opioid system located downstream of a7 nicotinic acetylcholine receptor participates in the...

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e160 Abstracts / Drug and Alcohol Dependence 146 (2015) e118–e201 Results: Preliminary data on 64 cases showed opioids (mainly desomorphine: “crocodile”) were the most commonly injected drugs (64%) during the past 30 days, followed by homemade stimulants (33%). Concomitant use of benzodiazepines (56%) and barbiturates (10%) was common. Results of urine screening revealed that stimulant and benzodiazepine use declined over time irrespective of condition (p < .02). Conclusions: Reaching this stigmatized and hidden population is essential to the welfare of families. Preliminary findings suggest either intervention? resulted in a marked reduction in use of illicit substances in both groups. Interventions that are women-centered, accessible, confidential, receptive, and provide a non-judgmental and caring environment are beneficial for women with substance- use-related problems. Financial Support: Supported by NIDA R01DA029880. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.351 Opioid system located downstream of a7 nicotinic acetylcholine receptor participates in the development of physical dependence on nicotine in mice Shiroh Kishioka, Norikazu Kiguchi, Yuka Kobayashi, Fumihiro Saika, Chizuko Yamamoto Pharmacology, Wakayama Medical University, Wakayama, Japan Aims: We previously reported that nicotine (NIC)-induced anal- gesia, but not glucocorticoid increase, was suppressed by opioid receptor antagonist, naloxone (NLX), indicating that nicotine effect is mediated in part by the activation of the endogenous opioid sys- tem. Moreover, it is well known that NIC has physical-dependence liability, but its mechanism is still unclear. Therefore, we examined whether physical dependence on NIC was mediated by activation of the opioid system. Furthermore, we clarified nicotinic acetylcholine receptor (nAChR) subtype connected to the opioid system. Methods: The activation of hypothalamic-pituitary-adrenal axis, i.e. serum corticosterone (SCS) increase, was employed as an indicator of NIC withdrawal sign. Firstly, we studied the effects of doses and periods of repeated NIC treatments on NLX-precipitated SCS increase using ICR mice. Secondary, we investigated the effects of concomitant treatments of opioid receptor antagonist or nAChR subtype antagonist with repeated NIC on NLX-precipitated SCS increase. Naltrexone (NTX) was employed as opioid receptor antag- onist. And methyllycaconitine (MLA) and dihydro-B-erythroidine (DH B E) were used as a7 nAChR antagonist and a4B2 nAChR antago- nist, respectively. SCS levels were quantified by fluorometric assay. Results: In this study, NLX precipitated an SCS increase in mice receiving repeated NIC, by a dose-dependent mechanism, and correlated with the dose and number of days of repeated NIC administration. When NTX was concomitantly administered with repeated NIC, the NLX-precipitated SCS increase was not elicited. Concomitant administration of MLA with repeated NIC, but not DH B E, did not elicit an SCS increase by NLX. Conclusions: A physical dependence on NIC was in part devel- oped by the activation of the endogenous opioid system, and the opioid system was located on the downstream of a7 nAChR. This opioid component in physical dependence on NIC might be a useful target for the cessation of tobacco smoking. Financial Support: This work was supported by a grant from the Smoking Research Foundation. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.352 Does the efficacy of medications for substance abuse treatment decrease over time? Elias M. Klemperer, John Hughes Psychiatry, University of Vermont, Burlington, VT, United States Aims: Prior research suggests the efficacy of some medications decline over time. A previous study suggests this trend may occur with nicotine replacement therapies (NRT) because remaining users are more difficult to treat. The present research aims to test this hypothesis by exploring 1) more recent trials of medications to treat tobacco use disorder, 2) medications to treat alcohol and opioid use disorder. Methods: Data were acquired from randomized controlled trials in the Cochrane Database. The analyses included abstinence rates from 122 NRT trials from 1979 to 2012 (N = 51,265), 24 acamprosate trials from 1985 to 2006 (N = 6,172), and 26 naltrexone trials from 1992 to 2008 (N = 4,693). We examined the incidence of a) absti- nence in the active condition, b) abstinence in the control condition, and c) the active vs placebo effect size via the Odds Ratio (OR). Thus, we conducted 9 fixed-effects meta-analyses (3 drugs × 3 out- comes). We then conducted regressions evaluating the effect of time in which study weights were determined by their sample size. Further analyses from methadone and buprenorphine trials will be included in the presentation. Results: The rate of abstinence from alcohol decreased over time in participants treated with acamprosate (15%/10 yrs; p < .01) but did not change in the controls; the OR decreased over time (1.00/10 yrs; p < .05). The rate of abstinence from heavy drink- ing in participants treated with naltrexone appeared to decrease (27%/10 yrs; p < .10), but did not change in controls. The nal- trexone treatment OR appeared to decrease (.72/10 yrs; p < .10). In NRT studies, the rate of abstinence in controls decreased (1.20%/10 yrs; p < .05) but the active group and the OR did not change over time. Conclusions: Our hypotheses that the OR would decrease over time was partially supported. Analyses exploring time effects with methadone and buprenorphine, and possible explanations for the differences in medication efficacy will be discussed. Financial Support: This work was supported by NIDA 5 T32 DA 7242-23. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.353 Effects of dissemination efforts to promote client engagement in recovery-oriented activities in community-based treatment Daniel J. Knoblach 1 , Amy Mericle 2 , Emily Hutz 2 , Adam C. Brooks 2 , Alexandre B. Laudet 3 , Deni Carise 4 1 University of Maryland, Baltimore County, Catonsville, MD, United States 2 Treatment Research Institute, Philadelphia, PA, United States 3 National Development and Research Institutes, New York, NY, United States 4 CRC Health Group, Inc., Cupertino, CA, United States Aims: Involvement in positive activities (e.g. physical, recre- ational, spiritual, and sober socializing) contributes to improved quality of life, a predictor of sobriety and of the broader goal of recovery. Using data from NIH-funded studies, we examined whether having a counselor trained to target positive activities in

