Hemodynamic performance of four mechanical bileaflet prosthetic valves in the mitral position: an echocardiographic study

Plasma methadone concentrations and its main metabolite D,L-2-ethylidiene-1,5-dimethyl-3,5-diphenylpyrrolidine (EDDP) were determined in 93 patients under methadone maintenance treatment to assess their relationship with heroin use and opioid withdrawal symptoms. Neither plasma concentrations of methadone nor EDDP were significantly different when patients that used heroin in last 3 months were compared with those testing negative for this drug (methadone, 355 +/- 217 versus 369 +/- 216 ng/ml, t = 0.29, P = NS; EDDP, 49 +/- 28 versus 54 +/- 40 ng/ml, t = 0.51, P = NS). No correlation between opioid withdrawal scale scores and plasma concentrations of methadone (r = 0.02, P = NS) and EDDP (r = -0.14, P = NS) was found. Therapeutic drug monitoring during methadone maintenance seems to be useful for assessing compliance with treatment but not for predicting heroin use and subjective withdrawal symptoms.     

Differential effects of maternal heroin and methadone use on birthweight

An analysis of birthweights of 337 neonates in relation to history of maternal narcotic usage was undertaken. Mean birthweight of infants born to mothers abusing heroin during the pregnancy was 2,490 gm, an effect primarily of intrauterine growth retardation. Low mean birthweight (2,615 gm) was also seen in infants born to mothers who had abused heroin only prior to this pregnancy, and mothers who had used both heroin and methadone during the pregnancy (2,535 gm). Infants born to mothers on methadone maintenance during the pregnancy had significantly higher mean birthweights (2.961 gm), but lower than the control group (3,176 gm). A highly significant relationship was observed between maternal methadone dosage in the first trimester and birthweight, i.e., the higher the dosage, the larger the infant. Heroin causes fetal growth retardation, an effect which may persist beyond the period of addiction. Methadone may promote fetal growth in a dose-related fashion after maternal use of heroin.     

Assessing the relationship between maternal opiate use and neonatal mortality

We undertook a number of meta-analyses to estimate more precisely the relationship between neonatal mortality and use of opiates in three groups of women. First, women who continued to use illicit heroin throughout pregnancy; secondly, women stabilized on methadone at the time of conception or shortly after and thirdly, women who use heroin well into pregnancy with late entry into methadone treatment, or who continued to use illicit heroin during pregnancy while receiving methadone. FINDINGS: The pooled estimates of the relative risks of neonatal mortality for separate heroin and methadone use were both near unity: 1.47 (95% CI 0.88-2.33) and 1.75 (95% CI 0.60-4.59), respectively. The result for heroin may be due to the inclusion in the meta-analysis of a particularly large study, which, unlike the two other smaller studies included found a relative risk near unity. When this study was excluded from the meta-analysis the pooled estimate of the relative risk of neonatal mortality for heroin use was 3.27 (95% CI 0.95-9.60). In contrast to the results for use of methadone only, the pooled relative risk associated with heroin and methadone use was 6.37 (95% CI 2.57-14.68). CONCLUSIONS: The increased relative risk for neonatal mortality associated with women using heroin and methadone during pregnancy, compared to those stabilized on methadone, is probably due to the chaotic and high-risk life-style associated with illicit heroin use and not solely to the use of heroin and methadone per se. It is recommended tht women who use heroin well into pregnancy with late entry into methadone treatment, or who continue to use illicit heroin during pregnancy while receiving methadone, receive special attention over and above that provided to women stabilized on methadone.     

Clinical aspects and evaluation of methadone substitution therapy]

For a long time, regrettable prejudices have slowed down the expansion of methadone treatment. The arrival of AIDS and the need to find new therapies for addicts have facilitated a reduction in the misunderstanding concerning methadone. Methadone does not induce a narcotic, analgesic, or tranquilizing state for dependant addicts, is medically very safe and is not necessarily a life-long cure. Methadone treatments have become the most efficient means of treating addicts who are not able or willing to start short term abstinence programmes or go to specialized institutions. An evaluation of methadone treatments at the Phoenix Foundation in Geneva has confirmed that these programmes were able to reduce heroin use, delinquency, prostitution, risk of AIDS, overdoses or suicides and to maintain a good medical and psychosocial stability for the majority of the patients.     

