Glucocorticoid–endocannabinoid interactions in the prelimbic cortex mediate stress-potentiated...

e36 Abstracts / Drug and Alcohol Dependence 146 (2015) e34–e117

(AUC = .81); drugs (illicit or prescription) 84% and 89% (AUC = .86).Sensitivity was lower for prescription drugs (57%) than for illicitdrugs (78%). For detecting a substance use disorder, sensitivity andspecificity were: tobacco 100% and 73% (AUC = .87); alcohol 93% and64% (AUC = .79); drugs 85% and 82% (AUC = .84).

Conclusions: The SUBS accurately identified unhealthy tobacco,alcohol, and drug use in this primary care sample, and had high sen-sitivity but lower specificity for identifying substance use disorders.Individuals screening positive on the SUBS should receive furtherassessment. Our findings support use of the SUBS for substance usescreening in primary care, but additional tools may be needed forprescription drugs.

Financial support: NIDA K23 DA030395 NIH/NCATS UL1TR000038.

http://dx.doi.org/10.1016/j.drugalcdep.2014.09.468

Osmotic-release methylphenidate randomizedcontrolled trial for adolescents withattention-deficit/hyperactivity disorders andsubstance use disorders: A missing datasensitivity analysis

Sterling McPherson, Mary Rose Mamey, CelestinaBarbosa-Leiker, Sean M. Murphy, John Roll

Washington State University, Spokane, WA, UnitedStates

Aims: To examine sensitivity to missing data procedures ontreatment effects in a randomized controlled trial (RCT) of osmotic-release methylphenidate (OROS) for adolescents with co-occurringattention-deficit/hyperactivity disorder (ADHD) and substance usedisorders (SUD).

Methods: Data came from a National Drug Abuse TreatmentClinical Trials Network study (N = 303, Riggs et al., 2011), whichevaluated the safety/efficacy of a 16-week RCT of OROS vs. placeboin adolescents (aged 13-18) with ADHD who were also receivingcognitive behavioral therapy for their SUD. The two primary out-comes were clinician-reported ADHD symptoms and self-reportedpast 28 days of substance use (SU). We fit a parallel growthmodel and assessed the effect sizes assuming missing at random(MAR) compared to two missing not at random (MNAR) models;Diggle–Kenward (DK) selection model and Wu–Carroll (WC) selec-tion model.

Results: Our MAR model found no significant treatment effecton ADHD or SU, and the effect sizes were small for both ADHD andSU (d = 0.16, 0.10, respectively). The MNAR DK model also producednon-significant treatment effects with similar effect sizes of ADHD(d = 0.03) and SU (d = 0.11). The MNAR WC model evidenced a sig-nificant effect of OROS relative to placebo on SU, and the effect sizesfor both ADHD (d = 2.11) and SU (d = 1.09) were larger than reportedin the other models.

Conclusions: While the MAR model and one MNAR model foundsimilarly sized effects as the original RCT, the second MNAR modelproduced different results for both of the outcomes. This sensitivityanalysis highlights an important need for future RCTs of co-morbidmental illness and SUDs to carefully evaluate the missing dataassumptions made when assessing treatment effects.

Financial support: Life Science Discovery Fund (Roll, PI), NIDAClinical Trials Network Pacific Northwest Node (5 U10 DA013714-10; Donovan and Roll, Co-PIs), Pilot Study Support Program at theCenter for Advancing Longitudinal Drug Abuse Research (CALDAR;P30DA016383; McPherson, PI).

http://dx.doi.org/10.1016/j.drugalcdep.2014.09.469

Glucocorticoid–endocannabinoid interactionsin the prelimbic cortex mediatestress-potentiated reinstatement of cocaineseeking

Jayme R. McReynolds 1, Oliver Vranjkovic 1, EvanN. Graf 1, Cecilia J. Hillard 2, John R. Mantsch 1

1 Biomedical Sciences, Marquette University,Milwaukee, WI, United States2 Pharmacology & Toxicology, Medical College ofWisconsin, Milwaukee, WI, United States

Aims: Under certain self-administration conditions, stress alonedoes not reinstate cocaine seeking. However, stress, such as elec-tric footshock stress (EFS), can potentiate reinstatement whenpaired with a low dose of cocaine and this effect is corticosterone-dependent. Corticosterone (CORT) may exert its action through aninteraction with the endocannbinoid (eCB) system as cannabinoidreceptor 1 (CB1R) dependent effects on neurotransmission in themedial prefrontal cortex, a region that is critical for reinstatement,are dependent upon glucocorticoids. The current study examinedthe involvement of the CB1R, specifically in the prelimbic cortex(PLC), in stress-potentiated reinstatement of cocaine seeking.

Methods: Male Sprague–Dawley rats self-administered cocaine(0.5 mg/kg/inf) 14 × 2 h/day on a FR4 schedule. Rats underwentextinction followed by stress-potentiated reinstatement tests,EFS + low dose cocaine (2.5 mg/kg i.p.). To test the involvementof the PLC, rats were given an intra-PLC infusion of CORT(0.05 ffJg/.03 ffJL) instead of EFS 15 min prior to the low dose cocaineinjection. To test the involvement of CB1R, rats were given a sys-temic injection of the CB1R antagonist, AM251 (0, 1, 3 mg/kg i.p.)30 min prior or an intra- PLC infusion of AM251 (0, 0.3 ffJg/0.3 ffJL)15 min prior to EFS.

Results: EFS paired with a low dose of cocaine-induced rein-statement of cocaine seeking whereas either given alone didnot. This effect was mimicked when intra-PLC infusions of CORTwere paired with low dose cocaine suggesting CORT actionsin the PLC mediate stress-potentiated reinstatement. SystemicAM251 blocked stress-potentiated reinstatement. Furthermore,preliminary data suggests that intra-PLC AM251 also blocks stress-potentiated reinstatement.

Conclusions: Taken together, these data suggest that corticos-terone actions in the PLC, likely through an interaction with the eCBsystem, mediate stress-potentiated reinstatement.

Financial support: NIH grant DA015758 to John Mantsch.

http://dx.doi.org/10.1016/j.drugalcdep.2014.09.470

Transitions in polydrug use among heroin andmethamphetamine injectors in Tijuana, Mexico

Meredith C. Meacham 1,2, Karla D. Wagner 1,Timothy Mackey 1, T.L. Patterson 1, SteffanieStrathdee 1, Scott Roesch 2

1 University of California, San Diego, La Jolla, CA,United States2 San Diego State University, San Diego, CA, UnitedStates

Aims: Although most people who inject drugs (PWID) in Tijuanaprimarily inject heroin, use of methamphetamine and co-injectionof meth and heroin is also common. We examined patterns andtransitions in polydrug use to inform prevention and treatment ofdrug use and its health and social consequences.

Methods: PWID residing in Tijuana aged ≥ 18 years wererecruited through respondent driven sampling from 2006 to