Alternative Matrices for Cocaine, Heroin, and Methadone In Utero Drug Exposure Detection.

Ther Drug Monit. 2013 Jul 11;
Concheiro M, González-Colmenero E, Lendoiro E, Concheiro-Guisán A, de Castro A, Cruz-Landeira A, López-Rivadulla M

Drug determination in biological matrices from the mother and the newborn is an objective measure of maternal and fetal drug exposure. The aim of this study was to compare maternal hair, meconium, umbilical cord, and placenta for detecting in utero drug exposure to cocaine, opiates, methadone, and amphetamines.Maternal hair, meconium, umbilical cord, and placenta were collected from 175 mother-newborn dyads. Maternal hair (segmented in trimesters) and meconium specimens were analyzed for cocaine, opiates, methadone, and amphetamines. If either maternal hair or meconium tested positive, umbilical cord and placenta were analyzed. Analyses were performed by liquid chromatography tandem mass spectrometry.In hair, 24 participants tested positive; 21 for cocaine [cocaine 20-50,605, benzoylecgonine (BE) 17-46,668 pg/mg], 7 for methadone (76-26,845 pg/mg), 2 for opiates (morphine 298-2398 pg/mg, codeine 65-914 pg/mg, 6-acetylmorphine 1635-15,657 pg/mg), and 1 for amphetamines (amphetamine 1990 pg/mg, 3,4-methylenedioxyamphetamine 30 pg/mg, 3,4-methylenedioxymethamphetamine 294 pg/mg). In meconium, 6 were positive; 5 for methadone [methadone 88-3752, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) 642-25,179 ng/g], 3 for cocaine (cocaine 7, BE 79, hydroxybenzoylecgonine 5-135, ecgonine-methyl ester 2-56 ng/g), and 2 for opiates (morphine 152-1025, morphine-3-glucuronide 22-23, codeine 4-34 ng/g). Placenta and umbilical cord were positive in 5 and 6 cases, respectively; 5 for methadone in placenta (methadone 7-543, EDDP 10-51 ng/g) and cord (methadone 3-183, EDDP 2-109 ng/g); 1 for cocaine in placenta (cocaine 7, BE 2 ng/g) and cord (BE 6 ng/g); and 1 for opiates in placenta (morphine 6, morphine-3-glucuronide 48 ng/g), and 2 in cord (morphine 2, morphine-3-glucuronide 15-38, morphine-6-glucuronide 5 ng/g). Meconium, placenta, and umbilical cord only tested positive if hair concentrations were greater than Society of Hair Testing cutoffs.Maternal hair is the most sensitive specimen to detect drug consumption during pregnancy. Placenta and umbilical cord could be alternatives to meconium for detecting high in utero drug exposure.
HubMed – Methadone

Suicide and other-cause mortality among heroin users in Taiwan: A prospective study.

Addict Behav. 2013 Mar 21; 38(10): 2619-2623
Lee CT, Chen VC, Tan HK, Chou SY, Wu KH, Chan CH, Gossop M

The present study investigates one-year incidence of mortality from suicide and other causes among heroin users in Taiwan.A prospective national register-based cohort study.All heroin users who attended the methadone maintenance treatment (MMT) programs in all treatment centers in Taiwan.The sample comprised 10,842 heroin users attending MMT. Between Jan 2006 and Dec 2007, cases were identified through the multiple-center register system and followed until Dec 2008 for date and cause of death on the Taiwan national mortality database.Standardized mortality ratios within one year of starting MMT were calculated as a ratio of actual versus expected numbers of deaths in the general population in Taiwan. Cox regression models were fitted to estimate the effects of gender, age, education and marital status as well as heroin related behaviors.In total, 256 cases died, 67 through suicide. The mortality rate (per 100 person-years) in the first year of all-cause and suicide was 1.71 and 0.45 respectively, representing 7.5- and 18.4-fold age- and gender-standardized mortality ratio (SMR) compared to the general population. Besides, the mortality rate in the first year of overdoses, murder, HIV, somatic was 0.19, 0.02, 0.07, and 0.75 respectively, representing 68.4-, 27.7-, 76.8-, and 4.3-fold SMR increases to the general population. Older age and unemployment were independent risk factors for mortality. Females had higher standardized mortality ratio than males for suicide and all-cause mortality.Results showed higher risk of suicide and other-cause mortality among heroin users in MMT than general population. Suicide is an important contributor to overall excess mortality among heroin users in MMT, and especially among women. Suicide prevention and physical health monitoring are important components of MMT programs.
HubMed – Methadone

Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the ex vivo Human Placental Perfusion Model.

