- Email: [email protected]
Smoking and trauma in Syrian refugees
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Abstracts / Drug and Alcohol Dependence 171 (2017) e2–e226
sivity to a sucrose solution (1%), or cocaine (0, 5, 10, or 20 mg/kg) place conditioning (CPP). Results: Here we show that adult mice pre-treated with ketamine during adolescence displayed enhanced preference for a sucrose solution, as well as environments previously paired with moderately low doses of cocaine, when compared to saline pretreated controls. Conclusions: Together, our findings suggest that exposure to ketamine during adolescence increases sensitivity to both natural and drug-rewards, later in life. Financial support: NIGMS (SC2GM109811). http://dx.doi.org/10.1016/j.drugalcdep.2016.08.263 Rates and correlates of syphilis reinfection among men who have sex with men in San Francisco Jennifer P. Jain 1,∗ , Glenn-Milo Santos 2 , Susan Scheer 3 , Steve Gibson 4 , Pierre-Cedric Crouch 4 , Robert Kohn 3 , Walter Chang 1 , Adam Carrico 1 1
CHS, UCSF, San Francisco, CA, United States Community Health Systems, University of California San Francisco, San Francisco, CA, United States 3 SFDPH, San Francisco, CA, United States 4 SFAF, San Francisco, CA, United States 2
Aims: In 2013, the rate of reported primary and secondary syphilis in the United States was 5.3 cases per 100,000 persons, which is more than double the rate of 2.1 in 2000. This resurgence of syphilis infection has occurred primarily among MSM. Over 83% of all primary and secondary cases of syphilis in the United States are among MSM. However, relatively little is known about the rates and correlates of syphilis reinfection in this population. Methods: From 2012 to 2013, 323 MSM received treatment for primary or secondary syphilis at a community-based clinic in San Francisco. Using clinical record data, we extracted demographic information, self-reported binge drinking in the past 30 days, and self-reported substance use in the past year. Our outcome was syphilis reinfection, defined primary or secondary syphilis infection reported to the San Francisco Department of Public Health following initial treatment. We evaluated correlates of reinfection using multivariable cox proportional hazards models. Results: The mean time to syphilis reinfection was 24.8 (SD = 7.9) months such that one in five men (71/323; 22%) were reinfected over follow-up. The rate of syphilis reinfection was greater among HIV-positive men (adjusted Hazard Ratio [aHR] = 1.84; 95% CI = 1.08–3.12) and those who reported any ketamine use in the past year (aHR = 3.99; 95% CI = 1.64–9.71). Ketamine users (n = 15) were significantly more likely to report using multiple substances in the past year (i.e., methamphetamine, cocaine, amyl nitrites, ecstasy, andgamma-hydroxybutric acid [GHB]) compared to those who did not report ketamine use (n = 317). Conclusions: Syphilis reinfection rates were high among MSM in San Francisco. Syphilis prevention efforts targeting MSM should address the unique needs of those who are HIV-positive and target substance use as a potential driver of syphilis reinfection. Financial support: UCSF, School of Nursing. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.264
Employment-based reinforcement of naltrexone adherence in unemployed heroin users: Effects on opiate use Brantley Jarvis ∗ , August Holtyn, Anthony DeFulio, Annie Umbricht, M. Fingerhood, George Bigelow, Kenneth Silverman Johns Hopkins University School of Medicine, Baltimore, MD, United States Aims: The aim of this study was to determine whether employment-based reinforcement of naltrexone adherence increased opiate abstinence. Methods: In three previously-reported randomized clinical trials with unemployed heroin users, employment-based reinforcement increased adherence to oral and extended-release naltrexone. However, effects on opiate abstinence were not significant in those within-study analyses with small per-group N’s ranging from 17 to 35. Here we analyze effects on opiate use with larger N’s by combining data from all three studies. Recently detoxified, heroin-dependent unemployed adults participated in a therapeutic workplace for 26 weeks where they could earn wages and receive job skills