This study aims to measure synaptic density in the brains (including in ventral striatum [VS] and medial prefrontal cortex [mPFC]) of abstinent subjects with Cocaine Use Disorder (CUD) or Opiate Use Disorder (OUD) as compared to healthy control (HC) subjects using 11C-UCB-J PET. Subjects will undergo a single 11C-UCB-J (also known as 11C-APP311) PET scan.

This would be the very first to image synaptic density in human cocaine and opiate users, thereby testing whether altered synaptic density in the rodent brain is recapitulated in CUD and OUD humans. If confirmed, the current study would provide compelling clinical-translational support for an important pathophysiological mechanism of addiction - aberrant structural synaptic plasticity. As such, the current study has considerable potential for advancing the neurobiological understanding of human cocaine and opiate addiction.

This study aims to measure synaptic density in the brains (including in ventral striatum [VS] and medial prefrontal cortex [mPFC]) of abstinent subjects with Cocaine Use Disorder (CUD) or Opiate Use Disorder (OUD) as compared to healthy control (HC) subjects using 11C-UCB-J PET. Subjects will undergo a single 11C-UCB-J (also known as 11C-APP311) PET scan.

This would be the very first to image synaptic density in human cocaine and opiate users, thereby testing whether altered synaptic density in the rodent brain is recapitulated in CUD and OUD humans. If confirmed, the current study would provide compelling clinical-translational support for an important pathophysiological mechanism of addiction - aberrant structural synaptic plasticity. As such, the current study has considerable potential for advancing the neurobiological understanding of human cocaine and opiate addiction.

A separate protocol from the study team, identified by the ClinicalTrials.gov ID NCT04721418, is conducting a comprehensive investigation into the cocaine use disorder group. Therefore, data for participants with cocaine use disorder are not included in the results for the current registration.

Inclusion Criteria:

• Age 21-55 years;
• Voluntary, written, informed consent;
• Physically healthy by medical history, physical, neurological, ECG and laboratory examinations;
• DSM-5 criteria for Opiate Use Disorder;
• Documented evidence (by urine toxicology) of 2 weeks abstinence from cocaine and 4 weeks abstinence from opiates;
• For females, a negative serum pregnancy (HCG) test;
• Full scale and verbal IQs > 80 (Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV)).

Exclusion Criteria:

• A history of other substance dependence (e.g., alcohol, sedative hypnotics), except for nicotine;
• A primary DSM-5 Axis I major psychiatric disorder (e.g., schizophrenia, bipolar disorder, major depression, etc.) as determined by the Structured Clinical Interview for DSM-5 (SCID-5);
• A history of significant and uncontrolled medical (e.g., cardiovascular, diabetic/metabolic) or neurological (e.g., cerebrovascular, seizures, traumatic brain injury) illness;
• A history of seizures;
• Current use of psychotropic and/or potentially psychoactive prescription medications;
• Medical contraindications to participation in a magnetic resonance (MR) imaging procedure (e.g., ferromagnetic implants/foreign bodies, claustrophobia, cardiac pacemaker, prosthetic valve, otologic implant, etc.) as recorded on the MR safety sheet;
• For females, physical or laboratory (HCG) evidence of pregnancy;
• PTT and PT/INR lab results not appropriate for arterial line placement;
• Taking anticoagulants;
• Being prescribed methadone/buprenorphine upon screening.

90 minutes