Intranasal Oxytocin: Myths and Delusions

Abstract

Despite widespread reports that intranasal application of oxytocin has a variety of behavioral effects, very little of the huge amounts applied intranasally appears to reach the cerebrospinal fluid. However, peripheral concentrations are increased to supraphysiologic levels, with likely effects on diverse targets including the gastrointestinal tract, heart, and reproductive tract. The wish to believe in the effectiveness of intranasal oxytocin appears to be widespread and needs to be guarded against with scepticism and rigor. Preregistering trials, declaring primary and secondary outcomes in advance, specifying the statistical methods to be applied, and making all data openly available should minimize problems of publication bias and questionable post hoc analyses. Effects of intranasal oxytocin also need proper dose-response studies, and such studies need to include control subjects for peripheral effects, by administering oxytocin peripherally and by blocking peripheral actions with antagonists. Reports in the literature of oxytocin measurements include many that have been made with discredited methodology. Claims that peripheral measurements of oxytocin reflect central release are questionable at best.

Oxytocin pathways in the intergenerational transmission of maternal early life stress

“…In addition, OT may contribute to enhanced emotion recognition of salient infant social cues through increased activation of specific brain regions (insula and inferior frontal gyrus) that are part of the empathy related brain network (Shamay-Tsoory, 2011). It should be acknowledged, however, that imaging studies using intranasal OT challenge are controversial (Leng and Ludwig, 2015). For example, although administering supraphysiological doses of OT, only a very small fraction can be detected in the CSF (Leng and Ludwig, 2015) and it is questionable whether this has direct modulating effects on brain functioning and behavior.…”

“…It should be acknowledged, however, that imaging studies using intranasal OT challenge are controversial (Leng and Ludwig, 2015). For example, although administering supraphysiological doses of OT, only a very small fraction can be detected in the CSF (Leng and Ludwig, 2015) and it is questionable whether this has direct modulating effects on brain functioning and behavior. Furthermore, it is very likely that strong increases of peripheral OT concentrations after intranasal OT application have effects on peripheral organs (e.g., the heart, gastrointestinal tract, reproductive tract) – and might confound the direct effects of OT in the brain.…”

Oxytocin und die suchterhaltenden Mechanismen der Alkoholabhängigkeit

“…Oxytocin wird zentral im PVN als Reaktion auf Stress ausgeschüttet, um die Stressreaktion abzudämpfen [32] [33]. Darüber hinaus weisen die Oxytocin-mRNA-und CRF-mRNAExpression im PVN nach akuter und auch chronischer Stressexposition eine negative Korrelation auf.…”

“…Außerdem ist es kaum ZNS-gängig. Dies limitiert den Einsatz von Oxytocin als zentral wirksames Therapeutikum bei peripherer Gabe, da Oxytocin die Blut-Hirn-Schranke nicht in nennenswertem Maße überqueren kann [33,54]. Zudem konnten nach i.v.…”

“…Zudem konnten nach i.v. Gabe von radioaktiv markiertem Vasopressin, ein Nonapeptid mit gleicher Bioverfügbarkeit, das sich in zwei Aminosäuren von Oxytocin unterscheidet, keine intakten Peptide im Liquor nachgewiesen werden [33]. Bei oraler Gabe würden das saure Milieu und die Enzyme des Magens das kurze Peptidhormon binnen kürzester Zeit inaktivieren.…”