A proposed approach to confirm heroin administration - Regional differences in heroin purity is a major factor.

In forensic toxicology, a marker of street heroin use is urgent especially in the absence of urinary 6-monoacetylmorphine. ATM4G, the Glucuronide of Acetylated product of Thebaine compound 4 Metabolite (ATM4), arising from byproducts of street heroin synthesis has been considered as a useful marker in some European studies. However, whether ATM4G is a universal marker particularly in Southeast Asia due to 'street' heroin with high purity, it's still unclear. To investigate putative markers for different regions, ATM4G and other metabolites including the Acetylated product of Thebaine compound 3 Metabolite (ATM3) and thebaol, also originated from thebaine were detected in 552 urine samples from heroin users in Taiwan. Results were compared with that from samples collected in the UK and Germany. Only a sulfo-conjugate of ATM4, ATM4S, was detected in 28 Taiwanese users using a sensitive MS3 method whilst out of 351 samples from the UK and Germany, ATM4G was present in 91. Thebaol-glucuronide was first time detected in 118. No markers were detected in urine following herbal medicine use or poppy seed ingestion. The presence of ATM4S/ATM4G might be affected by ethnicities and heroin supplied in regions. Thebaol-glucuronide is another putative marker with ATM4G and ATM4S for street heroin use.

"Tranq-dope": The first fatal intoxication due to xylazine-adulterated heroin in Italy.

BACKGROUND AND AIMS: The number of xylazine-involved overdose deaths tremendously increased from 2019 onwards in the US. This is due to the "tranq-dope" trend consisting in mixing opioids with the sedative to reduce drug manufacturing costs and enhance their effects. In this study, we report the first fatality involving xylazine-adulterated heroin in the EU. MATERIALS AND METHODS: The subject was a 33-year-old Caucasian male with a documented history of drug abuse who was found dead in a public area with puncture marks at the elbow. Peripheral blood and urine were collected at the autopsy and analyzed by liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) after protein precipitation. RESULTS: 6-Monoacetylmorphine, total/free morphine, and codeine blood concentrations of 20.3, 236/105, and 38.3 ng/mL, respectively, indicated recent heroin consumption. Methadone blood concentration was below 10 ng/mL. Alprazolam, nordiazepam, and flurazepam blood concentrations were 23.9, 61.4, and 55.0 ng/mL, respectively. Benzoylecgonine blood concentration was below 5 ng/mL. Xylazine blood and urine concentrations were 105 and 72.6 ng/mL, respectively. CONCLUSION: The combination of central nervous system depressants, i.e., opioids, benzodiazepines, and xylazine, was the principal cause of death by cardiorespiratory failure. The case was promptly reported to the UE Early Warning System on drugs.

Bedside urine testing for fentanyl in self-reported heroin users in a tertiary Brisbane emergency department.

OBJECTIVE: To determine if patients presenting to our toxicology unit following self-reported heroin use had positive urine immunoassay testing for fentanyl or its analogues. METHODS: Urine samples from consenting patients were tested at the bedside for the presence of opiates or fentanyl and its analogues. RESULTS: Over a 30-month period, 58 patients were recruited. All samples tested positive for opiates, but none tested positive for fentanyl or its analogues. CONCLUSION: In patients presenting to our toxicology unit in Brisbane, we did not find any cases where the urine of patients self-reporting heroin exposure tested positive for fentanyl or its analogues.

Retrospective study of outcomes, for patients admitted to a drug treatment centre board.

Retrospective study of urinary heroin outcomes of a cohort (123) of patients commenced on a methadone treatment program. Significantly poorer outcomes were associated with urines positive for cocaine (OR 0.69 CI 0.59-0.81) benzodiazepines (OR 0.7 CI 0.53-0.93) with prescribing of low dose methadone (OR 0.65 CI 0.48-0.87), with urines positive for heroin at time of admission (OR 0.74 CI 0.56-0.97) and with behavioural sanctions (OR 0.8, CI 0.65-0.98). Improved outcomes were associated with granting of take away methadone (OR 1.34 CI 1.1-1.62). with an indication of improved outcomes associated with alcohol positive urines (OR 1.34 CI 0.95-1.9) and increased duration of clinic attendance (OR 1.21 CI 0.99-1.47). On multiple regression analysis low dose methadone (0.07 CI 0.01-0.33) prescribing remained negatively associated with urine heroin outcomes.

