Study type: Human research · Status: Evidence verified by machine against declared source

Effects of route of administration on oxytocin-induced changes in regional cerebral blood flow in humans

Nature communications · 2020

Study scale: This hypothesis is in line with three recent studies.

Product or molecular entity relationships

Oxytocin: Exact entity relationship. Legacy citation custody associates this source with the catalog record; no product-relevance conclusion is implied.

Public plain-language summary

The published text is limited to the declared source and preserves reported uncertainty. It does not establish efficacy, safety, suitability, or evidence strength.

Research question

We address this question by contrasting two methods of intranasal administration (a standard nasal spray, and a nebulizer expected to improve OT deposition in nasal areas putatively involved in direct nose-to-brain transport) to intravenous administration in terms of effects on regional cerebral blood flow during two hours post-dosing.

Study design

Until a ligand allowing for direct quantification of in vivo penetration of OT in the brain after intranasal administration might be produced, a dose-response study using the nebulizer may allow us to gain further indirect insights about whether using the nebulizer may confer certain advantages regarding targeting the central OT system.

Participants or experimental system

Upper panel, Drug allocation scheme: In each session, participants received treatment via all three administration routes, in one of two fixed sequences: either nebulizer/intravenous infusion/standard nasal spray, or standard nasal spray/intravenous infusion/nebulizer.

Study scale

This hypothesis is in line with three recent studies.

Intervention or exposure

Our work has important translational implications and demonstrates the need to carefully consider the method of administration in our efforts to engage specific central oxytocinergic targets for the treatment of neuropsychiatric disorders.

Comparator

Intranasal delivery allows for fast absorption of small molecules into the peripheral circulation25,26, at the cost of poor and unreliable control of the amount of the drug absorbed25,26.

Outcomes examined

Harnessing the central OT system has been identified as a promising strategy in translational neuroscience for the development of targeted pharmacological interventions to improve outcome in several conditions currently lacking efficacious treatments (e.g. autism spectrum disorder7, schizophrenia8, migrain9, stroke6, obesity10, Prader-Willi11).

Key findings

We demonstrate that OT-induced decreases in amygdala perfusion, a key hub of the OT central circuitry, are explained entirely by OT increases in systemic circulation following both intranasal and intravenous OT administration.

Limitations and uncertainty

Human studies almost exclusively target the central OT system by administering synthetic OT using nasal sprays, despite a lack of understanding of the mechanisms underpinning its pharmacodynamic effects.

Product relevance and evidence boundary

This record is a published study, held here with its citation and review status. It is not a statement that any catalog item is effective, safe, or suitable for any use, and nothing in it is a dose or a protocol.

Evidence verified by machine against declared source. Verification is limited to the declared source and review scope. It does not mean independent replication or establish efficacy, safety, or suitability.