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No association between crack-cocaine dependence and functional intronic polymorphism at dopamine D2 receptor gene
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Abstracts / Drug and Alcohol Dependence 140 (2014) e169–e251
Methods: This is a secondary analysis of data from a randomized controlled trial of low-dose naltrexone augmentation of nicotine replacement designed to examine smoking cessation and postcessation weight gain in weight-concerned smokers (Toll et al., 2010). Results: In the primary study, seven-day point-prevalence smoking abstinence rates at 26 weeks post-quit date were not significantly different between the 2 groups (naltrexone: 22% vs. placebo: 27%, p = 0.43). However, analyses revealed that menthol use predicted quit success. Among menthol smokers (N = 61), 13% were abstinent at Week 26, and among non-menthol smokers (N = 105), 30% were abstinent (Wald = 6.02, p = .01; OR, 2.90; 95% CI, 1.24–6.81). Further, menthol smokers who quit smoking gained significantly more weight at Week 26 (M = 14.87 lbs., SD = 9.08; t(37) = −2.22, p = .03) than non-menthol smokers who quit (M = 7.95 lbs., SD = 7.53). Conclusions: Menthol cigarette use has not typically been evaluated as a mechanism for differences in smoking cessation outcomes, but emerging evidence suggests that use of menthol cigarettes may make smoking cessation more difficult. This study adds to the literature supporting the claim that smoking menthol cigarettes can have adverse effects on smoking cessation efforts and on other cessation-related outcomes, such as post-cessation weight gain. Financial support: Research supported by NIH grants T32DA007238 (AMR) and P50-AA15632 (SOM). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.525 Measurement of drug-liking in abuse potential studies: A comparison of bipolar vs. unipolar visual analog scales Carl L. Roland 1 , Beatrice Setnik 1 , G.C. Pixton 1 , L. Webster 2 1 2
Pfizer Inc, Cary, NC, United States CRI Lifetree, Salt Lake City, UT, United States
Aims: Measures of drug-liking used in abuse potential studies are typically quantified on 100-mm visual analog scales (VAS) that can be either unipolar (liking measured using the entire scale) or bipolar (liking and disliking measured with the mid-point considered neutral). The present analysis examined the relationship between these two rating scales in an abuse potential study of oxycodone. Methods: A single-center, randomized, double-blind, placebocontrolled, crossover study was conducted in two cohorts of healthy volunteers with a history of recreational drug abuse. Following a naloxone challenge and drug discrimination test, participants received one treatment per day; cohort 1: 40 mg oxycodone, 40 mg crushed OxyContin® , 40 mg or 80 mg OxyContin® , or placebo; cohort 2: 20, 40, or 80 mg oxycodone or placebo. As part of the abuse potential assessment, the Drug Effects Questionnaire (includes: Do you like the drug?) and bimodal drug-liking scale (Do you like the drug effect you are feeling now?) were administered at multiple post-dose intervals. Spearman correlation coefficients were calculated for individual VAS scores, Emax (highest post-dose score) and TEmax (time to Emax) combined and separately for each cohort and treatment. Results: 35 male, non-dependent, recreational drug users participated. Among all values (n = 2477), there was a positive correlation between bipolar and unipolar ratings (r = 0.64). A higher correlation (r = 0.85) was observed for Emax values and a weaker correlation (r = 0.23) for TEmax. Similar correlations were observed for each cohort. Among treatments within each cohort, individ-
ual score correlations were higher for oxycodone (0.44–0.74) than placebo (−0.16 and 0.09). Conclusions: These data suggest a reasonable positive correlation between unipolar vs. bipolar VAS ratings of drug-liking, especially for Emax. Data interpretation is limited by the use of one study drug and the systematic ordering of questions. Financial support: Analysis was sponsored by Pfizer Inc. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.526 No association between crack-cocaine dependence and functional intronic polymorphism at dopamine D2 receptor gene Tatiana Roman 1 , Anderson R. Stolf 2 , G.C. Akutagava-Martins 1 , D. Müller 1 , J.B. Schuch 1 , L.S. Guimarães 2 , F. Pechansky 2 , F.H. Kessler 2 1
