Effects of Pharmacological Stress and rTMS on Executive Function in Opioid Use Disorder

Effects of Pharmacological Stress and Repetitive Transcranial Magnetic Stimulation Interventions on Executive Function in Opioid Use Disorder

This preliminary study is designed to evaluate mechanisms by which excitatory dorsolateral prefrontal cortex (dlPFC) repetitive transcranial magnetic stimulation (rTMS) (vs. sham) and pharmacological stress (vs. placebo) alter behavior in non-treatment seeking individuals with opioid use disorder (OUD). Specific Aims are to (1) Evaluate how stress impacts domains of behavior including (1a) executive function and (1b) opioid-seeking behavior; and (2) Determine whether rTMS stimulation attenuates (2a) executive dysfunction, (2b) stress-reactivity, and (2c) opioid-seeking in individuals with OUD not receiving treatment.

This study will use a double-blind, 10Hz left dlPFC rTMS (vs. sham) and pharmacological stressor ([yohimbine + hydrocortisone] vs. placebo) within-subject, randomized crossover design. Each participant will complete 4 sessions (stressor vs. placebo, crossed with rTMS vs. sham), each separated by at least 1 week. Participants will complete these 4 (2x2 within subject) test conditions in randomized order: sham rTMS/placebo stress, sham rTMS/active stress, active rTMS/ placebo stress, and active rTMS/active stress.

The PI will perform randomization using a Latin Square and will assign participants to conditions and prepare medication (stressor or placebo) for each participant's sessions. The PI will keep others blinded and will not be involved in study assessments.

Inclusion Criteria:

• Meet DSM-5 criteria for OUD;
• Age 21-60 yr;
• Right handed;
• Males and non-pregnant/non-lactating females;
• cognitively intact (total IQ score >80 on Shipley Institute of Living Scale);
• Screening cardiovascular indices within ranges for safe use of the pharmacological stressor: resting HR 50-90 bpm, systolic BP 90-140 mmHg, and diastolic BP 50-90 mmHg;
• Use alcohol and/or marijuana <3 times/week; each "time" should consist of <1 marijuana "joint" equivalent and <3 alcoholic drinks.

Exclusion Criteria:

• Under influence of any substance during session;
• Past 7-day use of illicit drugs other than opioids (except marijuana, which is legal in Michigan);
• Urinalysis positive for cocaine metabolites, benzodiazepines, barbiturates, amphetamines or pregnancy;
• Medical conditions prohibiting use of rTMS (e.g. seizure history; based on rTMS screening questionnaire);
• Lifetime diagnosis of: psychotic disorder, bipolar disorder, generalized anxiety disorder, or obsessive compulsive disorder; major depression in the past 5 years; or potentially antisocial personality disorder (if the clinical psychologist judges such behaviors to be potentially disruptive or unsafe in our lab);
• Past-year SUD other than OUD;
• Acute/unstable illness: conditions making it unsafe for participation (e.g. neurological, cardiovascular, pulmonary, or systemic diseases);
• Lactose intolerance (placebo dose);
• Any prohibited medications: medications that lower seizure threshold, psychiatric medications, prescription pain medications, or blood pressure medications;
• Chronic head or neck pain; and
• Past-month participation in a research study.