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Cited by 39Pain Management and Placebo EffectNeuroendocrine regulation and behaviorStress Responses and Cortisol

Placebo treatment facilitates social trust and approach behavior

Open access
Yan, Xinyuan, Yong, Xue, Huang, Wenhao, Ma, Yina·2018·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1800779115PMC PMC5984523
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Abstract

Significance: The World Health Organization defines health as a state of physical, mental, and social well-being. Although placebo treatment has been widely shown to improve physical and mental well-being, it remains unknown whether placebo treatment facilitates social well-being. Here, we provide evidence that placebo treatment facilitates social approach by increasing trust in others and preference for being physically closer to others. The social placebo effects (SPEs) resemble the effect of intranasal administration of oxytocin, an important neuropeptide for social cognition, on social trust and approach behavior, but the SPE is more sensitive to motivational state. Our findings extend the understanding of placebo effects on improving physical, mental, and social well-being and suggest clinical potentials in the treatment of social dysfunction.

AI snapshot

Written from the paper’s full text.

TL;DR

Placebo treatment (saline nasal spray presented as oxytocin) increased social trust and preference for closer interpersonal distance in healthy heterosexual men, and reduced real-life interpersonal distance and perceived anxiety in a first-met female. Effects resembled intranasal oxytocin but were more sensitive to motivational/social context, such as betrayal feedback, eye contact, and romantic relationship status.

Key findings

  • Placebo treatment increased social trust in a trust game: Exp. 1 repeated-measures ANOVA showed a treatment main effect, \(F(2,56)=3.238\), \(P=0.047\), \(\eta_p^2=0.104\), with greater investment in spray+ than spray control, \(t(28)=2.443\), \(P=0.021\), Cohen \(d'=0.453\), and material control, \(t(28)=2.415\), \(P=0.023\), Cohen \(d'=0.448\); Exp. 2 replicated this, \(t(31)=3.540\), \(P=0.001\), Cohen \(d'=0.625\).
  • Placebo treatment increased preference for closer interpersonal distance: Exp. 1 treatment effect, \(F(2,56)=13.097\), \(P<0.001\), \(\eta_p^2=0.319\), with shorter preferred distance in spray+ than spray control, \(t(28)=-4.241\), \(P<0.001\), Cohen \(d'=0.787\), and material control, \(t(28)=-4.172\), \(P<0.001\), Cohen \(d'=0.774\); Exp. 2 replicated this, \(t(30)=-2.067\), \(P=0.047\), Cohen \(d'=0.371\).
  • The trust effect correlated with and partially mediated the distance effect: SPE on trust correlated with SPE on preferred distance, \(r(60)=-0.367\), \(P=0.004\); mediation Sobel test, \(Z=-2.498\), \(P=0.012\), partial mediation.
  • In real-life interaction, placebo reduced interpersonal distance, \(F(1,29)=4.312\), \(P=0.047\), \(\eta_p^2=0.129\), especially without eye contact, treatment × eye-contact \(F(1,29)=4.515\), \(P=0.042\), \(\eta_p^2=0.135\); it also reduced perceived anxiety in the female experimenter, \(F(1,29)=4.485\), \(P=0.043\), \(\eta_p^2=0.134\), especially with eye contact, interaction \(F(1,29)=5.009\), \(P=0.033\), \(\eta_p^2=0.147\). The real-life distance effect was selective for single males, treatment × relationship \(F(1,28)=13.933\), \(P<0.001\), \(\eta_p^2=0.332\); single males \(t(12)=-3.739\), \(P=0.003\), Cohen \(d'=1.037\), pair-bonded males \(t(16)=0.697\), \(P=0.496\), Cohen \(d'=0.169\). Placebo and active oxytocin showed comparable effects on trust, \(F(1,59)=10.944\), \(P=0.002\), \(\eta_p^2=0.156\), and real-life distance, \(F(1,57)=6.800\), \(P=0.012\), \(\eta_p^2=0.107\), though placebo trust was sensitive to betrayal, treatment × betrayal × group \(F(1,59)=5.242\), \(P=0.026\), \(\eta_p^2=0.082\).

