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This review aims to elucidate environmental and genetic factors, as well as their epigenetic and neuroendocrine moderators, that may underlie the association between early childhood experiences and Substance Use Disorders (SUD), through the lens of parental attachment. Here we review those attachment-related studies that examined the monoaminergic systems, the hypothalamic pituitary adrenal stress response system, the oxytoninergic system, and the endogenous opioid system from a genetic, epigenetic, and neuroendocrine perspective. Overall, the selected studies point to a moderating effect of insecure attachment between genetic vulnerability and SUD, reasonably through epigenetic modifications. Preliminary evidence suggests that vulnerability to SUDs is related with hypo-methylation (e.g. hyper-expression) of high-risk polymorphisms on the monoaminergic and hypothalamic pituitary adrenal system and hyper-methylation (e.g. hypo-expressions) of protective polymorphisms on the opioid and oxytocin system. These epigenetic modifications may induce a cascade of neuroendocrine changes contributing to the subclinical and behavioural manifestations that precede the clinical onset of SUD. Protective and supportive parenting could hence represent a key therapeutic target to prevent addiction and moderate insecure attachment.

Contains fulltext : 220219.pdf (Publisher’s version ) (Open Access) Introduction: As one of the major health problems in the present century, the COVID-19 pandemic affected all parts of the global communities and the health of substance users are potentially at a greater risk of harm. This global study has been designed and conducted by the International Society of Addiction Medicine Practice and Policy Interest Group (ISAM-PPIG) to understand better the health related issues of people with Substance Use Disorders (SUD) as well as responses of the relevant health care systems during the pandemic. Methods: This is a cross-sectional study using convenient sampling. The data gathering was carried out with two follow-up stages each two months apart through an online conducted survey prepared using Google platform. The survey started by emergence of COVID-19 as a pandemic in March 2020 and respondents were followed till September 2020 when most of the initial lockdowns by most countries are supposed to be reopened. Ethics and Dissemination: The study was approved by the ethics committee of University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. The results will be published in relevant peer reviewing journals and communicated with different international stakeholders. 8 p.

Both genetic and early environmental factors contribute to the pathogenesis of Alcohol Use Disorder (AUD). Gender and psychopathology symptoms might further moderate this association, resulting in an impairment of both the dopaminergic and serotoninergic pathways that sustain the binge, withdrawal and craving cycle. In a sample of of adult children of alcoholic parents (ACOAs) (n = 107) we compared those with and without an AUD, on socio-demographic variables, adverse childhood experiences, psychopathology symptoms and two polymorphisms associated with an impaired serotoninergic and dopaminergic neurotransmission (5HTTLPR and Taq1A/DRD2). A logistic regression revealed that an early caring environment might lower the risk of developing an AUD. When controlling for the actual psychopathology symptoms, being male and having the genotype associated with an impaired dopaminergic neurotransmission were still associated with AUD. Results were confirmed by an unsupervised approach that showed how the clusters characterised by being male and having the high risk genotypes were still associated with AUD compared to being female without the unfavourable dopamine genotype.Our results point to the need for implementing prevention strategies aimed at creating a caring environment especially in those families with an alcoholic parent. We further suggest that psycho-education as a symptom recognition and avoiding self-medication could improve the outcome in those subjects at higher risk, especially males.

