Olanzapine in OUD Patients

This study is designed to examine whether olanzapine (2.5 to 20mg/day) impacts opioid use in patients with opioid use disorder and comorbid SMI symptoms who are taking buprenorphine-naloxone. The specified outcomes (e.g., illicit opioid use, other drug use, sleep, MAT adherence, withdrawal and craving, thought and mood disorder symptoms) on olanzapine will be examined within-subjects for change (improvement) across the trial. Approximately 48 subjects will be enrolled. After enrollment, subjects will complete safety and baseline assessments and will be assigned open-label to 9-weeks olanzapine. Olanzapine will then be tapered over a 1-week period (or maintained if clinically indicated). Urines will be collected 2x/week throughout. The study has 4 distinct phases: 1) Screening (approx. 1-2 wks); 2) Baseline and Medication Initiation Visit (1 visit; includes safety, baseline and phenotyping measures, study medication dispensed) 3) Outpatient treatment (9 wks; 2 visits/wk, includes daily olanzapine and daily buprenorphine-naloxone (through the participants usual community treatment site and on-medication phenotyping measures); 4) Follow-up visit (1 wk after last dose of study medication).