J Vis Exp. 2013;
Grafmüller S, Manser P, Krug HF, Wick P, von Mandach U

Decades ago the human placenta was thought to be an impenetrable barrier between mother and unborn child. However, the discovery of thalidomide-induced birth defects and many later studies afterwards proved the opposite. Today several harmful xenobiotics like nicotine, heroin, methadone or drugs as well as environmental pollutants were described to overcome this barrier. With the growing use of nanotechnology, the placenta is likely to come into contact with novel nanoparticles either accidentally through exposure or intentionally in the case of potential nanomedical applications. Data from animal experiments cannot be extrapolated to humans because the placenta is the most species-specific mammalian organ (1). Therefore, the ex vivo dual recirculating human placental perfusion, developed by Panigel et al. in 1967 (2) and continuously modified by Schneider et al. in 1972 (3), can serve as an excellent model to study the transfer of xenobiotics or particles. Here, we focus on the ex vivo dual recirculating human placental perfusion protocol and its further development to acquire reproducible results. The placentae were obtained after informed consent of the mothers from uncomplicated term pregnancies undergoing caesarean delivery. The fetal and maternal vessels of an intact cotyledon were cannulated and perfused at least for five hours. As a model particle fluorescently labelled polystyrene particles with sizes of 80 and 500 nm in diameter were added to the maternal circuit. The 80 nm particles were able to cross the placental barrier and provide a perfect example for a substance which is transferred across the placenta to the fetus while the 500 nm particles were retained in the placental tissue or maternal circuit. The ex vivo human placental perfusion model is one of few models providing reliable information about the transport behavior of xenobiotics at an important tissue barrier which delivers predictive and clinical relevant data.
HubMed – Methadone

Text messages as a tool for assessing public concern about drug problems.

Int J Drug Policy. 2013 Jul 9;
Yoonessi A, Ekhtiari H

The prevalence of drug use and associated problems can change rapidly, necessitating rapid and accurate data collection. In addition, advances in telecommunication technology have allowed for fast-paced, interactive communication, facilitating both rapid data gathering and engagement of health-seekers in the data collection process. Text messaging to television (TV) programs, an example of such telecommunication technology, can be used to gather data on the rapidly changing concerns about drugs.One of the most popular Iranian TV shows on the topic of drug problems is called ‘Hobab’ (Bubble). This program has nearly one million viewers and interacts with them through a text messaging system. The first two sessions of Hobab, shown during the winter of 2011, addressed the topic of drugs. The viewers were urged to ask questions about drug use, problems of addiction and the program addressed these questions. We used content analysis to extract summaries of viewers’ text-messages and feedback.5443 messages were received. Methamphetamine (24%), opium (14%), crystalline-heroin (8%), methadone (4%), cigarette (2%), burned opium (2%), tramadol (2%), cannabis (1%), brown heroin (1%), Ritalin (0.3%), morphine (0.2%), and alcohol (0.2%) were the drugs most frequently mentioned in the questions. Other frequently mentioned topics related to drugs are also reported.Text messages during a live TV program can be considered as a method for gathering data on public health issues, including drugs and addiction. Public concern related to drugs reflected in text messages could potentially provide an indirect indication of the hidden and rapidly changing pattern of problem drug use. Methamphetamine was the most frequently mentioned drug for which the Iranian audience requested information.
HubMed – Methadone

Pharmacogenetic randomized trial for cocaine abuse: Disulfiram and ?1A-adrenoceptor gene variation.

Eur Neuropsychopharmacol. 2013 Jul 9;
Shorter D, Nielsen DA, Huang W, Harding MJ, Hamon SC, Kosten TR

Disulfiram is a cocaine addiction pharmacotherapy that inhibits dopamine ?-hydroxylase (D?H) and reduces norepinephrine production. We examined whether a functional variant of the ADRA1A gene (Cys to Arg at codon 347 in exon 2, Cys347Arg) may enhance treatment response through decreased stimulation of this ?1A-adrenoceptor, since antagonists of this receptor show promise in reducing cocaine use. Sixty-nine cocaine and opioid co-dependent (DSM-IV) subjects were stabilized on methadone for two weeks and subsequently randomized into disulfiram (250mg/day, N=32) and placebo groups (N=37) for 10 weeks. We genotyped the ADRA1A gene polymorphism (rs1048101) and evaluated its role for increasing cocaine free urines in those subjects treated with disulfiram using repeated measures analysis of variance, corrected for population structure. The 47 patients who carried at least one T allele of rs1048101 (TT or TC genotype) reduced their cocaine positive urines from 84% to 56% on disulfiram (p=0.0001), while the 22 patients with the major allele CC genotype showed no disulfiram effect. This study indicates that a patient’s ADRA1A genotype could be used to identify a subset of individuals for which disulfiram and, perhaps, other ?1-adrenoceptor blockers may be an effective pharmacotherapy for cocaine dependence.
HubMed – Methadone

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