# Pharmacological Facilitation of Behavioral Modification for Cocaine Use Disorders

> **NIH NIH U01** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2020 · $695,715

## Abstract

Project Summary
Alterations in glutamate neurotransmission are recognized as an important target of
pharmacotherapy for cocaine use disorders (CUDs). Our preliminary investigations with
ketamine, a glutamate modulator with potent prefrontal effects, suggest sub-anesthetic
infusions may work to facilitate behavioral modification by addressing critical CUD-
related vulnerabilities. Alongside being safely administered to active cocaine users, we
have found that sub-anesthetic ketamine, 24 hours post-infusion, significantly increases
motivation to stop cocaine use by 60%, decreases cue-induced craving by a similar
magnitude, and reduces the choice for cocaine now vs. money later by 67% when
compared to an active control. A pilot efficacy trial also indicates that a single infusion of
ketamine facilitates mindfulness-based relapse prevention (MBRP) and promotes
abstinence (53% ketamine vs. 11% midazolam). Expanding on these promising but
preliminary findings, this trial aims to evaluate whether ketamine promotes abstinence by
facilitating behavioral modification in a treatment model approximating a general clinical
setting. We will evaluate the effect of up to two outpatient sub-anesthetic doses of
ketamine (0.11 mg/kg over 2 minutes, followed by 0.60 mg/kg over 50 minutes) on
CUDs in 110 non-depressed individuals engaged in motivation enhancement therapy
followed by MBRP. We predict that, compared to the control midazolam, ketamine will
significantly promote 3 weeks of end-of-study abstinence in this 7-week trial. Secondary
aims pertain to the effects of ketamine on other drug use outcomes, such as reduction in
number of cocaine use days; and the evaluation of behavioral and biological mediators
of ketamine efficacy, such as serum brain-derived neurotrophic factor (BDNF) levels and
measures of behavioral non-reactivity. If successful, this project stands to contribute
significantly to the treatment of CUDs, for which there are no clearly effective
pharmacotherapies at present, and has the potential to lead the field in new directions of
combined medication-behavioral treatment development. Future studies might test other
medications using the design introduced in this proposal, as well as focus on clarifying
the mechanisms by which ketamine addresses CUDs.

## Key facts

- **NIH application ID:** 9922890
- **Project number:** 5U01DA040647-04
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** Elias Dakwar
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $695,715
- **Award type:** 5
- **Project period:** 2017-05-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9922890

## Citation

> US National Institutes of Health, RePORTER application 9922890, Pharmacological Facilitation of Behavioral Modification for Cocaine Use Disorders (5U01DA040647-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9922890. Licensed CC0.

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