The DOI matches its Crossref record; 111 of the 113 references it cites were found in a registry or an index; 30 of the 88 sources its claims cite were checked for support.
Intranasal Oxytocin: Myths and Delusions
Open accessAbstract
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.
Overview
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Written from the paper’s full text.
TL;DR
The review argues that despite widespread reports of behavioral effects, very little intranasally applied oxytocin reaches CSF while peripheral concentrations rise to supraphysiological levels. It contends that many findings are undermined by poor oxytocin assays, publication bias, and questionable analyses, and calls for preregistration, dose-response studies, and controls for peripheral effects.
Key findings
- Across seven studies of intranasal oxytocin/vasopressin, at most 0.005% of the intranasal dose reached CSF within an hour; two studies found no rise. Intranasal doses exceeded pituitary content as a bolus, yet produced only modest CSF increases.
- Intranasal administration produced large, prolonged rises in circulating oxytocin: four studies achieved plasma oxytocin >20 pg/ml from basal <5 pg/ml; Modi et al. reported a 100-fold increase in macaques to >300 pg/ml, and Dal Monte et al. reported a rise to 80 pg/ml after nasal spray but no significant rise with a nebuliser.
- Many plasma oxytocin measurements used unextracted ELISA yielding values >300 pg/ml; three studies comparing ELISA with and without extraction on the same samples reported no correlations. Peripheral measurements are questionable as reflections of central release.
- Recent trials with clear primary outcomes showed no effect of intranasal oxytocin in schizophrenia, healthy volunteers, early psychosis, Prader-Willi syndrome, MDMA users, or youths with autism spectrum disorders; in one autism study, caregivers who believed their children received oxytocin reported greater improvements than those who believed their child received placebo.
Methods
- Critical/narrative review of published animal and human literature on intranasal oxytocin pharmacokinetics, CSF and plasma measurements, behavioral effects, and publication bias; no new experimental data are reported.
- Synthesizes seven studies measuring CSF oxytocin or vasopressin after intranasal administration and compares reported CSF/plasma concentrations and estimated percentages of dose reaching CSF.
- Discusses assay validity, including extracted versus unextracted plasma measurements, radioimmunoassay, LC/mass spectrometry, and ELISA, and reviews trial-design issues such as preregistration and primary outcome reporting.
Limitations
- The authors state that it is not impossible that enormous intranasal doses achieve biologically significant brain elevations, and that intranasally applied oxytocin might penetrate some brain regions yet not enter CSF.
- They state that effects of intranasal oxytocin need proper dose-response studies and controls for peripheral effects, by administering oxytocin peripherally and by blocking peripheral actions with antagonists.
- Evident from the text: this is a narrative critical review, not a systematic review or meta-analysis, and its conclusions depend on cited studies with heterogeneous methods and measurements.
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Claims the paper makes
35 No full text of the sources · 13 Own interpretation · 11 Partly supported · 7 Supported · 7 No basis given · 3 Supported so far · 3 Not supported · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Comparing CSF levels of neurophysin and oxytocin suggests that only ~5% of the oxytocin that is released in the rat brain reaches the CSF (1).”
§ Intranasal oxytocin: myths and delusions > Peripheral targets for oxytocin
What the sources say
- Disputedcites [1] Leng, 2008, Neurotransmitters and peptides: Whispered secrets and public announcements, J Physiol sourceExperimental — accuracy not yet measured
The paper’s Abstract compares CSF oxytocin with co-released neurophysin and estimates that about 80 oxytocin vesicles per second reach the CSF, versus about 4,000 released centrally. That implies roughly 2%, not the cited sentence’s ~5%. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Disputed
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Chang et al. gave 25IU oxytocin to two macaques, and reported a rise in CSF from ~20 to ~50pg/ml at 35min (24).”
§ Intranasal oxytocin: myths and delusions > Oxytocin penetration of the brain after intranasal administration
What the sources say
- Partly supportedcites [24] Chang, 2012, Inhaled oxytocin amplifies both vicarious reinforcement and self reinforcement in rhesus macaques (Macaca mulatta), Proc Natl Acad Sci U S A sourceExperimental — accuracy not yet measured
The Results say two male macaques received 25 IU intranasal oxytocin, and the CSF OT Protocol says CSF was sampled on average 35 minutes after inhalation began. The Methods report an approximately 2.5-fold rise in CSF oxytocin, consistent with 20 to 50 pg/mL, but our copy does not state those absolute concentrations. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“or in MDMA users (92)”
§ Intranasal oxytocin: myths and delusions > Central and peripheral release of oxytocin
What the sources say
- Partly supportedcites [92] Kuypers, 2014, No evidence that MDMA-induced enhancement of emotional empathy is related to peripheral oxytocin levels or 5-HT1a receptor activation, PloS One sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says plasma and CSF oxytocin concentrations do not correlate when sampled at the same time, citing another study for that observation. But this paper measured serum oxytocin in MDMA users, not CSF oxytocin, so it does not establish that the two concentrations are uncorrelated in MDMA users. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, many papers have used an ELISA on unextracted plasma, yielding values of >300pg/ml (59)(60)(61)(62)(63)(64)(65).”
§ Intranasal oxytocin: myths and delusions > Measuring oxytocin and vasopressin
What the sources say
- Not checked — no full text of the sourcecites [59] Feldman, 2011, Maternal and paternal plasma, salivary, and urinary oxytocin and parent-infant synchrony: Considering stress and affiliation components of human bonding, Dev Sci source
- Supportedcites [60] Zhong, 2012, U-shaped relation between plasma oxytocin levels and behavior in the trust game, PloS One source
The Assay Procedures section says the study used a commercial oxytocin ELISA on unextracted plasma. The Results section reports 23 subjects with measured plasma oxytocin above 904 pg/ml, establishing that this cited paper obtained values above 300 pg/ml. (LLM, conf=0.91)
- Partly supportedcites [61] Rubin, 2014, Reduced levels of vasopressin and reduced behavioral modulation of oxytocin in psychotic disorders, Schizophr Bull sourceExperimental — accuracy not yet measured
The Measures section (page unavailable) says this study used an enzyme immunoassay on unextracted plasma and reran oxytocin samples above 2,000 pg/ml, supporting the method and values above 300 pg/ml for this study. It does not establish that many papers used the method and obtained such values. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Much of the interest in intranasal oxytocin followed a report that it enhanced trust (96)”
§ Intranasal oxytocin: myths and delusions > Publication bias
What the sources say
- Supportedcites [96] Kosfeld, 2005, Oxytocin increases trust in humans, Nature source
The paper’s Abstract reports that intranasal oxytocin substantially increased trust in humans, and the LETTERS section repeats the finding. The statement about how much subsequent interest followed is the citing authors’ framing, not a finding attributed to this source. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Three studies have compared ELISA oxytocin measurements of the same samples with and without extraction (69-71): all reported no correlations.”
§ Intranasal oxytocin: myths and delusions > Measuring oxytocin and vasopressin
What the sources say
- Supportedcites [69] Robinson, 2014, Validation of an enzyme-linked immunoassay (ELISA) for plasma oxytocin in a novel mammal species reveals potential errors induced by sampling procedure, J Neurosci Meth source
The Methods (p. 4) say this study measured oxytocin by ELISA in both raw and extracted plasma from the same 52 samples. The Results (section 3.3, p. 5) report no relationship between the paired measurements, supporting this paper as one of the three cited studies. This paper does not establish what the other two studies found. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [70] Suraev, 2014, Adolescent exposure to oxytocin, but not the selective oxytocin receptor agonist TGOT, increases social behavior and plasma oxytocin in adulthood, Horm Behav source
- Supportedcites [71] Szeto, 2011, Evaluation of enzyme immunoassay and radioimmunoassay methods for the measurement of plasma oxytocin, Psychosom Med source
The Results section reports that EIA oxytocin measurements from the same 39 plasma samples did not correlate between extracted and unextracted samples (r = 0.09, p = 0.60). This confirms the finding attributed to this study; the claim’s count of three studies refers to the three citations collectively, not to this paper alone. (LLM, conf=0.93)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Several recent trials conform to some of these conditions, particularly in reporting clear primary outcomes.”
§ Intranasal oxytocin: myths and delusions > Publication bias
What the sources say
- Not checked — no full text of the sourcecites [102] Horta de Macedo, 2014, Oxytocin does not improve performance of patients with schizophrenia and healthy volunteers in a facial emotion matching task, Psychiatry Res source
- Supportedcites [104] Cacciotti-Saija, 2015, A double-blind randomized controlled trial of oxytocin nasal spray and social cognition training for young people with early psychosis, Schizophr Bull source
The Methods (Primary Outcomes) explicitly identifies the trial’s primary outcomes and the three domains they assess. This supports citing the trial as an example of one that reports clear primary outcomes; the source need not itself document the other trials in the citing sentence. (LLM, conf=0.91)
- Partly supportedcites [106] Dadds, 2014, Nasal oxytocin for social deficits in childhood autism: A randomized controlled trial, J Autism Dev Disord sourceExperimental — accuracy not yet measured
The Design and statistical analysis section identifies this as a randomized controlled trial, and the Outcome measures section clearly describes its social-interaction and repetitive-behaviour measures. Our copy does not identify which outcomes were primary, so it supports this trial as an example with reported outcomes but not the specific claim that it reported clear primary outcomes. (LLM, conf=0.78)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Every source the paper cites for this claim was checked and supports it.
In the paper
“and there are similar concerns about basic biological research (98).”
§ Intranasal oxytocin: myths and delusions > Publication bias
What the sources say
- Supportedcites [98] Ioannidis, 2005, Why most published research findings are false, PLoS Med source
In “Most Research Findings Are False for Most Research Designs and for Most Fields” (page unavailable), the paper says that claimed relationships in gene-testing research can have extremely low probabilities of being true, even with standardized laboratory methods. Its genome-association example in Box 1 likewise illustrates reliability concerns in biological research. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“or in early psychosis (104)”
§ Intranasal oxytocin: myths and delusions > Publication bias
What the sources say
- Supportedcites [104] Cacciotti-Saija, 2015, A double-blind randomized controlled trial of oxytocin nasal spray and social cognition training for young people with early psychosis, Schizophr Bull source
The Abstract reports no benefit of oxytocin nasal spray versus placebo on any primary or secondary outcome in this early-psychosis trial. The Discussion likewise reports no improvement in social cognition, symptoms, or social functioning, while noting an exploratory association between greater spray use and reduced negative symptoms. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The recent trials cited as showing no effect had sufficient statistical power to detect effects of intranasal oxytocin.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“or in youths with autism spectrum disorders (106,107).”
