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Methylphenidate self-administration increases the potency and reinforcing effects of releasers through a dopamine transporter mechanism
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Abstracts / Drug and Alcohol Dependence 140 (2014) e2–e85
Client reasons for poor engagement early in substance abuse treatment John S. Cacciola 1,2 , A. Mericle 1 , Adam C. Brooks 1 , M. Ivey 2 , J. McKay 1,2 1 Treatment Research Institute, Philadelphia, PA, United States 2 University of Pennsylvania, Philadelphia, PA, United States
Aims: Numerous prediction studies have identified variables (e.g., substance use and psychiatric severity) associated with attrition from outpatient substance abuse treatment (SAT). Very few studies have examined factors associated with dropout from the client’s perspective. Those that have indicate that dissatisfaction with aspects of treatment as well as individual status factors are reported reasons for dropout. The present study rates clients’ selfreported reasons for early attrition from outpatient SAT. Methods: Clients (N = 106) recently admitted to two outpatient SAT programs, who irregularly attended treatment during the first 2–3 weeks, were contacted for a brief telephone motivational intervention. During this call they were queried about reasons for lack of attendance, which were then abstracted and coded. Results: Clients reported various and multiple reasons for poor early engagement in treatment that roughly paralleled those reported for dropping out of treatment by clients in previous studies. These reasons can be categorized as: Client Factors—particularly medical and psychological problems, and acute life stressors; Treatment Factors including issues with clients and staff, as well as the schedule and nature of the treatment itself; and Environmental or Logistical Factors such as transportation, finances, and competing employment demands. Conclusions: Client attributions for outpatient treatment attrition are not fully parallel with variables identified in prediction studies obtained via patient assessments. Further, clients identify many issues that appear to be actionable in some way, and that if prepared for or dealt with by the clinics at both the programmatic and individual client levels, could improve retention. Financial support: NIAAA 1-P01-AA016821-01A1 and NIDA 2P60-DA005186-21. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.086 Current thinking on the premarketing evaluation of abuse-deterrent opioid formulations Silvia N. Calderon, J.M. Tolliver, M. Klein Controlled Substance Staff, Food and Drug Administration, Silver Spring, MD, United States Aims: To provide an overview of the Food and Drug Administration (FDA) current thinking about the studies that should be conducted to demonstrate that a formulation has abuse deterrent (AD) properties. Methods: Abuse and misuse of prescription opioid analgesics is a serious and growing public health problem. Consequently, the development of AD formulations that are less prone to abuse or misuse is a public health priority. To that end, the Center for Drug Evaluation and Research at FDA is developing a guidance regarding the evaluation of AD opioid formulations. Results: A phased three tier approach for premarketing assessment has been proposed for formulations with potential AD features. The first tier consists of in-vitro manipulation and extraction studies, aimed to evaluate the ease with which AD features of a new formulation can be defeated or partially compromised under exper-
imental conditions. Pharmacokinetic/pharmacodynamic studies constitute the second tier. These studies are designed to understand the in-vivo properties of the new formulation by comparing the pharmacokinetic profiles of the “manipulated” formulation with the intact formulation and other comparator drugs through one or more routes of administration, and to collect pharmacodynamic outcomes such as adverse events associated with the administration of the manipulated formulation. The third tier consists on evaluating the relative abuse potential of the AD formulation to that of a positive control and placebo in human abuse potential studies. Conclusions: The development of formulations with abusedeterrent properties represents an evolving area of research. Abuse-deterrent technologies and the methodology for evaluating those technologies are rapidly evolving. Therefore, in addition to retaining a flexible, adaptive approach to the evaluation of AD formulations, there is considerable potential for additional scientific work to aid in the efforts to develop and assess AD formulations. Financial support: N/A. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.087 Methylphenidate self-administration increases the potency and reinforcing effects of releasers through a dopamine transporter mechanism Erin Calipari 1 , M.J. Ferris 1 , A. Salahpour 2 , M.G. Caron 3 , D.C. Roberts 1 , S.R. Jones 1 1 Wake Forest School of Medicine, Winston-Salem, NC, United States 2 University of Toronto, Toronto, ON, Canada 3 Duke University Medical Center, Durham, NC, United States
