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Persons with dual severe opioid and cocaine use disorders are at risk of considerable morbidity, and the bidirectional relationship of escalation of mu-opioid agonists and cocaine use is not well understood. The aim of this study was to examine the bidirectional relationship between escalation of heroin and cocaine use in volunteers dually diagnosed with opioid and cocaine dependence (OD + CD). Volunteers from New York with OD + CD (total n = 295; male = 182, female = 113; age ≥ 18 years) were interviewed with the Structured Clinical Interview for the DSM-IV Axis I Disorders and Kreek-McHugh-Schluger-Kellogg scales for dimensional measures of drug exposure, which also collect ages of 1st use and onset of heaviest use. Time of escalation was defined as age of onset of heaviest use minus age of 1st use in whole years. Times of escalation of heroin and cocaine were positively correlated in both men (Spearman r = .34, 95% confidence interval [CI: .17, .48], p < .0001) and women (Spearman r = .51, [.27, .50], p < .0001) volunteers. After we adjusted for demographic variables, a Cox regression showed that time of cocaine escalation was a predictor of time of heroin escalation (hazard ratio [HR] = 0.97, 95% CI [0.95, 0.99], p = .003). Another Cox regression showed that this relationship is bidirectional, because time of heroin escalation was also a predictor of time of cocaine escalation (HR = 0.98, [0.96-0.99], p = .016). In these adjusted models, gender was not a significant predictor of time of escalation of either heroin or cocaine. Therefore, escalation did not differ robustly by gender when adjusting for demographics and other major variables. Overall, rapid escalation of cocaine use was a predictor of rapid escalation of heroin use, and vice versa, in persons with dual severe opioid and cocaine use disorders. These findings suggest a shared vulnerability to rapid escalation of these 2 drugs in persons with dual severe opioid and cocaine use disorders. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Rationale: Many people being treated for opioid use disorder continue to use drugs during treatment. This use occurs in patterns that rarely conform to well-defined cycles of abstinence and relapse. Systematic identification and evaluation of these patterns could enhance analysis of clinical trials and provide insight into drug use., Objectives: To evaluate such an approach, we analyzed patterns of opioid and cocaine use from three randomized clinical trials of contingency management in methadone-treated participants., Methods: Sequences of drug test results were analyzed with unsupervised machine-learning techniques, including hierarchical clustering of categorical results (i.e., whether any samples were positive during each week) and K-means longitudinal clustering of quantitative results (i.e., the proportion positive each week). The sensitivity of cluster membership as an experimental outcome was assessed based on the effects of contingency management. External validation of clusters was based on drug craving and other symptoms of substance use disorder., Results: In each clinical trial, we identified four clusters of use patterns, which can be described as opioid use, cocaine use, dual use (opioid and cocaine), and partial/complete abstinence. Different clustering techniques produced substantially similar classifications of individual participants, with strong above-chance agreement. Contingency management increased membership in clusters with lower levels of drug use and fewer symptoms of substance use disorder., Conclusions: Cluster analysis provides person-level output that is more interpretable and actionable than traditional outcome measures, providing a concrete answer to the question of what clinicians can tell patients about the success rates of new treatments.

Background: Persons dually diagnosed with opioid and cocaine dependence (OD + CD) present a clinical challenge and are at risk of morbidity and mortality. The time of escalation of heroin and cocaine exposure in persons with OD + CD remain understudied, and the influence of gender and other variables have not been examined. This observational study focused on the time of escalation of heroin and cocaine in volunteers with OD + CD, examining gender and exposure to other drugs (e.g., cannabis or alcohol) as predictors. Ages of first use and of onset of heaviest use of each drug were collected (in whole years). Time of escalation was defined as the interval between age of first use and onset of heaviest use., Volunteers: sequentially ascertained adult volunteers recruited from the New York Metropolitan area, of which n = 297 were diagnosed with OD + CD., Methods: Instruments administered were the SCID-I diagnostic interview (DSM-IV criteria), BIS-11 impulsiveness scale, and KMSK scales, dimensional measures of maximal exposure to specific drugs., Results: In volunteers with OD + CD, ages of onset of heaviest use of cannabis (median age = 15) and alcohol (median age = 19) were in adolescence or emerging adulthood and preceded those for heroin and cocaine (median ages = 26 and 25, respectively). Maximal levels of cannabis and alcohol exposure were high, in volunteers with OD + CD. In adjusted Cox regressions, gender was not a significant predictor of time of heroin or cocaine escalation. However, more rapid time of alcohol escalation was a predictor of more rapid time of escalation of both heroin and cocaine, in volunteers with OD + CD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Methadone maintenance is an effective treatment for opioid use disorder (OUD), yet many methadone-maintained patients (MMPs) struggle with cocaine use during OUD recovery. The current study aimed to identify whether prefrontal cortex (PFC) activity during a risky decision-making task was associated with cocaine use during a 90-day follow-up in MMPs., Methods: MMPs (N = 28) attended a single neuroimaging session wherein PFC activity was measured using functional near-infrared spectroscopy (fNIRS) during the Balloon Analogue Risk Task (BART). Trait impulsivity was assessed via the Barratt Impulsiveness Scale version 11 (BIS-11). Following the neuroimaging session, MMPs were tracked via electronic health records for 90 days to determine treatment outcomes including cocaine use verified by urine drug screens., Results: During the BART, MMPs who used cocaine displayed increased neural activity in the right PFC during active decision-making (F 1, 22  = 14.75, p = 0.001) and the right dorsolateral PFC during active minus passive decision-making (F 1, 22  = 5.56, p = 0.028) compared to participants who did not use cocaine. Receiver operating characteristic curves confirmed that neural activity in the right PFC during active decision-making (AUC = 0.841, 95% CI, 0.697-0.985, p = 002), and in the right dorsolateral PFC during active minus passive decision-making (AUC = 0.805, 95% CI, 0.643-0.968, p = 0.006) was associated with continued cocaine use. MMPs who used cocaine versus those who did not reported increased trait impulsivity on the BIS-11 Total Score (t=-2.28, p = 0.031)., Conclusions: The fNIRS device is portable, relatively easy to use, and potentially feasible for use in methadone outpatient programs to assess propensity for negative treatment outcomes such as continued cocaine use., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Urine adulteration is a concern among patients treated for opioid use disorder. Quantitative urine testing for buprenorphine (B) and norbuprenorphine (NB), and the appropriate interpretation of B and NB levels, can facilitate constructive conversations with patients that may lead to modifications in the treatment plan, and strengthening of the patient-provider relationship., Case Summary: Three cases are presented in which discordant urine B and NB levels were recognized. Each patient was submerging buprenorphine/naloxone strips in their urine to mask ongoing illicit drug use. The authors used an approach to addressing intentional adulteration of urine samples that adheres to the principles of harm-reduction, the centrality of the patient-provider relationship, and the acknowledgment that ongoing illicit drug use and subsequent dishonesty about disclosure may be common among persons with substance use disorders. Each of the three patients ultimately endorsed diluting their urine, which allowed for strengthening of the patient-provider relationship and modifications to their treatment plans. Two of the three patients stabilized and achieved abstinence, while the third was eventually referred to a methadone treatment program., Conclusion: Providers should routinely monitor B and NB levels, rather than qualitative screening alone, and discordant levels should elicit a timely conversation with the patient. The authors use of a nonjudgmental approach to address urine adulteration, including giving patients an opportunity to reflect on potential solutions, has been effective at helping patients and providers to reestablish a therapeutic alliance and maintain retention in treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Sexually transmitted disease (STD) clinics provide critical public health services for screening and treatment of sexually transmitted infections throughout the United States. These settings serve high-risk populations, often on a walk-in basis, and may be promising venues for integrating substance use disorder (SUD) services., Methods: We report findings from 2 pilot studies conducted at Baltimore City Health Department's STD clinics. The screening study characterized rates of SUDs among STD clinic patients. Patients waiting for services completed a diagnostic interview mapping to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition SUD criteria (n = 100). The Treatment Linkage Feasibility study examined the feasibility of linking STD clinic patients with opioid and/or cocaine use disorders to SUD treatment in the community (n = 21), using SUD-focused Patient Navigation services for 1 month after the STD clinic visit. Assessments were conducted at baseline and 1-month follow-up., Results: In the screening study, the majority of STD clinic patients met diagnostic criteria for alcohol and/or drug SUD (57%). Substance-specific SUD rates among patients were 35% for alcohol, 31% for cannabis, 11% for opioids, and 8% for stimulants (cocaine/amphetamines). In the Treatment Linkage Feasibility study, 57% (12/21) of participants attended at least 1 SUD service, and 38% (8/21) were actively enrolled in SUD treatment by 1-month follow-up. The sample reported significant reductions in past 30-day cocaine use from baseline to follow-up (P = 0.01)., Conclusions: SUD rates are high among STD clinic patients. STD clinics are viable settings for initiating SUD treatment linkage services. Larger-scale research on integrating SUD services in these settings is needed.

