Drug Prevention and Health Branch

Vienna, Austria

Drug Prevention and Health Branch

Vienna, Austria
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Saracino M.A.,University of Bologna | Marcheselli C.,University of Bologna | Somaini L.,Addiction Treatment Center | Pieri M.C.,Addiction Treatment Center | And 3 more authors.
Analytical and Bioanalytical Chemistry | Year: 2012

A novel test has been developed for the analysis of methadone in dried blood spot specimens from patients undergoing methadone maintenance treatment. An isocratic reversed-phase high-performance liquid chromatography method with coulometric detection has been optimized for the determination of methadone. The clean-up of dried blood spots was performed by means of an original microextraction by packed sorbent procedure after microwaveassisted extraction of the drug with a suitable solvent. Extraction yields were satisfactory, always being higher than 90.0 %. The calibration curve was linear over the 4- 500 ng mL-1 concentration range. The method had satisfactory sensitivity (limit of quantitation of 4 ng mL-1), precision (relative standard deviation less than 5.8 %), selectivity and accuracy (recovery greater than 87.0 %). It was successfully applied to dried blood spot samples collected from heroinaddicted patients undergoing methadone maintenance therapy at dosages between 40 and 240 mg day-1. The statistical analysis (Bland-Altman plot) showed that the results were in good agreement with those found from the analysis of plasma samples obtained from the same patients. Thus, the method has proved to be suitable for the monitoring of methadone by means of dried blood spots. © Springer-Verlag 2012.

De Guglielmo G.,University of Camerino | Cippitelli A.,University of Camerino | Somaini L.,Addiction Treatment Center | Gerra G.,Drug Prevention and Health Branch | And 5 more authors.
Addiction Biology | Year: 2013

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. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

Gerra G.,Drug Prevention and Health Branch | Somaini L.,Addiction Treatment Center | Leonardi C.,Addiction Treatment Center | Cortese E.,Addiction Treatment Center | And 3 more authors.
Psychiatry Research | Year: 2014

A variety of studies were addressed to differentiate responders and non-responders to substitution treatment among heroin dependent patients, without conclusive findings. In particular, preliminary pharmacogenetic findings have been reported to predict treatment effectiveness in mental health and substance use disorders. Aim of the present study was to investigate the possible association of buprenorphine (BUP) treatment outcome with gene variants that may affect kappa-opioid receptors and dopamine system function. One hundred and seven heroin addicts (West European, Caucasians) who underwent buprenorphine maintenance treatment were genotyped and classified into two groups (A and B) on the basis of treatment outcome. Non-responders to buprenorphine (group B) have been identified taking into account early drop out, continuous use of heroin, severe behavioral or psychiatric problems, misbehavior and diversion during the 6 months treatment period. No difference was evidenced between responders and non-responders to BUP in the frequency of kappa opioid receptor (OPRK1) 36G>T SNP. The frequency of dopamine transporter (DAT) gene polymorphism (SLC6A3/DAT1), allele 10, was evidently much higher in "non-responder" than in "responder" individuals (64.9% vs. 55.93%) whereas the frequency of the category of other alleles (6, 7 and 11) was higher in responder than in non-responder individuals (11.02% vs. 2.13% respectively). On one hand, the hypothesis that possible gene-related changes in kappa-opioid receptor could consistently affect buprenorphine pharmacological action and clinical effectiveness was not confirmed in our study, at least in relation to the single nucleotide polymorphism 36G>T. On the other hand, the possibility that gene-related dopamine changes could have reduced BUP effectiveness and impaired maintenance treatment outcome was cautiously supported by our findings. DAT1 gene variants such as allele 10, previously reported in association with personality and behavioral problems, would have influenced the effects of BUP-induced dopamine release, modulated through mu and kappa opioid receptors, and probably the related reinforcing capacity of the drug. © 2013 Elsevier Ireland Ltd.

Saracino M.A.,University of Bologna | Iacono C.,University of Bologna | Somaini L.,Addiction Treatment Center | Gerra G.,Drug Prevention and Health Branch | And 2 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2014

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.

Stopponi S.,University of Camerino | Somaini L.,Addiction Treatment Center | Cippitelli A.,University of Camerino | De Guglielmo G.,University of Camerino | And 5 more authors.
Psychopharmacology | Year: 2012

Rationale Pregabalin (Lyrica™) is a structural analogue of γ-aminobutyric acid (GABA) approved by FDA for partial epilepsy, neuropathic pain and recently generalized anxiety disorder. While the exact cellular mechanism of action of pregabalin is still unclear, evidence from several studies suggests that it reduces excitatory neurotransmitter release and postsynaptic excitability. Objectives Based on these mechanisms we sought interesting to evaluate the effect of pregabalin on alcohol-abuse-related behaviours. Materials and methods For this purpose, using genetically selected alcohol-preferring Marchigian Sardinian (msP) rats, we evaluated the effect of pregabalin on alcohol drinking and relapse to alcohol seeking elicited by environmental conditioning factors or stress. Results Our results showed that treatment with pregabalin (0, 10, 30 and 60 mg/kg) given orally selectively reduced home cage alcohol drinking in msP rat. This effect was confirmed in self-administration experiments where prega-balin (0, 10 and 30 mg/kg) significantly reduced operant responding for alcohol but not for food. Using alcohol reinstatement models we also found that pregabalin (0, 10 and 30 mg/kg) abolished seeking behaviour elicited by the pharmacological stressor yohimbine as well as cues predictive of alcohol availability. Conclusions Results demonstrate that pregabalin may have potential in the treatment of alcohol addiction. © 2011 Springer-Verlag.

