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Evaluation of the effects of jzp-110 in nonclinical models of abuse liability
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Abstracts / Drug and Alcohol Dependence 171 (2017) e2–e226
Smoking cessation assistance pre- and post-implementation of stage 1 meaningful use Steffani R. Bailey 2,∗ , Megan J. Hoopes 3 , Jon Puro 3 , Jennifer E. DeVoe 2,3 , Timothy Burdick 4 , Deborah J. Cohen 4 , John Heintzman 2 , Miguel Marino 4 , Jessica Irvine 3 , Dennis McCarty 1 , Stephen P. Fortmann 5 1 CB 669 PHPM, Oregon Health & Science University, Portland, OR, United States 2 Family Medicine, Oregon Health & Science University, Portland, OR, United States 3 Research, OCHIN, Portland, OR, United States 4 Family Medicine, OHSU, Portland, OR, United States 5 Center for Health Research, Kaiser Permanente Northwest, Portland, OR, United States
Aims: The study examined the extent to which rates of smoking status assessment and smoking cessation assistance changed in a network of Federally Qualified Health Centers (FQHCs) after implementation of Stage 1 Meaningful Use (MU) of electronic health records (EHR). Methods: Data were extracted from 24 FQHCs primary care clinics with an EHR in place before January 2009. Analysis included changes in rates of documentation of smoking status, and readiness to quit, counseling given, and smoking cessation medications prescribed (for patients identified as smokers) in Years 2010 (pre-Stage 1 MU implementation), 2012 (discrete fields to document readiness to quit and counseling given moved to vital signs in preparation for Stage 1 MU), and 2014 (post-Stage 1 MU implementation). Results: Rates of assessment of smoking status, assessment of readiness to quit, counseling given, and cessation medications ordered increased over time (p < .001 for all outcomes). Participating clinics had high documentation of assessing smoking status throughout the study period and were already meeting both the Stage 1 (≥50% of patients) and Stage 2 (≥80% of patients) core measure requirements prior to MU implementation. Smoking cessation medications ordered increased by almost 5 percentage points from 2010 to 2014. Conclusions: The MU program appeared to improve rates of smoking assessment and smoking cessation assistance among FQHC patients. Future analyses will examine whether receipt of smoking cessation assistance is associated with increased quit attempts and smoking cessation. Financial Support: NIDA award (K23-DA037453) and NCAT award (UL1-TR000128). http://dx.doi.org/10.1016/j.drugalcdep.2016.08.053 Evaluation of the effects of jzp-110 in nonclinical models of abuse liability Michelle Baladi 2,∗ , Lawrence P. Carter 2,3 , Jed Black 2 , Jack Bergman 1 1 McLean Hospital/Harvard Medical School, Belmont, MA, United States 2 Jazz Pharmaceuticals, Palo Alto, CA, United States 3 University of Arkansas for Medical Sciences, Little Rock, AR, United States
Aims: Several stimulant medications are FDA approved to treat narcolepsy, but their utility is limited by their abuse potential. JZP-110 is a low potency reuptake inhibitor at dopamine (IC50 = 2.9 M) and norepinephrine (IC50 = 4.4 M) transporters and neither promotes norepinephrine release in rat brain synaptosomes nor produces rebound hypersomnia in mice. The aim of
these nonclinical studies was to evaluate the abuse potential of JZP-110. Methods: In these studies, standard conditioned place preference tests in Sprague-Dawley rats and drug discrimination and self-administration assays in rats and rhesus monkeys were used to evaluate the abuse potential of JZP-110. Results: JZP-110 (10, 30, 90 mg/kg) did not produce conditioned place preference but, in drug discrimination studies, partially substituted for D-amphetamine in rats, and fully substituted for cocaine in both rats (ED50 = 37.4 mg/kg) and monkeys (ED50 = 6.6 mg/kg). In rats, JZP-110 (0.25, 0.5, and 1.0 mg/kg per infusion), in contrast to cocaine (0.8 mg/kg per infusion), did not maintain self-administration (<5 infusions/session) under a fixed ratio schedule of reinforcement (FR1). In monkeys, pretreatment with JZP-110 (32 mg/kg) increased self-administration of low unit doses of cocaine and decreased self-administration of higher unit doses of cocaine. Conclusions: JZP-110, which has stimulant-like discriminative stimulus effects, did not produce conditioned place preference or maintain self-administration in rats, and decreased the selfadministration of high unit doses of cocaine in rhesus monkeys. JZP-110 is a second-generation wake-promoting agent with a mechanism of action and behavioral effects that may differ from those of the traditional stimulants. Financial Support: Sponsored by Jazz Pharmaceuticals. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.054 A longitudinal examination of the impact of childhood emotional abuse on cannabis use trajectories among community youth Anne Nicole Banducci 1,2,∗ , J.W. Felton 2 , Marcel O. Bonn-Miller 1 , C.W. Lejuez 2 , L. MacPherson 2 1
