# Pioglitazone as an adjunct to CBT for cocaine relapse prevention

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2022 · $664,976

## Abstract

PROJECT SUMMARY
 Over one million American adults suffer from cocaine use disorder (CUD) with recent trends showing
an increase in cocaine-related deaths since 2010. For the chronic cocaine user, significant changes in brain
function and structure set the stage for relapse that, unfortunately, continues to be the most common outcome
following treatment. For substance use disorders, cognitive-behavioral therapy (CBT) is arguably the most
empirically supported and widely used relapse prevention approach. Considered to be a cognitive control
therapy, CBT aims to improve ‘top-down’ executive control functions that are impaired in CUD and strongly
connected to relapse. Converging evidence suggests that CBT promotes meaningful changes in brain regions
associated with cognitive control. Still, many patients with cognitive impairments show suboptimal response
to CBT, bolstering the call for research aimed at improving effects with integrative treatments.
 The goal of the proposed project is to enhance the relapse-prevention effects of CBT with adjunctive use
of pioglitazone (PIO), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist. Unlike
traditional medications that target classic neurotransmitter systems, PIO’s activation of the PPAR pathway
confers broad spectrum anti-inflammatory and neuroprotective effects against insult to brain white matter
(WM). The functional significance of WM in CUD has been well established by evidence showing that: (1)
chronic cocaine exposure alters WM structural integrity; (2) WM alterations compromise cognitive function in
CUD; and (2) better WM integrity predicts better CUD treatment outcome. In a recent proof of concept trial
we found that PIO significantly improved brain WM integrity in a small sample of non-abstinent patients with
CUD. Treatment with PIO was well-tolerated and associated with reduced cocaine craving relative to placebo.
Collectively, these findings raise the exciting possibility that PIO may augment responding to CBT via improved
neural structure and cognitive function.
 We are proposing a randomized double-blind clinical trial to evaluate the efficacy of CBT with
adjunctive PIO in recently abstinent patients during the early phase of recovery when craving is prominent,
relapse risk is high, and intact cognitive control is required to actively maintain abstinence. During 5-day
inpatient detoxification, 60 adults with CUD will be randomized to receive PIO or placebo, followed by 12
weeks of outpatient CBT treatment while continuing to receive adjunctive study medication. Specific aims will
examine the effects of PIO on targeted mechanisms of change (WM integrity, cognitive function, cocaine
craving) and demonstrate evidence linking clinical efficacy (abstinence, functional health) with mechanism
engagement. Expected results will establish PIO as an adjunctive treatment that can be integrated with CBT to
reduce relapse risk following detoxification, thereby meeting NIDA’s strategic prio...

## Key facts

- **NIH application ID:** 10404968
- **Project number:** 5R01DA048026-03
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** SCOTT D LANE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $664,976
- **Award type:** 5
- **Project period:** 2020-07-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10404968

## Citation

> US National Institutes of Health, RePORTER application 10404968, Pioglitazone as an adjunct to CBT for cocaine relapse prevention (5R01DA048026-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10404968. Licensed CC0.

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