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Arrest for violent offenses in early adulthood: Predictions from prenatal and adolescent cocaine exposure
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Abstracts / Drug and Alcohol Dependence 140 (2014) e169–e251
Results: Given the heavy drinking style reported in this sample, the reported negative consequences were relatively low overall. Surprisingly, frequency of drinking days (past 30) was unrelated to any of the five InDUC subscales (r = .15, p < .19) and frequency of binge drinking days (past 30) was only significantly related to one of the five subscales on the InDUC-2R, physical consequences (r = .23, p < .04). Furthermore, there were no significant gender differences on any of the five InDUC subscales of negative consequences. Conclusions: The absence of a clear relationship between alcohol consumption and negative consequences is surprising given the binge style of drinking among our sample. Further qualitative research may help elucidate this lack of relationship and inform future substance use interventions meant to decrease health disparities for Native Americans. Financial support: Supported by NIDA R01-021672. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.646 Conditioned taste aversion predicts morphine, but not cocaine, self-administration: A role of drug aversion in drug-taking Andrey Verendeev, B.J. Tunstall, D.N. Kearns, A.L. Riley Psychology, American University, Washington, DC, United States Aims: Drugs of abuse are complex pharmacological compounds that have rewarding and aversive effects, both of which should be taken into account when modeling drug-taking behavior. Drug reward has been well implicated in drug use; however, the role of drug aversion has not been systematically examined. The present studies assessed the ability of conditioned place preferences (CPP) and conditioned taste aversions (CTA) to predict morphine and cocaine self-administration. Methods: Rats were first trained in a combined CTA/CPP procedure with either morphine (5 mg/kg) or cocaine (20 mg/kg). They were then trained to press a lever for intravenous morphine (0.56 mg/kg) or cocaine (0.75 mg/kg). The strength of both CTAs and CPPs was then examined in relation to subsequent drug selfadministration. Results: There was a significant relationship between the magnitude of CTA ( = 0.517; p < 0.05) but not CPP ( = −0.330; p > 0.05) and the number of morphine infusions taken. There was also a significant difference between high and low CTA responders in the number of morphine infusions taken (high < low; t(12) = −3.493; p < 0.01). There was no difference between the high and low CPP responders in the number of morphine infusions (t(12) = −0.179; p > 0.05). There was no significant relationship between the magnitude of CTA ( = −0.110; p > 0.05) or CPP ( = −0.053; p > 0.05) and number of cocaine infusions. There was also no significant difference between high and low CTA responders (t(12) = 0.833; p > 0.05) or high and low CPP responders (t(12) = −0.106; p > 0.05) in number of cocaine infusions taken. Conclusions: The aversive effects of morphine, but not cocaine, predict drug self-administration, suggesting that drug aversion should be taken into account in modeling drug taking. These results also add to the literature showing that opiates and psychostimulants differ on a number of behavioral, physiological and neurochemical measures. Financial support: Supported by grants from the Mellon Foundation to AV and ALR and from NIDA grant R01DA008651 to DNK. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.647
Fatty acid amide hydrolase gene variant influences acute responses to cocaine Christopher D. Verrico 1 , D.A. Nielsen 1 , C.J. Spellicy 1 , S.C. Hamon 2 , T.R. Kosten 1 , Thomas F. Newton 1 , Richard De La Garza Ii 1 1 Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine & Michael E. DeBakey V.A. Medical Center, Houston, TX, United States 2 Laboratory of Statistical Genetics, The Rockefeller University, New York, NY, United States