To determine whether participation in the United Nations Office on Drugs and Crime (UNODC) and the World Health Organization's (WHO) Stop Overdose Safely (S-O-S) take-home naloxone training project in Kazakhstan, Kyrgyzstan, Tajikistan and Ukraine resulted in naloxone use at witnessed opioid overdoses.An observational prospective cohort study was performed by recruiting participants in the implementation of the S-O-S project, which was developed as part of the broader S-O-S initiative. Training included instruction on overdose responses and naloxone use. Study participants were followed for 6 months after completing training. The primary study outcome was participants' naloxone use at witnessed overdoses, reported at follow-up.Between 400 and 417 S-O-S project participants were recruited in each country. Overall, 84% (1388/1646) of participants were interviewed at 6-month follow-up. The percentage who reported witnessing an overdose between baseline and follow-up was 20% (71/356) in Tajikistan, 33% (113/349) in Kyrgyzstan, 37% (125/342) in Ukraine and 50% (170/341) in Kazakhstan. The percentage who reported using naloxone at their most recently witnessed overdose was 82% (103/125) in Ukraine, 89% (152/170) in Kazakhstan, 89% (101/113) in Kyrgyzstan and 100% (71/71) in Tajikistan.Implementation of the UNODC-WHO S-O-S training project in four low- to middle-income countries resulted in the reported use of take-home naloxone at around 90% of witnessed opioid overdoses. The percentage varied between countries but was generally higher than found in previous studies. Take-home naloxone is particularly important in countries where emergency medical responses to opioid overdoses may be limited.Déterminer si la participation au projet de formation aux kits de naloxone à emporter Stop Overdose Safely (S-O-S), lancé conjointement par l'Office des Nations Unies contre les drogues et le crime (ONUDC) et l'Organisation mondiale de la Santé (OMS) au Kazakhstan, au Kirghizistan, au Tadjikistan et en Ukraine, a entraîné l'usage de naloxone lorsqu'une surdose d'opioïdes était constatée.Nous avons mené une étude de cohorte prospective observationnelle en recrutant des participants à la mise en œuvre du projet S-O-S, développé dans le cadre de la vaste initiative S-O-S. La formation leur expliquait notamment comment réagir face à une overdose et comment utiliser la naloxone. À l'issue de leur formation, les participants à l'étude ont fait l'objet d'un suivi pendant 6 mois. L'étude a essentiellement conclu que les participants ont bien fait usage de naloxone lorsqu'ils ont été confrontés à une overdose, conformément à ce qu'ils ont relaté durant la période de suivi.Entre 400 et 417 participants au projet S-O-S ont été recrutés dans chaque pays. Au total, 84% (1388/1646) d'entre eux ont été interrogés au terme des 6 mois de suivi. Le pourcentage de participants ayant indiqué avoir assisté à une overdose entre la formation initiale et la fin de la période de suivi s'élevait à 20% (71/356) au Tadjikistan, 33% (113/349) au Kirghizistan, 37% (125/342) en Ukraine et 50% (170/341) au Kazakhstan. Enfin, le pourcentage de ceux ayant indiqué avoir eu recours à la naloxone lors de l'overdose la plus récente à laquelle ils ont assisté s'élevait à 82% (103/125) en Ukraine, 89% (152/170) au Kazakhstan, 89% (101/113) au Kirghizistan et 100% (71/71) au Tadjikistan.Le déploiement du projet de formation S-O-S porté par l'ONUDC et l'OMS dans quatre pays à faible et moyen revenu a encouragé l'usage de kits de naloxone pour 90% des overdoses d'opioïdes constatées. Le pourcentage variait d'un pays à l'autre mais, dans l'ensemble, il était supérieur à celui des études précédentes. Les kits de naloxone à emporter sont particulièrement importants dans les pays où la prise en charge médicale urgente des surdoses d'opioïdes pourrait s'avérer limitée.Determinar si la participación en el proyecto de formación en naloxona para llevar a casa Stop Overdose Safely (S-O-S) de la Oficina de las Naciones Unidas contra la Droga y el Delito (ONUDD) y la Organización Mundial de la Salud (OMS) en Kazajistán, Kirguistán, Tayikistán y Ucrania generó el uso de naloxona cuando se presenciaron sobredosis de opiáceos.Se realizó un estudio de cohortes prospectivo y observacional mediante el reclutamiento de participantes en la aplicación del proyecto S-O-S, que se desarrolló como parte de la iniciativa más amplia S-O-S. La formación incluía enseñanzas sobre las respuestas a las sobredosis y el uso de la naloxona. Los participantes del estudio fueron seguidos durante 6 meses después de completar la formación. El desenlace primario del estudio fue el uso de naloxona por parte de los participantes ante la presencia de sobredosis, notificado durante el seguimiento.En cada país se reclutaron entre 400 y 417 participantes para el proyecto S-O-S. En general, el 84 % (1388/1646) de los participantes fueron entrevistados en el seguimiento a los 6 meses. El porcentaje que declaró haber presenciado una sobredosis entre el inicio y el seguimiento fue del 20 % (71/356) en Tayikistán, el 33 % (113/349) en Kirguistán, el 37 % (125/342) en Ucrania y el 50 % (170/341) en Kazajistán. El porcentaje que declaró haber utilizado naloxona en las sobredosis presenciadas más recientes fue del 82 % (103/125) en Ucrania, del 89 % (152/170) en Kazajistán, del 89 % (101/113) en Kirguistán y del 100 % (71/71) en Tayikistán.La ejecución del proyecto de formación S-O-S de la ONUDD y la OMS en cuatro países de ingresos bajos y medios permitió notificar el uso de naloxona para llevar a casa en alrededor del 90 % de las sobredosis de opiáceos presenciadas. El porcentaje varió entre los países, pero en general fue más alto que el encontrado en los estudios anteriores. La naloxona para llevar a casa es de especial importancia en los países donde la respuesta médica de emergencia a las sobredosis de opiáceos podría ser limitada.تحديد ما إذا كانت المشاركة في مكتب الأمم المتحدة الخاص بالمخدرات والجريمة (UNODC)، ومشروع التدريب على إيقاف الجرعة الزائدة من عقار نالوكسون المنزلي بأمان (S-O-S) التابع لمنظمة الصحة العالمية (WHO) في كازاخستان وقيرغيزستان وطاجيكستان وأوكرانيا، قد أدى إلى استخدام عقار نالوكسون في جرعات زائدة مشهودة من الأفيون.تم إجراء دراسة أترابية قائمة على الملاحظة من خلال تجنيد المشاركين في تنفيذ مشروع S-O-S، الذي تم تطويره كجزء من مبادرة S-O-S الأوسع نطاقًا. وشمل التدريب تعليمات حول الاستجابات للجرعات الزائدة واستخدام عقار نالوكسون. تمت متابعة المشاركين في الدراسة لمدة 6 أشهر بعد إكمال التدريب. كانت نتيجة الدراسة الأولية هي استخدام المشاركين لعقار نالوكسون بجرعات زائدة مشهودة، تم الإبلاغ عنها أثناء المتابعة.تم تجنيد ما بين 400 و417 مشاركًا في مشروع S-O-S في كل دولة. بشكل عام، تمت مقابلة 84% (1388/1646) من المشاركين بشكل شخصي في متابعة استمرت لمدة 6 أشهر. النسبة المئوية للذين أبلغوا عن مشاهدة جرعة زائدة بين خط الأساس والمتابعة كانت 20% (71/356) في طاجيكستان، و33% (113/349) في قيرغيزستان، و37% (125/342) في أوكرانيا، و50% (170/341) في كازاخستان. النسبة المئوية للذين أبلغوا عن استخدام عقار نالوكسون في أحدث جرعة زائدة مشهودة لديهم كانت 82% (103/125) في أوكرانيا، و89% (152/170) في كازاخستان، و89% (101/113) في قيرغيزستان، و100% (71/71) في طاجيكستان.إن تنفيذ مشروع التدريب S-O-S، التابع لمكتب الأمم المتحدة الخاص بالمخدرات والجريمة ومنظمة الصحة العالمية، في أربع دول ذات دخل منخفض إلى دخل متوسط، قد أدى إلى الإبلاغ عن استخدام عقار نالوكسون المنزلي في حوالي 90% من الجرعات الزائدة المشهودة من الأفيون. اختلفت النسبة المئوية بين الدول ولكنها كانت أعلى بشكل عام مما تم العثور عليه في الدراسات السابقة. يعتبر تناول عقار نالوكسون المنزلي مهمًا بشكل خاص في الدول التي قد تكون فيها الاستجابات الطبية الطارئة للجرعات الزائدة من الأفيون محدودة.旨在确定是否参加联合国毒品和犯罪问题办公室 (UNODC) 和世界卫生组织 (WHO) 在哈萨克斯坦、吉尔吉斯斯坦、塔吉克斯坦和乌克兰开展的安全消除药物过量 (S-O-S) 自主服用纳洛酮培训项目，因为这些国家的鸦片用药过量案例中普遍存在使用纳洛酮的现象。.通过招募参与者参与 S-O-S 项目的实施开展观察性前瞻性队列研究，该 S-O-S 项目是范围更大的 S-O-S 方案的组成部分。培训包括解答药物过量问题和指导纳洛酮的使用方法。完成培训后，会对研究参与者进行为其 6 个月的后续追踪。据后续追踪报道，主要研究结果为参与者表明其见证的用药过量案例中会使用纳洛酮。.在各个国家分别招募了 400 到 417 名 S-O-S 项目参与者。总体来看，对 84% (1388/1646) 参与者进行了为期 6 个月的后续追踪。在基线到后续追踪期间报告存在用药过量的参与者比例为：哈萨克斯坦 50% (170/341)、吉尔吉斯斯坦 33% (113/349)、塔吉克斯坦 20% (71/356) 和乌克兰 37% (125/342)。报告在其最近一次见证的用药过量中使用纳洛酮的参与者比例为：哈萨克斯坦 89% (152/170)、吉尔吉斯斯坦 89% (101/113)、塔吉克斯坦 100% (71/71)、 和乌克兰 82% (103/125)。.在四个中低收入国家实施 UNODC–WHO S-O-S 培训项目后发现，在报告的自主服用纳洛酮案例中，90% 存在鸦片用药过量现象。该比例因不同国家而异，但普遍高于之前研究中发现的数值。在鸦片用药过量应急医疗救治方面资源有限的国家，自主服用纳洛酮的问题尤为严重。.Определить, привело ли участие в проекте под названием «За безопасную профилактику передозировки» (S-O-S) Управления Организации Объединенных Наций по наркотикам и преступности (УНП ООН) и Всемирной организации здравоохранения (ВОЗ) по обучению использования налоксона в домашних условиях лицами, которые могут стать свидетелями передозировки опиоидов, в Казахстане, Кыргызстане, Таджикистане и на Украине.Было проведено обсервационное проспективное когортное исследование путем набора участников в рамках реализации проекта S-O-S, который был разработан на базе более широкой инициативы S-O-S. Обучение состояло из указаний по реагированию на передозировку и использованию налоксона. За участниками исследования наблюдали в течение 6 месяцев после завершения обучения. Главным результатом исследования, о котором сообщалось при последующем наблюдении, было использование налоксона лицами, которые могут стать свидетелями передозировки.В каждой стране было набрано от 400 до 417 участников проекта S-O-S. В целом 84% (1388/1646) участников были опрошены через 6 месяцев наблюдения. Процент тех, кто сообщил о том, что стал свидетелем передозировки, между исходным уровнем и последующим наблюдением составил 20% (71/356) в Таджикистане, 33% (113/349) в Кыргызстане, 37% (125/342) на Украине и 50% (170/341) в Казахстане. Процент лиц, которые стали свидетелями передозировки и использовали налоксон во время последнего такого случая, составил 82% (103/125) на Украине, 89% (152/170) в Казахстане, 89% (101/113) в Кыргызстане и 100% (71/71) в Таджикистане.Реализация проекта S-O-S от УНП ООН и ВОЗ в четырех странах с низким и средним уровнем дохода привела к тому, что примерно в 90% случаев сообщалось об использовании налоксона в домашних условиях лицами, которые стали свидетелями передозировки опиоидов. Процентное значение варьировалось между странами, но в целом было выше, чем в предыдущих исследованиях. Использование налоксона в домашних условиях особенно важно в тех странах, где неотложная медицинская помощь при передозировке опиоидов может быть ограничена.