Aims: Intravenous abuse of methylphenidate (MPH) has become prevalent, which is alarming given the lack of research on its consequences. We examined the effects of MPH selfadministration (SA) on the nucleus accumbens core (NAcc) dopamine (DA) system, as changes can influence reward and reinforcement. The DA transporter (DAT) is the primary site of action of psychostimulants, thus we assessed the potency of compounds to inhibit the DAT following MPH SA. Further, we assessed the reinforcing efficacy of cocaine (COC), MPH, and amphetamine (AMPH). MPH SA resulted in increased DAT levels, thus we increased DAT levels by transgenic over-expression [DAT(tg)] to determine if it was sufficient to cause the MPH SA-induced effects. Methods: Rats underwent fixed ratio one (FR1) SA. Kinetics of stimulated DA signals were measured with in vitro voltammetry. COC, MPH and AMPH were applied to slices to assess potency. To assess reinforcing efficacy animals were switched to a threshold procedure (Oleson et al., 2012) for AMPH, COC, and MPH. For locomotor analysis mice were placed into locomotor chambers, injected with drug and monitored. Results: MPH SA increased uptake rates and DAT levels. MPH SA increased the potency and reinforcing efficacy of AMPH and MPH, with no effect on COC. We replicated the effects with DAT(tg) mice, demonstrating increased AMPH and MPH, but not cocaine, induced potency and locomotor activity, suggesting that increased DAT levels are the mechanism by which theses effects occur. Conclusions: MPH SA resulted in enhanced potency and reinforcing efficacy of AMPH and MPH but not COC. These effects are likely through DAT increases as increasing DAT levels [DAT(tg)] had the same effects. This has implications for MPH abusers as well as individuals with differential DAT levels at baseline (e.g. ADHD, drug abusers) as it suggests an enhanced susceptibility to the reinforcing properties of some psychostimulants.
Abstracts / Drug and Alcohol Dependence 140 (2014) e2–e85
Financial support: T32DA007246, F31DA031533.
R01DA024095,
R01DA03016,
http://dx.doi.org/10.1016/j.drugalcdep.2014.02.088 Use of the Being Safe in Treatment (BEST) feedback tool to increase counselor knowledge of patient sexual behavior Donald A. Calsyn, Bryan Hartzler, E.A. Wells, B. Beadnell University of Washington, Seattle, WA, United States Aims: Determine if providing the Being Safe in Treatment (BEST) feedback report to substance abuse treatment counselors increased counselors’ knowledge about their patients’ sexual risk behavior. Methods: The BEST was administered to 48 men and 31 women in outpatient treatment. Participants were randomly assigned to receive (RR) or not receive (NR) a BEST feedback report in a 2:1 ratio. Those receiving a feedback report had the option of providing a copy of the report to their counselor (CR). The BEST assessment was repeated 3 months later and the patient’s counselor was asked in a self-report survey if the patient in the prior 90 days was: (1) sexually active; (2) had multiple sexual partners; (3) engaged in sex under the influence of drugs or alcohol, and (4) engaged in unprotected sex. Each variable was coded a 1 when there was concurrence between the counselor’s response and the actual behavior reported by the patient. These four variables were summed to obtain an overall congruence measure with a range from 0 to 4; higher scores indicating greater congruence between counselor’s belief about the patient’s sexual behavior and patient’s actual self-reported behavior. Results: Congruence between counselor belief and actual patient self-reported behavior was highest for having multiple partners (79.8%) and being sexually active (73.4%), whereas congruence was lower for sex under the influence (65.4%) and engaging in unprotected sex (59.5%). The summed congruence value for CR patients (n = 29) was significantly higher (M = 3.17, sd = 0.85) than NR patients (n = 25, M = 2.40, sd = 1.16) and RR patients (n = 25, M = 2.72, sd = 0.9, F = 4.13, p = 0.02). Conclusions: A counselor receiving a BEST feedback report was associated with the counselor having increased knowledge about the patient’s sexual behavior. Future studies are needed to determine if increased counselor knowledge can contribute to reduced patient sexual risk. Financial support: NIDA grants R21DA022940 (D. Calsyn, PI), U10 DA13714 (D. Donovan, PI), K23 DA025678 (Bryan Hartzler, PI). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.089 A qualitative study of young adults’ perceptions of modified-risk tobacco products for smoking cessation Deepa Camenga, Dana A. Cavallo, Grace Kong, A. Palmer, K. Carroll, S. O’Malley, S. Krishnan-Sarin Yale School of Medicine, New Haven, CT, United States Aims: Through the Family Smoking Prevention and Tobacco Control Act, the Food and Drug Administration has the potential to regulate modified risk tobacco products (MRTPs), or tobacco products that are sold or distributed for use to reduce harm or the risk of tobacco-related disease. The objective of this study is to examine young adults’ perceptions of MRTPs (electronic cigarettes and dissolvables) for cigarette smoking cessation.