§ Intranasal oxytocin: myths and delusions > Publication bias
What the sources say
- Supportedcites [106] Dadds, 2014, Nasal oxytocin for social deficits in childhood autism: A randomized controlled trial, J Autism Dev Disord source
The Discussion reports no benefit from daily nasal oxytocin for young individuals with autism spectrum disorders in this trial. The finding concerns the treatment regimen studied, not every possible use of oxytocin. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [107] Guastella, 2014, The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: A randomized controlled trial, J Child Psychol Psychiatry source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The recent trials cited as showing no effect had sufficient statistical power to detect effects of intranasal oxytocin.
- Supported
- It may state two separate claims as one. 39
- Probably not a substantial claim. 5
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Robertson et al. showed that two radioimmunoassays for vasopressin yielded measurements in unextracted plasma that were at least two orders of magnitude greater than those inferred from other evidence, and which did not fluctuate in parallel with endogenous authentic vasopressin (33,58).”
§ Intranasal oxytocin: myths and delusions > Measuring oxytocin and vasopressin
What the sources say
- Not checked — no full text of the sourcecites [33] Robertson, 1970, Immunoassay of plasma vasopressin in man, Proc Natl Acad Sci U S A source
- Disputedcites [58] Robertson, 1973, Development and clinical application of a new method for the radioimmunoassay of arginine vasopressin in human plasma, J Clin Invest sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“They show no effect of intranasal oxytocin on patients with schizophrenia or healthy volunteers (102,103)”
§ Intranasal oxytocin: myths and delusions > Publication bias
What the sources say
- Not checked — no full text of the sourcecites [102] Horta de Macedo, 2014, Oxytocin does not improve performance of patients with schizophrenia and healthy volunteers in a facial emotion matching task, Psychiatry Res source
- Disputedcites [103] Woolley, 2014, Oxytocin administration enhances controlled social cognition in patients with schizophrenia, Psychoneuroendocrinology sourceExperimental — accuracy not yet measured
The Abstract Results report that intranasal oxytocin significantly improved controlled social cognition in patients with schizophrenia, contrary to the claimed lack of effect. The Discussion (§4.3) also reports improved performance on difficult RMET items in healthy participants, although effects on other aspects of their social cognition were limited. (LLM, conf=0.91)
Checked by a reasoning model — may be wrong.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The recent trials cited as showing no effect had sufficient statistical power to detect effects of intranasal oxytocin.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Dal Monte et al. gave 48IU oxytocin (~10µg/kg body weight) intranasally to macaques, using either a spray or nebuliser (23).These increased CSF oxytocin from ~35pg/ml to ~90pg/ml after 40min.On the (very) conservative assumption that the CSF/ECF volume in the macaque is 40ml, then the additional content at this time is 2.2ng, 0.002% of the administered dose.”
§ Intranasal oxytocin: myths and delusions > Oxytocin penetration of the brain after intranasal administration
What the sources say
- Partly supportedcites [23] Dal Monte, 2014, CSF and blood oxytocin concentration changes following intranasal delivery in macaque, PloS One sourceExperimental — accuracy not yet measured
The Methods report 48 IU intranasal oxytocin given to macaques by spray or nebulizer, and the Results report a significant CSF increase at 40 minutes. Our copy does not state the approximate 35-to-90 pg/ml values; Figure 1’s caption identifies the measurements but gives no numbers. The 40 ml assumption and resulting 2.2 ng and 0.002% calculations are presented as the citing authors’ own, not as findings of Dal Monte et al. (Section passages have no page numbers in our copy.) (LLM, conf=0.82)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Of the above-mentioned studies, four (20,22,24,25) achieved oxytocin concentrations in excess of 20pg/ml from basal levels of <5pg/ml, while Dal Monte et al. reported a rise to 80pg/ml after nasal spray, but no significant rise with a nebulariser (23).Modi et al. reported a 100-fold increase in plasma in the macaque (to >300pg/ml), and a rise to ~60pg/ml (from 10pg/ml) after nebulariser”
§ Intranasal oxytocin: myths and delusions > Peripheral consequences of intranasal oxytocin
What the sources say
- Partly supportedcites [20] Striepens, 2013, Elevated cerebrospinal fluid and blood concentrations of oxytocin following its intranasal administration in humans, Sci Rep sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [22] Neumann, 2013, Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice, Psychoneuroendocrinology source
- Partly supportedcites [24] Chang, 2012, Inhaled oxytocin amplifies both vicarious reinforcement and self reinforcement in rhesus macaques (Macaca mulatta), Proc Natl Acad Sci U S A sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Striepens et al. (20) measured CSF oxytocin in 11 patients given 24IU oxytocin intranasally.Whereas Born et al. saw an increase after 10min (albeit with vasopressin, at a larger dose) (17), Striepens et al. saw no increase at 45 or 60min.However, three patients sampled at 75min had CSF levels 64% higher than controls (at ~30pg/ml).”
§ Intranasal oxytocin: myths and delusions > Oxytocin penetration of the brain after intranasal administration
What the sources say
- Supportedcites [20] Striepens, 2013, Elevated cerebrospinal fluid and blood concentrations of oxytocin following its intranasal administration in humans, Sci Rep source
Methods (Study design) reports 11 participants given 24 IU intranasal oxytocin, including three whose CSF was sampled at 75 minutes. Results finds no significant CSF difference from placebo at 45 or 60 minutes, but a significant increase at 75 minutes. Discussion describes the 75-minute increase as more than 60%, consistent with the cited 64%; Results gives a placebo mean of 19.1 pg/ml, consistent with a treated level of about 30 pg/ml. (LLM, conf=0.85)
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In a larger study, Modi et al. gave 24IU oxytocin (~5µg/kg body weight) to macaques by spray or aerosol; only the aerosol produced a significant increase in CSF (from ~20 to ~60pg/ml) (25).”
- Also stated in: § Oxytocin penetration of the brain after intranasal administration · plain
“Both spray and aerosol raised plasma oxytocin levels.Intravenous administration of the same dose raised plasma levels to ~60,000pg/ml with no increase in CSF.”
§ Intranasal oxytocin: myths and delusions > Oxytocin penetration of the brain after intranasal administration
What the sources say
- Partly supportedcites [25] Modi, 2014, Aerosolized oxytocin increases cerebrospinal fluid oxytocin in rhesus macaques, Psychoneuroendocrinology sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Oxytocin penetration of the brain after intranasal administration · plain
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“It is unsurprising that higher concentrations of oxytocin are needed for behavioral effects than for peripheral effects.As in most G protein-coupled receptors, agonist stimulation of oxytocin receptors leads to desensitization (27).Receptors at peripheral sites are exposed to much lower concentrations of oxytocin (1-10pg/ml), than receptors in the brain (1), so will be more sensitive to it.”
§ Intranasal oxytocin: myths and delusions > How much oxytocin must enter the brain for a behavioral effect?
What the sources say
- Not checked — no full text of the sourcecites [27] Conti, 2009, Intracellular trafficking of the human oxytocin receptor: Evidence of receptor recycling via a Rab4/Rab5 “short cycle.”, Am J Physiol Endocrinol Metabol source
- Partly supportedcites [1] Leng, 2008, Neurotransmitters and peptides: Whispered secrets and public announcements, J Physiol sourceExperimental — accuracy not yet measured
The indexed copy (section labeled Abstract; page unavailable) estimates oxytocin at approximately 1000 pg/ml in extracellular fluid of the supraoptic nucleus, supporting the cited point that brain concentrations can be high. It does not establish the stated peripheral concentration, greater peripheral receptor sensitivity, or the comparison of doses needed for behavioral and peripheral effects. The citing sentence attributes receptor desensitization to a different reference, (27). (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“By contrast, intranasal application of 1µg oxytocin in rats produced no activation at these or any other sites in the forebrain (28) -and no activation in the olfactory bulb, the postulated primary target of interneuronal transfer of oxytocin.”
§ Intranasal oxytocin: myths and delusions > How much oxytocin must enter the brain for a behavioral effect?
What the sources say
- Supportedcites [28] Ludwig, 2013, Intranasal application of vasopressin fails to elicit changes in brain immediate early gene expression, neural activity and behavioural performance of rats, J Neuroendocrinol source
The Methods (Fos expression; page unavailable) specify a 1 μg intranasal oxytocin dose and identify forebrain regions and the olfactory bulbs among the sites assessed. The paper reports no significant effect of intranasal oxytocin on Fos expression; thus, the claim is supported as a statement about the measured activation marker, not every possible form of neural activity. (LLM, conf=0.91)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“In response to i.v.cholecystokinin, oxytocin is released into the blood and in the hypothalamus (79), but several other agents affect release differentially: for instance, in dogs, opioids stimulate peripheral secretion but suppress central secretion (80).”
§ Intranasal oxytocin: myths and delusions > Central and peripheral release of oxytocin
What the sources say
- Not checked — no full text of the sourcecites [79] Neumann, 1994, Stimulation of oxytocin release within the supraoptic nucleus and into blood by CCK-8, Am J Physiol source
- Supportedcites [80] Brown, 2001, Effect of centrally administered opioid receptor agonists on CSF and plasma oxytocin concentrations in dogs, Am J Vet Res source
The Discussion reports that, in dogs, opioid agonists stimulated peripheral oxytocin release while inhibiting central release. It specifies that the peripheral effect involved µ and κ receptors, whereas the central inhibitory effect involved κ receptors. The cholecystokinin statement carries a different citation and is not attributed to this paper. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The discrepancy between measurements in unextracted and extracted plasma is two orders of magnitude, but when Wismer Fries et al. reported that urinary excretion of oxytocin and vasopressin in orphans was affected by early neglect, they reported levels that were, for both peptides, nearly a million fold too high, after applying a method that was neither sensitive enough or selective enough to”
§ Intranasal oxytocin: myths and delusions > Measuring oxytocin and vasopressin
What the sources say
- Partly supportedcites [72] Wismer Fries, 2005, Early experience in humans is associated with changes in neuropeptides critical for regulating social behavior, Proc Natl Acad Sci U S A sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [73] Anderson, 2006, Report of altered urinary oxytocin and AVP excretion in neglected orphans should be reconsidered, J Autism Dev Disord source
- Partly supportedcites [74] Young, 2010, Bioanalytical inaccuracy: A threat to the integrity and efficiency of research, J Psychiatry Neurosci sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Could not verifycites [75] Seltzer, 2010, Social vocalizations can release oxytocin in humans, Proc Biol Sci sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Oxytocin receptors are expressed in the heart, coupled to secretion of natriuretic hormone (48).Oxytocin has direct cardiac effects, and intranasal application in man increases heart rate variability (49).”