Methods

  • Recruited 651 paid volunteers total: \(n=503\) for Exp. 0a–c, \(n=30\) for Exp. 1, \(n=32\) for Exp. 2, \(n=57\) for Exp. 3, and \(n=29\) for Exp. 4. Formal experiments examining SPE or active oxytocin effects recruited heterosexual male participants who were healthy, right-handed, and had no history of neurological or psychiatric disorders.
  • Within-subject designs: Exp. 1 had three sessions (spray+, spray control, material control) separated by ≥7 d; Exp. 2 and Exp. 3 used spray+ vs. material control; Exp. 4 used double-blind, within-subject active oxytocin vs. placebo. Placebo manipulation combined oxytocin materials with self-administered saline nasal spray described as oxytocin. Tasks included a trust game, distance preference task, and real-life stop-distance task.
  • Main analyses used repeated-measures ANOVA, paired t tests, correlation, mediation with Sobel test and bias-corrected bootstrap resampling (5,000 resamples), and G*Power 3.1 for correlation/mediation sample-size planning.

Limitations

  • Stated in the paper: behavioral results do not allow examination of the neurobiological system involved in the social placebo effect; the authors note that future work needs to clarify whether and how SPE is linked to the oxytocinergic system and other neural systems such as dopaminergic and opioid systems.
  • Evident from the text: the formal experiments recruited only heterosexual male participants, limiting generalizability to females and non-heterosexual individuals; some subsamples were small, including Exp. 3 with 13 single males and 17 pair-bonded males, though an independent sample of 27 males was added to confirm the relationship-status modulation in a pooled sample of \(N=57\).

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Integrity signals

Registry

Crossref · 10.1073/pnas.1800779115

Cites

60 of 60 references verified0 citation errors · 0 not checkable

Statistics

32 tests recomputed · 0 with the reported and recomputed p on opposite sides of .05

Claims the paper makes

0 of 60 cited sources checked · 0 supported · 0 flagged

  • Findingown data
    § Results

    The effect of placebo treatment on real-life interpersonal distance is modulated by eye contact: it is present in the no-eye-contact situation but not in the eye-contact situation.

    “participants kept a closer distance with the female experimenter in the spray+ session (relative to control) in the no-eye contact situation [t(29) = −2.302, P = 0.029, Cohen d′ = 0.420], but not the eye-contact situation [t(29) = −1.210, P = 0.236, Cohen d′ = 0.221].”
    Quote in the paperSubstantial claim
  • Findingown data
    § Results

    The effect of placebo treatment on real-life interpersonal distance is selective to single males, not pair-bonded males.

    “reliable SPE on reducing interpersonal distance in single [t(12) = −3.739, P = 0.003, Cohen d′ = 1.037] but not pair-bonded males [t(16) = 0.697, P = 0.496, Cohen d′ = 0.169].”
    • Also stated in: § Results · boosted
      “The modulation of romantic relationship on SPE on interpersonal distance was further confirmed in the pooled sample (N = 57; SI Appendix, Section 9 and Fig. S5).”
    Quote in the paperSubstantial claim
  • Findingown data
    § Results

    The SPE on trust is significantly correlated with the SPE on preferred distance.

    “the SPE on trust (trustspray+ − trustcontrol) was significantly correlated with the SPE on preferred distance, i.e., spray+ manipulation decreased preferred distance to a greater degree in individuals who showed stronger SPE on trust [r(60) = −0.367, P = 0.004; Fig. 2].”
    Quote in the paperSubstantial claim
  • Findingown data
    § Results

    Placebo treatment decreases real-life interpersonal distance relative to material control.

    “The main effect of treatment was significant [F(1,29) = 4.312, P = 0.047, ηp2 = 0.129], as, relative to material control, spray+ manipulation decreased interpersonal distance.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Abstract

    Exposure to oxytocin materials alone (without nasal spray) did not affect social trust or preferred interpersonal distance.

    “exposure to oxytocin or control documents alone did not affect social trust (P > 0.3) or preferred interpersonal distance (P > 0.5, Exp. 0c; SI Appendix, Section 3).”
    Quote in the paperSubstantial claim
  • May combine two claims. 26
  • Classified as probably not a substantial claim. 39
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data
    § Results

    Placebo treatment reduces perceived anxiety in the female experimenter in the eye-contact situation but not in the no-eye-contact situation.