Aims: The endocannabinoid system mediates the effects of cannabis and influences responses to cocaine. The activities of several endocannabinoid receptor ligands are, in part, terminated by fatty acid amide hydrolase (FAAH). The common variant rs324420C/A, within the FAAH gene on chromosome 1, codes for a missense substitution (Pro129Thr). The rs324420 AA genotype increases the risk for substance use disorders. We hypothesized that the FAAH Pro129Thr variant would affect cocaine-induced subjective effects. Methods: Non-treatment seeking cocaine-dependent volunteers received placebo and cocaine (0 and 40 mg, IV; randomized). Visual analog scale (VAS) forms, which were used to rate cocaineinduced subjective effects on a scale from 0 (no effect) to 100 (strongest ever), were completed 15 min before (baseline) and 5, 10, 15, and 20 min after infusions. DNA was genotyped for the FAAH rs324420 variant. Results were corrected for population structure. Data was analyzed using repeated measures ANOVA. Results: On average, the participants (N = 47) were 44-yearold black (68%) men (87%) who smoked (94%) 2.2 g of cocaine per day. There were 18 CC, 14 AC, and 15 AA genotypes. FAAH rs324420 was associated with differential ratings of “Stimulated” (p = 8.89 × 10−6 ) and “Good Effects” (p = 2.70 × 10−4 ) following cocaine administration. Conclusions: This study suggests that in cocaine-dependent individuals the variant rs324420, which may lead to increased endocannabinoid levels, influences subjective responses to cocaine. Thus, medications that alter levels or activity of FAAH may decrease the rewarding effects of cocaine and have potential therapeutic efficacy for cocaine dependence. Financial support: NIH/NIDA SUPPORT: DA018197 (TRK); DA023624 (RDLG); DA018197 (TFN); DA026120 (DAN). This work was conducted at, and supported by the Michael E. DeBakey VA Medical Center, Houston, TX. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.648 Arrest for violent offenses in early adulthood: Predictions from prenatal and adolescent cocaine exposure Denise C. Vidot 1,2 , Veronica H. Accornero 2 , L. Xue 2 , J.C. Anthony 3 , E.S. Bandstra 2 1 Epidemiology & Public Health, University of Miami Miller School of Medicine, Miami, FL, United States 2 Pediatrics, University of Miami Miller School of Medicine, Miami, FL, United States 3 Epidemiology & Biostatistics, Michigan State University, East Lansing, MI, United States
Aims: To estimate single and combined effects of prenatal cocaine exposure (PCE) and adolescent cocaine exposure (ACE) on occurrence of arrest for violent offenses in early adulthood.
Abstracts / Drug and Alcohol Dependence 140 (2014) e169–e251
Methods: Data are from a large, well-retained urban, low socioeconomic status sample of 378 full-term African American infants (195 PCE, 183 non-PCE) who were enrolled prospectively at birth in the longitudinal Miami Prenatal Cocaine Study (MPCS) and were currently residing in Florida at the 18/19 year followup visit. PCE was assessed via maternal self-report and toxicology assays in maternal urine and infant urine and meconium. ACE was assessed by toxicology assays only. Arrests for violent offenses in early adulthood were based on search of official Florida arrest records. Estimates are presented, with and without consideration of other sources of variation such as prenatal exposure to alcohol, marijuana, and tobacco, and caregiver arrest record. Results: Estimates from stratified analyses found arrests for violent offenses in early adulthood for an estimated 22% of males with neither PCE nor ACE versus 46% for males with both PCE and ACE (p < 0.05); corresponding estimates for females were 14% and 23%, respectively (p > 0.05). The male risk ratio for combined PCE and ACE associated occurrence of arrest for violent offenses of approximately 2.0 (p < 0.05) did not change appreciably with covariate adjustments for other prenatal drug exposures and caregiver arrest record. Conclusions: PCE combined with ACE was robustly predictive of arrests for violent offenses, especially in young adult males. Limitations of adolescent self-report are constrained via focus on toxicological assays and official arrest statistics. Financial support: NIH National Institute on Drug Abuse and Office of Research on Women’s Health (ORWH): R01DA006556 (ESB); P50DA024584 (ESB); P50DA024584-S4 (ESB; DCV); K01DA016720 (VHA); K05DA15799 (JCA). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.649 Use of synthetic drugs among people who inject drugs in San Diego, CA Karla D. Wagner, J. Cuevas-Mota, R.F. Armenta, Steffanie Strathdee, R.S. Garfein University of California San Diego, San Diego, CA, United States Aims: Public concern over hospitalizations and poisonings attributed to the use of synthetic cathinones (SC; aka “Bath Salts”) and THC homologues (TH; e.g., Spice) have resulted in calls for a greater understanding of the epidemiology of their use. Methods: From June to October 2012 we surveyed persons who inject drugs (PWID) in San Diego about their lifetime use of SC and TH, as part of an ongoing cohort study. We hypothesized that users of SC and TH would display different demographic and drug use profiles. Results: Among 221 PWID enrolled to date, 15 (7%) and 69 (31%) reported lifetime use of SC and TH, respectively. Twenty percent of TH users also used SC. SC users were slightly younger and more frequently male and white than TH users. Most first used these drugs within the past year. Compared to non-users, SC users and TH users were significantly younger (p < 0.01) and more likely to report recent use of other drugs including: marijuana (TH only, p < 0.01), drug mixtures (p < 0.05), methamphetamine (TH only; p < 0.05), hallucinogens or inhalants (p < 0.05), club drugs (p < 0.05), and prescription drugs (p < 0.05). Curiosity was the main reason for use of synthetic drugs (60% SC, 47% TH); other reasons included wanting to avoid testing positive on a drug test (13% SC, 12% TH), greater availability (13% SC, 8% TH), and as a substitute for marijuana (9% TH only). Most were obtained from friends or purchased at gas stations/convenience stores; none reported obtaining the drugs via the Internet. No SC users and one TH
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user reported hospitalization due to using the drug. Two-thirds of SC users think SC is legal and 72% of TH users think TH is legal. Conclusions: Findings suggest that over one-third of surveyed PWIDs have used emerging synthetic drugs. Users may be characterized by different demographic and drug use profiles than other PWIDs and have largely obtained drugs through social contacts or convenience stores. Despite CA legislation passed in 2011 banning these drugs, most users think they are legal. Users may require interventions tailored to use of multiple substances. Financial support: NIH K01DA031031, R01DA031074. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.650 Attenuation of rate-frequency intracranial self-stimulation during nicotine withdrawal in rats D.M. Walentiny, K.M. Tobey, L.S. Harris Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, VA, United States Aims: Affective consequences of nicotine withdrawal are known to influence the high rate of recidivism in abstinent smokers. In humans, this affective withdrawal syndrome consists of anxiety, anhedonia, irritability, and other symptoms suggestive of decrements in brain reward function. In laboratory animals, drug effects on reward can be examined using intracranial self-stimulation (ICSS). Whereas many abused drugs facilitate responding reinforced by direct electrical stimulation of the mesolimbic dopaminergic reward pathway, several studies have indicated that withdrawal from a chronically administered drug (e.g., nicotine) results in an attenuation of ICSS-maintained responding. The goal of the present study was to model rewardrelated deficits during nicotine withdrawal using a rate-frequency ICSS procedure and examine their duration. Methods: Male Sprague Dawley rats were implanted with electrodes aimed at the medial forebrain bundle and trained in a rate-frequency ICSS paradigm, where they responded through a series of decreasing stimulation frequencies. Once behavior stabilized, subjects were implanted with osmotic minipumps containing either 3 mg/kg/day nicotine or saline (N = 8/group). Mecamylamine-precipitated withdrawal and spontaneous withdrawal tests were conducted 7 and 12–15 days after minipump implant, respectively. Withdrawal effects were operationally defined as rightward shifts in ICSS rate-frequency curves and increases in thresholds relative to baseline. Results: In rats receiving nicotine, mecamylamine produced a rightward shift in the rate-frequency response curve and a trend towards increased reward thresholds. Significant spontaneous withdrawal effects were seen at various times during the first three days of nicotine withdrawal. Thresholds were unaltered during any withdrawal tests in the saline group. Conclusions: These results indicate that under these conditions, nicotine withdrawal decreases brain reward function over the course of several days, with maximal effects observed approximately 2 and 24 h post-withdrawal. Financial support: Support provided by NIDA contract N01DA128904 to LSH. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.651
