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Cited by 61Neuroendocrine regulation and behaviorExperimental Behavioral Economics StudiesOlfactory and Sensory Function Studies

Failed Replication of Oxytocin Effects on Trust: The Envelope Task Case

Open access
Lane, Anthony, Mikolajczak, Moïra, Treinen, Evelyne, Samson, Dana, Corneille, Olivier, de Timary, Philippe, Luminet, Olivier·2015·PLOS ONE
DOI 10.1371/journal.pone.0137000PMC PMC4569325
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Abstract

The neurohormone Oxytocin (OT) has been one of the most studied peptides in behavioral sciences over the past two decades. Many studies have suggested that OT could increase trusting behaviors. A previous study, based on the "Envelope Task" paradigm, where trust is assessed by the degree of openness of an envelope containing participant's confidential information, showed that OT increases trusting behavior and reported one of the most powerful effects of OT on a behavioral variable. In this paper we present two failed replications of this effect, despite sufficient power to replicate the original large effect. The non-significant results of these two failed replications clearly exclude a large effect of OT on trust in this paradigm but are compatible with either a null effect of OT on trust, or a small effect, undetectable with small sample size (N = 95 and 61 in Study 1 and 2, respectively). Taken together, our results question the purported size of OT's effect on trust and emphasize the need for replications.

AI snapshot

Written from the paper’s full text.

TL;DR

Two high-powered conceptual replications failed to reproduce the large effect of intranasal oxytocin on trust in the Envelope Task. The results exclude a large effect but remain compatible with a null effect or a small, undetectable effect.

Key findings

  • In Study 1 (N = 95 males; OT n = 47, placebo n = 48), oxytocin did not increase envelope openness: one-way ANOVA F(1,93) = .229, p = .663; ordinal regression −2 Log-Likelihood = 17.801, p = .542.
  • In Study 2 (N = 61 males; OT n = 32, placebo n = 29), oxytocin again did not increase envelope openness: one-way ANOVA F(1,59) = .295, p = .589; ordinal regression −2 Log-Likelihood = 15.726, p = .522.
  • The original Envelope Task study had reported a very large effect (Cohen’s d = 2.29 by ANOVA; d = 3.07 by ordinal regression), whereas pooling Studies 1 and 2 yielded an aggregated effect size of d = −0.12, 95% CI [−0.43, 0.19].
  • The authors state that only 14 participants would have been needed to replicate d = 2.29, and 84 for d = 0.8, so the replications were sufficiently powered to detect a large effect; detecting the upper-bound small effect (d = 0.19) would require 1,442 participants.

Methods

  • Two double-blind, placebo-controlled studies in healthy young adult males received intranasal oxytocin (32 IU Syntocinon Spray, 4 puffs per nostril) or placebo.
  • Trust was assessed with the Envelope Task: participants completed intimate or evaluative questionnaires, placed them in an envelope, and could leave it open, seal it, or seal and tape it; openness was coded 1 = sealed and taped, 2 = sealed, 3 = left open.
  • Study 1 examined mimetic desire and visual perspective taking; Study 2 examined compassion. Analyses used one-way ANOVA and ordinal regression with condition as the between-subjects factor and envelope openness as the dependent variable.

Limitations

  • Stated: Study 1 was not a direct replication because it used a different questionnaire and is therefore a conceptual replication.
  • Stated: the results cannot distinguish a null effect of oxytocin on trust from a small effect; the studies were underpowered for a small effect, and the original single-blind study could not formally exclude experimenter bias or unconscious behavioral priming.
  • Stated: uncertainty remains about whether intranasal oxytocin crosses the blood-brain barrier and about effective dosing; the paper notes only one small pharmacokinetic study (n = 11) and possible contextual moderators such as experimenter sex, location, and preceding tasks.
  • Evident: both replication samples were male-only, and the paper reports no moderation effects with baseline personality measures.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0137000

Cites

35 of 35 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

6 of 12 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured

  • Findingown data

    In Study 1, there was no significant difference between oxytocin and placebo in the degree of openness of the envelope, by one-way ANOVA (F(1,93) = .229, p = .663) or ordinal regression (-2 Log-Likelihood = 17.801, p = .542).