Tetrodotoxin alleviates acute heroin withdrawal syndrome: a multicentre, randomized, double-blind, placebo-controlled study.

1. Tetrodotoxin (TTX) is a powerful sodium channel blocker extracted from the puffer fish. The efficacy and safety of TTX as monotherapy for the treatment of acute heroin withdrawal syndrome were evaluated in the present study. This 7-day, multicentre, randomized, double-blind, placebo-controlled study was carried out between December 2008 and October 2009. In total, 216 patients who met the Diagnostic and Statistical Manual of Mental Disorders IV diagnosis of heroin addiction were recruited. After providing written informed consent, subjects were randomly assigned to double-blind treatment in one of the following groups: 5 µg TTX group (group 1), 10 µg TTX group (group 2) or the placebo group (group 3). 2. Evidence suggests that both 5 and 10 µg TTX significantly reduced withdrawal symptoms by day 3 compared with placebo, and there was no significant difference in the incidence of adverse events in the three groups. 3. In conclusion, this clinical trial shows that TTX (5 and 10 µg given t.i.d.) is effective in alleviating opiate withdrawal symptoms with few side-effects.

Effect of psychiatric severity on the outcome of methadone maintenance treatment.

While psychiatric comorbidity has been shown to produce a negative impact on the outcome of opioid use disorders, longitudinal studies carried out in the context of methadone maintenance treatment programs (MMTP) to evaluate outcomes strictly linked to methadone efficacy have not demonstrated a similar negative influence. To verify whether results obtained considering psychopathology in terms of formal psychiatric diagnoses were replicated when assessing psychopathology in terms of global psychiatric severity, a retrospective cohort study was designed. 259 patients commencing methadone maintenance treatment were divided into two groups on the basis of SCL-90 severity score and compared for retention in treatment, toxicological urine test results and psychological/psychiatric status throughout a one year period of observation. The results of the study suggest that patients in MMTP with high psychiatric severity are not characterized by a lower retention in treatment or higher substance use than those with low psychiatric severity. Moreover, during treatment high severe psychiatric patient status appears to improve significantly for all psychological/psychiatric dimensions explored by SCL-90. These results are consistent with those obtained in previous studies on the efficacy of MMTP, comprehensive of psychiatric care, irrespective of the severity of psychopathology exhibited by patients at the beginning of treatment.

Using Urine Drug Testing to Estimate the Prevalence of Drug Use : Lessons Learned From the New York City Health and Nutrition Examination Survey, 2013-2014.

OBJECTIVES: Estimating the prevalence of drug use in the general population is important given its potential health consequences but is challenging. Self-reported surveys on drug use have inherent limitations that underestimate drug use. We evaluated the performance of linking urine drug testing with a local, representative health examination survey in estimating the prevalence of drug use in New York City (NYC). METHODS: We used urine drug testing from the NYC Health and Nutrition Examination Survey (NYC HANES) to estimate the prevalence of drug use (benzodiazepines, cocaine, heroin, and opioid analgesics) among the study sample and compare the findings with self-reported responses to questions about past-12-month drug use from the same survey. RESULTS: Of 1527 respondents to NYC HANES, urine drug testing was performed on 1297 (84.9%) participants who provided urine and consented to future studies. Self-reported responses gave past-12-month weighted estimates for heroin, cocaine, or any prescription drug misuse of 13.8% (95% CI, 11.6%-16.3%), for prescription drug misuse of 9.9% (95% CI, 8.1%-12.1%), and for heroin or cocaine use of 6.1% (95% CI, 4.7%-7.9%). Urine drug testing gave past-12-month weighted estimates for any drug use of 4.3% (95% CI, 3.0%-6.0%), for use of any prescription drug of 2.8% (95% CI, 1.9%-4.1%), and for heroin or cocaine use of 2.0% (95% CI, 1.2%-3.6%). CONCLUSION: Urine drug testing provided underestimates for the prevalence of drug use at a population level compared with self-report. Researchers should use other methods to estimate the prevalence of drug use on a population level.

