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OPIOIDS 2006 <621> Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Unique Identifier 17184524 Status PubMed-not-MEDLINE Authors Neasta J. Uttenweiler-Joseph S. Chaoui K. Monsarrat B. Meunier JC. Mouledous L. Authors Full Name Neasta, Jeremie. Uttenweiler-Joseph, Sandrine. Chaoui, Karima. Monsarrat, Bernard. Meunier, Jean-Claude. Mouledous, Lionel. Institution Unite Mecanismes d'action des substances opioides, Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique UMR 5089, 205 route de Narbonne, 31077 Toulouse cedex 04, France. [email protected] Title Effect of long-term exposure of SH-SY5Y cells to morphine: a whole cell proteomic analysis. Source Proteome Science. 4:23, 2006. Journal Name Proteome Science Other ID Source: NLM. PMC1766345 Country of Publication England Abstract BACKGROUND: Opiate addiction reflects plastic changes that endurably alter synaptic transmission within relevant neuronal circuits. The biochemical mechanisms of these adaptations remain largely unknown and proteomics-based approaches could lead to a broad characterization of the molecular events underlying adaptations to chronic drug exposure. RESULTS: Thus, we have started proteomic analyses of the effects of chronic morphine exposure in a recombinant human neuroblastoma SH-SY5Y clone that stably overexpresses the mu-opioid receptor. Cells were treated with morphine for 6, 24 and 72 hours, the proteins were separated by 2-D gel electrophoresis and stained with Coomassie blue, and the protein map was compared with that obtained from untreated cells. Spots showing a statistically significant variation were selected for identification using mass spectrometric analyses. CONCLUSION: A total of 45 proteins were identified, including proteins involved in cellular metabolism, cytoskeleton organization, vesicular trafficking, transcriptional and translational regulation, and cell signaling. Publication Type Journal Article. Date of Publication 2006 Year of Publication 2006 Volume 4 Page 23 OPIOIDS 2006 <629> Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Unique Identifier 16859549 Status PubMed-not-MEDLINE Authors Newman RG. Authors Full Name Newman, Robert G. Institution The Baron Edmond de Rothschild Chemical Dependency Institute of Beth Israel Medical Center, Albert Einstein College of Medicine of Yeshiva University, 555 West 57th Street, 18th Floor, New York, NY 10019, USA. [email protected] Title Expansion of opiate agonist treatment: an historical perspective. Source Harm Reduction Journal. 3:20, 2006. Journal Name Harm Reduction Journal Other ID Source: NLM. PMC1557846 Country of Publication England Abstract Untreated opiate addiction remains a major health care crisis in New York and in most other urban centers in America. Optimism for closing the gap between need and demand for treatment and its availability has greeted the recent approval of a new opiate medication for addiction, buprenorphine--which unlike methadone may be prescribed by independent, officebased practitioners. The likelihood of buprenorphine fulfilling its potential is assessed in the light of the massive expansion of methadone treatment more than 30 years earlier. It is concluded that the key, indispensable ingredient of success will be true commitment on the part of Government to provide care to all those who need it. Publication Type Editorial. Date of Publication 2006 Year of Publication 2006 Volume 3 Page 20 OPIOIDS 2006 <631> Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Unique Identifier 16542427 Status PubMed-not-MEDLINE Authors Wood E. Lim R. Kerr T. Authors Full Name Wood, Evan. Lim, Ronald. Kerr, Thomas. Institution British Columbia Centre for Excellence in HIV/AIDS, St, Paul's Hospital, 608 - 1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada. [email protected] Title Initiation of opiate addiction in a Canadian prison: a case report. Source Harm Reduction Journal. 3:11, 2006. Journal Name Harm Reduction Journal Other ID Source: NLM. PMC1421396 Country of Publication England Abstract BACKGROUND: In North America, the harms of illicit drug use have been responded to primarily through law enforcement interventions. This strategy has resulted in record populations of addicted individuals being incarcerated in both Canada and the United States. The incarceration of non-violent drug offenders has become increasingly controversial as studies demonstrate the harms, including elevated HIV risk behavior, of incarcerating injection drug users. Other harms, such as the initiation of illicit drug use by prison inmates who previously did not use drugs, have been less commonly described. CASE PRESENTATION: We report on the case of an individual who initiated non-injection opiate use in a Canadian prison and developed an addiction to the drug. Upon release into the community, the individual continued using opiates and sought treatment at a clinic. The patient feared that he might initiate injection use of opiates if his cravings could not be controlled. The patient was placed on methadone maintenance therapy. CONCLUSION: While anecdotal reports indicate that initiation in prison of the use of addictive illicit substances is frequent, documentation through clinical experience is rare, and the public health implications of this behavior have not been given sufficient attention in the literature. Strategies of incarcerating non-violent drug offenders and attempting to keep illicit drugs out of prisons have not reduced the harms and costs of illicit drug use. Effective, practical alternatives are urgently needed; expanded community diversion programs for non-violent drug offenders deserve particular attention. Publication Type Journal Article. Date of Publication 2006 Year of Publication 2006 Volume 3 Page 11 OPIOIDS 2006 <877> Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Unique Identifier 17139840 Status MEDLINE Authors McClung CA. Authors Full Name McClung, Colleen A. Institution Department of Psychiatry and Center for Basic Neuroscience, University of Texas, Southwestern Medical Center, Dallas, TX, USA. [email protected] Title The molecular mechanisms of morphine addiction. [Review] [85 refs] Source Reviews in the Neurosciences. 17(4):393-402, 2006. Journal Name Reviews in the Neurosciences Country of Publication England Abstract Addiction to opiates such as morphine is a major public health concern. A more thorough understanding of the molecular mechanisms of opiate addiction can lead to better treatment options in the future. Many of the changes in neuronal activity that occur upon morphine exposure have been known for some time, but until recently, little was known about the changes in gene expression that underlie these effects. Recent advances in molecular biology such as microarray analysis and quantitative (real time) PCR have allowed us to examine the gene expression changes that occur in response to morphine treatments and during morphine withdrawal. This review summarizes many of the known molecular and cellular actions of morphine, and some of the important gene expression changes that occur in response to morphine treatment. Many of these gene expression changes underlie the alterations in neuronal excitability, cell morphology and cell birth or death responsible for producing morphine's rewarding effects, the development of dependence, and withdrawal symptoms after treatment ends. [References: 85] ISSN Print 0334-1763 Publication Type Journal Article. Research Support, N.I.H., Extramural. Review. Date of Publication 2006 Year of Publication 2006 Issue/Part 4 Volume 17 Page 393-402 OPIOIDS 2006 <904> Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Unique Identifier 16856116 Status MEDLINE Authors Eisenberg E. McNicol E. Carr DB. Authors Full Name Eisenberg, E. McNicol, E. Carr, D B. Institution New England Medical Center, Pharmacy and Anesthesia, Box #420, 750 Washington Street, Boston, MA 02111, USA. [email protected] Title Opioids for neuropathic pain. [Review] [80 refs] Source Cochrane Database of Systematic Reviews. 