    “The placebo treatment reduced perceived anxiety in the female experimenter in the eye-contact situation [t(29) = −2.648, P = 0.013, Cohen d′ = 0.483] but not in the no-eye contact situation (P > 0.5).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Results

    The effect of placebo treatment on social trust is evident before receiving betrayal feedback but not after betrayal.

    “SPE on trust was only evident before receiving betrayal feedback but not after betrayal [treatment × betrayal, F(1,31) = 10.055, P = 0.003, ηp2 = 0.245]”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Oxytocin was shown to increase trust and adaptation to trust betrayal.

  • May combine two claims.

    Findingown data
    § Results

    The spray+ manipulation induced expectations of beneficial effects of oxytocin treatment, with higher willingness to trust and interact.

    “indeed brought expectations of beneficial effects of oxytocin treatment, with subjects reporting higher levels of willingness to trust others [F(2,56) = 5.155, P = 0.009, ηp2 = 0.155] and to interact with others [F(2,52) = 4.963, P = 0.011, ηp2 = 0.160].”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Abstract

    Placebo treatment (inert nasal spray believed to be oxytocin) increases social trust (investment in trust game) relative to control conditions.

    “show robust evidence that placebo treatment promotes trust in others and increases preference for a closer interpersonal distance.”
    • Also stated in: § Results · plain
      “the amount of investment was greater in the spray+ sessions than in controls [spray+ vs. spray control, t(28) = 2.443, P = 0.021, Cohen d′ = 0.453; spray+ vs. material control, t(28) = 2.415, P = 0.023, Cohen d′ = 0.448].”
    • Also stated in: § Results · plain
      “The SPE on increasing social trust was further replicated in Exp. 2 [t(31) = 3.540, P = 0.001, Cohen d′ = 0.625; Fig. 1B].”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Social trust and approach behavior are two fundamental aspects of social well-being.

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

    Findingown data
    § Results

    Similar analyses on one's own anxiety and perceived anxiety in others did not show reliable interactive effects.

    “Similar analyses on one’s own anxiety and perceived anxiety in others did not show reliable interactive effects (P values >0.05).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Discussion

    SPE reduces interpersonal distance and perceived anxiety in others in a real-life situation when individuals felt personal distress.

    “Specifically, we showed SPE on reduced interpersonal distance and perceived anxiety in others in a real-life situation when individuals felt personal distress.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Discussion

    Placebo treatment can increase trust and facilitate social approach.

    “We provide behavioral (rather than self-reported or evaluated by others) evidence that placebo treatment can increase trust and facilitate social approach”
    Quote in the paperSubstantial claim

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

    Findingown data
    § Methods

    The SPE on slightly uncomfortable distance was largely the same with that on very uncomfortable distance.

    “The SPE on slightly uncomfortable distance was largely the same with that on very uncomfortable distance (SI Appendix, Section 20 and Fig. S8).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data
    § Results

    Placebo treatment and active oxytocin both decrease real-life interpersonal distance, but the effect of placebo is modulated by eye contact whereas oxytocin's is not.

    “main effect of treatment [F(1,57) = 6.800, P = 0.012, ηp2 = 0.107], suggesting that placebo treatment and active oxytocin made participants get closer to the female experimenter.”
    • Also stated in: § Results · plain
      “The SPE was selectively observed in the no-eye contact situation (Fig. 3A) whereas AOE on interpersonal distance was not modulated by eye-contact situations (SI Appendix, Section 11 and Fig. S6).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data
    § Discussion

    Neither exposure to oxytocin materials without receiving inert treatment nor administration of inert treatment without acquisition of oxytocin expectation was able to elicit SPE.

    “Neither exposure to oxytocin materials without receiving inert treatment nor administration of inert treatment without acquisition of oxytocin expectation (SI Appendix, Section 15) was able to elicit SPE.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation
    § Abstract

    Oxytocin normalized abnormal neural responses to negative social stimuli in patients with social anxiety disorder.

    “normalized the abnormal neural responses to negative social stimuli in patients with social anxiety disorder (32, 33).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [32] Labuschagne I, et al. Oxytocin attenuates amygdala reactivity to fear in generalized social anxiety disorder. Neuropsychopharmacology. 2010;35:2403–2413. doi: 10.1038/npp.2010.123. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

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      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Discussion

    The SPE on social trust was diminished when initial trust was betrayed, as betrayal signaled untrustworthiness and dampened the motivation to trust.

