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
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Oxytocin in Schizophrenia: Pathophysiology and Implications for Future Treatment
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“The plasma oxytocin level may also be affected by peripheral organs such as the heart, gastrointestinal tract, and reproductive organs [78].”
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“…OT receptors’ distribution in the primate brain is not well understood; and although they have not been found in limbic areas of humans and macaques (Loup et al., 1991; Freeman et al., 2014; but see Boccia et al., 2013), administration of OT has consistently produced effects in these areas (Chang…”
BackgroundOxytocin–Oxytocin Receptor Systems Facilitate Social Defeat Posture in Male Mice
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“Although the aforementioned works provided evidence of long lasting effects of OT treatment in adolescence, it must be noted that no direct passage of peripherally administered OT through the blood brain barrier has been reported in humans and that the mechanisms of action of peripherally administered OT is under inte…”
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“1370 IN OT treatments (Leng and Ludwig, 2015) and have cautioned 1371 against hasty interpretations of these studies (Walum et al.”
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“The majority of oxytocin is transported to the neurohypophysis and thereby released into the bloodstream for peripheral distribution (Leng & Ludwig, 2016; Quirin, Kuhl, & Dusing, 2011).”
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“However, many of them used radioimmunoassays of unextracted plasma as a questioned method to assess oxytocin complicating interpretation of these data (Leng and Ludwig 2015).”
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“[25].”
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“The methodological concerns surrounding intranasal peptide administration have recently been reviewed by Leng and Ludwig (2015). activation of the Primary Olfactory system The most compelling finding in this imaging study was the significant activation of the POS by IP OT.”
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Oxytocin as Treatment for Social Cognition, Not There Yet
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“It has become the increasingly clear that oxytocin and vasopressin have divers actions within the brain that must result from central release because the hormones do not cross the blood brain barrier in appreciable quantities (275).”
Oxytocin Influences Male Sexual Activity via Non-synaptic Axonal Release in the Spinal Cord
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An analgesic pathway from parvocellular oxytocin neurons to the periaqueductal gray in rats
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What's Love Got to do with it: Role of oxytocin in trauma, attachment and resilience
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Oxytocin and anxiety disorders
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Oxytocin and love: myths, metaphors and mysteries.
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Effects of intranasal oxytocin on symptoms of schizophrenia: A multivariate Bayesian meta-analysis
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Intranasal delivery of antipsychotic drugs
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“Although it is possible that the concentrations of oxytocin achieved in the brain following IN delivery are higher than those observed in the CSF (Leng and Ludwig, 2016), and IN oxytocin seems to be well tolerated in clinical trials (Oya et al., 2016; Dagani et al., 2016), a lack of clarity surrounding its efficacy ne…”
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Oxytocin under opioid antagonism leads to supralinear enhancement of social attention
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“The effects of opioid receptor subtype were particularly pronounced in the three regions with greatestOXT expression: LHT [F(1,3) = 54.”
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Oxytocin Facilitates Social Learning by Promoting Conformity to Trusted Individuals
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“…trust/trustworthiness and blood concentrations of OXT (Zak et al., 2005; Zhong et al., 2012) others have not (Christensen et al., 2014) and some positive findings need to be treated with caution where unextracted assay protocols were employed which may not be reliable (see Leng and Ludwig, 2016).”
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Argiolas, A., Argiolas, F. M., Argiolas, G., & Melis, M. R. (2023) · Brain Sciences · doi:10.3390/brainsci13050802 · Cited by 63
Sniff and mimic–Intranasal oxytocin increases facial mimicry in a sample of men
Korb, S., Malsert, J., Strathearn, L., Vuilleumier, P., & Niedenthal, P. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2016.06.003 · Cited by 54
“Although the precise mechanisms through which intranasal OT reaches the brain are not well understood (Churchland and Winkielman, 2012; Leng and Ludwig, 2016; Quintana et al., 2015; Veening and Olivier, 2013), OT is believed to reach its maximum effect in the brain after about 45 min, and to alter resting regional cer…”
BackgroundInfluentialPutnam, P. T., Roman, J. M., Zimmerman, P. E., & Gothard, K. M. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.05.016 · Cited by 53
“, 2014) we also cannot rule out the possibility that the observed results are due, at least in part, to the peripheral effects of OT (Leng and Ludwig, 2015).”