    “No differences were found, either with the one-way ANOVA (F(1,93) = .229; p = .663) or with the ordinal regression (-2 Log-Likelihood = 17.801; p = .542).”
    Quote in the paperSubstantial claim
  • Findingown data

    In two studies, the authors were unable to replicate their own findings on oxytocin and trust.

    “In two studies (even if Study 1 is not a direct replication of the original study, as we did not use the same questionnaire, and has to be considered as a conceptual replication), we were unable to replicate our own findings on OT and trust.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The degree of openness of the envelope reflects participants' trust toward the experimenter.
  • Findingown data

    Pooling Study 1 and Study 2 yields an aggregated effect size of d = -0.12, 95% CI [-0.43; 0.19].

    “When we pool the findings of Study 1 and Study 2 (which are very close to one another), we obtain an aggregated effect size of d = -0.12, [95% CI: -0.43;0.19].”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The degree of openness of the envelope reflects participants' trust toward the experimenter.
  • Findingown data

    In Study 2, there was no significant difference between oxytocin and placebo in the degree of openness of the envelope, by one-way ANOVA (F(1,59) = .295, p = .589) or ordinal regression (-2 Log-Likelihood = 15.726, p = .522).

    “No differences were found, either with the one-way ANOVA (F(1,59) = .295; p = .589) or with the ordinal regression (-2 Log-Likelihood = 15.726; p = .522).”
    Quote in the paperSubstantial claim
  • Interpretationown data

    Taken together, the authors' results question the purported size of oxytocin's effect on trust.

    “Taken together, our results question the purported size of OT’s effect on trust”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The degree of openness of the envelope reflects participants' trust toward the experimenter.
  • May combine two claims. 12
  • Classified as probably not a substantial claim. 6
  • The quote only partly states this claim. 1

  • May combine two claims.

    Premisecitation

    An experimenter who knows the participants' condition may unintentionally act differently so that participants' behavior may be altered to confirm the researcher's hypothesis.

    “As demonstrated by Doyen et al. [25] the experimenter who knows the participants’ condition may unintentionally act differently so that participants’ behavior may be altered to confirm the researcher’s hypothesis.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [25] S Doyen, 2012, Behavioral Priming: It’s all in the Mind, but whose Mind?, PLOS ONE source

  • May combine two claims.

    Premisecitation

    Kosfeld's seminal finding on oxytocin and trust has not always been replicated; Baumgartner et al. found no significant effect of oxytocin on the pre-betrayal trust game, and two independent studies also failed to replicate Kosfeld's findings.

    “We noticed that Kosfeld’s [1] seminal finding was not always replicated either. Indeed, Baumgartner et al. [7] found no significant effect of OT on the pre-betrayal trust game. More recently, two independent studies also failed to replicate Kosfeld’s findings [20] [21].”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [7] T Baumgartner, 2008, Oxytocin shapes the neural circuitry of trust and trust adaptation in humans, Neuron source
    • cites [20] J Klackl, 2013, Who is to blame? Oxytocin promotes nonpersonalistic attributions in response to a trust betrayal, Biological psychology source
    • cites [21] S Yao, 2014, Oxytocin makes females, but not males, less forgiving following betrayal of trust, International Journal of Neuropharmacology source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Regarding trust, oxytocin effects are moderated by characteristics of the subject (sex and attachment type) and by characteristics of the target (perceived level of reliability).

    “Regarding trust, it has been shown that OT effects are moderated by the characteristics of the subject (i.e. sex [21] and attachment type [30]) and by those of the target (i.e. its perceived level of reliability [8]).”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [21] S Yao, 2014, Oxytocin makes females, but not males, less forgiving following betrayal of trust, International Journal of Neuropharmacology source
    • cites [30] K De Dreu, 2012, Oxytocin modulates the link between adult attachment and cooperation through reduced betrayal aversion, Psychoneuroendocrinology source
    • cites [8] M Mikolajczak, 2010, Oxytocin makes people trusting, not gullible, Psychological Science source

  • May combine two claims.

    Premisecitation

    Only one study has studied the exact pharmacokinetics of intranasal oxytocin; it showed an elevation of CSF oxytocin 75 minutes after intranasal administration.

