Variations in Infant CYP2B6 Genotype Associated with the Need for Pharmacological Treatment for Neonatal Abstinence Syndrome in Infants of Methadone-Maintained Opioid-Dependent Mothers.

Background Neonatal abstinence syndrome (NAS) in infants of methadone-maintained opioid-dependent (MMOD) mothers cannot be predicted in individual cases. We investigated whether variation in infant genotype is associated with severity of NAS. Methods This is a pilot observational cohort study of 21 MMOD mothers and their newborns. Infant buccal swabs were obtained soon after delivery, together with a maternal blood sample for the determination of maternal plasma methadone concentration. Genomic variation in five opioid-related genes (ABCB1, COMT, CYP2B6, CYP2D6, and OPRM1) was ascertained from infant buccal swabs and related to need for pharmacological treatment of NAS. Results Out of 21 infants, 11 (52%) required treatment for NAS. Mothers of treated infants tended to have been prescribed higher doses of methadone, but plasma methadone concentrations did not differ between mothers of treated or untreated babies. Treated and untreated babies did not differ in terms of method of feeding. Treated infants were more likely to carry the normal (homozygous) allele at 516 and 785 regions of CYP2B6 gene (p = 0.015 and 0.023, respectively). There were no differences in any other genes between infants who did or did not require treatment for NAS. Conclusion Genomic variation in CYP2B6 may explain, at least in part, severity of NAS

The effects and toxicity of cathinones from the users' perspectives: A qualitative study.

OBJECTIVE: The objective of this study is to explore the users' perspectives regarding the effects and toxicity of cathinones. METHODS: A systematic search of Internet discussion forums yielded 303 threads relevant to the research objectives. The threads were analysed by conventional content analysis where concepts were developed from codes and themes. RESULTS: The study identified 3 main themes in relation to cathinone use, effects, and toxicity. The first theme considered the modalities of intake of cathinones in relation to the derivative taken (mainly mephedrone, 3-methylmethcathinone, and methylenedioxypyrovalerone), route of administration (eyeballing, insufflation, smoking, intravenous, oral, rectal, and sublingual), multidrug use, and purity of the cathinone derivative. The second theme characterised the main effects of cathinones, that is, increased energy, euphoria, and empathogenic. Toxic effects were reported regarding the nervous system (anxiety, hallucinations, nervousness, and paranoia), cardiovascular system (angina, myocardial infarction, and tachycardia), skin (discolouration, itching, and allergy), and renal system (difficulty in urination). Drug-drug interactions were also reported including multiple drug use between cathinones, stimulants, depressants, and hallucinogens. CONCLUSIONS: The Internet discussion forums provide useful sources of information regarding the effects and toxicity of cathinones, which can be taken into account when assessing the safety of drugs

Wastewater analysis for new psychoactive substances and cocaine and cannabis in a Northern Ireland Prison

The global drug market has been significantly impacted by the emergence of new psychoactive substances, leading to challenges in creating effective legislative controls and their use within recreational drug consumption. This research explores the prevalence of new psychoactive substances and non-medicinal and medicinal compounds within a prison facility in Northern Ireland. Wastewater samples collected from seven different manholes within the prison were analysed for 37 target compounds including the two most found illicit substances: benzoylecgonine (primary metabolite of cocaine) and cannabis. Using solid phase extraction with Oasis HLB and liquid-chromatography-time-of-flight-mass spectrometry across a gradient of 9 min, our analysis revealed that benzoylecgonine was the sole compound consistently present in all collected samples. Following this finding, our target compound selection was broadened to encompass medicinal compounds and employing qualitative analysis we re-evaluated the samples and discovered the presence of buprenorphine, benzodiazepines, methadone, morphine, and codeine. Finally, the study explored the application of enzymatic beta-glucuronidase hydrolysis to the samples. This final phase yielded significant findings, indicating the presence of codeine and nordiazepam at higher peak intensities, thereby shedding light on the potential implications of this enzymatic process

Multidisciplinary analysis of a mummified cranium claimed to be that of a medieval execution victim

This article presents a multidisciplinary analysis of a human skull with preserved soft tissue curated by a small museum in Boscastle, Cornwall, UK. The skull lacks a mandible and is coated in a black tar-like substance. Records left by a previous museum curator (now deceased) claimed the skull to be the head of a medieval execution victim. The skull was purportedly recovered from a London church that was destroyed during the Second World War where it had been kept in a carved oak box. If these details are correct, the skull would appear to have been venerated as a relic. The skull and box have been analysed using a range of techniques including computerised tomography, laser scanning, microscopy, infrared spectroscopy and radiocarbon dating. These analyses demonstrated the skull in fact to be that of an Egyptian mummy dating from the Ptolemaic period. Other instances have been noted of parts of Egyptian mummies being presented as European saintly relics, and the ‘Boscastle skull’ would appear to be an example of such. A wider point illustrated by the work presented here is that sufficient application of modern analytical techniques may reveal considerable information regarding human remains which otherwise have little or no provenance. This point strengthens arguments for the retention of such remains by curating institutions

Increased DNA Methylation of ABCB1, CYP2D6, and OPRM1 Genes in Newborn Infants of Methadone-Maintained Opioid-Dependent Mothers.

