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.     

Temporal patterns of heroin and cocaine use among methadone patients

A sample of 1,038 patients newly admitted to 15 methadone clinics in New York City were studied for up to three years in treatment or until discharge. Cluster analysis identified distinct patient groups with very different heroin and cocaine usage patterns during treatment. About 80% either started in or transitioned to a low heroin use group and 50% either started in or transitioned to a low cocaine use group during treatment. One-third of patients used cocaine extensively during treatment. Other "high risk" groups, such as those not recently employed, younger, or involved with criminal justice, could benefit from special interventions very early in treatment.     

What effects does methadone maintenance treatment have on the rehabilitation of heroin addicts?]

The purpose of the study was to determine the effect of methadone maintenance treatment on heroin addicts. By searching in Medline and Cochrane Library two randomized controlled trials were found where methadone was the main intervention in the rehabilitation of heroin addicts. The trials were found among more than 2,350 articles on various aspects of methadone and were the only ones that met our criteria for inclusion in the study. The two studies comprised 347 participants. Both trials showed that methadone maintenance treatment had a positive effect on continuing participation in the treatment programme. One of the trials also showed that the treatment lowered the rates of opioid and cocaine use. It is alarming that only two randomized controlled trials could be found evaluating the effect of methadone maintenance treatment on the rehabilitation of heroin addicts. No trials demonstrating the effect of the treatment on mortality, crime, prostitution or risk behaviour related to communicable diseases were found.     

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)     

Effectiveness of methadone maintenance for heroin addiction

Methadone maintenance programs have effectively reduced heroin dependency and are available in most countries affected by heroin addiction. Methadone, developed in Germany during World War II as a pain killer, does not have the euphoric effects of heroin and the goal of treatment is to substitute methadone for heroin use. Recidivism is probably a life-long risk. Methadone maintenance programs began in the 1960s in the United States in New York City. Once tolerance is developed, it may be used continually without harmful side effects. Dosage is important for effectiveness as are counseling, rehabilitation services, and employment support. Reduction in criminality and AIDS has been associated with methadone maintenance programs.     

Reliability and validity of 6-month timeline reports of cocaine and heroin use in a methadone population.

59 persons addicted to heroin and maintained by methadone reported on daily heroin and cocaine use during 2 timeline calendar interviews administered 6 wks apart. Retrospective reports covering 6 mo were compared with urine samples taken weekly during the interval. Test–retest correlations were high and timeline estimates of drug use frequency were significantly correlated with the frequency of drug-positive urine results. Thus, timeline reports of drug-use frequency appeared both reliable and valid. Ss either over- or under-reported by an average of about 15%, and they did not identify instances of drug use with greater than chance accuracy when particular episodes of drug use occurred. These results support the use of timeline reports to make group comparisons of long-term drug use, but suggest that timeline data should not be used to identify specific drug-use episodes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of chronic maternal methadone exposure on perinatal development

The effect of perinatal exposure to methadone on body growth and brain development was studied in rat. Female Sprague-Dawley albino rats received daily intraperitoneal injections of 5 mg/kg dl-methadone-HCl during gestation and lactation. Body weights were reduced in drug-treated mothers during gestation and the first 2 weeks of lactation. No differences in gestation time, litter size, or infant mortality were recorded, however methadone-treated offspring grew more slowly than controls. Weight deficits persisted in rats observed 5-1/2 weeks after cessationof drug exposure (group 1) and in animals continuing to receive daily interperitoneal injections of 5 mg/kg (group 2). From birth to day 21, brain weight and length, cerebral width and cerebellar weight and width were generally smaller in methadone-exposed rats. Brain measurements of group 1 and group 2 animals on day 60 revealed a reduction in brain and cerebellar weights and cerebral and cerebellar widths from control values. Brain:body weight and cerebellum:brain weight ratios were similar to controls. Analysis of these results indicates that maternal methadone treatment retards the growth of young rats and affects brain development.     