Abstracts / Drug and Alcohol Dependence 140 (2014) e169–e251
Results: Given the heavy drinking style reported in this sample, the reported negative consequences were relatively low overall. Surprisingly, frequency of drinking days (past 30) was unrelated to any of the five InDUC subscales (r = .15, p < .19) and frequency of binge drinking days (past 30) was only significantly related to one of the five subscales on the InDUC-2R, physical consequences (r = .23, p < .04). Furthermore, there were no significant gender differences on any of the five InDUC subscales of negative consequences. Conclusions: The absence of a clear relationship between alcohol consumption and negative consequences is surprising given the binge style of drinking among our sample. Further qualitative research may help elucidate this lack of relationship and inform future substance use interventions meant to decrease health disparities for Native Americans. Financial support: Supported by NIDA R01-021672. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.646 Conditioned taste aversion predicts morphine, but not cocaine, self-administration: A role of drug aversion in drug-taking Andrey Verendeev, B.J. Tunstall, D.N. Kearns, A.L. Riley Psychology, American University, Washington, DC, United States Aims: Drugs of abuse are complex pharmacological compounds that have rewarding and aversive effects, both of which should be taken into account when modeling drug-taking behavior. Drug reward has been well implicated in drug use; however, the role of drug aversion has not been systematically examined. The present studies assessed the ability of conditioned place preferences (CPP) and conditioned taste aversions (CTA) to predict morphine and cocaine self-administration. Methods: Rats were first trained in a combined CTA/CPP procedure with either morphine (5 mg/kg) or cocaine (20 mg/kg). They were then trained to press a lever for intravenous morphine (0.56 mg/kg) or cocaine (0.75 mg/kg). The strength of both CTAs and CPPs was then examined in relation to subsequent drug selfadministration. Results: There was a significant relationship between the magnitude of CTA ( = 0.517; p < 0.05) but not CPP ( = −0.330; p > 0.05) and the number of morphine infusions taken. There was also a significant difference between high and low CTA responders in the number of morphine infusions taken (high < low; t(12) = −3.493; p < 0.01). There was no difference between the high and low CPP responders in the number of morphine infusions (t(12) = −0.179; p > 0.05). There was no significant relationship between the magnitude of CTA ( = −0.110; p > 0.05) or CPP ( = −0.053; p > 0.05) and number of cocaine infusions. There was also no significant difference between high and low CTA responders (t(12) = 0.833; p > 0.05) or high and low CPP responders (t(12) = −0.106; p > 0.05) in number of cocaine infusions taken. Conclusions: The aversive effects of morphine, but not cocaine, predict drug self-administration, suggesting that drug aversion should be taken into account in modeling drug taking. These results also add to the literature showing that opiates and psychostimulants differ on a number of behavioral, physiological and neurochemical measures. Financial support: Supported by grants from the Mellon Foundation to AV and ALR and from NIDA grant R01DA008651 to DNK. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.647
Fatty acid amide hydrolase gene variant influences acute responses to cocaine Christopher D. Verrico 1 , D.A. Nielsen 1 , C.J. Spellicy 1 , S.C. Hamon 2 , T.R. Kosten 1 , Thomas F. Newton 1 , Richard De La Garza Ii 1 1 Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine & Michael E. DeBakey V.A. Medical Center, Houston, TX, United States 2 Laboratory of Statistical Genetics, The Rockefeller University, New York, NY, United States