Quintana, D. S., Westlye, L. T., Smerud, K. T., Mahmoud, R. A., Andreassen, O. A., & Djupesland, P. G. (2018) · Hormones and Behavior · doi:10.1016/j.yhbeh.2018.05.004 · Cited by 52
“2, 3) were within the expected range (Leng and Ludwig, 2016).”
Yao, S., & Kendrick, K. M. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14020323 · Cited by 55
Everett, N. A., Turner, A. J., Costa, P. A., Baracz, S. J., & Cornish, J. L. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-0719-7 · Cited by 52
Oxytocin secretion is pulsatile in men and is related to social-emotional functioning
Baskaran, C., Plessow, F., Silva, L., Asanza, E., Marengi, D., Eddy, K. T., Sluss, P. M., Johnson, M. L., Misra, M., & Lawson, E. A. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.07.486 · Cited by 50
Mierop, A., Mikolajczak, M., Stahl, C., Béna, J., Luminet, O., Lane, A., & Corneille, O. (2020) · Perspectives on Psychological Science · doi:10.1177/1745691620921525 · Cited by 53
“However, both the reliability of intranasal OT (IN-OT) effects on psychological outcomes (Walum, Waldman, & Young, 2016) and the very physiological plausibility of such effects (Leng & Ludwig, 2016) have been questioned.”
BackgroundInfluentialGlasper, E. R., Kenkel, W. M., Bick, J. R., & Rilling, J. K. (2019) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2019.02.005 · Cited by 58
Oxytocin—a social peptide? Deconstructing the evidence
Leng, G., Leng, R., & Ludwig, M. (2022) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2021.0055 · Cited by 51
Self-citationZoratto, F., Sbriccoli, M., Martinelli, A., Glennon, J. C., Macrı̀, S., & Laviola, G. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.09.010 · Cited by 53
Methylenedioxymethamphetamine (MDMA) in Psychiatry
Schenk, S., & Newcombe, D. A. L. (2018) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000962 · Cited by 53
“The data concerning effective anxiolytic and prosocial effects of systemically administered oxytocin are not unequivocal, and several methodological issues concerning available studies have been raised.(127,135,136) Additional randomized-controlled treatment studies are required, and the role of MDMA-produced oxytocin…”
BackgroundBaracz, S. J., Everett, N. A., & Cornish, J. L. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.08.014 · Cited by 57
Oppong‐Damoah, A., Zaman, R. U., D’Souza, M. J., & Murnane, K. S. (2018) · Hormones and Behavior · doi:10.1016/j.yhbeh.2018.12.011 · Cited by 51
“While promising, this approach has yielded tentative support for the use of intranasal OT, potentially due to its poor bioavailability and brain penetrance even when administered using this route (Keech et al., 2018; Leng and Ludwig, 2016).”
On the role of oxytocin in borderline personality disorder
Brüne, M. (2015) · British Journal of Clinical Psychology · doi:10.1111/bjc.12100 · Cited by 55
Neuropeptide Regulation of Social Attachment: The Prairie Vole Model
Tabbaa, M., Paedae, B., Liu, Y., & Wang, Z. (2016) · Comprehensive physiology · doi:10.1002/cphy.c150055 · Cited by 53
“The extent to which intranasal administration activates central receptors is not entirely clear and sometimes even controversial (165).”
Oxytocin reduces neural activation in response to infant faces in nulliparous young women
Bos, P. A., Spencer, H., & Montoya, E. R. (2018) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsy080 · Cited by 47
“the validity of these assessments (McCullough et al., 2013; Leng and Ludwig, 2016), positive relations between OXT levels and attention toward infant faces have repeatedly been found in parents (Luo et al.”