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Page 1: Opioid system located downstream of a7 nicotinic acetylcholine receptor participates in the development of physical dependence on nicotine in mice

e160 Abstracts / Drug and Alcohol Dependence 146 (2015) e118–e201

Results: Preliminary data on 64 cases showed opioids (mainlydesomorphine: “crocodile”) were the most commonly injecteddrugs (64%) during the past 30 days, followed by homemadestimulants (33%). Concomitant use of benzodiazepines (56%)and barbiturates (10%) was common. Results of urine screeningrevealed that stimulant and benzodiazepine use declined over timeirrespective of condition (p < .02).

Conclusions: Reaching this stigmatized and hidden populationis essential to the welfare of families. Preliminary findings suggesteither intervention? resulted in a marked reduction in use of illicitsubstances in both groups. Interventions that are women-centered,accessible, confidential, receptive, and provide a non-judgmentaland caring environment are beneficial for women with substance-use-related problems.

Financial Support: Supported by NIDA R01DA029880.

http://dx.doi.org/10.1016/j.drugalcdep.2014.09.351

Opioid system located downstream of a7nicotinic acetylcholine receptor participates inthe development of physical dependence onnicotine in mice

Shiroh Kishioka, Norikazu Kiguchi, YukaKobayashi, Fumihiro Saika, Chizuko Yamamoto

Pharmacology, Wakayama Medical University,Wakayama, Japan

Aims: We previously reported that nicotine (NIC)-induced anal-gesia, but not glucocorticoid increase, was suppressed by opioidreceptor antagonist, naloxone (NLX), indicating that nicotine effectis mediated in part by the activation of the endogenous opioid sys-tem. Moreover, it is well known that NIC has physical-dependenceliability, but its mechanism is still unclear. Therefore, we examinedwhether physical dependence on NIC was mediated by activation ofthe opioid system. Furthermore, we clarified nicotinic acetylcholinereceptor (nAChR) subtype connected to the opioid system.