§ Intranasal oxytocin: myths and delusions > Peripheral targets for oxytocin
What the sources say
- Not checked — no full text of the sourcecites [48] Gutkowska, 2012, Oxytocin revisited: Its role in cardiovascular regulation, J Neuroendocrinol source
- Partly supportedcites [49] Kemp, 2012, Oxytocin increases heart rate variability in humans at rest: Implications for social approach-related motivation and capacity for social engagement, PloS One sourceExperimental — accuracy not yet measured
The Heart Rate Variability results report increased HRV after intranasal oxytocin relative to placebo. The Introduction says oxytocin and its receptors are present in cardiac tissue, but only suggests that peripheral mechanisms may affect HRV; it does not establish a direct cardiac effect. The natriuretic-hormone statement carries a separate citation (48), so it is not assessed as a claim attributed to this paper. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“attributed to a combination of publication bias, questionable statistical analysis and methodological weaknesses”
§ Intranasal oxytocin: myths and delusions > Publication bias
What the sources say
- Supportedcites [98] Ioannidis, 2005, Why most published research findings are false, PLoS Med source
The Corollaries section links flexible study designs and analytical methods to a lower likelihood that findings are true, and identifies selective reporting as a source of bias. Box 1 describes manipulation of analyses and reporting to produce statistically significant results; the same section explicitly mentions selective publication. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“or in MDMA users (92)”
§ Intranasal oxytocin: myths and delusions > Central and peripheral release of oxytocin
What the sources say
- Partly supportedcites [92] Kuypers, 2014, No evidence that MDMA-induced enhancement of emotional empathy is related to peripheral oxytocin levels or 5-HT1a receptor activation, PloS One sourceExperimental — accuracy not yet measured
The Abstract reports that intranasal oxytocin did not affect the study’s measures of empathy and social interaction in 20 MDMA users. But the Results (Empathy tests and questionnaires; page unavailable) report an effect on self-rated personal distress, so the unqualified claim of “no effect” is too broad. (LLM, conf=0.87)
plain- Asserted: fails — The authors may not put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The authors may not put it forward as true. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
- Rests on an assumption: The recent trials cited as showing no effect had sufficient statistical power to detect effects of intranasal oxytocin.
- Partly supported
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In lactating rats, suckling evokes bursts of action potentials in oxytocin cells that result in pulsatile oxytocin secretion, and this bursting is facilitated by 1-2ng oxytocin i.c.v.(26).Effects on maternal behavior in the rat need much higher doses (~400ng) (4).Partner preference effects in voles require infusions of oxytocin at 10-100ng/h (5), and, to stimulate maternal behavior in sheep, it”
§ Intranasal oxytocin: myths and delusions > How much oxytocin must enter the brain for a behavioral effect?
What the sources say
- Not checked — no full text of the sourcecites [26] Russell, 2003, The magnocellular oxytocin system, the fount of maternity: Adaptations in pregnancy, Front Neuroendocrinol source
- Not checked — no full text of the sourcecites [4] Pedersen, 1982, Oxytocin induces maternal behavior in virgin female rats, Science source
- Not checked — no full text of the sourcecites [5] Williams, 1994, Oxytocin administered centrally facilitates formation of a partner preference in female prairie voles (Microtus ochrogaster), J Neuroendocrinol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Intranasal application in dogs increases glucagon and insulin secretion (37), and this is probably mediated peripherally as intravenous oxytocin has a similar effect in goats (38) and dogs (39).”
§ Intranasal oxytocin: myths and delusions > Peripheral targets for oxytocin
What the sources say
- Not checked — no full text of the sourcecites [37] Altszuler, 1981, Intranasal instillation of oxytocin increases insulin and glucagon secretion, Proc Soc Exp Med source
- Not checked — no full text of the sourcecites [38] Roh, 2014, Actions of intravenous injections of AVP and oxytocin on plasma ACTH, GH, insulin and glucagon concentrations in goats, Anim Sci J source
- Not checked — no full text of the sourcecites [39] Stock, 1985, Oxytocin infusions increase plasma levels of insulin and VIP but not of gastrin in conscious dogs, Acta Physiol Scand source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Oxytocin regulates feeding and metabolism at multiple sites (34,35).Its receptors are expressed throughout the gastrointestinal tract, and on gastric vagal nerve endings (36).”
§ Intranasal oxytocin: myths and delusions > Peripheral targets for oxytocin
What the sources say
- Not checked — no full text of the sourcecites [34] Chaves, 2013, Role of oxytocin in energy metabolism, Peptides source
- Not checked — no full text of the sourcecites [35] Leng, 2008, Oxytocin and appetite, Prog Brain Res source
- Not checked — no full text of the sourcecites [36] Iwasaki, 2014, Peripheral oxytocin activates vagal afferent neurons to suppress feeding in normal and leptin-resistant mice: A route for ameliorating hyperphagia and obesity, Am J Physiol Regul Integr Comp Physiol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although intranasal applications deliver only modest rises in CSF concentrations, they produce large and prolonged increases in circulating oxytocin, to levels far above those needed for physiological effects.”
§ Intranasal oxytocin: myths and delusions > Peripheral consequences of intranasal oxytocin
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Maejima et al. reported that intranasal administration of a higher dose of oxytocin (10µg) activated Fos expression at the paraventricular nucleus, the area postrema and the dorsal motor nucleus of the vagus (29).The area postrema is outside the blood-brain barrier, and should not be accessible to oxytocin from the CSF.These same areas were also activated by oxytocin given systemically.”
§ Intranasal oxytocin: myths and delusions > How much oxytocin must enter the brain for a behavioral effect?
What the sources say
- Not checked — no full text of the sourcecites [29] Maejima, 2015, Nasal oxytocin administration reduces food intake without affecting locomotor activity and glycemia with c-Fos induction in limited brain areas, Neuroendocrinology source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“If 24IU oxytocin were delivered as a bolus intravenously, the peak plasma concentration would exceed 1,400pg/ml, three orders of magnitude higher than physiological concentrations.”
§ Intranasal oxytocin: myths and delusions > How much oxytocin must enter the brain for a behavioral effect?
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Hoover studied 1,806 women who had been given intranasal oxytocin during childbirth (31).Labor was stimulated by 1-4 doses of 0.4-0.8IUgiven at 20-min intervals -a total of, at most, 3.2IU.Equivalent effects were achieved by intravenous infusion of 1-2mU/min, giving rise to the estimate that ~1% of intranasally-applied oxytocin enters the circulation (32).”
§ Intranasal oxytocin: myths and delusions > Peripheral consequences of intranasal oxytocin
What the sources say
- Not checked — no full text of the sourcecites [31] Hoover, 1971, Intranasal oxytocin in eighteen hundred patients. A study on its safety as used in a community hospital, Am J Obstet Gynecol source
- Not checked — no full text of the sourcecites [32] Hendricks, 1960, Use of intranasal oxytocin in obstetrics. 1. A laboratory evaluation, Am J Obstet Gynecol source
hedgeddirectn = 1,806- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Reports in the literature of oxytocin measurements include many that have been made with discredited methodology.”
§ Intranasal oxytocin: myths and delusions > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All seven studies administered enormous amounts of peptide intranasally -in every case more than the pituitary content as a bolus -yet found only modest rises in CSF: two found no rise.At most, 0.005% of intranasally injected oxytocin reaches the CSF within an hour.”
§ Intranasal oxytocin: myths and delusions > Oxytocin penetration of the brain after intranasal administration
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The effectiveness of the blood-brain barrier for oxytocin was measured by Mens et al., who injected 5µg subcutaneously in rats, increasing plasma concentrations 500-fold to ~38,600pg/ml (10).Increases in CSF were modest; concentrations increased from ~40pg/ml to ~150pg/ml.The authors calculated that just 0.002% of the injected oxytocin had reached the CNS after 10min, when CSF concentrations were”
§ Intranasal oxytocin: myths and delusions > Oxytocin and the blood-brain barrier
What the sources say
- Not checked — no full text of the sourcecites [10] Mens, 1983, Penetration of neurohypophyseal hormones from plasma into cerebrospinal fluid (CSF): Half-times of disappearance of these neuropeptides from CSF, Brain Res source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Estimating the CSF volume as 300ml, it seems that ~4.5ng of vasopressin reached the CSF: 0.005% of the given dose -assuming that the rise was due to administered peptide and not endogenous release triggered indirectly.”
§ Intranasal oxytocin: myths and delusions > Oxytocin penetration of the brain after intranasal administration
What the sources say
- Not checked — no full text of the sourcecites [17] Born, 2002, Sniffing neuropeptides: A transnasal approach to the human brain, Nat Neurosci source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Intracranial microdialysis inevitably ruptures blood vessels around the probe, so these measurements might reflect local passage into the brain from damaged vessels.”
§ Intranasal oxytocin: myths and delusions > Oxytocin penetration of the brain after intranasal administration
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Born et al. achieved plasma concentrations of 20pg/ml after giving 40IU vasopressin (17).These are higher than Robertson et al. reported for any patient, including those with pathologically elevated vasopressin secretion; in man, maximal urine concentrating ability is achieved at a vasopressin concentration of ~5pg/ml (33).”
