Page 38 - ITPS-8-1

INNOSC Theranostics

and Pharmacological Sciences

REVIEW ARTICLE
Subanesthetic ketamine for reducing the harm

of cocaine use disorder

1†
1
1
Ambar Liriano , Xinyu Gu 2† , Wanhong Zuo , and Jiang-Hong Ye *
1 Department of Anesthesiology, Pharmacology, Physiology and Neuroscience, Rutgers University,
New Jersey Medical School, New Jersey, United States of America
2 Case Western Reserve University School of Medicine, Ohio, United States of America

Abstract

Subanesthetic ketamine offers promising potential for reducing harm in
individuals with cocaine use disorder (CUD). Research indicates that even a
single dose can lessen cravings and decrease drug-seeking behaviors, though
achieving long-term abstinence remains challenging. However, reduced
cocaine consumption itself is a meaningful outcome. Ketamine’s potential
in reducing the harm of CUD is also supported by its mechanism of action in
the dopaminergic system, as it counters cocaine’s effect by interacting with
dopamine receptors, stabilizing brain-derived neurotrophic factor levels, and
modulating lateral habenula neuron bursting. In addition, concerns about
† These authors contributed equally
to this work. ketamine’s abuse potential are minimized when it is administered in a clinical
setting under professional supervision. This is supported by its success as a
*Corresponding author:
Jiang-Hong Ye treatment for depression, indicating that, with appropriate safeguards, ketamine
(ye@njms.rutgers.edu) could be a valuable pharmacological strategy for harm reduction in CUD. When
Citation: Liriano A, Gu X, Zuo W, developing ketamine as a CUD harm-reduction strategy, it is also important to
Ye J. Subanesthetic ketamine for account for sex differences, which may affect patients’ sensitivity to ketamine and
reducing the harm of cocaine use the potential for misuse. Although the promising effects of ketamine in treating
disorder. INNOSC Theranostics
and Pharmacological Sciences. depression support its use for CUD, most studies have focused on depression
2025;8(1):32-46. models, and additional research is needed to confirm safety and understand its
doi: 10.36922/itps.4458 specific mechanisms in CUD. Nonetheless, subanesthetic ketamine is a promising
Received: August 6, 2024 CUD intervention and should be further explored to provide an efficient and safe
solution for patients in need. This narrative review mainly elucidates the ongoing
Revised: November 18, 2024
research regarding ketamine’s mechanisms of action, pharmacology, and clinical
Accepted: December 4, 2024 application potential in CUD.
Published online: December 27,
2024
Keywords: Cocaine use disorder; Ketamine; Dopamine; Nucleus accumbens; Ventral
Copyright: © 2024 Author(s). tegmental area; N-methyl-D-aspartate receptor; α-amino-3-hydroxy-5-methyl-4-
This is an Open-Access article
distributed under the terms of the isoxazolepropionic acid receptor; Brain-derived neurotrophic factor
Creative Commons Attribution
License, permitting distribution,
and reproduction in any medium,
provided the original work is
properly cited. 1. Introduction
Publisher’s Note: AccScience Cocaine, the second most used illicit drug worldwide, remains a significant public
Publishing remains neutral with health concern. According to the United Nations Office on Drugs and Crime, in 2020,
1
regard to jurisdictional claims in 2
published maps and institutional the number of past-year cocaine users reached over 20 million worldwide. Like other
affiliations substance use disorders, cocaine use disorder (CUD) is a chronic condition represented

Volume 8 Issue 1 (2025) 32 doi: 10.36922/itps.4458