Role of maintenance treatment in opioid dependence

Methadone maintenance treatment (MMT) involves the daily administration of the oral opioid agonist methadone as a treatment for opioid dependence-a persistent disorder with a substantial risk of premature death. MMT improves health and reduces illicit heroin use, infectious-disease transmission, and overdose death. However, its effectiveness is compromised if low maintenance doses of methadone (<60 mg) are used and patients are pressured to become prematurely abstinent from methadone. Pregnancy and psychiatric comorbidity are not contraindications for MMT. As an alternative to MMT, other oral opioid agents (eg, naltrexone, buprenorphine) may increase patient choice and avoid some of the more unpleasant aspects of MMT. The public-health challenge for the future is to develop and continue to deliver safe and effective forms of opioid maintenance treatment to as many opioid-dependent individuals as can benefit from them.     

The relationship between maternal use of heroin and methadone and infant birth weight

AIMS/DESIGN: Reduction in mean birth weight and increased incidence of low birth weight are both associated with exposure to illicit heroin in pregnancy. Many studies examining neonatal outcomes in pregnant heroin users treated with methadone report improvements in birth weight. As a consequence, methadone treatment has become the 'gold standard' for the management of the pregnant heroin user. However, not all studies report significant birth weight increases associated with methadone. We undertook a number of meta-analyses on reduction in mean birth weight and incidence of low birth weight to estimate more precisely the effect of illicit heroin and methadone. FINDINGS: Results showed mean reduction in birth weight associated with heroin use: 489 g (95% CI 284-693 g), compared with methadone: 279 g (229-328 g). Similarly, the pooled relative risk estimate for low birth weight for maternal heroin use was 4.61 (95% CI 2.78-7.65), compared with 1.36 (0.83-2.22) for methadone. Analysis of data on combined heroin and methadone use produced a pooled mean reduction in birth weight of 557 g (403-710 g), with a pooled relative risk estimate for low birth weight of 3.28 (2.47-4.39). Pooling 'any' methadone data, regardless of heroin use, produced an estimated reduction in birth weight of 395 g (311-478 g) and a relative risk estimate for low birth weight of 1.90 (1.29-2.81). Combining all data in an 'any' opiate use analysis also produced a mean reduction in birth weight of 483 g (386-583 g) and a relative risk estimate for low birth weight of 3.81 (2.57-5.65). CONCLUSIONS: The current findings suggest that heroin use while receiving methadone may counteract the birth weight advantage gained from methadone alone. Whether this is due to fetal exposure to heroin plus methadone, to reduced antenatal care, other behavioural and environmental factors associated with concurrent use of heroin and methadone or a combination of these is unclear. Nevertheless, these results challenge the current belief that the pregnant user is always better off receiving methadone than not, and suggests that methadone may not be the appropriate treatment for the pregnant women who continue to use illicit heroin.     

The acceptability, safety, and tolerability of methadone/naloxone in a 50:1 ratio.

Methadone is an effective therapy for heroin addiction, but the public health benefits are compromised by diversion and injection of prescribed methadone. Combination with naloxone is one way to reduce the risk of diversion and injection. Two studies were conducted. The first ascertained the safety, tolerability, pharmacokinetics, and pharmacodynamics of oral methadone-naloxone in a 50:1 ratio compared with methadone. The second study investigated the effectiveness of intramuscularly injected methadone-naloxone in precipitating withdrawal in methadone-maintained subjects. The first double-blind, crossover study randomized 10 stable methadone-maintained subjects equally to receive either methadone-naloxone or methadone over two alternate 14 day periods. In the second study, 5 subjects received intramuscular injections of methadone-naloxone before their scheduled methadone dose. Oral methadone-naloxone in a 50:1 ratio appeared to be well tolerated, although a taste difference between the preparations may have compromised blinding. There were no significant differences between methadone and methadone-naloxone in objective and subjective opioid withdrawal signs, and trough and peak plasma concentrations. Methadone-naloxone in a 50:1 ratio intramuscularly precipitated mild to moderate signs of opioid withdrawal in 4 out of 5 subjects whereas a 5th subject who did not experience withdrawal at a lower dose refused higher dose challenges. Withdrawal symptoms peaked 15 to 30 minutes postchallenge and returned to baseline levels at 60 minutes. Methadone-naloxone in 50:1 ratio has the pharmacological properties to be a useful combination product for treatment of heroin addiction with reduced risk of injection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Generalization and maintenance of appropriate behavior through self-control.