3:CD006146, 2006. Journal Name Cochrane Database of Systematic Reviews Country of Publication England Abstract BACKGROUND: The use of opioids for neuropathic pain remains controversial. Studies have been small, have yielded equivocal results, and have not established the long-term riskbenefit ratio of this treatment. OBJECTIVES: To assess the efficacy and safety of opioid agonists for the treatment of neuropathic pain. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (2nd Quarter 2005), MEDLINE (1966 to June 2005), and EMBASE (1980 to 2005 Week 27) for articles in any language, and reference lists of reviews and retrieved articles. SELECTION CRITERIA: Trials were included in which opioid agonists were given to treat central or peripheral neuropathic pain of any etiology, pain was assessed using validated instruments, and adverse events were reported. Studies in which drugs other than opioid agonists were combined with opioids or opioids were administered epidurally or intrathecally were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent investigators and included demographic variables, diagnoses, interventions, efficacy, and adverse effects. MAIN RESULTS: Twenty-three trials met the inclusion criteria and were classified as short-term (less than 24 hours; n = 14) or intermediate-term (median = 28 days; range = eight to 70 days; n = 9). The short-term trials had contradictory results. In contrast all nine intermediate-term trials demonstrated opioid efficacy for spontaneous neuropathic pain. Meta-analysis of seven intermediate-term studies showed mean post-treatment visual analog scale scores of pain intensity after opioids to be 13 points lower on a scale from zero to 100 than after placebo (95% confidence interval -16 to -9; P < 0.00001). The most common adverse events were nausea (33% opioid versus 9% control: number needed to treat to harm (NNH) 4.2) and constipation (33% opioid versus 10% control: NNH 4.2), followed by drowsiness (29% opioid versus 12% control: NNH 6.2), dizziness (21% opioid versus 6% control: NNH 7.1), and vomiting (15% opioid versus 3% control: NNH 8.3). Where reported, 23 (11%) of 212 participants withdrew because of adverse events during opioid therapy versus nine (4%) of 202 receiving placebo. AUTHORS' CONCLUSIONS: Short-term studies provide only equivocal evidence regarding the efficacy of opioids in reducing the intensity of neuropathic pain, whereas intermediate-term studies demonstrate significant efficacy of opioids over placebo, which is likely to be clinically important. Reported adverse events of opioids are common but not life threatening. Further randomized controlled trials are needed to establish long-term efficacy, safety (including addiction potential), and effects on quality of life. [References: 80] Publication Type Journal Article. Meta-Analysis. Review. Date of Publication 2006 Year of Publication 2006 Volume 3 Page CD006146 OPIOIDS (A) 2006 <911> Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Unique Identifier 16546223 Status MEDLINE Authors Gray AC. Coupar IM. White PJ. Authors Full Name Gray, Andrew C. Coupar, Ian M. White, Paul J. Institution Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, 381 Royal Pde, Parkville, VIC 3052, Melbourne, Australia. Title Comparison of opioid receptor distributions in the rat central nervous system. Source Life Sciences. 79(7):674-85, 2006 Jul 10. Journal Name Life Sciences Country of Publication England Abstract The opioid receptors, mu, delta and kappa, conduct the major pharmacological effects of opioid drugs, and exhibit intriguing functional relationships and interactions in the CNS. Previously established hypotheses regarding the mechanisms underlying these phenomena specify theoretical patterns of relative cellular localisation for the different receptor types. In this study, we have used double-label immunohistochemistry to compare the cellular distributions of delta and kappa receptors with those of mu receptors in the rat CNS. Regions of established significance in opioid addiction were examined. Extensive mu/delta colocalisation was observed in neuron-like cells in several regions. mu and kappa receptors were also often co-localised in neuron-like cell bodies in several regions. However, intense kappa immunoreactivity (ir) also appeared in a separate, morphologically distinct population of cells that did not express mu receptors. These small, ovoid cells were often closely apposed against the larger, mu-ir cell bodies. Such cellular appositions were seen in several regions, but were particularly common in the medial thalamus, the periaqueductal grey and brainstem regions. These findings support proposals that functional similarities, synergy and cooperativity between mu and delta receptors arise from widespread co-expression by cells and intracellular molecular interactions. Although co-expression of mu and kappa receptors was also detected, the appearance of a separate population of kappa-expressing cells supports proposals that the contrasting and functionally antagonistic properties of mu and kappa receptors are due to expression in physiologically distinct cell types. Greater understanding of opioid receptor interaction mechanisms may provide possibilities for therapeutic intervention in opioid addiction and other conditions. ISSN Print 0024-3205 Publication Type Comparative Study. Journal Article. Research Support, Non-U.S. Gov't. Date of Publication 2006 Jul 10 Year of Publication 2006 Issue/Part 7 Volume 79 Page 674-85 OPIOIDS 2006 / COMORBIDITY 2006 <932> Database Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Unique Identifier 16309810 Status MEDLINE Authors Gerra G. Leonardi C. D'Amore A. Strepparola G. Fagetti R. Assi C. Zaimovic A. Lucchini A. Authors Full Name Gerra, Gilberto. Leonardi, Claudio. D'Amore, Antonio. Strepparola, Giovanni. Fagetti, Roberto. Assi, Cinzia. Zaimovic, Amir. Lucchini, Alfio. Institution Addiction Treatment Centre, AUSL Parma, Italy. [email protected] Title Buprenorphine treatment outcome in dually diagnosed heroin dependent patients: A retrospective study. Source Progress in Neuro-Psychopharmacology & Biological Psychiatry. 