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Pharmacological mechanisms underlying cardiovascular effects of 3,4-methylenedioxypyrovalerone
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Abstracts / Drug and Alcohol Dependence 171 (2017) e2–e226
Conclusions: Among women, factors associated with treatment outcome and acceptability of technology-based interventions can assist in the refinement of innovative interventions. Female patients with concomitant risk factors—primary opioids or marijuana use, higher psychological distress, or greater substance use severity—appear to have worse treatment outcomes. More research on characteristics associated with acceptability of tech-based treatment for women is needed. Financial support: NIDA UG1 DA013035, R25 DA035161. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.503 Perceived harmfulness of marijuana and risk for adolescent use: Individual and collective beliefs Aaron L. Sarvet 1,∗ , Melanie Wall 1 , Katherine Keyes 1 , Magdalena Cerda 2 , John Schulenberg 3 , Deborah Hasin 1 1
Columbia University, New York, NY, United States University of California, Davis, CA, United States 3 University of Michigan, Ann Arbor, MI, United States 2
Aims: Adolescent perceptions of the harmfulness of marijuana are related to marijuana use. Less is known about the impact that collective beliefs about harmfulness have on individual patterns of marijuana use. We explore the relationship of collective schoollevel beliefs about marijuana harmfulness to individual marijuana use. Methods: Participants were 8th (N = 313,054), 10th (N = 304,827) and 12th (N = 242,633) graders in Monitoring the Future annual surveys (1991–2014). Marijuana use (MU) was defined as any past 30-day use. Individual perceived harmfulness of occasional MU was dichotomized as little/no risk of harm vs. moderate/great risk. Collective beliefs were measured at the school level by aggregating students’ beliefs within schools, and then dichotomized at the median. Logistic regression models adjusted for individual, school and state variables, time, and the MTF complex design. Effect modification was tested with interaction terms. Results: Among 8th, 10th and 12th graders, those who perceived marijuana as having little or no risk were more likely to use marijuana (adjusted risk ratio [aRR] = 5.4–6.5; p < .01). Adjusting for individual beliefs, students in schools that collectively believed MU to pose little or no risk were also more likely to use marijuana (aRR = 1.1–1.2; p < .01). Individuals’ beliefs were stronger predictors of MU when their classmates collectively believed MU to be more harmful (pinteraction < .01). The effects of individual and collective beliefs on MU, and the interaction between these beliefs, were strongest among 8th grade students. Conclusions: Collective beliefs in the form of school-level perceptions of marijuana influenced individuals’ risks of MU beyond their own beliefs. Results suggest that group-based approaches to substance use prevention are important, and in particular, that increasing a school’s collective beliefs that MU poses harm can make interventions on an individual’s beliefs more effective. Financial support: R01DA034244, NY State Psychiatric Institute. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.504
The impact of addiction medications on outcomes for persons with co-occurring PTSD and opioid use disorders Elizabeth Saunders 1,∗ , Mark P. McGovern 2 , Chantal Lambert-Harris 2 , Andrea Meier 2 , Bethany McLeman 3 1 The Dartmouth Institute, Lebanon, NH, United States 2 Psychiatry, Dartmouth Geisel School of Medicine, Lebanon, NH, United States 3 Dartmouth Psychiatric Research Center, Lebanon, NH, United States
Aims: Previous research has been inconclusive about whether adding psychosocial treatment to medication assisted treatment (MAT) improves outcomes for patients with co-occurring psychiatric and opioid use disorders. This study evaluated the impact of MAT and psychosocial therapies for patients with co-occurring opioid use and posttraumatic stress disorders (PTSD). We hypothesized that the combination of MAT and integrated treatment would be the most effective condition for substance use and psychiatric outcomes. Methods: Patients meeting criteria for PTSD and substance use disorders were randomly assigned to one of three treatment conditions: Standard Care (SC) alone, Integrated Cognitive Behavioral Therapy (ICBT) plus SC, or Individual Addiction Counseling (IAC) plus SC. Substance and psychiatric symptoms were assessed at baseline and 6 months with urine drug screens, the Clinician Administered PTSD Scale (CAPS), and the Addiction Severity Index (ASI). Two-way ANOVAS and logistic regression analyses were used to examine associations between treatment conditions and MAT for patients with opioid use disorders and PTSD (N = 126). Results: MAT patients receiving ICBT had significantly decreased odds of positive urine drug screens, compared to non-MAT patients receiving SC alone (OR = 0.07, 95% CI = 0.01, 0.81, p = 0.03). For PTSD symptoms, a significant MAT by psychosocial treatment condition interaction (F(2, 88) = 4.74, p = 0.011) showed that MAT patients had comparable declines in PTSD symptoms regardless of psychosocial treatment type. Non-MAT patients in ICBT had significantly larger reductions in PTSD than non-MAT patients receiving IAC (p = 0.02) or TAU (p = 0.02). Conclusions: For patients with co-occurring opioid use disorders and PTSD, MAT plus ICBT is associated with more significant improvement in substance use. For non-MAT patients, ICBT may be most beneficial for PTSD symptoms. Financial support: NIDA grant R01 DA027650. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.505 Pharmacological mechanisms underlying cardiovascular effects of 3,4-methylenedioxypyrovalerone Charles W. Schindler 1,∗ , Eric Thorndike 1 , Masaki Suzuki 4 , Kenner Rice 4 , Michael Baumann 5 1 Preclinical Pharmacology Section, NIH/NIDA Intramural Research, Baltimore, MD, United States 4 Drug Design and Synthesis Section, NIH/NIDA Intramural Reserach, Baltimore, MD, United States 5 Designer Drug Unit, NIH/NIDA Intramural Reserach, Baltimore, MD, United States
Aims: MDPV is a synthetic stimulant whose mechanism of action involves blockade of monoamine transporters similar to
Abstracts / Drug and Alcohol Dependence 171 (2017) e2–e226
cocaine. Like cocaine, MDPV has potent cardiovascular effects that can lead to untoward medical complications and even death. The aim of the current study was to examine the pharmacological mechanisms leading to MDPV’s cardiovascular effects. Methods: Male Sprague-Dawley rats received surgicallyimplanted telemetry transmitters for the measurement of blood pressure (BP) and heart rate (HR). Rats were injected with s.c. drug or vehicle and placed in an isolation cubicle on top of a telemetry receiver which detected cardiovascular parameters for 3 h sessions. Results: Racemic MDPV produced dose-dependent (0.3–3.0 mg/kg) increases in BP and HR. Over the same dose range, the (+) isomer of MDPV produced effects that were similar to the racemate, while the (−) isomer did not. Neither of the hydroxylated phase I metabolites of MDPV produced increases in BP or HR. Pretreatment with the ganglionic blocker chlorisondamine (1–3 mg/kg) antagonized the increases in both BP and HR. The alpha-adrenergic antagonist prazosin (0.3 mg/kg) antagonized BP responses following MDPV while the beta-adrenergic antagonist propranolol (1 mg/kg) antagonized the HR responses. Conclusions: The cardiovascular effects of MDPV seem to mediated by the (+) isomer, and the metabolites of MDPV do not appear to contribute to its cardiovascular effects. MDPV produces increases in BP and HR as a result of increases in central sympathetic outflow. Treatment with adrenergic antagonists, particularly mixed-action alpha/beta receptor antagonists, may be useful in counteracting the adverse cardiovascular effects of MDPV in emergency situations. Financial support: Supported by IRP, NIDA, NIH, DHHS. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.506 A behavioral and neurophysiological examination of the impact of smoking abstinence on drug and non-drug reinforcement Nicolas Schlienz 1,2,∗ , Larry Hawk 2 1 Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, United States 2 Psychology, State University of New York at Buffalo, Amherst, NY, United States
Aims: Prominent models of drug addiction suggest that abstinence increases the value of drug reinforcement and decreases the value of non-drug reinforcement. To address gaps in the literature, the present study provided independent tests of both hypotheses using behavioral and neurophysiological outcomes in the context of a cognitive task. Methods: Adult smokers (n = 36; ≥10 cigarettes per day) attended two laboratory visits, one following overnight abstinence and during regular smoking. In each visit, participants completed a flanker task in three reinforcement conditions: cigarette, money, and no reinforcement (control). Speeded accuracy and the errorrelated negativity (ERN) were analyzed with separate repeated measures ANOVA. Results: Compared to no reinforcement, cigarette and money reinforcement each increased accuracy and ERN amplitude (all ps ≤ .10). Smoking abstinence reduced speeded accuracy and ERN amplitude only among participants tested with a more challenging RT deadline (ps < .05). Most importantly, the impact of drug reinforcement was enhanced during abstinence for accuracy (p < .10) but not the ERN; there was no evidence that non-drug reinforcement (money) was diminished during abstinence (all ps > .20). Conclusions: The present study extended prior work suggesting abstinence increases drug reinforcement to a cognitively demand-
e185
