# Role of the circadian rhythm on endocannabinoid response to an acute stress

> **NIH NIH K01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $181,006

## Abstract

Project Summary
Cardiovascular (CV) disease is the leading cause of death in the US. Night and rotating shift work, ~20% of the
labor force, is associated with a greater incidence of both psychosocial stress and CV disease suggesting that
wakefulness and activity when the body is optimized for sleep and recovery is harmful to one’s health. Acute
stressors in the form of both heightened emotions in response to a psychosocial stress and moderate exercise
can trigger a CV event, however, the underlying physiology remains unclear. Endocannabinoids (eCB) are lipid
messengers that modulate the emotional and physiological response to stress and have also been demonstrated
to regulate CV function. Colleagues and I have recently demonstrated a robust endogenous circadian rhythm in
basal levels of circulating eCBs with a trough during the biological night. However, the circadian variation in eCB
reactivity, change from baseline in response to an acute stress, remains unclear. A difference in eCB response
and associated CV reactivity to an acute stress across the circadian system provides a plausible pathway that
could underlie risks for development of CV disease in shift workers. Thus, I aim to test the hypotheses that
changes of circulating eCBs in response to (a) an acute psychosocial stress and (b) a mild somatic stress
(exercise) are dependent upon circadian phase and will correlate with changes in emotional and CV reactivity.
The proposed research will take advantage of the opposite effects on mood of psychosocial stress (depressed
mood) and exercise stress (improved mood) to further examine how eCB regulation of emotional processing is
related to CV function. Additionally, as Black Americans have the highest age-adjusted CV disease mortality and
persistently demonstrate differential responses to stress this proposal will test the hypothesis that Blacks
compared to Whites will have attenuated eCB responses to psychosocial and somatic stressors. These aims will
be achieved via a multi-day circadian protocol (dim lighting free of time cues) with sleep-wake cycles adjusted
to recurring 18h cycles so that after numerous cycles all behaviors occur evenly across all circadian phases.
Assessments include circadian phase and amplitude from salivary melatonin, circulating eCBs from blood
plasma and mood from questionnaires. Relevant markers of CV function will include autonomic function and
markers of hemostasis. This protocol will be performed in 40 healthy adults as an additional component to my
primary mentor’s active project (R01HL142064, PI, Steven Shea). Elucidation of mechanisms that impact stress
reactivity across the circadian system integrates my prior training and is a logical progression in my research
career that will provide valuable information for evaluating the utility of evidence-based interventions. To achieve
my long-term goal of becoming an independent scientist translating stress and circadian research between the
laboratory and community...

## Key facts

- **NIH application ID:** 10320481
- **Project number:** 5K01HL151745-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Nicole P Bowles
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $181,006
- **Award type:** 5
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320481

## Citation

> US National Institutes of Health, RePORTER application 10320481, Role of the circadian rhythm on endocannabinoid response to an acute stress (5K01HL151745-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10320481. Licensed CC0.

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