30(2):265-72, 2006 Mar. Journal Name Progress in Neuro-Psychopharmacology & Biological Psychiatry Country of Publication England Abstract The present study compared retrospectively in a clinical non-experimental setting the efficacy of buprenorphine (BUP) in different subgroups of dually diagnosed and non-dually diagnosed opioid-dependent patients: all the subjects included in the study showed severe long-lasting heroin addiction and 68.4% were affected by psychiatric comorbidity. Participants (206) (mean age 32.2+/-8.9, 177 males-29 females) were applicants to a long-term buprenorphine treatment program (mean doses 7.9+/-0.42 mg). Aim of the study was to evaluate dual diagnosis variables possibly influencing retention rate and abstinence from illicit drugs. The patients were divided into 5 subgroups on the basis of dual diagnosis: group 1: major depression (MD) 29.61%; group 2: generalized anxiety (GAD) (11.2%); group 3: personality disorders (PD), antisocial-borderline (21.84%); group 4: schizophrenia (SC)(6.3%); group 5: substance use disorder without overt psychiatric comorbidity (SUD) (31.1%). Group 1 patients affected by MD showed the highest retention rate at 12 months (72.1%) in comparison with the other groups of patients: group 2 GAD (39.1%), group 3 PD (17.8%), group 4 SC (7.7%) and group 5 SUD, without comorbidity (45.3%) (p=0.006, p<0.001, p<0.001, p=0.002). Similarly, at 12 months, the patients affected by MD showed less risk of illicit opioid use (16.4%) than those affected by GAD (34.8%), PD (42.2%), SC (53.8%) and SUD without comorbidity (34.4%) (p=0.06, p=0.003, p=0.008, p=0.017). When evaluated on the whole sample, retention rate was not influenced by dose. In contrast, the higher BUP doses were associated with less risk of illicit opioid use, than lower doses (p<0.001). Multivariate analysis and factor analysis showed a greater association of outcome measures (retention rate and negative urines rate) with comorbid diagnosis (depression) (respectively 0.64) than with buprenorphine doses (respectively 0.54). Our data need to be interpreted with caution because of the retrospective methodology applied to a clinical nonexperimental setting. BUP seems to be more effective in opioid-dependent patients affected by depression, probably due to the kappa opioid-receptors antagonist action, counteracting dysphoria, negativism and anxiety. High doses of BUP appear to predict a better outcome, in terms of negative urines, but not in terms of retention. ISSN Print 0278-5846 Publication Type Clinical Trial. Comparative Study. Journal Article. Research Support, Non-U.S. Gov't. Date of Publication 2006 Mar Year of Publication 2006 Issue/Part 2 Volume 30 Page 265-72 OPIOIDS 2006 <373> Database EMBASE Accession Number 2007004567 Authors Mohan D. Dhawan A. Chopra A. Sethi H. Institution (Mohan, Dhawan, Chopra, Sethi) National Drug Dependence Treatment Centre, All India Institute of Medical Sciences, New Delhi, India. Country of Publication United Kingdom Title A 24-week outcome following buprenorphine maintenance among opiate users in India. Source Journal of Substance Use. 11(6)(pp 409-415), 2006. Date of Publication: Dec 2006. Abstract Aims: To evaluate the outcome at 24 weeks following a community-based treatment programme using buprenorphine maintenance among male opiate users in Dimapur, Nagaland (India). Design: Quasi-experimental prospective follow-up study. Participants: Fiftyfour male current opiate users were recruited following fulfilment of inclusion criteria from a community. All users seeking treatment met the DSM III-R criteria for opioid dependence. Methods: All subjects received buprenorphine (1.2-1.8 mg sublingually per day) from a community clinic and attended psychosocial sessions. Measurements included an assessment of demographic and clinical variables, Addiction Severity Index (ASI), retention in treatment, drug use at baseline and follow-up at 24 weeks. Findings: The mean age of sample was 26.3+/-4.1 years, with a mean duration of opioid use of 4.0+/-3.8 years. The retention rate was 81.5% at 24 weeks. Scores on the Addiction Severity Index decreased and injecting use reduced. No adverse events were reported. Conclusion: Buprenorphine was found to be effective with greater retention rates and less opioid use. Results support the theory that community-based setting to provide maintenance treatment with very low staff investment from a community clinic can be initiated and replicated safely and effectively in India. However, future work on evaluation of higher doses is recommended. ISSN 1465-9891 Publication Type Journal: Article Journal Name Journal of Substance Use Volume 11 Issue Part 6 Page 409-415 Year of Publication 2006 Date of Publication Dec 2006 OPIOIDS 2006 <378> Database EMBASE Accession Number 2006597109 Authors Kristensen O. Lolandsmo T. Isaksen A. Vederhus J.-K. Clausen T. Institution (Kristensen, Lolandsmo, Isaksen, Vederhus) Addiction Unit, Sorlandet Hospital, Kristiansand, Norway. (Clausen) Unit for Addiction Medicine, Institute of Psychiatry, University of Oslo, Oslo, Norway. Country of Publication United Kingdom Title Treatment of polydrug-using opiate dependents during withdrawal: Towards a standardisation of treatment. Source BMC Psychiatry. 6, 2006. Article Number: 54. Date of Publication: 15 Nov 2006. Abstract Background: The growing tendency among opioid addicts to misuse multiple other drugs should lead clinicians and researchers to search for new pharmacological strategies in order to prevent life-threatening complications and minimize withdrawal symptoms during polydrug detoxification. Methods: A non-randomised, open-label in-patient detoxification study was used to compare the short-time efficacy of a standardised regimen comprising 6 days Buprenorphine and 10 days Valproate (BPN/VPA) (n = 12) to a control group (n = 50) who took a 10-day traditional Clonidine/ Carbamazepine (CLN/CBZ) regimen. Sixty-two dependent subjects admitted to a detoxification unit were included, all dependent on at least opioids and benzodiazepines. Other dependencies were not excluded. Results: In the BPN/VPA group, 8 out of 12 patients (67%) completed treatment compared with 25 of 50 patients (50%) in the CLN/CBZ group; this difference between the groups was non-significant (p = 0.15). Withdrawal symptoms were reduced in both groups, but only the BPN/VPA group achieved a reduction in withdrawal symptoms from day one. The difference between the two groups was significantly in favour of the BPN/ VPA group for days 2 (p < 0.001), 3 (p < 0.05), 4 (p < 0.001), 5 (p < 0.01), 7 (p < 0.01) and 8 (p < 0.05). The BPN/VPA combination did not affect blood pressure, pulse or liver function, and the total burden of side-effects was experienced as modest. There appeared to be no pharmacological interactions of clinical concern, based on measurement of Buprenorphine and Valproate serum levels. Both the patients and the staff were satisfied with the standardised treatment combination. Conclusion: Overall, the combination of Buprenorphine and Valproate seems to be a safe and promising method for treating multiple drug withdrawal symptoms. The results of this study suggest that the BPN/VPA combination is potentially a better detoxification treatment for polydrug withdrawal than the traditional treatment with Clonidine and Carbamazepine. However, a randomised, double-blind study with a larger sample size to confirm our results is recommended. copyright 2006 Kristensen et al; licensee BioMed Central Ltd. ISSN 1471-244X Publication Type Journal: Article Journal Name BMC Psychiatry Volume 6 Year of Publication 2006 Date of Publication 15 Nov 2006 OPIOIDS 2006 <380> Database EMBASE Accession Number 2006521273 Authors Gerra G. Fantoma A. Zaimovic A. Institution (Gerra, Fantoma) National Department on Drug Policy, Rome, Italy. (Zaimovic) Addiction Research Centre, Ser.T., AUSL, Parma, Italy. (Gerra) National Department on Drug Policy, Via Quintino Sella, 69, 00187 Roma, Italy. Country of Publication United Kingdom Title Naltrexone and buprenorphine combination in the treatment of opioid dependence. Source Journal of Psychopharmacology. 