This study extends existing research on the relationship between psychoactive substance use among young people and violent behaviour, by evaluating the possible effect of the modification of parenting in a nationally representative sample of 14,685 Italian students drawn from the 2019 wave of the ESPAD Italia survey (51% male; mean age about 17 years). Parental dimensions considered in the study were rule-setting, monitoring, and emotional support, as well as the possible absence of a parent. Relative risk ratios and binary logistic regressions were used to estimate the associations separately for adolescents (15–17) and young adults (18–19). Overall, parental rule-setting, perceived parental monitoring, and emotional support were protective factors for substance use, and the strength of this relationship increased with the frequency of use. Among adolescents, the absence of a parent represented a risk factor. In both age groups, the odds of engaging in violent behaviour was increased among those reporting alcohol intoxication and substance use and the greater the frequency of use, the greater the increase in the odds. As parental monitoring and emotional support decreased, the odds of engaging in violent behaviour increased (except in the case of lower parental support among young adults), while the opposite applies to parental rule-setting. The odds of engaging in violent behaviour were increased among those reporting the absence of a parent only in the adolescent age group. Parental rule-setting was found to have an effect only among adolescents, increasing the odds of violent behaviour among frequent drinkers. Our results might be helpful to signal adolescents who would be more prone to adopt violent behaviour in order to target prevention policies.

Agonist-based pharmacologic intervention is an accepted approach in treatment of opioid and tobacco use disorders. We conducted a systematic review and meta-analysis to evaluate usefulness of an agonist approach as treatment of (psycho)stimulant use disorder (PSUD). We reviewed PubMed/Medline, LILACS, and ClinicalTrials.gov databases searching for randomized, double-blind, placebo-controlled, parallel-design studies evaluating outcomes of individuals treated for cocaine- or amphetamine-type substance use disorder. We combined results of all trials that included the following prescription psychostimulants (PPs): modafinil, methylphenidate, or amphetamines (mixed amphetamine salts, lisdexamphetamine, and dextroamphetamine). The combined sample consisted of 2889 patients. Outcomes of interest included the following: drug abstinence (defined as 2–3 weeks of sustained abstinence and the average maximum days of consecutive abstinence), percentage of drug-negative urine tests across trial, and retention in treatment. We conducted random-effects meta-analyses and assessed quality of evidence using the GRADE system. Thirty-eight trials were included. Treatment with PPs increases rates of sustained abstinence [risk ratio (RR) = 1.45, 95% confidence interval (CI) = (1.10, 1.92)] and duration of abstinence [mean difference (MD) = 3.34, 95% CI = (1.06, 5.62)] in patients with PSUD, particularly those with cocaine use disorder (very low-quality evidence). Prescription amphetamines were particularly efficacious in promoting sustained abstinence in patients with cocaine use disorder [RR = 2.44, 95% CI = (1.66, 3.58)], and higher doses of PPs were particularly efficacious for treatment of cocaine use disorder [RR = 1.95, 95% CI = (1.38, 2.77)] (moderate-quality evidence). Treatment with prescription amphetamines also yielded more cocaine-negative urines [MD = 8.37%, 95% CI = (3.75, 12.98)]. There was no effect of PPs on the retention in treatment. Prescription psychostimulants, particularly prescription amphetamines given in robust doses, have a clinically significant beneficial effect to promote abstinence in the treatment of individuals with PSUD, specifically the population with cocaine use disorder.

Psychoactive substance use among children in Afghanistan is an issue of concern. Somewhere around 300,000 children in the country have been exposed to opioids that either parents directly provided to them or by passive exposure. Evidence-based and culturally appropriate drug prevention and treatment programs are needed for children and families. The goals of this study were to: (1) examine lifetime psychoactive substance use in girls and boys at treatment entry; and (2) examine differential changes in substance use during and following treatment between girls and boys. Children ages 10–17 years old entering residential treatment were administered the Alcohol, Smoking and Substance Involvement Screening Test for Youth (ASSIST-Y) at pre- and post-treatment, and at three-month follow-up. Residential treatment was 45 days for children and 180 days for adolescents and consisted of a comprehensive psychosocial intervention that included education, life skills, individual and group counseling and, for older adolescents, vocational skills such as embroidery and tailoring. Girls and boys were significantly different regarding lifetime use of five substances at treatment entry, with girls less likely than boys to have used tobacco, cannabis, stimulants, and alcohol, and girls more likely than boys to have used sedatives. Differences between boys and girls were found for past-three-month use of four substances at treatment entry, with girls entering treatment with higher past-three-month use of opioids and sedatives, and boys with higher past-three-month use of tobacco, cannabis, and alcohol. Change over the course of treatment showed a general decline for both girls and boys in the use of these substances. Girls and boys in Afghanistan come to treatment with different substance use histories and differences in past-three-month use. Treatment of children for substance use problems must be sensitive to possible differences between girls and boys in substance use history.

Coronavirus Disease 2019 (COVID-19) is escalating all over the world and has higher morbidities and mortalities in certain vulnerable populations. People Who Use Drugs (PWUD) are a marginalized and stigmatized group with weaker immunity responses, vulnerability to stress, poor health conditions, high-risk behaviors, and lower access to health care services. These conditions put them at a higher risk of COVID-19 infection and its complications. In this paper, an international group of experts on addiction medicine, infectious diseases, and disaster psychiatry explore the possible raised concerns in this issue and provide recommendations to manage the comorbidity of COVID-19 and Substance Use Disorder (SUD).

Very little evidence has been reported in literature regarding the misuse of substances in rural areas. Despite the common perception of rural communities as a protective and risk-mitigating environment, the scientific literature demonstrated the existence of many risk factors in rural communities. The Drug Prevention and Health Branch (DHB) of the United Nations Office on Drugs and Crime (UNODC), and the World Health Organization (WHO), in June 2016, organized a meeting of experts in treatment and prevention of SUDs in rural settings. The content presented during the meeting and the related discussion have provided materials for the preparation of an outline document, which is the basis to create a technical tool on SUDs prevention and treatment in rural settings. The UNODC framework for interventions in rural settings is a technical tool aimed to assist policy makers and managers at the national level. This paper is a report on UNODC/WHO efforts to improve the clinical conditions of people affected by SUDs and living in rural areas. The purpose of this article is to draw attention on a severe clinical and social problem in a reality forgotten by everyone.

A disruption of the oxytocin system seems to affect a variety of brain functions including emotions, mood and social behavior possibly underlying severe social deficits and susceptibility for substance use and mental health disorders. Early life adversity, such as insecure attachment in childhood, has been suggested to influence oxytocin tone contributing to a condition of neurobiological vulnerability. Aim of the present study was to investigate oxytocin serum levels in abstinent heroin addicted patients, in comparison with healthy controls, and the possible correlation with co-occurring psychiatric symptoms, aggressiveness and perception of parental neglect. Eighteen (18) abstinent patients, affected by heroin use disorders, and 18 control subjects, who never used drugs or abused alcohol, were included in the study and submitted to 1) collection of a blood sample for oxytocin assay, 2) Symptoms Check List 90 for psychiatric symptoms evaluation 3) Buss Durkee Hostility Inventory to measure aggressiveness 4) Child Experience of Care and Abuse-Questionnaire to retrospectively test the perception of parental neglect. Heroin exposure extent and heroin dosages were also recorded. Oxytocin serum levels were unexpectedly significantly higher among abstinent patients affected by heroin use disorders and positively correlated with psychiatric symptoms, aggressiveness and mother neglect scores. No correlation was evidenced between oxytocin and heroin exposure extent or dosages. Our findings appear to contradict the simplistic view of oxytocin as a pro-social hormone and confirm previous evidence concerning the peptide levels direct association with aggressive behavior and mood disorders. Considering a more complex mechanism, oxytocin would increase the sensitivity to social salience cues related to contextual or inter-individual factors, promoting pro-sociality in “safe” conditions and, in contrast, inducing more defensive and “anti-social” emotions and behaviors when the social cues are interpreted as “unsafe”. This latter condition is often characterizing the clinical history of addicted patients.

