Recommendations for the standardisation of oxytocin nasal administration and guidelines for its reporting in human research
Abstract
A series of studies have reported on the salubrious effects of oxytocin nasal spray on social cognition and behavior in humans, across physiology (e.g., eye gaze, heart rate variability), social cognition (e.g., attention, memory, and appraisal), and behavior (e.g., trust, generosity). Findings suggest the potential of oxytocin nasal spray as a treatment for various psychopathologies, including autism and schizophrenia. There are, however, increasing reports of variability of response to oxytocin nasal spray between experiments and individuals. In this review, we provide a summary of factors that influence transmucosal nasal drug delivery, deposition, and their impact on bioavailability. These include variations in anatomy and resultant airflow dynamic, vascularisation, status of blood vessels, mode of spray application, gallenic formulation (including presence of uptake enhancers, control release formulation), and amount and method of administration. These key variables are generally poorly described and controlled in scientific reports, in spite of their potential to alter the course of treatment outcome studies. Based on this review, it should be of no surprise that differences emerge across individuals and experiments when nasal drug delivery methods are employed. We present recommendations for researchers to use when developing and administering the spray, and guidelines for reporting on peptide nasal spray studies in humans. We hope that these recommendations assist in establishing a scientific standard that can improve the rigor and subsequent reliability of reported effects of oxytocin nasal spray in humans.
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Oxytocin has a role in regulating complex social behavior, including parental care, social bonding and social cognition in general.
“More recently, attention has turned to its role in regulating complex social behavior, including parental care, social bonding and social cognition in general (1–6).”
From Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies (2016) · cites this paper as [4]
Recommendations regarding administration procedures made by Guastella et al. were followed, although participants' nasal cavities were not medically examined.
“Recommendations regarding administration procedures made by Guastella et al. [19] were followed, although participants’ nasal cavities were not medically examined.”
From Salivary oxytocin concentrations in males following intranasal administration of oxytocin: a double-blind, cross-over study (2015) · cites this paper as [19]
There is no standard operating procedure for saliva collection in oxytocin research.
“It is important to note that although many studies use the same commercial ELISA kit, there is no standard operating procedure for saliva collection (an issue raised by [19]).”
From Salivary oxytocin concentrations in males following intranasal administration of oxytocin: a double-blind, cross-over study (2015) · cites this paper as [19]
Three potential routes of intranasal OT delivery to the brain have been identified: two direct nose-to-brain pathways and an indirect pathway across the BBB via systemically circulating OT.
“Three potential routes have been identified (Guastella et al., 2013;Quintana et al., 2015a): two direct nose-to-brain pathways and an indirect pathway across the BBB via systematically circulating OT.”
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 Guastella et al., 2013
Currently used pump-actuated conventional nasal spray devices for intranasal oxytocin administration are not optimal for the delivery of molecules to the brain.
“Third, currently used pump-actuated conventional nasal spray devices for intranasal oxytocin administration are not optimal for the delivery of molecules to the brain.32”
Applying multiple sprays per dose carries a risk of ineffective delivery of intranasal oxytocin.
“Another limitation with regard to the dose and administration method used is that it carries a risk of ineffective delivery, since we apply multiple sprays per dose [106].”
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 [106]
Chronic powder cocaine use may influence rhinoanatomy and intranasal oxytocin absorption, which may influence the results presented here.
“Chronic powder cocaine use may also influence rhinoanatomy and intranasal oxytocin absorption, which may influence the results presented here (Guastella et al., 2013).”
From Effects of adverse childhood experiences on the association between intranasal oxytocin and social stress reactivity among individuals with cocaine dependence (2015) · cites this paper as Guastella et al., 2013
Volunteers were randomly assigned to intranasal administration of either oxytocin (24 IU) or placebo in accordance with current guidelines.
“Volunteers were randomly assigned to intranasal administration of either OXT (24 IU; Syntocinon-Spray, Novartis; three puffs per nostril, each with 4 IU OXT) or PLC (0.9% sodium chloride solution) in accordance with current guidelines (Guastella et al, 2013).”
From Oxytocin Facilitates Pavlovian Fear Learning in Males (2016) · cites this paper as Guastella et al, 2013
Subjects received oxytocin/placebo treatment in accordance with a standardized protocol, and fMRI acquisition started 45 minutes after treatment.
“Subjects received OT/PLC treatment in accordance with a standardized protocol (Guastella et al., 2013), and fMRI acquisition started 45 minutes after treatment.”
From Oxytocin facilitates approach behavior to positive social stimuli via decreasing anterior insula activity (2018) · cites this paper as Guastella et al., 2013
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References 111 · Cited by 357
- Authors
- Guastella, A. J., Hickie, I. B., McGuinness, M. M., Otis, M., Woods, E. A., Disinger, H. M., Chan, H.-K., Chen, T. F., & Banati, R. B.
- Affiliations
- The University of Sydney (AU)
- Boston University (US)
- Corresponding author
- Guastella, Adam J.
- ORCID
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 38
- Issue
- 5
- Pages
- 612-625
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W2055559081
- Cited by
- 357
- References
- 111
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 22 · 2023: 18 · 2022: 25 · 2021: 29 · 2020: 33 · 2019: 36 · 2018: 35 · 2017: 35 · 2016: 17 · 2015: 32 · 2014: 29 · 2013: 13
- FWCI
- 35.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- The Australian Nuclear Science and Technology Organisation Institutional Repository (The Australian Nuclear Science and Technology Organisation) (submittedVersion)
- Funders
- NHMRC (623624, 623625, 1043664)
- ARC Linkage grant (LP110100513)
- BUPA health foundation grant (2012-00004)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- oxytocin, nasal spray, mucosal drug delivery, bioavailability, reporting guidelines, standardization, social cognition, autism spectrum disorder, schizophrenia, interindividual variability
- MeSH terms
- Administration, Intranasal, Adsorption, Humans, Human Experimentation, Nasal Mucosa, Nose, Oxytocin, Research Design, Practice Guidelines as Topic, Nasal Sprays
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