8 7-11 yr old disruptive children attended an after school reading tutorial program 1 hr a day for 72 days. After baseline, Ss evaluated their academic and social behavior. A token program was instituted and then modified to include the following procedures: (a) Points and backup reinforcers were made contingent upon accurate self-ratings; (b) the requirement of accurately matching teacher ratings was faded until the children had complete control over point distribution; and (c) backup reinforcers were also faded and eliminated. While there was a lack of generalization of appropriate social behavior to the regular classroom situation, generalization was demonstrated in the 15-min control period of every class, and maintenance was demonstrated in the final week of the program after all backup reinforcers were withdrawn. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Early impact of methadone induction for heroin dependence: Differential effects of two dose sequences in a randomized controlled study.

The pharmacodynamic and pharmacokinetic effects of 2 methadone (METH) induction dose sequences were evaluated in this 15-day outpatient experimental protocol. Heroin-dependent, non-treatment-seeking volunteers were randomly assigned (stratified for gender, race, and route of heroin use) to 2 groups. In 1 sequence, METH doses ascended (28, 56, then 84 mg/day; stepwise, n = 18), whereas in the other sequence doses escalated, then tapered (28-84 mg on Days 1-6 to 56 mg/day; rapid, n = 16). A contingency-management intervention was common to both groups. Drug use and heroin craving and opioid withdrawal symptoms decreased, whereas agonist symptoms and positive mood increased overall across days for both groups. Plasma concentrations and the acute reinforcing effects of METH paralleled each dose sequence. Stepwise relative to rapid METH induction significantly decreased heroin craving and opioid withdrawal symptoms and increased agonist symptoms and positive mood but did not significantly improve drug use or retention. Although these specific dosing procedures would not necessarily be used in clinical settings, they provide a procedural template that might be applied safely and effectively with a broader range of treatment-seeking individuals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characteristics of target-reaching in cats. III. Lifting and protraction with an obstacle in the movement path and after its removal

We have established a rat model that reflects the course of development of alcohol and opiate addiction. The present study with d-amphetamine aimed to define general principles in the development of an addiction. Male rats had a continuous free choice between d-amphetamine solutions (100, 200 and 400 mg/l) and water for 47 weeks. An initial intake of high doses of d-amphetamine during the first weeks of drug choice was followed by an individually stable pattern of drug consumption of moderate drug doses. During this period of controlled consumption (from week 10 to week 40), the voluntary intake of d-amphetamine depended on individual factors (dominant rats: 0.37+/-0.02 mg/kg per day, subordinate rats: 0.57+/-0.05 mg/kg per day) and environmental variables (group housing: 0.21+/-0.02 mg/kg per day, single housing: 0.41+/-0.03 mg/kg per day). Beginning with week 41, voluntary d-amphetamine consumption progressively increased (1.9+/-0.2 mg/kg per day in week 47), although the experimental conditions remained unchanged. Drug intake during a retest (free choice as before) after 6 months of drug deprivation revealed that the rats had persistently lost their control over drug intake and were no longer able to adjust drug taking to internal and external conditions. These addicted rats took very high drug doses, even when all d-amphetamine solutions but not water were adulterated with bitter tasting quinine (6.6+/-0.6 mg/kg per day; age-matched controls: 0.37+/-0.04 mg/kg per day). Forced intake of d-amphetamine for 47 weeks (7.1+/-0.3 mg/kg per day) via the drinking fluid caused physical dependence (hyperreactivity during withdrawal) but did not lead to drug addiction (voluntary intake in the retest with adulteration: 0.42+/-0.04 mg/kg per day). Both the temporal development and the prerequisites of psychostimulant addiction were in principle the same as for alcohol and opiates.     

