply and demand reduction measures, when both are implemented successfully, may be complementary. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Does naltrexone treatment lead to depression? Findings from a randomized controlled trial in subjects with opioid dependence

Objective: Dysphoria and depression have been cited as side effects of the opioid antagonist naltrexone. We aimed to assess whether depressive symptoms are a clinically relevant side effect in a population receiving naltrexone as a treatment for opioid dependence. Methods: We carried out a randomized controlled, open-label trial comparing rapid opiate detoxification under anesthesia and naltrexone treatment with continued methadone maintenance at the Alcohol and Drug Service, Royal Brisbane and Women's Hospital, Brisbane, Australia. The study subjects were patients stabilized on methadone maintenance treatment for heroin dependence who wished to transfer to naltrexone treatment. The Beck Depression Inventory, State-Trait Anxiety Inventory and Opiate Treatment Index subscales for heroin use and social functioning were used at baseline and follow-up assessments at 1, 2, 3 and 6 months. Results: Forty-two participants were allocated to receive naltrexone treatment, whereas 38 continued methadone maintenance as the control condition. Participants who received naltrexone did not exhibit worsening of depressive symptoms. In participants attending all follow-up assessments, there was a trend for those receiving naltrexone to exhibit an improvement in depression over time compared with the control group. Participants who were adherent to naltrexone treatment exhibited fewer depressive symptoms than those who were nonadherent. Conclusions: These results suggest that depression need not be considered a common adverse effect of naltrexone treatment or a treatment contraindication and that engaging with or adhering to naltrexone treatment may be associated with fewer depressive symptoms.

Referring heroin users from compulsory detoxification centers to community methadone maintenance treatment: a comparison of three models.

BACKGROUND: Both compulsory detoxification treatment and community-based methadone maintenance treatment (MMT) exist for heroin addicts in China. We aim to examine the effectiveness of three intervention models for referring heroin addicts released from compulsory detoxification centers to community methadone maintenance treatment (MMT) clinics in Dehong prefecture, Yunnan province, China. METHODS: Using a quasi-experimental study design, three different referral models were assigned to four detoxification centers. Heroin addicts were enrolled based on their fulfillment to eligibility criteria and provision of informed consent. Two months prior to their release, information on demographic characteristics, history of heroin use, and prior participation in intervention programs was collected via a survey, and blood samples were obtained for HIV testing. All subjects were followed for six months after release from detoxification centers. Multi-level logistic regression analysis was used to examine factors predicting successful referrals to MMT clinics. RESULTS: Of the 226 participants who were released and followed, 9.7% were successfully referred to MMT(16.2% of HIV-positive participants and 7.0% of HIV-negative participants). A higher proportion of successful referrals was observed among participants who received both referral cards and MMT treatment while still in detoxification centers (25.8%) as compared to those who received both referral cards and police-assisted MMT enrollment (5.4%) and those who received referral cards only (0%). Furthermore, those who received referral cards and MMT treatment while still in detoxification had increased odds of successful referral to an MMT clinic (adjusted OR = 1.2, CI = 1.1-1.3). Having participated in an MMT program prior to detention (OR = 1.5, CI = 1.3-1.6) was the only baseline covariate associated with increased odds of successful referral. CONCLUSION: Findings suggest that providing MMT within detoxification centers promotes successful referral of heroin addicts to community-based MMT upon their release.

Methadone as Social Control: Institutionalized Stigma and the Prospect of Recovery

Methadone maintenance treatment (MMT) is an intervention used to treat opioid (heroin) dependence. Several investigators have found that MMT is effective in reducing heroin use and other behaviors; however, a disproportionate number of MMT clients leave treatment prematurely. Moreover, MMT outcome variables are often limited in terms of their measurement. Utilizing an integrated theoretical framework of social control and stigma, we focused on the experiences of methadone maintenance from the perspective of clients. We pooled interview data from four qualitative studies in two jurisdictions and found linkages between social control and institutional stigma that serve to reinforce "addict" identities, expose undeserving customers to the public gaze, and encourage clients to be passive recipients of treatment. We discuss the implications for recovery and suggest recommendations for change.