    “the SPE on social trust was diminished when the initial trust was betrayed, as betrayal signaled untrustworthiness and dampened the motivation to trust.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Oxytocin was shown to increase trust and adaptation to trust betrayal.

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

    Premisecitation
    § Abstract

    Oxytocin increases physical approach leading to closer interpersonal distance.

    “and increase physical approach leading to closer interpersonal distance (24, 25).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [24] Cohen D, Shamay-Tsoory SG. Oxytocin regulates social approach. Soc Neurosci. 2017;17:1–8. doi: 10.1080/17470919.2017.1418428. [DOI] [PubMed] [Google Scholar]

      Not checked in the free run.

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      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Discussion

    The SPE is sensitive to social context and personal state linked to social motivation.

    “Taken together, the SPE is sensitive to social context and personal state linked to social motivation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data
    § Discussion

    The SPE could not be attributed to exposure to oxytocin materials, perceived experimenter's expectation, or social desirability.

    “the SPE could not be simply attributed to exposure to oxytocin materials (SI Appendix, Section 3) or perceived experimenter’s expectation (Experimenter-Blind Procedure) or social desirability (SI Appendix, Section 14).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation
    § Abstract

    Social approach behavior, assessed by interpersonal distance, provides a basis for social interactions and initiation of interpersonal relationship.

    “Social approach behavior, which can be assessed by (close) interpersonal distance (19), provides a basis for social interactions and initiation of interpersonal relationship (20).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [19] Perry A, Levy-Gigi E, Richter-Levin G, Shamay-Tsoory SG. Interpersonal distance and social anxiety in autistic spectrum disorders: A behavioral and ERP study. Soc Neurosci. 2015;10:354–365. doi: 10.1080/17470919.2015.1010740. [DOI] [PubMed] [Google Scholar]

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    Premisecitation
    § Abstract

    Social cognition is context-dependent and influenced by internal thoughts and processing context.

    “social cognition is context-dependent and influenced by internal thoughts and processing context (15).”
    Quote in the paperSubstantial claim0 of 1 sources checked
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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Abstract

    Placebo effects are shaped by the desire for personal well-being and expectations of efficacy of inert treatment.

    “Placebo effect refers to health benefits induced by the use of inert treatment and is shaped by the desire for personal well-being and expectations of efficacy of inert (but believed active) treatment (1, 2).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § Abstract

    Social dysfunctions negatively impact personal health and well-being, and are recognized as integral to various physical and mental conditions and difficult to treat.

    “Social dysfunctions negatively impact personal health and well-being, and are recognized as integral to various physical and mental conditions (10) and difficult to treat (11).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation
    § Abstract

    Trust signals prosocial approach to others and is an important determinant to establish and maintain interpersonal relationships.

    “Trust signals prosocial approach to others (16) and is an important determinant to establish and maintain interpersonal relationships (17).”
    Quote in the paperSubstantial claim0 of 2 sources checked
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    Premisecitation
    § Abstract

    Keeping too far away from others signals low social motivation and keeping close to others, especially strangers, may induce personal distress or social anxiety.

    “In real-life situations, keeping too far away from others signals low social motivation (26) and keeping close to others, especially strangers, may induce personal distress or social anxiety (26, 27).”
    Quote in the paperSubstantial claim0 of 2 sources checked
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    Premisecitation
    § Abstract

    The expectation of beneficial effects of treatment and receiving the inert treatment are necessary to induce placebo effects.

    “The expectation of beneficial effects of treatment and receiving the inert (believed as active) treatment are necessary to induce placebo effects (12).”
    Quote in the paperSubstantial claim0 of 1 sources checked
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    Premisecitation
    § Abstract

    Abnormal perception or regulation of interpersonal distance has been linked with social dysfunction.

    “Abnormal perception or regulation of interpersonal distance has been linked with social dysfunction (28).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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  • Classified as probably not a substantial claim.

    Premisecitation
    § Abstract

    Oxytocin is emerging as a pharmacological target for social dysfunction in clinical trials.