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Methods: Eight focus groups will be conducted with a sample of 18–25 year old smokers and non-smokers attending two public colleges in Connecticut; 4 focus groups (N = 29 young adults) have been completed and four will be completed in early 2013. Groups were stratified by gender and smoking status. A standard focus group guide was used to ask participants about their knowledge of MRTPs (electronic cigarettes and dissolvables) and usefulness in smoking cessation. Group discussions were recorded, transcribed, and examined using thematic analysis. Results: Evidence collected to date indicates that smokers and non-smokers were aware of electronic cigarettes, but not dissolvables. Smokers believed that electronic cigarettes were more appealing than existing smoking cessation aids because they mimicked the act of smoking, could be flavored, and did not have widely known side effects. Many smokers experimented with electronic cigarettes and reported that they were not as satisfying as traditional cigarettes. Smokers would exclusively switch to electronic cigarettes when attempting to quit. Smokers and non-smokers did not believe dissolvables were appealing for smoking cessation because they did not mimic smoking, and did not appear tasty or pleasurable. Conclusions: Both smokers and non-smokers have high awareness of electronic cigarettes but not dissolvables. Evidence from the remaining four focus groups will also be presented. This formative qualitative data suggests that electronic cigarettes appeal to young adults as smoking cessation aids. Financial support: This work was supported by the National Institute on Drug Abuse grant P50DA009241. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.090 Smoking prevalence and exposure to second hand-smoke in Mexican pregnant women Octavio Campollo 1 , F. Hernandez 2 , E. Angulo 3 , A. Guzman 2 , I. Navarro 1 , M. García 3 , A. Munguía 1 , J.K. Cunningham 4 1 Center of Studies on Alcohol and Addictions, University of Guadalajara, Guadalajara, Mexico 2 Obstetrics, Hospital Civil Guadalajara, GDL, Mexico 3 Neonatology, Hospital Civil Guadalajara, GDL, Mexico 4 Family & Community Medicine, University of Arizona, Tucson, AZ, United States
Aims: The prevalence of smoking among women in Mexico has increased to 12.6% of the adult population. The aims were to assess the prevalence of tobacco smoking and of exposure to second hand smoke (SHS) among pregnant women in a major pre-natal care clinic in Guadalajara. Methods: Face-to-face interviews were conducted with 454 women attending the pre-natal care clinic to assess smoking and exposure to SHS. Patients found to be smokers received brief intervention and were referred to a smoking cessation program for pregnant women. Results: The patients’ mean age was 24.4 (± 7.5) years; their mean months of pregnancy was 6.7 (± 1.9). Regarding smoking, 3.0% were active smokers, while 27.5% had smoked before pregnancy. Regarding SHS, 49.5% lived on average with 1.4 (±1) smokers who smoked a mean 3.9 cigarettes in their presence. In particular, this included a husband/partner (31.0%), father (17.3%), mother (12.5%), parents in-law (6.9%), brothers (9.1%), sisters (4.0%), brothers in-law (2.5%), uncles/aunts (1.6%), and other relatives (2.5%). Outside their homes (including work), 22.5% of the women were exposed to a mean of 3.5 (±3.3) persons who consumed a daily mean of 7.9 (±9) cigarettes.