§ Intranasal oxytocin: myths and delusions > Peripheral consequences of intranasal oxytocin
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Neumann et al. gave 20μg of oxytocin intranasally to rats (20 times the pituitary content) and found no change in CSF oxytocin after 45min (22).However, they found a doubling of oxytocin levels in microdialysates of brain regions collected at 30-60min, correlated with a four-fold rise in plasma.”
§ Intranasal oxytocin: myths and delusions > Oxytocin penetration of the brain after intranasal administration
What the sources say
- Not checked — no full text of the sourcecites [22] Neumann, 2013, Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice, Psychoneuroendocrinology source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Thus 1ng oxytocin is the lowest i.c.v.dose shown to elicit a behavioural effect in animal studies, and 2ng induces expression of the immediate-early gene c-fos in rat brain regions where oxytocin receptors are expressed, including in the amygdala and hypothalamus.”
§ Intranasal oxytocin: myths and delusions > How much oxytocin must enter the brain for a behavioral effect?
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Intranasal application achieves higher concentrations of peptide in blood than in CSF, and, as basal concentrations in plasma are lower than in CSF, the proportional change in blood is much greater.”
§ Intranasal oxytocin: myths and delusions > Oxytocin penetration of the brain after intranasal administration
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Oxytocin is released into the brain in large amounts from the soma and dendrites of neurons that project to the pituitary-but this is semi-independent of axonal release, being governed in part by mobilisation of intracellular calcium, a mechanism not present at the terminals (2).”
§ Intranasal oxytocin: myths and delusions > Central and peripheral release of oxytocin
What the sources say
- Not checked — no full text of the sourcecites [2] Ludwig, 2006, Dendritic peptide release and peptide-dependent behaviours, Nat Rev Neurosci source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Some magnocellular neurons project sparsely to some other brain areas, including the amygdala and septum, but it seems likely that most of the central innervations derives from non-neuroendocrine neurons of the paraventricular nucleus (76) that do not project to the pituitary.”
§ Intranasal oxytocin: myths and delusions > Central and peripheral release of oxytocin
What the sources say
- Not checked — no full text of the sourcecites [76] Knobloch, 2012, Evoked axonal oxytocin release in the central amygdala attenuates fear response, Neuron source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Finally, oxytocin at moderately high concentrations is an agonist at V1 vasopressin receptors, and these are expressed at many peripheral sites (including the olfactory epithelium (56); the consequences of activating these is not known).”
§ Intranasal oxytocin: myths and delusions > Peripheral targets for oxytocin
What the sources say
- Not checked — no full text of the sourcecites [56] Levasseur, 2004, Anatomical and functional evidence for a role of arginine-vasopressin (AVP) in rat olfactory epithelium cells, Eur J Neurosci source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Oxytocin is released into blood and brain during parturition, but in sheep (81), plasma concentrations were only elevated for 15min postpartum whereas those in CSF were increased for >120min.”
§ Intranasal oxytocin: myths and delusions > Central and peripheral release of oxytocin
What the sources say
- Not checked — no full text of the sourcecites [81] Kendrick, 1991, Cerebrospinal fluid and plasma concentrations of oxytocin and vasopressin during parturition and vaginocervical stimulation in the sheep, Brain Res Bull source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“One of those papers concludes that adolescent exposure to oxytocin increases plasma oxytocin in adulthood, and it might be expected that this conclusion was drawn from data on extracted plasma (70).Not so: the data from extracted samples showed no differences between groups: instead, the authors built their interpretation on the measurements of unextracted plasma.”
§ Intranasal oxytocin: myths and delusions > Measuring oxytocin and vasopressin
What the sources say
- Not checked — no full text of the sourcecites [70] Suraev, 2014, Adolescent exposure to oxytocin, but not the selective oxytocin receptor agonist TGOT, increases social behavior and plasma oxytocin in adulthood, Horm Behav source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“while CSF oxytocin correlated with social behaviour, plasma levels did not, nor did they correlate with CSF levels collected in the same session (88).”
§ Intranasal oxytocin: myths and delusions > Central and peripheral release of oxytocin
What the sources say
- Not checked — no full text of the sourcecites [88] Winslow, 2003, Rearing effects on cerebrospinal fluid oxytocin concentration and social buffering in rhesus monkeys, Neuropsychopharmacology source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Appetite-related stimuli and some reproductive stimuli activate both central and peripheral oxytocin release, but the timings and extent of these actions differ, and differences are exaggerated by the different pharmacokinetics in the two compartments.”
§ Intranasal oxytocin: myths and delusions > Central and peripheral release of oxytocin
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Stress affects both central and peripheral secretion of oxytocin-but while swim stress in rats increases oxytocin release in the hypothalamus and into plasma (82), novelty stress increases CSF but not plasma concentrations (83).”
§ Intranasal oxytocin: myths and delusions > Central and peripheral release of oxytocin
What the sources say
- Not checked — no full text of the sourcecites [82] Wotjak, 1998, Dissociated central and peripheral release of vasopressin, but not oxytocin, in response to repeated swim stress: New insights into the secretory capacities of peptidergic neurons, Neuroscience source
- Not checked — no full text of the sourcecites [83] Ivanyi, 1991, Differential effects of emotional and physical stress on the central and peripheral secretion of neurohypophysial hormones in male rats, Life Sci source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Many studies have drawn conclusions from highly questionable measurements of plasma oxytocin, and others mistakenly claim that plasma measurements reliably reflect oxytocin release in the brain.”
§ Intranasal oxytocin: myths and delusions > Measuring oxytocin and vasopressin
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Hyperosmotic stimuli increase oxytocin release from both dendrites and nerve terminals in rats, but on different time scales; dendritic release is increased as plasma concentrations fall (2).”
§ Intranasal oxytocin: myths and delusions > Central and peripheral release of oxytocin
What the sources say
- Not checked — no full text of the sourcecites [2] Ludwig, 2006, Dendritic peptide release and peptide-dependent behaviours, Nat Rev Neurosci source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In response to α-melanocyte stimulating hormone (acting at MC4 receptors), oxytocin is released from dendrites of magnocellular neurons, but their electrical activity and peripheral oxytocin secretion is inhibited (78).”
§ Intranasal oxytocin: myths and delusions > Central and peripheral release of oxytocin
What the sources say
- Not checked — no full text of the sourcecites [78] Sabatier, 2003, Alpha-melanocyte-stimulating hormone stimulates oxytocin release from the dendrites of hypothalamic neurons while inhibiting oxytocin release from their terminals in the neurohypophysis, J Neurosci source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In lactating rhesus monkeys, Amico et al. (86) found that”
- Also stated in: § Central and peripheral release of oxytocin · plain
“variations in the concentrations of oxytocin in CSF were independent of the suckling stimulus and plasma oxytocin concentrations”
- Also stated in: § Central and peripheral release of oxytocin · plain
“release of oxytocin into the CSF of lactating monkeys is disassociated from release into the peripheral circulation”
§ Intranasal oxytocin: myths and delusions > Central and peripheral release of oxytocin
What the sources say
- Not checked — no full text of the sourcecites [86] Amico, 1990, Pattern of oxytocin concentrations in the plasma and cerebrospinal fluid of lactating rhesus monkeys (Macaca mulatta): evidence for functionally independent oxytocinergic pathways in primates, J Clin Endocrinol Metabol source
- Not checked — no full text of the sourcecites [87] Perlow, 1982, Oxytocin, vasopressin, and estrogen-stimulated neurophysin: Daily patterns of concentration in cerebrospinal fluid, Science source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Central and peripheral release of oxytocin · plain
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In lactating rats, oxytocin is released in the hypothalamus in response to suckling before any peripheral secretion (84), but in guinea pigs, simultaneous measurements revealed a large increase in plasma during suckling but no change in CSF (85), leading the authors to conclude that CSF levels reflect secretion from centrally projecting neurons that are functionally independent of the magno”
§ Intranasal oxytocin: myths and delusions > Central and peripheral release of oxytocin
What the sources say
- Not checked — no full text of the sourcecites [84] Moos, 1989, Release of oxytocin within the supraoptic nucleus during the milk ejection reflex in rats, Exp Brain Res source
- Not checked — no full text of the sourcecites [85] Robinson, 1982, Oxytocin and neurophysin in plasma and CSF during suckling in the guinea-pig, Neuroendocrinology source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“the field often constructs arguments to block the publication and interpretation of null results and that null results may be extinguished through questionable researcher practices”
§ Intranasal oxytocin: myths and delusions > Publication bias
What the sources say
- Not checked — no full text of the sourcecites [99] Ferguson, 2012, A vast graveyard of undead theories: Publication bias and psychological science’s aversion to the null, Perspect Psychol Sci source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
CSF oxytocin concentration is a valid proxy for behaviorally relevant oxytocin penetration into the brain.
“At most, 0.005% of intranasally injected oxytocin reaches the CSF within an hour.”
The paper relies on this without support.
Doses of oxytocin required to produce behavioral effects in animals indicate the brain concentrations needed for behavioral effects in humans.
“Are these enormous intranasal doses enough to deliver effective concentrations of oxytocin into the brain?”
The paper relies on this without support.
The recent trials cited as showing no effect had sufficient statistical power to detect effects of intranasal oxytocin.
“Several recent trials conform to some of these conditions, particularly in reporting clear primary outcomes.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“it is uncertain whether the standard doses used in OT research (between 24 and 40 IU) can deliver sufficient quantities of OT to the brain in order to produce significant changes in individuals”
From Is there a Publication Bias in Behavioural Intranasal Oxytocin Research on Humans? Opening the File Drawer of One Laboratory (2016) · cites this paper as [24]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The dosage of IN-OT and typical timing of tasks following IN-OT administration is based on three assumptions that to our knowledge have not been directly or reliably (i.e. through several replications) tested: that IN-OT crosses the brain-blood barrier following administration, that 24-40 IU is a sufficient dose to produce behavioral changes, and that IN-OT pharmacokinetics mimics that of vasopres”
From Is there a Publication Bias in Behavioural Intranasal Oxytocin Research on Humans? Opening the File Drawer of One Laboratory (2016) · cites this paper as [24]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Although the idea that manipulating OT in humans could influence social behavior is supported by rigorous animal research, we argue that the pre-study odds of studies investigating the effect of IN-OT still would be low, primarily due to limitations in deep brain penetration of OT when administered intranasally (2, 19).”
From Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies (2016) · cites this paper as [19]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“They showed that low doses of OT led to a decrease of locomotor activity and that higher doses led to clear signs of sedation.”
From Is there a Publication Bias in Behavioural Intranasal Oxytocin Research on Humans? Opening the File Drawer of One Laboratory (2016) · cites this paper as [24]
Experimental — accuracy not yet measuredIn the citing paper
“it is unclear whether these peripheral measures of OXT are accurate approximations for levels of OXT in the central nervous system24.”
From Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain (2018) · cites this paper as [24]
In the citing paper
“The efficacy of oxytocin (OT) in improving social abilities is under debate, largely due to frequently observed weak effect sizes and problems with replicability (1–3).”
From Oxytocin under opioid antagonism leads to supralinear enhancement of social attention (2017) · cites this paper as [3]
In the citing paper
“Specifically, there has been a significant gap in the understanding of the neural systems responsive to OT and AVP in primates, and the use of intranasal OT (IN-OT) in humans, in particular, has advanced rapidly despite a lack of knowledge of the mechanism or neurological targets engaged by this manipulation (11-13).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [12]
In the citing paper
“Although intranasal delivery of OT in NHP more accurately models current human IN-OT studies, this approach does not provide information on whether the effects are mediated by central or peripheral receptors, or whether they are mediated by OXTR or AVPR1a (12).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [12]
In the citing paper
“The fallacies in this supposition have been discussed elsewhere 2.”
From Measuring Oxytocin and Vasopressin: Bioassays, Immunoassays and Random Numbers (2016) · cites this paper as [2]
In the citing paper
“In response to recent reviews that are critical of the quality and rigor of OXT research (Churchland & Winkielman, 2012;Leng & Ludwig, 2016;Walum, Waldman, & Young, 2016)”
From Oxytocin increases attention to the eyes and selectively enhances self-reported affective empathy for fear (2017) · cites this paper as Leng & Ludwig, 2016
In the citing paper
“Oxytocin (OT) and arginine-vasopressin (AVP) act in the brain to regulate social cognition/social behavior and in the periphery to influence a variety of physiological processes.”
From Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery (2018) · cites this paper as [2]
In the citing paper
“The commonly used intranasal concentrations of OT and AVP (i.e., 20 IU to 40 IU) produce high, supraphysiological levels of peptide in the periphery, and these concentrations are likely high enough to also produce biologically active levels in the brain [2].”
From Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery (2018) · cites this paper as [2]
In the citing paper
“in smaller animals, 1 ng has been reported as the lowest i.c.v. dose shown to elicit a behavioural effect 75.”
From The Analgesic Effect of Oxytocin in Humans: A Double‐Blind, Placebo‐Controlled Cross‐Over Study Using Laser‐Evoked Potentials (2016) · cites this paper as [75]
In the citing paper
“The intranasal dose administered in the present study has been associated with changes in central function in humans 58, and similar or smaller doses of oxytocin or vasopressin (24–48 IU for oxytocin; 40–80 IU for vasopressin) have been associated with elevations in peptide levels in the cerebrospinnal fluid in humans or macaques of no more than approximately 55 pg/ml in actual levels 70, 71, 72,”
From The Analgesic Effect of Oxytocin in Humans: A Double‐Blind, Placebo‐Controlled Cross‐Over Study Using Laser‐Evoked Potentials (2016) · cites this paper as [75]
In the citing paper
“Some important questions have also been raised regarding if and how intranasal oxytocin accesses the brain and in what quantities (Leng and Ludwig, 2016).”
From Meta-analysis of the effects of intranasal oxytocin on interpretation and expression of emotions (2017) · cites this paper as Leng and Ludwig, 2016
In the citing paper
“There has also recently been some doubt regarding the effects of intranasal oxytocin on social-emotional functioning in general and criticism directed at the lack of compelling theoretical framework to explain the contradictory findings reported thus far (Lane et al., 2016;Leng and Ludwig, 2016).”
From Meta-analysis of the effects of intranasal oxytocin on interpretation and expression of emotions (2017) · cites this paper as Leng and Ludwig, 2016
In the citing paper
“The biological validity of peripheral oxytocin measurements with respect to central oxytocin patterns nonetheless is debated (33–35).”
From Oxytocin reactivity during intergroup conflict in wild chimpanzees (2017) · cites this paper as [33]
In the citing paper
“likely because intranasal OT targets magnocellular but not parvocellular OT neurons (Dölen, 2015; Leng and Ludwig, 2016).”
From Parallel social information processing circuits are differentially impacted in autism (2020) · cites this paper as Leng and Ludwig, 2016
In the citing paper
“Safety outcomes have been recently reported from a modified maximum-tolerateddose study in ASD, 70 confirming the mild to moderate side effects reported in adult studies, 71 however the open-label design limits interpretations about these reports.”
From Beyond the hype and hope: critical considerations for intranasal oxytocin research in autism spectrum disorder (2017) · cites this paper as [70]
In the citing paper
“Leng and Ludwig48 reported that a maximum of 0.005% of intranasally injected oxytocin reaches the cerebrospinal fluid within 1 h.48”
From Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial (2016) · cites this paper as [48]
In the citing paper
“Non-extracted approaches may not have been appropriate as a methodology.48, 59”
From Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial (2016) · cites this paper as [48]
In the citing paper
“However, the mechanisms underlying nose-to-brain OT activity are poorly understood (Quintana et al., 2016), particularly in respect to potential peripheral effects, required dosage (Leng and Ludwig, 2016), and the origin (i.e., endogenous vs. exogenous) of observed increases in CSF OT concentrations after intranasal administration (Neumann et al., 2013).”
From 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 (2016) · cites this paper as Leng and Ludwig, 2016
In the citing paper
“IV-OT administration can plausibly influence central activity through the stimulation of peripheral OT receptors (Leng and Ludwig, 2016) or via small amounts of OT crossing the BBB (Neumann et al., 2013).”
From 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 (2016) · cites this paper as Leng and Ludwig, 2016
In the citing paper
“which would provide more robust outcomes as small samples sizes may inflate the issue of spurious findings in oxytocin research (Lane et al., 2016;Leng and Ludwig, 2016).”
From 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 (2016) · cites this paper as Leng and Ludwig, 2016
In the citing paper
“First, the means of transport of oxytocin from the nasal cavity to the brain is not well understood.34”
In the citing paper
“There is ongoing debate on pharmacodynamics of intranasal oxytocin administration (70)(71)(72)(73).”
From Intranasal Oxytocin to Prevent Posttraumatic Stress Disorder Symptoms: A Randomized Controlled Trial in Emergency Department Patients (2017) · cites this paper as [71]
In the citing paper
“The overarching link among studies of OXT and human cooperation is the role of OXT in enhancing group-level cooperation, though there is considerable debate about the robustness of these OXT studies (Leng & Ludwig, 2015; Nave, Camerer, & McCullough, 2015; Van IJzendoorn & Bakermans-Kranenburg, 2012; Walum, Waldman, & Young, 2015).”
From Inequity aversion strategies between marmosets are influenced by partner familiarity and sex but not by oxytocin (2016) · cites this paper as Leng & Ludwig, 2015
In the citing paper
“Intranasal administration of OXT, given in doses ranging from 24–48 IU, may enter the CNS via a transnasal route, but the majority of it appears to increase plasma OXT to supraphysiological levels (Leng and Ludwig, 2015).”
From Marmosets treated with oxytocin are more socially attractive to their long-term mate (2015) · cites this paper as Leng and Ludwig, 2015
In the citing paper
“Although oxytocin facilitates parturition and lactation in females, decreased oxytocin levels have been linked with depression (not only postpartum depression) and maternal neglect [362,363].”
From Anxiety, depression, and the microbiome: A role for gut peptides (2018) · cites this paper as [362]
In the citing paper
“it has been suggested that the central nervous effects of oxytocin might be a consequence of its peripheral actions [57]”
Citations
Cites
Why Most Published Research Findings Are False
Ioannidis, J. P. A. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020124 · Cited by 10,505
Simmons, J. P., Nelson, L. D., & Simonsohn, U. (2011) · Psychological Science · doi:10.1177/0956797611417632 · Cited by 6,567
Structure and function of the blood–brain barrier
Abbott, N. J., Patabendige, A. A. K., Dolman, D. E. M., Yusof, S. R., & Begley, D. J. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.07.030 · Cited by 5,185
Why Most Published Research Findings Are False
Ioannidis, J. P. A. (2005) · CHANCE · doi:10.1080/09332480.2005.10722754 · Cited by 4,702 · cited 1×
“The 356 unreliability of small clinical trials is recognised, and attributed to a combination of 357 publication bias, questionable statistical analysis and methodological weaknesses, and there 358 are similar concerns about basic biological research (98).”