Methods: The activation of hypothalamic-pituitary-adrenalaxis, i.e. serum corticosterone (SCS) increase, was employed as anindicator of NIC withdrawal sign. Firstly, we studied the effects ofdoses and periods of repeated NIC treatments on NLX-precipitatedSCS increase using ICR mice. Secondary, we investigated the effectsof concomitant treatments of opioid receptor antagonist or nAChRsubtype antagonist with repeated NIC on NLX-precipitated SCSincrease. Naltrexone (NTX) was employed as opioid receptor antag-onist. And methyllycaconitine (MLA) and dihydro-B-erythroidine(DH B E) were used as a7 nAChR antagonist and a4B2 nAChR antago-nist, respectively. SCS levels were quantified by fluorometric assay.

Results: In this study, NLX precipitated an SCS increase inmice receiving repeated NIC, by a dose-dependent mechanism,and correlated with the dose and number of days of repeated NICadministration. When NTX was concomitantly administered withrepeated NIC, the NLX-precipitated SCS increase was not elicited.Concomitant administration of MLA with repeated NIC, but not DHB E, did not elicit an SCS increase by NLX.

Conclusions: A physical dependence on NIC was in part devel-oped by the activation of the endogenous opioid system, and theopioid system was located on the downstream of a7 nAChR. Thisopioid component in physical dependence on NIC might be a usefultarget for the cessation of tobacco smoking.

Financial Support: This work was supported by a grant fromthe Smoking Research Foundation.

http://dx.doi.org/10.1016/j.drugalcdep.2014.09.352

Does the efficacy of medications for substanceabuse treatment decrease over time?

Elias M. Klemperer, John Hughes

Psychiatry, University of Vermont, Burlington, VT,United States

Aims: Prior research suggests the efficacy of some medicationsdecline over time. A previous study suggests this trend may occurwith nicotine replacement therapies (NRT) because remainingusers are more difficult to treat. The present research aims to testthis hypothesis by exploring 1) more recent trials of medicationsto treat tobacco use disorder, 2) medications to treat alcohol andopioid use disorder.

Methods: Data were acquired from randomized controlled trialsin the Cochrane Database. The analyses included abstinence ratesfrom 122 NRT trials from 1979 to 2012 (N = 51,265), 24 acamprosatetrials from 1985 to 2006 (N = 6,172), and 26 naltrexone trials from1992 to 2008 (N = 4,693). We examined the incidence of a) absti-nence in the active condition, b) abstinence in the control condition,and c) the active vs placebo effect size via the Odds Ratio (OR).Thus, we conducted 9 fixed-effects meta-analyses (3 drugs × 3 out-comes). We then conducted regressions evaluating the effect oftime in which study weights were determined by their sample size.Further analyses from methadone and buprenorphine trials will beincluded in the presentation.

Results: The rate of abstinence from alcohol decreased over timein participants treated with acamprosate (−15%/10 yrs; p < .01)but did not change in the controls; the OR decreased over time(−1.00/10 yrs; p < .05). The rate of abstinence from heavy drink-ing in participants treated with naltrexone appeared to decrease(−27%/10 yrs; p < .10), but did not change in controls. The nal-trexone treatment OR appeared to decrease (−.72/10 yrs; p < .10).In NRT studies, the rate of abstinence in controls decreased(−1.20%/10 yrs; p < .05) but the active group and the OR did notchange over time.

Conclusions: Our hypotheses that the OR would decrease overtime was partially supported. Analyses exploring time effects withmethadone and buprenorphine, and possible explanations for thedifferences in medication efficacy will be discussed.

Financial Support: This work was supported by NIDA 5 T32 DA7242-23.

http://dx.doi.org/10.1016/j.drugalcdep.2014.09.353

Effects of dissemination efforts to promoteclient engagement in recovery-orientedactivities in community-based treatment

Daniel J. Knoblach 1, Amy Mericle 2, Emily Hutz 2,Adam C. Brooks 2, Alexandre B. Laudet 3, DeniCarise 4

1 University of Maryland, Baltimore County,Catonsville, MD, United States2 Treatment Research Institute, Philadelphia, PA,United States3 National Development and Research Institutes,New York, NY, United States4 CRC Health Group, Inc., Cupertino, CA, United States

Aims: Involvement in positive activities (e.g. physical, recre-ational, spiritual, and sober socializing) contributes to improvedquality of life, a predictor of sobriety and of the broader goalof recovery. Using data from NIH-funded studies, we examinedwhether having a counselor trained to target positive activities in