Implications of Cannabis Use and Heavy Alcohol Use on HIV Drug Risk Behaviors in Russian Heroin Users

Cannabis and heavy alcohol use potentially increase HIV transmission by increasing risky drug behaviors. We studied 404 subjects entering treatment for heroin dependence, in St. Petersburg, Russia. We used the HIV Risk Assessment Battery (RAB) drug subscale to measure risky drug behavior. Although all heavy alcohol users had risky drug behaviors, their drug RAB scores did not differ from non-heavy alcohol users in unadjusted or adjusted analyses. Cannabis use was significantly associated with drug RAB scores in unadjusted analyses (mean difference 1.7 points) and analyses adjusted for age, sex, and employment (mean difference 1.3 points). When also adjusting for stimulant use, the impact of cannabis use was attenuated and no longer statistically significant (mean difference 1.1 points). Because of the central role of risky drug behaviors in the Russian HIV epidemic, it is important to understand how the use of multiple substances, including cannabis and alcohol, impacts risky drug behaviors

Feasibility and initial efficacy of a culturally sensitive women-centered substance use intervention in Georgia: Sex risk outcomes

This paper reports on the feasibility and initial efficacy of a culturally sensitive, comprehensive women-centered substance use intervention for women who inject drugs in Georgia in terms of the primary and secondary sex risk outcomes. The hypothesis under examination was that, relative to case management participants, participants in a culturally sensitive, comprehensive women-specific and -centered intervention would, on average, show significant decreases in past-30-day frequency of unprotected sex, unprotected sex at the last sexual encounter, and increases in condom use and safer sex actions. The study was a two-arm randomized trial, in which 173 potentially eligible women were screened, and those 128 women determined to be eligible were assigned at random to either Reinforcement-based Treatment plus Women’s Co-Op (RBT + WC) or case management (CM). RBT + WC participants received 12 sessions of a structured intervention with the goal of reducing risky sex and substance use and improving physical and mental health. CM participants received 12 sessions of case management and informational brochures that focused on the same issues on which RBT + WC focused. Participants were assessed at baseline, post-treatment, and 3 months following treatment enrollment. Analyses revealed case management having significantly overall higher Safer Sex action scores than RBT + WC, and a significant decrease over time for past 30-day number of unprotected sex acts. Unprotected sex at the last encounter and Condom Use action scores were nonsignificant. Women who inject drugs in Georgia are engaging in risky sexual practices, and are in need of an intervention that addresses these risky behaviors. Reasons for the failure to find differences between a culturally sensitive, comprehensive women-centered intervention and case management tailored to the needs of women who inject drugs in Georgia may have been the result of inadequate power to detect an effect in a sample whose drug use was not as serious as warranted by the intervention. (ClinicalTrials.gov Identifier: NCT01331460)https://doi.org/10.1186/s13011-015-0043-