The aim of this study is to compare the features of two groups of cocaine dependent patients in treatment, one of them with co-morbid diagnosis of antisocial personality disorder and the other not. Cross-sectional design, with 143 cocaine-dependent patients attending a drug unit, distributed in two groups: patients with and without Antisocial Personality Disorder. As results, we found that the 15.38% of the sample were diagnosed with an Antisocial Personality Disorder. In relation to socio-demographic variables, Antisocial Personality Disorder patients have less probability of being working or studying (9.1% vs. 47.9%). After multivariate analysis it was found that significantly Antisocial Personality Disorder patients have more opiates dependence (OR: 0.219; 95% IC 0.072-0.660), sedative dependence (OR: 0.203; 95% IC 0.062-0.644) and in more cases show Borderline Personality Disorder (OR: 0.239; 95% IC 0.077-0.746). This study highlights significant differences between cocaine addicts with or without an Antisocial Personality Disorder. All these differences are good indicators of the complexity of the patients with this personality disorder. Better knowledge of their profile will help us to improve the design of specific treatment programs., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Rationale: Stress's role in drug use is supported by retrospective interview and laboratory studies, but prospective data confirming the association in daily life are sparse., Objectives: This study aims to assess the relationship between drug use and stress in real time with ambulatory monitoring., Methods: For up to 16 weeks, 133 outpatients on opiate agonist treatment used smartphones to report each time they used drugs or felt more stressed than usual. They rated stress-event severity on a 10-point scale and as a hassle, day spoiler, or more than a day spoiler. For analysis, stress reports made within 72 h before a reported use of cocaine or opioid were binned into 24-h periods., Results: Of 52 participants who reported stress events in the 72-h timeframe, 41 reported stress before cocaine use and 26 before opioid use. For cocaine use, the severity of stressors, rated numerically (r effect = 0.42, CL95 0.17-0.62, p = 0.00061) and percent rated as "more than a day spoiler" (r effect = 0.34, CL95 0.07-0.56, p = 0.0292)], increased linearly across the three days preceding use. The number of stressors did not predict cocaine use, and no measure of stress predicted opioid use. In ecological momentary assessment (EMA) from the whole sample of 133, stress and drug use occurred independently and there was no overall relationship., Conclusions: EMA did not support the idea that stress is a necessary or sufficient trigger for cocaine or heroin use after accounting for the base rates of stress and use. But EMA did show that stressful events can increase in severity in the days preceding cocaine use.

Background: A number of demographic factors, psychiatric disorders, and childhood risk factors have been associated with cocaine dependence (CD) and opioid dependence (OD), but little is known about their relevance to the rate at which dependence develops. Identification of the subpopulations at elevated risk for rapid development of dependence and the risk factors that accelerate the course of dependence is an important public health goal., Methods: Data were derived from cocaine dependent (n=6333) and opioid dependent (n=3513) participants in a multi-site study of substance dependence. Mean age was approximately 40 and 40% of participants were women; 51.9% of cocaine dependent participants and 29.5% of opioid dependent participants self-identified as Black/African-American. The time from first use to dependence was calculated for each substance and a range of demographic, psychiatric, and childhood risk factors were entered into ordinal logistic regression models to predict the (categorical) transition time to CD and OD., Results: In both the cocaine and opioid models, conduct disorder and childhood physical abuse predicted rapid development of dependence and alcohol and nicotine dependence diagnoses were associated with slower progression to CD or OD. Blacks/African Americans were at greater risk than European Americans to progress rapidly to OD., Conclusions: Only a subset of factors known to be associated with CD and OD predicted the rate at which dependence developed. Nearly all were common to cocaine and opioids, suggesting that sources of influence on the timing of transitions to dependence are shared across the two substances., (© 2013.)

