- Email: [email protected]
Effects of varenicline and GZ-793A on methamphetamine and food self-administration under a multiple schedule of reinforcement in rats
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Abstract / Drug and Alcohol Dependence 156 (2015) e183–e245
features and practices of the PMPs in Canada was obtained by reviewing program websites and telephone interviews conducted with key contacts from each program. Results: PMPs have varied features and practices, including models of administrative oversight, drugs targeted for monitoring, methods of data collection, types of interventions and degree of information sharing. There are very few research studies evaluating the effectiveness of PMP features or overall performance; primarily observational studies are available. Several best practice recommendations have been suggested based on opinion and experience. In Canada, there are currently seven provinces operating some form of a PMP and two provinces with programs in development; all have different histories and features and are not linked. Conclusions: There is limited supporting research evidence for most aspects of PMPs at this time, although there is growing research attention in the area, and the number of research reports is increasing each year. As programs across Canada continue to be developed and expanded, further work is needed to evaluate the various features of PMPs to determine their impact, and to establish the overall value of PMPs in promoting the safe and effective use of prescription products that are associated with significant harms. Financial Support: Alberta Health. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.565 Health related issues among people who inject drugs in Australia Jennifer Stafford ∗ , Lucy Burns National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia Aims: The Illicit Drug Reporting System (IDRS) monitors the price, purity and availability and use of illicit drugs annually in Australia. The IDRS focuses mainly on: heroin and other opioids, methamphetamines, cocaine and cannabis. The IDRS also looks at other issues related to drug use including injection-related problems and mental health. This presentation provides a closer look at health-related issues among people who inject drugs interviewed in the 2014 IDRS. Methods: The IDRS involves the collection and analysis of three data sources: (1) interviews with people who inject drugs (IDRS), (2) interviews with experts who work with drug users such as treatment personnel and (3) existing databases on drug-related issues such as customs and overdose data. Results: Nationally, around 900 people who inject drugs were interviewed for the IDRS in 2014. Less than one-fifth of people who injected drugs reported lending a needle or using a needle after somebody else. Around one-quarter reported sharing injecting equipment (not including needles), around half re-used their own needle and over half re-used injecting equipment. Over half reported an injection-related issue in the last month, mainly scarring/bruising. Self-reported mental health problems in the last six months were reported by around half of the national sample. The most common mental health problem reported was depression followed by anxiety. IDRS participants reported higher levels of distress on the Kessler Psychological Distress Scale 10 compared to the Australian general population. Conclusions: A greater understanding of the health-related issues among people who inject drugs regularly is required to better inform policy decisions and treatment delivery.
Financial Support: The IDRS Project is supported by funding from the Australian Government under the Substance Misuse Prevention and Service Improvement Grants Fund. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.566 Does urban size and region predict outpatient substance abuse treatment completion? Gerald Stahler ∗ , Jeremy Mennis Geography & Urban Studies, Temple University, Philadelphia, PA, United States Aims: This study examines the influence of urban size and region on the likelihood of treatment completion for outpatient settings using the 2011 SAMHSA TEDS-D dataset. Methods: Logistic regression was employed using treatment completion as the dependent variable (N = 897,888). Two geographic variables served as independent variables. ‘City size’ is a five-class ordinal variable representing the population of the U.S. Census metropolitan or micropolitan region in which the subject resides, ranging from areas with a population of less than 50,000 to greater than 750,000. ‘Geographic division’ distinguishes among the ten U.S. Census-defined regional divisions of the U.S. (e.g. Mid-Atlantic, New England). The Mid-Atlantic division (New York, Pennsylvania, and New Jersey), which is the division with the highest number of subjects in the data set, served as the reference category. We also controlled for the subject’s age, race, sex, primary substance use problem, and severity of use. Results: The resulting model had an overall percentage correct = 60.4%, and a Receiver Operating Curve (ROC) analysis resulted in an Area Under the Curve = 0.63, p < 0.005). Results indicate that larger city size is associated with a greater likelihood of treatment completion, and while the city size odds ratio is relatively small (OR = 1.05, p < 0.005), it is of greater magnitude than the odds ratio for sex (where males are significantly more likely to complete treatment). Geographic division was also highly significant, with certain divisions such as the Mountain division (e.g. Colorado, Utah) showing a particularly higher likelihood of treatment completion (OR = 2.07, p < 0.005) compared to the Mid- Atlantic division. Other divisions, such as the East North Central division (e.g., Ohio and Michigan) showed a significantly lower likelihood (OR = 0.73, p < 0.005). Conclusions: Treatment effectiveness at a system level may be improved by examining these geographic variations in outpatient outcomes. Further research needs to identify the reasons for these locational differences in treatment completion. Financial Support: None. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.567 Effects of varenicline and GZ-793A on methamphetamine and food self-administration under a multiple schedule of reinforcement in rats Dustin J. Stairs 1,∗ , Megan Kangiser 1 , Markus N. Pfaff 1 , Sarah Ewin 1 , Linda P. Dwoskin 2 1 Psychology, Creighton University, Omaha, NE, United States 2 Pharmaceutical Sciences, University of Kentucky, Lexington, KY, United States
Aims: Currently there is no FDA pharmacological treatment for methamphetamine (METH) addiction. A widely accepted
Abstract / Drug and Alcohol Dependence 156 (2015) e183–e245
preclinical model used to develop and test potential pharmacotherapies is the rodent intravenous (i.v.) self-administration paradigm. The aim of the current study was establish rodent i.v. self-administration under a multiple schedule with alternating components of METH and food reinforcement. Once behavior stabilized on this schedule we tested two potential pharmacotherapies for METH addiction: GZ-793A, a vesicular monoamine transporter 2 (VMAT2) inhibitor and varenicline, a partial agonist at a4b2 nicotinic acetylcholine receptors (nAChR). Methods: Following catheterization surgery, male SpragueDawley rats acquired both i.v. METH (0.3 mg/kg/infusion) and food self-administration under a multiple schedule of reinforcement. Following stable responding pretreatments of GZ-793A (0, 10, 15, or 30 mg/kg, s.c.) and varenicline (0, 0.3, 1, or 2 mg/kg, s.c.) were administered in a Latin Square design with half of the animals receiving GZ-793A first while the other half received varenicline first. Results: Both GZ-793A and varenicline decreased METH self-administration. However, GZ-793A was more selective at decreasing METH intake without altering food-maintained responding. More specifically, the 20 mg/kg of GZ-793A significantly decreased METH intake compared to saline without effecting food-maintained responding. Also, the lowest dose of GZ-793A significantly decreased METH intake compared to the lowest dose of varenicline, again without disrupting food-maintained responding. No dose of varenicline significantly lowered METH intake compared to a saline control. Conclusions: Cumulatively, this suggests that VMAT2 inhibition, rather than nAChR partial agonism, is a more promising avenue to pursue for a potential pharmacotherapy for METH addiction. Financial Support: This project was funded by the Ferlic Summer Research Fund to MMK. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.568 Women’s intervention to stop HIV/HCV (WISH) Michele Staton-Tindall 5,∗ , Matthew Webster 3 , Carl Leukefeld 2 , Jennifer R. Havens 4 , Carrie B. Oser 1 1 Sociology, University of Kentucky, Lexington, KY, United States 2 University of Kentucky, Lexington, LA, United States 3 Behavioral Science, University of Kentucky, Lexington, KY, United States 4 Center on Drug and Alcohol Research, University of Kentucky, Lexington, KY, United States 5 Social Work, University of Kentucky, Lexington, KY, United States
Aims: The Appalachian region has been the focus of national media highlighting the serious problems arising from prescription opiate abuse. Rural drug users report that injection is the primary method of drug administration in this area. Injection drug use creates significant public health concern among an understudied and vulnerable group of high-risk rural women and their risks associated with HIV and HCV. Thus, there is significant need to implement evidence-based practices focused on rural HIV/HCV risks. The overall aim is to describe the implementation of an evidence-based intervention (Motivational Interviewing for HIV Risk Reduction) with high-risk incarcerated rural women. The program uses rural jails to outreach to drug-using rural women at high-risk for HIV/HCV. Participants are randomly selected, screened for substance use using the NIDA-modified ASSIST, and randomly assigned to four brief
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jail intervention sessions using MI-HIV or to the NIDA education comparison group. MI-HIV includes four private individual sessions in the jail. Sessions are recorded and reviewed to ensure intervention fidelity. The therapist follows a basic structure to guide each session. This presentation will highlight session content, describe fidelity approaches, and review adaptations for this culturally unique population of high-risk women in the jail context. Conclusions: Little is known about implementing evidencebased practices in non-therapeutic environments such as jails. This program is promising as an approach to high-risk drug use behavior in Appalachia among vulnerable women. Considering service limitations in the area, this program utilizes a real-world setting to identify and intervene with high-risk women drug users. Financial Support: Research was supported by the National Institute on Drug Abuse of the National Institutes of Health under Awards R01DA033866 and K02DA35116. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.569 Subjective and objective evidence of low abuse potential of the peripherally-acting kappa opioid, CR845, compared with pentazocine Joseph W. Stauffer 1,∗ , Frédérique Menzaghi 1 , Lynn R. Webster 2 , Robert H. Spencer 1 , Nacer E. Abrouk 3 , Michael Lewis 1 , Derek Chalmers 1 1