    “oxytocin is emerging as a pharmacological target for social dysfunction in clinical trials (29, 30).”
    Quote in the paperSubstantial claim0 of 2 sources checked
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    Study design and conductcitation
    § Results

    A sample size of 61 participants was needed to detect a moderate correlation between SPE on trust and on interpersonal distance with α = 0.05 and 90% power.

    “To detect a moderate correlation (r = 0.4; ref. 37) between SPE on trust and on interpersonal distance with α = 0.05 and 90% power, a sample size of 61 participants was needed (G*Power 3.1; ref .38).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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    Premisecitation
    § Discussion

    The placebo effects on pain analgesia and negative affect reduction have been well-documented.

    “The placebo effects on pain analgesia and negative affect reduction have been well-documented (3, 4)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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    Premisecitation
    § Results

    Interpersonal distance is crucially influenced by one's relationship with others.

    “Interpersonal distance is crucially influenced by one’s relationship with others (41, 42).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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      Not checked in the free run.

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

    Premisecitation
    § Discussion

    Trust in others and close social distance signal approach to social interactions and provide opportunities to establish close relationships.

    “Trust in others and close social distance signal approach to social interactions and provide opportunities to establish close relationships (13).”
    Quote in the paperSubstantial claim0 of 1 sources checked
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      Not checked in the free run.

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

    Premisecitation
    § Results

    Eye contact signals social motivation and plays an important role in real-life social interaction.

    “eye contact signals social motivation and has been shown to play an important role in real-life social interaction; ref. 40”
    Quote in the paperSubstantial claim0 of 1 sources checked
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      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation
    § Results

    Social trust provides a basis of close interpersonal distance.

    “As social trust provides a basis of close interpersonal distance (36)”
    Quote in the paperSubstantial claim0 of 1 sources checked
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      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Discussion

    Placebo treatment may impact well-being in different domains (physical, emotional, and social) and different dimensions of each domain.

    “These findings together indicate that placebo treatment may impact well-being in different domains (physical, emotional, and social) and different dimensions of each domain (e.g., placebo analgesia in multiple pain conditions or placebo effect on different social behaviors).”
    Quote in the paperSubstantial claim

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

    Premisecitation
    § Abstract

    Trust in others has been proven to be a key predictor of subjective well-being and the quality of interpersonal relationships.

    “Trust in others has been proven to be a key predictor of subjective well-being and the quality of interpersonal relationships (18).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] DeNeve KM, Cooper H. The happy personality: A meta-analysis of 137 personality traits and subjective well-being. Psychol Bull. 1998;124:197–229. doi: 10.1037/0033-2909.124.2.197. [DOI] [PubMed] [Google Scholar]

      Not checked in the free run.

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

    Premisecitation
    § Discussion

    Placebo treatment reduces pain and negative emotion through a top-down modulation, with high-level expectation driving downstream changes in sensory feelings and affective physiology.

    “It has been recognized that placebo treatment reduces pain and negative emotion through a top-down modulation, with “high-level” expectation driving the downstream changes in one’s own sensory feelings and affective physiology (2, 46, 47).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [2] Wager TD, Atlas LY. The neuroscience of placebo effects: Connecting context, learning and health. Nat Rev Neurosci. 2015;16:403–418. doi: 10.1038/nrn3976. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [46] Wager TD, et al. Placebo-induced changes in FMRI in the anticipation and experience of pain. Science. 2004;303:1162–1167. doi: 10.1126/science.1093065. [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [47] Geuter S, Koban L, Wager TD. The cognitive neuroscience of placebo effects: Concepts, predictions, and physiology. Annu Rev Neurosci. 2017;40:167–188. doi: 10.1146/annurev-neuro-072116-031132. [DOI] [PubMed] [Google Scholar]

      Not checked in the free run.

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

    Premisecitation
    § Discussion

    The opioid system was involved in placebo effect on analgesia and social behavior.

