Epstein David H, Kennedy Ashley P, Furnari Melody, Heilig Markus, Shaham Yavin, Phillips Karran A, Preston Kenzie L
National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 251 Bayview Blvd., BRC Building, Suite 200, Baltimore, MD, 21224, USA.
Psychopharmacology (Berl). 2016 Dec;233(23-24):3921-3932. doi: 10.1007/s00213-016-4424-5. Epub 2016 Sep 5.
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 CRF antagonist 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 (r = 0.30, 95 % CL = -0.12, 0.63, Bayes factor 11.30). Similarly, nightly YFAS ratings were lower with pexacerfont than placebo (r = 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 CRF antagonists, especially for food.
在啮齿动物中，促肾上腺皮质激素释放因子（CRF）受体拮抗剂可阻断应激诱导的药物或美味食物寻求行为的恢复。
测试CRF拮抗剂培沙舍丰对人类的抗渴望特性。
我们研究了体重指数（BMI）>22且在饮食抑制（食物专注和长期节食失败）方面得分较高的人群的应激诱导进食情况。在一项双盲、组间试验中，31名“抑制型”进食者被稳定给予培沙舍丰（300毫克/天，持续7天，然后100毫克/天，持续21天）或安慰剂。在第15天，他们接受了数学测试应激源；在随后的三次访视中，他们听取了个性化的渴望诱导脚本。在每次试验中，通过虚假味觉测试和视觉模拟量表评估应激诱导的食物消耗和渴望程度。我们使用数字视频监测研究胶囊的每日摄入量以及耶鲁食物成瘾量表（YFAS）上食物问题/专注程度的夜间评分。
由于对美国联邦法律的行政解释，该研究提前终止，与安全性或结果无关。虚假味觉测试表明培沙舍丰对实验室应激源后的进食有一定的保护作用（r = 0.30，95%置信区间 = -0.12，0.63，贝叶斯因子11.30）。同样，培沙舍丰组的夜间YFAS评分低于安慰剂组（r = 0.39，置信区间0.03，0.66），但由于尽管培沙舍丰的药代动力学较慢，但从服药的第一晚就出现了这种效果，因此应谨慎解释这一结果。
这些发现可能支持进一步研究CRF拮抗剂的抗渴望特性，尤其是对食物的抗渴望特性。