training. Participants were randomized to a Prescription (n = 68) or Contingency (n = 72) group. Contingency group participants were required to adhere to naltrexone to gain access to the workplace. Prescription group participants could access the workplace independent of their naltrexone adherence. Naltrexone formulation and dosing varied across trials: 3×/week (oral), 1×/3 weeks (Depotrex injection), or 1×/4 weeks (Vivitrol injection). Adherence was measured as the percentage of doses directly observed to be accepted (injection studies) or by monthly urinalysis for naltrexone (oral study). Results: Analyses showed that Contingency group participants had significantly higher rates of naltrexone adherence than Prescription group participants (78.0% vs. 35.0%) and significantly higher rates of thrice-weekly opiate-negative urine samples (missing-missing: 87.4% vs. 75.6%; missing-positive: 68.9% vs. 55.6%). Conclusions: Employment-based contingencies for adherence to naltrexone are effective and can increase opiate abstinence among unemployed heroin-dependent adults. Financial support: R01DA019386, R01DA019497, T32DA07209. Alkermes, Inc., supplied Vivitrol at no cost. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.265 Smoking and trauma in Syrian refugees Hussam Jefee-Bahloul 1,2,∗ , Mohammad Jaafar 3 1
Psychiatry – Division of Substance Use, University of Massachusetts Medical School, Boston, MA, United States 2 Psychiatry, Yale School of Medicine, New Haven, CT, United States 3 Union of Syrian Medical Relief Organizations, Reyhanli, Turkey Aims: This study is aiming to characterize smoking patterns and trauma, and to identify interest for different smoking cessation interventions in a sample of Syrian refugee smokers in Turkey. Methods: Syrian refugees recruited in this study were selfidentified as smokers. A cross-sectional assessment was done using expired Carbon monoxide (eCO), Fagerstrom Nicotine Dependence (FTND), Harvard Trauma Questionnaire, in addition to question-
Abstracts / Drug and Alcohol Dependence 171 (2017) e2–e226
naires of smoking habits and openness/motivation to quit smoking. Recruitment and data collection for this study are still ongoing. Results: Preliminary data analysis (n = 53) indicates that 35.8% of the sample fall in the Post-traumatic stress disorder (PTSD) category, and 13% of the sample reported onset of smoking after the war. The current average of cigarettes smoked a day is 25.6 cigarettes/day compared to 18 cigarettes before the war (p < 0.001). Half of the sample had an eCO level above 40 ppm, indicating severe tobacco use. Subjects with PTSD had higher scores on the FTND scale and eCO levels compared to those who are not (FTND score 5.2 vs 6.8, p < 0.05, and eCO level 45.7 ppm vs. 36.7 ppm, p = .168). On average, subjects reported 3.9 unsuccessful past quitting attempts and 2.1 successful ones. In their past attempts to quit, the sample reported use of: E-cigarettes (11%), Nicotine gum (8%), Counselling (8%), and Nicotine patch (2%). On the “Motivation To Quit Smoking scale”, 56% of the sample fell in the (strong desire and no intention) and (moderate desire and intention) categories. Finally, 73% of the sample reported having smartphones, 51% are interested in receiving SMS “text-messages, and 39% are interested in using a downloadable mobile application to help them quit smoking. Conclusions: In our sample, heavy smoking Syrian refugees are showing moderate to high levels of motivation to quit smoking and identifying psychosocial interventions delivered via mobile phones as potential venues of future research. Financial support: Study is funded by Grant R25DA033211, Research in Addiction Medicine Program. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.266 Characterization of the behavioral phenotypes underlying the reinforcing effects of cannabinoid receptor agonists in rhesus monkeys William S. John ∗ , Michael Nader Wake Forest School of Medicine, Winston-Salem, NC, United States Aims: The lack of a widespread method to establish 9 tetrahydrocannabinol (THC) self-administration (SA) remains an impediment for developing treatments for human marijuana abuse. Therefore, the major objective of this study was to establish the experimental conditions necessary for demonstrating intravenous SA of THC as well as the cannabinoid receptor (CBR) agonist CP 55,940 in rhesus monkeys. In addition, behavioral phenotypes underlying the individual differences in CBR agonist SA were characterized in order to determine critical variables that could be modified to optimize the procedure. Methods: Rhesus monkeys (n = 8), implanted with indwelling intravenous catheters, served as subjects and were trained to respond under a fixed-ratio 10 schedule of food presentation, with a 60-s timeout after each reinforcer. Once responding was stable, CP 55,940 (0.005–1.0 g/kg), THC (0.03–10 g/kg), and saline were substituted for food pellets, with each dose available for at least 5 sessions and until responding was deemed stable. There was a return to food-maintained responding between different CBR agonist doses. Results: CP 55,940 functioned as a reinforcer in three of eight rhesus monkeys at doses lower than previously tested. In those three monkeys, non-contingent administration of CP 55,940 was least potent in decreasing food-maintained responding indicating an inverse relationship between the rate-decreasing effects and reinforcing effects (r = 0.81, p < 0.05). No relationship was found between the reinforcing effects and CP 55,940-induced hypothermia nor the unconditioned behavioral effects of the dopamine
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D2/D3 receptor agonist quinpirole. THC did not maintain responding higher than vehicle in any monkey. Conclusions: These data indicate a potentially critical behavioral determinant of CBR agonist SA. Future experiments will determine if tolerance to the rate-decreasing effects of THC will enhance the reinforcing effects of THC. Such an outcome would suggest that preclinical models require a period of repeated drug treatment before assessing THC SA. Financial support: DA06634 (MAN) and T32 AA007565 (WSJ). http://dx.doi.org/10.1016/j.drugalcdep.2016.08.267 Effects of chronic amphetamine on abuse-related behavioral and neurochemical effects of cocaine in rats Amy Johnson ∗ , S. Steven Negus Virginia Commonwealth University, Richmond, VA, United States Aims: Cocaine use disorder is a major public health concern with no FDA-approved pharmacotherapies. Amphetamine maintenance is effective to decrease both cocaine self-administration in preclinical studies and metrics of cocaine use in clinical trials. The mechanisms responsible for the anti-cocaine effects of amphetamine maintenance are not well understood. Toward that end, this study evaluated abuse-related effects of cocaine in intracranial self-stimulation (ICSS) and on nucleus accumbens dopamine and serotonin (NAc DA and 5HT) levels. We hypothesize that amphetamine maintenance will decrease both cocaine-induced ICSS facilitation and enhancement of NAc DA without altering enhancement of NAc 5HT. Methods: Male Sprague-Dawley rats were used for all studies. For ICSS, electrodes were implanted in the medial forebrain bundle, and responding on a lever produced pulses of electrical brain stimulation in frequency-rate ICSS procedure. Effects of cumulative cocaine doses (1–10 mg/kg) were determined before and after 7-day treatment with saline (n = 6) or 0.32 mg/kg/hr amphetamine (n = 6) delivered by a subcutaneous osmotic minipump. Two-way ANOVA was used to compare frequency-rate curves. For microdialysis, separate groups (n = 18) of rats were implanted with cannulae targeting the NAc, and dialysates were analyzed for concentrations of DA and 5HT before and after administration of cocaine (1–10 mg/kg). Results: Cocaine facilitated ICSS and increased NAc levels of both DA and 5HT. Amphetamine maintenance produced facilitation of ICSS throughout treatment, and cocaine effects on ICSS were blunted after 7 days of amphetamine treatment. Evaluation of amphetamine maintenance effects on basal and cocainestimulated NAc DA and 5HT levels are in progress. Conclusions: Completed studies have identified conditions under which amphetamine maintenance decreases abuse-related behavioral effects of cocaine. Ongoing studies will correlate these behavioral results to amphetamine maintenance effects on abuserelated neurochemical effects of cocaine. Financial support: Supported by R01DA026946 and T32DA007027-40 from NIH. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.268