Attention Deficit Hyperactivity Disorder (ADHD) is a risk for substance use disorders. The aim of this study was to investigate the association between adult ADHD symptoms, opioid use disorder, life dysfunction and co-occurring psychiatric symptoms. 1057 heroin dependent patients on opioid substitution treatment participated in the survey. All patients were screened for adult ADHD symptoms using the Adult ADHD Self-Report Scale (ASRS-v1.1). 19.4% of the patients screened positive for concurrent adult ADHD symptoms status and heroin dependence. Education level was lower among patients with ADHD symptoms, but not significant with respect to non-ADHD patients. Patients with greater ADHD symptoms severity were less likely to be employed. A positive association was observed between ADHD symptoms status and psychiatric symptoms. Patients with ADHD symptoms status were more likely to be smokers. Patients on methadone had a higher rate of ADHD symptoms status compared to buprenorphine. Those individuals prescribed psychoactive drugs were more likely to have ADHD symptoms. In conclusion, high rate of ADHD symptoms was found among heroin dependent patients, particularly those affected by the most severe form of addiction. These individuals had higher rates of unemployment, other co-morbid mental health conditions, heavy tobacco smoking. Additional psychopharmacological interventions targeting ADHD symptoms, other than opioid substitution, is a public health need.

BackgroundOpioid use disorder (OUD) continues to be the driving force behind drug overdoses in the United States, killing nearly 47,000 people in 2018 alone. The increasing presence of deadlier fentanyl analogues in the heroin drug supply are putting users at a greater risk for overdose than ever before. Admissions to treatment programs for OUD have also nearly doubled since 2006, yet relapse rates remain high. In response to these alarming statistics, developing approaches to reduce overdose deaths has become an area of high priority. As it is not yet known which patients are most likely to benefit from a specific treatment, there is a dire need to utilize new molecular tools to guide precision medicine approaches and improve treatment outcomes. Here we describe a proof-of-concept study evaluating plasma-derived extracellular vesicle (EV) signatures and how they differ in patients who responded to two pharmacologically contrasting treatments for OUD: the μOR agonist methadone, and the μOR antagonist naltrexone.MethodsWe obtained blood samples from patients with OUD who remained abstinent from illicit opioids for at least 3 months during treatment with methadone (n=5) and naltrexone (n=5), as well as matched healthy controls (n=5). EVs were isolated from plasma and histones were isolated from peripheral blood mononuclear cells (PBMCs). EVs were then analyzed for lipid and histone post-translational modification (PTM) content using liquid chromatography-mass spectrometry. EV miRNA cargo was determined by RNA sequencing.ResultsWe found one lipid class and six miRNAs that differed significantly between the naltrexone group and the methadone and control groups. We also found that histone H3acK9acK14 was increasingly acetylated in PMBCs from both the methadone and naltrexone groups compared to controls.DiscussionNaltrexone, which is used in treatment of OUD and other substance use disorders as well as disorders of impulse control, was found to have multiple potential corresponding molecular signatures that can be identified after long-term treatment. It remains to be seen if these markers can also be a good predictor for treatment response. In addition, significant gender differences in EV content are found between men and women with OUD, which supports the importance of examining changes in response to treatment in a gender informed way.

The development and validation of a bioanalytical assay for the simultaneous determination of cortisol, cortisone and corticosterone levels in several matrices, such as saliva, plasma, blood and urine samples have been described. The method is based on a rapid test which combines a microextraction by packed sorbent procedure and liquid chromatography-diode array technique. Chromatographic separation of the analytes (cortisol, cortisone and corticosterone) and the internal standard (methylprednisolone) was achieved in less than 10 min on a reversed-phase pentafluorophenyl column using a mobile phase com-posed of phosphate buffer and acetonitrile. The assay was performed after an innovative microextraction procedure by means of C8 sorbent which guaranteed good clean-up of the matrices and satisfactory extraction yield of the analytes. Moreover, the method gave linear results over a range of 5–100 ng mL−1 and showed good selectivity and precision. This method was successfully applied for quantifying corticosteroids in specific matrices derived from some healthy volunteers in comparison to two socially diversified groups, namely former heroin addicts undergoing opioid replacement therapy and poly-drug abusers The development and validation of a bioanalytical assay for the simultaneous determination of cortisol, cortisone and corticosterone levels in several matrices, such as saliva, plasma, blood and urine samples have been described. The method is based on a rapid test which combines a microextraction by packed sorbent procedure and liquid chromatography-diode array technique. Chromatographic separation of the analytes (cortisol, cortisone and corticosterone) and the internal standard (methylprednisolone) was achieved in less than 10min on a reversed-phase pentafluorophenyl column using a mobile phase composed of phosphate buffer and acetonitrile. The assay was performed after an innovative microextraction procedure by means of C8 sorbent which guaranteed good clean-up of the matrices and satisfactory extraction yield of the analytes. Moreover, the method gave linear results over a range of 5-100ngmL-1 and showed good selectivity and precision.This method was successfully applied for quantifying corticosteroids in specific matrices derived from some healthy volunteers in comparison to two socially diversified groups, namely former heroin addicts undergoing opioid replacement therapy and poly-drug abusers. © 2013 Elsevier B.V.

Background and Aims: Families who live in a disadvantaged socioeconomic situation frequently face substandard housing, unsafe neighborhoods, inadequate schools and more stress in their daily lives than more affluent families, with a host of psychological and developmental consequences that can hinder their children’s development in many ways. However, the measurement of socioeconomic status among youth and its link with different forms of illicit substance use is challenging and still unclear. This paper extends existing research on the relationship between socioeconomic status and illicit drug use among adolescents by focusing on three different patterns of use (experimental, episodic and frequent) and making use of two indicators to improve the measurement of individual socioeconomic characteristics in a big sample of European students. Methods: Data were drawn from the European school Survey Project on Alcohol and other Drugs (ESPAD), which, since 1995, collects comparable data among 15-to-16-year-old students to monitor trends in drug use and other risk behaviors across Europe. The sample comes from 28 countries that participated in the 2015 data collection. The consumption of cannabis, cocaine and heroin are considered, and the related patterns are identified based on the frequency of use. Family characteristics at student level are defined through two dimensions: parental educational level and perceived socioeconomic status. Multivariate multilevel mixed-effects logistic regression was performed in order to measure the association between individual characteristics and vulnerability for drug use. Results: Some patterns of use, episodic and frequent in particular, were found strongly associated with a lower socioeconomic status and lower parental education. Conclusions: Our results suggest that drug policies should be combined with actions aimed at removing barriers to social inclusion that are attributable to the socioeconomic background of adolescents.

Oxycodone is a widely prescribed, full agonist opioid analgesic. As such, it is used clinically to treat different kinds of painful conditions, with a relatively high potential for doping practices in athletes. In this paper, different classic and innovative miniaturised matrices from blood and urine have been studied and compared, to evaluate their relative merits and drawbacks within therapeutic drug monitoring (TDM) and to implement new protocols for anti-doping analysis. Plasma, dried blood spots (DBS) and dried plasma spots (DPS) have been studied for TDM purposes, while urine, dried urine spots (DUS) and volumetric absorptive microsamples (VAMS) from urine for anti-doping. These sampling techniques were coupled to an original bioanalytical method based on liquid chromatography-tandem mass spectrometry (LC–MS/MS) for the evaluation and monitoring of the levels of oxycodone and its major metabolites (noroxycodone and oxymorphone) in patients under pain management and in athletes. The method was validated according to international guidelines, with good results in terms of precision, extraction yield and accuracy for all considered micromatrices. Thus, the proposed sampling, pre-treatment and analysis are attractive strategies for oxycodone determination in human blood and urine, with advanced options for application to derived micromatrices. Microsampling procedures have significant advantages over classic biological matrices like simplified sampling, storage and processing, but also in terms of precision (73% for DBS, >78% for DPS, >74% for DUS, >78% for VAMS). As regards extraction yield, traditional and miniaturised sampling approaches are comparable (>67% for DBS, >74% for DPS, >75% for DUS, >75% for VAMS). All dried matrices have very low volumes, leading to a significant advantage in terms of analysis feasibility. On the other hand, this also leads to a corresponding decrease in the overall sensitivity.