OBJECTIVE: To investigate whether in utero opioid exposure, which has been linked to adverse neurodevelopmental and social outcomes, is associated with altered DNA methylation of opioid-related genes at birth. STUDY DESIGN: Observational cohort study of 21 healthy methadone-maintained opioid-dependent mother-infant dyads consecutively delivered at >36 weeks of gestation, and 2 comparator groups: smoking, "deprived" opioid-naïve mother-infant dyads (n = 17) and nonsmoking, "affluent" opioid-naïve mother-infant dyads (n = 15). DNA methylation of ABCB1, CYP2D6, and OPRM1 genes for mothers and babies was determined from buccal swabs. Plasma methadone concentrations were additionally measured for methadone-maintained opioid-dependent mothers. RESULTS: DNA methylation for ABCB1 and CYP2D6 was similar in opioid-naïve infants compared with their mothers, but was less for OPRM1 (3 ± 1.6% vs 8 ± 1%, P < .0005). Opioid-exposed newborns had similar DNA methylation to their mothers for all genes studied and greater methylation of ABCB1 (18 ± 4.8% vs 3 ± 0.5%), CYP2D6 (92 ± 1.2% vs 89 ± 2.4%), and OPRM1 (8 ± 0.3% vs 3 ± 1.6%) compared with opioid-naïve newborns (P < .0005 for all 3 genes). Infant DNA methylation was not related to birth weight, length of hospital stay, maternal smoking, dose or plasma concentration of methadone at delivery, or postcode of residence. CONCLUSIONS: In utero exposure to opioids is associated with increased methylation of opioid-related genes in the newborn infant. It is not clear whether these findings are due to opioid exposure per se or other associated lifestyle factors

The effect of sodium fluoride preservative and storage temperature on the stability of cocaine in horse blood, sheep vitreous and deer muscle

The in vitro stability of cocaine in horse blood, sheep vitreous humour (VH) and homogenised deer muscle is described. The stability of cocaine in horse blood was of interest because many toxicology laboratories utilise horse blood for the preparation of calibration and check standards and the latter are typically stored during routine use. The storage stability of cocaine in human VH and muscle has not been previously reported. In the absence of blank human VH and muscle, cocaine stability under varying conditions was demonstrated in animal tissues. Blood and VH were stored with and without addition of NaF at room temperature (RT), 4 degrees C and -18 degrees C for 84 days. Muscle homogenates were prepared in water, water/2% NaF, and phosphate buffer (pH 6.0)/2% NaF, and stored for 31 days at RT, 4 degrees C and -18 degrees C. Cocaine stability in human muscle obtained from cocaine positive forensic cases was assessed following storage at -18 degrees C for 13 months. Cocaine and benzoylecgonine (BZE) were extracted using SPE and quantified by GC-MS/MS. Cocaine was stable for 7 days in refrigerated (4 degrees C) horse blood fortified with 1 and 2% NaF. In the absence of NaF, cocaine was not detectable by day 7 in blood stored at RT and 4 degrees C and had declined by 81% following storage at -18 degrees C. At 4 degrees C the rate of cocaine degradation in blood preserved with 2% NaF was significantly slower than with 1% NaF. The stability of cocaine in horse blood appeared to be less than that reported for human blood, probably attributable to the presence of carboxylesterase in horse plasma. Cocaine stored in VH at -18 degrees C was essentially stable for the study period whereas at 4 degrees C concentrations decreased by &gt;50% in preserved and unpreserved VH stored for longer than 14 days. Fluoride did not significantly affect cocaine stability in VH. The stability of cocaine in muscle tissue homogenates significantly exceeded that in blood and VH at every temperature. In preserved and unpreserved samples stored at 4 degrees C and below, cocaine loss did not exceed 2%. The increased stability of cocaine in muscle was attributed to the low initial pH of post-mortem muscle. In tissue from one human case stored for 13 months at -18 degrees C the muscle cocaine concentration declined by only 15% (range: 5-22%). These findings promote the use of human muscle as a toxicological specimen in which cocaine may be detected for longer compared with blood or VH. (C) 2011 Elsevier Ireland Ltd. All rights reserved.Bournemouth UniversityBournemouth UniversityFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), BrazilFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Brazil [2010/11517-6