Cocaine Tolerance in Honey Bees.

Cocaine tolerance in honey bees.

PLoS One. 2013; 8(5): e64920
Søvik E, Cornish JL, Barron AB

Increasingly invertebrates are being used to investigate the molecular and cellular effects of drugs of abuse to explore basic mechanisms of addiction. However, in mammals the principle factors contributing to addiction are long-term adaptive responses to repeated drug use. Here we examined whether adaptive responses to cocaine are also seen in invertebrates using the honey bee model system. Repeated topical treatment with a low dose of cocaine rendered bees resistant to the deleterious motor effects of a higher cocaine dose, indicating the development of physiological tolerance to cocaine in bees. Cocaine inhibits biogenic amine reuptake transporters, but neither acute nor repeated cocaine treatments caused measurable changes in levels of biogenic amines measured in whole bee brains. Our data show clear short and long-term behavioural responses of bees to cocaine administration, but caution that, despite the small size of the bee brain, measures of biogenic amines conducted at the whole-brain level may not reveal neurochemical effects of the drug. HubMed – addiction


STAT3 mediates oncogenic addiction to TEL-AML1 in t(12;21) acute lymphoblastic leukemia.

Blood. 2013 Jun 5;
Mangolini M, de Boer J, Walf-Vorderwülbecke V, Pieters R, den Boer ML, Williams O

The t(12;21)(p13;q22) translocation is the most common chromosomal abnormality in pediatric leukemia. Although this rearrangement involves two well characterized transcription factors, TEL and AML1, the molecular pathways affected by the result of the translocation remain largely unknown. Also in light of recent studies showing genetic and functional heterogeneities in cells responsible for cancer clone maintenance and propagation, targeting a single common deregulated pathway may be critical for the success of novel therapies. Here we describe a novel signaling pathway that is essential for oncogenic addiction in TEL-AML1 leukemia. Our data indicate a direct role for TEL-AML1, via increasing the activity of RAC1, in regulating the phosphorylation of STAT3 that results in transcriptional induction of MYC. We demonstrate that human leukemic cell lines carrying this translocation are highly sensitive to treatment with S3I-201, a specific STAT3 inhibitor, and, more interestingly, that primary human leukemic samples are also responsive to the drug in the same concentration range. Thus, STAT3 inhibition represents a promising possible therapeutic strategy for the treatment of TEL-AML1 leukemia. HubMed – addiction


Slow-release oral morphine as maintenance therapy for opioid dependence.

Cochrane Database Syst Rev. 2013 Jun 5; 6: CD009879
Ferri M, Minozzi S, Bo A, Amato L

BACKGROUND: Opioid substitution treatments are effective in retaining people in treatment and suppressing heroin use. An open question remains whether slow-release oral morphine (SROM) could represent a possible alternative for opioid-dependent people who respond poorly to other available maintenance treatments. OBJECTIVES: To evaluate the efficacy of SROM as an alternative maintenance pharmacotherapy for the treatment of opioid dependence. SEARCH METHODS: We searched Cochrane Drugs and Alcohol Group’s Register of Trials, Cochrane Central Register of Controlled Trials (CENTRAL – The Cochrane Library Issue 3, 2013), MEDLINE (January 1966 to April 2013), EMBASE (January 1980 to April 2013) and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-randomised trials assessing efficacy of SROM compared with other maintenance treatment or no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently selected articles for inclusion, extracted data and assessed risk of bias of included studies. MAIN RESULTS: Three studies with 195 participants were included in the review. Two were cross-over trials and one was a parallel group RCT. The retention in treatment appeared superior to 80% in all the three studies (without significant difference with controls). Nevertheless, it has to be underlined that the studies had different durations. One lasted six months, and the other two lasted six and seven weeks. The use of opioids during SROM provision varied from lower to non-statistically or clinically different from comparison interventions, whereas there were no differences as far as the use of other substances was concerned.SROM seemed to be equal to comparison interventions for severity of dependence, or mental health/social functioning, but there was a trend for less severe opiate withdrawal symptoms in comparison with methadone (withdrawal score 2.2 vs. 4.8, P value = 0.06). Morphine was generally well tolerated and was preferred by a proportion of participants (seven of nine people in one study). Morphine appeared to reduce cravings, depressive symptoms (measured using the Beck Depression Inventory; P value < 0.001), physical complaints (measured using the Beschwerde-Liste (BL); P value < 0.001) and anxiety symptoms (P value = 0.008). Quality of life in people treated with SROM resulted in no significant difference or a worst outcome than in those taking methadone and buprenorphine. Other social functioning measures, such as finances, family and overall satisfaction, scored better in people maintained with the comparison substances than in those maintained with SROM. In particular, people taking methadone showed more favourable values for leisure time (5.4 vs. 3.7, P value < 0.001), housing (6.1 vs. 4.7, P value < 0.023), partnerships (5.7 vs. 4.2, P value = 0.034), friend and acquaintances (5.6 vs. 4.4, P value = 0.003), mental health (5.0 vs. 3.4, P value = 0.002) and self esteem (8.2 vs. 5.7, P value = 0.002) compared to people taking SROM; while people taking buprenorphine obtained better scores for physical health.Medical adverse events were consistently higher in people in SROM than in the comparison groups. None of the studies included people with a documented poor response to other maintenance treatment. AUTHORS' CONCLUSIONS: The present review did not identify sufficient evidence to assess the effectiveness of SROM for opioid maintenance because only three studies meeting our inclusion criteria have been identified. Two studies suggested a possible reduction of opioid use in people taking SROM. In another study, the use of SROM was associated with fewer depressive symptoms. Retention in treatment was not significantly different among compared interventions while the adverse effects were more frequent with the people given SROM. HubMed – addiction