BackgroundSpontaneous thought and microstate activity modulation by social imitation
Tomescu, M. I., Papasteri, C., Sofonea, A., Boldasu, R., Kebets, V., Pistol, C., Poalelungi, C., Benescu, V., Podina, I. R., Nedelcea, C., et al. (2022) · NeuroImage · doi:10.1016/j.neuroimage.2022.118878 · Cited by 50
Quintana, D. S., & Woolley, J. D. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.06.021 · Cited by 46
The two fold role of oxytocin in social developmental disorders: A cause and a remedy?
Lefèvre, A., & Sirigu, A. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.01.011 · Cited by 48
The neurocircuitry involved in oxytocin modulation of methamphetamine addiction
Baracz, S. J., & Cornish, J. L. (2016) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2016.08.001 · Cited by 46
“However, the efficiency of intranasal oxytocin delivery into the brain has come into question and is coupled with concerns regarding high peripheral oxytocin levels following intranasal administration and the potential unwanted effects this could have on peripheral targets (Leng and Ludwig, 2016).”
BackgroundTabak, B. A., Teed, A. R., Castle, E., Dutcher, J. M., Meyer, M. L., Bryan, R., Irwin, M. R., Lieberman, M. D., & Eisenberger, N. I. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.04.019 · Cited by 43
“A healthy dialogue between engaged skeptics and nuanced proponents is emerging, prompting research groups to recalibrate their efforts toward more careful and systematic approaches to understanding the complex relationships between OT, AVP, and human sociality (Leng and Ludwig, 2016; Quintana and Woolley, 2016).”
BackgroundMartins, D., Paduraru, M., & Paloyelis, Y. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15451 · Cited by 42
Role of oxytocin in parental behaviour
Olazábal, D. E. (2018) · Journal of Neuroendocrinology · doi:10.1111/jne.12594 · Cited by 49
Yeomans, D. C., Hanson, L. R., Carson, D. S., Tunstall, B. J., Lee, M. R., Tzabazis, A., Jacobs, D. L., & Frey, W. H. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01511-7 · Cited by 42
Oxytocin Reduces Face Processing Time but Leaves Recognition Accuracy and Eye-Gaze Unaffected
Hubble, K., Daughters, K., Manstead, A. S. R., Rees, A., Thapar, A., & van Goozen, S. H. M. (2016) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617716000886 · Cited by 42
“In response to recent reviews that have been critical of the quality and rigor of OXT research (Churchland & Winkielman, 2002; Leng & Ludwig, 2016; Walum, Waldman & Young, 2016), we aimed to replicate previous findings of the effects of OXT on facial emotion recognition using a larger sample.”
Intranasal Oxytocin and Vasopressin Modulate Divergent Brainwide Functional Substrates
Galbusera, A., Felice, A. D., Girardi, S., Bassetto, G., Maschietto, M., Nishimori, K., Chini, B., Papaleo, F., Vassanelli, S., & Gozzi, A. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.283 · Cited by 38
Dai, D., Li, Q., Zhu, Q., Hu, S., Balesar, R. A., Swaab, D. F., & Bao, A. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.76 · Cited by 41
“However, the belief that all effects of intranasal OXT can be explained by a direct OXT action on brain systems has been challenged (Leng and Ludwig, 2016).”
BackgroundThe drug treatment of delayed ejaculation
Abdel‐Hamid, I. A., Elsaied, M. A., & Mostafa, T. (2016) · Translational Andrology and Urology · doi:10.21037/tau.2016.05.05 · Cited by 44
“It appears that very little of the huge amounts applied intranasally reach the cerebrospinal fluid and peripheral concentrations are increased to supraphysiologic levels, with likely effects on diverse targets including and the genital tract (127).”
BackgroundOxytocin Enhances the Neural Efficiency of Social Perception
Tillman, R. M., Gordon, I., Naples, A. J., Rolison, M. J., Leckman, J. F., Feldman, R., Pelphrey, K. A., & McPartland, J. C. (2019) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2019.00071 · Cited by 43
“Since the mechanism by which OT is delivered to the brain following intranasal administration has not yet been fully established (Leng and Ludwig, 2016), researchers have called for caution when interpreting OT’s effects following nasal administration (Miller, 2013).”
