Matthew Worley

Research grounded in behavioral economics has previously linked addictive behavior to disrupted decision-making and reward-processing, but these principles have not been examined in prescription opioid addiction, which is currently a major public health problem. This study examined whether pre-treatment drug reinforcement value predicted opioid use during outpatient treatment of prescription opioid addiction. Secondary analyses examined participants with prescription opioid dependence who received 12 weeks of buprenorphine-naloxone and counseling in a multi-site clinical trial (N=353). Baseline measures assessed opioid source and indices of drug reinforcement value, including the total amount and proportion of income spent on drugs. Weekly urine drug screens measured opioid use. Obtaining opioids from doctors was associated with lower pre-treatment drug spending, while obtaining opioids from dealers/patients was associated with greater spending. Controlling for demographics, opioid ...

Oral naltrexone is an efficacious medication for treatment of alcohol dependence, but small effect sizes and variability in outcomes suggest the presence of person-level moderators of naltrexone response. Identification of contextual or psychosocial moderators may assist in guiding clinical recommendations. Given the established importance of social networks in drinking outcomes, as well as the potential effects of naltrexone in reducing cue reactivity which may be especially important among those with more heavy drinkers and more alcohol cues in their networks, we examined pretreatment social network variables as potential moderators of naltrexone treatment effects in the COMBINE study. The sample included all COMBINE study participants in medication conditions with full data on the Important People Inventory (IPI) and covariates at intake (N = 1,197). The intake IPI assessed whether participants had any frequent drinkers in their network and the average frequency of contact with t...

We have established that the efficacy of a heterologous poxvirus vectored HIV vaccine, fowlpox virus (FPV)-HIV gag/pol prime followed by attenuated vaccinia virus (VV)-HIV gag/pol booster immunisation, is strongly influenced by the cytokine milieu at the priming vaccination site, with endogenous IL-13 detrimental to the quality of the HIV specific CD8+ T cell response induced. We have now developed a novel HIV vaccine that co-expresses a C-terminal deletion mutant of the mouse IL-4, deleted for the essential tyrosine (Y119) required for signalling. In our vaccine system, the mutant IL-4C118 can bind to IL-4 type I and II receptors with high affinity, and transiently prevent the signalling of both IL-4 and IL-13 at the vaccination site. When this IL-4C118 adjuvanted vaccine was used in an intranasal rFPV/intramuscular rVV prime-boost immunisation strategy, greatly enhanced mucosal/systemic HIV specific CD8+ T cells with higher functional avidity, expressing IFN-γ, TNF-α and IL-2 and greater protective efficacy were detected. Surprisingly, the IL-4C118 adjuvanted vaccines also induced robust long-lived HIV gag-specific serum antibody responses, specifically IgG1 and IgG2a. The p55-gag IgG2a responses induced were of a higher magnitude relative to the IL-13Rα2 adjuvant vaccine. More interestingly, our recently tested IL-13Rα2 adjuvanted vaccine which only inhibited IL-13 activity, even though induced excellent high avidity HIV-specific CD8+ T cells, had a detrimental impact on the induction of gag-specific IgG2a antibody immunity. Our observations suggest that (i) IL-4 cell-signalling in the absence of IL-13 retarded gag-specific antibody isotype class switching, or (ii) IL-13Rα2 signalling was involved in inducing good gag-specific B cell immunity. Thus, we believe our novel IL-4R antagonist adjuvant strategy offers great promise not only for HIV-1 vaccines, but also against a range of chronic infections where sustained high quality mucosal and systemic T and B cell immunity are required for protection.

Among patients with substance dependence and comorbid major depressive disorder (MDD) receiving treatment in a controlled trial, we examined if group differences in depression were mediated by 12-Step involvement, and if the effects of 12-Step involvement on future alcohol and drug use were mediated by reductions in depression. Controlled trial of Twelve-Step facilitation (TSF) and integrated cognitive-behavioral therapy (ICBT), delivered in out-patient groups for 6 months with adjunct pharmacotherapy. Out-patient dual diagnosis clinic in Veteran's Affairs Healthcare Center. Veterans (n = 209) diagnosed with alcohol, stimulant or marijuana dependence and substance-independent MDD. Twelve-Step attendance and affiliation, depression severity, percentage of days drinking and percentage of days using drugs assessed at baseline and months 3, 6 and 9. In multi-level analyses greater 12-Step meeting attendance predicted lower depression and mediated the superior depression outcomes of the TSF group, explaining 24.3% of the group difference in depression. Independent of treatment group, lower depression severity predicted lower future alcohol use and mediated the effects of 12-Step meetings, explaining 15.7% of their effects on future drinking. Controlled, lagged models indicated these effects were not confounded by current substance use, suggesting that depression had unique associations with 12-Step meeting attendance and future drinking. For patients with substance dependence and major depressive disorder, attendance at 12-Step meetings is associated with mental health benefits that extend beyond substance use, and reduced depression could be a key mechanism whereby 12-Step meetings reduce future drinking in this population.