An Early Phase 1 interventional study of Baseline [C-11]NOP-1A PET Scan and Hydrocortisone in Cocaine Use Disorder, sponsored by Rajesh Narendran. Recruiting at 1 site in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-07-06.
Sponsored by Rajesh Narendran · Early Phase 1, Interventional, and Basic science
This study uses [11C]NOP-1A positron emission tomography (PET) and a hydrocortisone challenge to image the interaction between nociceptive opioid peptide (NOP) receptors and cortisol/corticotrophin releasing factor (CRF) in subjects with cocaine use disorders (CUD) and matched healthy controls (HC). It will also examine whether alterations in CRF x NOP interactions predict relapse in subjects with CUD.
Cocaine use disorder (CUD) is a chronic disorder associated with numerous relapses and periods of abstinence.
Studies in CUD suggest that \~ 60 to 75% of abstinent addicts relapse over twelve months Documenting specific neurochemical abnormalities that lead to relapse in individuals with CUD has the potential to accelerate the development of medications to prevent relapse. Basic investigations postulate an imbalance between brain stress and anti-stress/resilience systems as the underlying mechanism that drives negative reinforcement, craving, and relapse in addiction. Nociceptin (N/OFQ), which binds to the nociceptive opioid peptide receptors (NOP) is a critical component of the brain's anti-stress system. N/OFQ counteracts the functional effects of the primary stress-promoting neuropeptide corticotrophin releasing factor (CRF) in the brain to exert its anti-stress effects. Studies have also shown that acute increases in CRF and stress are countered by increased NOP receptor expression (\~ 10% ) in brain regions that regulate stress such as bed nucleus of the stria terminalis. PET studies with the NOP radiotracer [11C]NOP-1A show increased binding to NOP in CUD compared to HC. PET studies also show NOP receptors to upregulate (\~ 15%) in response to an acute intravenous hydrocortisone challenge (1 mg/Kg). NOP upregulation may represent an adaptive mechanism in the brain to counteract stress-induced increases in cortisol and CRF. Here, we postulate a failure in this adaptive mechanism as a reason that leads to relapse in CUD. CUD subjects and HC will be studied with [11C]NOP-1A before and after an intravenous hydrocortisone challenge (aim 1). Hydrocortisone is used as a challenge because it increases cortisol and CRF in brain regions that regulate stress. We hypothesize that hydrocortisone-induced increases in [11C]NOP-1A binding (DELTA VT) will be smaller in CUD relative to HC, and this will be associated with less time to relapse in a 12-week follow up.
Rajesh Narendran is the lead sponsor of 7 studies on the registry; 5 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Cocaine use disorders (CUD)
Healthy Controls (HC)
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
\[C-11\]NOP-1A
Radiation: Baseline [C-11]NOP-1A PET Scan · Drug: Hydrocortisone · Radiation: Post-hydrocortisone [C-11]NOP-1A PET Scan
Radiotracer
Intravenous, 1mg/Kg
Radiotracer
DELTA VT
VT is the volumes of distribution expressed relative to total plasma ligand concentration; Delta VT is the change in VT from baseline to 3-hours post-hydrocortisone.
Time frame: Baseline, and 3 hours post-hydrocortisone
Plan to share: No
No publications or documents are linked to this record.
Started Dec 2020 (actual). Primary completion is estimated for Sep 2028, 92 months after the start.
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Studies of the drug tested here: Hydrocortisone
Rajesh Narendran