# The Effects of the Histamine-3 Receptor Inverse Agonist Pitolisant on Alcohol Self-Administration in Heavy Drinkers

> **NIH NIH R21** · BOSTON MEDICAL CENTER · 2021 · $211,375

## Abstract

Project Summary
More
annual
causes
have
the
than 16 million adults suffer from Alcohol Use Disorder (AUD) in the United States and the estimated
economic burden of AUD is $249 billion. Approximately 88,000 Americans die from alcohol-related
each year; untreated AUD is t he fourth most preventable cause of death in the US. Four medications
been FDA-approved for treating AUD, but none of these medications have proven to be effective across
heterogeneous groups of drinkers. Treating addiction more effectively is goal with national importance and
accelerating drug development for AUD is one of the priorities for NIAAA. This proposal is intended to answer
this call for accelerating drug development by exploring the potential of the histamine-3 (H-3) receptor inverse
agonist/antagonist, pitolisant, as a candidate medication for the treatment of AUD. There is now substantial
preclinical evidence that H-3 receptor antagonists and inverse agonists/antagonists can suppress behaviors
that model both alcohol consumption and reward. These drugs have been shown to reduce alcohol
consumption by rodents and attenuate alcohol-induced place preference. The administration of either an H-3
antagonist or of an antagonist/inverse agonist can block cue-induced reinstatement of responding for alcohol in
mice. These findings are consistent with idea that alcohol seeking behaviors can be attenuated by agents that
counteract the actions of H-3 receptor activation. There
pitolisant
intended
agent
AUD
aims
craving,
days
days
method.
order
priming
consume
induced
may This study may provide a rationale for phase II RCTs testing pitolisant
with a treatment-seeking AUD population. These results may also help to spur further clinical investigation of
the effects of pitolisant on the factors implicated in the regulation of alcohol consumption.
.
are no published clinical studies testing the effects of
or any other H-3 receptor inverse agonist/antagonist on human alcohol consumption. This study is
to accelerate medication development for AUD by testing a commercially-available and well-tolerated
 at a fraction of the cost of new drug discovery. None of the FDA-approved AUD medications or off-label
medications target H-3 receptors, making pitolisant a promising compound for development. The specific
of this study are to test the effects of pitolisant administration on 1) alcohol self-administration and
2) alcohol consumption and craving during a 5-day period of exposure, 3) sleep quality during the 5
of pitolisant administration, and, 4) the stimulant effects of a priming drink of alcohol. The effects of 5-
of pitolisant or placebo will be evaluated in a human laboratory using an alcohol self-administration
 In this within-subjects crossover design study, 36 heavy drinkers will be randomized to exposure
(pitolisant or placebo) prior to completing two alcohol self-administration trials. Subjects will receive a
drink of alcohol and will have access to 8 drinks over a 2-hour period. We...

## Key facts

- **NIH application ID:** 10266182
- **Project number:** 5R21AA028864-02
- **Recipient organization:** BOSTON MEDICAL CENTER
- **Principal Investigator:** ERIC G. DEVINE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $211,375
- **Award type:** 5
- **Project period:** 2020-09-20 → 2023-08-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10266182

## Citation

> US National Institutes of Health, RePORTER application 10266182, The Effects of the Histamine-3 Receptor Inverse Agonist Pitolisant on Alcohol Self-Administration in Heavy Drinkers (5R21AA028864-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10266182. Licensed CC0.

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