Abstracts / Drug and Alcohol Dependence 171 (2017) e2–e226
sivity to a sucrose solution (1%), or cocaine (0, 5, 10, or 20 mg/kg) place conditioning (CPP). Results: Here we show that adult mice pre-treated with ketamine during adolescence displayed enhanced preference for a sucrose solution, as well as environments previously paired with moderately low doses of cocaine, when compared to saline pretreated controls. Conclusions: Together, our findings suggest that exposure to ketamine during adolescence increases sensitivity to both natural and drug-rewards, later in life. Financial support: NIGMS (SC2GM109811). http://dx.doi.org/10.1016/j.drugalcdep.2016.08.263 Rates and correlates of syphilis reinfection among men who have sex with men in San Francisco Jennifer P. Jain 1,∗ , Glenn-Milo Santos 2 , Susan Scheer 3 , Steve Gibson 4 , Pierre-Cedric Crouch 4 , Robert Kohn 3 , Walter Chang 1 , Adam Carrico 1 1
CHS, UCSF, San Francisco, CA, United States Community Health Systems, University of California San Francisco, San Francisco, CA, United States 3 SFDPH, San Francisco, CA, United States 4 SFAF, San Francisco, CA, United States 2
Aims: In 2013, the rate of reported primary and secondary syphilis in the United States was 5.3 cases per 100,000 persons, which is more than double the rate of 2.1 in 2000. This resurgence of syphilis infection has occurred primarily among MSM. Over 83% of all primary and secondary cases of syphilis in the United States are among MSM. However, relatively little is known about the rates and correlates of syphilis reinfection in this population. Methods: From 2012 to 2013, 323 MSM received treatment for primary or secondary syphilis at a community-based clinic in San Francisco. Using clinical record data, we extracted demographic information, self-reported binge drinking in the past 30 days, and self-reported substance use in the past year. Our outcome was syphilis reinfection, defined primary or secondary syphilis infection reported to the San Francisco Department of Public Health following initial treatment. We evaluated correlates of reinfection using multivariable cox proportional hazards models. Results: The mean time to syphilis reinfection was 24.8 (SD = 7.9) months such that one in five men (71/323; 22%) were reinfected over follow-up. The rate of syphilis reinfection was greater among HIV-positive men (adjusted Hazard Ratio [aHR] = 1.84; 95% CI = 1.08–3.12) and those who reported any ketamine use in the past year (aHR = 3.99; 95% CI = 1.64–9.71). Ketamine users (n = 15) were significantly more likely to report using multiple substances in the past year (i.e., methamphetamine, cocaine, amyl nitrites, ecstasy, andgamma-hydroxybutric acid [GHB]) compared to those who did not report ketamine use (n = 317). Conclusions: Syphilis reinfection rates were high among MSM in San Francisco. Syphilis prevention efforts targeting MSM should address the unique needs of those who are HIV-positive and target substance use as a potential driver of syphilis reinfection. Financial support: UCSF, School of Nursing. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.264
Employment-based reinforcement of naltrexone adherence in unemployed heroin users: Effects on opiate use Brantley Jarvis ∗ , August Holtyn, Anthony DeFulio, Annie Umbricht, M. Fingerhood, George Bigelow, Kenneth Silverman Johns Hopkins University School of Medicine, Baltimore, MD, United States Aims: The aim of this study was to determine whether employment-based reinforcement of naltrexone adherence increased opiate abstinence. Methods: In three previously-reported randomized clinical trials with unemployed heroin users, employment-based reinforcement increased adherence to oral and extended-release naltrexone. However, effects on opiate abstinence were not significant in those within-study analyses with small per-group N’s ranging from 17 to 35. Here we analyze effects on opiate use with larger N’s by combining data from all three studies. Recently detoxified, heroin-dependent unemployed adults participated in a therapeutic workplace for 26 weeks where they could earn wages and receive job skills training. Participants were randomized to