Oxytocin increases trust in humans
Kosfeld, M., Heinrichs, M., Zak, P. J., Fischbacher, U., & Fehr, E. (2005) · Nature · doi:10.1038/nature03701 · Cited by 3,690
Measuring the Prevalence of Questionable Research Practices With Incentives for Truth Telling
John, L. K., Loewenstein, G., & Prelec, D. (2012) · Psychological Science · doi:10.1177/0956797611430953 · Cited by 2,239
Sniffing neuropeptides: A transnasal approach to the human brain
Born, J., Lange, T., Kern, W., McGregor, G. P., Bickel, U., & Fehm, H. L. (2002) · Nature Neuroscience · doi:10.1038/nn0602-849 · Cited by 1,356
Evoked axonal oxytocin release in the central amygdala attenuates fear response
Knobloch, H. S., Charlet, A., Hoffmann, L. C., Eliava, M., Khrulev, S., Cetin, A. H., Osten, P., Schwarz, M. K., Seeburg, P. H., Stoop, R., et al. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.030 · Cited by 1,049
Dendritic peptide release and peptide-dependent behaviours
Ludwig, M., & Leng, G. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1845 · Cited by 945
Self-citationA new look at cerebrospinal fluid circulation
Brinker, T., Stopa, E., Morrison, J., & Klinge, P. (2014) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-11-10 · Cited by 819
Cited by
Sorted by citations
Items 401–500 of 608
Kang, H., Glaser, B. D., Sartorius, A. M., Audunsdottir, K., Kildal, E. S.-M., Nærland, T., Andreassen, O. A., Westlye, L. T., & Quintana, D. S. (2025) · Molecular Psychiatry · doi:10.1038/s41380-024-02871-4 · Cited by 10
Arginine Vasopressin Deficiency and Oxytocin Deficiency in the Endocrine Clinic
Atila, C., Refardt, J. C., & Christ‐Crain, M. (2025) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaf651 · Cited by 9
Does oxytocin shield against negative effects of ostracism? A replication and extension
Pfundmair, M., & Echterhoff, G. (2021) · Biological Psychology · doi:10.1016/j.biopsycho.2021.108128 · Cited by 11
Placebo Effects in the Neuroendocrine System: Conditioning of the Oxytocin Responses
Skvortsova, A., Veldhuijzen, D. S., Pacheco‐López, G., Bakermans‐Kranenburg, M. J., van IJzendoorn, M. H., Smeets, M. A. M., Wilderjans, T. F., Dahan, A., den Bergh, O. V., Chavannes, N. H., et al. (2019) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000759 · Cited by 10
Leng, G., & Ludwig, M. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.06.022 · Cited by 7
“We are very pleased that Quintana and Woolley (1) have engaged with the issues raised in our review (2); we believe that the field is best advanced by frank exchanges that identify issues of concern and ways to resolve them.”
Self-citationA Systematic Review of the MDMA Model to Address Social Impairment in Autism
Chaliha, D. R., Mamo, J. C. L., Albrecht, M. A., Lam, V., Takechi, R., & Vaccarezza, M. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210101130258 · Cited by 7
“But in fact, one paper says that, when intra-nasally administered, very little oxytocin enters the central nervous system, and most accumulates in the peripheral bloodstream causing a myriad of adverse effects such as cardiac arrhythmias [141].”
BackgroundLong‐range projections of oxytocin neurons in the marmoset brain
Lefèvre, A., Meza, J., & Miller, C. T. (2024) · Journal of Neuroendocrinology · doi:10.1111/jne.13397 · Cited by 7
Emerging medications and pharmacological treatment approaches for substance use disorders
Raymond, J. S., Athanasopoulos, A. G., Badolato, C. J., Doolan, T. M., Scicluna, R. L., Everett, N. A., Bowen, M. T., & James, M. H. (2024) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2024.173952 · Cited by 9
“…the clinical hypothesis of OXTR agonism sufficiently, and are unlikely to be overcome by nanoparticle formulations (for example), or marginally optimized intranasal administration methods (Leng and Ludwig, 2016), which do not address these substantial limitations inherent to the OXT peptide.”
Oxytocin and Vasopressin Blood Levels in People with Post-Traumatic Stress Disorder
Zayman, E. P., Karabulut, A. B., Özdemir, S., & Kartalcı, Ş. (2023) · ALPHA PSYCHIATRY · doi:10.5152/alphapsychiatry.2023.21628 · Cited by 7
“43,44 These data show that OT is important in the chronicity of disease in PTSD or that a disorder in the modulation of the HPA axis may play a role in its pathogenesis.”
Unchanged food approach‐avoidance behaviour of healthy men after oxytocin administration
Melkonyan, A., Liu, L., Brown, E. C., Meyer, W., Madipakkam, A. R., Ringelmann, L., Lange, F., Schmid, S. M., Münte, T. F., & Park, S. Q. (2020) · Journal of Neuroendocrinology · doi:10.1111/jne.12923 · Cited by 7
Sniffing submissiveness? Oxytocin administration in severe psychopathy
Rijnders, R. J. P., Dykstra, A. H., Terburg, D., Kempes, M. M., & van Honk, J. (2021) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2021.105330 · Cited by 7
Johnson, E. G., Kuiper, W. J., Ahmed, R. M., Halliday, G. M., Burrell, J. R., Hodges, J. R., Guastella, A. J., Piguet, O., & Kumfor, F. (2022) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000525087 · Cited by 7
Wang, J., & Zou, Z. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.1072896 · Cited by 6
“While there has been debate as to whether central and peripheral OT are related (45, 46), animal research has revealed coupled central and peripheral OT release during stress (47) and axonal projections from magnocellular OT neurons to forebrain structures, the amygdala, and the posterior pituitary (48).”
BackgroundShort communication: pharmacokinetics of oxytocin administered intranasally to beef cattle
Wagner, B. K., Relling, A. E., Kieffer, J. D., Moraes, L. E., & Parker, A. J. (2019) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2019.106387 · Cited by 7
The role of oxytocin on self‐serving lying
Sindermann, C., Luo, R., Becker, B., Kendrick, K. M., & Montag, C. (2020) · Brain and Behavior · doi:10.1002/brb3.1518 · Cited by 12
“Also, the possibility of publication bias, as well as the questions about whether, and how much OXT enters the brain represent important topics in the field of OXT research (Leng & Ludwig, 2016; Walum, Waldman, & Young, 2016).”
BackgroundThe Effects of Augmenting Clozapine with Oxytocin in Schizophrenia: An Initial Case Series
Marotta, R. F., Buono, F. D., Garakani, A., Collins, E. D., Cerrito, B., & Rowe, D. (2020) · Annals of Clinical Psychiatry · doi:10.1177/104012372003200211 · Cited by 7
“31 .”
Hopkins, W. D., & Latzman, R. D. (2021) · Cambridge University Press eBooks · doi:10.1017/9781108671187.010 · Cited by 7
Hayashi, S., Tsuru, A., Kishida, F., Kim, Y.-K., Higuchi, S., & Motomura, Y. (2019) · Journal of PHYSIOLOGICAL ANTHROPOLOGY · doi:10.1186/s40101-019-0196-z · Cited by 7
Parallel social information processing circuits are differentially impacted in autismPreprint
Lewis, E. M., Stein-O’Brien, G., Patino, A. V., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.03.13.990549 · Cited by 7
“, 2007), likely because intranasal OT targets magnocellular but not parvocellular OT neurons (Dölen, 2015; Leng and Ludwig, 2016).”
BackgroundReframing oxytocin as a behavioral flexibility hormone
Walle, K. M., Sartorius, A. M., Deilhaug, E., Kang, H., Nærland, T., Andreassen, O. A., Westlye, L. T., & Quintana, D. S. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106628 · Cited by 10
Early life adversity in primates: Behavioral, endocrine, and neural effects
Tromp, D., Fox, A. S., Riedel, M. K., Oler, J. A., Zhou, X., Roseboom, P. H., Alexander, A. L., & Kalin, N. H. (2024) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2023.106953 · Cited by 9
“Oxytocin is thought to only minimally penetrate the blood-brain-barrier (Leng and Ludwig, 2016) and there is considerable support for independent but coordinated functions of peripheral and brain oxytocin systems (Meyer-Lindenberg et al., 2011).”
BackgroundFrom Parental Behavior to Sexual Function: Recent Advances in Oxytocin Research
Dale, J. K., Harberson, M. T., & Hill, J. W. (2024) · Current Sexual Health Reports · doi:10.1007/s11930-024-00386-1 · Cited by 7
“%) even when given at supraphysiological levels [113].”
BackgroundOxytocin-Trust Link in Oxytocin-Sensitive Participants and Those Without Autistic Traits
Kurokawa, H., Kinari, Y., Okudaira, H., Tsubouchi, K., Sai, Y., Kikuchi, M., Higashida, H., & Ohtake, F. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.659737 · Cited by 6
Kerry, N., & Murray, D. R. (2021) · Oxford University Press eBooks · doi:10.1093/oxfordhb/9780190674687.013.27 · Cited by 6
Grieb, Z. A., Cross, E. A., & Albers, H. E. (2022) · Physiology & Behavior · doi:10.1016/j.physbeh.2022.113828 · Cited by 7
Oxytocin and social gaze during a dominance categorization task in tufted capuchin monkeys
Sosnowski, M. J., Kano, F., & Brosnan, S. F. (2022) · Frontiers in Psychology · doi:10.3389/fpsyg.2022.977771 · Cited by 6
“Why would naturally-occurring oxytocin impact gaze behavior differently than exogenously administered oxytocin? One oft-considered possibility is that intranasally administered exogenous oxytocin might not cross the blood-brain barrier due to its large molecular size (Leng and Ludwig, 2016), although recent literature…”
BackgroundYonekura, H., Kato, I., Yamamoto, Y., Ikeda, T., Higashida, H., & Okamoto, H. (2023) · Endocrinology · doi:10.1210/endocr/bqad121 · Cited by 6
Emerging therapeutic landscape on delivery of oxytocin to brain for treating neurological disorders
Kumar, S., Garg, N. K., Jain, A., Pandey, P., Khopade, A. J., & Sawant, K. K. (2024) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2024.105370 · Cited by 6
Effects of intranasal oxytocin on fear extinction learning
Rashidi, M., Simon, J. J., Bertsch, K., Wegen, G. V., Ditzen, B., Flor, H., Grinevich, V., Wolf, R. C., & Herpertz, S. C. (2024) · Neuropsychopharmacology · doi:10.1038/s41386-024-01996-y · Cited by 5
Vasopressin: Roles in Modulating Social Behaviors
Williams, S. K., & Cymerblit‐Sabba, A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803592-4.00057-2 · Cited by 5
Salivary oxytocin after oxytocin administration: Examining the moderating role of childhood trauma
Fragkaki, I., Glennon, J. C., & Cima, M. (2020) · Biological Psychology · doi:10.1016/j.biopsycho.2020.107903 · Cited by 7
A bench-to-bedside narrative review of the sleep-social-oxytocin nexus
Raymond, J. S., Troxel, W., & Bowen, M. T. (2025) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2025.102077 · Cited by 6
Plasma pharmacokinetics of intravenous and intranasal oxytocin in nonpregnant adults
Shafer, S. L., Ririe, D. G., Miller, S., Curry, R. S., Hsu, D. T., Sullivan, G. M., & Eisenach, J. C. (2025) · British Journal of Anaesthesia · doi:10.1016/j.bja.2024.12.046 · Cited by 5
Utility of Downstream Biomarkers to Assess and Optimize Intranasal Delivery of Oxytocin
DuBois, M. C., Tseng, A., Francis, S. M., Haynos, A. F., Peterson, C. B., & Jacob, S. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14061178 · Cited by 5
“In recent decades, interest in the therapeutic potential of intranasal drugs has been on the rise; noninvasive delivery of neurohormones that target the central nervous system (CNS) has gained attention because this approach may effectively alter brain chemistry and behavior [1,2].”
