Intranasal oxytocin attenuates the cortisol response to physical stress: a dose-response study
Abstract
INTRODUCTION Intranasal oxytocin attenuates cortisol levels during social stress inductions. However, no research to date has documented the dose-response relation between intranasal oxytocin administration and cortisol, and researchers examining intranasal oxytocin have not examined the cortisol response to physical stress. We therefore examined the effects of 24IU and 48IU of intranasal oxytocin on the cortisol response to vigorous exercise. METHOD Seventeen males participated in a randomized, placebo-controlled, double-blind, and within-subject experiment. Participants engaged in vigorous exercise for 60min following the administration of placebo or intranasal oxytocin on three occasions. Saliva samples and mood ratings were collected at eight intervals across each session. RESULTS Salivary cortisol concentrations changed over time, peaking after 60min of exercise (quadratic: F(1,16)=7.349, p=.015, partial η(2)=.32). The 24IU dose of oxytocin attenuated cortisol levels relative to placebo (F(1,16)=4.496, p=.05, partial η(2)=.22) and the 48IU dose, although the latter fell just short of statistical significance (F(1,16)=3.054, p=.10, partial η(2)=.16). There was no difference in the cortisol response to exercise in participants who were administered 48IU of intranasal oxytocin relative to placebo. Intranasal oxytocin had no effect on mood. CONCLUSION This is the first study to demonstrate that the effect of intranasal oxytocin on salivary cortisol is dose-dependent, and that intranasal oxytocin attenuates cortisol levels in response to physical stress. Future research using exogenous oxytocin will need to consider the possibility of dose-response relations.
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24 IU but not 48 IU of inhaled oxytocin attenuated salivary cortisol levels during a subsequent physical stressor.
“Furthermore, Cardoso et al. (2013) showed that 24 IU but not 48 IU of inhaled oxytocin attenuated salivary cortisol levels during a subsequent physical stressor.”
From Endogenous peripheral oxytocin measures can give insight into the dynamics of social relationships: a review (2014) · cites this paper as Cardoso et al., 2013
Middle doses (20-24 IU) of oxytocin have the greatest positive effects, whereas low (10 IU) or high doses (48 IU) show blunted effects.
“Middle doses (20–24 IU) have the greatest positive effects, whereas low (10 IU) or high doses (48 IU) show blunted effects (Goldman et al., 2011; Hall et al., 2012; Cardoso et al., 2013).”
From Endogenous peripheral oxytocin measures can give insight into the dynamics of social relationships: a review (2014) · cites this paper as Cardoso et al., 2013
There is no consensus on optimal doses for inhaled oxytocin, and dosage has been hard to control.
“The current limitations of the inhaled oxytocin approach are that as yet, dosage has been hard to control and indeed there is no consensus on optimal doses for use in studies (Cardoso et al., 2013).”
From Endogenous peripheral oxytocin measures can give insight into the dynamics of social relationships: a review (2014) · cites this paper as Cardoso et al., 2013
Studies that controlled for dose show important dose-dependent variation on physiology or social cognition.
“Studies that have controlled for dose show important dose-dependent variation on physiology (Cardoso et al., 2013) or social cognition (Goldman et al., 2011; Hall et al., 2012).”
From Endogenous peripheral oxytocin measures can give insight into the dynamics of social relationships: a review (2014) · cites this paper as Cardoso et al., 2013
In humans, 24-IU, but not 48-IU, of intranasal oxytocin attenuates cortisol levels in response to physical stress.
“In voles, the propensity to display behaviors such as pair bonding is modulated in a dose-dependent manner (142), and in humans, 24-IU, but not 48-IU, of OXT IN attenuates cortisol levels in response to physical stress (143).”
From Dissecting the Role of Oxytocin in the Formation and Loss of Social Relationships (2016) · cites this paper as [143]
The dose and timing of medication administration is based on past research in our group and others.
“The dose and timing of medication administration is based on past research in our group and others (Cardoso et al., 2013; Flanagan et al., 2015; MacDonald et al., 2011).”
From Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: a randomized, placebo-controlled pilot trial (2018) · cites this paper as Cardoso et al., 2013
Dose-dependent effects of OT on social behavior in animals and humans indicate that lower doses of OT may be more efficacious.
“Dose-dependent effects of OT on social behavior in animals (Benelli et al., 1995;Popik et al., 1992) and humans (Cardoso et al., 2013;Hall et al., 2012;Quintana et al., 2015b) that indicate that lower doses of OT may be more efficacious warrants further research.”
From Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial (2016) · cites this paper as Cardoso et al., 2013
In studies examining differential oxytocin doses, the dose around 20 IU (24 IU or 20 IU) had more favorable effects compared to the other dose studied (48, 40 or 10 IU).
“In these studies the dose around 20 IU (24 IU or 20 IU) had more favorable effects compared to the other dose studied (48, 40 or 10 IU).”
From Efficacy of oxytocin administration early after psychotrauma in preventing the development of PTSD: study protocol of a randomized controlled trial (2014) · cites this paper as [104]
Only a few studies have examined the differential effects of higher (24, 40 or 48 IU) and lower (10, 20 or 24 IU) oxytocin doses.
“Only a few studies examined the differential effects of higher (24, 40 or 48 IU) and lower (10, 20 or 24 IU, respectively) oxytocin doses [103-105].”
From Efficacy of oxytocin administration early after psychotrauma in preventing the development of PTSD: study protocol of a randomized controlled trial (2014) · cites this paper as [104]
The studies examining differential oxytocin doses were single administration studies on non-clinical outcome measures.
“However, these studies were single administration studies on non-clinical outcome measures.”
From Efficacy of oxytocin administration early after psychotrauma in preventing the development of PTSD: study protocol of a randomized controlled trial (2014) · cites this paper as [104]
In healthy individuals, OT effects seem to follow an inverted u-shape, with doses around 24 IU resulting in more anxiolytic effects than higher doses.
“In healthy individuals, OT effects seem to follow an inverted u-shape (Rilling et al, 2014), with doses ~24 IU, resulting in more anxiolytic effects than higher doses of OT (Cardoso et al, 2013).”
From Intranasal oxytocin administration dampens amygdala reactivity towards emotional faces in male and female PTSD patients (2016) · cites this paper as Cardoso et al, 2013
OT applied at higher doses, such as 40 IU used in this study, may result in anxiogenic effects in healthy individuals, owing to competitive binding to AVP receptors.
“Moreover, OT applied at higher doses (eg, 40 IU used in this study) may result in anxiogenic effects in healthy individuals, owing to competitive binding to argininevasopressin (AVP) receptors (Cardoso et al, 2013).”
From Intranasal oxytocin administration dampens amygdala reactivity towards emotional faces in male and female PTSD patients (2016) · cites this paper as Cardoso et al, 2013
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References 60 · Cited by 187
- Authors
- Cardoso, C., Ellenbogen, M. A., Orlando, M. A., Bacon, S. L., & Joober, R.
- Affiliations
- Concordia University (CA)
- Montreal Heart Institute (CA)
- Douglas Mental Health University Institute (CA)
- Corresponding author
- Ellenbogen, Mark A.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 38
- Issue
- 3
- Pages
- 399-407
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W1981648524
- Semantic Scholar
- 181f6fb291906db50d696e9c39c2137cbfced8fb
- Cited by
- 187
- References
- 60
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 11 · 2023: 5 · 2022: 10 · 2021: 10 · 2020: 14 · 2019: 20 · 2018: 19 · 2017: 22 · 2016: 16 · 2015: 20 · 2014: 15 · 2013: 10 · 2012: 1
- FWCI
- 22.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- intranasal oxytocin, salivary cortisol, physical stress, high-intensity exercise, dose-response relationship, stress response attenuation, mood, social stress
- MeSH terms
- Administration, Intranasal, Adolescent, Adult, Affect, Dose-Response Relationship, Drug, Double-Blind Method, Humans, Hydrocortisone, Male, Oxytocin, Saliva, Stress, Physiological, Time Factors, Exercise
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