Comparison of urine results concerning co-consumption of illicit heroin and other drugs in heroin and methadone maintenance programs.

Urine samples of patients from a heroin maintenance program (HMP) and a methadone maintenance program (MMP) were chromatographically analyzed 1 month before and 6 and 12 months into treatment for the presence of classical markers of heroin use as well as for the presence of markers for illicit heroin abuse. Furthermore, the samples were immunochemically tested for cannabinoids, cocaine metabolites, amphetamine, methylendioxyamphetamines and benzodiazepines. A co-consumption of illicit heroin (HER) in the HMP was determined to be 50% but was significantly lower compared to the MMP with a co-use of 71%. The incidence was high because not only acetylcodeine (AC) as a very specific marker was considered but also other marker substances for illicit HER use. Amphetamines played only a minor part in both collectives, and the proportion of HER and methadone patients using cocaine was similar and decreased during treatment. Also, the benzodiazepine use decreased, and cannabis use was high in both collectives during treatment. Considering only the AC in the present study, a co-use of illicit HER in the HMP was similar to previous reports concerning HER-assisted treatment programs. If additional marker substances were examined, the suspicion of a co-use of illicit HER is markedly enhanced.

Evaluation of prooxidant-antioxidant balance in chronic heroin users in a single assay: an identification criterion for antioxidant supplementation.

BACKGROUND: Opiate abuse has been linked to oxidative stress, through the separate evaluation of oxidants and antioxidants. OBJECTIVES: To determine prooxidant-antioxidant balance (PAB) in chronic heroin users in a single assay, easily applied in a clinical setting. Specifically, to examine whether PAB values correlate with the duration of abuse or with the presence of anti-HCV antibodies. METHODS: Sixty-four chronic heroin users - 34 cases and 30 controls - participated in this study. PAB was determined by an Enzyme-linked immunosorbent assay (ELISA) method, developed by members of the study group. RESULTS: In heroin users, oxidative balance was disrupted in favor of prooxidants. There was no correlation of PAB values with the duration of abuse or with the presence of anti-Hepatitis C virus (HCV) antibodies. CONCLUSIONS: Chronic heroin users can benefit from an antioxidant therapy, and the method currently presented can be used as an identification criterion.

Identification of characteristic heroin metabolites in urine based on data-mining technology and multivariate statistics analysis combined with a targeted verification approach for distinguishing heroin abusers.

A common phenomenon shows that ingestion of opium poppy shell-containing drugs can result in a "false-positive" urinalysis test result for mandatory or workplace heroin abuse screening. Owing to the short detection window (8 h in urine) of the characteristic heroin metabolite 6-monoacetylmorphine (6-MAM) confirmation or exclusion of heroin abusers still presents major challenges for toxicologists. In this work, we developed an ultra-performance liquid chromatography-time-of-flight mass spectrometry method (UPLC-TOF-MS) with online data acquisition and multiple post-data-mining technologies combined with a multivariate statistical and batch validation analysis workflow to assess the characteristic urine metabolites of heroin abusers. Based on the proposed methods, 28 characteristic metabolites were structurally identified, and their fragmentation patterns and metabolite pathways were also summarized. Correlation analysis was used to investigate the internal relationship and similarities among the identified metabolites, and seven representative metabolites were selected as "Target-metabolites". Multi-batch urine of samples of heroin abusers were certified based on the UPLC-MS/MS method for further validation of the practicability of using this method for routine analysis. Overall, the target-metabolites can be utilized as assistant "biomarkers" in workplace or mandatory drug screenings. This approach encourages further studies on the development of the "false-positive" identification system.