Background/aim: We analysed gender differences in national fatal overdose (FOD) cases related to opiates and cocaine use between 1985 and 2011 (n = 340)., Methods: Cross-examination of national data from law enforcement and drug use surveillance sources and of forensic evidence. Bivariate and logistic regression analysis of male/female differences according to sociodemographics, forensic evidence and drug use trajectories., Results: The burden of deaths caused by FOD on the general national mortality was higher for men (PMR/100=0.55) compared with women (PMR/100=0.34). Compared with their male peers, women were younger at the time of death (t=3.274; p=0.001) and showed shorter drug use careers (t=2.228; p=0.028). Heroin use was recorded more frequently in first drug offences of female victims (AOR=6.59; 95% CI 2.97-14.63) and according to forensic evidence, psychotropic prescription drugs were detected to a higher degree in females (AOR=2.019; 95% CI 1.065-3.827)., Conclusion: The time window between the onset of illicit drug use and its fatal outcome revealed to be shorter for women versus men included in our study. Early intervention in female drug users, routine involvement of first-line healthcare providers and increased attention to use of poly- and psychotropic prescription drugs might contribute to prevent premature drug-related death and reduce gender differences., (© 2013 S. Karger AG, Basel.)

Background: Ascertaining agreement between DSM-IV and DSM-5 is important to determine the applicability of treatments for DSM-IV conditions to persons diagnosed according to the proposed DSM-5., Methods: Data from a nationally representative sample of US adults were used to compare concordance of past-year DSM-IV opioid, cannabis, cocaine and alcohol dependence with past-year DSM-5 disorders at thresholds of 3+, 4+, 5+ and 6+ positive DSM-5 criteria among past-year users of opioids (n=264), cannabis (n=1622), cocaine (n=271) and alcohol (n=23,013). Substance-specific 2 × 2 tables yielded overall concordance (kappa), sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV)., Results: For DSM-IV alcohol, cocaine and opioid dependence, optimal concordance occurred when 4+ DSM-5 criteria were endorsed, corresponding to the threshold for moderate DSM-5 alcohol, cocaine and opioid use disorders. Maximal concordance of DSM-IV cannabis dependence and DSM-5 cannabis use disorder occurred when 6+ criteria were endorsed, corresponding to the threshold for severe DSM-5 cannabis use disorder. At these optimal thresholds, sensitivity, specificity, PPV and NPV generally exceeded 85% (>75% for cannabis)., Conclusions: Overall, excellent correspondence of DSM-IV dependence with DSM-5 substance use disorders was documented in this general population sample of alcohol, cannabis, cocaine and opioid users. Applicability of treatments tested for DSM-IV dependence is supported by these results for those with a DSM-5 alcohol, cocaine or opioid use disorder of at least moderate severity or severe cannabis use disorder. Further research is needed to provide evidence for applicability of treatments for persons with milder substance use disorders., (Published by Elsevier Ireland Ltd.)

Background: Buprenorphine is increasingly being used in community-based treatment programs, but little is known about the optimal level of psychosocial counseling in these settings. The aim of this study was to compare the effectiveness of OP and IOP level counseling when provided as part of buprenorphine treatment for opioid-dependent African Americans., Methods: Participants were African American men and women starting buprenorphine treatment at one of two community-based clinics (N=300). Participants were randomly assigned to OP or IOP. Measures at baseline, 3- and 6-month included the primary outcome of DSM-IV opioid and cocaine dependence criteria, as well as additional outcomes of illicit opioid and cocaine use (urine test and self-report), criminal activity, retention in treatment, Quality of Life, Addiction Severity Index composite scores, and HIV risk behaviors., Results: Participants assigned to OP received, on average, 3.67 (SD=1.30)h of counseling per active week in treatment. IOP participants received an average of 5.23 (SD=1.68)h of counseling per active week (less than the anticipated 9h per week of counseling). Both groups showed substantial improvement over a 6-month period on nearly all measures considered. There were no significant differences between groups in meeting diagnostic criteria for opioid (p=.67) or cocaine dependence (p=.63). There were no significant between group differences on any of the other outcomes. A secondary analysis restricting the sample to participants meeting DSM-IV criteria for baseline cocaine dependence also revealed no significant between-group differences (all ps>.05)., Conclusions: Buprenorphine patients receiving OP and IOP levels of care both show short-term improvements., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) will soon replace the DSM-IV, which has existed for nearly two decades. The changes in diagnostic criteria have important implications for research and for the clinical care of individuals with Substance Use Disorders (SUDs)., Methods: We used the Semi-Structured Assessment for Drug Dependence and Alcoholism to evaluate the lifetime presence of DSM-IV abuse and dependence diagnoses and DSM-5 mild, moderate, or severe SUDs for alcohol, cocaine, opioids, and cannabis in a sample of 7,543 individuals recruited to participate in genetic studies of substance dependence., Results: Switches between diagnostic systems consistently resulted in a modestly greater prevalence for DSM-5 SUDs, based largely on the assignment of DSM-5 diagnoses to DSM-IV "diagnostic orphans" (i.e., individuals meeting one or two criteria for dependence and none for abuse, and thus not receiving a DSM-IV SUD diagnosis). The vast majority of these diagnostic switches were attributable to the requirement that only two of 11 criteria be met for a DSM-5 SUD diagnosis. We found evidence to support the omission from DSM-5 of the legal criterion due to its limited diagnostic utility. The addition of craving as a criterion in DSM-5 did not substantially affect the likelihood of an SUD diagnosis., Conclusion: The greatest advantage of DSM-5 for the diagnosis of SUDs appears to be its ability to capture diagnostic orphans. In this sample, changes reflected in DSM-5 had a minimal impact on the prevalence of SUD diagnoses., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Addiction susceptibility and treatment responsiveness are greatly influenced by genetic factors. Sequence variation in genes involved in the mechanisms of drug action have the potential to influence addiction risk and treatment outcome. The opioid receptor system is involved in mediating the rewarding effects of cocaine and opioids. The μ-opioid receptor (MOR) has traditionally been considered the primary target for opioid addiction. The MOR, however, interacts with and is regulated by many known MOR interacting proteins (MORIPs), including the δ-opioid receptor (DOR)., Methods: The present study evaluated the contribution of OPRD1, the gene encoding the DOR, to the risk of addiction to opioids and cocaine. The association of OPRD1 polymorphisms with both opioid addiction (OA) and cocaine addiction (CA) was analyzed in African American (OA n=336, CA n=503) and European American (OA n=1007, CA n=336) populations., Results: The primary finding of this study is an association of rs678849 with cocaine addiction in African Americans (allelic p=0.0086). For replication purposes, this SNP was analyzed in a larger independent population of cocaine addicted African Americans and controls and the association was confirmed (allelic p=4.53 × 10(-5); n=993). By performing a meta-analysis on the expanded populations, the statistical evidence for an association was substantially increased (allelic p=8.5 × 10(-7)) (p-values non-FDR corrected)., Conclusion: The present study suggests that polymorphisms in OPRD1 are relevant for cocaine addiction in the African American population and provides additional support for a broad role for OPRD1 variants in drug dependence., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Dependence on illicit drugs during pregnancy is a major public health concern as there may be associated adverse maternal, fetal, and neonatal consequences. Sweat patches (n = 389) were collected from 39 pregnant volunteers who provided written informed consent for this Institutional Review Board-approved protocol and wore patches, replaced approximately weekly, from study entry until delivery. Patches were analyzed for opiates (heroin, 6-acetylmorphine, 6-acetylcodeine, morphine and codeine) and cocaine (cocaine, benzoylecgonine, ecgonine methyl ester, anhydroecgonine methyl ester) by solid phase extraction and gas chromatography mass spectrometry. Seventy-one percent (276) of collected sweat patches were > or =5 ng per patch (limit of quantification) for one or more analytes. Cocaine was present in 254 (65.3%) patches in concentrations ranging from 5.2 to 11,835 ng per patch with 154 of these high enough to satisfy the proposed Substance Abuse and Mental Health Services Administration guidelines for a confirmatory drug test (25 ng per patch). Interestingly, 6-acetylmorphine was the most prominent opiate analyte documented in 134 patches (34.4%) with 11.3% exceeding the proposed opiate Substance Abuse and Mental Health Services Administration cut-off (25 ng per patch). Heroin was identified in fewer patches (77), but in a similar concentration range (5.3-345.4 ng per patch). Polydrug use was evident by the presence of both cocaine and opiate metabolites in 136 (35.0%) patches. Sweat testing is an effective method for monitoring abstinence or illicit drug use relapse in this high-risk population of pregnant opiate- and/or cocaine-dependent women.

