Understanding Drug Abuse Treatment Outcomes

OBJECTIVE:

The primary objective of this pilot study is to collect data for a NIH RO1 grant submission that aims to elucidate cognitive, emotional regulatory and neurobiological mechanisms that both moderate and mediate effects of cognitive behavioral therapy (CBT) in individuals with opiate dependence. CBT has proven moderately effective in treating substance abuse; however, significant variability in treatment outcomes remains. CBT curricula teach adaptive decision making and cognitive reappraisal skills to down-regulate emotional responses to drug-related cues, thereby promoting avoidance of drug use situations. A certain level of cognitive and emotion regulatory functioning is, however, required for assimilating and executing these skills which is often deficient in substance abusers. Consequently, many addicts cannot effectively process and act on CBT curriculum, leading to poor treatment outcomes. Tailoring interventions requires systematic investigation of neurobiological indicators that interfere with or promote favorable treatment responsivity.

The small pilot study outlined below will provide the feasibility and supportive data for a larger effort.

Aim 1: Moderation. Identify baseline ECF and emotion regulatory functions and their neural substrates that predict treatment variability in the form of: (a) program responsivity (e.g., treatment engagement, motivation, social competences) and (b) posttreatment outcomes (e.g., substance use frequency, days of continuous abstinence). Functional magnetic resonance imaging (fMRI) will be used during performance of tasks that measure ECF (decision-making; inhibitory control) and cognitive reappraisal of emotional cues to investigate the neuromodulatory role of PFC regions (e.g., OFC, ACC) on emotion (e.g., amygdala) and reward (e.g., ventral striatum) structures and autonomic activity.

Aim 2: Mediation. Determine whether change in these neurocognitive functions in response to CBT mediate intervention effects. Evidence suggests that CBT alters PFC and limbic function; such changes are associated with clinical outcomes in depression and anxiety. Similarly, in drug abusers, we predict treatment response will be associated with changes in neural activation patterns, ECF, and emotional regulation, and that little to no change will occur in those with relatively poorer outcomes.

Study Population: Participants will be 18 primary opioid dependent individuals between the ages of 18 and 60. These individuals will either be enrolled in NIDA Protocol 09-DA-N020, (Dr. Kenzie Preston, PI) or patients at the University of Maryland Medical Center outpatient substance abuse clinics (i.e., Alcohol and Drug Abuse Program (ADAP) or Outpatient Addiction Treatment Service (OATS) and are receiving buprenorphine.

DESIGN:

Study participants visit their treatment facility daily for buprenorphine and receive standard counseling as part of Protocol 09-DA-N020 or their treatment protocol at ADAP or

OATS. They will be screened by MMG for eligibility into the present study then randomly assigned to a TAU control group or a CBT group. This study consists of 3 assessment time points (baseline, midway, post-treatment) and 16 bi-weekly counseling visits (CBT or standard TAU counseling). Baseline assessments will consist of functional magnetic resonance imaging (fMRI) during performance of decision making, inhibitory control and emotional regulatory tasks. Questionnaires will be used to evaluate historical and current drug use, background and psychological traits, and other relevant factors. Those in the TAU group visit their treatment facility routinely for buprenorphine and standard counseling but will not receive CBT. The CBT group participants will undergo 8 weeks of CBT in the

Archway Clinic twice a week provided by a CBT clinician from Mountain Manor Treatment

Center who will be supervised by Dr. Marc Fishman, treatment director at MMTC; this CBT counseling will be in place of the TAU counseling they would be receiving as part of the parent protocol. Midway through CBT/TAU counseling, participants in this pilot study will be evaluated outside the scanner with the same cognitive tasks used in the scanner and questionnaires from baseline. After treatment completion, they will receive a post-treatment fMRI scan where they will perform the same tasks and questionnaires. Also, we will preliminarily assess mediation by examining variability in level of responsivity within the treatment group to determine whether this outcome is related to functional baseline characteristics and change over time. Expectations are that baseline features will predict intervention response and that these same characteristics will change over time in response to intervention in those with favorable outcomes.

OUTCOME MEASURES:

The focus of our outcome evaluation will be use of opioid (e.g., frequency, days of continuous abstinence, etc.), coping strategies, and change in lifestyle measures (e.g., employment, relationships, behavioral problems, treatment engagement).