Synthetic cannabinoids are new psychoactive substances (NPS) with similar effects when compared to natural ones found in Cannabis derivatives. They have rapidly integrated into the illicit market, often sold as alternatives under international control. The need to identify and quantify an unprecedented and growing number of new compounds represents a unique challenge for toxicological, forensic and anti-doping analysis. Dried blood spots have been used within the bioanalytical framework in place of plasma or serum, in order to reduce invasiveness, lower sample size, simplify handling, storage and shipping of samples and to facilitate home-based and on-field applications. However, DBS implementation has been limited mainly by concerns related to haematocrit effect on method accuracy. Volumetric absorptive microsampling (VAMS™), a second generation dried miniaturized sampling technology, has been developed just in order to eliminate haematocrit effect, thus providing accurate sampling but still granting feasible sample processing. An original LC-MS/MS method was herein developed and validated for the analysis of THC and its 2 main metabolites, together with 10 representative synthetic cannabinoids in both DBS and VAMS dried microsamples. The ultimate goal of this work is to provide highly innovative DBS and VAMS analytical protocols, whose performances were extensively optimized and compared, in order to provide effective and alternative tools that can be applied for natural and synthetic cannabinoid determination, in place of classical analytical strategies.

The services for drug-dependence treatment and care, particularly in low-income countries, should not be fragmented and uncoordinated. A basic package of interventions should be provided in the same place and managed by the same team, with a one-stop-shop approach. The services for substance use disorders should be appealing, accessible, voluntary-based, and science-based. They should also, like efforts to fight other diseases, be included in the community and the public health systems; that is, those who are affected by drug use and those who serve them should not face discrimination. The first-line assistance and the second-line essential elements of the comprehensive package are described in this article. The work of the United Nations Office on Drugs and Crime (UNODC) and the World Health Organization (WHO) to promote science-based and voluntary-based ethical treatment in Asia is also illustrated.

Studies evidenced the relationship between adverse childhood experiences (ACEs) and tobacco smoking in adulthood. An appropriate parenting style has been found to be associated with children's less frequent tobacco consumption. Hypothalamus-pituitary-adrenal (HPA) axis hyperactivity could represent the potential link between ACEs, mood disorders and smoking susceptibility. We studied a sample of 50 male smokers, affected by nicotine dependence and 50 controls who never smoked. Self-reported retrospective perception of neglect (Child Experience of Care and Abuse: CECA-Q questionnaire), age of smoking onset, number of cigarette/day, psychiatric symptoms (Symptoms Check List 90 scale: SCL 90) and basal level of ACTH and cortisol have been evaluated. Total SCL-90 scores, CECA-Q values and cortisol plasma level were significantly higher among smokers. Cortisol and ACTH values showed a significant direct correlation with CECA-Q and SCL90 total score and an inverse significant correlation with the age of smoking. Cortisol and ACTH did not correlate with the number of cigarette smoked. Once controlled for SCL90 and CECA-Q with multiple regression measures, the association between smoking and hormone levels reversed, suggesting that increased cortisol and ACTH basal levels were attributable to preexisting conditions such as early-life exposure to emotional neglect, psychological problems and a predisposition to addictive behavior.

Pregabalin (Lyrica™) is a structural analog of γ-aminobutyric acid (GABA) and is approved by the FDA for partial epilepsy, neuropathic pain and generalized anxiety disorders. Pregabalin also reduces excitatory neurotransmitter release and post-synaptic excitability. Recently, we demonstrated that pregabalin reduced alcohol intake and prevented relapse to the alcohol seeking elicited by stress or environmental stimuli associated with alcohol availability. Here, we sought to extend these findings by examining the effect of pregabalin on cocaine self-administration (0.25 mg/infusion) and on cocaine seeking elicited by both conditioned stimuli and stress, as generated by administration of yohimbine (1.25 mg/kg). The results showed that oral administration of pregabalin (0, 10 or 30 mg/kg) reduced self-administration of cocaine over an extended period (6 hours), whereas it did not modify self-administration of food. In cocaine reinstatement studies, pregabalin (10 and 30 mg/kg) abolished the cocaine seeking elicited by both the pharmacological stressor yohimbine and the cues predictive of cocaine availability. Overall, these results demonstrate that pregabalin may have potential in the treatment of some aspects of cocaine addiction.

Cocaine dependence is characterized by compulsive drug seeking and high vulnerability to relapse. Overall, cocaine remains one of the most used illicit drugs in the world. Given the difficulty of achieving sustained recovery, pharmacotherapy of cocaine addiction remains one of the most important clinical challenges. Recent advances in neurobiology, brain imaging and clinical trials suggest that certain medications show promise in the treatment of cocaine addiction. The pharmacotherapeutic approaches for cocaine dependence include medications able to target specific subtypes of dopamine receptors, affect different neurotransmitter systems (i.e. noradrenergic, serotonergic, cholinergic, glutamatergic, GABAergic and opioidergic pathways), and modulate neurological processes. The systematic reviews concerning the pharmacological treatment of cocaine dependence appear to indicate controversial findings and inconclusive results. The aim of future studies should be to identify the effective medications matching the specific needs of patients with specific characteristics, abandoning the strategies extended to the entire population of cocaine dependent patients. In the present review we summarize the current pharmacotherapeutic approaches to the treatment of cocaine dependence with a focus on the new patents.

Methadone maintenance therapy (MMT) has been found effective in treating heroin addiction. Serious consideration should be given to the modality of methadone distribution, as it influences not only treatment outcome but the attitudes of policy makers and the community, too. On one hand, the choice of take-home methadone removes the need for daily attendance at a methadone clinic, which seems to improve patients' quality of life. On the other, this method, because of its lack of supervision and the absence of strict consumption monitoring, runs the risk of methadone misuse and diversion. In this study, we compared A) supervised daily consumption, B) contingent take-home incentives and C) non-contingent take-home in methadone maintenance in three groups of heroin-addicted patients attending three different MMT programmes. Retention rates at 12 months were significantly higher in contingent take-home patients (group B) than in those with supervised daily consumption (group A) and the non-contingent take-home (group C). Retention rates were higher in group A than in group C patients. Compared to patients in groups A and B, those in group C showed fewer negative urinalyses and higher rates of self-reported diversion and episodes of crime or violence. Results indicate a more positive outcomes following take-home methadone associated with behavioural incentives and other measures that aim to facilitate treatment compliance than those following daily supervised consumption. By contrast, non-contingent take-home methadone given to non-stabilized patients is associated with a high rate of diversion, along with more crime episodes and maladaptive behaviours.

An original HPLC method coupled to spectrofluorimetric detection is presented for the simultaneous anal- ysis in dried blood spots (DBS) of cocaine and two important metabolites, namely benzoylecgonine (its main metabolite) and cocaethylene (the active metabolite formed in the presence of ethanol). The chro- matographic analysis was carried out on a C8 column, using a mobile phase containing phosphate buffer (pH 3.0) – acetonitrile (85:15, v/v). Native analyte fluorescence was monitored at 315 nm while exciting at 230 nm. A fast and feasible sample pre-treatment was implemented by solvent extraction, obtaining good extraction yields (>91%) and satisfactory precision values (RSD < 4.8%). The method was successfully applied to DBS samples collected from some cocaine users, both with and without concomitant ethanol intake. The results were in good agreement with those obtained from plasma samples subjected to an original solid-phase extraction procedure on C8 cartridges. The method has demonstrated to be suitable for the monitoring of cocaine/ethanol use by means of DBS or plasma testing. Assays are in progress to apply this method on the street, for the control of subjects suspected of driving under the influence of psychotropic substances.