Telepathology diagnosis by means of digital still images: an international validation study

Methadone usually is taken orally for drug abuse treatment in humans but oral methadone self-administration by laboratory animals has not been investigated extensively. The present study examines acquisition and maintenance of oral methadone maintained responding in four adult male rhesus monkeys. Drug solution was available from one liquid delivery system and water from a second system during daily 3-h sessions. Locations of liquids were reversed each session, and liquid (0.65 ml per delivery) was delivered according to a fixed-ratio reinforcement schedule. Initially a test for the reinforcing effects of 0.00625-0.4 mg/ml methadone solutions was carried out but a consistent preference for drug over water was not seen. To establish methadone as a reinforcer, a fading procedure was used in which responding was first maintained by solutions of methadone (0.00625-0.4 mg/ml) combined with ethanol (0.0325-2.0% w/v). Subsequently, the concentration of the ethanol in the combination was gradually reduced to zero. Methadone-maintained responding (0.4 mg/ml) persisted when ethanol was no longer present. To confirm that the drug was serving as a reinforcer, the dose was varied: (a) by changing the volume delivered while the concentration was held constant and (b) by changing the concentration of the methadone while the volume per delivery was held constant. Over a wide range of doses, deliveries of methadone solution usually exceeded deliveries of concurrently available water. Orderly relationships were observed among methadone dose, response rate, and drug intake. The study of oral self-administration of opioid drugs by nonhuman primates may be a useful strategy for the development and evaluation of new drug substitution or replacement therapies.     

Changes in mortality, arrests, and hospitalizations in nonvoluntarily treated heroin addicts in relation to methadone treatment

This study analyzes the mortality, hospitalizations, and arrests in a cohort of severe intravenous heroin users divided into three groups: those in methadone treatment, those discharged from treatment, and those who never received treatment. The study population consists of 101 heroin users, of whom 56 were HIV-seropositive. Because of intensive drug misuse, they underwent coercive residential treatment in Stockholm during the 3-year period 1986-1988. The mortality was lower in the methadone group, and all seven deaths were related to HIV-infection. Outside the program, 24 of 29 persons died from external violence and poisoning.     

Calcium antagonist activity of methadone, l-acetylmethadol and l-pentazocine in the rat aortic strip

These studies described physiologic evidence that methadone and related compounds can function as calcium antagonists. Methadone (1 X 10(-5)-1 X 10(-4) M) inhibited the contraction of the isolated rat aortic strip preparation produced by potassium chloride, norepinephrine, l-pentazocine or morphine. Methadone was most effective in diminishing aortic contractions which were highly dependent on the concentration of extracellular calcium. The d- and l-isomers of methadone were equipotent inhibitors of aortic contraction. l-Acetylmethadol (1 X 10(-6)-1 X 10(-5) M) was a potent inhibitor of vascular contraction. l-Pentazocine inhibited its own ability to contract the aorta as the dose was raised 3 X 10(-5) M. The inhibition of aortic contraction produced by methadone, l-acetylmethadol and l-pentazocine was overcome by raising the concentration of calcium in the tissue baths. The inhibition of contraction and the apparent calcium-antagonist activity of these drugs best correlates with their lipid solubility. Since calcium is a critical regulator of cellular function, the calcium-antagonist action of methadone and l-acetylmethadol may prove to be important in mediating some of their pharmacologic and toxicologic effects.     

Quantitative analysis of methadone in biological fluids using deuterium-labeled methadone and GLC-chemical-ionization mass spectrometry

The (+)-,(-)-, and (+/-)-2H5-methadones, which contained five deuterium atoms in one aromatic ring, were synthesized for use in clinical pharmacological studies and as internal standards. GLC-chemical-ionization mass spectrometry was used to determine plasma and urinary methadone levels by an inverse isotope dilution assay. Plasma drug levels could be determined to 10 pmoles/ml, and urine levels could be measured to 5 pmoles/ml. Plasma methadone levels were examined in several patients undergoing methadone maintenance therapy. These levels generally ranged between 100 and 400 ng/ml (320-1300 pmoles/ml) after an average oral dose of 1 mg/kg/day. The methadone half-life was 28.8 +/- 4.8 hr.     

Changes in cigarette smoking not observed following repeated cocaine self-administration.

