Changes in attentional bias to drug cues and fMRI Stroop with behavioral treatment for cocaine dependence

s / Drug and Alcohol Dependence 146 (2015) e202–e284 e265 Is opioid dose a strong predictor of the risk of opioid overdose? Important confounding factors that change the dose–overdose relationship Angela DeVeaugh-Geiss, Paul Coplan, Aditi Kadakia, Howard Chilcoat Purdue Pharma LP, Stamford, CT, United States Aims: Recent studies have reported higher opioid overdose risk at higher opioid doses, and have been used to suggest employing restrictions on patient access to analgesic doses >100mg/day morphine equivalent dose (MED). However, these studies did not explore thedose–risk relationship above100mg/dayMEDor adjust for several potential confounders, e.g., use of immediate-release vs. extended-release opioids, which have different indications, use of sedative/hypnotics (SH), andpsychiatric or substance use disorders (SAD). Therefore, we assessed the opioid dose–overdose relationship adjusting for these variables across the range of opioid doses used in clinical practice. Methods: Adults with a new opioid dispensing were identified in theMarketScanCommercial dataset (01/2008–03/2012) and were followed until first of: overdose (ICD-9-CM codes: 965.00, 965.02, 965.09), insurance enrolment discontinuation, or end of study period. Daily opioid exposure and person-years (PY) for all patients was categorized (1–19 to >350mg/day MED). Results: In 9.6million individuals dispensed a new opioid, 3224 cases of overdose were identified during 14 million PY, including 585,000 PY of opioid exposure, 90% at 350mg/day). The crude RR for >350mg/day vs. 1–19mg/day was 8.37 (95%CI 6.18, 11.33) while the adjusted RRwas 2.05 (1.46, 2.88). The adjustedmodel included strong predictors of overdose (opioid type, SH use, age, psychiatric diagnoses, SAD) and gender. In the adjusted model, the highest risk of overdose was observed at 50–99mg/day vs. 1–19mg/day (incidence rate =2.80 [2.34, 3.34]; risk did not increase significantly above 100mg/day. Conclusions: These results suggest that opioid dose is not a strong independent predictor of overdose risk, while other factors are. Restricting patient access to <100mg/day MEDmay not be the best criterion to enhance the benefit-risk ratio of opioid use in the community. Financial support: Purdue Pharma LP. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.186 Changes in attentional bias to drug cues and fMRI Stroop with behavioral treatment for cocaine dependence Elise E. DeVito, Charla Nich, Marc N. Potenza, Kathleen M. Carroll Yale, New Haven, CT, United States Aims: Poor cognitive control and attentional bias to drug cues may contribute to the maintenance of substance use disorders. Cognitive behavioral therapy may exert its effects in part through targeting these processes. Methods: Cocaine-dependent individuals were randomized to 8-weeks of outpatient treatment as usual (TAU) or TAU plus computer based cognitive behavioral therapy (CBT4CBT). At preand post-treatment, participants completed an out-of-scanner Drug Stroop – a measure of attentional bias to drug-related stimuli. A subset also completed a functional magnetic resonance imaging (fMRI) Color-Word Stroop, a measure of cognitive control. Results: Participants (N=61) had diminishedDrug Stroop Effect (less slowing to drug vs neutral) at postvs pre-treatment. A treatment X trial type X time interaction indicatedmore change in Drug StroopEffect inCBT4CBTvs TAU frompretopost-treatment.When splitting participants by whether they attained 3+ weeks continuous abstinence during treatment, a similar interaction indicated patients who achieved longer abstinence changed more in Drug Stroop Effect from preto post-treatment. Pre-treatment fMRI Color–Word Stroop correlatedwith cocaine use during treatment (N=24). Stroop-related activitywas higher at prevs. post-treatment in regions implicated in cognitive control. Conclusions: Drug Stroop findingswere consistentwith diminished attentional bias to drug-related stimuli following treatment, particularly among individuals who received CBT4CBT or achieved 3+ weeks abstinence. fMRI Stroop results of diminished Strooprelated activity at postvs pre-treatment replicated our previous findings andmay indicate improved efficiency of cognitive-control processes following treatment. Pre-treatment fMRI Stroop correlations with within-treatment cocaine use were consistent with relevance of cognitive control to treatment success. These findings suggest CBT4CBT and TAU may differentially affect cognitive control (including attentional bias to drug stimuli), which may relate to clinical outcomes. Financial support: R01-015969, P50 DA 09241, K12 DA031050 from NIDA, ORWH, OD, NIAAA. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.187 Cardiovascular safety of ibudilast treatment with intravenous methamphetamine administration Dustin DeYoung1, Keith G. Heinzerling1, Aimee-Noelle Swanson2, John Tsuang3, Ben Furst3, Yi Yi4, Yian Nian Wu4, Steven Shoptaw1 1 Family Medicine, UCLA, Los Angeles, CA, United States 2 Psychiatry, Stanford University, Stanford, CA, United States 3 Psychiatry, Harbor-UCLA Medical Center, Torrance, CA, United States 4 Statistics, UCLA, Los Angeles, CA, United States Aims: Methamphetamine (MA) dependence causes devastating personal and public health consequences. While there are effective behavioral therapies, no effective pharmacotherapy exists at this time. Combination treatment would likely reduce the growing public health burden. Given knownMA-related cognitive dysfunction/degeneration, we tested a novel approach to pharmacologic treatment via suppression of MA-induced glial activation. We assessed the safety and tolerability of intravenous MA administration during treatment with ibudilast, a modulator of CNS glial activation. Methods: Non-treatment seeking MA dependent volunteers (N=11) were hospitalized in an inpatient research unit for 28 days during which they received intravenous MA (0mg, 15mg, or 30mg) during treatment with ibudilast (20mg BID and 50mg BID) and placebo using a randomized double-blind, placebo-controlled within-subjects crossover design. Peak change in heart rate and blood pressure following MA infusion under each ibudilast dose as well as reported adverse events were compared. Results: There were no significant main effects for ibudilast on peak change in heart rate, systolic, or diastolic blood pressure