Department of Genetics, UFRGS, Porto Alegre, Brazil Center for Drug and Alcohol Research, UFRGS, Porto Alegre, Brazil 2
Aims: DRD2 gene is commonly expressed in two distinct isoforms, the short and the long variant, due to alternative splicing. The change G > T (rs2283265), located in intron 5, influences the splicing, where the T allele favors the long form. The aim of this study was to verify if this DRD2 polymorphism is associated with CCD, since T allele has already been associated with cocaine abuse. Methods: A cross-sectional sample of 237 current adult crack abusers or dependents (DSM-IV TR criteria) from in- and outpatient clinics and 210 community non-crack-cocaine users (controls) were collected in southern Brazil. Subjects were evaluated with ASRS, ASI6 and MINI-Short. IQ was estimated using WAIS. DNA samples extracted from whole blood were genotyped for the DRD2 rs2283265. The hypothesis of association was investigated using Chi-square. Results: The G allele and the GG genotype were the most prevalent in both cases (80.2% and 62.9%, respectively) and controls (80.3% and 63%, respectively). A paired analysis comparing the frequencies for G and T alleles showed no differences between cases and controls (Mcnemar p = 0.56; 189 pairs regarding sex, age and ethnic group). The non-paired analyzes including all the 447 subjects also did not show differences (Pearson Chi-square p = 0.98). The comparison of GG, GT and TT genotype frequencies between cases and controls did not evidenced associations in both paired (Mcnemar p = 0.60) and non-paired (Pearson Chi-square p = 0.99) analyses. Conclusions: This study suggests that DRD2 gene, namely intron 5 G > T change, is not associated with CCD. However, in our population, this polymorphism has been recently implicated in alcohol dependence when interacting to the dopamine D4 receptor gene (DRD4). Thus, further analyses including DRD4 gene might be able to reveal a role for DRD2 gene in CCD. Financial support: SENAD, FAPERGS, CNPq, CAPES, PRODAH. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.527
Abstracts / Drug and Alcohol Dependence 140 (2014) e169–e251
Methods: This is a secondary analysis of data from a randomized controlled trial of low-dose naltrexone augmentation of nicotine replacement designed to examine smoking cessation and postcessation weight gain in weight-concerned smokers (Toll et al., 2010). Results: In the primary study, seven-day point-prevalence smoking abstinence rates at 26 weeks post-quit date were not significantly different between the 2 groups (naltrexone: 22% vs. placebo: 27%, p = 0.43). However, analyses revealed that menthol use predicted quit success. Among menthol smokers (N = 61), 13% were abstinent at Week 26, and among non-menthol smokers (N = 105), 30% were abstinent (Wald = 6.02, p = .01; OR, 2.90; 95% CI, 1.24–6.81). Further, menthol smokers who quit smoking gained significantly more weight at Week 26 (M = 14.87 lbs., SD = 9.08; t(37) = −2.22, p = .03) than non-menthol smokers who quit (M = 7.95 lbs., SD = 7.53). Conclusions: Menthol cigarette use has not typically been evaluated as a mechanism for differences in smoking cessation outcomes, but emerging evidence suggests that use of menthol cigarettes may make smoking cessation more difficult. This study adds to the literature supporting the claim that smoking menthol cigarettes can have adverse effects on smoking cessation efforts and on other cessation-related outcomes, such as post-cessation weight gain. Financial support: Research supported by NIH grants T32DA007238 (AMR) and P50-AA15632 (SOM). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.525 Measurement of drug-liking in abuse potential studies: A comparison of bipolar vs. unipolar visual analog scales Carl L. Roland 1 , Beatrice Setnik 1 , G.C. Pixton 1 , L. Webster 2 1 2
Pfizer Inc, Cary, NC, United States CRI Lifetree, Salt Lake City, UT, United States
