# Anandamide in blood pressure control

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2024 · $94,500

## Abstract

PROJECT SUMMARY
Hypertension (HTN) is a primary risk factor for cardiovascular disease (CVD). The Systolic Blood Pressure
Intervention Trial (SPRINT) was performed in hypertensive individuals with high CVD risk. The study showed
that blood pressure (BP) target of <120mm Hg compared with <140mm Hg significantly reduced CVD events
and all-cause deaths [1]. However, almost 15% of all SPRINT participants experienced serious adverse events
(SAEs) including hypotension, syncope, bradycardia, acute kidney injury (AKI), and electrolyte abnormalities [1].
Our data point towards the contribution of the endocannabinoid system (ECS) in this process.
EC system is an ancient, preserved, but only recently discovered biological system shown to play a pivotal role
in regulation of BP [2]. The ECS is composed of endocannabinoids, including anandamide (AEA), the enzymes
that produce and degrade endocannabinoids and their receptors. Interestingly, similarly to subjects that reported
SAEs within the SPRINT trial, acute cannabis users present with bradycardia, hypotension, syncope and
electrolyte abnormalities [3, 4]. Supporting studies in hypertensive animals have indicated the essential role of
AEA-mediated signaling in the development of bradycardia and hypotension [5-10]. Interestingly, renin-
angiotensin system, which is the main target of antihypertensive therapy, seems to be reciprocally regulated with
the ECS e.g. increase in AEA reduces vasoconstrictive and hypertensive effects of angiotensin II [11, 12].
In our previous data, we showed reduced plasma levels of AEA in hypertensive non-CKD subjects and CKD as
well as autosomal dominant polycystic kidney disease (ADPKD) patients as compared to healthy subjects [13].
Furthermore, intensive BP control in ADPKD patients (SBP <110mm Hg) as performed within the HALT-PKD
trial, led to an increase of plasma levels of AEA and its congeners [13]. Based on these data, we hypothesize
that intensive (<120mm Hg) as compared to standard (<140mm Hg) BP control in SPRINT participants
will be accompanied by higher levels of AEA and its congeners. We also hypothesize that subjects with
a greater rate of AEA increase will present with a higher incidence of SEAs including hypotension,
syncope and bradycardia.
The knowledge gained from this first-of-its-kind study will allow to better understand the role of the EC system in
regulation of the blood pressure. With the increased use of cannabis and its active ingredients among general
population, the understanding of the interplay between the EC system and the cardiovascular function will be of
utmost importance for current patient management and future drug development studies.

## Key facts

- **NIH application ID:** 10871182
- **Project number:** 1R21HL169709-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Jelena Klawitter
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $94,500
- **Award type:** 1
- **Project period:** 2024-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10871182

## Citation

> US National Institutes of Health, RePORTER application 10871182, Anandamide in blood pressure control (1R21HL169709-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10871182. Licensed CC0.

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