Maintenance therapy with methadone or buprenorphine-based regimens reduces opioid dependence and associated harms. The perception that methadone is more effective than buprenorphine for maintenance treatment has been based on low buprenorphine doses and excessively slow induction regimens used in early buprenorphine trials. Subsequent studies show that the efficacy of buprenorphine sublingual tablet (Subutex®) or buprenorphine/naloxone sublingual tablet (Suboxone®) is equivalent to that of methadone when sufficient buprenorphine doses, rapid induction, and flexible dosing are used. Although methadone remains an essential maintenance therapy option, buprenorphine-based regimens increase access to care and provide safer, more appropriate treatment than methadone for some patients.

The aim of this study was to assess the attitudes of Italian physicians regarding buprenorphine and its clinical use approximately 6 years after the medication was introduced into clinical practice. The sample consisted of 305 randomly selected physicians, working in public centers of drug addiction. In Italy buprenorphine seems a valid tool in the field of drug addiction treatment, although it is far from replacing methadone even though it seems to guarantee better compliance. Interviewees follow clinical experience more than international guidelines, with pharmaceutical company representatives as the most cited source for information about the medication. The data also suggests a need for the development of formal guidelines for treatment with buprenorphine in Italy.

Many studies have documented the safety, efficacy, and effectiveness of long-acting opioids (L-AOs), such as methadone and buprenorphine, in the treatment of heroin addiction. This article reviews the pharmacological differences between L-AO medications and short-acting opioids (heroin) in terms of reinforcing properties, pharmacokinetics, effects on the endocrine and immune systems. Given their specific pharmacological profile, L-AOs contribute to control addictive behavior, reduce craving, and restore the balance of disrupted endocrine function. The use of the term "substitution," referring to the fact that methadone or buprenorphine replace heroin in binding to brain opioid receptors, has been generalized to consider L-AOs as simple replacement of street drugs, thus contributing to the widespread misunderstanding of this treatment approach.

Opiate addiction influences many physiological functions including immune responses. The objective of this study was to investigate the immune system function in heroin addicted patients submitted to methadone or buprenorphine maintenance treatment compared to untreated heroin addicts and healthy controls. Four groups were studied: group A included nine heroin addicted subjects, who were still injecting heroin; groups B and C were composed of 12 patients previously addicted to heroin, being treated with methadone (mean dosage 58+/-12.7 mg/day) or buprenorphine (mean dose 9.3+/-2.3mg/day) since at least 6 months; group D was composed of 15 sex and age matched healthy controls. Lymphoproliferation and peripheral mononuclear cell cultures production of the Th1 cytokines IL-2 and IFN-gamma, the Th2 cytokine IL-4, and of the pro-inflammatory cytokine TNF-alpha were evaluated in all the patients and controls. PHA-lymphoproliferation was lower in untreated heroin addicts than in controls, while it was normal in methadone and buprenorphine treated patients. An altered Th1/Th2 balance, characterized by reduced IL-4, IFN-gamma and TNF-alpha but normal IL-2 levels, was present in untreated heroin addicted subjects, while the Th1/Th2 balance was well conserved in the methadone and buprenorphine groups. These findings suggest that the immune system abnormalities in heroin addicted patients can be restored to almost normal values by controlled treatment with methadone and buprenorphine.

Objective: The aim of this study was to compare the long-term outcomes of treatment-resistant heroin addicts with and without DSM-IV axis I psychiatric comorbidity (dual diagnosis). Method: 129 heroin addicts who also met criteria for treatment resistance, 66 with one or more DSM-IV axis I psychiatric diagnosis (DD patients), and 63 without DSM-IV axis I psychiatric comorbidity (NDD patients) were monitored prospectively (6 years on average, min. 1, max. 9) along a methadone maintenance treatment program (MMTP). Results: The rates for survival-in-treatment were about 50% for NDD patients and about 70% for DD patients. After 4 years of treatment onwards, such rates tended to become stable. DD patients showed better outcome measures than NDD patients. A significantly higher methadone dose was needed to have DD patients stabilized. Conclusions: Contrary to expectations, treatment-resistant patients with psychiatric comorbidity showed a better long-term outcome than treatment-resistant patients without psychiatric comorbidity.

The link between specific personality profiles and a single psychotropic drug of choice is still unclear and only partially explored. The present study compares three groups of male subjects: 85 patients manifesting heroin dependence (age: 30.07 +/- 2.78), 60 patients manifesting cocaine dependence (age: 31.96 +/- 3.1), and 50 healthy subjects from a random population sample (age: 33.25 +/- 1.45). The patients included in the study showed a long-lasting history of dependence on heroin or cocaine, respectively, 5.2 +/- 2.5 years, 4.6 +/- 2.9 years, and were stabilized in treatment, and abstinent, at least 4 weeks at the time of the diagnostic assessment. Heroin addicts (52.90%) were on methadone maintenance treatment. Cocaine addicts (11.60%) were treated with selective serotonin reuptake inhibitors. Personality traits were measured by the Minnesota Multiphasic Personality Inventory (MMPI-2) and Cloninger's Three-dimensional Personality Questionnaire (TPQ). Character and quantification of aggressiveness were measured by the Buss-Durkee Hostility Inventory (BDHI). Heroin-dependent patients (group A) scored significantly higher on hysteria, masculine-feminine and social introversion subscales of the MMPI, and significantly lower on the harm avoidance (HA) subscale of the TPQ than cocaine addicts. In contrast, scores on the MMPI for hypochondria, psychopathic deviance, and paranoia dimensions were more elevated in cocaine addicts than in heroin-dependent patients. Cocaine addicts scored higher than heroin addicts on the "direct" aggressiveness subscale and on the BDHI total score. Cocaine addicts did not differ from healthy controls on harm avoidance (behavioral control). Although cocaine addicts showed more consistent psychopathic deviance and overt aggressiveness than heroin addicts, higher harm avoidance (behavioral control), hypochondria (or worry about their health), and social extroversion may reduce their proneness to overt antisocial behavior and allow relatively higher levels of social integration. The study's limitations are noted.

Methadone and buprenorphine are two of the drugs most frequently used for abstinence from illicit opioids and in the treatment of pain. A sensitive and selective high-performance liquid chromatographic method with diode array detection for the simultaneous determination of methadone, buprenorphine and norbuprenorphine has been developed. Separation of the three analytes was obtained by using a reversed-phase column (C8, 250 mm × 4.6 mm i.d., 5 μm) and a mobile phase composed of 40% phosphate buffer containing triethylamine, 50% methanol and 10% acetonitrile (final apparent pH 6.0). Loxapine was used as the internal standard. An accurate pre-treatment procedure of biological samples was developed, using solid-phase extraction with C8 cartridges (100 mg, 1 mL) and needing small amounts of plasma or urine (300 μL). The calibration curves were linear over a working range of 10.0–1500.0 ng/mL for methadone and of 5.0–500.0 ng/mL for buprenorphine and norbuprenorphine in both matrices. The limit of quantitation (LOQ) and the limit of detection (LOD) were 1.0 and 0.4 ng/mL for methadone and 0.5 and 0.2 ng/mL for both buprenorphine and norbuprenorphine, respectively. The method was successfully applied to the analysis of plasma and urine samples from patients undergoing treatment with these drugs. Precision and accuracy results were satisfactory and no interference from endogenous or exogenous compounds was found. The method is suitable for the simultaneous determination of methadone and buprenorphine in human plasma and urine for therapeutic drug monitoring purposes.

