title: Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment.
abstract: Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel 'Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device.
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: D S
authors.initials: DS
authors.lastname: Quintana
authors.affiliation: 1] NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, University of Oslo, Oslo, Norway [2] Department of Psychology, University of Oslo, Oslo, Norway.
authors.forename: L T
authors.initials: LT
authors.lastname: Westlye
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Ø G
authors.initials: ØG
authors.lastname: Rustan
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: N
authors.initials: N
authors.lastname: Tesli
authors.affiliation: 1] NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, University of Oslo, Oslo, Norway [2] Department of Psychology, University of Oslo, Oslo, Norway.
authors.forename: C L
authors.initials: CL
authors.lastname: Poppy
authors.affiliation: 1] NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, University of Oslo, Oslo, Norway [2] Department of Psychology, University of Oslo, Oslo, Norway.
authors.forename: H
authors.initials: H
authors.lastname: Smevik
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: M
authors.initials: M
authors.lastname: Tesli
authors.affiliation: Smerud Medical Research International AS, Oslo, Norway.
authors.forename: M
authors.initials: M
authors.lastname: Røine
authors.affiliation: OptiNose US Inc, Yardley, PA, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Mahmoud
authors.affiliation: Smerud Medical Research International AS, Oslo, Norway.
authors.forename: K T
authors.initials: KT
authors.lastname: Smerud
authors.affiliation: OptiNose AS, Oslo, Norway.
authors.forename: P G
authors.initials: PG
authors.lastname: Djupesland
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: O A
authors.initials: OA
authors.lastname: Andreassen
mesh_terms: D000281:Administration, Intranasal / Q000295:instrumentation / Q000379:methods*; D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005149:Facial Expression; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D009296:Nasal Cavity / Q000033:anatomy & histology; D059906:Neuroimaging; D010121:Oxytocin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D012919:Social Behavior; D012938:Social Perception; D014667:Vasopressins / Q000097:blood; D055815:Young Adult
chemical_list: D014667:Vasopressins; D010121:Oxytocin; D006854:Hydrocortisone