a Prescription (n = 68) or Contingency (n = 72) group. Contingency group participants were required to adhere to naltrexone to gain access to the workplace. Prescription group participants could access the workplace independent of their naltrexone adherence. Naltrexone formulation and dosing varied across trials: 3×/week (oral), 1×/3 weeks (Depotrex injection), or 1×/4 weeks (Vivitrol injection). Adherence was measured as the percentage of doses directly observed to be accepted (injection studies) or by monthly urinalysis for naltrexone (oral study). Results: Analyses showed that Contingency group participants had significantly higher rates of naltrexone adherence than Prescription group participants (78.0% vs. 35.0%) and significantly higher rates of thrice-weekly opiate-negative urine samples (missing-missing: 87.4% vs. 75.6%; missing-positive: 68.9% vs. 55.6%). Conclusions: Employment-based contingencies for adherence to naltrexone are effective and can increase opiate abstinence among unemployed heroin-dependent adults. Financial support: R01DA019386, R01DA019497, T32DA07209. Alkermes, Inc., supplied Vivitrol at no cost. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.265 Smoking and trauma in Syrian refugees Hussam Jefee-Bahloul 1,2,∗ , Mohammad Jaafar 3 1
Psychiatry – Division of Substance Use, University of Massachusetts Medical School, Boston, MA, United States 2 Psychiatry, Yale School of Medicine, New Haven, CT, United States 3 Union of Syrian Medical Relief Organizations, Reyhanli, Turkey Aims: This study is aiming to characterize smoking patterns and trauma, and to identify interest for different smoking cessation interventions in a sample of Syrian refugee smokers in Turkey. Methods: Syrian refugees recruited in this study were selfidentified as smokers. A cross-sectional assessment was done using expired Carbon monoxide (eCO), Fagerstrom Nicotine Dependence (FTND), Harvard Trauma Questionnaire, in addition to question-
Abstracts / Drug and Alcohol Dependence 171 (2017) e2–e226
naires of smoking habits and openness/motivation to quit smoking. Recruitment and data collection for this study are still ongoing. Results: Preliminary data analysis (n = 53) indicates that 35.8% of the sample fall in the Post-traumatic stress disorder (PTSD) category, and 13% of the sample reported onset of smoking after the war. The current average of cigarettes smoked a day is 25.6 cigarettes/day compared to 18 cigarettes before the war (p < 0.001). Half of the sample had an eCO level above 40 ppm, indicating severe tobacco use. Subjects with PTSD had higher scores on the FTND scale and eCO levels compared to those who are not (FTND score 5.2 vs 6.8, p < 0.05, and eCO level 45.7 ppm vs. 36.7 ppm, p = .168). On average, subjects reported 3.9 unsuccessful past quitting attempts and 2.1 successful ones. In their past attempts to quit, the sample reported use of: E-cigarettes (11%), Nicotine gum (8%), Counselling (8%), and Nicotine patch (2%). On the “Motivation To Quit Smoking scale”, 56% of the sample fell in the (strong desire and no intention) and (moderate desire and intention) categories. Finally, 73% of the sample reported having smartphones, 51% are interested in receiving SMS “text-messages, and 39% are interested in using a downloadable mobile application to help them quit smoking. Conclusions: In our sample, heavy smoking Syrian refugees are showing moderate to high levels of motivation to quit smoking and identifying psychosocial interventions delivered via mobile phones as potential venues of future research. Financial support: Study is funded by Grant R25DA033211, Research in Addiction Medicine Program. