A Secondary, Subgroup Analysis of Alcohol Cue‐Exposure Craving in Response to Pharmacological Inhibition of the Growth Hormone Secretagogue Receptor With PF ‐5190457

ABSTRACT 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 (AUQ Alc ‐AUQ Rel ) 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.