BackgroundOxytocin in autism: Rethinking treatment and research through a neurodivergent perspective
Phan, J., Dwyer, P. S. R., Elsherif, M. M., Friedel, E., & Kapp, S. K. (2024) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2024.107220 · Cited by 9
“Less is more”: a dose-response account of intranasal oxytocin pharmacodynamics in the human brainPreprint
Martins, D., Broadmann, K., Veronese, M., Dipasquale, O., Mazibuko, N., Schuschnig, U., Zelaya, F., Fotopoulou, A., & Paloyelis, Y. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.18.427062 · Cited by 7
Oxytocin: Vom Geburts- zum Sozialhormon
Steinbach, X., & Maasen, S. (2018) · NTM Zeitschrift für Geschichte der Wissenschaften Technik und Medizin · doi:10.1007/s00048-018-0186-y · Cited by 5
Melby, K., Spigset, O., Gråwe, R. W., Aamo, T. O., & Quintana, D. S. (2022) · Hormones and Behavior · doi:10.1016/j.yhbeh.2022.105268 · Cited by 5
Sosnowski, M. J., Reilly, O. T., Brosnan, S. F., & Benítez, M. E. (2023) · American Journal of Primatology · doi:10.1002/ajp.23490 · Cited by 5
“…about whether exogenous peripherally‐administered oxytocin is able to cross the blood‐brain barrier to take neurological effect (Ermisch et al., 1985; Leng & Ludwig, 2016), although, even if it does not, it may act in other parts of the body to induce the release of endogenous oxytocin on its own…”
BackgroundGarakani, A., Buono, F. D., & Marotta, R. F. (2020) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000001248 · Cited by 5
The Current Status of Drug Discovery for the Oxytocin Receptor
Nashar, P. E., Whitfield, A. A., Mikušek, J., & Reekie, T. A. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1759-5_10 · Cited by 4
Oxytocin und die suchterhaltenden Mechanismen der Alkoholabhängigkeit
Faehrmann, T., Zernig, G., & Mechtcheriakov, S. (2017) · Neuropsychiatrie · doi:10.1007/s40211-017-0229-y · Cited by 5
“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].”
BackgroundInfluentialReply to: Improving Research Standards to Restore Trust in Intranasal Oxytocin
Leng, G., & Ludwig, M. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.08.030 · Cited by 6
Self-citationMartins, D. A., Mazibuko, N., Zelaya, F. O., Vasilakopoulou, S., Loveridge, J., Oates, A., Maltezos, S., Mehta, M. A., Wastling, S. J., Howard, M. A., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/563056 · Cited by 9
“It is also possible that the small amount of synthetic OT that crosses the BBB from systemic circulation (17) may be sufficient to induce functional effects in the brain, either by directly activating receptors in the brain or by stimulating OT autoreceptors on OT-synthesizing hypothalamic neurons to induce the releas…”
BackgroundAcute and repeated intranasal oxytocin differentially modulate brain-wide functional connectivityPreprint
Pagani, M., Felice, A. D., Montani, C., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/798025 · Cited by 5
“The heterogeneity of ASD and our inability to stratify patient population, together with the presence of robust placebo effects, are all likely primary contributors to such inconsistent clinical findings (Leng and Ludwig, 2016; Yamasue et al., 2018).”
BackgroundEverett, N. A., Turner, A. J., Costa, P. A., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2019.12.18.880914 · Cited by 5
A novel analgesic pathway from parvocellular oxytocin neurons to the periaqueductal grayPreprint
Iwasaki, M., Lefèvre, A., Althammer, F., Łąpieś, O., Hilfiger, L., Kerspern, D., Melchior, M., Küppers, S., Krablicher, Q., Patwell, R., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.02.23.481531 · Cited by 5
“, 2018) may be due to the limitations of intranasal OT administration (Leng and Ludwig, 2015).”
BackgroundResultImproving the precision of intranasal oxytocin researchPreprint
Winterton, A., Westlye, L. T., Steen, N. E., et al. (2020) · doi:10.31219/osf.io/gz5jb · Cited by 5
Stable clique membership in mouse societies requires oxytocin-enabled social sensory statesPreprint
Nelias, C., Ghanayem, S., Wolf, D., Moor, M., Scheller, M. F., Grinevich, V., Reinwald, J., & Kelsch, W. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.26.672298 · Cited by 3
“This discrepancy raises the question of whether our mechanistic understanding of oxytocin function is sufficient [23], particularly in the context of higher-order social behaviors.”
Winterdahl, M., Nielsen, E. N., Hansen, S. B., Dias, A. H., Vendelbo, M. H., Jakobsen, S., & Yeomans, D. C. (2025) · EJNMMI Research · doi:10.1186/s13550-025-01329-0 · Cited by 4
“Oxytocin is frequently administered intranasally in both clinical and experimental settings, with robust evidence from animal research supporting its absorption through the nasal mucosa and subsequent transport to the brain via a trigeminal nerve pathway [15, 20].”
Zablocki‐Thomas, P., Lau, A. R., Witczak, L. R., Dufek, M. E., Wright, A., Savidge, L. E., Paulus, J. P., BAXTER, A. B., Karaskiewicz, C. L., Seelke, A. M. H., et al. (2023) · Journal of Neuroendocrinology · doi:10.1111/jne.13339 · Cited by 3
“Mens et al. 51 measured cerebrospinal fluid (CSF) levels in rats at various timepoints after delivering large doses of intravenous or subcutaneous OT and AVP, and calculated that about 0.002% of the administered dose entered the CSF. 51 There has been no comparably detailed study since, but Leng and Ludwig 52 analyzed…”
InfluentialDose-response effects of exogenous oxytocin on social cognition: A systematic review
Barton, S., Pruin, A., Schulze, J., Kiebs, M., Scheele, D., & Hurlemann, R. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106350 · Cited by 7
“However, this route remains controversial, and the mechanisms by which oxytocin may reach central targets are not fully understood (Churchland and Winkielman, 2012; Leng and Ludwig, 2016).”
Association between salivary oxytocin levels and the amygdala and hippocampal volumes
Shou, Q., Yamada, J., Nishina, K., Matsunaga, M., Matsuda, T., & Takagishi, H. (2022) · Brain Structure and Function · doi:10.1007/s00429-022-02543-5 · Cited by 4
“Previous studies have found that unextracted plasma oxytocin levels are higher than the extracted ones (Leng and Ludwig 2016) and hence, researchers pointed out the necessity to measure oxytocin levels with the extraction step especially in blood oxytocin measurement (Szeto et al.”
BackgroundBehavioural Endocrinology in the Social Sciences
Botzet, L. J., Kordsmeyer, T. L., Ostermann, S., Ruß, J., & Penke, L. (2024) · KZfSS Kölner Zeitschrift für Soziologie und Sozialpsychologie · doi:10.1007/s11577-024-00945-3 · Cited by 7
“%) crosses the blood–brain barrier (Leng and Ludwig 2016).”
心理学の再現可能性：我々はどこから来たのか我々は何者か 我々はどこへ行くのか:―特集号の刊行に寄せて―
雅己, 友., 麻子, 三., & 針生, 悦. (2016) · 心理学評論 · doi:10.24602/sjpr.59.1_1 · Cited by 4
Influence of intranasal oxytocin on fear consolidation in healthy humans
Hoge, E. A., Bui, É., Rosencrans, P. L., Orr, S. P., Ross, R., Ojserkis, R. A., & Simon, N. M. (2019) · General Psychiatry · doi:10.1136/gpsych-2019-100131 · Cited by 4
Norholt, H. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2020.590051 · Cited by 4
“, somatosensory stimulation), in part because exogenously administered OT may not readily cross the blood–brain barrier (Leng and Ludwig, 2016; Uvnäs Moberg et al., 2019).”
BackgroundRoux, M. L., Möller, M., & Harvey, B. H. (2021) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2021.06.003 · Cited by 4
“Though peripheral neuropeptide expression cannot directly account for drug-related changes in the HNS, and vice versa (as reviewed by Leng and Ludwig, 2016; Neumann and Landgraf, 2012), plasma neuropeptide measurements (and accompanying psychobehavioral changes) may yet be translatable to humans…”
BackgroundHenningsson, S., Leknes, S., Asperholm, M., Eikemo, M., & Westberg, L. (2021) · Biological Psychology · doi:10.1016/j.biopsycho.2021.108164 · Cited by 4
Measuring oxytocin release in response to gavage: Computational modelling and assay validation
Hassan, S., Baradey, H. E., Madi, M. M., Shebl, M., Leng, G., Lozić, M., Ludwig, M., Menzies, J. R. W., & MacGregor, D. J. (2023) · Journal of Neuroendocrinology · doi:10.1111/jne.13303 · Cited by 2
Self-citationFam, J. P., Holmes, N. M., & Westbrook, R. F. (2023) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2023.106917 · Cited by 5
“Although there is some evidence that peripherally administered OT can affect central levels (Jurek and Neumann, 2018; Neumann et al., 2013; Smith et al., 2019), it is unclear how this occurs and how much OT crosses the blood-brain barrier (Leng and Ludwig, 2016; Tabak et al., 2023).”
BackgroundOxytocin amplifies the influence of good intentions on social judgments
Zhang, J., Zhou, C., & Yu, R. (2019) · Hormones and Behavior · doi:10.1016/j.yhbeh.2019.104589 · Cited by 5
Add-on Oxytocin in the Treatment of Postpartum Acute Schizophrenia: A Case Report
Medved, S., Janović, M. B., Štimac, Z., & Mihaljević-Peleš, A. (2021) · Journal of Psychiatric Practice · doi:10.1097/pra.0000000000000557 · Cited by 4
Kang, H., Glaser, B. D., Sartorius, A. M., Audunsdottir, K., Nærland, T., Andreassen, O. A., Westlye, L. T., & Quintana, D. S. (2022) · OSF Preprints (OSF Preprints) · doi:10.31219/osf.io/8fzdy · Cited by 3
The therapeutic pipeline in migraine: What does the future hold?
