Effect of the CRF1-receptor antagonist pexacerfont on stress-induced eating and food craving

Abstract

Rationale: In rodents, antagonism of receptors for corticotropin-releasing factor (CRF) blocks stress-induced reinstatement of drug or palatable food seeking.

Objective: To test anticraving properties of the CRF1 antagonist pexacerfont in humans.

Methods: 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).

Results: 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 (r effect = 0.30, 95 % CL = -0.12, 0.63, Bayes factor 11.30). Similarly, nightly YFAS ratings were lower with pexacerfont than placebo (r effect = 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.

Conclusions: The findings may support further investigation of the anticraving properties of CRF1 antagonists, especially for food.

Trial registration: ClinicalTrials.gov NCT01656577.

Keywords: Bogus taste test; CRF1 antagonists; Craving; Dietary restraint; Stress-induced eating.

Conflict of interest statement

Conflict of interest The authors declare that they have no conflict of interest.

Figures

Fig. 1

Kilocalories (kcal) of four snack foods eaten in the 30-min bogus taste test immediately after the PASAT-C stressor. Each circle shows data from a single participant, with the group means displayed as horizontal lines. The means are also shown, with SEMs, in the inset bar graph (with the y-axis truncated). A total of 4000 kcal of food was available

Fig. 2

Ratings of craving (“Is this food causing you to have any food cravings right now?”) for each of four snack foods after the 30-min bogus taste test in the PASAT-C stressor session. Each circle shows data from a single participant, with the group means displayed as horizontal lines. The means are also shown, with SEMs, in the inset bar graphs (with the y-axis truncated). The asterisk marks a group difference of p < 0.05. The scale was anchored at 1 and 10 with “none” and “most possible”

Fig. 3

Kilocalories (kcal) of four snack foods eaten in the 30-min bogus taste test immediately after each of three imagery scripts (neutral, food, or stress) in three separate sessions. Each filled circle shows data from a single participant, with the group means displayed as horizontal lines. The means are also shown, with SEMs, in the inset bar graph (with the y-axis truncated). A total of 4000 kcal of food was available

Fig. 4

Mean (±SEM) nightly ratings of food problems/preoccupation on the Yale Food Addiction Scale (YFAS) during maintenance on pexacerfont or placebo. Scores were the sum of ten items such as “I ended up eating much more than I had planned,” “I worried about not eating certain types of food or cutting down on certain types of food,” and “My behavior with respect to food and eating caused me significant distress,” all in a time frame of the past 24 h

Fig. 5

Raster display of video-confirmed compliance with study-pill ingestion. Each row shows daily data for one participant

Fig. 6

Raster display of the time courses of adverse events classified as possibly related to pexacerfont. Each row shows daily data for one participant