Opiates, cocaine, and metabolites were quantified by liquid chromatography-mass spectrometry (LC-MS) in 284 urine specimens, collected thrice weekly, to monitor possible drug relapse in 15 pregnant heroin-dependent women. Opiates were detected in 149 urine specimens (52%) with limits of quantification (LOQ) of 10-50 microg/L. Morphine, morphine-3-glucuronide, and/or morphine-6-glucuronide were positive in 121 specimens; 6-acetylmorphine, a biomarker of heroin ingestion, was quantifiable in only 7. No heroin, 6-acetylcodeine, papaverine, or noscapine were detected. One hundred and sixty-five urine specimens (58%) from all 15 participants were positive for one or more cocaine analytes (LOQ 10-100 microg/L). Ecgonine methylester (EME) and/or benzoylecgonine were the major cocaine biomarkers in 142. Anhydroecgonine methylester, a biomarker of smoked cocaine, was positive in six; cocaethylene and/or ecgonine ethylester, biomarkers of cocaine and ethanol co-ingestion, were found in 25. At the current Substance Abuse Mental Health Services Administration cutoffs for total morphine (2000 microg/L), codeine (2000 microg/L), 6-acetylmorphine (10 microg/L), and benzoylecgonine (100 microg/L), 16 opiate- and 29 cocaine-positive specimens were identified. Considering 100 microg/L EME as an additional urinary cocaine biomarker would identify 51 more positive cocaine specimens. Of interest is the differential pattern of opiate and cocaine biomarkers observed after LC-MS as compared to gas chromatography-mass spectrometry analysis.

Methadone dosing has been an issue of controversy among clinicians for a long time. Few recent studies reported that doses above 100 mg daily seem promising in better control of illicit opiate use for some patients, but more research is needed to support that notion. A retrospective chart review for patients maintained on methadone at Atlanta Veterans Affairs Medical Center was conducted. Patients were categorized into two groups: patients on a methadone dose of 60 to 100 mg daily (n = 34) and patients on a methadone dose greater than 100 mg daily (n = 25). Those charts were compared for urine drug screens for opiates and cocaine (first four from admission and most recent four screens), retention or drop out from the program, and Addiction Severity Index (ASI) composite score at admission and most recent score. The results of the first and last four urine drug screens for opiates showed that the moderate dose group was positive 23% and 17%, respectively. However, the high dose group was positive 14% and 8%, respectively. These results showed statistical significance (Chi-Square = 8.04, df = 3 and p =.03). ASI scores for drugs did not show statistically significant improvement for the moderate dose group (p =.19) but showed statistically significant improvement for the high dose group (p =.0002) when the result of the first and last ASI scores among each group were compared. The ASI scores for family problems showed statistically significant improvement for the moderate dose group (p =.03). High doses of methadone greater than 100 mg daily may provide a better outcome for illicit opiate use among some patients who would not respond to moderate doses.

Introduction: Although DSM-IV criteria are widely used in making diagnoses of substance use disorders, gaps exist regarding diagnosis classification, use of dependence criteria, and effects of measurement bias on diagnosis assessment. We examined the construct and measurement equivalence of diagnostic criteria for cocaine and opioid dependences, including whether each criterion maps onto the dependence construct, how well each criterion performs, how much information each contributes to a diagnosis, and whether symptom-endorsing is equivalent between demographic groups., Methods: Item response theory (IRT) and multiple indicators-multiple causes (MIMIC) modeling were performed on a sample of stimulant-using methadone maintenance patients enrolled in a multisite study of the National Drug Abuse Treatment Clinical Trials Network (CTN) (N=383). Participants were recruited from six community-based methadone maintenance treatment programs associated with the CTN and major U.S. providers. Cocaine and opioid dependences were assessed by DSM-IV Checklist., Results: IRT modeling showed that symptoms of cocaine and opioid dependences, respectively, were arrayed along a continuum of severity. All symptoms had moderate to high discrimination in distinguishing drug users between severity levels. "Withdrawal" identified the most severe symptom of the cocaine dependence continuum. MIMIC modeling revealed some support for measurement equivalence., Conclusions: Study results suggest that self-reported symptoms of cocaine and opioid dependences and their underlying constructs can be measured appropriately among treatment-seeking polysubstance users.