ing context and to a neurophysiological index of performance monitoring (the ERN). We conclude that the reinforcing effects of money are not attenuated by abstinence, but recognize that abstinence may affect other non-drug reinforcers differently. Financial support: The University at Buffalo’s Mark Diamond Research Fund and Research Institute on Addictions. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.507 A pilot study of the feasibility and potential effectiveness of using smartphones to provide recovery support Christy K. Scott 1,∗ , Michael L. Dennis 1 , David Gustafson 2 , Kimberly Johnson 2 1 Lighthouse Institute, Chestnut Health Systems, Chicago, IL, United States 2 CHESS, University of Wisconsin, Madison, WI, United States
Aims: Smartphone applications can potentially provide recovery monitoring and support in real-time, real-life contexts. Study aims included determining feasibility using smartphones to: (a) teach self-monitoring through ecological momentary assessments (EMA), (b) provided recovery support through phone-based ecological momentary interventions (EMI); and (c) Use EMA and EMI data to predict substance use in the subsequent week. Methods: Data are from 52 adolescents (40%) and adults (60%) recruited at or after discharge (54% within 3 months) who were 65% African American, and 52% Male. During the 6-week pilot, participants were prompted to complete an EMA at 6 random times per day and were provided continuous access to the Addiction Comprehensive Health Enhancement Support System (ACHESS) suite of recovery support EMI. Over 90% of the targeted EMA were completed and EMI were accessed an average of 23.2 times per day. Using 5892 EMA observations with a week or more of additional observations after them, we used survival analysis to predict the time to first use. These observations were categorized based on whether they included a report of current use (6%), past week use (27%), or no past week use (67%) and based on whether the participant used the EMI within the hour (17%) or not (83%). These are true repeated measure with all participants being in multiple groups. Results: When compared to current use observations, the rate of use in the next week was significantly lower for those who had only used in the past week (98% vs. 89%, OR = .20) or who had not used (98% vs. 22%, OR = .01), as well as for those who used EMI (vs not) within the hour (45% vs. 33%, OR = 0.67). There was an interaction with the largest effect being for use of EMI within the no past week group (24% vs. 14%, OR = .63). Conclusions: Results demonstrate the feasibility and promise of using smart- phones for recovery monitoring and support. Financial support: NIDA grant DA035879, DA11323 & R01 DA021174. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.508
Abstracts / Drug and Alcohol Dependence 171 (2017) e2–e226
Conclusions: Among women, factors associated with treatment outcome and acceptability of technology-based interventions can assist in the refinement of innovative interventions. Female patients with concomitant risk factors—primary opioids or marijuana use, higher psychological distress, or greater substance use severity—appear to have worse treatment outcomes. More research on characteristics associated with acceptability of tech-based treatment for women is needed. Financial support: NIDA UG1 DA013035, R25 DA035161. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.503 Perceived harmfulness of marijuana and risk for adolescent use: Individual and collective beliefs Aaron L. Sarvet 1,∗ , Melanie Wall 1 , Katherine Keyes 1 , Magdalena Cerda 2 , John Schulenberg 3 , Deborah Hasin 1 1
Columbia University, New York, NY, United States University of California, Davis, CA, United States 3 University of Michigan, Ann Arbor, MI, United States 2
Aims: Adolescent perceptions of the harmfulness of marijuana are related to marijuana use. Less is known about the impact that collective beliefs about harmfulness have on individual patterns of marijuana use. We explore the relationship of collective schoollevel beliefs about marijuana harmfulness to individual marijuana use. Methods: Participants were 8th (N = 313,054), 10th (N = 304,827) and 12th (N = 242,633) graders in Monitoring the Future annual surveys (1991–2014). Marijuana use (MU) was defined as any past 30-day use. Individual perceived harmfulness of occasional MU was dichotomized as little/no risk of harm vs. moderate/great risk. Collective beliefs were measured at the school level by aggregating students’ beliefs within schools, and then dichotomized at the median. Logistic regression models adjusted for individual, school and state variables, time, and the MTF complex design. Effect modification was tested with interaction terms. Results: Among 8th, 10th and 12th graders, those who perceived marijuana as having little or no risk were more likely to use marijuana (adjusted risk ratio [aRR] = 5.4–6.5; p < .01). Adjusting for individual beliefs, students in schools that collectively believed MU to pose little or no risk were also more likely to use marijuana (aRR = 1.1–1.2; p < .01). Individuals’ beliefs were stronger predictors of MU when their classmates collectively believed MU to be more harmful (pinteraction < .01). The effects of individual and collective beliefs on MU, and the interaction between these beliefs, were strongest among 8th grade students. Conclusions: Collective beliefs in the form of school-level perceptions of marijuana influenced individuals’ risks of MU beyond their own beliefs. Results suggest that group-based approaches to substance use prevention are important, and in particular, that increasing a school’s collective beliefs that MU poses harm can make interventions on an individual’s beliefs more effective. Financial support: R01DA034244, NY State Psychiatric Institute. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.504
