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.
It is unclear if and how exogenous oxytocin (OT) reaches the brain to improve social behavior and cognition and what is the optimal dose for OT response. To better understand the delivery routes of intranasal OT administration to the brain and the dose-response, we compared amygdala response to facial stimuli by means of functional magnetic resonance imaging (fMRI) in four treatment conditions, including two different doses of intranasal OT using a novel Breath Powered device, intravenous (IV) OT, which provided similar concentrations of blood plasma OT, and placebo. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults administering a single-dose of these four treatments. We observed a treatment effect on right amygdala activation during the processing of angry and happy face stimuli, with pairwise comparisons revealing reduced activation after the 8IU low dose intranasal treatment compared to placebo. These data suggest the dampening of amygdala activity in response to emotional stimuli occurs via direct intranasal delivery pathways rather than across the blood-brain barrier via systemically circulating OT.



This trial is registered at the U.S. National Institutes of Health clinical trial registry (www.clinicaltrials.gov; NCT01983514) and as EudraCT no. 2013-001608-12.
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, University of Oslo, Oslo, Norway.
Daniel S
DS
Quintana
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, University of Oslo, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
Lars T
LT
Westlye
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, University of Oslo, Oslo, Norway.
Dag
D
Alnæs
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, University of Oslo, Oslo, Norway.
Øyvind G
ØG
Rustan
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, University of Oslo, Oslo, Norway.
Tobias
T
Kaufmann
Smerud Medical Research International AS, Oslo, Norway.
Knut T
KT
Smerud
OptiNose US Inc, Yardley, PA, USA.
Ramy A
RA
Mahmoud
OptiNose AS, Oslo, Norway.
Per G
PG
Djupesland
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, University of Oslo, Oslo, Norway. Electronic address: o.a.andreassen@medisin.uio.no.
Ole A
OA
Andreassen
D000281:Administration, Intranasal; D000328:Adult; D000679:Amygdala / Q000187:drug effects*; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004644:Emotions / Q000502:physiology; D005149:Facial Expression; D000066499:Facial Recognition / Q000187:drug effects*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010121:Oxytocin / Q000378:metabolism / Q000494:pharmacology*; D012919:Social Behavior; D055815:Young Adult
D010121:Oxytocin
Dose-response; Intranasal; Intravenous; Oxytocin; fMRI