Prevalence of prescription opioid abuse has increased dramatically in recent years in the United States generally, and a similar pattern of increasing prescription opioid use has also been noted among patients seeking treatment for opioid dependence. This study presents results from an internal quality assurance project conducted by an outpatient methadone maintenance (MM) treatment clinic which sought to examine the extent of ongoing oxycodone abuse among patients that might be going undetected with current urinalysis-testing methods. One hundred five MM patients provided 437 urine samples over a 6-week period. Samples were analyzed using the clinic's usual enzyme multiplied immunoassay test (EMIT) opiate assay (300 ng/ml opiate cutpoint) and a supplemental oxycodone test strip (100 ng/ml oxycodone cutpoint). The EMIT assay identified only 6% (20/437) of samples as positive for oxycodone, whereas the oxycodone test strip indicated that 19% (83/437) tested positive for recent oxycodone use. Inspection of patient characteristics revealed that oxycodone users were more likely to report a prescription opioid as their primary drug at intake, be in MM treatment for a significantly shorter duration, and provide significantly more opioid- and cocaine-positive urine samples. Overall, these data illustrate the potential importance of monitoring for ongoing oxycodone use in MM clinics. Although future efforts should examine this question using more rigorous experimental methods, findings from this initial project have implications for clinical issues such as evaluating patient stability in treatment, making medication-dosing decisions, and determining patient eligibility for methadone take-home privileges.

This study compared the characteristics of opioid-addicted adults seeking (n = 169) and not seeking (n = 74) methadone treatment in Baltimore, Maryland. Participants entering treatment were recruited from six methadone treatment programs, while out-of-treatment participants were recruited from the streets using targeted sampling methods. Measures included the Addiction Severity Index, a Supplemental Questionnaire, and urine drug test. Data were analyzed using ANOVA, chi(2), and regression, holding key background variables constant. Despite the lack of differences between the samples in demographic characteristics, the out-of-treatment sample reported significantly more days of heroin, cocaine, and alcohol use and spent significantly more money on drugs and earned more illegal income at baseline.

Background: Depression is widely prevalent among former heroin addicts in methadone maintenance treatment (MMT). The risk factors for depression among MMT patients that have not been well characterized, was studied., Methods: In a cross-sectional study (January, 2004-August, 2005), 90 MMT patients were evaluated for depression by the 21-item Hamilton Rating Scale for Depression (21-HAM-D) and the Brief Psychiatric Rating scale (BPRS). To study possible induction of depression by drug abuse, urine samples tested for opiates, cocaine metabolite (benzoylecgonine), benzodiazepines (BDZ), cannabis (THC), amphetamines and methadone metabolite during 1 month preceding study entry: a drug was defined as being positive if at least one sample was positive., Results: The 21-HAM-D and BPRS scores were significantly correlated (Pearson R=0.76, p<0.0005). Fifty percent were found to be suffering from depression (21-HAM-D, scored > or = 18). Fifteen new patients in MMT had better scores (5.1+/-5.7) than continuous patients (17.7+/-6.2, p<0.0005), independent of treatment duration. Higher scores were in 51 patients with any Axis I psychiatric diagnosis (18.9+/-5.7 vs. 11.4+/-7.9, p<0.0005), 74 abusing and or using prescribed BDZ (16.3+/-7.4 vs. 11.7+/-8, p=0.03), and 36 prescribed more than one type of medication (17.5+/-7.3 vs. 14.2+/-7.7, p=0.05). Females (N=40) had poorer scores than males (17.6+/-7 vs. 14.1+/-7.9, p=0.03), especially 12 admitted into treatment while pregnant (20.2+/-4.1)., Limitation: Patient drug abuse and withdrawal could distort evaluation and lead to misclassification of depression., Conclusion: The major risk factors for depression were already being in MMT, female gender, any DSM-IV Axis I psychiatric diagnosis, taking any psychotropic medication, abuse or using prescribed BDZ, and methadone dose > 120 mg/day.

Interest in oral fluid as an alternative matrix for monitoring drug use is due to its ease-of-collection and non-invasiveness; however, limited data are available on the disposition of drugs into oral fluid. The objective of this research was to provide data on the presence and concentrations of heroin, cocaine and multiple metabolites in oral fluid after illicit opioid and cocaine use. Thrice weekly oral fluid specimens (N=403) from 16 pregnant opiate-dependent women were obtained with the Salivette oral fluid collection device. Evidence of heroin (N=62) and cocaine (N=130) use was detected in oral fluid by LC-APCI-MS/MS. 6-Acetylmorphine (6-AM), heroin and morphine were the major opiates detected, with median concentrations of 5.2, 2.3, and 7.5 microg/L, respectively. Cocaine and benzoylecgonine (BE) had median concentrations of 6.4 and 3.4 microg/L. Application of the Substance Abuse Mental Health Services Administration (SAMHSA) recommended cutoffs for morphine and codeine (40 microg/L), 6-AM (4 microg/L) and cocaine and BE (8 microg/L), yielded 28 opiate- and 50 cocaine-positive specimens. Oral fluid is a promising alternative matrix to monitor opiate and cocaine use in drug testing programs. These data guide interpretation of oral fluid test results and evaluate currently proposed SAMHSA oral fluid testing cutoffs.

