No Evidence of Moderated Impulsivity Following Administration of the IMPase Inhibitor Ebselen in Healthy Adults

Journal article

Objective: Impulsivity is a transdiagnostic risk factor for numerous health morbidities and is strongly associated with early relapse and poor treatment outcomes in addictions and mood‐disorders. Lithium carbonate can be helpful in moderating the impulsive behaviors associated with mania, possibly mediated by reduced myo‐inositol activity following inhibition of the enzyme inositol monophosphatase (IMPase). We tested the hypothesis that impulsivity—as motor disinhibition, decisions without adequate information, and stronger preferences for small immediate rewards over larger later rewards—can be moderated by the IMPase inhibitor ebselen in healthy adult volunteers. Methods: One hundred and thirty healthy adults completed a between‐subjects, double‐blind, placebo‐controlled protocol. Over 2 days, participants received a previously validated dose of 1800 mg of ebselen or placebo before completing tests of impulsivity and decision‐making. Results: There were no substantive changes in any measure of impulsivity following treatment with ebselen compared with placebo. Neither was there any convincing evidence of stronger treatment effects in high‐trait impulsive participants compared with low‐trait participants. Conclusion: These results fail to replicate findings that ebselen administration moderates validated measures of impulsivity in healthy adults, at least at doses shown to reduce myo‐inositol within the medial prefrontal cortex and produce changes in emotional processing and reward‐based learning.

Authors: John, MPG; Earnshaw, L; Shankar, NG; Raja, JS; Davies, TJ

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Human Psychopharmacology: Clinical & Experimental
• Volume: 41
• Issue: 3
• Article number: e70040
• Publication date: 2026-04-21
• Acceptance date: 2026-03-25
• DOI: 10.1002/hup.70040
• EISSN: 1099-1077
• ISSN: 0885-6222
• Language: English
• Keywords: ebselen; myo‐inositol; inositol monophosphatase; impulsivity