Effect of positive urine fentanyl screen on attitudes toward heroin use.

BACKGROUND: It is unknown if targeted risk reduction counseling in the health care setting, after documented exposure to fentanyl, can affect behavior change to reduce risks and increase utilization of evidence-based overdose prevention strategies. METHODS: We conducted a retrospective analysis of results (7/2018-6/2019) from questionnaire-facilitated counseling by recovery coaches in the emergency department (ED) and primary care settings following disclosure of a urine toxicology positive for fentanyl. RESULTS: Seventy-five percent of N = 101 respondents were neither aware of nor expecting fentanyl in their substances of use. Fifty-three (70 %) of those initially unaware answered that learning about exposure to and the risks from fentanyl changed their thoughts about reducing or abstaining from use. A greater proportion of patients seen in the ED expressed desire to stop or reduce opioid use as compared to ambulatory clinic patients (91 % vs. 46 %, p < 0.001). Of those not already engaged in treatment, 18 % and 15 % were interested in medication and behavioural health treatment, respectively, and each of them indicated a change in thought based on the counseling. Forty-five percent of individuals not yet receiving naloxone endorsed interest in receiving it, and 22 % of all respondents were somewhat or very interested in access to safe consumption sites. CONCLUSION: This study suggests a novel clinical utility in toxicology screens to inform behavior in the setting of illicit fentanyl exposure. In addition to linkages to evidence-based treatment, linkages to harm-mitigating strategies associated with ongoing substance use may be critical to a comprehensive overdose prevention strategy in the clinical setting.

Cocaine and opiates use in pregnancy: detection of drugs in neonatal meconium and urine.

In this study, the case of a newborn with symptoms of hyperexcitability was analyzed. After it was confirmed in the hospital that the mother had consumed drugs during pregnancy using an enzyme multiplied immunoassay technique, samples of the newborn's urine and meconium were sent to our laboratory to observe the evolution in the distribution of cocaine and opiates during the days following birth. For urine analysis, screening was done with an immunoassay technique, and the confirmation was done by gas chromatography-mass spectrometry (GC-MS) according to a published method. A GC-MS method for simultaneous analysis of cocaine, benzoylecgonine, codeine, morphine, and 6-acetylmorphine in meconium is described. GC-MS confirmation of urine and meconium results showed consumption of cocaine and codeine during pregnancy and also showed the levels of drugs gradually declined, totally disappearing by the third day.

Diacetylmorphine (heroin) body packer presenting with respiratory arrest.

Intracorporeal concealment of illicit drugs known as 'body packing' is uncommonly reported. A body packer with swallowed capsules containing Diacetylmorphine (heroin) for smuggling purposes presented with respiratory arrest and recovered after ventilatory support and nalaxone infusion.

The effects of extended-release injectable naltrexone and incentives for opiate abstinence in heroin-dependent adults in a model therapeutic workplace: A randomized trial.