Psychopathology and mood during heroin use: acute vs chronic effects

In the context of evaluating the effects of a narcotic antagonist on opiate acquisition, 14 detoxified addicts self-administered increasing doses of unblocked heroin intravenously over a ten-day period. Early in the addiction cycle, subjects experienced tension relief and euphoria but this was followed shortly by a shift in the direction of increasing dysphoria and psychopathology. Nonetheless, individual injections of the drug continued to induce brief episodes of positive mood, an effect enhanced by frequent injection. Heroin self-administration was sharply reduced when subjects were blocked with naltrexone, a narcotic antagonist, and the negative effects observed during unblocked drug use were not observed.     

Implosive therapy treatment of heroin addicts during methadone detoxification.

Examined the effectiveness of implosive therapy with heroin addicts during detoxification from methadone. 24 Ss with comparable histories of heroin addicition and similar maintenance levels of methadone were assigned to an implosive therapy, eclectic counseling, or control group. The 2 treatment groups received 12 sessions of implosive therapy or eclectic counseling and were followed for a subsequent 6-wk period. The implosive therapy Ss were the only ones to reduce significantly their methadone level during treatment and the follow-up period. (1 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of maternal and sibling presence on hyperactivity of 6-hydroxydopamine-treated developing rats.

Assessed the influence of test environment on the expression of hyperactivity produced by neonatal 6-hydroxydopamine (6-OHDA) administration in Sprague-Dawley rat pups at 15, 19, and 22 days of age in 3 experiments. The 6-OHDA Ss and an equal number of controls were tested in isolation, mixed groupings of 2 treated and 2 control pups, mixed groupings with their anesthetized mothers, mixed groupings with an anesthetized sibling, and homogeneous groupings of all treated and all control siblings. Social factors had differential effects on activity, particularly at 19 days of age: the 6-OHDA Ss were hyperactive relative to controls in isolation, and both treated and control pups were equally active in the mixed grouping and were hyperactive relative to control isolation levels. The addition of an anesthetized mother sharply attenuated the activity of both types of pups. It is concluded that social factors strongly influenced the behavior of rat pups with whole brain dopamine depletion produced by 6-OHDA and, within the confines of this animal model of hyperactivity, exerted greater attenuating effects on their activity than previously observed with stimulant medication. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Personality dynamics of heroin use.

Compared 59 white male heroin addicts with 26 psychiatric patients, 142 incarcerated delinquents, 37 undergraduate marihuana users, and 108 police officers using the California Psychological Inventory. Results suggest that the heroin users were relatively normal in terms of social poise and self-esteem; however, they were significantly more hostile, rebellious, and irresponsible than any of the comparison groups. The addicts seemed relatively well adjusted, suggesting that their drug use is symptomatic not of neurosis but of a generalized antisocial disposition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Granulocyte defects and opioid receptors in chronic exposure to heroin or methadone in humans

In order to elucidate better the immunological effect of opioid abuse in the absence of HIV infection as a confounding factor, granulocyte function was investigated in three groups of HIV-negative subjects, including 20 active parenteral heroin abusers (H), 20 long-term methadone-maintained former opiate abusers (M) and 20 healthy controls (C). Chemotaxis to N-formyl methionyl-leucyl-phenylalanine (fMLP), casein and activated plasma were markedly and similarly reduced (approx. 50%) in both H and M groups, as was true for superoxide production after fMLP and PMA stimulation, 47% decrease of C values. Polymorphonuclear (PMN) of H and M subjects also exhibited a very marked and similar reduction in the expression of CD11b/CD18 integrin receptors after fMLP treatment, with values that were less than 10% of those in controls, as observed by flow cytometry. In parallel, PMN of H and M individuals presented an approximately four-fold increase in opioid receptors numbers compared to controls, a significant inverse correlation existing between the increase in opiate receptors and defective chemotaxis. The possible mechanism underlying the observed changes in PMN of H and M individuals is discussed.     