The effects of the opioid pharmacotherapies methadone, LAAM and buprenorphine, alone and in combination with alcohol, on simulated driving

While methadone is currently the primary pharmacotherapy used in the treatment of heroin dependence in Australia, levo-alpha-acetyl-methodol (LAAM) and buprenorphine are new pharmacotherapies that are being examined as alternatives to methadone maintenance treatment. The aim of this research is to consider the effects of the methadone, buprenorphine and LAAM, as used in maintenance pharmacotherapy for heroin dependence, upon simulated driving. Clients stabilised in methadone, LAAM and buprenorphine treatment programs for 3 months, and a control group of non-drug-using participants, took part in this study which involved operating a driving simulator over a 75 min period.

The fine line between harm reduction and harm production - development of a clinical policy on femoral (groin) injecting

The femoral region ('groin') appears to be increasingly commonly used by injecting drug users in the UK. With the advent of Britain's first supervised prescribed injectable opioid treatment clinic, unprecedented decisions and judgements were required about the safe supervision of this practice, or whether to permit this behaviour on site at all. This paper reports the reasons for, and outcome of, development of a clinical policy on injecting into the deep femoral vein (groin injecting)

Trends in morphine prescriptions, illicit morphine use and associated harms among regular injecting drug users in Australia

This paper examines population trends in morphine prescriptions in Australia, and contrasts them with findings from annual surveys with regular injecting drug users (IDU). Data on morphine prescriptions from 1995 to 2003 were obtained from the Drug Monitoring System (DRUMS) run by the Australian Government Department of Health and Ageing. Data collected from regular IDU as part of the Australian Illicit Drug Reporting System (IDRS) were analysed (2001-2004). The rate of morphine prescription per person aged 15-54 years increased by 89% across Australia between 1995 and 2003 (from 46.3 to 85.9 mg per person). Almost half (46%) of IDU surveyed in 2004 reported illicit morphine use, with the highest rates in jurisdictions where heroin was less available. Recent morphine injectors were significantly more likely to be male, unemployed, out of treatment and homeless in comparison to IDU who had not injected morphine. They were also more likely to have injected other pharmaceutical drugs and to report injection related problems. Among those who had injected morphine recently, the most commonly reported injecting harms were morphine dependence (38%), difficulty finding veins into which to inject (36%) and scarring or bruising (27%). Morphine use and injection is a common practice among regular IDU in Australia. In some cases, morphine may be a substitute for illicit heroin; in others, it may be being used to treat heroin dependence where other pharmacotherapies, such as methadone and buprenorphine, are perceived as being unavailable or undesirable by IDU. Morphine injection appears to be associated with polydrug use, and with it, a range of problems related to drug injection. Further research is required to monitor and reduce morphine diversion and related harms by such polydrug injectors.

Differences in onset and abuse/dependence episodes between prescription opioids and heroin: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

OBJECTIVES: To examine patterns of onset and abuse/dependence episodes of prescription opioid (PO) and heroin use disorders in a national sample of adults, and to explore differences by gender and substance abuse treatment status. METHODS: Analyses of data from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093). RESULTS: Of all respondents, 5% (n = 1815) reported a history of nonmedical PO use (NMPOU) and 0.3% (n = 150) a history of heroin use. Abuse was more prevalent than dependence among NMPOUs (PO abuse, 29%; dependence, 7%) and heroin users (heroin abuse, 63%; dependence, 28%). Heroin users reported a short mean interval from first use to onset of abuse (1.5 years) or dependence (2.0 years), and a lengthy mean duration for the longest episode of abuse (66 months) or dependence (59 months); the corresponding mean estimates for PO abuse and dependence among NMPOUs were 2.6 and 2.9 years, respectively, and 31 and 49 months, respectively. The mean number of years from first use to remission from the most recent episode was 6.9 years for PO abuse and 8.1 years for dependence; the mean number of years from first heroin use to remission from the most recent episode was 8.5 years for heroin abuse and 9.7 years for dependence. Most individuals with PO or heroin use disorders were remitted from the most recent episode. Treated individuals, whether their problem was heroin or POs, tended to have a longer mean duration of an episode than untreated individuals. CONCLUSION: Periodic remissions from opioid or heroin abuse or dependence episodes occur commonly but take a long time. Timely and effective use of treatment services are needed to mitigate the many adverse consequences from opioid/heroin abuse and dependence.