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.266 Characterization of the behavioral phenotypes underlying the reinforcing effects of cannabinoid receptor agonists in rhesus monkeys William S. John ∗ , Michael Nader Wake Forest School of Medicine, Winston-Salem, NC, United States Aims: The lack of a widespread method to establish 9 tetrahydrocannabinol (THC) self-administration (SA) remains an impediment for developing treatments for human marijuana abuse. Therefore, the major objective of this study was to establish the experimental conditions necessary for demonstrating intravenous SA of THC as well as the cannabinoid receptor (CBR) agonist CP 55,940 in rhesus monkeys. In addition, behavioral phenotypes underlying the individual differences in CBR agonist SA were characterized in order to determine critical variables that could be modified to optimize the procedure. Methods: Rhesus monkeys (n = 8), implanted with indwelling intravenous catheters, served as subjects and were trained to respond under a fixed-ratio 10 schedule of food presentation, with a 60-s timeout after each reinforcer. Once responding was stable, CP 55,940 (0.005–1.0 g/kg), THC (0.03–10 g/kg), and saline were substituted for food pellets, with each dose available for at least 5 sessions and until responding was deemed stable. There was a return to food-maintained responding between different CBR agonist doses. Results: CP 55,940 functioned as a reinforcer in three of eight rhesus monkeys at doses lower than previously tested. In those three monkeys, non-contingent administration of CP 55,940 was least potent in decreasing food-maintained responding indicating an inverse relationship between the rate-decreasing effects and reinforcing effects (r = 0.81, p < 0.05). No relationship was found between the reinforcing effects and CP 55,940-induced hypothermia nor the unconditioned behavioral effects of the dopamine
e95
D2/D3 receptor agonist quinpirole. THC did not maintain responding higher than vehicle in any monkey. Conclusions: These data indicate a potentially critical behavioral determinant of CBR agonist SA. Future experiments will determine if tolerance to the rate-decreasing effects of THC will enhance the reinforcing effects of THC. Such an outcome would suggest that preclinical models require a period of repeated drug treatment before assessing THC SA. Financial support: DA06634 (MAN) and T32 AA007565 (WSJ). http://dx.doi.org/10.1016/j.drugalcdep.2016.08.267 Effects of chronic amphetamine on abuse-related behavioral and neurochemical effects of cocaine in rats Amy Johnson ∗ , S. Steven Negus Virginia Commonwealth University, Richmond, VA, United States Aims: Cocaine use disorder is a major public health concern with no FDA-approved pharmacotherapies. Amphetamine maintenance is effective to decrease both cocaine self-administration in preclinical studies and metrics of cocaine use in clinical trials. The mechanisms responsible for the anti-cocaine effects of amphetamine maintenance are not well understood. Toward that end, this study evaluated abuse-related effects of cocaine in intracranial self-stimulation (ICSS) and on nucleus accumbens dopamine and serotonin (NAc DA and 5HT) levels. We hypothesize that amphetamine maintenance will decrease both cocaine-induced ICSS facilitation and enhancement of NAc DA without altering enhancement of NAc 5HT. Methods: Male Sprague-Dawley rats were used for all studies. For ICSS, electrodes were implanted in the medial forebrain bundle, and responding on a lever produced pulses of electrical brain stimulation in frequency-rate ICSS procedure. Effects of cumulative cocaine doses (1–10 mg/kg) were determined before and after 7-day treatment with saline (n = 6) or 0.32 mg/kg/hr amphetamine (n = 6) delivered by a subcutaneous osmotic minipump. Two-way ANOVA was used to compare frequency-rate curves. For microdialysis, separate groups (n = 18) of rats were implanted with cannulae targeting the NAc, and dialysates were analyzed for concentrations of DA and 5HT before and after administration of cocaine (1–10 mg/kg). Results: Cocaine facilitated ICSS and increased NAc levels of both DA and 5HT. Amphetamine maintenance produced facilitation of ICSS throughout treatment, and cocaine effects on ICSS were blunted after 7 days of amphetamine treatment. Evaluation of amphetamine maintenance effects on basal and cocainestimulated NAc DA and 5HT levels are in progress. Conclusions: Completed studies have identified conditions under which amphetamine maintenance decreases abuse-related behavioral effects of cocaine. Ongoing studies will correlate these behavioral results to amphetamine maintenance effects on abuserelated neurochemical effects of cocaine. Financial support: Supported by R01DA026946 and T32DA007027-40 from NIH. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.268