Variants of the opioid receptors are the obvious candidates underlying addiction. The kappa opioid receptor (KOR) system seems to play a role in stress responsivity, opiate withdrawal and responses to psycho-stimulants, inhibiting mesolimbic dopamine. KOR gene polymorphisms have been reported to contribute to predisposition to voluntary alcohol-drinking behavior in experimental animals. In humans, the 36G > T single nucleotide polymorphism (SNP) on KOR gene, that was recently identified, has been found associate with substance dependence, with inconclusive findings. In the present study, 106 heroin addicts (West European, Caucasians) and 70 healthy control subjects matched for race and gender, with no history of substance use disorder, have been genotyped. The frequency of KOR 36G > T SNP was significantly higher among heroin-dependent individuals compared with control subjects (Fisher's exact = 0.044; Pearson chi(2) = 4.2734, P = 0.039; likelihood ratio chi(2) tests = 4.6156, P = 0.032). Although KOR silent polymorphisms may apparently have no consequences on mRNA transcription, post-transcriptional mechanisms, such as mRNA stability, translation efficiency, and regulability may impair the function of kappa receptors system, with increased risk for substance use disorders. In specific, the neurobiological changes induced by mu-kappa opioid imbalance could underlie vulnerable personality traits and risk behavior.

A variety of studies evidenced a relationship between drug use disorders and sexual dysfunction. In particular, heroin and opioid agonist medications to treat heroin dependence have been found to be associated with erectile dysfunction and reduced libido. Controversial findings also indicate the possibility of factors other than the pharmacological effects of opioid drugs concurring to sexual dysfunction. With the present study, we investigated the link between sexual dysfunction and long-term exposure to opioid receptor stimulation (heroin dependence, methadone maintenance treatment, methadone dosage), the potentially related hormonal changes reflecting hypothalamus-pituitary-gonadal axis function and prolactin (PRL) pituitary release, the role of adverse childhood experiences in the clinical history and the concomitant symptoms of comorbid mental health disorders in contributing to sexual problems. Forty male patients participating in a long-term methadone treatment program were included in the present study and compared with 40 healthy control subjects who never used drugs nor abused alcohol. All patients and controls were submitted to the Arizona Sexual Experiences Scale (ASEX), Child Experiences of Care and Abuse-Questionnaire (CECA-Q) and the Symptom Check List-90 Scale. A blood sample for testosterone and PRL assays was collected. Methadone dosages were recorded among heroin-dependent patients on maintenance treatment. Methadone patients scored significantly higher than controls on the 5-item rating ASEX scale, on CECA-Q and on Symptoms Check List 90 (SCL 90) scale. Testosterone plasma levels were significantly lower and PRL levels significantly higher in methadone patients with respect to the healthy control group. ASEX scores reflecting sexual dysfunction were directly and significantly correlated with CECA-Q neglect scores and SCL 90 psychiatric symptoms total score. The linear regression model, when applied only to addicted patients, showed that methadone dosages were not significantly correlated with sexual dysfunction scores except for ‘erectile dysfunction', for which an inverse association was evidenced. Testosterone values showed a significant inverse correlation with ASEX sexual dysfunction scores, CECA-Q neglect scores and psychiatric symptom at SCL 90 among methadone patients. PRL levels were directly and significantly correlated with sexual dysfunction scores, psychiatric symptoms at SCL 90 and CECA-Q neglect scores. Both testosterone and PRL did not correlate with methadone dosages. The present findings appear to support the view of childhood adversities and comorbid psychiatric symptoms contributing to sexual dysfunction and related hormonal changes among methadone patients, challenging the assumption that attributes sexual problems entirely to the direct pharmacological effects of opioid agonist medications.

γ-Hydroxybutyric acid (GHB) is a powerful central nervous system depressant, currently used in medicine for the treatment of narcolepsy and alcohol dependence. In recent years, it has gained popularity among illegal club drugs, mainly because of its euphoric effects as well as doping agent and date rape drug. The purpose of the present work was the development of a rapid analytical method for the analysis of GHB in innovative biological matrices, namely dried blood spots (DBSs) and dried urine spots (DUSs). The analytical method is based on capillary zone electrophoresis with indirect UV absorption detection at 210 nm and capillary wall dynamic coating. The background electrolyte is composed of a phosphate buffer containing nicotinic acid (probe for detection) and cetyltrimethylammonium bromide (CTAB, reversal of electroosmosis in wall dynamic coating). The influence of probe and CTAB concentration, together with buffer pH, on migration time and signal response was investigated. Under the optimized conditions, analytical linearity and precision were satisfactory; absolute recovery values were also high (>90 %); the use of dried matrices (DBSs and DUSs) was advantageous as an alternative matrix to classical ones. No interferences were found either from the most common exogenous or from endogenous compounds. This analytical approach can offer a rapid, precise and accurate method for GHB determination in innovative biological samples, which could be important for screening purposes in clinical and forensic toxicology. Graphical Abstract CE method, by combined indirect UV detection and dynamic coating, for GHB determination in DBSs and DUSs.

Low parental care during childhood, a pattern characteristic of an ‘‘affectionless control’’ rearing style was frequently reported in the history of addicted individuals. Parents’ childrearing regimes and children’s genetic predispositions, with their own behavioral characteristics, have been seen to be closely interwoven, probably affecting children’s development and addictive behavior susceptibility. In the present study, parents care perception, aggressive personality traits, and genotype (serotonin transporter promoter gene—5-HTTLPR) have been investigated in cocaine users and healthy control subjects. PBI scores (maternal and paternal care) were lower and BDHI scores (aggressiveness) higher in cocaine users in comparison with controls and significant differences in the perception of either paternal or maternal care were observed between cocaine users and non-users. The short-short (SS) genotype frequency was significantly higher among cocaine users compared with control subjects (P ¼ 0.04). Logistic regression proves that persons bearing the SS genotype have a risk of becoming cocaine user almost three times higher than those having the LL genotype. Estimations of the effects of other factors potentially affecting the risk of being cocaine addicted clearly prove the significant impact of aggressiveness: the highest the score, the highest the risk of becoming cocaine user. Moreover, paternal and maternal care perception significantly improve the fit of the model (the log likelihood decreases passing from � 105.9 to � 89.8, LR test ¼ 32.17, P-value ¼ 0.0000). Each unit increase in the PBI score yields a significant 12% and 10% decrease of the risk of becoming cocaine user, respectively for paternal and maternal care. Interestingly, once controlled for the PBI score, the relative risk associated to the SS genotype drops strikingly and becomes no longer statistically significant. On the whole, our preliminary data suggest that the association between 5-HT transporter polymorphism and psycho-stimulant use may be mediated by mother–child relationship and parental attachment perception, both being environmental and genetic factors involved in the proneness to substance use disorders, particularly in aggressive-antisocial individuals. 2006 Wiley-Liss, Inc.

Dual Diagnosis (DD) is a double pathology afflicting drug users that involves both addiction and psychiatric diseases. This specific condition is currently attracting attention from the scientific community. There are limited data available relating to this area and even less specifically relating to problematic drug use and addiction among prisoners and the general lack of adequate treatments and therapeutic tools that are required by this population. This study is divided into four phases, and this article discusses only the preliminary data. Each prisoner in the sample with addiction problems was subjected to an initial screening, and if the slightest element of DD was highlighted, the client was assessed with specific clinical tools (MMPI‐2, SCID II) and an interview with a psychiatrist. The data collected from the Minnesota Multiphasic Personality Inventory (MMPI‐2) test highlighted that the most recurrent disorder in both of the sample prisons was borderline personality disorder with the majority of the subjects presenting personality disorders in axis II of the DSM‐IV TR, using the Structured Clinical Interview Diagnosis II (SCID II). The data gathered demonstrated that two‐thirds of the prisoners with addiction in these prisons suffer from a DD, and it is therefore important to distinguish the addiction from the psychiatric diagnoses and the DD condition in order to decide the specific treatment. This research suggests that in cases of Dual Diagnosis, both clinical conditions must be addressed, or there is a risk that these prisoners will only be partially treated, and this will create further difficulties in their rehabilitation.

