Investigation of Cocaine Addiction Using mGluR5 PET and fMRI
Condition: Cocaine Dependence
MeSH terms: Cocaine-Related Disorders; Behavior, Addictive
Intervention: Psychiatric and Cognitive Testing; Cocaine Self-adminstration; Positron Emission Tomography; Magnetic Resonance Imaging
Intervention description: Interviews, questionnaires, and computer testing.; The intervention will include a training and safety session that consists of physician/nurse-administered cocaine followed by a self-regulated cocaine administration period under carefully controlled and closely monitored conditions.; PET scans will be performed on a High Resolution Research Tomograph (HRRT), the highest resolution human brain scanner available. Antecubital venous catheters will be used for IV administration of the radiotracer and for venous blood sampling. A radial artery catheter may also be inserted by an experienced physician before the PET scan. At the beginning of each scan, the participants's head will be immobilized and a 6-minute transmission scan, using an orbiting 137Cs point-source, is obtained and used for attenuation correction. PET scans will be acquired using bolus or bolus plus constant infusion administration of [18F]FPEB.; Structural and functional MRI data will be acquired using a Siemens Trio TIM 3.0T system at the Yale Magnetic Resonance Research Center. High-resolution structural MRI data will be acquired to facilitate analysis of PET data and may be used in additional analysis of tissue volume and brain structure. Resting-state and task-based functional MRI data will be acquired using state-of-the-art multiband echo-planar imaging (EPI) gradient-echo sequences. Diffusion-weighted MRI data will also be acquired using multiband imaging sequences to investigate anatomical connectivity.
Intervention MeSH terms: Cocaine
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Cocaine Dependence; Cocaine Addiction

Summary:

      The proposed research program will investigate the changes in brain chemistry and circuitry
      that 're-wire' the brain during chronic cocaine use, promote relapse, and complicate
      treatment efforts. Currently-using and non-treatment-seeking individuals with a cocaine use
      disorder will undergo a cocaine self-administration paradigm 2-5 days prior to completing
      positron emission tomography (PET) and functional magnetic resonance imaging (fMRI).
    

Eligibility criteria:

        Inclusion Criteria:

          -  All participants:

               -  Age 21 - 60 years

               -  Provide voluntary, written, informed consent

               -  Physically healthy by medical history, physical, neurological, ECG, and
                  laboratory examinations

               -  For females: non-lactating, no longer of child-bearing potential or agreeing to
                  practice effective contraception during the study (e.g., established use of oral,
                  injected or implanted hormonal methods of contraception; placement of an
                  intrauterine device [IUD] or intrauterine system [IUS]; barrier methods: condom
                  or occlusive cap [diaphragm or cervical/vault caps] with spermicidal
                  foam/gel/film/cream/suppository; male partner sterilization; true abstinence when
                  this is in line with the preferred and usual lifestyle of the subject), and a
                  negative serum pregnancy test

          -  Participants with a cocaine use disorder:

               -  DSM-5 criteria for moderate or severe cocaine-use disorder

               -  Recent street cocaine use in excess of quantities used in the current study

               -  Intravenous and/or smoked (crack/freebase) cocaine use

               -  Positive urine toxicology screen for cocaine

          -  Healthy comparison participants:

               -  Successful completion of an [18F]FPEB scan as part of another Yale approved
                  protocol as a healthy control/comparison subject

        Exclusion Criteria:

          -  All participants:

               -  Any condition that, in the opinion of investigators, would prevent compliance
                  with the study protocol

               -  A history of significant medical or neurological illness (e.g., coronary artery
                  disease, significant anemia, seizures)

               -  Current use of psychotropic and/or potentially psychoactive medications

               -  Physical or laboratory evidence of pregnancy

               -  Meet any additional PET/MR imaging-related exclusion criteria, including:

               -  Presence of MRI incompatible implants and other contraindications for MRI (e.g.,
                  pacemaker, artificial joints, non-removable body piercings, etc.)

               -  Participation in other research studies involving ionizing radiation within one
                  year of the PET scans that would cause the participant to exceed the yearly dose
                  limits

               -  History of a bleeding disorder or are currently taking anticoagulants (such as
                  Coumadin, Heparin, Pradaxa, Xarelto).

               -  Claustrophobia

               -  Severe motor problems that prevent the subject from lying still for PET/MR
                  imaging

               -  Complaints of chronic pain (e.g., as the result of rheumatoid arthritis)

               -  Current, past or anticipated exposure to radiation in the work place

          -  Participants with a cocaine use disorder:

               -  Other drug use disorder (except for tobacco-use disorder)

               -  Less than 1 year of cocaine use disorder

               -  A DSM-5 major psychiatric diagnosis (schizophrenia, bipolar disorder, etc.)
                  unrelated to cocaine

          -  Healthy comparison participants:

               -  Any DSM-5 major psychiatric diagnosis (schizophrenia, bipolar disorder, etc.),
                  except tobacco-use disorder

               -  Positive drug screen