AIM: To determine whether extended-release injectable naltrexone (XR-NTX), incentives for opiate abstinence, and their combination reduce opiate use compared to a usual care control and whether the combination reduces opiate use compared to either treatment alone. DESIGN: Randomized 2 × 2 single-site controlled trial conducted from November 2012 through May 2016. After a detoxification and oral naltrexone induction, participants were assigned to a Usual Care, Abstinence Incentives, XR-NTX, or XR-NTX plus Abstinence Incentives group for a six-month intervention period. SETTING: A model therapeutic workplace where participants could work on automated computer programs that targeted job-skills training for 4 h every weekday for 24 weeks and earn about $10 per hour. PARTICIPANTS: 84 heroin-dependent adults who were unemployed and medically approved for naltrexone. Most participants were male (71.4%), African American (80.1%), and cocaine dependent (71.4%). MEASUREMENTS: The primary outcome measure was the percentage of urine samples negative for opiates that were collected at once weekly assessments (24 per participant) that were not part of the intervention and for which participants were paid $10 for completing. INTERVENTION: Participants who attended the workplace provided thrice-weekly urine samples. Abstinence Incentives participants had to provide opiate-free urine samples to maintain maximum pay. XR-NTX participants received one injection every 4 weeks and were required to take injections in order to work and to maintain maximum pay. Usual Care participants were not offered XR-NTX and opiate urinalysis results did not affect pay. FINDINGS: A large percentage (65 of 149; 43.6%) of individuals failed the induction protocol required for randomization and to be eligible to receive XR-NTX. When missing urine samples were considered positive, there was no significant interaction between XR-NTX and Abstinence Incentives. XR-NTX plus Abstinence Incentives participants provided significantly more opiate-negative samples (81.3%, SD 39.0%) than XR-NTX participants (64.5%, SD 47.9%; aOR 10.4, 95% CI 1.3-85.5; P = .030). When urine samples were not replaced, there was a significant interaction between XR-NTX and Abstinence Incentives (aOR 77.0, 95% CI 1.3-4432;P = 0.036); XR-NTX plus Abstinence Incentives participants provided significantly more opiate-negative samples (99.6%, SD 0.1%) than XR-NTX participants (85.0%, SD 35.7%; aOR 147.6, 95% CI 6.3-3472; P = 0.002), Abstinence Incentives participants (91.9%, SD 27.3%; aOR 121.7, 95% CI 4.8-3067; P =0.004), and Usual Care participants (78.7%, SD 41.0%; aOR 233.4, 95% CI 9.4-5814; P <.001). No other group differences were significant. CONCLUSION: XR-NTX plus incentives for opiate abstinence increased opiate abstinence, but XR-NTX alone did not. XR-NTX can promote opiate abstinence when it is combined with incentives for opiate abstinence in a model therapeutic workplace.

Predictors of induction onto extended-release naltrexone among unemployed heroin-dependent adults.

BACKGROUND AND AIM: Extended-release naltrexone (XR-NTX) blocks the effects of opioids for 4weeks; however, starting treatment can be challenging because it requires 7 to 10days of abstinence from all opioids. In the present study we identified patient and treatment characteristics that were associated with successful induction onto XR-NTX. METHODS: 144 unemployed heroin-dependent adults who had recently undergone opioid detoxification completed self-report measures and behavioral tasks before starting an outpatient XR-NTX induction procedure. Employment-based reinforcement was used to promote opioid abstinence and adherence to oral naltrexone during the induction. Participants were invited to attend a therapeutic workplace where they earned wages for completing jobs skills training. Participants who had used opioids recently were initially invited to attend the workplace for a 7-day washout period. Then those participants were required to provide opioid-negative urine samples and then take scheduled doses of oral naltrexone to work and earn wages. Participants who had not recently used opioids could begin oral naltrexone immediately. After stabilization on oral naltrexone, participants were eligible to receive XR-NTX and were randomized into one of four treatment groups, two of which were offered XR-NTX. Binary and multiple logistic regressions were used to identify characteristics at intake that were associated with successfully completing the XR-NTX induction. RESULTS: 58.3% of participants completed the XR-NTX induction. Those who could begin oral naltrexone immediately were more likely to complete the induction than those who could not (79.5% vs. 25.0%). Of 15 characteristics, 2 were independently associated with XR-NTX induction success: legal status and recent opioid detoxification type. Participants who were not on parole or probation (vs. on parole or probation) were more likely to complete the induction (OR [95% CI]=2.5 [1.1-5.7], p=0.034), as were those who had come from a longer-term detoxification program (≥21days) (vs. a shorter-term [<21days]) (OR [95% CI]=7.0 [3.0-16.6], p<0.001). CONCLUSIONS: Our analyses suggest that individuals recently leaving longer-term opioid detoxification programs are more likely to complete XR-NTX induction. Individuals on parole or probation are less likely to complete XR-NTX induction and may need additional supports or modifications to induction procedures to be successful.