Aims: Measures of drug-liking used in abuse potential studies are typically quantified on 100-mm visual analog scales (VAS) that can be either unipolar (liking measured using the entire scale) or bipolar (liking and disliking measured with the mid-point considered neutral). The present analysis examined the relationship between these two rating scales in an abuse potential study of oxycodone. Methods: A single-center, randomized, double-blind, placebocontrolled, crossover study was conducted in two cohorts of healthy volunteers with a history of recreational drug abuse. Following a naloxone challenge and drug discrimination test, participants received one treatment per day; cohort 1: 40 mg oxycodone, 40 mg crushed OxyContin® , 40 mg or 80 mg OxyContin® , or placebo; cohort 2: 20, 40, or 80 mg oxycodone or placebo. As part of the abuse potential assessment, the Drug Effects Questionnaire (includes: Do you like the drug?) and bimodal drug-liking scale (Do you like the drug effect you are feeling now?) were administered at multiple post-dose intervals. Spearman correlation coefficients were calculated for individual VAS scores, Emax (highest post-dose score) and TEmax (time to Emax) combined and separately for each cohort and treatment. Results: 35 male, non-dependent, recreational drug users participated. Among all values (n = 2477), there was a positive correlation between bipolar and unipolar ratings (r = 0.64). A higher correlation (r = 0.85) was observed for Emax values and a weaker correlation (r = 0.23) for TEmax. Similar correlations were observed for each cohort. Among treatments within each cohort, individ-
ual score correlations were higher for oxycodone (0.44–0.74) than placebo (−0.16 and 0.09). Conclusions: These data suggest a reasonable positive correlation between unipolar vs. bipolar VAS ratings of drug-liking, especially for Emax. Data interpretation is limited by the use of one study drug and the systematic ordering of questions. Financial support: Analysis was sponsored by Pfizer Inc. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.526 No association between crack-cocaine dependence and functional intronic polymorphism at dopamine D2 receptor gene Tatiana Roman 1 , Anderson R. Stolf 2 , G.C. Akutagava-Martins 1 , D. Müller 1 , J.B. Schuch 1 , L.S. Guimarães 2 , F. Pechansky 2 , F.H. Kessler 2 1
Department of Genetics, UFRGS, Porto Alegre, Brazil Center for Drug and Alcohol Research, UFRGS, Porto Alegre, Brazil 2
Aims: DRD2 gene is commonly expressed in two distinct isoforms, the short and the long variant, due to alternative splicing. The change G > T (rs2283265), located in intron 5, influences the splicing, where the T allele favors the long form. The aim of this study was to verify if this DRD2 polymorphism is associated with CCD, since T allele has already been associated with cocaine abuse. Methods: A cross-sectional sample of 237 current adult crack abusers or dependents (DSM-IV TR criteria) from in- and outpatient clinics and 210 community non-crack-cocaine users (controls) were collected in southern Brazil. Subjects were evaluated with ASRS, ASI6 and MINI-Short. IQ was estimated using WAIS. DNA samples extracted from whole blood were genotyped for the DRD2 rs2283265. The hypothesis of association was investigated using Chi-square. Results: The G allele and the GG genotype were the most prevalent in both cases (80.2% and 62.9%, respectively) and controls (80.3% and 63%, respectively). A paired analysis comparing the frequencies for G and T alleles showed no differences between cases and controls (Mcnemar p = 0.56; 189 pairs regarding sex, age and ethnic group). The non-paired analyzes including all the 447 subjects also did not show differences (Pearson Chi-square p = 0.98). The comparison of GG, GT and TT genotype frequencies between cases and controls did not evidenced associations in both paired (Mcnemar p = 0.60) and non-paired (Pearson Chi-square p = 0.99) analyses. Conclusions: This study suggests that DRD2 gene, namely intron 5 G > T change, is not associated with CCD. However, in our population, this polymorphism has been recently implicated in alcohol dependence when interacting to the dopamine D4 receptor gene (DRD4). Thus, further analyses including DRD4 gene might be able to reveal a role for DRD2 gene in CCD. Financial support: SENAD, FAPERGS, CNPq, CAPES, PRODAH. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.527