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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 \u2018Breath Powered\u2019 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\u2009IU (international units) or 24\u2009IU OT, 1\u2009IU 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\u2009IU OT in comparison to both placebo and 24\u2009IU 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.<\/jats:p>","DOI":"10.1038\/tp.2015.93","type":"journal-article","created":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T13:44:16Z","timestamp":1436881456000},"page":"e602-e602","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":104,"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"],"prefix":"10.1038","volume":"5","author":[{"given":"D S","family":"Quintana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L T","family":"Westlye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d8 G","family":"Rustan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Tesli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C L","family":"Poppy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Smevik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Tesli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"R\u00f8ine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R A","family":"Mahmoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K T","family":"Smerud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P G","family":"Djupesland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O A","family":"Andreassen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,7,14]]},"reference":[{"key":"BFtp201593_CR1","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/j.yhbeh.2012.01.002","volume":"61","author":"AJ Guastella","year":"2012","unstructured":"Guastella AJ, MacLeod C . 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RAM is an employee of OptiNose US, Yardley, PA, USA and owns stock and stock options in OptiNose. OAA has received speaker\u2019s honoraria from GSK, Lundbeck and Otsuka for work not directly relevant to the submitted manuscript. MT has received speaker\u2019s honorarium from Medivir for work not directly relevant to the submitted manuscript. MR and KTS are employed (and KTS owner) by Smerud Medical Research International AS, a CRO receiving fees for clinical trial services from OptiNose AS. The remaining authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}