No Evidence of Moderated Impulsivity Following Administration of the IMPase Inhibitor Ebselen in Healthy Adults
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
- Trevor Sharp (ORCID: https://orcid.org/0000-0001-7434-9713)
- Jawad Sultan Raja
- Alberto Salmoiraghi (ORCID: https://orcid.org/0000-0001-5464-9639)
- Nikhil Gauri Shankar
- Robert D. Rogers (ORCID: https://orcid.org/0000-0001-5010-069X)
- Timothy J. Davies
- Phillip J. Cowen (ORCID: https://orcid.org/0000-0001-5518-6138)
- Luke Earnshaw
- Matthew P. G. John (ORCID: https://orcid.org/0000-0002-4752-5440)
Institutions
- Bangor University (GB)
- Oxford Health NHS Foundation Trust (GB)
- Warneford Hospital (GB)
- University of Oxford (GB)
- Ysbyty Gwynedd Hospital NHS Trust (GB)
Publication Details
- Journal
- Human Psychopharmacology Clinical and Experimental
- Published
- 2026-04-21
- DOI
- https://doi.org/10.1002/hup.70040
- Primary Topic
- Neurotransmitter Receptor Influence on Behavior
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Medical Research Council