Imaging brain mu-opioid receptors in abstinent cocaine users: time course and relation to cocaine craving.
BACKGROUND
Cocaine treatment upregulates brain mu-opioid receptors (mOR) in animals. Human data regarding this phenomenon are limited. We previously used positron emission tomography (PET) with [11C]-carfentanil to show increased mOR binding in brain regions of 10 cocaine-dependent men after 1 and 28 days of abstinence.


METHODS
Regional brain mOR binding potential (BP) was measured with [11C]carfentanil PET scanning in 17 cocaine users over 12 weeks of abstinence on a research ward and in 16 healthy control subjects.


RESULTS
Mu-opioid receptor BP was increased in the frontal, anterior cingulate, and lateral temporal cortex after 1 day of abstinence. Mu-opioid receptor BP remained elevated in the first two regions after 1 week and in the anterior cingulate and anterior frontal cortex after 12 weeks. Increased binding in some regions at 1 day and 1 week was positively correlated with self-reported cocaine craving. Mu-opioid receptor BP was significantly correlated with percentage of days with cocaine use and amount of cocaine used per day of use during the 2 weeks before admission and with urine benzoylecgonine concentration at the first PET scan.


CONCLUSIONS
These results suggest that chronic cocaine use influences endogenous opioid systems in the human brain and might explain mechanisms of cocaine craving and reinforcement.
Gorelick
David A
DA
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 21224, USA. dgorelic@intra.nida.nih.gov
Kim
Yu Kyeong
YK
Bencherif
Badreddine
B
Boyd
Susan J
SJ
Nelson
Richard
R
Copersino
Marc
M
Endres
Christopher J
CJ
Dannals
Robert F
RF
Frost
J James
JJ
D000328:Adult; D000701:Analgesics, Opioid / Q000493:pharmacokinetics; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D012189:Retrospective Studies; D013997:Time Factors
D000701:Analgesics, Opioid; D002247:Carbon Isotopes; D017450:Receptors, Opioid, mu; C017114:carfentanil; D005283:Fentanyl