Vitamin D in OUD: Exploration of Alterations on the Dopamine D2/D3 Receptor System

Inclusion Criteria:

1. Age 18-50 years

2. Voluntary, written, informed consent

3. Physically healthy by medical history, physical, neurological, ECG, and laboratoryexaminations

4. Meets the criteria for OUD, as determined by the Structured Clinical Interview forDSM-5 (SCID)

5. Stable and receiving buprenorphine treatment for OUD

6. For females, non-lactating, with a negative serum or urine pregnancy (hCG) test

7. Lab results without clinically relevant findings (e.g., renal function,electrolytes, and vitamin D levels)

8. English speaking

Exclusion criteria:

1. Medical contraindication to calcitriol administration (e.g., history ofhypersensitivity to calcitriol or any component of the formulation, hypercalcemia orvitamin D toxicity)

2. History of substance dependence (e.g., alcohol, sedative hypnotics), except fornicotine and opiates.

3. A primary major DSM-5 psychiatric disorder (e.g., schizophrenia, bipolar disorder,major depression, etc.) as determined by the SCID, except for Opioid Use Disorderand related conditions.

4. A history of significant medical (e.g., cardiovascular, diabetic/metabolic) orneurological (e.g., cerebrovascular accidents, seizure, traumatic brain injury)illness

5. Positive answers on the cardiac history questionnaire that may place the subject athigher risk, as determined by the study physician's review of both the questionnaireresponses and screening ECG. If there is concern for the subject's safety due tothese assessments, research staff will consult a Yale PET Center affiliatedcardiologist prior to including the subject for the study.

6. Current use of psychotropic and/or potentially psychoactive prescription medications

7. Receiving medications for OUD other than buprenorphine (e.g., methadone treatment)

8. For females, laboratory (β-HCG) or physical evidence of pregnancy/lactation

9. MRI-incompatible implants and other contraindications for MRI (i.e., aneurysm clip,metal fragments, internal electrical devices such as a cochlear implant, spinal cordstimulator or pacemaker)

10. History of claustrophobia or feeling of inability to lie still on his/her back forthe PET or MRI scans

11. History of any bleeding disorder or current anticoagulant therapy

12. Donation or loss of 550 mL of blood or more (including plasmapheresis) or receipt ofa transfusion of any blood product within 8 weeks prior to the first test day.

13. Use of any prescription medications and/or over-the-counter medications, vitaminsand/or herbal supplements which could have a negative clinical interaction withcalcitriol or which could confound scientific results of the study, within 2 weeksprior to each test day (e.g., thiazide diuretics, Mg based antiacids, digoxin,etc,).

14. Serum levels of 25(OH)D3 below 12 ng/ml.

15. Morbid obesity i.e., BMI over 35 (more prone to lower vitamin D levels)

16. Subjects with history of prior radiation exposure for research purposes within thepast year such that participation in this study would place them over FDA limits forannual radiation exposure. This guideline is an effective dose of 5 rem received peryear.

17. Subjects with current, past or anticipated exposure to radiation in the workplace

18. History of kidney stones within the past 5 years

19. Any degree of renal failure

20. History of parathyroid disorder (hyper or hypoparathyroidism)

21. History of osteoporosis or any pathologic fractures

22. Vitamin D supplementation in any form in the past 3 months

23. Known hypersensitivity to [11C]-PHNO or calcitriol

24. Malabsorption syndromes (i.e., Celiac sprue)

25. Serum corrected calcium > 10.5 mg/dl or phosphate > 4.2 mg/dL