A review of safety, side-effects and subjective reactions to intranasal oxytocin in human research

doi:10.1016/j.psyneuen.2011.02.015

Psychoneuroendocrinology

Volume 36, Issue 8, September 2011, Pages 1114-1126

https://doi.org/10.1016/j.psyneuen.2011.02.015 Get rights and content

Summary

Background

Human research investigating the impact of intranasal oxytocin on psychological processes has accelerated over the last two decades. No review of side effects, subjective reactions and safety is available.

Method

A systematic review of 38 randomised controlled trials conducted between 1990 and 2010 that investigated the central effects of intranasal oxytocin was undertaken. A systematic search for reports of adverse reactions involving intranasal oxytocin was also completed.

Results

Since 1990, research trials have reported on N = 1529 (79% male) of which 8% were participants with developmental or mental health difficulties. Dosages ranged from 18 to 40 IU, mainly in single doses but ranged up to 182 administrations. Diverse methods have been used to screen and exclude participants, monitor side effects and subject reactions. Side effects are not different between oxytocin and placebo and participants are unable to accurately report on whether they have received oxytocin and placebo. Three case reports of adverse reactions due to misuse and longer-term use of intranasal oxytocin were reported.

Conclusions

The evidence shows that intranasal oxytocin: (1) produces no detectable subjective changes in recipients, (2) produces no reliable side-effects, and (3) is not associated with adverse outcomes when delivered in doses of 18–40 IU for short term use in controlled research settings. Future research directions should include a focus on the dosage and duration of use, and application with younger age groups, vulnerable populations, and with females.

Section snippets

Selection criteria

The search, retrieval and screening of studies were undertaken by the first author. Data sources included regulatory websites, such as the Therapeutic Goods Association (TGA) and The Foods and Drugs Administration (FDA), Medline, the Cochrane Library, Google scholar and a general internet search. Key works used in this search included oxytocin, pitocin, syntocinon, intranasal oxytocin, nasal spray oxytocin, adverse reactions oxytocin, and side-effects oxytocin. A recent systematic review of

Results

All studies collected data on side-effects for both oxytocin and placebo; in the results below, the term ‘side effects’ is thus used with reference to both unless otherwise specified. Questionnaires were returned from authors of 68% (26 out of 38) of studies, no corrections where made although additional information was provided by 21 authors. This additional information included, a statement highlighting that no side-effects occurred (n = 13), details regarding side-effects when they did

Discussion

This paper reviewed side effects and safety data on the use of intranasal oxytocin in 38 controlled trials conducted over the last 20 years. To date, 1529 participants have received intranasal oxytocin or placebo, of which only 279 reported mild side-effects. The main categories included: (1) increased calmness/euphoria or more energy; (2) light headedness, drowsiness and/or headache and (3) nasal irritation, dry mouth/throat. No difference in the type, frequency and severity of side effects

Role of the funding source

The authors did not receive funding for this project and so there is no role to report.

Conflict of interest

The authors have no conflict of interest in providing an impartial report. The authors report no biomedical financial interest. The authors are conducting a clinical trial investigating the impact of intranasal oxytocin with youth within the autism spectrum.

Acknowledgements

We would like to thank the researchers who kindly provided additional information regarding the monitoring and reporting of side-effects from their studies.

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ReviewA review of safety, side-effects and subjective reactions to intranasal oxytocin in human research

Summary

Background

Method

Results

Conclusions

Section snippets

Selection criteria

Results

Discussion

Role of the funding source

Conflict of interest

Acknowledgements

Psychoneuroendocrinology

Neuron

Psychoneuroendocrinology

Psychoneurocrinology

Peptides

Biol. Psychiatry

Psychoneurodocrinology

Biol. Psychiatry

Biol. Psychiatry

J. Biol. Chem.

Biol. Psychiatry

Peptides

Neuropsychologia

Psychoneuroendocrinology

Biol. Psychiatry

Psychoneurocrinology

Biol. Psychiatry

Biol. Psychiatry

Biol. Psychiatry

Physiol. Behav.

Biol. Psychiatry

Front Neuroend.

Psychoneuroendocrinology

Biol. Psychiatry

Am. J. Obstet. Gynecol.

Prog. Brain Res.

Psychiatry Res.

Psychoneuroendocrinology

Biol. Psychiatry

Horm. Behav.

Acute effects of intranasal oxytocin on subjective and behavioural responses to social rejection

Exp. Clin. Psychopharmacol.

Promoting social behaviour with oxytocin in high-functioning autism spectrum disorders

PNAS

A Visual Motor Gestalt Test and Its Clinical Use

The Revised Visual Retention Test: Clinical and Experimental Applications

Sniffing neuropeptides: a transnasal approach to the human brain

Nature

Goldman & Gilmas: The Pharmacological Basis of Therapeutics

Review
A review of safety, side-effects and subjective reactions to intranasal oxytocin in human research