    “and that the opioid system was involved in placebo effect on analgesia (48, 49) and social behavior (51).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [48] Zubieta JK, et al. Placebo effects mediated by endogenous opioid activity on mu-opioid receptors. J Neurosci. 2005;25:7754–7762. doi: 10.1523/JNEUROSCI.0439-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [49] Wager TD, Scott DJ, Zubieta J-K. Placebo effects on human mu-opioid activity during pain. Proc Natl Acad Sci USA. 2007;104:11056–11061. doi: 10.1073/pnas.0702413104. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [51] Panksepp J, Herman BH, Vilberg T, Bishop P, DeEskinazi FG. Endogenous opioids and social behavior. Neurosci Biobehav Rev. 1980;4:473–487. doi: 10.1016/0149-7634(80)90036-6. [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

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

    Premisecitation
    § Discussion

    The placebo effect on analgesia is linked to the opioid system, which plays an important role in modulating pain.

    “The placebo effect on analgesia was linked to the opioid system, which plays an important role in modulating pain (48, 49).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [48] Zubieta JK, et al. Placebo effects mediated by endogenous opioid activity on mu-opioid receptors. J Neurosci. 2005;25:7754–7762. doi: 10.1523/JNEUROSCI.0439-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [49] Wager TD, Scott DJ, Zubieta J-K. Placebo effects on human mu-opioid activity during pain. Proc Natl Acad Sci USA. 2007;104:11056–11061. doi: 10.1073/pnas.0702413104. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given
    § Methods

    In all experiments, experimenters of the placebo manipulations were blind to experimental hypotheses.

    “In all experiments, experimenters of the placebo manipulations were blind to experimental hypotheses.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given
    § Methods

    The experimental procedures of all experiments met the standards set by the Declaration of Helsinki and were approved by a local research ethics committee at the State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University.

    “The experimental procedures of all experiments met the standards set by the Declaration of Helsinki and were approved by a local research ethics committee at the State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given
    § Discussion

    SPE resembles the effects of active oxytocin on social behavior.

    “In addition, SPE resembles the effects of active oxytocin on social behavior.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning
    § Discussion

    Placebo treatment not only influences one's own feelings but also influences interactions with others; it not only attenuates negative affect but also facilitates positive aspect.

    “Thus, placebo treatment not only influences one’s own feelings but also influences interactions with others; it not only attenuates negative affect but also facilitates positive aspect.”
    Quote in the paperSubstantial claim

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

    Premisecitation
    § Discussion

    The dopaminergic system mediated expectation formation in placebo manipulation.

    “Previous studies have provided evidence that the dopaminergic system mediated expectation formation in placebo manipulation (50)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50] Scott DJ, et al. Individual differences in reward responding explain placebo-induced expectations and effects. Neuron. 2007;55:325–336. doi: 10.1016/j.neuron.2007.06.028. [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

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

    Study design and conductnone given
    § Methods

    All participants provided written informed consent after the experimental procedures were fully explained and were informed of their right to withdraw at any time.

    “All participants provided written informed content after the experimental procedures were fully explained and were informed of their right to withdraw at any time.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given
    § Methods

    We matched females' attractiveness across sessions as it may influence interpersonal distance.

    “We matched females’ attractiveness across sessions as it may influence interpersonal distance (SI Appendix, Section 19).”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning
    § Methods

    The material control condition was set up to avoid potential influence of exposure to the same materials twice.

    “To avoid potential influence of exposure to the same materials twice, we also set up a material control condition whereby participants were exposed to control materials without receiving nasal spray.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given
    § Methods

    In Exp. 3, the experimenter who conducted the stop-distance task was blind to experimental conditions and the hypothesis.

    “The experimenter who conducted the stop-distance task was blind to experimental conditions and the hypothesis.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data
    § Methods

    In Exp. 1-3, session order was counterbalanced across participants.

    “In Exp. 1–3, participants were invited to the spray+ and control manipulation sessions ≥7 d apart (Exp. 1, mean ± SD = 7.30 ± 0.65 d; Exp. 2, 7.63 ± 1.07 d; Exp. 3, 7.33 ± 0.61 d; session order counterbalanced across participants).”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given
    § Methods

    All data and materials have been made publicly available via the Open Science Framework.

    “All data and materials have been made publicly available via the Open Science Framework and can be accessed at https://osf.io/nvsfr/.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given
    § Methods

    In Exp. 4, we employed a standard double-blind, PL-controlled procedure for active oxytocin/PL administration.