20(6)(pp 806-814), 2006. Date of Publication: Nov 2006. Abstract Naltrexone treatment has demonstrated some advantages for special populations of heroin addicted individuals, but patients' compliance seems to be very poor, with a low adherence and low retention rate. Kappa-opioid system overdrive seems to contribute to opioid protracted abstinence syndrome, with dysphoria and psychosomatic symptoms during naltrexone treatment. The objective of this observational study was to determine the effectiveness of a functional k antagonist in improving naltrexone treatment outcome. A partial mu agonist/kappa antagonist (buprenorphine) and a mu antagonist (naltrexone) were combined during a 12 weeks protocol, theoretically leaving k antagonism as the major medication effect. Sixty patients were submitted to outpatient rapid detoxification utilizing buprenorphine and opioid antagonists. Starting on the fifth day, 30 patients (group A) received naltrexone alone. Alternatively, 30 patients (group B) received naltrexone (50 mg oral dose) plus buprenorphine (4 mg sublingual) for the 12 weeks of the observational study. The endpoints of the study were: retention in treatment, negative urinalyses, changes in psychological symptoms (Symptom Checklist-90 Revised: SCL-90) and craving scores (visual analysis scale (VAS)). Thirty-four subjects (56.67%) completed the 12 weeks study. Twentyone patients (35.0%) had all urine samples negative for opiates and cocaine, nine subjects (15.0%) had urine samples negative for cocaine and opiates for the last 4 weeks of the study, five subjects (8.3%) continued to use cocaine during the 12 weeks of the study. No significant change in pupillary diameter after buprenorphine administration was evidenced during clinical observations from baseline across the weekly measurements. Retention rates in group A (naltrexone) and group B (naltrexone + buprenorphine) at week 12 were respectively 40% (12 patients) and 73.33% (22 patients), with a significant difference in favour of group B (p = 0.018). Patients treated with naltrexone in combination with buprenorphine (B patients) showed a significantly lower rate of positive urines for morphine (4.45%) and cocaine metabolites (9.09%) than those treated with naltrexone alone (A) (25%, morphine; 33.33% cocaine) (p < 0.05; p < 0.05). Irritability, depression, tiredness, psychosomatic symptoms and craving scores decreased significantly less in Group A patients than in group B patients. The dysfunction of opioid system with kappa receptors hyper-activation provoked by heroin exposure, probably underlying dysphoric and psychosomatic symptoms during naltrexone treatment, seems to be counteracted, at least in part, by buprenorphine. The combination of buprenorphine and naltrexone may significantly improve the outcome of opioid antagonists treatment in terms of retention, negative urinalyses, and reduced dysphoria, mood symptoms and craving. copyright 2006 British Association for Psychopharmacology. ISSN 0269-8811 Publication Type Journal: Article Journal Name Journal of Psychopharmacology Volume 20 Issue Part 6 Page 806-814 Year of Publication 2006 Date of Publication Nov 2006 OPIOIDS 2006 <387> Database EMBASE Accession Number 2007066093 Authors Neasta J. Uttenweiler-Joseph S. Chaoui K. Monsarrat B. Meunier J.-C. Mouledous L. Institution (Neasta, Chaoui, Meunier, Mouledous) Unite Mecanismes d'Action des Substances Opioides, Institut Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique UMR 5089, 205 route Narbonne, 31077 Toulouse cedex 04, France. (Uttenweiler-Joseph, Monsarrat) Unite Spectrometrie de Masse et Structure des Biomolecules, Institut Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique UMR 5089, 205 route Narbonne, 31077 Toulouse cedex 04, France. Country of Publication United Kingdom de de de de Title Effect of long-term exposure of SH-SY5Y cells to morphine: A whole cell proteomic analysis. Source Proteome Science. 4, 2006. Article Number: 23. Date of Publication: 2006. Abstract Background: Opiate addiction reflects plastic changes that endurably alter synaptic transmission within relevant neuronal circuits. The biochemical mechanisms of these adaptations remain largely unknown and proteomics-based approaches could lead to a broad characterization of the molecular events underlying adaptations to chronic drug exposure. Results: Thus, we have started proteomic analyses of the effects of chronic morphine exposure in a recombinant human neuroblastoma SH-SY5Y clone that stably overexpresses the mu-opioid receptor. Cells were treated with morphine for 6, 24 and 72 hours, the proteins were separated by 2-D gel electrophoresis and stained with Coomassie blue, and the protein map was compared with that obtained from untreated cells. Spots showing a statistically significant variation were selected for identification using mass spectrometric analyses. Conclusion: A total of 45 proteins were identified, including proteins involved in cellular metabolism, cytoskeleton organization, vesicular trafficking, transcriptional and translational regulation, and cell signaling. copyright 2006 Neasta et al; licensee BioMed Central Ltd. Publication Type Journal: Article Journal Name Proteome Science Volume 4 Year of Publication 2006 Date of Publication 2006 OPIOIDS 2006 <388> Database EMBASE Accession Number 2007062050 Authors Morgan O. Griffiths C. Hickman M. Institution (Morgan) Department of Primary Care and Social Medicine, Imperial College London, London, United Kingdom. (Morgan, Griffiths) Health and Care Division, Office for National Statistics, 1 Drummond Gate, London SW1V 2QQ, United Kingdom. (Hickman) Department of Social Medicine, University of Bristol, Bristol, United Kingdom. Country of Publication United Kingdom Title Association between availability of heroin and methadone and fatal poisoning in England and Wales 1993-2004. Source International Journal of Epidemiology. 35(6)(pp 1579-1585), 2006. Date of Publication: Dec 2006. Abstract Background: The UK heroin market is the biggest in Europe and [similar to]70% of heroin deaths are due to fatal poisoning. Methadone treatment for heroin addiction in the UK, the 'British system', is unique as it is largely provided by General Practitioners. Methods: The Office for National Statistics provided data on deaths, the Home Office provided law enforcement data on drug seizures and the Department of Health data on prescriptions. For methadone treatment we calculated the death rate per 1000 patient years. We used Spearman's rank correlation to assess the association between illicit drug seizures for heroin and methadone and deaths. Results: Between 1993 and 2004 there were 7072 deaths involving heroin/ morphine (86% males) and 3298 deaths involving methadone (83% male). From 1993-1997, directly age-standardized mortality rates for males were similar for both drugs, increasing from [similar to]5 to 15 per million. Mortality rates for heroin continued to increase until 2000, subsequently decreasing from 30 to 20 per million by 2003, and rising again to 24 per million in 2004. In contrast, mortality rates for methadone decreased between 1997 and 2004 to just above 1993 levels. Among females the mortality rate for both drugs was lower than for males throughout the study period, remaining relatively stable. Methadone deaths per 1000 patient years remained similar between 1993 and 1997, after which they fell by three quarters. For both heroin/morphine and methadone, deaths were strongly associated with seizures (Spearmans' coefficient for males: heroin, P = 0.95, P < 0.001 and methadone, P = 0.83, P = 0.0013). Conclusions: Our study suggests the 'British System' can deliver substantial expansion of treatment without increased mortality risk. The fall in heroin/morphine deaths since 2000 may also be an indication of success of increasing methadone treatment. Data on mortality risk is needed to determine whether increased methadone treatment has reduced drug-related deaths. copyright 2006 Oxford University Press. ISSN 0300-5771 Publication Type Journal: Article Journal Name International Journal of Epidemiology Volume 35 Issue Part 6 Page 1579-1585 Year of Publication 2006 Date of Publication Dec 2006 OPIOIDS (A) 2006 <398> Database EMBASE Accession Number 2007221740 Authors Sharifzadeh M. Hadjiakhoondi A. Khanavi M. Susanabadi M. Institution (Sharifzadeh) Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran, Islamic Republic of. (Sharifzadeh, Hadjiakhoondi, Khanavi, Susanabadi) Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran, Islamic Republic of. (Sharifzadeh) Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran, Islamic Republic of. (Hadjiakhoondi, Khanavi, Susanabadi) Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran, Islamic Republic of. (Sharifzadeh) Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran, Islamic Republic of. Country of Publication United Kingdom Title Effects of aqueous, methanolic and chloroform extracts of rhizome and aerial parts of Valeriana officinalis L. on naloxone-induced jumping in morphine-dependent mice. Source Addiction Biology. 