Urine drug screening for early detection of unwitting use of fentanyl and its analogues among people who inject heroin in Sydney, Australia.

INTRODUCTION AND AIMS: North America has witnessed a dramatic rise in fatal opioid overdoses due to the unwitting consumption of non-pharmaceutical fentanyl and its analogues. While some of the drivers of this crisis-including profitability and access to high-potency opioids through internet sources-also apply in Australia, to our knowledge, there have been no ongoing surveillance studies of local populations. Therefore, this pilot study aimed to detect unintentional fentanyl consumption among people who inject heroin through instant urine screening, and determine the feasibility and acceptability of voluntary urinalysis of clients at the Medically Supervised Injecting Centre, Kings Cross, Sydney. DESIGN AND METHODS: Brief surveys and urine drug screens were conducted with 67 participants in Wave 1 (October 2017) and 51 participants in Wave 2 (March 2018). Urine samples were tested with BTNX Rapid Response™ fentanyl urine strip test at a detection level of 20 ng/mL norfentanyl. These strips also cross-react to numerous fentanyl analogues. RESULTS: There were no cases where positive urine tests suggested unwitting fentanyl use detected in this study. DISCUSSION AND CONCLUSIONS: These negative findings contrast sharply with similar Canadian studies. While no cases of fentanyl-laced heroin use have been detected so far, we have demonstrated that this surveillance design is low-cost, feasible and scalable approach to monitoring the considerable public-health threat of undetected fentanyl and its analogues in Australia. Further validation of cross-reactivity of test strips would strengthen this method.

Influence of social network on drug use among clients of methadone maintenance treatment centers in Kunming, China.

AIMS: To examine drug use behavior of clients attending Methadone Maintenance Treatment (MMT) programs and its relationship with the clients' social network characteristics. DESIGN: Cross-sectional study. SETTING: Four MMT clinics in Kunming, Yunnan province, China. PARTICIPANTS: 324 consecutive MMT clients. MEASUREMENTS: A structured, self-completed questionnaire on background characteristics and existing social network. Current drug use was assessed by urine test for opiate metabolites. ANALYSIS: The association between client's social network characteristics and their own current drug use behavior is analysed using multiple logistic regression adjusting for socio-demographic characteristics. Adjusted odds ratios (AOR) with 95% confidence intervals (CI) are obtained to give the strength of the associations. FINDINGS: MMT clients were more likely to concurrently use heroin while attending MMT if their social network had any of the following characteristics: more than half of the members were older than them (AOR = 1.03, 95% CI = 1.00,1.06), any member had a high level of influence on them (AOR = 6.47, 95% CI = 2.86,14.65) and any member joined them in using drugs (AOR = 1.94, 95% CI = 1.04,3.63). Having a social network member who could provide emotional support (AOR = 0.11, 95% CI = 0.03,0.35), having a spouse and/or child in their social network (AOR = 0.44, 95% CI = 0.24,0.81) and having a social network member with a high level of closeness (AOR = 0.28, 95% CI = 0.09,0.90) were associated with a decreased odds of heroin use. CONCLUSION: Social networks who could provide MMT clients with emotional support and a close relationship were significant factors for reducing the risk of concurrent drug use among clients attending MMT clinics in Kunming, China. Behavioral interventions should address the role of family and social network members in providing support to these clients.

Metabolites of Heroin in Several Different Post-mortem Matrices.