РЕЦЕПТОР ДОФАМИНА D2 (DRD2) ЛИМФОЦИТОВ ПЕРИФЕРИЧЕСКОЙ КРОВИ КАК БИОМАРКЕР ПРОГНОЗА АНТИПСИХОТИЧЕСКОЙ ТЕРАПИИ

Introduction. Despite the evolution of antipsychotic drugs, the problem of the therapy effectiveness and safety of schizophrenia spectrum disorders and comorbid conditions is very acute. The dopamine receptor D2 gene (DRD2) is one of the key targets of modern pharmacogenetic studies of mental disorders.The objective of the study was to analyze the DRD2 mRNA level in peripheral blood lymphocytes and to identify genetic variations of –141С Ins/Del as potential biomarkers for antipsychotic therapy prognosis.Methods and materials. The study included 112 patients with mental disorders: 61 – with a diagnosis of schizophrenia spectrum disorder, 51 – with a comorbid disease course with alcohol dependence syndrome, and 112 people as a control group. Psychometric evaluation was carried out using PANSS scale. The material was peripheral blood lymphocytes (PBLs). The DRD2 mRNA level was determined by real-time polymerase chain reaction with TaqMan probe. Genotyping –141С Ins/Del was performed by the restriction fragment length polymorphism assay.Results. –141C Ins/Del DRD2 genetic variations are not associated with a risk of mental disorder development, and they did not affect the DRD2 mRNA level in PBLs. There were no significant differences in the gene expression of DRD2 in the control group and patients (p=0.194). Despite the improvement of the mental state in all patients included in the study, the studied DRD2 parameters did not affect either the mental disorder symptoms or the normalization of the patient status against the background of antipsychotic therapy. Ins/Ins genetic variation of –141C Ins/Del was significantly associated with an increase weight gain of more than 7 % on the 28th day of antipsychotic therapy.Conclusion. Ins/Ins genetic variation of –141C Ins/Del can be considered as a biomarker for the prognosis of antipsychotic-induced weight gain. Введение. Несмотря на эволюцию антипсихотических препаратов, проблема эффективности и безопасности терапии расстройств шизофренического спектра и коморбидных с ними состояний стоит очень остро. Ген рецептора дофамина Д2 (DRD2) – один из объектов современных фармакогенетических исследований в психиатрии.Цель исследования – определение биомаркеров прогноза антипсихотической терапии на основе молекулярно-генетических характеристик гена DRD2 в лимфоцитах периферической крови (уровня мРНК и генетических вариантов –141С Ins/Del).Методы и материалы. В исследование включены 112 пациентов с психическими патологиями: 61 – с диагнозом «Расстройство шизофренического спектра», 51 – с коморбидным течением расстройства шизофренического спектра и синдрома алкогольной зависимости и 112 лиц контрольной группы. Психометрическую оценку проводили на основании шкалы PANSS. Материалом служили лимфоциты периферической крови (ЛПК). Уровень мРНК гена DRD2 определяли методом ПЦР в реальном времени с использованием зонда TaqMan. Генотипирование –141С Ins/Del – методом полиморфизма длины рестрикционных фрагментов.Результаты. Генетические варианты –141С Ins/Del DRD2 не ассоциированы с риском развития психических патологий и уровнем мРНК гена DRD2 в ЛПК. Экспрессия гена DRD2 у лиц контрольной группы и психически больных не различалась (р=0,194). Несмотря на улучшение психического состояния у всех пациентов, включенных в исследование, изучаемые показатели DRD2 не оказывали влияния ни на симптоматику психических патологий, ни на нормализацию статуса пациентов на фоне антипсихотической терапии. Генетический вариант Ins/Ins –141С Ins/Del статистически значимо ассоциировался с увеличением массы тела более 7 % на 28-й деньтерапии антипсихотиками.Выводы. Генетический вариант Ins/Ins –141С Ins/Del может быть рассмотрен в качестве биомаркера прогноза антипсихотик-индуцированного набора массы тела.

Comparing sexual risks and patterns of alcohol and drug use between injection drug users (IDUs) and non-IDUs who report sexual partnerships with IDUs in St. Petersburg, Russia

<p>Abstract</p> <p>Background</p> <p>To date, the great majority of Russian HIV infections have been diagnosed among IDUs and concerns about the potential for a sexual transmission of HIV beyond the IDU population have increased. This study investigated differences in the prevalence of sexual risk behaviors between IDUs and non-IDUs in St. Petersburg, Russia and assessed associations between substance use patterns and sexual risks within and between those two groups.</p> <p>Methods</p> <p>Cross-sectional survey data and biological test results from 331 IDUs and 65 non-IDUs who have IDU sex partners were analyzed. Multivariate regression was employed to calculate measures of associations.</p> <p>Results</p> <p>IDUs were less likely than non-IDUs to report multiple sexual partners and unprotected sex with casual partners. The quantity, frequency and intensity of alcohol use did not differ between IDUs and non-IDUs, but non-IDUs were more likely to engage in alcohol use categorized as risky per the alcohol use disorders identification test (AUDIT-C). Risky sexual practices were independently associated with monthly methamphetamine injection among IDUs and with risky alcohol use among non-IDUs. Having sex when high on alcohol or drugs was associated with unprotected sex only among IDUs.</p> <p>Conclusions</p> <p>Greater prevalence of sexual risk among non-IDUs who have IDU sex partners compared to IDUs suggests the potential for sexual transmission of HIV from the high-prevalence IDU population into the general population. HIV prevention programs among IDUs in St. Petersburg owe special attention to risky alcohol use among non-IDUs who have IDU sex partners and the propensity of IDUs to have sex when high on alcohol or drugs and forgo condoms.</p

