Alcohol, clinical & experimental research · 2026
A Secondary, Subgroup Analysis of Alcohol Cue-Exposure Craving in Response to Pharmacological Inhibition of the Growth Hormone Secretagogue Receptor With PF-5190457.
СтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Tyler Ryan E, Abreu Valerie Espinal, Farokhnia Mehdi, Leggio Lorenzo
Аннотация
BACKGROUND: Ghrelin is the endogenous agonist of the growth hormone secretagogue receptor (GHSR), which is a potential novel pharmacotherapeutic target for alcohol use disorder (AUD). PF-5190457 is a GHSR inverse agonist and the first GHSR inhibitor to advance to human trials. Our lab conducted two placebo-controlled human laboratory studies to investigate the effects of PF-5190457 (100 mg/day) on alcohol craving in an alcohol cue-exposure paradigm. Study 1 found reduced craving under drug versus placebo, whereas Study 2 did not replicate these findings, likely due to a floor effect and reflective of the differences in AUD populations (Study 1: active drinkers; Study 2: abstinent, inpatient).
METHODS: The present work is a secondary analysis combining these datasets and using subgroups based on alcohol cue-reactivity ("cue-reactors," CR+ vs. "nonreactors," CR-) or the Penn Alcohol Craving Scale ("PACS high cravers" vs. "PACS low cravers") as an additional independent variable to reanalyze the effects of PF-5190457 on alcohol craving (Alcohol Urge Questionnaire [AUQ]) following a "relaxation" trial (no cues) and an "alcohol cue" trial (mock bar-lab and preferred alcohol-containing drink). Cue-reactivity was calculated as the difference in AUQ between trials (AUQAlc-AUQRel) and analyzed by subgroups as a separate outcome.
RESULTS: PF-5190457 reduced AUQ scores relative to placebo following the alcohol cue trial in the CR+ subgroup, but not the CR- subgroup. PF-5190457 also reduced AUQ compared to placebo following both the relaxation and alcohol cue trial in the PACS high craver subgroup, but not in the PACS low craver subgroup. Cue-reactivity was not affected by PF-5190457 in any subgroup analysis.
CONCLUSIONS: These results are preliminary and based on secondary analyses, but suggest that PF-5190457 could help reduce general, self-reported craving for alcohol in high-craving individuals.
METHODS: The present work is a secondary analysis combining these datasets and using subgroups based on alcohol cue-reactivity ("cue-reactors," CR+ vs. "nonreactors," CR-) or the Penn Alcohol Craving Scale ("PACS high cravers" vs. "PACS low cravers") as an additional independent variable to reanalyze the effects of PF-5190457 on alcohol craving (Alcohol Urge Questionnaire [AUQ]) following a "relaxation" trial (no cues) and an "alcohol cue" trial (mock bar-lab and preferred alcohol-containing drink). Cue-reactivity was calculated as the difference in AUQ between trials (AUQAlc-AUQRel) and analyzed by subgroups as a separate outcome.
RESULTS: PF-5190457 reduced AUQ scores relative to placebo following the alcohol cue trial in the CR+ subgroup, but not the CR- subgroup. PF-5190457 also reduced AUQ compared to placebo following both the relaxation and alcohol cue trial in the PACS high craver subgroup, but not in the PACS low craver subgroup. Cue-reactivity was not affected by PF-5190457 in any subgroup analysis.
CONCLUSIONS: These results are preliminary and based on secondary analyses, but suggest that PF-5190457 could help reduce general, self-reported craving for alcohol in high-craving individuals.