    “only one study [23] has studied its exact pharmacokinetics. This study showed an elevation of CSF OT occurs 75 minutes after intranasal administration (whereas most of the behavioral tasks in the literature take place 45 minutes post-administration).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [23] N Striepens, 2013, Elevated cerebrospinal fluid and blood concentration of oxytocin following its intranasal administration in humans, Scientific Reports source

      The Results report significantly elevated CSF oxytocin 75 minutes after intranasal administration, and the Discussion describes this as the first study to show increased human CSF concentrations. The broader claim that only one study had examined the exact pharmacokinetics is not supported: the paper cites earlier studies of plasma concentrations and says the precise duration of elevated CSF concentrations remains unknown. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Study design and conductreasoning

    Even for a large effect of d = 0.8, 84 participants would have been enough to replicate it, and Study 1 had 95 participants.

    “Even when we take the lower bound of a large effect size regarding Cohen's norms (i.e., d = 0.8), 84 participants should have been enough to replicate a large effect (we had 95 participants in Study 1).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Interpretationown data

    Study 2's findings suggest that oxytocin does not enhance trust toward the experimenter.

    “These findings suggest that OT does not enhance trust toward the experimenter (Fig 1).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The degree of openness of the envelope reflects participants' trust toward the experimenter.
    • Rests on an assumption: The intimate nature of the questionnaire ensures that participants would not want to disclose the information to a stranger.

  • May combine two claims.

    Study design and conductreasoning

    The two studies had sufficient power to replicate a large effect of oxytocin on trust; only 14 participants would have been needed to replicate an effect size of d = 2.29.

    “This hypothesis is however not likely as only 14 participants would have been needed to replicate such a large effect size (d = 2.29).”
    • Also stated in: § Discussion · boosted
      “Therefore, we can exclude a priori the idea that our studies were underpowered to replicate a large effect.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The non-significant results are compatible with either a null effect of oxytocin on trust or a small effect undetectable with the small sample sizes (N = 95 and 61 in Study 1 and Study 2, respectively).

    “but are compatible with either a null effect of OT on trust, or a small effect, undetectable with small sample size (N = 95 and 61 in Study 1 and 2, respectively).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The degree of openness of the envelope reflects participants' trust toward the experimenter.

  • May combine two claims.

    Premisecitation

    Nave and colleagues' analysis of seven studies found that the combined effect size of intranasal oxytocin on trust was small and not reliably different from zero (Cohen's d = 0.077, 95% CI [-0.124; 0.278]).

    “Nave and colleagues [22] computed the effect sizes of seven studies that have investigated the effect of intranasal OT on trust trough the trust game. Their analysis revealed that the combined effect size of intranasal OT on trust was small and not reliably different from zero (Cohen’s d = 0.077, 95%CI: [-0.124;0.278]).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [22] G Nave, 2015, Does Oxytocin increase trust in humans? Critical review of research, Perspectives on Psychological Science source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    In Study 2, oxytocin administration followed a double-blind procedure, the same as in Study 1.

    “The administration followed a double blind procedure (the blinding procedure was the same as the one reported in Study 1).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    In Study 2, 61 healthy young adult males were randomly assigned to receive intranasal placebo or oxytocin.

    “61 healthy young adult males (Mage = 21.28; SD = 2.1) took part in the study and were randomly assigned to receive either the intranasal placebo (PL; n = 29) or OT (n = 32; 32 IU Syntocinon Spray – 4 puffs in each nostril–Fuerte Farmaceutica, Funchal, Portugal).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    In Study 1, 95 healthy young adult males were randomly assigned to receive intranasal placebo or oxytocin.

    “95 healthy young adult males (Mage = 22.53; SD = 2.89) took part in the study and were randomly assigned to receive either intranasal placebo (PL; n = 48) or OT (n = 47; 32 IU Syntocinon Spray – 4 puffs in each nostril–Fuerte Farmaceutica, Funchal, Portugal).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    A recent meta-analytic investigation demonstrated that published studies involving intranasal oxytocin in humans are generally underpowered, report overestimated effects, and have low positive predictive value.