VA Palo Alto Health Care System, The National Center for PTSD, Palo Alto, CA, United States 2 University Of Maryland, College Park, College Park, MD, United States Aims: As childhood abuse is a potent risk factor for the development of substance use (SU), research has focused on understanding when and for whom abuse exerts its effects. Among adults, women appear to be more strongly impacted by child abuse than men, and across development, childhood emotional abuse (CEA) may place individuals at a greater risk for SU than physical/sexual abuse. Given that women are more likely to engage in SU when experiencing stress than men, it is possible CEA-exposed girls might be more likely engage in SU than CEA-exposed boys. Unfortunately, the majority of research in this area is cross-sectional, retrospective, or focused on adult samples. To address these limitations, we examined the impact of CEA on cannabis use (CU) trajectories among community youth. We hypothesized that (1) CEA would predict increases in CU over time and (2) sex would moderate relations between CEA and CU, such that CEA-exposed girls would have higher CU than CEA-exposed boys. Methods: 115 boys and 89 girls (Mage baseline = 13, SD = 0.5) self-reported substance use (Youth Risk Behavior Survey) and CEA (Childhood Trauma Questionnaire) annually across 5 years. We tested a latent growth model of the CU trajectory from grades 9–12. We examined the influence of CEA, gender, and their interaction, on the latent CU intercept and slope. Results: Cannabis use increased over time; more severe CEA was associated with greater baseline CU (std. est. = 0.25, p = .038), but did not predict changes in use over time. The addition of the sex by CEA
Abstracts / Drug and Alcohol Dependence 171 (2017) e2–e226
Smoking cessation assistance pre- and post-implementation of stage 1 meaningful use Steffani R. Bailey 2,∗ , Megan J. Hoopes 3 , Jon Puro 3 , Jennifer E. DeVoe 2,3 , Timothy Burdick 4 , Deborah J. Cohen 4 , John Heintzman 2 , Miguel Marino 4 , Jessica Irvine 3 , Dennis McCarty 1 , Stephen P. Fortmann 5 1 CB 669 PHPM, Oregon Health & Science University, Portland, OR, United States 2 Family Medicine, Oregon Health & Science University, Portland, OR, United States 3 Research, OCHIN, Portland, OR, United States 4 Family Medicine, OHSU, Portland, OR, United States 5 Center for Health Research, Kaiser Permanente Northwest, Portland, OR, United States
Aims: The study examined the extent to which rates of smoking status assessment and smoking cessation assistance changed in a network of Federally Qualified Health Centers (FQHCs) after implementation of Stage 1 Meaningful Use (MU) of electronic health records (EHR). Methods: Data were extracted from 24 FQHCs primary care clinics with an EHR in place before January 2009. Analysis included changes in rates of documentation of smoking status, and readiness to quit, counseling given, and smoking cessation medications prescribed (for patients identified as smokers) in Years 2010 (pre-Stage 1 MU implementation), 2012 (discrete fields to document readiness to quit and counseling given moved to vital signs in preparation for Stage 1 MU), and 2014 (post-Stage 1 MU implementation). Results: Rates of assessment of smoking status, assessment of readiness to quit, counseling given, and cessation medications ordered increased over time (p < .001 for all outcomes). Participating clinics had high documentation of assessing smoking status throughout the study period and were already meeting both the Stage 1 (≥50% of patients) and Stage 2 (≥80% of patients) core measure requirements prior to MU implementation. Smoking cessation medications ordered increased by almost 5 percentage points from 2010 to 2014. Conclusions: The MU program appeared to improve rates of smoking assessment and smoking cessation assistance among FQHC patients. Future analyses will examine whether receipt of smoking cessation assistance is associated with increased quit attempts and smoking cessation. Financial Support: NIDA award (K23-DA037453) and NCAT award (UL1-TR000128). http://dx.doi.org/10.1016/j.drugalcdep.2016.08.053 Evaluation of the effects of jzp-110 in nonclinical models of abuse liability Michelle Baladi 2,∗ , Lawrence P. Carter 2,3 , Jed Black 2 , Jack Bergman 1 1 McLean Hospital/Harvard Medical School, Belmont, MA, United States 2 Jazz Pharmaceuticals, Palo Alto, CA, United States 3 University of Arkansas for Medical Sciences, Little Rock, AR, United States
