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Do alcohol-focused interventions reduce marijuana use in mandated college students?
Abstract / Drug and Alcohol Dependence 156 (2015) e183–e245
days of consecutive abstinence during treatment and positively associated with reductions in negative affect during treatment. Conclusions: These data suggest neurofunctional differences related to treatment outcomes between individuals with cocaine dependence with and without methadone treatment, which may relate to differences in the efficacies of existing treatments. Financial support: This research was supported by NIH grants from NIDA (P50 DA009241, R01 DA030058). SWY receives support from DA007238-23 (PI: Petrakis). http://dx.doi.org/10.1016/j.drugalcdep.2015.07.653 Eye tracking measures of attentional bias to individually-calibrated marijuana cues Jin H. Yoon ∗ , Anka Vujanovic, Mike Weaver, Robert Suchting, C. Green, Joy Schmitz, Scott D. Lane Psychiatry and Behavioral Sciences, University of Texas Health Science Center – Houston, Houston, TX, United States Aims: The aim of this ongoing study is to examine eye-tracking based measurement of AB in individuals with cannabis use disorder (CUD) using cues calibrated to individual subject reactivity, and examine correlations among AB, stress, and CUD-severity. Methods: Twenty-five subjects (12 female) who met DSM-5 criteria for CUD were first exposed to MJ and matched neutral pictures. Measures of pupillary, cardiovascular, respiratory, and subjective reactivity were acquired and scored as a composite. For each subject, 6 high-reactivity MJ pictures and 6 low-reactivity neutral pictures were then used in AB testing. AB testing utilized eye-tracking methodology in a pro-saccade (look at) and antisaccade (look away from) test paradigm. AB was defined as the number of anti-saccade errors (MJ vs. neutral). Results: The reactivity score for MJ pictures was greater than for neutral pictures (p < .001). Subjects made more anti-saccade errors on MJ vs. neutral trials (p = .001). There were no differences in errors on pro-saccade trials (p = .687), and no significant associations among AB and measures of CUD severity or stress. Conclusions: Eye tracking-based measurement of reactivity to MJ cues, using individually-calibrated stimuli, provides a sensitive index of AB to MJ stimuli. AB is not related currently to stress or CUD severity. The measurement system is amenable to repeated measures and pharmacological interventions for drug-cue reactivity. Financial support: NIH/NIDA grants R21 034825 and P50 09262. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.654 A rapidly changing recreational drug market: Findings from the Canadian Community Epidemiology network on drug use Matthew M. Young Canadian Centre on Substance Abuse, Ottawa, ON, Canada Aims: Since 2000, the recreational psychoactive drug market has undergone unprecedented changes. Abuse of prescription drugs and the introduction of many new synthetic drugs, has blurred the line between illicit and non-illicit drug use. These changes have made monitoring emerging drug use trends challenging. In response, the Canadian Centre on Substance Abuse
e243
developed the Canadian Community Epidemiology Network on Drug Use (CCENDU), a sentinel surveillence, early warning system. We will present information on the new and emerging drugpatterns and trends in Canada using data from the network. Methods: Between June, 2012 and September, 2014, a variety of leading-edge indicators were collected from CCENDU sites across Canada. Information was analyzed in real-time and CCENDU notifications were issued on drug-related topics of significance to public health. Information was also analysed to identify overarching themes/trends. Results: Ongoing surveillence and analysis of data led to eight CCENDU notifications being issued on the following: an amphetamine type stimulant colloquially referred to as “bath-salts”, the misuse of opioids in Canadian communities; nonpharmaceutical fentanyl, unconfirmed reports of desomorphine (“Krocodil”), recreational use of bupropion, abuse of counterfeit oxycodone tablets containing fentanyl, synthetic cannabinoids, and drug overdoses at music festivals. In addition, analysis revealed three overall trends/themes in the data: (1) the emergence of new psychoactive substances, (2) adulteration of heroin, (3) abuse of pharmaceutical agents. Conclusions: Themes identified support the assertion that the Canadian illicit drug market is rapidly changing. Unlike The United States and Europe, Canada has no national early warning system designed to detect new drugs and new drug use trends. The results suggest that the CCENDU surveillance system can reliably function to detect drug-related adverse events and alert stakeholders to new trends in drug use, however there is a need to strengthen and expand its capabilities. Financial support: CCSA is supported through a financial contribution from Health Canada. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.655 Do alcohol-focused interventions reduce marijuana use in mandated college students? Ali Yurasek 2,∗ , Anne Fernandez 2 , Mary Beth Miller 2 , Jane Metrik 1 , Brian Borsari 2 1