BackgroundGeng, Y., Zhao, W., Zhou, F., Ma, X., Yao, S., Becker, B., & Kendrick, K. M. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00572 · Cited by 42
Espinoza, S. E., Lee, J. L., Wang, C.-P., Ganapathy, V., MacCarthy, D., Pascucci, C., Musi, N., & Volpi, E. (2021) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2021.04.015 · Cited by 44
Oxytocin, Erectile Function and Sexual Behavior: Last Discoveries and Possible Advances
Melis, M. R., & Argiolas, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910376 · Cited by 45
Arginine vasopressin deficiency: diagnosis, management and the relevance of oxytocin deficiency
Atila, C., Refardt, J. C., & Christ‐Crain, M. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-00985-x · Cited by 52
Quintana, D. S., Dieset, I., Elvsåshagen, T., Westlye, L. T., & Andreassen, O. A. (2017) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2016.12.004 · Cited by 39
“Although only very little peripherally administered OT appears to cross the BBB (Leng and Ludwig, 2016; Mens et al., 1983), others argue that these small amounts can still be physiologically relevant (Neumann et al., 2013).”
BackgroundResultInfluentialOxytocin improves facial emotion recognition in young adults with antisocial personality disorder
Timmermann, M., Jeung, H., Schmitt, R., Boll, S., Freitag, C. M., Bertsch, K., & Herpertz, S. C. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.07.483 · Cited by 46
Bienboire‐Frosini, C., Chabaud, C., Cozzi, A., Codecasa, E., & Pageat, P. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00524 · Cited by 44
“This kit has been increasingly used in studies assaying OT in various animal species in the last decade (Robinson et al., 2014; Leng and Ludwig, 2016).”
BackgroundMethodMustoe, A. C., Harnisch, A. M., Hochfelder, B., Cavanaugh, J., & French, J. A. (2016) · Animal Behaviour · doi:10.1016/j.anbehav.2016.01.025 · Cited by 40
“…of OXT inmacaques and humans leads to increases in OXT concentrations in both plasma and cerebrospinal fluid (CSF) (Dal Monte, Noble, Turchi, Cummins, & Averbeck, 2014; Striepens et al., 2013; but see Leng & Ludwig, 2015, about important considerations of intranasal OXT administration).”
BackgroundOxytocin regulates reunion affiliation with a pairmate following social separation in marmosets
Cavanaugh, J., Mustoe, A. C., & French, J. A. (2018) · American Journal of Primatology · doi:10.1002/ajp.22750 · Cited by 42
“…reviews have communicated important statistical and methodological concerns regarding the efficacy of intranasal neuropeptide treatments (Leng & Ludwig, 2015; Walum, Waldman, & Young, 2016), the effects of intranasal OT administration on social cognition and behavior are well-established…”
BackgroundInfluentialOxytocin Receptor Signaling in Vascular Function and Stroke
McKay, E. C., & Counts, S. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.574499 · Cited by 45
“, 2014), but again, CNS penetration is relatively low (Leng and Ludwig, 2016).”
BackgroundHubble, K., Daughters, K., Manstead, A. S. R., Rees, A., Thapar, A., & van Goozen, S. H. M. (2017) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2017.10.019 · Cited by 41
“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) and in view of evidence of large variations in individual responsivity to OXT across participants (Daughters et al., 2015), we…”
A Novel Role of CD38 and Oxytocin as Tandem Molecular Moderators of Human Social Behavior
Tolomeo, S., Chiao, B., Lei, Z., Chew, S. H., & Ebstein, R. P. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.04.013 · Cited by 40
“Less is more”: A dose-response account of intranasal oxytocin pharmacodynamics in the human brain
Martins, D., Brodmann, K., Veronese, M., Dipasquale, O., Mazibuko, N., Schuschnig, U., Zelaya, F. O., Fotopoulou, A., & Paloyelis, Y. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102239 · Cited by 43
“While doubts persist about the exact mechanisms through which oxytocin may reach and induce functional effects in the brain when administered intranasally (Leng and Ludwig, 2016), our findings provide an extra level of evidence strengthening our confidence on the utility of intranasal administrations of oxytocin as a…”
BackgroundSniffing oxytocin: Nose to brain or nose to blood?