11(2)(pp 145-151), 2006. Date of Publication: Jun 2006. Abstract In the present study, the effects of rhizomes and aerial parts extracts of Valeriana officinalis L. on morphine dependence in mice have been investigated. Animals were treated subcutaneously with morphine (50, 50 and 75 mg/kg) three times daily (10 am, 1 pm and 4 pm) for 3 days, and a last dose of morphine (50 mg/kg) was administered on the fourth day. Withdrawal syndrome (jumping) was precipitated by naloxone (5 mg/kg) which was administered intraperitoneally 2 hours after the last dose of morphine. To study the effects of the aqueous, methanolic and chloroform extracts of both aerial parts and rhizome of the V. officinalis L. on naloxone-induced jumping in morphine-dependent animals, 10 injections of morphine (three administrations each day) for dependence and a dose of 5 mg/kg of naloxone for withdrawal induction were employed. Intraperitoneal injection of different doses (1, 5, 25 and 50 mg/kg) of aqueous, methanolic and chloroform extracts of the rhizome of V. officinalis L. 60 minutes before naloxone injection decreased the jumping response dosedependently. Pre-treatment of animals with different doses (1, 5, 25, 50 and 100 mg/kg) of aqueous and methanolic extracts of aerial parts of V. officinalis L. 60 minutes before naloxone injection caused a significant decrease on naloxone-induced jumping. The chloroform extract of the aerial parts of V. officinalis L. did not show any significant changes on jumping response in morphine-dependent animals. It is concluded that the extracts of V. officinalis L. could affect morphine withdrawal syndrome via possible interactions with inhibitory neurotransmitters in nervous system. copyright 2006 The Authors. ISSN 1355-6215 Publication Type Journal: Article Journal Name Addiction Biology Volume 11 Issue Part 2 Page 145-151 Year of Publication 2006 Date of Publication Jun 2006 COCAINE / OPIOIDS 2006 <401> Database EMBASE Accession Number 2007221706 Authors Aouizerate B. Ho A. Schluger J.H. Perret G. Borg L. Le Moal M. Piazza P.V. Kreek M.J. Institution (Aouizerate, Le Moal, Piazza) Laboratory of Pathophysiology of Behavior, Victor Segalen's University (Bordeaux 2), France. (Ho, Schluger, Perret, Borg, Kreek) Laboratory of the Biology of Addictive Diseases, Rockefeller University, United States. (Kreek) Laboratory of the Biology of Addictive Diseases, Rockefeller University, 1230 York Avenue, New York, NY 10021, United States. Country of Publication United Kingdom Title Glucocorticoid negative feedback in methadone-maintained former heroin addicts with ongoing cocaine dependence: Dose-response to dexamethasone suppression. Source Addiction Biology. 11(1)(pp 84-96), 2006. Date of Publication: Mar 2006. Abstract Combined cocaine and illicit opiate use is common. This study aimed to test the hypothesis that cocaine dependence in former heroin-addicted patients maintained on methadone treatment is associated with enhanced glucocorticoid negative feedback. Multiple dose dexamethasone suppression tests, using a conventional 2.0 mg dose, and two lower doses, 0.5 mg and 0.125 mg, were performed in 10 methadone-maintained former heroin addicts with ongoing cocaine dependence (C-MM), 10 stabilized methadone-maintained former heroin addicts with no ongoing drug or alcohol use (MM), and 22 normal volunteers (NV). At 9 hours, there was no difference in plasma adrenocorticotropin hormone (ACTH) and/or cortisol levels among groups on the baseline day, as well as after the two lower doses of dexamethasone. At 17 hours, C-MM and MM had significantly lower plasma ACTH and/or cortisol levels than NV. However, C-MM did not significantly differ from MM in their hormonal levels. When the hormonal responses to dexamethasone are expressed as magnitude of lowering from baseline, there was no significant difference at any dose among groups. Therefore, C-MM exhibited a normal glucocorticoid negative feedback in the morning. Using the standard interpretation of dexamethasone suppression testing based on the examination of the actual hormonal levels rather than the difference from baseline condition, C-MM appear to have glucocorticoid effects similar to MM, yet were both greater than NV in the late afternoon. Thus, further studies are needed to know whether altered glucocorticoid negative feedback is related to chronic cocaine exposure, or is the result of former heroin addiction and/or its long-term treatment with methadone. copyright 2006 The Authors. ISSN 1355-6215 Publication Type Journal: Article Journal Name Addiction Biology Volume 11 Issue Part 1 Page 84-96 Year of Publication 2006 Date of Publication Mar 2006 OPIOIDS 2006 <404> Database EMBASE Accession Number 2007009696 Authors Cameron I.M. Matheson C.I. Bond C.M. McNamee P. Lawrie T. Robinson A. Robertson G. Eagles L.E. Institution (Cameron) Department of Mental Health, University of Aberdeen, Aberdeen, United Kingdom. (Matheson, Bond, Lawrie) Department of General Practice and Primary Care, University of Aberdeen, Aberdeen, United Kingdom. (McNamee) Health Economics Research Unit, University of Aberdeen, Aberdeen, United Kingdom. (Robinson, Robertson) Substance Misuse Service, Royal Cornhill Hospital, Aberdeen, United Kingdom. (Eagles) NHS Grampian, Aberdeen, United Kingdom. (Matheson) Department of General Practice and Primary Care, University of Aberdeen, Westburn Health Centre, Westburn Road, Aberdeen AB25 2AY, United Kingdom. Country of Publication United Kingdom Title Pilot randomised controlled trial of community pharmacy administration of buprenorphine versus methadone. Source International Journal of Pharmacy Practice. 14(4)(pp 243-248), 2006. Date of Publication: Dec 2006. Abstract Objectives: The established regime for opiate substitute prescribing for drug misusers is daily methadone administered under supervision in community pharmacies. Buprenorphine has recently been introduced as an alternative. However there is a lack of evidence of the effectiveness of buprenorphine maintenance therapy (BMT) in the UK treatment setting. This study aimed to assess methods for a randomised controlled trial (RCT) and the feasibility of pharmacy-based supervised self-administration (SSA) of buprenorphine compared to methadone. Setting: Specialist substance misuse service, general practices and community pharmacies in Aberdeen, Scotland. Method: The design was a pilot RCT. Opiate-dependent drug misusers, newly referred for maintenance treatment were randomised to receive BMT or methadone maintenance therapy (MMT). Clients and pharmacists were interviewed at baseline and at the end of a 12-week intervention period. Clients completed the quality of life measure EQ-5D. Pharmacy activities were timed. Key findings: Twenty-one opiate-dependent clients were recruited (BMT = 11, MMT = 10). Recruitment levels improved as the trial progressed. Clients' treatment preferences were evident. Withdrawals occurred early