# Neurobiology of Ketamine Addiction

> **NIH NIH R01** · FLORIDA STATE UNIVERSITY · 2020 · $371,847

## Abstract

PROJECT SUMMARY
A single injection of small dose of ketamine induced a rapid resolution of suicidal ideation.
Since acute ketamine effects are short lived, recent clinical studies are testing whether
subchronic treatments with ketamine can prevent relapse to depression. The results of these
studies are promising as they clearly show that repeated ketamine infusions achieved superior
outcome when compared to acute treatment. It is clear therefore that the viability of ketamine
as an antidepressant treatment will necessitate repeated infusions of small doses under a
chronic regimen. The safety of such treatments is still not very clear when one acknowledges
that ketamine is considered a drug of abuse. Furthermore, the comorbidity of depression with
other drugs of abuse, especially alcohol adds further complications to the viability of ketamine
as a treatment for depression. Finally, the effects of ketamine in both sexes are still
understudied. The ketamine doses that are used to treat Treatment Resistant Depression
[TRD] in humans work for both sexes and, so far, there were no efforts made to examine the
antidepressant effects of lower doses of ketamine in women. This is despite some evidence in
humans showing that ketamine use leads to severe cognitive impairments in women when
compared to men and some evidence in rodents, showing higher sensitivity of female rodents to
the analgesic and the antidepressant effects of ketamine. In rodents, ketamine also leads to
greater neurotoxicity in females when compared to males. Accordingly, it is critical that further
clinical and preclinical studies examine the safety of repeated treatments with low doses of
ketamine, in both sexes, before approving ketamine as a safe treatment for TRD. Through this
application we shall answer very specific questions about the safety of long term treatment with
ketamine: 1- In both sexes, do repeated treatments with low doses of ketamine induce
addictive-like behaviors? 2- Does female hormonal status play a role in response to ketamine's
addictive properties?; 3- Does alcohol abuse enhance the addictive properties of ketamine in
either sex? 4- What are the physiological adaptations that occur in the brain with repeated
ketamine treatments? We truly believe that the response to these questions will inform clinicians
about the safety or not of chronic ketamine treatment for TRD.

## Key facts

- **NIH application ID:** 9990760
- **Project number:** 5R01DA043461-03
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** MOHAMED KABBAJ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $371,847
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990760

## Citation

> US National Institutes of Health, RePORTER application 9990760, Neurobiology of Ketamine Addiction (5R01DA043461-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9990760. Licensed CC0.

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