# Proof-of-Concept Clinical Trial of Lamotrigine as a Candidate Pharmacotherapy for Adolescent Alcohol Use Disorder

> **NIH NIH R21** · BROWN UNIVERSITY · 2020 · $246,212

## Abstract

PROJECT SUMMARY
The goal of this exploratory proposal is to evaluate the feasibility and potential efficacy of lamotrigine (LTG), a
voltage-gated sodium channel inhibitor that blunts glutamatergic transmission, for treating adolescents with
alcohol use disorder (AUD). Alcohol use typically begins during adolescence and prevalence rates for AUD
peak before age 21. Yet, despite clinical demand, treatments for youth rely on psychosocial interventions that
yield only modest benefits; most return to hazardous drinking. One potential way to improve adolescent alcohol
treatment is to augment the best available psychosocial interventions with pharmacotherapy. Although the FDA
approved four medications to treat AUD in adults, no medication is indicated for adolescents, and controlled
clinical trials with teenagers are almost nonexistent. Optimizing treatment options for youth will require closing
this gap in medication development research. Prior work shows that anticonvulsants attenuate alcohol
withdrawal, blunt craving, and reduce alcohol and other drug use. While these medications yield medium
additive effects on drinking outcomes when paired with psychosocial treatments, they are poorly tolerated,
especially by youth, which undermines their clinical utility. We propose to explore LTG, an anticonvulsant with
a minimal side effect profile that is well-tolerated and shown to reduce alcohol and other drug use in adults. Its
effects on adolescent AUD, however, are untested. This proof-of-concept study will leverage an innovative
approach to medication development for youth with AUD that pairs human laboratory and ecological
momentary assessment (EMA) methods. Adolescents with alcohol use disorder (N = 50, ages 16-19 years) will
be randomized to LTG or placebo. A 6-week titration period will be followed by 3 weeks at the target dose (200
mg/day) and a two-week taper period. As in our prior work, all youth will receive a five session behavioral
platform comprised of motivational enhancement therapy and alcohol-focused cognitive behavioral therapy.
This behavioral platform affords the most meaningful and ethical test of LTG in this vulnerable and high-risk
population. A 3-month follow-up will evaluate sustained benefit. Our major aims are to evaluate the feasibility
and tolerability of LTG among adolescents with AUD, apply our human laboratory and EMA paradigms to
evaluate the effects of LTG on intermediate phenotypes associated with alcohol use and outcomes in clinical
trials, and evaluate the effects of LTG on alcohol use at the target dose and at the 3-month follow-up. This
study is intended to fill a critical void in medication development for adolescents with AUD. Our aims also
address national priorities to gather safety and efficacy data on medications for treating AUD in youth. Results
from this proof-of-concept study will inform whether a larger (R01) clinical trial is warranted.

## Key facts

- **NIH application ID:** 9958642
- **Project number:** 1R21AA028394-01
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** ROBERT MIRANDA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $246,212
- **Award type:** 1
- **Project period:** 2020-06-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9958642

## Citation

> US National Institutes of Health, RePORTER application 9958642, Proof-of-Concept Clinical Trial of Lamotrigine as a Candidate Pharmacotherapy for Adolescent Alcohol Use Disorder (1R21AA028394-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9958642. Licensed CC0.

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