Bipolar spectrum disorders and addiction often co-occur and constitute reciprocal risk factors that the authors believe are best considered under a unitary perspective. In particular, we submit that patients whose disorders fall under the bipolar spectrum - and its hyperthymic and cyclothymic temperamental substrates are at increased risk for substance use, possibly moving towards addiction through exposure to intrinsically dependence-producing substances. In our experience, the contribution of bipolar spectrum disorders to the addictive process is often clinically missed, because attenuated and subclinical expressions of such mood disorders as bipolar II and cyclothymia are not adequately appreciated by our current formal diagnostic system (e.g. DSM-IV, as well as research and clinical practice based on it). The use of agonist treatment in dual diagnosis heroin addicts has allowed us to gather valuable knowledge about the intrinsic, and historically and clinically documented mood-regulating effects of opiates. From the therapeutic point of view, the challenge of double diagnosis requires double competence from clinicians. The combination of opiate agonists and mood stabilizers often produces results difficult to obtain with the use of the two types of drugs separately. We therefore submit that the present conceptualization of the link between bipolar spectrum and addictive disorders has not only heuristic and scientific values, but also an important message for the clinician.

Background: Although methadone maintenance is the standard treatment of opiate addiction in pregnancy, opinion as to its utility is divided. The aim of this study was to analyze polydrug abuse, pregnancy outcome and fetomaternal complications among pregnant women in a major Swiss methadone maintenance program., Methods: Prospective data collection of all pregnant opiate addicts and their neonates from 1996 to 2001., Results: Maternal complications occurred in 73% and fetal complications in 34% of the pregnancies. The average methadone dose at delivery in the 89 pregnancies was 40.9 +/- 32.7 (0-150) mg/day. Sixty-four percent of the women were co-users of cocaine and/or heroin. Birthweight was lower in polydrug abusers than in near-exclusive methadone users (p = 0.001)., Conclusion: The high rate of maternal complications demonstrates the need for further improvement in antenatal management of opiate addiction in pregnancy. Methadone maintenance is inefficient in preventing pregnancy exposure to additional illicit drug consumption. Additional illicit heroin and/or cocaine abuse does not seem to increase the incidence of fetomaternal complications during pregnancy, but reverses the positive impact of methadone on birthweight. Heroin-assisted treatment may be a more effective method of minimizing the use of street drugs.

Objective: Physicians may prescribe buprenorphine for opioid agonist maintenance treatment outside of narcotic treatment programs, but treatment guidelines for patients with co-occurring cocaine and opioid dependence are not available. This study compares effects of buprenorphine and methadone and evaluates the efficacy of combining contingency management with maintenance treatment for patients with co-occurring cocaine and opioid dependence., Method: Subjects with cocaine and opioid dependence (N=162) were provided manual-guided counseling and randomly assigned in a double-blind design to receive daily sublingual buprenorphine (12-16 mg) or methadone (65-85 mg p.o.) and to contingency management or performance feedback. Contingency management subjects received monetary vouchers for opioid- and cocaine-negative urine tests, which were conducted three times a week; voucher value escalated during the first 12 weeks for consecutive drug-free tests and was reduced to a nominal value in weeks 13-24. Performance feedback subjects received slips of paper indicating the urine test results. The primary outcome measures were the maximum number of consecutive weeks abstinent from illicit opioids and cocaine and the proportion of drug-free tests. Analytic models included two-by-two analysis of variance and mixed-model repeated-measures analysis of variance., Results: Methadone-treated subjects remained in treatment significantly longer and achieved significantly longer periods of sustained abstinence and a greater proportion drug-free tests, compared with subjects who received buprenorphine. Subjects receiving contingency management achieved significantly longer periods of abstinence and a greater proportion drug-free tests during the period of escalating voucher value, compared with those who received performance feedback, but there were no significant differences between groups in these variables during the entire 24-week study., Conclusions: Methadone may be superior to buprenorphine for maintenance treatment of patients with co-occurring cocaine and opioid dependence. Combining methadone or buprenorphine with contingency management may improve treatment outcome.

The prevalence, severity, and location of white matter signal hyperintensities (WMH) on brain magnetic resonance images were compared in patients with cocaine or opiate dependence and healthy subjects. Patients with cocaine (n=32) and opiate dependence (n=32), whose diagnoses were confirmed with the Structured Clinical Interview for DSM-IV, and age- and sex-matched healthy subjects (n=32) were scanned using a 1.5 T whole body GE magnetic resonance scanner. Axial proton-density and T2-weighted images were obtained as well as fluid-attenuated inversion recovery axial images. The severity of WMH was assessed separately for deep (and insular) and periventricular WMH, using a modified composite version of the rating scales of Fazekas and Coffey. The cocaine-dependent group had greater severity of WMH than the opiate-dependent group, which in turn had greater severity of WMH than the healthy comparison group (odds ratios=2.54 and 2.90, respectively). The cocaine-dependent group had greater lesion severity of deep and insular WMH than the opiate-dependent group and the healthy comparison group (odds ratio>3.25 for deep WMH; odds ratio>4.38 for insular WMH). For periventricular WMH, there were no significant differences between the three groups. The frontal lobes were the predominant locations of WMH in both substance-dependent groups. The greater prevalence and severity of WMH in cocaine-dependent subjects than in opiate-dependent subjects may reflect the fact that cocaine induces more ischemia via vasoconstriction than opiates. Also, there was a trend for lower WMH severity in substance-dependent women relative to the healthy comparison group, possibly due to estrogen's protective effect against cerebrovascular accidents.

The aim of this study was the assessment of disorders after chronic intake of psychoactive drugs, like marijuana, amphetamine, ecstasy, cocaine and opiates. In 2002 in the Department of Clinical Toxicology detoxification unit were treated 117 chronic drug abusers. The 76 of them use the opiates predominantly, the next 41 persons (35 men, 6 women), were heavy abusers of psychostimulant drugs. In opiate abusers typical withdrawal signs and symptoms were observed. In the group of psychostimulants users, the mean time of marijuana use was 6 years, amphetamine--5 years. The cocaine was used rarely. Among 25 persons (61%) from these group the withdrawal syndrome were established. The excitation of neurovegetative system, depression, or psychomotor effects were observed. We concluded the necessity of estimation of neurobiological changes after using of psychostimulants and that more controlled research might uncover a clinically diagnosable withdrawal syndrome in human psychostimulants users.