with BMT. Clients found SSA of buprenorphine acceptable, but found daily administration more manageable than three times weekly. Pharmacists found the dispensing of buprenorphine to be an acceptable role, but felt less certain of ensuring against diversion with buprenorphine than they were with methadone. Pharmacy activities associated with buprenorphine took longer than those associated with methadone (mean = 7 min 25s versus mean = 3 min 27s, respectively). Conclusion: Recruitment to a trial comparing MMT to BMT for opiate-dependent clients within a UK treatment setting is feasible. Clients and pharmacists found buprenorphine acceptable. copyright 2006 The Authors. ISSN 0961-7671 Publication Type Journal: Article Journal Name International Journal of Pharmacy Practice Volume 14 Issue Part 4 Page 243-248 Year of Publication 2006 Date of Publication Dec 2006 COMORBIDITY 2006 / OPIOIDS 2006 <426> Database EMBASE Accession Number 2007003794 Authors Shiri R. Hassani K.F. Ansari M. Institution (Shiri, Hassani) Tampere School of Public Health, University of Tampere, Tampere, Finland. (Ansari) Department of Internal Medicine, Ekbatan Hospital, Hamadan University of Medical Sciences, Hamadan, Iran, Islamic Republic of. (Shiri) Klaneettitie 1 D 105, FIN-00420 Helsinki, Finland. Country of Publication United Kingdom Title Association between opium abuse and comorbidity in diabetic men. Source American Journal on Addictions. 15(6)(pp 468-472), 2006. Date of Publication: Nov 2006. Abstract The aims of this study were to determine the prevalence of opium abuse in diabetic men and to investigate its association with comorbidity. The study population was comprised of 312 consecutive diabetic men aged 20 years or older residing in the study area in 2005. The prevalence of self-reported opium abuse was 11.2%. Opium use was associated with low socioeconomic status, smoking, tea consumption, and a higher prevalence of erectile dysfunction (ED) and severe depression. The prevalence of severe depression was 22.8% among 35 men who used opium and 13.4% among 277 who did not use it. The prevalence of moderate or severe ED was 85.7% among opium users and 66.1% among non-users. The risk of ED was two times (95% CI 1.0-7.4) higher in opium users compared with nonusers. Copyright copyright American Academy of Addiction Psychiatry. ISSN 1055-0496 Publication Type Journal: Article Journal Name American Journal on Addictions Volume 15 Issue Part 6 Page 468-472 Year of Publication 2006 Date of Publication Nov 2006 OPIOIDS 2006 <441> Database EMBASE Accession Number 2006615085 Authors Crettol S. Deglon J.-J. Besson J. Croquette-Krokar M. Hammig R. Gothuey I. Monnat M. Eap C.B. Institution (Crettol, Deglon, Besson, Croquette-Krokar, Hammig, Gothuey, Monnat, Eap) Unite de Biochimie et Psychopharmacologie Clinique, Centre de Neurosciences Psychiatriques, Departement de Psychiatrie, PrillyLausanne, Switzerland. Country of Publication United Kingdom Title ABCB1 and cytochrome P450 genotypes and phenotypes: Influence on methadone plasma levels and response to treatment. Source Clinical Pharmacology and Therapeutics. 80(6)(pp 668-681), 2006. Date of Publication: Dec 2006. Abstract Background and Objective: The in vivo implication of various cytochrome P450 (CYP) isoforms and of P-glycoprotein on methadone kinetics is unclear. We aimed to thoroughly examine the genetic factors influencing methadone kinetics and response to treatment. Methods: Genotyping for CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, ABCB1, and UGT2B7 polymorphisms was performed in 245 patients undergoing methadone maintenance treatment. To assess CYP3A activity, the patients were phenotyped with midazolam. Results: The patients with lower CYP3A activity presented higher steadystate trough (R,S)-methadone plasma levels (4.3, 3.0, and 2.3 ng/mL . mg for low, medium, and high activity, respectively; P = .0002). As previously reported, CYP2B6*6/*6 carriers had significantly higher trough (S)-methadone plasma levels (P = .0001) and a trend toward higher (R)-methadone plasma levels (P = .07). CYP2D6 ultrarapid metabolizers presented lower trough (R,S)-methadone plasma levels compared with the extensive or intermediate metabolizers (2.4 and 3.3 ng/mL . mg, respectively; P = .04), whereas CYP2D6 poor metabolizer status showed no influence. ABCB1 3435TT carriers presented lower trough (R,S)-methadone plasma levels (2.7 and 3.4 ng/mL . mg for 3435TT and 3435CC carriers, respectively; P = .01). The CYP1A2, CYP2C9, CYP2C19, CYP3A5, and UGT2B7 genotypes did not influence methadone plasma levels. Only CYP2B6 displayed a stereoselectivity in its activity. Conclusion: In vivo, CYP3A4 and CYP2B6 are the major CYP isoforms involved in methadone metabolism, with CYP2D6 contributing to a minor extent. ABCB1 genetic polymorphisms also contribute slightly to the interindividual variability of methadone kinetics. The genetic polymorphisms of these 4 proteins had no influence on the response to treatment and only a small influence on the dose requirement of methadone. copyright 2006 American Society for Clinical Pharmacology and Therapeutics. ISSN 0009-9236 Publication Type Journal: Article Journal Name Clinical Pharmacology and Therapeutics Volume 80 Issue Part 6 Page 668-681 Year of Publication 2006 Date of Publication Dec 2006 OPIOIDS 2006 <442> Database EMBASE Accession Number 2006615084 Authors Coller J.K. Barratt D.T. Dahlen K. Loennechen M.H. Somogyi A.A. Institution (Coller, Barratt, Dahlen, Loennechen, Somogyi) Discipline of Pharmacology, School of Medical Sciences, The University of Adelaide, Adelaide, Australia. Country of Publication United Kingdom Title ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals. Source Clinical Pharmacology and Therapeutics. 80(6)(pp 682-690), 2006. Date of Publication: Dec 2006. Abstract Background and Objectives: The most common treatment for opioid dependence is substitution therapy with another opioid such as methadone. The methadone dosage is individualized but highly variable, and program retention rates are low due in part to nonoptimal dosing resulting in withdrawal symptoms and further heroin craving and use. Methadone is a substrate for the P-glycoprotein transporter, encoded by the ABCB1 gene, which regulates central nervous system exposure. This retrospective study aimed to investigate the influence of ABCB1 genetic variability on methadone dose requirements. Methods: Genomic deoxyribonucleic acid was isolated from opioid-dependent subjects (n = 60) and non-opioid-dependent control subjects (n = 60), and polymerase chain reactionrestriction fragment length polymorphism and allele-specific polymerase chain reaction were used to determine the presence of single nucleotide polymorphisms at positions 61, 1199, 1236, 2677, and 3435. ABCB1 haplotypes were inferred with PHASE software (version 2.1). Results: There were no significant differences in the allele or genotype frequencies of the individual single nucleotide polymorphisms or haplotypes between the 2 populations. ABCB1 genetic variability influenced daily methadone dose requirements, such that subjects carrying 2 copies of the wild-type haplotype required higher doses compared with those with 1 copy and those with no copies (98.3 +/- 10.4, 58.6 +/- 20.9, and 55.4 +/- 26.1 mg/d, respectively; P = .029). In addition, carriers of the AGCTT haplotype required significantly lower doses than noncarriers (38.0 +/- 16.8 and 61.3 +/- 24.6 mg/d, respectively; P = .04). Conclusion: Although ABCB1 genetic variability is not related to the development of opioid dependence, identification of variant haplotypes may, after larger prospective studies have been performed, provide clinicians with a tool for methadone dosage individualization. copyright 2006 American Society for Clinical Pharmacology and Therapeutics. ISSN 0009-9236 Publication Type Journal: Article Journal Name Clinical Pharmacology and Therapeutics Volume 80 Issue Part 6 Page 682-690 Year of Publication 2006 Date of Publication Dec 2006 OPIOIDS 2006 <467> Database EMBASE Accession Number 2006565552 Authors Chen S.A. O'Dell L.E. Hoefer M.E. Greenwell T.N. Zorrilla E.P. Koob G.F. Institution (Chen, O'Dell, Hoefer, Greenwell, Zorrilla, Koob) Molecular and Integrative Neurosciences Department, Scripps Research Institute, San Diego, CA, United States. (Chen) Laboratory of Clinical and Translational Studies, NIH/NIAAA, NIH Animal Center, PO Box 529, Poolesville, MD 20837, United States. Country of Publication United Kingdom Title Unlimited access to heroin self-administration: Independent motivational markers of opiate dependence. Source Neuropsychopharmacology. 