Behavioral and Social Sciences, Brown University, Providence, RI, United States 2 Public Health, Brown University, Providence, RI, United States Aims: Marijuana use among college students is highly prevalent and associated with poorer academic outcomes. Although brief motivational interventions (BMIs) have been shown to be efficacious with reducing alcohol use in college students, little is known about the utility of alcohol BMIs in reducing other addictive behaviors, such as marijuana use, that often co-occur with drinking. The purpose of the current study was to examine the impact of alcohol-focused BMIs implemented within a stepped care approach in reducing marijuana use. Methods: Participants were 530 college students who violated campus alcohol policy and were mandated to receive an alcoholfocused brief advice (BA) session. Of the 530 participants, 39% (N = 208) reported baseline marijuana use and were included in the current analyses. Participants who reported continued risky alcohol use (4 or more heavy drinking episodes and/or 5 or more alcohol-related problems in the past month) six weeks following the BA session were randomized to BMI (n = 92) or assessment only (n = 90). Follow-up assessments were conducted 3, 6, and 9 months post-intervention. Results: Repeated measures ANOVA revealed that students did not reduce their frequency of marijuana use following a BA session,
e244
Abstract / Drug and Alcohol Dependence 156 (2015) e183–e245
nor did the BMI significantly reduce marijuana use compared to the assessment-only group. Conclusions: Despite reductions in alcohol use, marijuana use did not change following alcohol-focused intervention efforts. This suggests that marijuana users can still benefit from alcohol-related interventions yet may need a more intense and targeted marijuana focused intervention to induce changes in marijuana use. Financial support: Ali Yurasek’s contribution to this manuscript was supported by the National Institute on Drug Abuse grant T32 DA016184. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.656 Problematic pregabalin and gabapentin use: Results from the Canada Vigilance Adverse Reaction Online Database M. Zhang 1,2,∗ , Beth Sproule 1,2 1
Centre for Addiction and Mental Health, Toronto, ON, Canada 2 University of Toronto, Toronto, ON, Canada
Aims: Pregabalin and gabapentin are increasingly used gammaaminobutyric acid (GABA) analogues indicated for the treatment of anxiety, seizures, and neuropathic pain. Both are being investigated as treatments for opioid, alcohol, and benzodiazepine withdrawal and dependence. Analyses of adverse drug reaction registries in Germany and Sweden have demonstrated problematic pregabalin use since 2008. The aim of this study was to evaluate trends and characteristics of reports of problematic pregabalin or gabapentin use in Canada. Methods: A search for adverse effects suspected to have been caused by pregabalin and gabapentin was completed using the Canada Vigilance Adverse Reaction Online Database (1965–30 June 2014). Adverse effects are classified by the Medical Dictionary for Regulatory Activities (MedDRA) v.17.0. Reports listing terms suggesting problematic gabapentinoid use (i.e., Drug abuse, Euphoric mood, Drug dependence, Intentional drug misuse) or possible problematic use [i.e., (Drug) withdrawal syndrome, Drug tolerance (increased)] were evaluated. Cases of Intentional drug overdose were reviewed separately. Results: The total number of unique cases suggesting problematic use of pregabalin was 48 (earliest 2006), and for gabapentin was 18 (earliest 2003). Where data was available, results showed that problematic users of pregabalin were predominantly female (65.1%), mean age 52 ± 15 years, with mean daily doses interpreted as 552 mg/day (range 25–3750 mg/day), and concurrent use of other psychoactive substances in 56% of cases (opioids in 41% of cases). Problematic users of gabapentin also tended to be female (78%), mean age 54 ± 16 years, with mean daily doses interpreted as 1650 mg/day (range 300–4200 mg/day), and concurrent use of psychoactive substances in 78% of cases (opioids in 67% of cases). Intentional drug overdose was reported in 4 cases with pregabalin and 6 cases with gabapentin. Conclusions: Problematic use of pregabalin and gabapentin has been reported in Canada since 2003 and 2006, respectively. Financial support: None. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.657
Retinoic acid signaling in the nucleus accumbens: A novel mechanism controlling addiction-related behavior Yafang Zhang 2,∗ , Elizabeth Crofton 2 , D. Li 2 , X. Fan 2 , Thomas Green 1 1
UTMB, Galveston, TX, United States University of Texas Medical Branch, Galveston, TX, United States 2