Abstracts / Drug and Alcohol Dependence 140 (2014) e2–e85
Client reasons for poor engagement early in substance abuse treatment John S. Cacciola 1,2 , A. Mericle 1 , Adam C. Brooks 1 , M. Ivey 2 , J. McKay 1,2 1 Treatment Research Institute, Philadelphia, PA, United States 2 University of Pennsylvania, Philadelphia, PA, United States
Aims: Numerous prediction studies have identified variables (e.g., substance use and psychiatric severity) associated with attrition from outpatient substance abuse treatment (SAT). Very few studies have examined factors associated with dropout from the client’s perspective. Those that have indicate that dissatisfaction with aspects of treatment as well as individual status factors are reported reasons for dropout. The present study rates clients’ selfreported reasons for early attrition from outpatient SAT. Methods: Clients (N = 106) recently admitted to two outpatient SAT programs, who irregularly attended treatment during the first 2–3 weeks, were contacted for a brief telephone motivational intervention. During this call they were queried about reasons for lack of attendance, which were then abstracted and coded. Results: Clients reported various and multiple reasons for poor early engagement in treatment that roughly paralleled those reported for dropping out of treatment by clients in previous studies. These reasons can be categorized as: Client Factors—particularly medical and psychological problems, and acute life stressors; Treatment Factors including issues with clients and staff, as well as the schedule and nature of the treatment itself; and Environmental or Logistical Factors such as transportation, finances, and competing employment demands. Conclusions: Client attributions for outpatient treatment attrition are not fully parallel with variables identified in prediction studies obtained via patient assessments. Further, clients identify many issues that appear to be actionable in some way, and that if prepared for or dealt with by the clinics at both the programmatic and individual client levels, could improve retention. Financial support: NIAAA 1-P01-AA016821-01A1 and NIDA 2P60-DA005186-21. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.086 Current thinking on the premarketing evaluation of abuse-deterrent opioid formulations Silvia N. Calderon, J.M. Tolliver, M. Klein Controlled Substance Staff, Food and Drug Administration, Silver Spring, MD, United States Aims: To provide an overview of the Food and Drug Administration (FDA) current thinking about the studies that should be conducted to demonstrate that a formulation has abuse deterrent (AD) properties. Methods: Abuse and misuse of prescription opioid analgesics is a serious and growing public health problem. Consequently, the development of AD formulations that are less prone to abuse or misuse is a public health priority. To that end, the Center for Drug Evaluation and Research at FDA is developing a guidance regarding the evaluation of AD opioid formulations. Results: A phased three tier approach for premarketing assessment has been proposed for formulations with potential AD features. The first tier consists of in-vitro manipulation and extraction studies, aimed to evaluate the ease with which AD features of a new formulation can be defeated or partially compromised under exper-
imental conditions. Pharmacokinetic/pharmacodynamic studies constitute the second tier. These studies are designed to understand the in-vivo properties of the new formulation by comparing the pharmacokinetic profiles of the “manipulated” formulation with the intact formulation and other comparator drugs through one or more routes of administration, and to collect pharmacodynamic outcomes such as adverse events associated with the administration of the manipulated formulation. The third tier consists on evaluating the relative abuse potential of the AD formulation to that of a positive control and placebo in human abuse potential studies. Conclusions: The development of formulations with abusedeterrent properties represents an evolving area of research. Abuse-deterrent technologies and the methodology for evaluating those technologies are rapidly evolving. Therefore, in addition to retaining a flexible, adaptive approach to the evaluation of AD formulations, there is considerable potential for additional scientific work to aid in the efforts to develop and assess AD formulations. Financial support: N/A. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.087 Methylphenidate self-administration increases the potency and reinforcing effects of releasers through a dopamine transporter mechanism Erin Calipari 1 , M.J. Ferris 1 , A. Salahpour 2 , M.G. Caron 3 , D.C. Roberts 1 , S.R. Jones 1 1 Wake Forest School of Medicine, Winston-Salem, NC, United States 2 University of Toronto, Toronto, ON, Canada 3 Duke University Medical Center, Durham, NC, United States