The present study compared in a clinical non-experimental setting the efficacy of buprenorphine (BUP) and methadone (METH) in the treatment of opioid dependence: all the subjects included in the study showed severe long-lasting heroin addiction. Participants (154) were applicants to a 12 weeks treatment program, who were assigned to either METH (78) (mean doses 81.5 +/- 36.4 mg) or BUP (76) (mean doses 9.2 +/- 3.4 mg) treatment. Aim of the study was to evaluate patient/treatment variables possibly influencing retention rate, abstinence from illicit drugs and mood changes. METH patients showed a higher retention rate at week 4 (78.2 versus 65.8) (P < 0.05), but BUP and METH were equally effective in sustaining retention in treatment and compliance with medication at week 12 (61.5 versus 59.2). Retention rate was influenced by dose, psychosocial functioning and not by psychiatric comorbidity in METH patients. In contrast, BUP maintained patients who completed the observational period showed a significantly higher rate of depression than those who dropped out (P < 0.01) and the intention to treat sample (P < 0.05). No relationship between retention and dose, or retention and psychosocial functioning was evidenced for BUP patients. The risk of positive urine testing was similar between METH and BUP, as expression of illicit drug use in general. At week 12, the patients treated with METH showed more risk of illicit opioid use than those treated with BUP (32.1% versus 25.6%) (P < 0.05). Negative urines were associated with higher doses in both METH and BUP patients. As evidenced for retention, substance abuse history and psychosocial functioning appear unable to influence urinalyses results in BUP patients. Buprenorphine maintained patients who showed negative urines presented a significantly higher rate of depression than those with positive urines (P < 0.05). Alternatively, psychiatric comorbidity was found unrelated to urinalyses results in METH patients. Our data need to be interpreted with caution because of the observational clinical methodology and non-random procedure. The present findings provide further support for the utility of BUP in the treatment of opioid dependency and demonstrate efficacy equivalent to that of METH during a clinical procedure. BUP seems to be more effective than METH in patients affected by depressive traits and dysphoria, probably due to antagonist action on kappa-opioid receptors. Psychosocial functioning and addiction severity cannot be used as valuable predictors of BUP treatment outcome. High doses appear to predict a better outcome, in term of negative urines, for both METH and BUP, but not in term of retention for BUP patients.

The comparison of two HPLC methods, one with electrochemical detection and the other with coulometric detection, for the simultaneous analysis of catecholamines and 4-hydroxy-3-methoxyphenylethylene glycol (MHPG) in human plasma is presented. The careful pre-treatment of plasma samples is based on an innovative two-step procedure by means of solid-phase extraction (SPE) which uses one single hydrophilic-lipophilic balance cartridge. The extraction yield values found were higher than 85% for epinephrine, norepinephrine and MHPG, and higher than 70% for dopamine. The assays carried out on real plasma samples with the coulometric system gave good results in terms of sensitivity (limits of quantitation: 0.10-0.15 ng ml(-1) for catecholamines, 0.6 ng ml(-1) for MHPG) and selectivity, while interference was sometimes found when using the amperometric system. Precision was also satisfactory, with relative standard deviation values for intermediate precision always lower than 6%. The HPLC method with coulometric detection coupled to a novel SPE procedure is thus suitable for the simultaneous determination of catecholamines and MHPG in plasma of volunteers subjected to experimental stress.

In previous studies, serotonin (5-HT) system disturbance was found involved in a variety of behavioral disorders, psychopathologies, and substance use disorders. A functional polymorphism in the promoter region of the human serotonin transporter gene (5-HTTLPR) was recently identified and the presence of the short (S) allele found to be associated with a lower level of expression of the gene, lower levels of 5-HT uptake, type 2 alcoholism, violence and suicidal behavior. In the present study, 101 heroin addicts (males, West European, Caucasians) and 101 healthy control subjects matched for race and gender, with no history of substance use disorder, have been genotyped. Aggressiveness levels were measured in both heroin addicts and controls utilizing Buss-Durkee-Hostility-Inventory (BDHI). Data about suicide attempt and violent criminal behavior in subject history have been collected. The short–short (SS) genotype frequency was significantly higher among heroin dependent individuals compared with control subjects (P = 0.025). The odds ratio for the SS genotype versus the long–long (LL) genotype frequency was 0.69, 95% Cl (0.49–0.97), when heroin addicts were compared with healthy controls. The SS genotype frequency was significantly higher among violent heroin dependent individuals compared with addicted individuals without aggressive behavior (P = 0.02). BDHI mean total scores and suspiciousness and negativism subscales scores were significantly higher in SS individuals, in comparison with LL subjects, among heroin addicts. No association was found between SS genotype and suicide history. Our data suggest that a decreased expression of the gene encoding the 5-HTT transporter, due to “S” promoter polymorphism, may be associated with an increased risk for substance use disorders, particularly in the subjects with more consistent aggressiveness and impulsiveness. © 2004 Wiley-Liss, Inc.

Neurosteroids are physiological regulators of anxiety in experimental animals, but there are no data for humans about the modulatory effects of the hormones on normal aspects of this emotional parameter. Plasma concentrations of four neurosteroids, pregnenolone, progesterone (PROG), allopregnanolone and tetrahydrodeoxycorticosterone, suggested to be major anxiety regulators in experimental animals, were measured in a group of 58 physically and psychologically normal adult male subjects. In parallel, trait (genotypical) and state (phenotypical) anxiety scores were measured by the State-Trait Anxiety Inventory. The possible correlations between the hormonal secretions and the psychological parameters were statistically analyzed. The neurosteroid concentrations and the anxiety scores of the probands were within the ranges of normality according to data of the literature and our own. PROG concentrations correlated significantly with state anxiety scores. These data suggest that neurosteroids may physiologically modulate anxiety not only in experimental animals but also in humans.

Alcohol use, "alcohol abuse," and illicit drug use were investigated in a representative sample of 1076 urban, northern Italian high school students aged 14 to 19 years in 2001. In addition to questions on substance use, the participants were asked about school achievements and perceived substance use among friends. All the students were submitted to Zuckerman Sensation Seeking Scale (SSS) scale, Eysenck Personality Questionnaire (EPQ), Buss-Durkee Hostility Inventory (BDHI), and Parental Bonding Instrument (PBI). Lifetime alcohol use was found in 80.5%, "alcohol abuse" in 37.7%, cannabis use in 26.2%, ecstasy in 2.8%, heroin in 3.8%, and cocaine in 8.3% of the students: gender differences were significant for alcohol use, "alcohol abuse" and ecstasy use, with male subjects outnumbering females, but not for reported cannabis, heroin, and cocaine use. Early substance use onset among adolescents aged 14-16 years was detected. Higher sensation seeking on SSS, social coping impairment on EPQ, direct aggressiveness on BDHI, poor school achievements, and lower parental care on PBI were found associated with illicit drug use and "alcohol abuse" (multiple drugs users). Increased levels of aggressiveness and sensation seeking were evidenced both in minimal experimenters (ME) and habitual users (HU), without any significant difference, in comparison with abstinent students. Similarly, ME scored higher than abstinent subjects on EPQ for social coping impairment, but lower than HU. Parental care perception was lower in HU, but not in ME with, respect to abstinent subjects. Pearson inverse correlation was demonstrated between PBI scores and EPQ maladaptation and BDHI aggressiveness. Data from this preliminary pilot study suggest that temperamental traits and personality changes may be associated to early substance use "proneness" and reduced perception of parental care.