Brain mu-opioid receptor binding predicts treatment outcome in cocaine-abusing outpatients.
BACKGROUND
Cocaine users not seeking treatment have increased regional brain mu-opioid receptor (mOR) binding that correlates with cocaine craving and tendency to relapse. In cocaine-abusing outpatients in treatment, the relationship of mOR binding and treatment outcome is unknown.


METHODS
We determined whether regional brain mOR binding before treatment correlates with outcome and compared it with standard clinical predictors of outcome. Twenty-five individuals seeking outpatient treatment for cocaine abuse or dependence (DSM-IV) received up to 12 weeks of cognitive-behavioral therapy and cocaine abstinence reinforcement, whereby each cocaine-free urine was reinforced with vouchers redeemable for goods. Regional brain mOR binding was measured before treatment using positron emission tomography with [¹¹C]]-carfentanil (a selective mOR agonist). Main outcome measures were: 1) overall percentage of urines positive for cocaine during first month of treatment; and 2) longest duration (weeks) of abstinence from cocaine during treatment, all verified by urine toxicology.


RESULTS
Elevated mOR binding in the medial frontal and middle frontal gyri before treatment correlated with greater cocaine use during treatment. Elevated mOR binding in the anterior cingulate, medial frontal, middle frontal, middle temporal, and sublobar insular gyri correlated with shorter duration of cocaine abstinence during treatment. Regional mOR binding contributed significant predictive power for treatment outcome beyond that of standard clinical variables such as baseline drug and alcohol use.


CONCLUSIONS
Elevated mOR binding in brain regions associated with reward sensitivity is a significant independent predictor of treatment outcome in cocaine-abusing outpatients, suggesting a key role for the brain endogenous opioid system in cocaine addiction.
Ghitza
Udi E
UE
Intramural Research Program, Clinical Pharmacology and Therapeutics Research Branch, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland, USA. ghitzau@nida.nih.gov
Preston
Kenzie L
KL
Epstein
David H
DH
Kuwabara
Hiroto
H
Endres
Christopher J
CJ
Bencherif
Badreddine
B
Boyd
Susan J
SJ
Copersino
Marc L
ML
Frost
J James
JJ
Gorelick
David A
DA
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003042:Cocaine / Q000652:urine; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000628:therapy* / Q000652:urine; D015928:Cognitive Behavioral Therapy / Q000379:methods*; D005260:Female; D005283:Fentanyl / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D011237:Predictive Value of Tests; D011869:Radioligand Assay / Q000379:methods; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D016896:Treatment Outcome
D017450:Receptors, Opioid, mu; D003042:Cocaine; C017114:carfentanil; D005283:Fentanyl