Aims: Intravenous abuse of methylphenidate (MPH) has become prevalent, which is alarming given the lack of research on its consequences. We examined the effects of MPH selfadministration (SA) on the nucleus accumbens core (NAcc) dopamine (DA) system, as changes can influence reward and reinforcement. The DA transporter (DAT) is the primary site of action of psychostimulants, thus we assessed the potency of compounds to inhibit the DAT following MPH SA. Further, we assessed the reinforcing efficacy of cocaine (COC), MPH, and amphetamine (AMPH). MPH SA resulted in increased DAT levels, thus we increased DAT levels by transgenic over-expression [DAT(tg)] to determine if it was sufficient to cause the MPH SA-induced effects. Methods: Rats underwent fixed ratio one (FR1) SA. Kinetics of stimulated DA signals were measured with in vitro voltammetry. COC, MPH and AMPH were applied to slices to assess potency. To assess reinforcing efficacy animals were switched to a threshold procedure (Oleson et al., 2012) for AMPH, COC, and MPH. For locomotor analysis mice were placed into locomotor chambers, injected with drug and monitored. Results: MPH SA increased uptake rates and DAT levels. MPH SA increased the potency and reinforcing efficacy of AMPH and MPH, with no effect on COC. We replicated the effects with DAT(tg) mice, demonstrating increased AMPH and MPH, but not cocaine, induced potency and locomotor activity, suggesting that increased DAT levels are the mechanism by which theses effects occur. Conclusions: MPH SA resulted in enhanced potency and reinforcing efficacy of AMPH and MPH but not COC. These effects are likely through DAT increases as increasing DAT levels [DAT(tg)] had the same effects. This has implications for MPH abusers as well as individuals with differential DAT levels at baseline (e.g. ADHD, drug abusers) as it suggests an enhanced susceptibility to the reinforcing properties of some psychostimulants.
Abstracts / Drug and Alcohol Dependence 140 (2014) e2–e85
Financial support: T32DA007246, F31DA031533.
R01DA024095,
R01DA03016,
http://dx.doi.org/10.1016/j.drugalcdep.2014.02.088 Use of the Being Safe in Treatment (BEST) feedback tool to increase counselor knowledge of patient sexual behavior Donald A. Calsyn, Bryan Hartzler, E.A. Wells, B. Beadnell University of Washington, Seattle, WA, United States Aims: Determine if providing the Being Safe in Treatment (BEST) feedback report to substance abuse treatment counselors increased counselors’ knowledge about their patients’ sexual risk behavior. Methods: The BEST was administered to 48 men and 31 women in outpatient treatment. Participants were randomly assigned to receive (RR) or not receive (NR) a BEST feedback report in a 2:1 ratio. Those receiving a feedback report had the option of providing a copy of the report to their counselor (CR). The BEST assessment was repeated 3 months later and the patient’s counselor was asked in a self-report survey if the patient in the prior 90 days was: (1) sexually active; (2) had multiple sexual partners; (3) engaged in sex under the influence of drugs or alcohol, and (4) engaged in unprotected sex. Each variable was coded a 1 when there was concurrence between the counselor’s response and the actual behavior reported by the patient. These four variables were summed to obtain an overall congruence measure with a range from 0 to 4; higher scores indicating greater congruence between counselor’s belief about the patient’s sexual behavior and patient’s actual self-reported behavior. Results: Congruence between counselor belief and actual patient self-reported behavior was highest for having multiple partners (79.8%) and being sexually active (73.4%), whereas congruence was lower for sex under the influence (65.4%) and engaging in unprotected sex (59.5%). The summed congruence value for CR patients (n = 29) was significantly higher (M = 3.17, sd = 0.85) than NR patients (n = 25, M = 2.40, sd = 1.16) and RR patients (n = 25, M = 2.72, sd = 0.9, F = 4.13, p = 0.02). Conclusions: A counselor receiving a BEST feedback report was associated with the counselor having increased knowledge about the patient’s sexual behavior. Future studies are needed to determine if increased counselor knowledge can contribute to reduced patient sexual risk. Financial support: NIDA grants R21DA022940 (D. Calsyn, PI), U10 DA13714 (D. Donovan, PI), K23 DA025678 (Bryan Hartzler, PI). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.089 A qualitative study of young adults’ perceptions of modified-risk tobacco products for smoking cessation Deepa Camenga, Dana A. Cavallo, Grace Kong, A. Palmer, K. Carroll, S. O’Malley, S. Krishnan-Sarin Yale School of Medicine, New Haven, CT, United States Aims: Through the Family Smoking Prevention and Tobacco Control Act, the Food and Drug Administration has the potential to regulate modified risk tobacco products (MRTPs), or tobacco products that are sold or distributed for use to reduce harm or the risk of tobacco-related disease. The objective of this study is to examine young adults’ perceptions of MRTPs (electronic cigarettes and dissolvables) for cigarette smoking cessation.