Acute administration of some psychoactive drugs (e.g., cocaine, heroin, methadone, d-amphetamine) has been found to increase spontaneous cigarette smoking for 1-3 hr, but the effects of chronic drug administration have not been systematically studied. Computerized cigarette dispensers were used to study the effects of multiple daily cocaine administrations on cigarette smoking. Participants were 8 (5 male) cocaine-dependent cigarette smokers who resided on a closed clinical research ward and smoked an average of 16.7 cigarettes per day during the week prior to starting the study. During test sessions on Monday, Wednesday, and Friday of each week, participants could obtain either cocaine (25 mg iv) on 2 days or saline (1 ml iv) on the other day, 3 times per day at 2-hr intervals under double-blind conditions. The number of cigarettes dispensed during study days was analyzed in 2-hr increments. No significant cocaine effect was found. These findings fail to show a change in the number of cigarettes smoked after chronic cocaine self-administration over time intervals longer than 1-3 hr. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Radioimmunuassay compared to thin-layer and gas--liquid chromatography for detecting methadone in human urine

Radioimmunoassay was compared to thin-layer and gas--liquid chromatographic methods for detection of methadone in the urine of patients undergoing methadone maintenance therapy as treatment of heroin abuse. With urine samples known to contain methadone, 84% were positive by thin-layer chromatography as compared to 99% positives by the other two methods. This difference is attributed to the difference in sensitivity of the three methods. All three methods gave consistently positive results with urine samples from patients receiving 25 mg of methadone per day or more. With smaller daily doses the percentage of positive results obtained with thin-layer chromatography decreased. Analysis of urine samples not containing methadone showed no incidence of cross reaction of other drugs with the methadone radioimmunoassay. The methadone radioimmunoassay appears to be both sensitive and reliable; however, certain other factors limit its use as a primary screening method.     

Cloning of a thermostable ascorbate oxidase gene from Acremonium sp. HI-25 and modification of the azide sensitivity of the enzyme by site-directed mutagenesis

Concurrent abuse of cocaine and opioids is frequently observed clinically, and we have developed a model of "speedball" self-administration involving the simultaneous injection of cocaine and heroin combinations in rhesus monkeys (Mello et al. (1995) J Pharmacol Exp Ther 274:1325). In the present study, we evaluated the effects of buprenorphine (0.0075-0.75 mg/kg/day i.v.) and saline on speedball combinations of cocaine [0.001, 0.01 or 0.10 mg/kg/inj] and heroin [0.0001-0.032 mg/kg/inj]. We also examined the effects of buprenorphine (0.075 and 0.237 mg/kg/day i.v.) on self-administration of heroin alone (0.0001-0.01 mg/kg/inj). Drug and food (1-g banana pellets) self-administration were maintained on a second-order FR4 (VR16:S) schedule in four 1-hr sessions each day. Each buprenorphine or saline control treatment was evaluated for 10 consecutive days, and monkeys returned to base-line performance between each treatment condition. Buprenorphine (0.075-0.75 mg/kg/day) selectively reduced self-administration of speedball combinations of low-dose cocaine (0.001 mg/kg/inj) and heroin (0.001 or 0.0032 mg/kg/inj) (P < .05-.01), and buprenorphine (0.237 mg/kg/day) shifted dose-effect curves for speedball combinations of cocaine (0.001 mg/kg/inj) and heroin (0.0001-0.032 mg/kg/inj) downward (P < .05-.01) and approximately 1 log unit to the right. Buprenorphine treatment was less effective in decreasing responding maintained by speedball combinations of heroin and 0.01 and 0.10 mg/kg/inj cocaine. Buprenorphine treatment (0.075 and 0.237 mg/kg/day) also shifted the heroin dose-effect curve downward (P < .01-.001) and to the right. Both speedball and heroin self-administration were associated with dose-dependent decreases in food-maintained responding during saline control treatment. However, food-maintained responding was often higher than control levels during buprenorphine treatment (P < .05-.001), which suggests that buprenorphine antagonized the rate-decreasing effects of speedballs and of heroin. Buprenorphine's selective reduction of speedball and heroin self-administration is consistent with clinical treatment trials in opioid abusers and polydrug abusers. Thus, these primate models of speedball and heroin self-administration should be useful for preclinical evaluation of novel drug abuse treatment medications.     