Aims: Previous research has shown that environmental enrichment produces a protective addiction phenotype. A next generation RNA sequencing study in our lab revealed that retinoic acid (RA) signaling pathway was significantly regulated in the nucleus accumbens (NAc) of rats by environmental enrichment. It is known that RA signaling pathway plays an important role in brain development and homeostasis. However, the role of RA pathway in addiction is not clear. CYP26b1 is an essential enzyme responsible for RA degradation, the lack of which leads to increased RA signal in brain. Therefore, the purpose of this project is to investigate the behavioral response of rats with CYP26b1 knocked down in the NAc shell in cocaine self-administration. Methods: Twenty-four Sprague Dawley rats were injected with either an adeno-associated virus (AAV) expressing CYP26b1 shRNA or AAV expressing a non-targeted hairpin in the NAc shell. After three weeks, spontaneous locomotor activity was tested in a 2 h session. Before the cocaine self-administration study rats were first placed in a two-lever operant chamber and allowed to respond for sucrose pellets. Following sucrose responding, rats self-administered cocaine in acquisition, maintenance responding (dose–response), extinction and reinstatement. Results: Our results demonstrate that rats with CYP26b1 knockdown in the NAc shell exhibited higher spontaneous locomotor activity. In cocaine self-administration, knocking down CYP26b1 enhanced acquisition of low dose of cocaine and increased extinction responding. In addition, CYP26b1 knockdown showed leftward and an upward shift in dose response curve compared to control rats. Ongoing experiments are testing cocaine induced reinstatement. Conclusions: Increasing RA signaling in the NAc shell produces a susceptible addiction phenotype. Thus, decreased retinoic acid signaling may underlie the protective phenotype of environmental enrichment. Financial support: These experiments were funded by NIDA and supported by DA 029091. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.658 The effect of 1-substitution on tetrahydroisoquinolines as selective antagonists for the Orexin-1 receptor Yanan Zhang 1,∗ , David A. Perrey 1 , Nadezhda A. German 1 , Ann M. Decker 1 , David Thorn 2 , Jun-Xu Li 2 , Brian P. Gilmour 1 , B.F. Thomas 1 , Danni L. Harris 1 , Scott P. Runyon 1 1
Research Triangle Institute, Research Triangle Park, NC, United States 2 Pharmacology and Toxicology, University at Buffalo, Buffalo, NY, United States Aims: Selective blockade of the Orexin-1 receptor has been suggested as a potential approach to drug addiction therapy because of its role in modulating the brain’s reward system. We have recently reported a series of OX1 selective antagonists based on the tetrahydroisoquinoline scaffold, the core structure in both the dual
days of consecutive abstinence during treatment and positively associated with reductions in negative affect during treatment. Conclusions: These data suggest neurofunctional differences related to treatment outcomes between individuals with cocaine dependence with and without methadone treatment, which may relate to differences in the efficacies of existing treatments. Financial support: This research was supported by NIH grants from NIDA (P50 DA009241, R01 DA030058). SWY receives support from DA007238-23 (PI: Petrakis). http://dx.doi.org/10.1016/j.drugalcdep.2015.07.653 Eye tracking measures of attentional bias to individually-calibrated marijuana cues Jin H. Yoon ∗ , Anka Vujanovic, Mike Weaver, Robert Suchting, C. Green, Joy Schmitz, Scott D. Lane Psychiatry and Behavioral Sciences, University of Texas Health Science Center – Houston, Houston, TX, United States Aims: The aim of this ongoing study is to examine eye-tracking based measurement of AB in individuals with cannabis use disorder (CUD) using cues calibrated to individual subject reactivity, and examine correlations among AB, stress, and CUD-severity. Methods: Twenty-five subjects (12 female) who met DSM-5 criteria for CUD were first exposed to MJ and matched neutral pictures. Measures of pupillary, cardiovascular, respiratory, and subjective reactivity were acquired and scored as a composite. For each subject, 6 high-reactivity MJ pictures and 6 low-reactivity neutral pictures were then used in AB testing. AB testing utilized eye-tracking methodology in a pro-saccade (look at) and antisaccade (look away from) test paradigm. AB was defined as the number of anti-saccade errors (MJ vs. neutral). Results: The reactivity score for MJ pictures was greater than for neutral pictures (p < .001). Subjects made more anti-saccade errors on MJ vs. neutral trials (p = .001). There were no differences in errors on pro-saccade trials (p = .687), and no significant associations among AB and measures of CUD severity or stress. Conclusions: Eye tracking-based measurement of reactivity to MJ cues, using individually-calibrated stimuli, provides a sensitive index of AB to MJ stimuli. AB is not related currently to stress or CUD severity. The measurement system is amenable to repeated measures and pharmacological interventions for drug-cue reactivity. Financial support: NIH/NIDA grants R21 034825 and P50 09262. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.654 A rapidly changing recreational drug market: Findings from the Canadian Community Epidemiology network on drug use Matthew M. Young Canadian Centre on Substance Abuse, Ottawa, ON, Canada Aims: Since 2000, the recreational psychoactive drug market has undergone unprecedented changes. Abuse of prescription drugs and the introduction of many new synthetic drugs, has blurred the line between illicit and non-illicit drug use. These changes have made monitoring emerging drug use trends challenging. In response, the Canadian Centre on Substance Abuse