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Экспрессия рецептора дофамина DRD1 (мРНК, белок) в лимфоцитах периферической крови и прогноз антипсихотической терапии

Introduction. There is a problem in predicting the efficacy and safety of antipsychotic therapy. Dopamine receptor D1 is one of the targets of antipsychotics. Peripheral blood lymphocytes (PBL) are the research object of neurotransmission receptors.The objective was to study DRD1 gene expression (mRNA, protein level) in PBL as a possible biomarker of olanzapine and haloperidol therapy prognosis.Methods and Materials. Sample: 106 patients diagnosed with schizophrenic spectrum disorder. Study design: prospective longitudinal follow-up with drug administration by randomization. Assessment of mental status and development of Parkinsonism: Positive and Negative Syndrome Scale (PANSS) and Simpson-Agnus Scale (SAS), respectively. PBL was study material. DRD1 mRNA level was determined by real-time PCR. DRD1 protein concentration in PBL was measured by enzyme immunoassay.Results. Haloperidol (but not olanzapine) treatment for 28 days, leads to DRD1 protein concentration decrease in PBL in a manner dependent on its initial level. DRD1 mRNA level in PBL remained unchanged during the treatment. Patients with effective therapy by olanzapine had lower DRD1 mRNA levels. Side effects of the therapy (Parkinsonism, weight gain) were not associated with studied DRD1 parameters.Conclusions. Haloperidol treatment leads to a decrease of DRD1 protein concentration in PBL, which depends on the initial protein level. Effective olanzapine therapy is associated with reduced DRD1 mRNA level in PBL before the treatment. Введение. Существует проблема прогноза эффективности и безопасности терапии антипсихотическими препаратами, одна из мишеней которых – рецептор дофамина D1. Лимфоциты периферической крови (ЛПК) – объект исследования рецепторов нейротрансмиссии.Цель – изучение экспрессии гена DRD1 (мРНК, белок) в ЛПК как возможного биомаркера прогноза терапии оланзапином и галоперидолом.Методы и материалы. Выборка: 106 пациентов с диагнозом «Расстройство шизофренического спектра». Дизайн исследования: проспективное лонгитудинальное наблюдение с назначением препарата путем рандомизации. Оценка психического статуса и развития паркинсонизма: шкалы Позитивных и негативных синдромов (PANSS) и Симпсона Агнуса (SAS). Материал исследования – ЛПК. Уровень мРНК гена DRD1 определяли методом полимеразной цепной реакции в режиме реального времени. Концентрацию белка DRD1 в ЛПК измеряли методом иммуноферментного анализа.Результаты. При воздействии галоперидола (но не оланзапина) в течение 28 дней концентрация белка DRD1 в ЛПК снижалась зависимо от его начального уровня. Уровень мРНК гена DRD1 в ЛПК оставался неизменным при действии препаратов. Пациенты с эффективной терапией оланзапином имели более низкие значения уровня мРНК DRD1. Побочные эффекты терапии (паркинсонизм, набор веса) не были ассоциированы с изучаемыми характеристиками DRD1.Заключение. Действие галоперидола приводит к снижению концентрации белка DRD1 в ЛПК, которое зависит от начального уровня белка. Эффективная терапия оланзапином ассоциирована с пониженным уровнем мРНК DRD1 в ЛПК до начала лечения.