Aims: The endocannabinoid system mediates the effects of cannabis and influences responses to cocaine. The activities of several endocannabinoid receptor ligands are, in part, terminated by fatty acid amide hydrolase (FAAH). The common variant rs324420C/A, within the FAAH gene on chromosome 1, codes for a missense substitution (Pro129Thr). The rs324420 AA genotype increases the risk for substance use disorders. We hypothesized that the FAAH Pro129Thr variant would affect cocaine-induced subjective effects. Methods: Non-treatment seeking cocaine-dependent volunteers received placebo and cocaine (0 and 40 mg, IV; randomized). Visual analog scale (VAS) forms, which were used to rate cocaineinduced subjective effects on a scale from 0 (no effect) to 100 (strongest ever), were completed 15 min before (baseline) and 5, 10, 15, and 20 min after infusions. DNA was genotyped for the FAAH rs324420 variant. Results were corrected for population structure. Data was analyzed using repeated measures ANOVA. Results: On average, the participants (N = 47) were 44-yearold black (68%) men (87%) who smoked (94%) 2.2 g of cocaine per day. There were 18 CC, 14 AC, and 15 AA genotypes. FAAH rs324420 was associated with differential ratings of “Stimulated” (p = 8.89 × 10−6 ) and “Good Effects” (p = 2.70 × 10−4 ) following cocaine administration. Conclusions: This study suggests that in cocaine-dependent individuals the variant rs324420, which may lead to increased endocannabinoid levels, influences subjective responses to cocaine. Thus, medications that alter levels or activity of FAAH may decrease the rewarding effects of cocaine and have potential therapeutic efficacy for cocaine dependence. Financial support: NIH/NIDA SUPPORT: DA018197 (TRK); DA023624 (RDLG); DA018197 (TFN); DA026120 (DAN). This work was conducted at, and supported by the Michael E. DeBakey VA Medical Center, Houston, TX. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.648 Arrest for violent offenses in early adulthood: Predictions from prenatal and adolescent cocaine exposure Denise C. Vidot 1,2 , Veronica H. Accornero 2 , L. Xue 2 , J.C. Anthony 3 , E.S. Bandstra 2 1 Epidemiology & Public Health, University of Miami Miller School of Medicine, Miami, FL, United States 2 Pediatrics, University of Miami Miller School of Medicine, Miami, FL, United States 3 Epidemiology & Biostatistics, Michigan State University, East Lansing, MI, United States
Aims: To estimate single and combined effects of prenatal cocaine exposure (PCE) and adolescent cocaine exposure (ACE) on occurrence of arrest for violent offenses in early adulthood.
Abstracts / Drug and Alcohol Dependence 140 (2014) e169–e251
Methods: Data are from a large, well-retained urban, low socioeconomic status sample of 378 full-term African American infants (195 PCE, 183 non-PCE) who were enrolled prospectively at birth in the longitudinal Miami Prenatal Cocaine Study (MPCS) and were currently residing in Florida at the 18/19 year followup visit. PCE was assessed via maternal self-report and toxicology assays in maternal urine and infant urine and meconium. ACE was assessed by toxicology assays only. Arrests for violent offenses in early adulthood were based on search of official Florida arrest records. Estimates are presented, with and without consideration of other sources of variation such as prenatal exposure to alcohol, marijuana, and tobacco, and caregiver arrest record. Results: Estimates from stratified analyses found arrests for violent offenses in early adulthood for an estimated 22% of males with neither PCE nor ACE versus 46% for males with both PCE and ACE (p < 0.05); corresponding estimates for females were 14% and 23%, respectively (p > 0.05). The male risk ratio for combined PCE and ACE associated occurrence of arrest for violent offenses of approximately 2.0 (p < 0.05) did not change appreciably with covariate adjustments for other prenatal drug exposures and caregiver arrest record. Conclusions: PCE combined with ACE was robustly predictive of arrests for violent offenses, especially in young adult males. Limitations of adolescent self-report are constrained via focus on toxicological assays and official arrest statistics. Financial support: NIH National Institute on Drug Abuse and Office of Research on Women’s Health (ORWH): R01DA006556 (ESB); P50DA024584 (ESB); P50DA024584-S4 (ESB; DCV); K01DA016720 (VHA); K05DA15799 (JCA). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.649 Use of synthetic drugs among people who inject drugs in San Diego, CA Karla D. Wagner, J. Cuevas-Mota, R.F. Armenta, Steffanie Strathdee, R.S. Garfein University of California San Diego, San Diego, CA, United States Aims: Public concern over hospitalizations and poisonings attributed to the use of synthetic cathinones (SC; aka “Bath Salts”) and THC homologues (TH; e.g., Spice) have resulted in calls for a greater understanding of the epidemiology of their use. Methods: From June to October 2012 we surveyed persons who inject drugs (PWID) in San Diego about their lifetime use of SC and TH, as part of an ongoing cohort study. We hypothesized that users of SC and TH would display different demographic and drug use profiles. Results: Among 221 PWID enrolled to date, 15 (7%) and 69 (31%) reported lifetime use of SC and TH, respectively. Twenty percent of TH users also used SC. SC users were slightly younger and more frequently male and white than TH users. Most first used these drugs within the past year. Compared to non-users, SC users and TH users were significantly younger (p < 0.01) and more likely to report recent use of other drugs including: marijuana (TH only, p < 0.01), drug mixtures (p < 0.05), methamphetamine (TH only; p < 0.05), hallucinogens or inhalants (p < 0.05), club drugs (p < 0.05), and prescription drugs (p < 0.05). Curiosity was the main reason for use of synthetic drugs (60% SC, 47% TH); other reasons included wanting to avoid testing positive on a drug test (13% SC, 12% TH), greater availability (13% SC, 8% TH), and as a substitute for marijuana (9% TH only). Most were obtained from friends or purchased at gas stations/convenience stores; none reported obtaining the drugs via the Internet. No SC users and one TH
e235
user reported hospitalization due to using the drug. Two-thirds of SC users think SC is legal and 72% of TH users think TH is legal. Conclusions: Findings suggest that over one-third of surveyed PWIDs have used emerging synthetic drugs. Users may be characterized by different demographic and drug use profiles than other PWIDs and have largely obtained drugs through social contacts or convenience stores. Despite CA legislation passed in 2011 banning these drugs, most users think they are legal. Users may require interventions tailored to use of multiple substances. Financial support: NIH K01DA031031, R01DA031074. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.650 Attenuation of rate-frequency intracranial self-stimulation during nicotine withdrawal in rats D.M. Walentiny, K.M. Tobey, L.S. Harris Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, VA, United States Aims: Affective consequences of nicotine withdrawal are known to influence the high rate of recidivism in abstinent smokers. In humans, this affective withdrawal syndrome consists of anxiety, anhedonia, irritability, and other symptoms suggestive of decrements in brain reward function. In laboratory animals, drug effects on reward can be examined using intracranial self-stimulation (ICSS). Whereas many abused drugs facilitate responding reinforced by direct electrical stimulation of the mesolimbic dopaminergic reward pathway, several studies have indicated that withdrawal from a chronically administered drug (e.g., nicotine) results in an attenuation of ICSS-maintained responding. The goal of the present study was to model rewardrelated deficits during nicotine withdrawal using a rate-frequency ICSS procedure and examine their duration. Methods: Male Sprague Dawley rats were implanted with electrodes aimed at the medial forebrain bundle and trained in a rate-frequency ICSS paradigm, where they responded through a series of decreasing stimulation frequencies. Once behavior stabilized, subjects were implanted with osmotic minipumps containing either 3 mg/kg/day nicotine or saline (N = 8/group). Mecamylamine-precipitated withdrawal and spontaneous withdrawal tests were conducted 7 and 12–15 days after minipump implant, respectively. Withdrawal effects were operationally defined as rightward shifts in ICSS rate-frequency curves and increases in thresholds relative to baseline. Results: In rats receiving nicotine, mecamylamine produced a rightward shift in the rate-frequency response curve and a trend towards increased reward thresholds. Significant spontaneous withdrawal effects were seen at various times during the first three days of nicotine withdrawal. Thresholds were unaltered during any withdrawal tests in the saline group. Conclusions: These results indicate that under these conditions, nicotine withdrawal decreases brain reward function over the course of several days, with maximal effects observed approximately 2 and 24 h post-withdrawal. Financial support: Support provided by NIDA contract N01DA128904 to LSH. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.651