31(12)(pp 2692-2707), 2006. Date of Publication: 04 Dec 2006. Abstract The goal of the present study was to develop and validate an animal model of unlimited access to intravenous heroin self-administration combined with responding for food and water to characterize the transition to drug dependence. Male Wistar rats were allowed to lever press for heroin (60 mug/kg/0.1 ml infusion/s; fixed ratio 1; 20-s time out) and nosepoke for food and water in consecutive, daily 23-h sessions. Daily heroin intake increased over days, reaching significance by Day 14. Drug-taking increased across the circadian cycle, reflected as increases in both the nocturnal peak and diurnal nadir of heroin intake. Changes in the circadian pattern of food intake and meal patterning preceded and paralleled the changes in heroin intake. By Day 7, the circadian amplitude of feeding was blunted. Nocturnal intake decreased because rats consumed smaller and briefer meals. Diurnal intake increased due to increased meal frequency, whereas total daily food intake decreased. To control for time or experience in the self-administration boxes as a possible confound, rats with saline (no drug) tethers were tested and did not display significant changes in food intake pattern. Body weight gain slowed slightly in heroin rats relative to saline controls. Separate groups of rats revealed that significant physical dependence as measured by physical signs of opiate withdrawal following a naloxone injection (1.0 mg/kg, subcutaneous (s.c.)) was reached by Day 14. Significant increases in heroin intake could be produced using low doses of naloxone (0.0030.03 mg/kg, s.c.) on days 28-31 of heroin access. After 6 weeks of heroin self-administration, rats injected with buprenorphine (0, 0.01, 0.04, and 0.2 mg/kg, s.c.) showed a dosedependent reduction in heroin intake. Changes in the pattern of drug and food intake in the present unlimited heroin access model may serve as independent motivational markers for the transition to a drug-dependent state. copyright 2006 Nature Publishing Group All rights reserved. ISSN 0893-133X Publication Type Journal: Article Journal Name Neuropsychopharmacology Volume 31 Issue Part 12 Page 2692-2707 Year of Publication 2006 Date of Publication 04 Dec 2006 OPIOIDS 2006 <482> Database EMBASE Accession Number 2006533616 Authors Bohn L.M. Raehal K.M. Institution (Bohn, Raehal) Departments of Pharmacology and Psychiatry, The Ohio State University College of Medicine, 333 W 10th Ave, 5184A Graves Hall, Columbus, OH 43210, United States. Country of Publication United Kingdom Title Opioid receptor signaling: relevance for gastrointestinal therapy. Source Current Opinion in Pharmacology. 6(6)(pp 559-563), 2006. Date of Publication: Dec 2006. Abstract Opiate drugs, such as morphine, are renowned for their analgesic properties. To date, opioid narcotics represent the largest and most potent class of pain relievers available to treat both acute and chronic pain conditions. The use of opiates, however, is severely limited by several adverse side effects. Upon chronic use, opiates can produce tolerance, physical dependence and addiction. Although these conditions warrant consideration, there are acute effects that present more immediate concerns when choosing opiate narcotics for pain therapy. One of the most prevalent side effects, which continues for as long as the opiate is used for pain control, is constipation. This can impact patient compliance, as it is often one of the top reasons why patients discontinue opiate treatment. The challenge, therefore, is to develop pain therapies that preserve potent analgesia while preventing constipation. copyright 2006 Elsevier Ltd. All rights reserved. ISSN 1471-4892 Publication Type Journal: Review Journal Name Current Opinion in Pharmacology Volume 6 Issue Part 6 Page 559-563 Year of Publication 2006 Date of Publication Dec 2006 OPIOIDS (A) 2008 <489> Database EMBASE Accession Number 2006526603 Authors Yoo J.-H. Yang E.-M. Cho J.-H. Lee J.-H. Jeong S.M. Nah S.-Y. Kim H.-C. Kim K.-W. Kim S.-H. Lee S.-Y. Jang C.-G. Institution (Yoo, Yang, Cho, Lee, Jang) Department of Pharmacology, College of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Korea, Republic of. (Lee, Jeong, Nah) Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, 143-701, Korea, Republic of. (Kim) Neurotoxicology Program, College of Pharmacy, Korea Institute of Drug Abuse, Chunchon, 200-701, Korea, Republic of. (Kim) Department of Pharmacology, College of Medicine, Chonbuk National University, Chonju, Korea, Republic of. (Kim) College of Physical Education, Kyunghee University, Youngin, 449-701, Korea, Republic of. Country of Publication United Kingdom Title Inhibitory effects of berberine against morphine-induced locomotor sensitization and analgesic tolerance in mice. Source Neuroscience. 142(4)(pp 953-961), 2006. Date of Publication: 03 Nov 2006. Abstract We previously reported that a methanolic extract of Coptis japonica, which is a well-known traditional oriental medicine, inhibits morphine-induced conditioned place preference (CPP) in mice. Berberine is a major component of Coptis japonica extract, and it has been established that the adverse effects of morphine on the brain involve dopamine (DA) receptors. However, to our knowledge, no study has investigated the inhibitory effects of berberine on morphineinduced locomotor sensitization and analgesic tolerance in mice. Here, we investigated the effects of berberine on morphine-induced locomotor sensitization and on the development of analgesic tolerance. Furthermore, we examined the effects of berberine treatment on Nmethyl-d-aspartate (NMDA) receptor channel activity expressed in Xenopus laevis oocytes. Berberine was found to completely block both morphine-induced locomotor sensitization and analgesic tolerance, and reduce D<sub>1</sub> and NMDA receptor bindings in the cortex. Moreover, berberine markedly inhibited NMDA current in Xenopus laevis oocytes expressing NMDA receptor subunits. Our results suggest that the inhibitory effects of berberine on morphine-induced locomotor sensitization and analgesic tolerance are closely related to the modulation of D1 and NMDA receptors, and that berberine should be viewed as a potential novel means of attenuating morphine-induced sensitization and analgesic tolerance. copyright 2006 IBRO. ISSN 0306-4522 Publication Type Journal: Article Journal Name Neuroscience Volume 142 Issue Part 4 Page 953-961 Year of Publication 2006 Date of Publication 03 Nov 2006 OPIOIDS (A) 2006 <494> Database EMBASE Accession Number 2006516459 Authors Streel E. Dan B. Campanella S. Meyvaert A. Hanak C. Pelc I. Verbanck P. Institution (Streel, Hanak, Pelc, Verbanck) Universite Libre de Bruxelles, CHU Brugmann, Laboratoire de Recherche sur la Biologie des Dependances, Bruxelles, Belgium. (Dan) Universite Libre de Bruxelles, HUDERF, Bruxelles, Belgium. (Campanella) Universite Catholique de Louvain-la-Neuve, Faculte de Psychologie et des Sciences de l'Education, Unite de Neurosciences Cognitives (NESC), Louvain la Neuve, Belgium. (Meyvaert) Universite Libre de Bruxelles, Service Pharmacie, Bruxelles, Belgium. (Streel) CHU Brugmann, ULB, Service de Psychiatrie, Place Van Gehuchten, 4, B-1020 Bruxelles, Belgium. Country of Publication United Kingdom Title A pharmacological modulation of opiate withdrawal using an up-/down-regulation of the noradrenergic system in opiate-dependent rats. Source International Journal of Neuropsychopharmacology. 