Objective: The aim of the study was to validate a French adaptation of the 5th version of the Addiction Severity Index (ASI) instrument in a Swiss sample of illicit drug users., Participants and Setting: The participants in the study were 54 French-speaking dependent patients, most of them with opiates as the drug of first choice., Procedure: Analyses of internal consistency (convergent and discriminant validity) and reliability, including measures of test-retest and inter-observer correlations, were conducted., Results: Besides good applicability of the test, the results on composite scores (CSs) indicate comparable results to those obtained in a sample of American opiate-dependent patients. Across the seven dimensions of the ASI, Cronbach's alpha ranged from 0.42 to 0.76, test-retest correlations coefficients ranged from 0.48 to 0.98, while for CSs, inter-observer correlations ranged from 0.76 to 0.99., Conclusions: Despite several limitations, the French version of the ASI presents acceptable criteria of applicability, validity and reliability in a sample of drug-dependent patients., (Copyright 2004 S. Karger AG, Basel)

Cocaine and the opiates are--together with alcohol--involved in the genesis of the "three great addictions". The medical conceptualisation of the dependence phenomenon has evolved on the grounds of a critical observation of different ways of use and treatment endeavours, mainly during the last three centuries. Whereas the prohibitionists favoured (and still favour) total abstinence from all psychotropic drugs, defect theoreticians emphasise analytically-oriented psychotherapeutic procedures aiming at healing a supposed underlying self-defect. Contrarily, proponents of the "Metabolic Theory" of the addictions suggest a mainly medication-based approach in order to normalise a--in their eyes causal--still in some aspects hypothetical metabolic defect. Based on a short survey of recently emerging trends of consumption patterns (speed-balling, chasing, multi-substance-use) in Europe, the most important newer treatment types and forms are presented. Finally, a multimodal, integrated, and individualized approach is recommended.

Background: Recent studies suggest that a progression occurs from alcohol abuse to alcohol dependence. Although DSM-IV criteria for all substance use-related diagnoses are based largely on the alcohol dependence syndrome, progression from abuse to dependence might not generalize to other substances., Aims: This study tested whether a progression from DSM-IV abuse to dependence occurs related to the use of cannabis, cocaine and opiates., Design: Retrospective data from the DSM-IV Substance Use Disorders Work Group (n = 1226) were reanalysed using McNemar's chi2, configural frequency analyses and survival analyses. Participants were men and women who were primarily African-Americans or Caucasians., Settings: Participants were recruited from community and clinical settings. The measure was the Composite International Diagnostic Interview-Substance Abuse Module., Findings: For all substances, life-time dependence in the absence of life-time abuse was rare. Results were consistent with a progression occurring for alcohol and cannabis, but not for cocaine and opiates. Abuse and dependence occurred in the same year for 66% of the cocaine users who experienced both disorders (57% of users with any cocaine disorder) and 65% of the opiate users who experienced both disorders (46% of users with any opiate disorder). Because cocaine and opiate dependence in the absence of abuse were rare, it is possible that progressions in cocaine and opiate disorders occur more rapidly than cannabis and alcohol., Conclusions: Research is needed to clarify the mechanisms that influence progressions of substance use disorders. Potential factors leading to between-drug variation in rate of progression of disorders are discussed.

Introduction: In Austria, methadone, buprenorphine as well as oral slow-release morphine are used for the treatment of opioid dependence. This controlled examination marks the first time that oral slow-release morphine hydrochloride is applied for maintenance therapy in opioid dependent subjects., Methods: In order to evaluate the effectiveness of this psychopharmacological medication, we examined patients over a three-week period. Outcome measures were retention rate, additional consumption and the evaluation of opioid withdrawal 24 hours after the last oral medication., Results: Sixty-seven patients were included; sixty-four patients completed the study, representing a retention rate of 94%. During the three-week period, a significant improvement in well-being and a significant reduction in heroin, cocaine and benzodiazepine craving (p < 0.0001) was evaluated. Furthermore, there was a significant reduction of additional consumption of benzodiazepines in supervised urinalysis. Additional consumption of cocaine remained unchanged. Laboratory results showed a significant reduction of CK over the course of investigation., Discussion: The high retention rate of 94% implies a good acceptance and efficacy of the substance. The reduced CK is consistent with a reduction in intravenous application of illegal substances. However, randomized double-blind, double-dummy studies with oral slow-release morphine are needed in order to meet criteria for evidence based medicine.

Objective: The present paper describes the type and prevalence of co-morbid psychiatric disorders in a group of opioid dependent addicts., Methods: In 17 Swiss centres for heroin-assisted treatment 85 opiate addicts were assessed at entry using the SKID interview., Results: Lifetime prevalence of co-morbid Axis I or Axis II disorders was 86 %. Most frequently patients were diagnosed with a personality disorder (58 %). Second frequently were mood disorders with a prevalence of 55 %, followed by anxiety disorders with a prevalence of 26 %., Conclusions: The high prevalence of co-morbid psychiatric disorders indicate the urgent necessity to further develop and adapt health services for opioid addicts.

This study addresses the issue of whether the increased rates of substance-related problems for family members of cocaine abusers are specific for each substance. The present analysis examined the prevalence of problems due to alcohol or drug use separately for mothers, fathers, sisters, and brothers using the Family History Assessment Module. The probands were 343 out-of-treatment subjects with DSM-III-R cocaine disorders who did or did not have additional alcohol and opiate disorders. After accounting for age, race, gender, and antisocial personality, family history of alcohol-related problems had an odds ratio of 1.6 (p <.05) if a participant was alcoholic in addition to abusing cocaine. Specifically, a significantly greater proportion of participants' sisters (p <.001) and brothers (p <.05) had alcohol-related problems if the participant had a history of alcoholism. Among probands who reported opiate abuse or dependence, 38% had relatives with drug-related problems, while participants without opiate abuse or dependence had less than 31% of relatives with drug-related problems (p <.05). However, this association with opiate abuse or dependence and family history of drug-related problems was non-significant after controlling for participants' age, race, gender, treatment status, and antisocial personality diagnosis (odds ratio = 1.4, 95% C.I. = 0.8-2.4). Associations between participants' alcoholism and first-degree relatives' drug-related problems (and vice versa) showed that participants' history of opiate addiction did improve prediction of first-degree relatives' alcohol-related problems, except for participants' brothers. Additional familial risks for alcoholism were seen among siblings of drug abusers who also reported abuse of or dependence on alcohol even after controlling for relatives' ages. Furthermore, parental prevalence of alcohol-related problems were greater when participants had opiate addiction in addition to cocaine addiction. This seems to indicate that opiate addiction in addition to cocaine addiction has particularly strong inheritance patterns. In contrast, parental prevalence of drug-related problems was not greater when participants had alcohol addiction in addition to cocaine addiction. Thus, the cross-substance parent-child familial risk is limited to the dually diagnosed illicit drug.