e243
developed the Canadian Community Epidemiology Network on Drug Use (CCENDU), a sentinel surveillence, early warning system. We will present information on the new and emerging drugpatterns and trends in Canada using data from the network. Methods: Between June, 2012 and September, 2014, a variety of leading-edge indicators were collected from CCENDU sites across Canada. Information was analyzed in real-time and CCENDU notifications were issued on drug-related topics of significance to public health. Information was also analysed to identify overarching themes/trends. Results: Ongoing surveillence and analysis of data led to eight CCENDU notifications being issued on the following: an amphetamine type stimulant colloquially referred to as “bath-salts”, the misuse of opioids in Canadian communities; nonpharmaceutical fentanyl, unconfirmed reports of desomorphine (“Krocodil”), recreational use of bupropion, abuse of counterfeit oxycodone tablets containing fentanyl, synthetic cannabinoids, and drug overdoses at music festivals. In addition, analysis revealed three overall trends/themes in the data: (1) the emergence of new psychoactive substances, (2) adulteration of heroin, (3) abuse of pharmaceutical agents. Conclusions: Themes identified support the assertion that the Canadian illicit drug market is rapidly changing. Unlike The United States and Europe, Canada has no national early warning system designed to detect new drugs and new drug use trends. The results suggest that the CCENDU surveillance system can reliably function to detect drug-related adverse events and alert stakeholders to new trends in drug use, however there is a need to strengthen and expand its capabilities. Financial support: CCSA is supported through a financial contribution from Health Canada. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.655 Do alcohol-focused interventions reduce marijuana use in mandated college students? Ali Yurasek 2,∗ , Anne Fernandez 2 , Mary Beth Miller 2 , Jane Metrik 1 , Brian Borsari 2 1
Behavioral and Social Sciences, Brown University, Providence, RI, United States 2 Public Health, Brown University, Providence, RI, United States Aims: Marijuana use among college students is highly prevalent and associated with poorer academic outcomes. Although brief motivational interventions (BMIs) have been shown to be efficacious with reducing alcohol use in college students, little is known about the utility of alcohol BMIs in reducing other addictive behaviors, such as marijuana use, that often co-occur with drinking. The purpose of the current study was to examine the impact of alcohol-focused BMIs implemented within a stepped care approach in reducing marijuana use. Methods: Participants were 530 college students who violated campus alcohol policy and were mandated to receive an alcoholfocused brief advice (BA) session. Of the 530 participants, 39% (N = 208) reported baseline marijuana use and were included in the current analyses. Participants who reported continued risky alcohol use (4 or more heavy drinking episodes and/or 5 or more alcohol-related problems in the past month) six weeks following the BA session were randomized to BMI (n = 92) or assessment only (n = 90). Follow-up assessments were conducted 3, 6, and 9 months post-intervention. Results: Repeated measures ANOVA revealed that students did not reduce their frequency of marijuana use following a BA session,
e244
Abstract / Drug and Alcohol Dependence 156 (2015) e183–e245
nor did the BMI significantly reduce marijuana use compared to the assessment-only group. Conclusions: Despite reductions in alcohol use, marijuana use did not change following alcohol-focused intervention efforts. This suggests that marijuana users can still benefit from alcohol-related interventions yet may need a more intense and targeted marijuana focused intervention to induce changes in marijuana use. Financial support: Ali Yurasek’s contribution to this manuscript was supported by the National Institute on Drug Abuse grant T32 DA016184. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.656 Problematic pregabalin and gabapentin use: Results from the Canada Vigilance Adverse Reaction Online Database M. Zhang 1,2,∗ , Beth Sproule 1,2 1
Centre for Addiction and Mental Health, Toronto, ON, Canada 2 University of Toronto, Toronto, ON, Canada
