Evaluation of Doxazosin to Alter the Abuse of Oxycodone

Participants must meet all of the following inclusion criteria to be enrolled into the study:

1. 21-59 years of age. Ascertained by: Self-reported age and/or verification with legal identification.
2. Diagnostic criteria for Opioid Use Disorder moderate-severe (304.00) as per DSM-V Ascertained by: Clinical interviews (telephone, psychologist, nurse, physician), naloxone challenge test/visual evidence of opioid withdrawal.
3. No current or past diagnosis of schizophrenia, schizoaffective disorder, or other psychotic disorder; bipolar I or bipolar II disorder, other major mood, psychotic, or anxiety disorder that might interfere with the study. Ascertained by: Clinical interview with physician or nurse.
4. Physically healthy. Ascertained by: Clinical interview with physician, laboratory tests (urinalysis, blood chemistry, 12-lead ECG), physical examination, self-reported medical history.
5. Able to perform study procedures. Ascertained by: Practice session or Clinical Judgement (Psychologist or Physician)
6. Normal body weight. Ascertained by: Body Mass Index <30.
7. Current or history of intranasal opioid use. Ascertained by: Clinical interviews (telephone, psychologist, and psychiatric NP, or physician).
8. Current intranasal or intravenous use of opioids in amounts and/or frequencies that meet or exceed those used in the proposed study (e.g., 3-4 tablets of a prescription opioid medication per day or 1-2 bags of heroin per day). Ascertained by: Clinical interviews (telephone, psychologist, psychiatric NP, or physician)
9. If female and using oral contraceptives, must use alternative forms of contraception as well (e.g. condoms in combination with spermicide). Ascertained by: Clinical interviews (telephone, psychologist, nurse, physician), physical examination.
10. Has not participated in another opioid laboratory study within the past 3 months. Ascertained by: Clinical interviews (psychologist physician, or psychiatric NP), review of laboratory records.

Participants will be excluded from study participation if they meet any of the following exclusion criteria:

1. Meeting DSM-V criteria for substance use disorder (moderate-severe) on drugs other than opioids, nicotine or caffeine (must be less than 500 mg caffeine daily). Ascertained by: Clinical interview with physician or psychiatric NP, urine screen, observation.
2. Participants requesting treatment. Ascertained by: Self-report during interview.
3. Treatment with any investigational drug during the last 30 days. Ascertained by: Self-report during interview.
4. Participants on parole or probation. Ascertained by: Self-report during interview, criminal background check upon admission.
5. Currently pregnant or trying to conceive, or currently lactating. Ascertained by: Blood pregnancy testing at screening, on admission and (beta hCG), and self-report during interview and study visits.
6. Current or recent history of significant violent or suicidal behavior and/or suicidal/homicidal risk. Ascertained by: Clinical interview with a psychiatrist or psychiatric NP, and C-SSRS, MINI, and Beck Depression Inventory (based on current state and history).
7. Cannot read or understand the self-report assessment forms unaided, or are so severely disabled that they cannot comply with the requirements of the study. Ascertained by: Clinical interview (psychologist, physician, or psychiatric NP), or practice session.
8. Elevated liver function tests (i.e., AST and ALT > 3 times the upper limit of normal (ULN); bilirubin > 2x ULN; hepatitis B or chronic hepatitis C). Ascertained by: Laboratory tests.
9. Physical disorders that might make participation hazardous such as AIDS, cancer, baseline hypotension, orthostatic hypotension or syncope, hypertension (blood pressure > 140/90), uncontrolled diabetes, pulmonary hypertension or heart disease (please note that participants will be asked about previous visits to a cardiologist, chest pain, or strong palpitations; if these exist, they will be referred to a cardiologist and excluded unless cleared for participation by a cardiologist). Ascertained by: Clinical interview (psychologist, physician, or psychiatric NP) physical examination, 12-lead ECG.
10. Current major Axis I psychopathology other than opioid use disorder (e.g., mood disorder with functional impairment or suicide risk, schizophrenia), that might interfere with ability to participate in the study. Ascertained by: Clinical interviews (psychologist, physician, or psychiatric NP).
11. Sensitivity, allergy, or contraindication to opioids, doxazosin, adrenergic antagonists or agonists, or similar compounds. Ascertained by: Clinical interview (psychologist, physician, or psychiatric NP).
12. Planning to conceive within 6 months of study participation. Ascertained by: Clinical interview (psychologist, physician, or psychiatric NP).
13. Use of any prescription, over-the-counter medication that affects CYP3A4 activity are prohibited for at least 7 days prior to the anticipated study start date; or the use of phosphodiesterase inhibitors and MAOIs 14 days prior to the study. Ascertained by: Medical History, Clinical Interview ((psychologist, physician, or psychiatric NP).