While urinalysis is used regularly as a tool to validate self-reported recent drug use, past research has been inconclusive in evaluating concordance between the two measures. In the current study, urinalysis results for cocaine and opiates are compared to self-reported three-day cocaine and opiate use with data collected through Houston's Arrestee Drug Abuse Monitoring (ADAM) Program between 1990 and 1999. Separate analyses are conducted for each year during the decade. Kappa statistics indicate that the strength of agreement between the two drug use measures is consistent over time. These findings suggest that the need for urinalysis should be reconsidered.

Background: Although reports have documented alcohol and other drug use by trauma patients, no studies of long-term trends have been published. We assessed substance use trends in a large cohort of patients admitted to a regional Level I adult trauma center between July 1984 and June 2000., Methods: Positive toxicology results, collected via retrospective database review, were analyzed for patients admitted directly to the center. Data were abstracted from a clinical toxicology database for 53,338 patients. Results were analyzed for alcohol, cocaine, and opiates relative to sex, age (< 40/> or = 40 years), and injury type (nonviolence/violence). Positive toxicology test result trends were assessed for the 3 years at the beginning and end of the period (chi2). Testing biases were assessed for sex, race, and injury type., Results: The patient profile was as follows: men, 72%; age < 40 years, 69%; nonviolence victims, 77%. Alcohol-positive results decreased 37%, but cocaine-positive and opiate-positive results increased 212% and 543%, respectively (all p < 0.001). Cocaine-positive/opiate-positive results increased 152%/640% for nonviolence and 226%/258% for violence victims, respectively (all p < 0.001). In fiscal year 2000, cocaine-positive and opiate-positive results were highest among violence victims (27.4% for both drugs). Cocaine-positive and opiate-positive results among nonviolence victims were 9.4% and 17.6%, respectively. Patients who were minorities or victims of violence were not tested more frequently than other patients., Conclusion: Epidemic increases in cocaine and opiate use were documented in all groups of trauma patients, with the greatest increases being in violence victims. Alcohol use decreased for all groups.

Clinical dimensions (CDs) for the Addiction Severity Index recently have been established for application among opioid-dependent patients in methadone treatment (P. A. McDermott et al., 1996). This article examines the generalizability of the CDs to other substance-dependent patients. A sample of 2,027 adult nonopioid-dependent patients was identified; it comprised 581 primarily cocaine-dependent, 544 primarily alcohol-dependent, and 803 polydrug-dependent patients and 99 patients who were dependent on other varied drugs. Generality of dimensions was assessed through confirmatory components analysis, structural congruence, internal consistency, and variance partitioning in higher order factoring. The CDs were found generalizable overall and to specific nonopioid-dependent subgroups, and across patient gender and age, and to African American and White patients. Preliminary concurrent and predictive validity data supported the CD structure.

While methadone maintenance treatment (MMT) has been demonstrated to be an effective treatment for opiate dependence, its impact on the treatment outcome of other illicit drug abuse is not as clear. Using the initial urine drug screen (UDS) and follow-up UDS at 1, 6, 12, and 24 months, 167 patients consecutively admitted to MMT were evaluated for opiate, sedative (predominantly benzodiazepine), and stimulant (predominantly cocaine) use. Retention for the opiate only group was 97.32 days longer on average than for patients using opiates along with stimulants, sedatives, or both stimulants and sedatives. Patients abusing opiates only had the greatest decrease in drug use; however, MMT was also associated with decreases in cocaine and sedative use over the 24 month follow-up period. There was no evidence that patients "switched" their drugs of abuse with time in treatment. The negative impact of non-opiate drug use on outcome in MMT and its implications for treatment planning are discussed.

This study uses an algorithm to determine whether patients dually diagnosed with a mood disorder and cocaine dependence have either (a) an autonomous mood disorder (onset of mood disorder prior to substance use disorder (SUD) or mood disorder symptoms persist during periods of abstinence or (b) a nonautonomous mood disorder (onset of SUD preceded mood disorder and mood disorder symptoms remit during periods of abstinence). The relationship among autonomy, patient characteristics, and treatment completion is examined. The sample included 67 methadone patients with a mood disorder (87% major depression, 13% bipolar) who were enrolling in a 6-month psychosocial treatment for cocaine use. Of these subjects, 27% were rated as having an autonomous mood disorder and 73% a nonautonomous mood disorder. Mean age was 37 years; 55% were female and 82% were Hispanic or African-American. All subjects had been stabilized on methadone (mean = 70 mg). During the 30 days prior to study intake, subjects with an autonomous mood disorder, compared to subjects with a nonautonomous mood disorder, reported fewer days using cocaine (12.5 versus 21.1) and fewer days drinking four or more drinks of alcohol (1.1 versus 6. 1). Treatment completion was associated with less cocaine use, autonomy, and African-American ethnicity. However, when these variables were controlled using logistic regression, only autonomous mood disorder and ethnicity predicted treatment completion. These results suggest that autonomy may be a useful construct to measure, and that subjects with nonautonomous mood disorders may need special efforts to ensure treatment retention.

The drug addiction spread and its speed in Russia endanger the health and future of a substantial part of this country's youth in the nearest prospect. Military service is not a serious obstacle for the drug spread, so its real scale far exceeds the official statistics. The author recommends some measures which, if realized, would lead to the elimination of the problem.

This study a) compared the effects of buprenorphine versus methadone maintenance on benzodiazepine and alcohol use and b) evaluated the prognostic significance of gender and psychopathology and their interaction with maintenance treatment. Eighty male and 36 female patients were randomly assigned to daily sublingual buprenorphine (4 or 12 mg) or oral methadone (20 or 65 mg). Maintenance medication was not associated with significant differences in alcohol or benzodiazepine use. Rates of abstinence from illicit opioids were significantly higher for females, within the buprenorphine 4-mg group, females also had significantly better retention, lower rates of opioid-positive urine samples, and higher rates of abstinence from illicit opioids. Lifetime sedative dependence was associated with significantly better retention, decreased rates of cocaine-positive urine samples, and increased rates of cocaine abstinence; among buprenorphine- but not methadone-maintained patients, it was also associated with increased rates of abstinence from illicit opioids.