Aims: Pregabalin and gabapentin are increasingly used gammaaminobutyric acid (GABA) analogues indicated for the treatment of anxiety, seizures, and neuropathic pain. Both are being investigated as treatments for opioid, alcohol, and benzodiazepine withdrawal and dependence. Analyses of adverse drug reaction registries in Germany and Sweden have demonstrated problematic pregabalin use since 2008. The aim of this study was to evaluate trends and characteristics of reports of problematic pregabalin or gabapentin use in Canada. Methods: A search for adverse effects suspected to have been caused by pregabalin and gabapentin was completed using the Canada Vigilance Adverse Reaction Online Database (1965–30 June 2014). Adverse effects are classified by the Medical Dictionary for Regulatory Activities (MedDRA) v.17.0. Reports listing terms suggesting problematic gabapentinoid use (i.e., Drug abuse, Euphoric mood, Drug dependence, Intentional drug misuse) or possible problematic use [i.e., (Drug) withdrawal syndrome, Drug tolerance (increased)] were evaluated. Cases of Intentional drug overdose were reviewed separately. Results: The total number of unique cases suggesting problematic use of pregabalin was 48 (earliest 2006), and for gabapentin was 18 (earliest 2003). Where data was available, results showed that problematic users of pregabalin were predominantly female (65.1%), mean age 52 ± 15 years, with mean daily doses interpreted as 552 mg/day (range 25–3750 mg/day), and concurrent use of other psychoactive substances in 56% of cases (opioids in 41% of cases). Problematic users of gabapentin also tended to be female (78%), mean age 54 ± 16 years, with mean daily doses interpreted as 1650 mg/day (range 300–4200 mg/day), and concurrent use of psychoactive substances in 78% of cases (opioids in 67% of cases). Intentional drug overdose was reported in 4 cases with pregabalin and 6 cases with gabapentin. Conclusions: Problematic use of pregabalin and gabapentin has been reported in Canada since 2003 and 2006, respectively. Financial support: None. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.657
Retinoic acid signaling in the nucleus accumbens: A novel mechanism controlling addiction-related behavior Yafang Zhang 2,∗ , Elizabeth Crofton 2 , D. Li 2 , X. Fan 2 , Thomas Green 1 1
UTMB, Galveston, TX, United States University of Texas Medical Branch, Galveston, TX, United States 2
Aims: Previous research has shown that environmental enrichment produces a protective addiction phenotype. A next generation RNA sequencing study in our lab revealed that retinoic acid (RA) signaling pathway was significantly regulated in the nucleus accumbens (NAc) of rats by environmental enrichment. It is known that RA signaling pathway plays an important role in brain development and homeostasis. However, the role of RA pathway in addiction is not clear. CYP26b1 is an essential enzyme responsible for RA degradation, the lack of which leads to increased RA signal in brain. Therefore, the purpose of this project is to investigate the behavioral response of rats with CYP26b1 knocked down in the NAc shell in cocaine self-administration. Methods: Twenty-four Sprague Dawley rats were injected with either an adeno-associated virus (AAV) expressing CYP26b1 shRNA or AAV expressing a non-targeted hairpin in the NAc shell. After three weeks, spontaneous locomotor activity was tested in a 2 h session. Before the cocaine self-administration study rats were first placed in a two-lever operant chamber and allowed to respond for sucrose pellets. Following sucrose responding, rats self-administered cocaine in acquisition, maintenance responding (dose–response), extinction and reinstatement. Results: Our results demonstrate that rats with CYP26b1 knockdown in the NAc shell exhibited higher spontaneous locomotor activity. In cocaine self-administration, knocking down CYP26b1 enhanced acquisition of low dose of cocaine and increased extinction responding. In addition, CYP26b1 knockdown showed leftward and an upward shift in dose response curve compared to control rats. Ongoing experiments are testing cocaine induced reinstatement. Conclusions: Increasing RA signaling in the NAc shell produces a susceptible addiction phenotype. Thus, decreased retinoic acid signaling may underlie the protective phenotype of environmental enrichment. Financial support: These experiments were funded by NIDA and supported by DA 029091. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.658 The effect of 1-substitution on tetrahydroisoquinolines as selective antagonists for the Orexin-1 receptor Yanan Zhang 1,∗ , David A. Perrey 1 , Nadezhda A. German 1 , Ann M. Decker 1 , David Thorn 2 , Jun-Xu Li 2 , Brian P. Gilmour 1 , B.F. Thomas 1 , Danni L. Harris 1 , Scott P. Runyon 1 1
Research Triangle Institute, Research Triangle Park, NC, United States 2 Pharmacology and Toxicology, University at Buffalo, Buffalo, NY, United States Aims: Selective blockade of the Orexin-1 receptor has been suggested as a potential approach to drug addiction therapy because of its role in modulating the brain’s reward system. We have recently reported a series of OX1 selective antagonists based on the tetrahydroisoquinoline scaffold, the core structure in both the dual