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).

- INCLUSION CRITERIA:

Participants will be eligible for inclusion in the study if they meet the following
criteria:

1. Right-handed individuals between the ages of 18 and 60;

2. Good physical condition;

3. Participating and receiving buprenorphine treatment in protocol 09-DA-N020, a study
being conducted in the NIDA Intramural Archway Clinic (Dr. Kenzie Preston, PI) in
Baltimore, MD OR at outpatient treatment facilities at UMMC (ADAP or OATS);

4. Heroin or other opioid dependent;

5. Suitable for MRI scanning;

EXCLUSION CRITERIA:

Participants will be excluded from this study if they:

1. History of neurological illnesses including but not limited to CVA, CNS tumor, head
trauma, MS or other demyelinating diseases, epilepsy, movement disorders, or migraine
in treatment.

2. Are HIV infected.

3. Have deep vein thrombosis (DVT): Assessment tool: self report during H&P of
thrombosis, family history of thrombosis, or a medical condition that may lead to a
hypercoagulable state Rationale: Lying still for an hour (plus the mock scanning
session) may be a risk for the development of DVT in persons with certain medical
conditions. As such, persons with will be excluded.

4. Have current suicidal ideation.

5. Are unable to undergo MRI scanning due to metallic devices in the body including
dental braces, claustrophobia or body morphometry.

6. Are currently using respiratory, cardiovascular or anticonvulsant medications that may
interfere with the BOLD MRI signal.

7. Cognitively impaired;

8. Continued noncompliance (after the 3rd time) with respect to testing positive for
illicit drugs or reporting caffeine use in the past 12 hours or alcohol use in the
past 24 hours when they visit for their scanning sessions will lead to discontinuing
their participation in the #480 protocol.