# Ketamine-induced Hypertensive Episodes: Adverse Central and Peripheral Neurovascular Actions

> **NIH NIH F32** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $50,398

## Abstract

PROJECT SUMMARY/ABSTRACT
National Institutes of Health Director Francis Collins, MD, PhD and drug abuse expert Nora Volkow, MD recently
stated that we need to prioritize “finding safe and effective interventions to manage chronic pain” and that we
must “find new, innovative medications…to treat opioid addiction.” Low dose ketamine, a N-methyl-D-aspartate
antagonist, effectively reduces pain in pre-hospital and hospital settings and reduces opioid use in acute pain
settings. Recent clinical trials have demonstrated that low dose ketamine reduces psychiatric symptoms
associated with major depressive disorders, anxiety disorders, alcohol withdrawal syndrome, and chronic
migraine. However, future clinical applications of low dose ketamine are currently limited due to well-founded
cardiovascular safety concerns. Thus, the poorly understood cardiovascular safety profile of low dose ketamine
remains a critical barrier, potentially limiting its future therapeutic usage. Specifically, ketamine elicits
hypertensive episodes that sometimes require immediate pharmacological treatment, and can last for several
hours, even in healthy non-hypertensive adults. Currently, we are only partially informed of the mechanisms
underlying these adverse effects through reports in anesthetized animals, which suggest that sympathetic
nervous system overactivity and impaired cardiovascular function contribute to ketamine-induced elevations in
blood pressure. Therefore, the primary objective of this proposed work is to determine the contribution of the
autonomic nervous system and vasculature that cause prolonged hypertensive responses to low dose ketamine
using direct in vivo assessment of sympathetic nervous system activity. We proposed a randomized, double-
blind, crossover, placebo-controlled trial in which each participant will complete ketamine and placebo
experimental trials. During each visit we will assess neural and cardiovascular function following the ketamine
(or placebo) administration. The proposed work will, for the first time, comprehensively examine the mechanisms
by which low dose ketamine causes hypertensive episodes in healthy humans. The results generated from this
project will contribute fundamental knowledge about the cardiovascular safety profile of low dose ketamine in
humans. This research directly supports the mission of NHLBI in that we will uncover and translate mechanistic
physiological findings from human participants with the goal of translating these findings to guide future clinical
practice. To ensure that this study was designed to maximize clinical relevance and my scientific training, I
assembled a strong interdisciplinary clinical research team consisting of expert cardiovascular physiologists
Craig Crandall, PhD, and Paul Fadel, PhD, anesthesiologist Joseph Hendrix, MD, clinician-scientists Benjamin
Levine, MD, Satyam Sarma, MD, David Goldstein, MD, PhD, and Arthur Westover, MD. My primary goals during
this fellowship are to complete t...

## Key facts

- **NIH application ID:** 10232905
- **Project number:** 1F32HL154559-01A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Joseph Watso
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $50,398
- **Award type:** 1
- **Project period:** 2021-06-01 → 2022-03-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10232905

## Citation

> US National Institutes of Health, RePORTER application 10232905, Ketamine-induced Hypertensive Episodes: Adverse Central and Peripheral Neurovascular Actions (1F32HL154559-01A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10232905. Licensed CC0.

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