    “a recent meta-analytic investigation on published studies involving intranasal administration of OT in humans [28] demonstrated that those studies are generally underpowered and report overestimated effects. This meta-analysis also demonstrated that the positive predictive value of those studies (using information on power, the pre-study odds and the alpha level) is low.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] H Walum, Statistical and methodological considerations for the interpretation of intranasal oxytocin studies, Biological Psychiatry

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Study design and conductreasoning

    The two studies were underpowered to detect a small effect; if the true effect were as small as d = 0.19, 1442 participants would have been needed to render it significant.

    “If the “true” effect of OT on trust in the envelope task is not large (as suggested by the original study) but rather small, as suggested by the upper bound value of the CI in Study 1 & 2 (d = 0.19), we would have needed a sample of 1442 participants to render such a small effect significant.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    The first and fifth hypotheses about oxytocin's effect on the Envelope Task seem much less likely than the other three hypotheses.

    “As we write these lines, we do not know which hypothesis is true, although the first and last seem much less likely than the other three.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    In Study 1, oxytocin administration followed a double-blind procedure.

    “The administration followed a double-blind procedure (the product samples were blinded with a sticky label by a colleague of the experimenter.”
    Quote in the paperNot a substantial claim
16 of 16

  • The paper relies on this without support.

    The degree of openness of the envelope reflects participants' trust toward the experimenter.

    “the level of confidence granted to a stranger (here the experimenter) is reflected in the degree of openness of the envelope”
    “Trustful people will tend to leave the envelope open (they trust the experimenter and think that he will not betray them), distrustful ones will be more likely to seal the envelope and even to add sticky tape (they do not trust the experimenter and think that he might betray them).”

  • The paper relies on this without support.

    The intimate nature of the questionnaire ensures that participants would not want to disclose the information to a stranger.

    “The very intimate nature of the questions aims to ensure that participants would not want to disclose such information to a stranger.”
    “The nature of some questions aimed to ensure that participants would not wish to disclose the opinions they held about the experimenter (i.e. “What are the experimenter’s 3 greatest flaws?”).”
2 of 2

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?

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • ConsistentF(1, 90) = 7.66reported p < .007 · recomputed p = .007

    “F (1,90) = 7.66, p < .007”

  • ConsistentF(1, 58) = 78.069reported p < .001 · recomputed p < .001

    “F(1,58) = 78.069, p < .001”

  • ConsistentF(1, 93) = 0.229reported p = .633 · recomputed p = .633

    “F(1,93) = .229, p = .633”

  • ConsistentF(1, 59) = 0.295reported p = .589 · recomputed p = .589

    “F(1,59) = .295, p = .589”

4 of 4

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Study 1 reports two different ANOVA p-values

    Minor

    The Results section gives p = .663 for the Study 1 envelope-task ANOVA, while Table 1 gives p = .633 for the same F(1,93) = .229 result.

1 of 1

Cites

Flagged first, then by citations

4 of the 39 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. J Tournois, 2000, Autoduperie et hétéroduperie: un instrument de mesure de la désirabilité sociale, European Review of Applied Psychology, 50, 219
  2. Bodley Scott SE. Understanding empathy for the good and bad fortunes of others. PhD thesis. University of Nottingham. 2011; Available: <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://eprints.nottingham.ac.uk/12945/" xlink:type="simple">http://eprints.nottingham.ac.uk/12945/</ext-link>

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Related

Authors
Lane, A., Mikolajczak, M., Treinen, E., Samson, D., Corneille, O., de Timary, P., & Luminet, O.
Affiliations
  • UCLouvain (BE)
  • University of Denver (US)
Corresponding author
Lane, Anthony
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2015-09-14
Volume
10
Issue
9
Pages
e0137000
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0137000
PMC
PMC4569325
OpenAlex
W1846667482
Semantic Scholar
c5b3f6260783405df5b81fb6e5472202bf6cb7dd
Cited by
61
References
39
Citations by year
2026: 1 · 2025: 6 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 7 · 2020: 7 · 2019: 5 · 2018: 8 · 2017: 11 · 2016: 3 · 2015: 3
FWCI
13.06
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Digital Access to Libraries (submittedVersion, public-domain)
  • Digital Access to Libraries (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Social Sciences › Safety Research › Experimental Behavioral Economics Studies
  • Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
Keywords
oxytocin, trust, replication failure, replication study, neurohormones, social behavior, effect size, sample size
MeSH terms
Adult, Behavior, Humans, Male, Oxytocin, Trust

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