Psilocybin on Brain Mechanisms of Motivation in OUD

Exclusion Criteria

• •Participation in clinical trial and receipt of investigational drug(s) during 30 days prior to the research study, except as explicitly approved by the Principal Investigator.
• •Currently meets DSM-5 criteria for moderate to severe substance use disorder for any substance other than cocaine, alcohol, marijuana or nicotine as determined by the semi-structured interview. Any prior use of psilocybin is exclusionary. Patients with comorbid Alcohol Use Disorder will be accepted if their alcohol use disorder is not severe enough to require a medicated alcohol detoxification.
• •Meets current or lifetime DSM-5 criteria for schizophrenia or any psychotic disorder, or organic mental disorder or has a first-degree family history of these disorders, this includes a history of hallucinogen-persistent perception disorder (HPPD)
• •Meets current DSM-5 criteria for bipolar disorder
• •--Meets current DSM-5 criteria for severe Major Depressive Disorder (mild and moderate MDD as well as in stable remission are allowed if no suicidal risk and no ongoing antidepressant therapy).
• •Current or past significant trauma exposure with elevated Post-Traumatic Stress symptoms at the discretion of the PI.
• •Presence of any another psychiatric disorder that in the opinion of the PI will interfere with completion of the study or place the patient at heightened risk through participation in the study.
• •Current or past month active suicidal ideations or lifetime history of serious suicidal attempt.
• •Has evidence of significant hepatocellular injury as evidenced by elevated bilirubin levels (greater than 1.3), or, pulmonary (e.g., COPD), endocrine, cardiovascular, renal (creatinine clearance less than or equal to 60ml/min) or gastrointestinal disease (e.g., Crohn's disease), or current HIV infection, and/or clinically significant levels (over 3.5x upper limit of normal) of aspartate aminotransferase (AST), and serumalanine aminotransferase (ALT). Patients with documented Gilbert's syndrome will be included regardless of bilirubin levels.
• •History of serious head trauma or injury causing loss of consciousness that lasted more than 3 minutes and/or associated with skull fracture or intracranial bleeding or abnormal MRI.
• •Seizure disorder or history of seizures not related to drug or alcohol withdrawal (excluding childhood febrile seizure).
• •Presence of magnetically active prosthetics, plates, pins, broken needles, permanent retainer, bullets, etc. in patient's body (unless a radiologist confirms that its presence is unproblematic). An x-ray may be obtained to determine eligibility.
• •Claustrophobia or other medical condition that disables the participant from lying in the MRI for approximately 60 minutes.
• •Non-removable skin patches, at discretion of PI.
• •Has received medication that could interact adversely with psilocybin within the time of administration of study agent based on the Medical Director's guidance.
• •Needs treatment with any psychoactive (e.g., anti-depressants) medications (with the exception of Benadryl used sparingly, if necessary, for sleep).
• •\*Have the following cardiovascular conditions:
• •1. coronary artery disease, congenital long QT syndrome (prior diagnosis), cardiac hypertrophy, cardiac ischemia, congestive heart failure, myocardial infarction (prior diagnosis);
• •2. tachycardia (defined as heart rate greater than 100 beats per minute);
• •3. a clinically significant Screening ECG abnormality (e.g., atrial fibrillation); Note: A QTcF interval greater than 450 milliseconds is considered a clinically significant ECG abnormality
• •4. artificial heart valve;
• •5. any other significant current or history of cardiovascular condition, based on the clinical judgment of Medical Director, that would make a participant unsuitable for the study.
• •\*At Screening or Baseline have elevated blood pressure as defined as:
• •1. Screening blood pressure SBP greater than135 mmHg or DBP greater than 85 mmHg on three separate readings; or
• •2. Baseline blood pressure SBP greater than140 mmHg or DBP greater than 90 mmHg on three separate readings