Yao, S., Chen, Y., Zhuang, Q., Zhang, Y., Lan, C., Zhu, S., Becker, B., & Kendrick, K. M. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02075-2 · Cited by 41
“Five subjects were excluded due to failure of blood sampling (3 subjects), falling asleep (1 subject), or technical problems during data recording (1 subject).”
BackgroundCommon variant in OXTR predicts growth in positive emotions from loving-kindness training
Isgett, S. F., Algoe, S. B., Boulton, A. J., Way, B. M., & Fredrickson, B. L. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.08.010 · Cited by 41
Ma, Q., Li, X., Yan, Z., Jiao, H., Wang, T., Hou, Y., Jiang, Y.-M., Liu, Y., & Chen, J. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00910 · Cited by 40
Kou, J., Lan, C., Zhang, Y., Wang, Q., Zhou, F., Zhao, Z., Montag, C., Yao, S., Becker, B., & Kendrick, K. M. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01241-w · Cited by 39
Buchanan, R. W., Kelly, D. L., Weiner, E., Gold, J. M., Strauss, G. P., Koola, M. M., McMahon, R. P., & Carpenter, W. T. (2017) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000720 · Cited by 41
“of the pharmacodynamics, pharmacokinetics, and optimal dosing strategy for oxytocin may be inadequate.(53,54) Our selected dose was based on the dosage used in single-dose-challenge studies with control subjects.”
Understanding the Oxytocin System and Its Relevance to Psychiatry
Shamay‐Tsoory, S., & Young, L. J. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.10.014 · Cited by 39
“Leng G, Ludwig M. Intranasal oxytocin: Myths and delusions.”
BackgroundInfluentialOxytocin and emotion processing
Simplicio, M. C. D., & Harmer, C. J. (2016) · Journal of Psychopharmacology · doi:10.1177/0269881116641872 · Cited by 38
“Leaving aside the debate on if and how exogenous intranasal oxytocin reaches brain sites of action (Leng and Ludwig, 2016), some inconsistencies are probably the result of methodological shortcomings and small sample sizes (Guastella and MacLeod, 2012; Walum et al., 2016).”
BackgroundDumais, K. M., Kulkarni, P. P., Ferris, C. F., & Veenema, A. H. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.04.003 · Cited by 34
Horrell, N. D., Hickmott, P. W., & Wendy Saltzman, A. (2018) · Current topics in behavioral neurosciences · doi:10.1007/7854_2018_55 · Cited by 45
Chen, X., Nishitani, S., Haroon, E., Smith, A. K., & Rilling, J. K. (2019) · Genes Brain & Behavior · doi:10.1111/gbb.12555 · Cited by 39
Revisiting non-significant effects of intranasal oxytocin using equivalence testing
Quintana, D. S. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.10.010 · Cited by 38
Variation in the oxytocin receptor gene (OXTR) is associated with differences in moral judgment
Bernhard, R. M., Chaponis, J., Siburian, R., Gallagher, P., Ransohoff, K. J., Wikler, D. I., Perlis, R. H., & Greene, J. D. (2016) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsw103 · Cited by 41
“, 2011), and the mechanism by which intranasal oxytocin potentially affects behavior remains an open question (Leng and Ludwig, 2016).”
BackgroundXu, X., Yao, S., Xu, L., Geng, Y., Zhao, W., Ma, X., Kou, J., Luo, R., & Kendrick, K. M. (2017) · Scientific Reports · doi:10.1038/srep40589 · Cited by 33
Wei, J., Ma, L., Ju, P., Yang, B., Wang, Y., & Chen, J. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.564485 · Cited by 39
“OT has quite a limited ability to penetrate the blood–brain barrier and can only rely on related receptor transport (Leng and Ludwig, 2016; Duarte-Guterman et al., 2020), which is the reason that the current clinical administration is mainly through intranasal administration.”
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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