In some forensic autopsies blood is not available, and other matrices are sampled for toxicological analysis. The aims of the present study were to examine whether heroin metabolites can be detected in different post-mortem matrices, and investigate whether analyses in other matrices can give useful information about concentrations in peripheral blood. Effects of ethanol on the metabolism and distribution of heroin metabolites were also investigated. We included 45 forensic autopsies where morphine was detected in peripheral blood, concomitantly with 6-acetylmorphine (6-AM) detected in any matrix. Samples were collected from peripheral blood, cardiac blood, pericardial fluid, psoas muscle, lateral vastus muscle, vitreous humor and urine. Opioid analysis included 6-AM, morphine, codeine, and morphine glucuronides. The 6-AM was most often detected in urine (n = 39) and vitreous humor (n = 38). The median morphine concentration ratio relative to peripheral blood was 1.3 (range 0-3.6) for cardiac blood, 1.4 (range 0.07-5.3) for pericardial fluid, 1.2 (range 0-19.2) for psoas muscle, 1.1 (range 0-1.7) for lateral vastus muscle and 0.4 (range 0.2-3.2) for vitreous humor. The number of 6-AM positive cases was significantly higher (P = 0.03) in the ethanol positive group (n = 6; 86%) compared to the ethanol negative group (n = 14; 37%) in peripheral blood. The distribution of heroin metabolites to the different matrices was not significantly different between the ethanol positive and the ethanol negative group. This study shows that toxicological analyses of several matrices could be useful in heroin-related deaths. Urine and vitreous humor are superior for detection of 6-AM, while concentrations of morphine could be assessed from peripheral or cardiac blood, pericardial fluid, psoas muscle and lateral vastus muscle.

A stepped care strategy using buprenorphine and methadone versus conventional methadone maintenance in heroin dependence: a randomized controlled trial.

OBJECTIVE: Both methadone and buprenorphine are effective therapy for heroin dependence. Efficacy is best documented for methadone maintenance therapy, but safety concerns limit its use. Buprenorphine offers lower overdose risk and improved access, but efficacy may be lower. The authors compared adaptive, buprenorphine-based stepped care to optimal methadone maintenance treatment. METHOD: This randomized controlled trial was undertaken 2004-2006. It consisted of a 24-day uniform double-blind induction phase followed by single-blind flexible dosing based on structured clinical criteria, for a total of 6 months. Ninety-six self-referred subjects with heroin dependence were randomly assigned to methadone or to stepped treatment initiated with buprenorphine/naloxone and escalated to methadone if needed. All subjects received intensive behavioral treatment. Primary outcome was retention in treatment. Secondary outcomes were completer analyses of problem severity (Addiction Severity Index) and proportion of urine samples free of illicit drugs. RESULTS: Overall, 6-month retention was 78%. Stepped treatment and methadone maintenance therapy outcomes were virtually identical. Among completers of stepped therapy, 46% remained on buprenorphine/naloxone. Proportion of urine samples free of illicit opiates increased over time and ultimately reached approximately 80% in both arms. Problem severity decreased significantly and uniformly in both arms. CONCLUSIONS: A stepped treatment of heroin dependence as described here appears equally efficacious compared to optimally delivered methadone maintenance therapy. Together with prior data on the advantageous safety of buprenorphine, this suggests that broad implementation of strategies using buprenorphine as first-line treatment should be considered.

Validation of meconin as a marker for illicit opiate use.

The detection of markers for illicit opiate misuse is important both in the management of substance misuse and in the postmortem identification of illicit opiate use. In addition to 6-monoacetylmorphine and acetyl codeine, other markers, such as papaverine, noscapine, and their metabolites, have been proposed as markers of illicit opiate use. Urine samples (362) from individuals attending substance misuse services and 26 postmortem cases were analyzed for meconin, a noscapine metabolite by gas chromatography-mass spectrometry. Three hundred of the substance misuse service samples and 14 of the postmortem samples had morphine present as the major opiate. Meconin was detected in 284 (94.7%) of these substance misuse samples and 11 (78%) of the postmortem samples. There was a specificity of 100% in both groups. In the 62 substance misuse cases where morphine was not the major opiate detected and four separate cases in which medicinal diamorphine was known to have been administered, meconin was not detected. The use of meconin as a useful adjunct in detecting illicit opiate use is recommended.