Attention-deficit/hyperactivity disorder adversely impacts everyday functioning in chronic methamphetamine users

s / Drug and Alcohol Dependence 140 (2014) e86–e168 e165 as this is essential to develop age-appropriate and gender-sensitive prevention strategies. Financial support: The National Institute on Health 5T32DA007238-22 (Petrakis), P50DA033945 (ORWH and NIDA; McKee). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.463 Attention-deficit/hyperactivity disorder adversely impacts everyday functioning in chronic methamphetamine users Lisa C. Obermeit, J.E. Cattie, K. Bolden, M. Marquine, Erin E. Morgan, D. Franklin, I. Grant, S.P. Woods Psychiatry, University of California, San Diego, San Diego, CA, United States Aims: Methamphetamine (MA) use commonly accompanied by significant clinical disabilities, the severity which is associated with neurocognitive impairment, polysubstance use, and psychiatric comorbidity (e.g., depression). One previously unstudied psychiatric comorbidity that may be particularly relevant to real-world functional outcomes among MA users is AttentionDeficit/Hyperactivity Disorder (ADHD), which is independently associated with a wide range of problems in everyday functioning. Methods: In the current study, we evaluated 400 individuals with DSM-IV diagnoses of MA use disorders within 18 months of evaluation who completed a comprehensive neuropsychiatric and medical research battery. 21% (n=83) of the MA subjects met lifetime diagnostic criteria for ADHD (13% with current diagnoses) as determined by structured clinical interview. All participants completed self-reportmeasures of everyday functioning, including declines in instrumental activities of daily living (IADL), cognitive complaints, and employment status. Results: Separate regressions predicting the three everyday functioning outcomes from ADHD group, along with important co-factors (i.e., demographics, depression, other substance use disorders, and regency of MA use) were significant at the omnibus level (p’s < .01). Examination of individual predictors in thesemodels revealed that ADHD diagnoses were uniquely associated with greater concurrent risk of declines in IADL, elevated cognitive complaints, and unemployment (p’s < .01). Conclusions: Findings indicate that ADHD may play an important role in MA-associated disability in a wide range of real-world activities, whichmay reflect increased comorbidity burden on neurocognitive abilties, premorbid risk factors, and/or psychosocial competencies in already vulnerable chronic MA users. Efforts to screen for and treat ADHD in individuals withMA dependencemay help to improve real-world outcomes. Financial support: This research was supported by National Institutes of Health grants P01DA12065, P50DA026306, T32DA031098 and P30MH62512. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.464 Subsecond dopamine release in cannabinoid tolerance Erik B. Oleson, A. Ranganath, M. Karamsetty, J. Cheer Neurobiology and Anatomy, University of Maryland School of Medicine, Baltimore, MD, United States Aims: Cannabinoids, includingmarijuana and its synthetic analogues, are the most frequently abused class of illicit drugs in the United States. The brain’s mesolimbic dopamine system is thought to mediate the rewarding/reinforcing properties of all drugs of abuse, including cannabinoids. Although repeated cannabinoid exposure is known to produce tolerance to several behavioral and physiologicalmeasures, it remainsunclearwhether suchapharmacological history also produces tolerance to its dopamine releasing effects. Methods: Rats were treated with either vehicle or a synthetic cannabinoid (WIN55-212-2;WIN) using an escalating dosing approach (0.2–0.8mg/kg IV over 9 treatments). We then assessed whether this dosing regimen produced tolerance to a series of behavioral/physiological measures that are routinely observed when rodents are treated with WIN (i.e., tetrad test: catalepsy, hypothermia, antinociception, and spontaneous activity). Finally, we used fast-scan cyclic voltammetry to measure real-time WIN-evoked dopamine release in the nucleus accumbens in freelymoving and behaving rats. Results: WIN-treated rats showed a rightward dose effect curve shift (0.002–0.8mg/kg IV) in each behavioral/physiological measure versus vehicle treated controls. Likewise, the dopamine releasing potency of WIN was significantly reduced in the WINtreated rats when tested at the 0.2mg/kg IV dose. Conclusions: These results demonstrate that subchronic administration of the synthetic cannabinoid WIN can produce tolerance to its dopamine releasing effects. A diminished ability to increase dopamine release may contribute to the abuse of larger cannabinoid doses and quantities, thereby advancing the addiction process. Financial support: Funded by NIDA grants: R01DA015718, R01DA022340, R01DA025890, R21DA033926 (JFC); F32DA032266 (EBO). http://dx.doi.org/10.1016/j.drugalcdep.2014.02.465 Mediators of response to sertraline vs. placebo among recently abstinent, cocaine-dependent patients Alison Oliveto1, J. Thostenson1, T.R. Kosten2, M. Mancino1 1 UAMS, Little Rock, AR, United States 2 Baylor College of Medicine, Houston, TX, United