e25
Methods: Eight focus groups will be conducted with a sample of 18–25 year old smokers and non-smokers attending two public colleges in Connecticut; 4 focus groups (N = 29 young adults) have been completed and four will be completed in early 2013. Groups were stratified by gender and smoking status. A standard focus group guide was used to ask participants about their knowledge of MRTPs (electronic cigarettes and dissolvables) and usefulness in smoking cessation. Group discussions were recorded, transcribed, and examined using thematic analysis. Results: Evidence collected to date indicates that smokers and non-smokers were aware of electronic cigarettes, but not dissolvables. Smokers believed that electronic cigarettes were more appealing than existing smoking cessation aids because they mimicked the act of smoking, could be flavored, and did not have widely known side effects. Many smokers experimented with electronic cigarettes and reported that they were not as satisfying as traditional cigarettes. Smokers would exclusively switch to electronic cigarettes when attempting to quit. Smokers and non-smokers did not believe dissolvables were appealing for smoking cessation because they did not mimic smoking, and did not appear tasty or pleasurable. Conclusions: Both smokers and non-smokers have high awareness of electronic cigarettes but not dissolvables. Evidence from the remaining four focus groups will also be presented. This formative qualitative data suggests that electronic cigarettes appeal to young adults as smoking cessation aids. Financial support: This work was supported by the National Institute on Drug Abuse grant P50DA009241. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.090 Smoking prevalence and exposure to second hand-smoke in Mexican pregnant women Octavio Campollo 1 , F. Hernandez 2 , E. Angulo 3 , A. Guzman 2 , I. Navarro 1 , M. García 3 , A. Munguía 1 , J.K. Cunningham 4 1 Center of Studies on Alcohol and Addictions, University of Guadalajara, Guadalajara, Mexico 2 Obstetrics, Hospital Civil Guadalajara, GDL, Mexico 3 Neonatology, Hospital Civil Guadalajara, GDL, Mexico 4 Family & Community Medicine, University of Arizona, Tucson, AZ, United States
Aims: The prevalence of smoking among women in Mexico has increased to 12.6% of the adult population. The aims were to assess the prevalence of tobacco smoking and of exposure to second hand smoke (SHS) among pregnant women in a major pre-natal care clinic in Guadalajara. Methods: Face-to-face interviews were conducted with 454 women attending the pre-natal care clinic to assess smoking and exposure to SHS. Patients found to be smokers received brief intervention and were referred to a smoking cessation program for pregnant women. Results: The patients’ mean age was 24.4 (± 7.5) years; their mean months of pregnancy was 6.7 (± 1.9). Regarding smoking, 3.0% were active smokers, while 27.5% had smoked before pregnancy. Regarding SHS, 49.5% lived on average with 1.4 (±1) smokers who smoked a mean 3.9 cigarettes in their presence. In particular, this included a husband/partner (31.0%), father (17.3%), mother (12.5%), parents in-law (6.9%), brothers (9.1%), sisters (4.0%), brothers in-law (2.5%), uncles/aunts (1.6%), and other relatives (2.5%). Outside their homes (including work), 22.5% of the women were exposed to a mean of 3.5 (±3.3) persons who consumed a daily mean of 7.9 (±9) cigarettes.