Effect of the CRF1-receptor antagonist pexacerfont on stress-induced eating and food craving.
In rodents, antagonism of receptors for corticotropin-releasing factor (CRF) blocks stress-induced reinstatement of drug or palatable food seeking.



To test anticraving properties of the CRF1antagonist pexacerfont in humans.



We studied stress-induced eating in people scoring high on dietary restraint (food preoccupation and chronic unsuccessful dieting) with body-mass index (BMI) >22. In a double-blind, between-groups trial, 31 "restrained" eaters were stabilized on either pexacerfont (300 mg/day for 7 days, then 100 mg/day for 21 days) or placebo. On day 15, they underwent a math-test stressor; during three subsequent visits, they heard personalized craving-induction scripts. In each session, stress-induced food consumption and craving were assessed in a bogus taste test and on visual analog scales. We used digital video to monitor daily ingestion of study capsules and nightly rating of food problems/preoccupation on the Yale Food Addiction Scale (YFAS).



The study was stopped early due to an administrative interpretation of US federal law, unrelated to safety or outcome. The bogus taste tests suggested some protective effect of pexacerfont against eating after a laboratory stressor (reffect= 0.30, 95 % CL = -0.12, 0.63, Bayes factor 11.30). Similarly, nightly YFAS ratings were lower with pexacerfont than placebo (reffect= 0.39, CI 0.03, 0.66), but this effect should be interpreted with caution because it was present from the first night of pill ingestion, despite pexacerfont's slow pharmacokinetics.



The findings may support further investigation of the anticraving properties of CRF1antagonists, especially for food.
National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 251 Bayview Blvd., BRC Building, Suite 200, Baltimore, MD, 21224, USA. depstein@intra.nida.nih.gov.
David H
DH
Epstein
National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 251 Bayview Blvd., BRC Building, Suite 200, Baltimore, MD, 21224, USA.
Ashley P
AP
Kennedy
National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 251 Bayview Blvd., BRC Building, Suite 200, Baltimore, MD, 21224, USA.
Melody
M
Furnari
National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 251 Bayview Blvd., BRC Building, Suite 200, Baltimore, MD, 21224, USA.
Markus
M
Heilig
National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 251 Bayview Blvd., BRC Building, Suite 200, Baltimore, MD, 21224, USA.
Yavin
Y
Shaham
National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 251 Bayview Blvd., BRC Building, Suite 200, Baltimore, MD, 21224, USA.
Karran A
KA
Phillips
National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 251 Bayview Blvd., BRC Building, Suite 200, Baltimore, MD, 21224, USA.
Kenzie L
KL
Preston
D000328:Adult; D001499:Bayes Theorem; D003192:Compulsive Behavior / Q000188:drug therapy*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D066249:Craving / Q000187:drug effects*; D004032:Diet; D004311:Double-Blind Method; D005247:Feeding Behavior / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000494:pharmacology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D013315:Stress, Psychological / Q000150:complications*; D014227:Triazines / Q000494:pharmacology*; D055815:Young Adult; D000099052:CRF Receptor, Type 1
D011720:Pyrazoles; D018019:Receptors, Corticotropin-Releasing Hormone; D014227:Triazines; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; C542342:pexacerfont
Bogus taste test; CRF1 antagonists; Craving; Dietary restraint; Stress-induced eating