Aims: Several stimulant medications are FDA approved to treat narcolepsy, but their utility is limited by their abuse potential. JZP-110 is a low potency reuptake inhibitor at dopamine (IC50 = 2.9 M) and norepinephrine (IC50 = 4.4 M) transporters and neither promotes norepinephrine release in rat brain synaptosomes nor produces rebound hypersomnia in mice. The aim of
these nonclinical studies was to evaluate the abuse potential of JZP-110. Methods: In these studies, standard conditioned place preference tests in Sprague-Dawley rats and drug discrimination and self-administration assays in rats and rhesus monkeys were used to evaluate the abuse potential of JZP-110. Results: JZP-110 (10, 30, 90 mg/kg) did not produce conditioned place preference but, in drug discrimination studies, partially substituted for D-amphetamine in rats, and fully substituted for cocaine in both rats (ED50 = 37.4 mg/kg) and monkeys (ED50 = 6.6 mg/kg). In rats, JZP-110 (0.25, 0.5, and 1.0 mg/kg per infusion), in contrast to cocaine (0.8 mg/kg per infusion), did not maintain self-administration (<5 infusions/session) under a fixed ratio schedule of reinforcement (FR1). In monkeys, pretreatment with JZP-110 (32 mg/kg) increased self-administration of low unit doses of cocaine and decreased self-administration of higher unit doses of cocaine. Conclusions: JZP-110, which has stimulant-like discriminative stimulus effects, did not produce conditioned place preference or maintain self-administration in rats, and decreased the selfadministration of high unit doses of cocaine in rhesus monkeys. JZP-110 is a second-generation wake-promoting agent with a mechanism of action and behavioral effects that may differ from those of the traditional stimulants. Financial Support: Sponsored by Jazz Pharmaceuticals. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.054 A longitudinal examination of the impact of childhood emotional abuse on cannabis use trajectories among community youth Anne Nicole Banducci 1,2,∗ , J.W. Felton 2 , Marcel O. Bonn-Miller 1 , C.W. Lejuez 2 , L. MacPherson 2 1
VA Palo Alto Health Care System, The National Center for PTSD, Palo Alto, CA, United States 2 University Of Maryland, College Park, College Park, MD, United States Aims: As childhood abuse is a potent risk factor for the development of substance use (SU), research has focused on understanding when and for whom abuse exerts its effects. Among adults, women appear to be more strongly impacted by child abuse than men, and across development, childhood emotional abuse (CEA) may place individuals at a greater risk for SU than physical/sexual abuse. Given that women are more likely to engage in SU when experiencing stress than men, it is possible CEA-exposed girls might be more likely engage in SU than CEA-exposed boys. Unfortunately, the majority of research in this area is cross-sectional, retrospective, or focused on adult samples. To address these limitations, we examined the impact of CEA on cannabis use (CU) trajectories among community youth. We hypothesized that (1) CEA would predict increases in CU over time and (2) sex would moderate relations between CEA and CU, such that CEA-exposed girls would have higher CU than CEA-exposed boys. Methods: 115 boys and 89 girls (Mage baseline = 13, SD = 0.5) self-reported substance use (Youth Risk Behavior Survey) and CEA (Childhood Trauma Questionnaire) annually across 5 years. We tested a latent growth model of the CU trajectory from grades 9–12. We examined the influence of CEA, gender, and their interaction, on the latent CU intercept and slope. Results: Cannabis use increased over time; more severe CEA was associated with greater baseline CU (std. est. = 0.25, p = .038), but did not predict changes in use over time. The addition of the sex by CEA