# Neuroscience-informed Treatment Development for Adolescent Alcohol Use Disorders

> **NIH NIH K23** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $200,772

## Abstract

PROJECT SUMMARY/ABSTRACT
Relevance: Adolescent alcohol use is problematic and has long-term negative cognitive and social
consequences. Decreasing substance use at this early stage could have significant long-term benefits to
psychosocial outcomes and deter progression to habitual use; however, efforts to prevent or decrease alcohol
use during adolescence have only been modestly effective, and pharmacotherapy research focused on
adolescent alcohol use has been sparse. Evaluation of alternative and more efficacious treatments for
adolescent alcohol users is warranted.
Description: N-acetylcysteine (NAC) is an over-the-counter antioxidant supplement with glutamatergic
properties that has shown promise in treating marijuana dependence in adolescents. Preclinical findings
suggest NAC works through restoring glutamate homeostasis disrupted by addiction, a finding replicated
across multiple substances of abuse. No published clinical trials to date have examined the efficacy of NAC on
alcohol use. This is surprising, given previous promising NAC findings in marijuana-dependent adolescents
and the safety, tolerability, and affordability of this over-the-counter supplement. This K23 application proposes
to examine the effects of NAC on alcohol cue reactivity, adolescent glutamatergic systems, and drinking
behaviors in a randomized, double-blind, placebo-controlled within-subjects crossover study. In
counterbalanced order, 40 participants will receive a 10-day course of NAC 1200 mg twice daily and a
subsequent 10-day course of matched placebo twice daily, separated by washout period. Human laboratory
and imaging procedures will be conducted at baseline and after each course of medication treatment to clarify
NAC's effect on glutamatergic systems and alcohol cue reactivity. Functional magnetic resonance imaging
(fMRI) will examine alcohol reactivity and magnetic resonance spectroscopy will examine glutamate levels in
the anterior cingulate after NAC versus placebo over the same interval.
Aims: This proposal provides optimal training for the applicant to gain expertise in substance use disorder
clinical trials research, evidence based treatments for adolescent substance users, and magnetic resonance
spectroscopy methods and analysis needed to conduct independent, patient-oriented, developmental research
on neural mechanisms associated with adolescent substance use and treatment. Findings from this study will
help establish if NAC could be a promising treatment for adolescent substance users, an area of research that
is consistent with trans-NIH initiative to identify and generate novel substance use treatments for adolescents
(see PA-15-036 and PA-15-256).

## Key facts

- **NIH application ID:** 9984922
- **Project number:** 5K23AA025399-05
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Lindsay Squeglia
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $200,772
- **Award type:** 5
- **Project period:** 2016-09-20 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984922

## Citation

> US National Institutes of Health, RePORTER application 9984922, Neuroscience-informed Treatment Development for Adolescent Alcohol Use Disorders (5K23AA025399-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9984922. Licensed CC0.

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