Gamal‐Eltrabily, M., Salinas-Abarca, A. B., Romero‐Reyes, M., & Akerman, S. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2025.e00826 · Cited by 3
“For a detailed analysis of challenges in the use of intranasal OXT we refer the reader to several recent publications [104,122].”
Uzar, M., Dmitrzak‐Węglarz, M., & Słopień, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252212046 · Cited by 5
“As a result, peripheral oxytocin levels may rise to supraphysiologic levels [138].”
Pawsitive selection : Genetics of dog-human communication
Persson, M. E. (2020) · Linköping studies in science and technology. Dissertations · doi:10.3384/diss.diva-163173 · Cited by 3
Azab, A. E. (2022) · Journal of Clinical Research and Reports · doi:10.31579/2690-1919/256 · Cited by 3
Future perspectives on peptide therapeutics
Ünsal, Ö., Liu, J., Sicinski, K. M., & Kumar, K. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-820141-1.00003-0 · Cited by 4
Şentürk, G. E., Sezer, Z., Sahin, H., Işıldar, B., & Abdulova, A. (2023) · Peptides · doi:10.1016/j.peptides.2023.171006 · Cited by 3
Sorenson, K., Kendall, E., Grell, H., Kang, M., Shaffer, C. L., & Hwang, S. (2023) · Journal of Psychiatry and Brain Science · doi:10.20900/jpbs.20230008 · Cited by 3
“Autism spectrum disorder (ASD) is characterized by the DSM-5 as a neurodevelopmental disorder marked by impaired social abilities and restricted and repetitive behaviors [31].”
BackgroundInfluentialNisbett, K. E. (2024) · Comprehensive Psychoneuroendocrinology · doi:10.1016/j.cpnec.2024.100244 · Cited by 3
“Second, with respect to MOXAIC treatment, the previously mentioned drawbacks inherent in the intranasal route of oxytocin delivery [105], such as low blood-brain barrier penetrance and suboptimal dose titration, may supersede any benefits of MOXAIC treatment if the same route of administration is…”
Gully, B. J., Brown, Z. E., Hornbacher, R., Brown, J. C., Back, S. E., McCance‐Katz, E. F., Swift, R. M., & Haass‐Koffler, C. L. (2024) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2024.100395 · Cited by 5
“Extensive review of pharmacodynamic evidence suggests that of the large amounts of oxytocin administered in experimental trials, very little actually reaches the brain and cerebrospinal fl uid (55).”
Ahmed, A., Ahmed, A. M., Zahra, Z., Alnefeesi, Y., Hanif, A., Ali, M., Jawad, Y., & Shad, M. U. (2024) · Physiology & Behavior · doi:10.1016/j.physbeh.2024.114777 · Cited by 3
Oxytocin's Influence on Social Decision-Making
Lefèvre, A., & Sirigu, A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-805308-9.00031-2 · Cited by 3
Nasal Oxytocin: Facts and Routes
Lima, J. P. C., & Rodrigues, A. L. (2019) · Acta Psychopathologica · doi:10.4172/2469-6676.100181 · Cited by 3
Recent Advancement in Self Emulsifing Drug Delivery System
Bist, V. L., & Faruk, A. (2023) · Journal for Research in Applied Sciences and Biotechnology · doi:10.55544/jrasb.2.2.14 · Cited by 3
Human, L. J., Thorson, K. R., Woolley, J. D., & Mendes, W. B. (2017) · Hormones and Behavior · doi:10.1016/j.yhbeh.2017.03.002 · Cited by 3
“, 2013), although itwas only detectable 75 min after administration and there is controversy surrounding the nature and the mechanisms of the effects of OT administration on the brain (Leng and Ludwig, 2015).”
BackgroundGuoynes, C. D., & Marler, C. A. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.12.03.409557 · Cited by 3
Evidence for intranasal oxytocin delivery to the brain: recent advances and future perspectivesPreprint
Quintana, D. S., Smerud, K. T., Andreassen, O. A., & Djupesland, P. G. (2018) · OSF Preprints (OSF Preprints) · doi:10.31219/osf.io/fnhx5 · Cited by 3
Oxytocin and opioid antagonists: A dual approach to improving social behavior
Monte, O. D., Gangopadhyay, P., Putnam, P. T., & Chang, S. W. C. (2025) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.15376 · Cited by 3
“125 129 Theseconcernscallfortheneedtodevelopstandard-ized and validated OT assays to enhance cross-study comparability 130 and precise investigations into dose–response relationships to disentangle the pharmacological and physiological effects of intranasal OT administration.”
Budniok, S., Bakermans‐Kranenburg, M. J., Bosmans, G., & van IJzendoorn, M. H. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106500 · Cited by 2
Neuropeptidergic systems in psychiatric disorders
Hodzic, S., & Riedemann, T. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1654292 · Cited by 2
The effects of oxytocin on social behavior and eye gaze: Insights from dog-human partnership
Yuan, S., & Zhang, Y. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106602 · Cited by 3
Oxytocin promotes action prediction
Burgstaller, J., Paulus, M., & Pfundmair, M. (2018) · Hormones and Behavior · doi:10.1016/j.yhbeh.2018.09.004 · Cited by 2
“Action prediction plays a crucial role in language processing and learning (Elman, 2009; Maia, 2009) as well as in purely social tasks (Bar, 2009; Enns and Lleras, 2008).”
Intranasal Delivery of a Ghrelin Mimetic Engages the Brain Ghrelin Signaling System in Mice
Poelman, R., May, M. V. L., Schéle, E., Stoltenborg, I., & Dickson, S. L. (2025) · Endocrinology · doi:10.1210/endocr/bqae166 · Cited by 3
The active monitoring of oxytocin research evidence (AMORE) platform
Iversen, I. A., Alaerts, K., Bakermans‐Kranenburg, M. J., Becker, B., Blair, J., Bartz, J. A., Connelly, J. J., Ditzen, B., Ebner, N. C., Kang, H., et al. (2025) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2025.107713 · Cited by 3
“Second, methodological and experimental challenges have raised questions about the validity of existing findings (Leng & Ludwig, 2016; Quintana, 2022; Walum et al., 2016), meaning that the certainty of current evidence base can be considered generally low.”
Oxytocin and the altruistic ‘Goldilocks zone’
Roberts, I. D., Teoh, Y. Y., & Hutcherson, C. A. C. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0362-y · Cited by 2
Noxious or Non-noxious Inputs to Oxytocin Neurons: Possible Roles in the Control of Behaviors
Onaka, T., Okabe, S., Takayanagi, Y., & Yoshida, M. (2015) · Interdisciplinary Information Sciences · doi:10.4036/iis.2015.b.03 · Cited by 3
“mechanisms underlying the majority of oxytocin actions remain to be clarified [39, 81].”
BackgroundBeyond the social stereotypes of hormones
Koren, L., & Gordon, I. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.06.007 · Cited by 2
“In addition, since the mechanism by which oxytocin is delivered to the brain following such nasal administration has not been established (Leng and Ludwig, 2016), researchers have been cautious of oxytocin’s potential effects (Miller, 2013).”
BackgroundParvocellular Oxytocin Neurons and Autism Spectrum Disorders
Sundaram, S. M., & Schwaninger, M. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.01.004 · Cited by 1
Samson, W. K. (2016) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00307.2016 · Cited by 2
“The potential behavioral and cardiovascular consequences resulting from this approach, of course, will have to be carefully scrutinized, as the efficacy of, and the mechanisms underlying, the effects of intranasal oxytocin remain controversial (25, 43).”
BackgroundNuman, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0008 · Cited by 2
Hormonal Control of Maternal Behavior in Nonhuman Mammals
Numan, M. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190848675.003.0003 · Cited by 2
Domestication: Neuroendocrine Mechanisms ofCanidae‐human Bonds
Herbeck, Y. E., Gulevich, R. G., Eliava, M., Shepeleva, D. V., Trut, L. N., & Grinevich, V. (2018) · Wiley eBooks · doi:10.1002/9781119391128.ch14 · Cited by 2
Martins, D., Gabay, A. S., Mehta, M. A., & Paloyelis, Y. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.14.202622 · Cited by 2
Lindenmaier, Z., Ellegood, J., Stuive, M., Easson, K., Yee, Y., Fernandes, D., Foster, J., Anagnostou, E., & Lerch, J. (2021) · bioRxiv · doi:10.1101/2021.01.13.426562 · Cited by 10
Modelos experimentais para o estudo do transtorno obsessivo compulsivo: perspectivas e limitações
Raminelli, A. O. (2021) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.17.2021.tde-10052021-142439 · Cited by 2
Quintana, D. S., Westlye, L. T., Smerud, K. T., et al. (2018) · doi:10.31219/osf.io/s7ngd · Cited by 2
Quintana, D. S. (2021) · doi:10.31234/osf.io/48ayg · Cited by 2
“Some have questioned this assumption, suggesting that very little intranasally administered oxytocin actually reaches the brain (Leng and Ludwig, 2016).”
Background
Metadata
- Authors
- Leng, G., & Ludwig, M.
- Affiliations
- University of Edinburgh (GB)
- Corresponding author
- Leng, Gareth
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 79
- Issue
- 3
- Pages
- 243-250
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W1750764127
- Cited by
- 616
- References
- 113
- Citations by year
- 2026: 27 · 2025: 26 · 2024: 30 · 2023: 33 · 2022: 34 · 2021: 72 · 2020: 79 · 2019: 63 · 2018: 68 · 2017: 76 · 2016: 77
- FWCI
- 8.25
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/J004723)
- Edinburgh Patrick Wild Centre, and the European Union’s Seventh Framework Programme for research, technological development and demonstration (245009, 607310)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- intranasal oxytocin, cerebrospinal fluid, dose-response relationship, publication bias, questionable research practices, oxytocin antagonist
- MeSH terms
- Administration, Intranasal, Brain, Dose-Response Relationship, Drug, Humans, Oxytocin, Social Behavior
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