Social context and perceived effects of drugs on sexual behavior among individuals who use both heroin and cocaine.

Researchers have identified the association between the use of cocaine and sexual behavior as an important risk factor for HIV infection and have attempted to elucidate the nature of this association. Several lines of research have suggested that facilitation of sexual behavior during intoxication with cocaine may be because of the direct pharmacological effects of the drug (e.g., increase in sexual desire), whereas others have pointed to the importance of factors related to the context of drug use (e.g., opportunities for sexual behavior, expectations about the effects of the drug, social norms). The present study explored the perceived effects of cocaine and heroin on sexual behavior, as well as the social context of drug use as a function of drug type (cocaine vs. heroin), among 46 inner-city drug users who reported a history of regular use of both crack cocaine and heroin. Results indicated that compared to heroin, cocaine had deleterious effects on participants' perceived sexual desire and performance. Despite such deleterious effects on sexual behavior, cocaine was more frequently used with an intimate partner than heroin. Furthermore, participants did not differ in the extent to which they used the two drugs in other social contexts (e.g., with friends, family, or neighbors). These preliminary results suggest that the relationship between cocaine and sexual behavior, especially among long-term cocaine users, may be facilitated by opportunities for sex that exist in the context of cocaine use, rather than by the pharmacological effects of the drug. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Therapeutic effects of methadone and 1-alpha-acetylmethadol

Many heroin addicts prefer methadone maintenance treatment to 1-alpha-acetylmethadol(LAAM) because of the "rush-like" effect of methadone. Although there have been no observable differences in the safety and effectiveness of the two drugs, LAAM appears to lead to a more stable, consistent physiological state. The authors report on two patients who had ego defects characterized by severe mood swings. Both patients preferred LAAM to methadone because of its stabilizing effect and smoother action.     

Correlates of alcohol use among methadone patients

A combination of low-dose penicillin (75,000 IU/kg twice daily [b.i.d.]) vancomycin (30 mg/kg b.i.d.) and gentamicin (6 mg/kg b.i.d.) has been shown to be as effective as a combination of high-dose penicillin (500,000 IU/kg b.i.d.) and gentamicin (6 mg/kg b.i.d.) in the treatment of rabbit endocarditis caused by an Enterococcus faecium strain moderately resistant to beta-lactams and highly resistant to glycopeptides. The same regimens were evaluated against an E. faecium strain highly resistant to both penicillin (MIC, 128 micrograms/mL) and vancomycin (MIC, 512 micrograms/mL). High doses of penicillin-gentamicin and vancomycin-gentamicin had no effect in in vitro killing-curve studies or in rabbits after treatment for 5 days. High doses of penicillin-vancomycin were only bacteriostatic in killing curves and provided a small reduction in the bacterial titers of the vegetations. In contrast, high-dose penicillin-vancomycin-gentamicin was bactericidal in vitro and highly effective in treating rabbits. However, the emergence of a bacterial subpopulation resistant to the synergistic effect of penicillin and vancomycin could reduce the clinical utility of this combination.     

Infective endocarditis as a complication of heroin use

Infective endocarditis in heroin addicts has been reported to have a mortality as high as 85% and reports have varied widely regarding predominant valvular involvement and infecting microorganisms. A retrspective study was done and 61 cases of heroin-associated infective endocarditis were identified at Freedmen's Hospital and the District of Columbia General Hospital, Washington, DC between January 1969 and January 1973. Our results indicate that staphylococcal infection of the tricuspid valve has a much higher incidence in this population than has generally been believed and that it is the predominant presentation of infective endocarditis in these patients. The outcome of patients in our series compares favorably with previous reports and suggests that early diagnosis and prompt institution of appropriate antimicrobial therapy are important and may lead to improved survival in addicts with tricuspid endocarditis.