Cara Therapeutics, Shelton, CT, United States PRA, Salt Lake City, UT, United States 3 Innovexe, Mountain View, CA, United States 2
Aims: CR845, a potent, peripherally-acting, selective kappa opioid, is being developed for the treatment of acute and chronic pain. The primary objective of the trial was to measure the relative abuse potential of 2 doses of CR845 compared to an intravenous (iv) dose of pentazocine, a Schedule IV opioid analgesic with mixed mu and kappa opioid activity. Methods: Recreational polydrug users with opioid and hallucinogenic drug experience were enrolled in this single-center, randomized, double-blind, active- and placebo-controlled study. Subjects (N = 39) received a single bolus iv dose of the following 4 treatments in a balanced Williams crossover design, with 48-hour washout periods: CR845 5 mcg/kg (therapeutic dose), CR845 15 mcg/kg (supra-therapeutic dose), placebo, and pentazocine 0.5 mg/kg. In addition to subjective measures of drug abuse liability, changes in pupillary diameter were measured. Results: The primary measure of “drug liking” Emax on a visual analog scale (VAS) for CR845 was significantly lower than pentazocine (p < .0001). Similarly, the VAS scores for “drug liking” and drug effect “high” for CR845 were lower than those for pentazocine over the entire 8-hour observation period. In addition, “overall drug liking” and “take drug again” VAS scores were lower for CR845 compared to pentazocine (p < .0001) and were equivalent to placebo. Pentazocine produced a decrease in the mean pupillary diameter compared with no change with either dose of CR845 or placebo (p < .0001). Conclusions: This study provides evidence that CR845 exhibits substantially less abuse potential than pentazocine. The lack of effect of CR845 on pupillary diameter is consistent with preclinical studies demonstrating an absence of CNS mu opioid activity, which further supports a low abuse potential compared with mu opioids. Financial Support: The study was funded by Cara Therapeutics, Inc. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.570
Abstract / Drug and Alcohol Dependence 156 (2015) e183–e245
features and practices of the PMPs in Canada was obtained by reviewing program websites and telephone interviews conducted with key contacts from each program. Results: PMPs have varied features and practices, including models of administrative oversight, drugs targeted for monitoring, methods of data collection, types of interventions and degree of information sharing. There are very few research studies evaluating the effectiveness of PMP features or overall performance; primarily observational studies are available. Several best practice recommendations have been suggested based on opinion and experience. In Canada, there are currently seven provinces operating some form of a PMP and two provinces with programs in development; all have different histories and features and are not linked. Conclusions: There is limited supporting research evidence for most aspects of PMPs at this time, although there is growing research attention in the area, and the number of research reports is increasing each year. As programs across Canada continue to be developed and expanded, further work is needed to evaluate the various features of PMPs to determine their impact, and to establish the overall value of PMPs in promoting the safe and effective use of prescription products that are associated with significant harms. Financial Support: Alberta Health. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.565 Health related issues among people who inject drugs in Australia Jennifer Stafford ∗ , Lucy Burns National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia Aims: The Illicit Drug Reporting System (IDRS) monitors the price, purity and availability and use of illicit drugs annually in Australia. The IDRS focuses mainly on: heroin and other opioids, methamphetamines, cocaine and cannabis. The IDRS also looks at other issues related to drug use including injection-related problems and mental health. This presentation provides a closer look at health-related issues among people who inject drugs interviewed in the 2014 IDRS. Methods: The IDRS involves the collection and analysis of three data sources: (1) interviews with people who inject drugs (IDRS), (2) interviews with experts who work with drug users such as treatment personnel and (3) existing databases on drug-related issues such as customs and overdose data. Results: Nationally, around 900 people who inject drugs were interviewed for the IDRS in 2014. Less than one-fifth of people who injected drugs reported lending a needle or using a needle after somebody else. Around one-quarter reported sharing injecting equipment (not including needles), around half re-used their own needle and over half re-used injecting equipment. Over half reported an injection-related issue in the last month, mainly scarring/bruising. Self-reported mental health problems in the last six months were reported by around half of the national sample. The most common mental health problem reported was depression followed by anxiety. IDRS participants reported higher levels of distress on the Kessler Psychological Distress Scale 10 compared to the Australian general population. Conclusions: A greater understanding of the health-related issues among people who inject drugs regularly is required to better inform policy decisions and treatment delivery.