The impact of addiction medications on outcomes for persons with co-occurring PTSD and opioid use disorders Elizabeth Saunders 1,∗ , Mark P. McGovern 2 , Chantal Lambert-Harris 2 , Andrea Meier 2 , Bethany McLeman 3 1 The Dartmouth Institute, Lebanon, NH, United States 2 Psychiatry, Dartmouth Geisel School of Medicine, Lebanon, NH, United States 3 Dartmouth Psychiatric Research Center, Lebanon, NH, United States
Aims: Previous research has been inconclusive about whether adding psychosocial treatment to medication assisted treatment (MAT) improves outcomes for patients with co-occurring psychiatric and opioid use disorders. This study evaluated the impact of MAT and psychosocial therapies for patients with co-occurring opioid use and posttraumatic stress disorders (PTSD). We hypothesized that the combination of MAT and integrated treatment would be the most effective condition for substance use and psychiatric outcomes. Methods: Patients meeting criteria for PTSD and substance use disorders were randomly assigned to one of three treatment conditions: Standard Care (SC) alone, Integrated Cognitive Behavioral Therapy (ICBT) plus SC, or Individual Addiction Counseling (IAC) plus SC. Substance and psychiatric symptoms were assessed at baseline and 6 months with urine drug screens, the Clinician Administered PTSD Scale (CAPS), and the Addiction Severity Index (ASI). Two-way ANOVAS and logistic regression analyses were used to examine associations between treatment conditions and MAT for patients with opioid use disorders and PTSD (N = 126). Results: MAT patients receiving ICBT had significantly decreased odds of positive urine drug screens, compared to non-MAT patients receiving SC alone (OR = 0.07, 95% CI = 0.01, 0.81, p = 0.03). For PTSD symptoms, a significant MAT by psychosocial treatment condition interaction (F(2, 88) = 4.74, p = 0.011) showed that MAT patients had comparable declines in PTSD symptoms regardless of psychosocial treatment type. Non-MAT patients in ICBT had significantly larger reductions in PTSD than non-MAT patients receiving IAC (p = 0.02) or TAU (p = 0.02). Conclusions: For patients with co-occurring opioid use disorders and PTSD, MAT plus ICBT is associated with more significant improvement in substance use. For non-MAT patients, ICBT may be most beneficial for PTSD symptoms. Financial support: NIDA grant R01 DA027650. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.505 Pharmacological mechanisms underlying cardiovascular effects of 3,4-methylenedioxypyrovalerone Charles W. Schindler 1,∗ , Eric Thorndike 1 , Masaki Suzuki 4 , Kenner Rice 4 , Michael Baumann 5 1 Preclinical Pharmacology Section, NIH/NIDA Intramural Research, Baltimore, MD, United States 4 Drug Design and Synthesis Section, NIH/NIDA Intramural Reserach, Baltimore, MD, United States 5 Designer Drug Unit, NIH/NIDA Intramural Reserach, Baltimore, MD, United States
Aims: MDPV is a synthetic stimulant whose mechanism of action involves blockade of monoamine transporters similar to
Abstracts / Drug and Alcohol Dependence 171 (2017) e2–e226
cocaine. Like cocaine, MDPV has potent cardiovascular effects that can lead to untoward medical complications and even death. The aim of the current study was to examine the pharmacological mechanisms leading to MDPV’s cardiovascular effects. Methods: Male Sprague-Dawley rats received surgicallyimplanted telemetry transmitters for the measurement of blood pressure (BP) and heart rate (HR). Rats were injected with s.c. drug or vehicle and placed in an isolation cubicle on top of a telemetry receiver which detected cardiovascular parameters for 3 h sessions. Results: Racemic MDPV produced dose-dependent (0.3–3.0 mg/kg) increases in BP and HR. Over the same dose range, the (+) isomer of MDPV produced effects that were similar to the racemate, while the (−) isomer did not. Neither of the hydroxylated phase I metabolites of MDPV produced increases in BP or HR. Pretreatment with the ganglionic blocker chlorisondamine (1–3 mg/kg) antagonized the increases in both BP and HR. The alpha-adrenergic antagonist prazosin (0.3 mg/kg) antagonized BP responses following MDPV while the beta-adrenergic antagonist propranolol (1 mg/kg) antagonized the HR responses. Conclusions: The cardiovascular effects of MDPV seem to mediated by the (+) isomer, and the metabolites of MDPV do not appear to contribute to its cardiovascular effects. MDPV produces increases in BP and HR as a result of increases in central sympathetic outflow. Treatment with adrenergic antagonists, particularly mixed-action alpha/beta receptor antagonists, may be useful in counteracting the adverse cardiovascular effects of MDPV in emergency situations. Financial support: Supported by IRP, NIDA, NIH, DHHS. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.506 A behavioral and neurophysiological examination of the impact of smoking abstinence on drug and non-drug reinforcement Nicolas Schlienz 1,2,∗ , Larry Hawk 2 1 Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, United States 2 Psychology, State University of New York at Buffalo, Amherst, NY, United States
Aims: Prominent models of drug addiction suggest that abstinence increases the value of drug reinforcement and decreases the value of non-drug reinforcement. To address gaps in the literature, the present study provided independent tests of both hypotheses using behavioral and neurophysiological outcomes in the context of a cognitive task. Methods: Adult smokers (n = 36; ≥10 cigarettes per day) attended two laboratory visits, one following overnight abstinence and during regular smoking. In each visit, participants completed a flanker task in three reinforcement conditions: cigarette, money, and no reinforcement (control). Speeded accuracy and the errorrelated negativity (ERN) were analyzed with separate repeated measures ANOVA. Results: Compared to no reinforcement, cigarette and money reinforcement each increased accuracy and ERN amplitude (all ps ≤ .10). Smoking abstinence reduced speeded accuracy and ERN amplitude only among participants tested with a more challenging RT deadline (ps < .05). Most importantly, the impact of drug reinforcement was enhanced during abstinence for accuracy (p < .10) but not the ERN; there was no evidence that non-drug reinforcement (money) was diminished during abstinence (all ps > .20). Conclusions: The present study extended prior work suggesting abstinence increases drug reinforcement to a cognitively demand-
e185
ing context and to a neurophysiological index of performance monitoring (the ERN). We conclude that the reinforcing effects of money are not attenuated by abstinence, but recognize that abstinence may affect other non-drug reinforcers differently. Financial support: The University at Buffalo’s Mark Diamond Research Fund and Research Institute on Addictions. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.507 A pilot study of the feasibility and potential effectiveness of using smartphones to provide recovery support Christy K. Scott 1,∗ , Michael L. Dennis 1 , David Gustafson 2 , Kimberly Johnson 2 1 Lighthouse Institute, Chestnut Health Systems, Chicago, IL, United States 2 CHESS, University of Wisconsin, Madison, WI, United States
Aims: Smartphone applications can potentially provide recovery monitoring and support in real-time, real-life contexts. Study aims included determining feasibility using smartphones to: (a) teach self-monitoring through ecological momentary assessments (EMA), (b) provided recovery support through phone-based ecological momentary interventions (EMI); and (c) Use EMA and EMI data to predict substance use in the subsequent week. Methods: Data are from 52 adolescents (40%) and adults (60%) recruited at or after discharge (54% within 3 months) who were 65% African American, and 52% Male. During the 6-week pilot, participants were prompted to complete an EMA at 6 random times per day and were provided continuous access to the Addiction Comprehensive Health Enhancement Support System (ACHESS) suite of recovery support EMI. Over 90% of the targeted EMA were completed and EMI were accessed an average of 23.2 times per day. Using 5892 EMA observations with a week or more of additional observations after them, we used survival analysis to predict the time to first use. These observations were categorized based on whether they included a report of current use (6%), past week use (27%), or no past week use (67%) and based on whether the participant used the EMI within the hour (17%) or not (83%). These are true repeated measure with all participants being in multiple groups. Results: When compared to current use observations, the rate of use in the next week was significantly lower for those who had only used in the past week (98% vs. 89%, OR = .20) or who had not used (98% vs. 22%, OR = .01), as well as for those who used EMI (vs not) within the hour (45% vs. 33%, OR = 0.67). There was an interaction with the largest effect being for use of EMI within the no past week group (24% vs. 14%, OR = .63). Conclusions: Results demonstrate the feasibility and promise of using smart- phones for recovery monitoring and support. Financial support: NIDA grant DA035879, DA11323 & R01 DA021174. http://dx.doi.org/10.1016/j.drugalcdep.2016.08.508