Relationship between auditory intensity discrimination in noise and olivocochlear efferent system activity in humans

The intravenous (i.v.) steroid anesthetic, eltanolone, compares favorably to propofol with respect to its induction characteristics. This double-blind investigation was designed to compare the induction and recovery profile of eltanolone (versus propofol) when it was used for both induction and maintenance of ambulatory anesthesia. Eighty-three consenting ASA physical status I-III outpatients undergoing minor gynecologic or urologic procedures lasting 10-40 min were randomly assigned to one of three anesthetic treatment groups. All patients received midazolam, 2 mg i.v., and fentanyl, 50 micrograms i.v., before induction of anesthesia. The control group (Group 1) was induced with propofol, 2.4 mg/kg i.v. (18-60 yr or ASA physical status I or II) or 1.6 mg/kg i.v. (61-80 yr and/or ASA physical status III), followed by intermittent bolus doses of 0.6 mg/kg i.v. in combination with N2O 67% for maintenance of anesthesia. In Group 2, anesthesia was induced with eltanolone, 0.75 mg/kg i.v., (18-60 yr and/or ASA physical status I or II) or 0.5 mg/kg i.v. (61-80 yr and/or ASA physical status III), and maintained with intermittent bolus injections of 0.2 mg/kg i.v. and N2O 67%. Group 3 received eltanolone, 1.0 mg/kg i.v. (18-60 yr and/or ASA physical status I or II), or 0.75 mg/kg i.v. (61-80 yr and/or ASA physical status III), followed by intermittent bolus injections of 0.2 mg/kg i.v. and N2O 67%. In addition to recording the induction and recovery times and side effects, psychomotor testing was performed before and at 30-min intervals after anesthesia. Induction times (57 +/- 23, 67 +/- 26, and 61 +/- 22s, respectively) were similar in all three groups. Although eltanolone produced no pain on injection (versus 52% in the propofol group), 10% of the eltanolone-treated patients (versus none in the propofol group) developed transient cutaneous (rash-like) reactions. The total dose of study medication used during the anesthetic period was 9.2 +/- 3.7 mg.kg-1.h-1 in the propofol group compared with 3.3 +/- 1.4 mg.kg-1.h-1 and 3.3 +/- 1.9 mg.kg-1.h-1 in Groups 2 and 3, respectively. Early recovery times were significantly shorter after propofol anesthesia. However, times to ambulation, micturition, and being judged "fit for discharge," as well as recovery of cognitive function, were similar in all three groups. Although ethanolone seems to be a safe and effective i.v. anesthetic, these data suggest that it is unlikely to replace propofol in the ambulatory setting. Implications: Eltanolone is an investigational steroid anesthetic that causes less pain on injection and less cardiovascular depression than propofol (the most widely used intravenous anesthetic in the outpatient setting). Unfortunately, emergence from anesthesia after ambulatory surgery is slower with eltanolone compared with propofol. Therefore, it is unlikely that eltanolone will replace propofol for outpatient anesthesia.     

Buprenorphine versus methadone maintenance for opioid dependence

Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients. As hypothesized, 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use, but higher dosage did not improve treatment retention. Self-reported illicit opioid use declined substantially in all groups, but by the third month, significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone. From an initial average of $1860/month, month 3 usage dropped to $41 (methadone 65 mg), $73 (methadone 35 mg), $118 (buprenorphine 6 mg), and $351/month (buprenorphine 2 mg). Days of use also dropped from 29 days to 1.7 (methadone 65 mg), 2.8 (methadone 35 mg), 4.0 (buprenorphine 6 mg), and 6.6 days/month (buprenorphine 2 mg). This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial, with 7.2 days/month and $235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $65/month for the other three groups. Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms. Our secondary hypothesis, that buprenorphine would be equivalent to methadone in efficacy, was not supported. Treatment retention was significantly better on methadone (20 vs. 16 weeks), and methadone patients had significantly more opioid-free urines (51% vs. 26%). Abstinence for at least 3 weeks was also more common on methadone than buprenorphine (65% vs. 27%).(ABSTRACT TRUNCATED AT 250 WORDS)