9(5)(pp 621-626), 2006. Date of Publication: Oct 2006. Abstract Chronic opioid exposure induces neuroadaptative changes in several brain systems. Amongst others the alpha adrenergic system appears to be extremely sensitive to opioid exposure and has, therefore, been proposed to play a key role in opiate withdrawal symptoms. In order to better understand the influence of the noradrenergic system in opioid withdrawal and be able to develop new therapeutic strategies, we studied the effect of pretreatment with the alpha<sub>2</sub> agonist (clonidine) and alpha<sub>2</sub> antagonist (yohimbine) on naloxone-precipitated withdrawal in opiate-dependent rats. As is already known clonidine pre-treatment significantly enhances autonomic and behavioural signs of opioid withdrawal whereas yohimbine significantly attenuates them with dose-related effect. We also tested the effect of clonidine (0.1 mg/kg) during naloxone-precipitated opiate withdrawal in rats pre-treated with yohimbine (5 mg/kg) and we observed that yohimbine pretreatment potentiates clonidine efficiency in decreasing opiate withdrawal signs. This study supports the possibility of using a noradrenergic antagonist in order to regulate adrenoreceptors chronically exposed to opioids, therefore interfering with the intensity of naloxone-precipitated opiate withdrawal and potentiating later effectiveness of noradrenergic agonists like clonidine. These results may have various applications in clinical opiate detoxification protocols and are discussed through an up-/down-regulation of adrenoreceptors. Copyright copyright 2005 CINP. ISSN 1461-1457 Publication Type Journal: Article Journal Name International Journal of Neuropsychopharmacology Volume 9 Issue Part 5 Page 621-626 Year of Publication 2006 Date of Publication Oct 2006 OPIOIDS 2006 <510> Database EMBASE Accession Number 2006494260 Authors Frick U. Rehm J. Kovacic S. Ammann J. Uchtenhagen A. Institution (Frick, Rehm, Kovacic, Ammann, Uchtenhagen) Research Institute for Addiction and Public Health, Zurich, Switzerland. (Frick) Carinthia Tech. Institute, University of Applied Sciences, Austria. (Kovacic) University of Applied Sciences, Ulm, Germany. (Rehm) Centre for Addiction and Mental Health, Toronto, Ont., Canada. (Rehm) University of Toronto, Canada. (Frick) Research Institute for Addiction and Public Health, Konradstr. 32, CH-8031 Zurich, Switzerland. Country of Publication United Kingdom Title A prospective cohort study on orally administered heroin substitution for severely addicted opioid users. Source Addiction. 101(11)(pp 1631-1639), 2006. Date of Publication: Nov 2006. Abstract Aims: To assess the efficacy and safety of orally administered heroin [diacetylmorphine (DAM)] tablets in substitution treatment of severely addicted opioid users. Design: An openlabel, prospective cohort study with two non-randomly assigned treatment arms and historical controls: DAM tablets only versus DAM tablets combined with injected DAM and/or other opioids, with an observation period of 1 year. Setting: Twenty-one out-patient treatment centres of the Swiss heroin-assisted treatment programme. Participants: A total of 128 patients received DAM tablets only, and 237 patients received a combination of orally and intravenously applied DAM and other opioids. Measurements: Retention rate after 1 year; number of serious adverse events; dosage of DAM over time; subjective tolerance of study medication. Findings: In the intention-to-treat analysis, 1-year retention rates after 1 year in the DAM tablets-only group [0.804, 95% confidence interval (CI) = 0.735-0.873] as well as in the subgroup combining oral application of DAM with intravenous application or other opioids (0.843, 95% CI = 0.797-0.889) were higher compared to historical controls (Swiss cohort of patients who had been substituted intravenously with DAM; 1-year retention rate = 0.70). Rates of serious adverse events under study medication (tablets only = 0.038 per application year; tablets in combination = 0.028 per application year) were comparable to the historical rate of the Swiss heroin-assisted treatment (0.043). Conclusions: DAM tablets seem to be an effective and safe application mode of heroin-assisted substitution treatment. Randomized clinical trials to compare its relative efficacy to other substances are necessary. copyright 2006 The Authors. ISSN 0965-2140 Publication Type Journal: Article Journal Name Addiction Volume 101 Issue Part 11 Page 1631-1639 Year of Publication 2006 Date of Publication Nov 2006 OPIOIDS 2006 <511> Database EMBASE Accession Number 2006494256 Authors Martin L. Clair J. Davis P. O'Ryan D. Hoshi R. Curran H.V. Institution (Martin, Clair, Hoshi, Curran) Clinical Psychopharmacology Unit, UCL, London, United Kingdom. (Davis, O'Ryan) Substance Misuse Services, Camden, United Kingdom. (Curran) Islington Mental Health and Social Care Trust, London, United Kingdom. (Curran) Clinical Psychopharmacology Unit, Clinical Health Psychology, University College London, Gower Street, London WC1 6BT, United Kingdom. Country of Publication United Kingdom Title Enhanced recognition of facial expressions of disgust in opiate users receiving maintenance treatment. Source Addiction. 101(11)(pp 1598-1605), 2006. Date of Publication: Nov 2006. Abstract Aims: Accurate recognition of facial expressions of emotion is critical in interpersonal interaction but is impaired in alcoholics, even after a period of abstinence. Little is known of whether other drug-dependent populations also show these impairments. This study aimed to investigate facial expression recognition by chronic opiate users. Design: An independent group design was used to compare 20 participants receiving opiate substitution treatment, 20 ex-opiate users in rehabilitation (average abstinence of 6 months) and 21 unemployed healthy controls. Measurements: The accuracy and speed of recognizing morphed emotional facial expressions were assessed using an emotional hexagon task. Findings: Current opiate users were significantly more accurate than ex-users at recognizing expressions of disgust. They were also generally slower than controls in recognizing all expressions, and slower than ex-opiate users in recognizing surprise, happy and fearful expressions. Conclusions: Opiate users in maintenance treatment show a heightened ability to recognize facial expressions of disgust. We suggest that this may reflect increased exposure to other people's expressions of disgust and/or priming by the physical and social environments encountered by opiatedependent individuals. Further, opiate maintained individuals' global slowness in processing emotional expressions may reflect the sedative effects of methadone. copyright 2006 The Authors. ISSN 0965-2140 Publication Type Journal: Article Journal Name Addiction Volume 101 Issue Part 11 Page 1598-1605 Year of Publication 2006 Date of Publication Nov 2006