Somaini L.,Health Local Unit BI | Manfredini M.,University of Parma | Amore M.,University of Parma | Zaimovic A.,Addiction Treatment Center | And 5 more authors.
European Archives of Psychiatry and Clinical Neuroscience | Year: 2012

Aim of this paper is to investigate the psychobiological reactions to experimentally induced negative emotional states in active marijuana-dependent mokers and whether changes in emotional reactivity were reversed by prolonged abstinence. Twenty-eight patients were randomly included into group A (fourteen active marijuanadependent smokers) or group B (fourteen abstinent marijuana-dependent subjects). Emotional response evaluation of group B subjects was assessed after 6 months of abstinence. Fourteen healthy volunteers, matched for age and sex, were used as controls. Psychometric and emotional response evaluations were performed by administering Symptoms Check List-90 and State-Trait Anxiety Inventory Y-1 (STAI). Neutral and unpleasant set of pictures selected from the international affective picture system and the Self-Assesment Manikin procedure (SAM) have been used to determine ratings of pleasure and arousal. Before and after the experimental session, blood samples were collected to determine ACTH and cortisol plasma levels. Active cannabis users displayed significantly higher levels of pleasantness SAM scores and lower levels of arousal SAM scores compared to abstinent cannabis users and controls in response to emotional task. In a close parallel with psychological data, hormonal findings indicate a persistent hyperactivity of hypothalamus-pituitary-adrenal (HPA) axis in cannabis users particularly among active marijuana smokers and an impaired hormonal reaction to negative emotions in comparison with healthy subjects. The capacity of the HPA axis to respond to stressful stimuli/negative emotions seems to be only partially recovered after 6 months of abstinence. Ours findings although obtained in a small number of subjects suggest an association between active cannabis use subjective reduced sensitivity to negative emotions and threat and HPA axis dysfunction. © 2011 Springer-Verlag.

Somaini L.,Addiction Treatment Center | Saracino M.A.,University of Bologna | Marcheselli C.,University of Bologna | Zanchini S.,University of Bologna | And 2 more authors.
Analytica Chimica Acta | Year: 2011

The sublingual combination of buprenorphine and naloxone (Suboxone ®) and Methadone Maintenance Therapy have been found effective in treating heroin addiction. A new analytical method suitable for the simultaneous determination of buprenorphine, norbuprenorphine, methadone and naloxone in human plasma by means of liquid chromatography with coulometric detection has been developed. The chromatographic separation was achieved with a phosphate buffer-acetonitrile mixture as the mobile phase on a cyano column. The monitoring cell of the coulometric detector was set at an oxidation potential of +0.600V. A rapid clean-up procedure of the biological samples using a microextraction by packed sorbent technique has been implemented, employing a C8 sorbent inserted into a syringe needle. The extraction yield values were satisfactory for all analytes (>85%). The calibration curves were linear over a range of 0.25-20.0ngmL -1 for buprenorphine and norbuprenorphine, 3.0-1000.0ngmL -1 for methadone and 0.13-10.0ngmL -1 for naloxone. The sensitivity was also high with limits of detection of 0.08ngmL -1 for both buprenorphine and norbuprenorphine, 0.9ngmL -1 for methadone and 0.04ngmL -1 for naloxone. The intraday and interday precision data were always satisfactory.The method was successfully applied to plasma samples obtained from former heroin addicts treated with opioid replacement therapy. © 2011 Elsevier B.V.

PubMed | Addiction Treatment Center, University of Parma, University of Bologna and Drug Prevention and Health Branch
Type: | Journal: Progress in neuro-psychopharmacology & biological psychiatry | Year: 2017

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.

Maremmani I.,University of Pisa | Maremmani I.,Institute of Behavioral science | Gerra G.,Drug Prevention and Health Branch
American Journal on Addictions | Year: 2010

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. Copyright © 2010 American Academy of Addiction Psychiatry.

Maalouf W.,Drug Prevention and Health Branch | Campello G.,Drug Prevention and Health Branch
Aggression and Violent Behavior | Year: 2014

Families can be one of the most protective forces in the lives of children and youth. Family skills interventions have been found to be effective in encouraging safe and nurturing relationships between parents (or caregivers) and children in their early years and as such preventing many problem behaviours including violence. Most of the evidence in this regards is generated from high income countries. In this article UNODC reports on variables associated with violence (including conduct problems, stress management, pro-social behaviours, family aggression and conflict) generated from a multisite project aimed at piloting family skills programmes in low and middle income countries. The countries of concern are Panama, Honduras, Guatemala, Serbia, Kazakhstan, Kyrgyzstan, Turkmenistan, Tajikistan and Uzbekistan. The family skills piloted were Strengthening the Families Programme 10-14 (SFP 10-14) and Families And Schools Together (FAST). The data generated indicates high level of replicability with fidelity, affinity and need for such programmes in low and middle income countries with very encouraging in preventing violence. Significant changes at the post-test level, assessed through multi-sources, were recorded across most of the violence indicators assessed related to youth violence and child maltreatment at least on a comparable level to high-income countries. © 2014 Elsevier Ltd.

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