# A Novel Nutrition-Based Anti-Relapse Intervention for Cocaine Addiction

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2020 · $201,875

## Abstract

ABSTRACT
Relapse to drug seeking after abstinence is a major challenge in treating substance use disorder. Abstinent
drug users remain at risk of relapse even after extended drug-free periods. Exposure to drug-associated cues
or stress during abstinence can trigger intense craving and precipitate relapse. New and more effective anti-relapse interventions are critically needed, particularly for cocaine use disorder since no effective
pharmacological intervention is available. We discovered that a nutritional supplement we developed for
clinical use, as part of a nutritional approach for managing substance use disorder, had the benefit of being a
potentially robust anti-relapse therapy. This supplement, SMAASH-C, contains a combination of vitamins,
omega-3 fatty acids, and minerals, as well as tyrosine and other amino acids that are known to be depleted by
chronic cocaine exposure. We originally learned of its potential therapeutic value through anecdotal reports
from our patients of reduced drug craving, reduced stress and anxiety, and less frequent relapses. As a follow-up, we screened SMAASH-C in a rat model of relapse, and confirmed its potential efficacy as an anti-relapse
intervention. Specifically, we found that 15-days of SMAASH-C treatment during abstinence, via a clinically
relevant oral route (mixed in food), resulted in a 50% reduction in extinction and cue-induced cocaine-seeking
as compared to control treatment (non-supplemented food). Notably, SMAASH-C did not affect body weight,
food intake, or non-specific responding during the cocaine-seeking tests indicating its potential as a safe and
selective intervention. In fact, results from toxicology analyses of a 12-week SMAASH-C treatment regime in
saline and cocaine-withdrawn rats suggests that it offsets markers of cocaine-induced toxicity (e.g., oxidative
stress, hepatic injury). The overall objective of this R21 application is to provide preclinical proof-of-concept data for the use of SMAASH-C as an effective, safe, and selective anti-cocaine relapse
intervention. To do so, we will determine its efficacy at reducing cocaine-seeking following extended access
self-administration and protracted abstinence, and in response to two of the most common triggers of craving
and relapse in humans: drug-associated cues (Aim 1) and stress (Aim 2). Selectivity will be assessed by
comparing effects on cocaine- versus sucrose-seeking. Both males and females will be included given
literature highlighting the need for sex-specific interventions. As a first step toward understanding the
mechanisms underlying its efficacy, we will examine markers of dopaminergic and glutamatergic signaling in
the reward pathway following relapse testing using qPCR and Western Blot analysis. Our overall hypothesis is
that SMAASH-C will robustly (>50%), selectively (no effect on sucrose-seeking), and dose-dependently
decrease relapse vulnerability and associated neuroadaptations in both males and females. Our long-term ...

## Key facts

- **NIH application ID:** 9968214
- **Project number:** 5R21DA047856-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Wendy Jean Lynch
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $201,875
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968214

## Citation

> US National Institutes of Health, RePORTER application 9968214, A Novel Nutrition-Based Anti-Relapse Intervention for Cocaine Addiction (5R21DA047856-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9968214. Licensed CC0.

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