Investigation of Cocaine Addiction Using mGluR5 PET and fMRI

  • End date
    Jan 9, 2023
  • participants needed
  • sponsor
    Yale University
Updated on 9 August 2022
cocaine use
self administration
functional magnetic resonance imaging
cocaine user
cocaine use disorder
toxicology screen
Accepts healthy volunteers


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).


Cocaine use disorder (CUD) remains a significant public health concern that is resistant to current treatments. Challenges to treating CUD include an imbalance in neurobiological systems that 're-wire' the brain such that appetitive and habitual processes influence decision-making and behavior. This research project aims to provide insight into this reorganized circuitry in CUD by investigating neurofunctional systems related to glutamatergic plasticity and functional brain networks during initial (2-5 days) abstinence. To target this potentially critical period of recovery, currently-using and non-treatment-seeking individuals with CUD will undergo a cocaine self-administration paradigm 2-5 days prior to completing [18F]FPEB positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Healthy comparison (HC) subjects that have participated in [18F]FPEB PET as part of other Yale approved protocols will be recruited to participate in the fMRI portion of this study.

Aim 1: To determine the availability of mGluR5 using [18F]FPEB PET during initial abstinence in individuals with CUD. The investigators hypothesize individuals with CUD, relative to HC, will exhibit concurrently and regionally specific increases (e.g., in the striatum) and decreases (e.g., in the prefrontal cortex) in mGluR5 availability.

Aim 2: To determine patterns of resting-state, response-inhibition, an automaticity related connectivity within and between large-scale functional networks using fMRI during initial abstinence in individuals with CUD. The investigators hypothesize network-based analyses of fMRI will reveal lower frontoparietal and greater limbic network modulation in CUD as compared to HC.

Aim 3: To explore the relationships between mGluR5 availability and functional network activity during initial abstinence in individuals with CUD. The investigators will perform multi-modal analysis of PET and fMRI data to examine links between molecular and functional systems in CUD using emerging 'fusion' approaches. While exploratory in nature, the investigators expect to find links between alterations in mGluR5 systems and functional reorganization in CUD (e.g., greater dorsostriatal mGluR5 may be linked to blunted frontoparietal inhibition).

Aim 4: To explore the relationships between mGluR5 availability, functional network activity (and their linkages) with cocaine self-administration, disease severity and chronicity, and psychometric assessments of impulsivity and compulsivity. While exploratory in nature, the investigators expect more substantial neurofunctional alterations during initial abstinence will be associated with greater cocaine self-administration, disease severity, impulsivity and compulsivity in individuals with CUD.

Condition Cocaine Dependence
Treatment magnetic resonance imaging, positron emission tomography, Psychiatric and Cognitive Testing, Cocaine Self-adminstration
Clinical Study IdentifierNCT03471182
SponsorYale University
Last Modified on9 August 2022


Yes No Not Sure

Inclusion Criteria

All participants
Age 21 - 55 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)
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
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