Media campaigns for the prevention of illicit drug use in young people.

Cochrane Database Syst Rev. 2013 Jun 5; 6: CD009287
Ferri M, Allara E, Bo A, Gasparrini A, Faggiano F

BACKGROUND: Substance-specific mass media campaigns which address young people are widely used to prevent illicit drug use. They aim to reduce use and raise awareness of the problem. OBJECTIVES: To assess the effectiveness of mass media campaigns in preventing or reducing the use of or intention to use illicit drugs amongst young people. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2013, Issue 1), including the Cochrane Drugs and Alcohol Group’s Specialised Register; MEDLINE through PubMed (from 1966 to 29 January 2013); EMBASE (from 1974 to 30 January 2013) and ProQuest Dissertations & Theses A&I (from 1861 to 3 February 2013). SELECTION CRITERIA: Cluster-randomised controlled trials, prospective and retrospective cohort studies, interrupted time series and controlled before and after studies evaluating the effectiveness of mass media campaigns in influencing drug use, intention to use or the attitude of young people under the age of 26 towards illicit drugs. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures of The Cochrane Collaboration. MAIN RESULTS: We included 23 studies involving 188,934 young people, conducted in the USA, Canada and Australia between 1991 and 2012. Twelve studies were randomised controlled trials (RCT), two were prospective cohort studies (PCS), one study was both a RCT and a PCS, six were interrupted time series and two were controlled before and after (CBA) studies. The RCTs had an overall low risk of bias, along with the ITS (apart from the dimension ‘formal test of trend’), and the PCS had overall good quality, apart from the description of loss to follow-up by exposure.Self reported or biomarker-assessed illicit drug use was measured with an array of published and unpublished scales making comparisons difficult. Pooled results of five RCTs (N = 5470) show no effect of media campaign intervention (standardised mean difference (SMD) -0.02; 95% confidence interval (CI) -0.15 to 0.12).We also pooled five ITS studies (N = 26,405) focusing specifically on methamphetamine use. Out of four pooled estimates (two endpoints measured in two age groups), there was evidence of a reduction only in past-year prevalence of methamphetamine use among 12 to 17 years old.A further five studies (designs = one RCT with PCS, two PCS, two ITS, one CBA, N = 151,508), which could not be included in meta-analyses, reported a drug use outcome with varied results including a clear iatrogenic effect in one case and reduction of use in another. AUTHORS’ CONCLUSIONS: Overall the available evidence does not allow conclusions about the effect of media campaigns on illicit drug use among young people. We conclude that further studies are needed. HubMed – addiction


[Pharmacogenetics and the treatment of addiction].

Ned Tijdschr Geneeskd. 2013; 157(23): A5725
Schellekens A

– This article describes the current scientific knowledge regarding pharmacogenetic predictors of treatment outcome for substance-dependent patients.- PubMed was searched for articles on pharmacogenetics and addiction. This search yielded 53 articles, of which 27 were selected.- The most promising pharmacogenetic findings are related to the treatment of alcohol dependence. Genetic variation in the µ-opioid receptor (OPRM1) and the serotonin transporter (5-HTTLPR) appear to be associated with treatment outcomes for naltrexone and ondansetron, respectively. – Genetic variation in CYP2D6 is related to efficacy of methadone treatment for opiate dependence. – Pharmacogenetics may help explain the great inter-individual variation in treatment response. In the future, treatment matching, based on genetic characteristics of individual patients, could lead to a ‘personalized medicine’ approach. Pharmacogenetic matching of naltrexone in alcohol-dependent carriers of the OPRM1 G-allele currently seems most promising. HubMed – addiction



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