Financial Support: The IDRS Project is supported by funding from the Australian Government under the Substance Misuse Prevention and Service Improvement Grants Fund. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.566 Does urban size and region predict outpatient substance abuse treatment completion? Gerald Stahler ∗ , Jeremy Mennis Geography & Urban Studies, Temple University, Philadelphia, PA, United States Aims: This study examines the influence of urban size and region on the likelihood of treatment completion for outpatient settings using the 2011 SAMHSA TEDS-D dataset. Methods: Logistic regression was employed using treatment completion as the dependent variable (N = 897,888). Two geographic variables served as independent variables. ‘City size’ is a five-class ordinal variable representing the population of the U.S. Census metropolitan or micropolitan region in which the subject resides, ranging from areas with a population of less than 50,000 to greater than 750,000. ‘Geographic division’ distinguishes among the ten U.S. Census-defined regional divisions of the U.S. (e.g. Mid-Atlantic, New England). The Mid-Atlantic division (New York, Pennsylvania, and New Jersey), which is the division with the highest number of subjects in the data set, served as the reference category. We also controlled for the subject’s age, race, sex, primary substance use problem, and severity of use. Results: The resulting model had an overall percentage correct = 60.4%, and a Receiver Operating Curve (ROC) analysis resulted in an Area Under the Curve = 0.63, p < 0.005). Results indicate that larger city size is associated with a greater likelihood of treatment completion, and while the city size odds ratio is relatively small (OR = 1.05, p < 0.005), it is of greater magnitude than the odds ratio for sex (where males are significantly more likely to complete treatment). Geographic division was also highly significant, with certain divisions such as the Mountain division (e.g. Colorado, Utah) showing a particularly higher likelihood of treatment completion (OR = 2.07, p < 0.005) compared to the Mid- Atlantic division. Other divisions, such as the East North Central division (e.g., Ohio and Michigan) showed a significantly lower likelihood (OR = 0.73, p < 0.005). Conclusions: Treatment effectiveness at a system level may be improved by examining these geographic variations in outpatient outcomes. Further research needs to identify the reasons for these locational differences in treatment completion. Financial Support: None. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.567 Effects of varenicline and GZ-793A on methamphetamine and food self-administration under a multiple schedule of reinforcement in rats Dustin J. Stairs 1,∗ , Megan Kangiser 1 , Markus N. Pfaff 1 , Sarah Ewin 1 , Linda P. Dwoskin 2 1 Psychology, Creighton University, Omaha, NE, United States 2 Pharmaceutical Sciences, University of Kentucky, Lexington, KY, United States
Aims: Currently there is no FDA pharmacological treatment for methamphetamine (METH) addiction. A widely accepted
Abstract / Drug and Alcohol Dependence 156 (2015) e183–e245
preclinical model used to develop and test potential pharmacotherapies is the rodent intravenous (i.v.) self-administration paradigm. The aim of the current study was establish rodent i.v. self-administration under a multiple schedule with alternating components of METH and food reinforcement. Once behavior stabilized on this schedule we tested two potential pharmacotherapies for METH addiction: GZ-793A, a vesicular monoamine transporter 2 (VMAT2) inhibitor and varenicline, a partial agonist at a4b2 nicotinic acetylcholine receptors (nAChR). Methods: Following catheterization surgery, male SpragueDawley rats acquired both i.v. METH (0.3 mg/kg/infusion) and food self-administration under a multiple schedule of reinforcement. Following stable responding pretreatments of GZ-793A (0, 10, 15, or 30 mg/kg, s.c.) and varenicline (0, 0.3, 1, or 2 mg/kg, s.c.) were administered in a Latin Square design with half of the animals receiving GZ-793A first while the other half received varenicline first. Results: Both GZ-793A and varenicline decreased METH self-administration. However, GZ-793A was more selective at decreasing METH intake without altering food-maintained responding. More specifically, the 20 mg/kg of GZ-793A significantly decreased METH intake compared to saline without effecting food-maintained responding. Also, the lowest dose of GZ-793A significantly decreased METH intake compared to the lowest dose of varenicline, again without disrupting food-maintained responding. No dose of varenicline significantly lowered METH intake compared to a saline control. Conclusions: Cumulatively, this suggests that VMAT2 inhibition, rather than nAChR partial agonism, is a more promising avenue to pursue for a potential pharmacotherapy for METH addiction. Financial Support: This project was funded by the Ferlic Summer Research Fund to MMK. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.568 Women’s intervention to stop HIV/HCV (WISH) Michele Staton-Tindall 5,∗ , Matthew Webster 3 , Carl Leukefeld 2 , Jennifer R. Havens 4 , Carrie B. Oser 1 1 Sociology, University of Kentucky, Lexington, KY, United States 2 University of Kentucky, Lexington, LA, United States 3 Behavioral Science, University of Kentucky, Lexington, KY, United States 4 Center on Drug and Alcohol Research, University of Kentucky, Lexington, KY, United States 5 Social Work, University of Kentucky, Lexington, KY, United States
Aims: The Appalachian region has been the focus of national media highlighting the serious problems arising from prescription opiate abuse. Rural drug users report that injection is the primary method of drug administration in this area. Injection drug use creates significant public health concern among an understudied and vulnerable group of high-risk rural women and their risks associated with HIV and HCV. Thus, there is significant need to implement evidence-based practices focused on rural HIV/HCV risks. The overall aim is to describe the implementation of an evidence-based intervention (Motivational Interviewing for HIV Risk Reduction) with high-risk incarcerated rural women. The program uses rural jails to outreach to drug-using rural women at high-risk for HIV/HCV. Participants are randomly selected, screened for substance use using the NIDA-modified ASSIST, and randomly assigned to four brief
e211
jail intervention sessions using MI-HIV or to the NIDA education comparison group. MI-HIV includes four private individual sessions in the jail. Sessions are recorded and reviewed to ensure intervention fidelity. The therapist follows a basic structure to guide each session. This presentation will highlight session content, describe fidelity approaches, and review adaptations for this culturally unique population of high-risk women in the jail context. Conclusions: Little is known about implementing evidencebased practices in non-therapeutic environments such as jails. This program is promising as an approach to high-risk drug use behavior in Appalachia among vulnerable women. Considering service limitations in the area, this program utilizes a real-world setting to identify and intervene with high-risk women drug users. Financial Support: Research was supported by the National Institute on Drug Abuse of the National Institutes of Health under Awards R01DA033866 and K02DA35116. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.569 Subjective and objective evidence of low abuse potential of the peripherally-acting kappa opioid, CR845, compared with pentazocine Joseph W. Stauffer 1,∗ , Frédérique Menzaghi 1 , Lynn R. Webster 2 , Robert H. Spencer 1 , Nacer E. Abrouk 3 , Michael Lewis 1 , Derek Chalmers 1 1
Cara Therapeutics, Shelton, CT, United States PRA, Salt Lake City, UT, United States 3 Innovexe, Mountain View, CA, United States 2
Aims: CR845, a potent, peripherally-acting, selective kappa opioid, is being developed for the treatment of acute and chronic pain. The primary objective of the trial was to measure the relative abuse potential of 2 doses of CR845 compared to an intravenous (iv) dose of pentazocine, a Schedule IV opioid analgesic with mixed mu and kappa opioid activity. Methods: Recreational polydrug users with opioid and hallucinogenic drug experience were enrolled in this single-center, randomized, double-blind, active- and placebo-controlled study. Subjects (N = 39) received a single bolus iv dose of the following 4 treatments in a balanced Williams crossover design, with 48-hour washout periods: CR845 5 mcg/kg (therapeutic dose), CR845 15 mcg/kg (supra-therapeutic dose), placebo, and pentazocine 0.5 mg/kg. In addition to subjective measures of drug abuse liability, changes in pupillary diameter were measured. Results: The primary measure of “drug liking” Emax on a visual analog scale (VAS) for CR845 was significantly lower than pentazocine (p < .0001). Similarly, the VAS scores for “drug liking” and drug effect “high” for CR845 were lower than those for pentazocine over the entire 8-hour observation period. In addition, “overall drug liking” and “take drug again” VAS scores were lower for CR845 compared to pentazocine (p < .0001) and were equivalent to placebo. Pentazocine produced a decrease in the mean pupillary diameter compared with no change with either dose of CR845 or placebo (p < .0001). Conclusions: This study provides evidence that CR845 exhibits substantially less abuse potential than pentazocine. The lack of effect of CR845 on pupillary diameter is consistent with preclinical studies demonstrating an absence of CNS mu opioid activity, which further supports a low abuse potential compared with mu opioids. Financial Support: The study was funded by Cara Therapeutics, Inc. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.570