    “In Exp. 4, we employed a standard double-blind, PL-controlled procedure for active oxytocin/PL administration.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given
    § Methods

    Placebo manipulation and experimental tasks were conducted separately by different experimenters or in different settings.

    “Moreover, placebo manipulation and experimental tasks were conducted separately by different experimenters or in different settings.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Study design and conductnone given
    § Methods

    We employed two no-treatment control conditions: spray control and material control.

    “We employed two no-treatment control conditions (SI Appendix, Section 17).”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data
    § Methods

    In Exp. 4, treatment order was counterbalanced across subjects.

    “treatment order counterbalanced across subjects”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data
    § Methods

    Exp. 4 employed a randomized, within-subject, double-blind, placebo-controlled design.

    “Exp. 4 employed a randomized, within-subject, double-blind, placebo-controlled design”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given
    § Methods

    Each participant met different female experimenters in different sessions to avoid familiarity.

    “Each participant met different female experimenters in different sessions to avoid familiarity.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given
    § Methods

    All of the materials were based on real research without deception.

    “All of the materials were based on real research without deception.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given
    § Methods

    All pictures were adjusted in luminance and contrast.

    “All pictures were adjusted in luminance and contrast.”
    Quote in the paperNot a substantial claim
54 of 54

  • The paper relies on this without support.

    It remains unknown whether placebo treatment facilitates social well-being.

    “it remains unknown whether placebo treatment facilitates social well-being.”

  • The paper relies on this without support.

    Oxytocin was shown to increase trust and adaptation to trust betrayal.

    “Given that oxytocin was shown to increase trust and adaptation to trust betrayal, we included trust betrayal manipulation in Exp. 2 and Exp. 4”

  • The paper relies on this without support.

    Social trust and approach behavior are two fundamental aspects of social well-being.

    “Social trust and approach behavior are two fundamental aspects of social well-being.”

  • The paper relies on this without support.

    The amount the investor sent in the trust game indicates his trust for others.

    “The amount the investor sent indicated his trust for others.”
4 of 4

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?

  • Oxytocin has been implicated in many social behaviors, from promoting trust, generosity and cooperation to aggravating mistrust and aggressive behavior.

    “Oxytocin has been implicated in many social behaviors, from promoting trust, generosity and cooperation 21,22,46,47 to aggravating mistrust and aggressive behavior 48,49 .”

    From Oxytocin modulates social value representations in the amygdala (2019) · cites this paper as [47]

Statistics that don’t add up

Each reported p-value recomputed from its test statistic and degrees of freedom.

  • Inconsistent p-value: r(60) = −0.367, p = .004

    Minor

    The paper reports p = .004 here; recomputing from the test statistic and its degrees of freedom gives p = .003 (two-tailed). The check cannot tell whether the statistic or the p-value is the misprint.

    Reported p = .004 · recomputed p = .003

1 of 1

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.

  • Doesn’t add upr(60) = -0.367reported p = .004 · recomputed p = .003

    “r(60) = −0.367, p = .004”

  • ConsistentF(2, 56) = 5.155reported p = .009 · recomputed p = .009

    “F(2,56) = 5.155, p = .009”

  • ConsistentF(2, 52) = 4.963reported p = .011 · recomputed p = .011

    “F(2,52) = 4.963, p = .011”

  • ConsistentF(2, 56) = 3.238reported p = .047 · recomputed p = .047

    “F(2,56) = 3.238, p = .047”

  • Consistentt(28) = 2.443reported p = .021 · recomputed p = .021

    “t(28) = 2.443, p = .021”

  • Consistentt(28) = 2.415reported p = .023 · recomputed p = .023

    “t(28) = 2.415, p = .023”

  • Consistentt(31) = 3.54reported p = .001 · recomputed p = .001

    “t(31) = 3.540, p = .001”

  • ConsistentF(2, 56) = 13.097reported p < .001 · recomputed p < .001

    “F(2,56) = 13.097, p < .001”

  • Consistentt(28) = -4.241reported p < .001 · recomputed p < .001

    “t(28) = −4.241, p < .001”

  • Consistentt(28) = -4.172reported p < .001 · recomputed p < .001

    “t(28)=-4.172, p < .001”

  • Consistentt(30) = -2.067reported p = .047 · recomputed p = .047

    “t(30) = −2.067, p = .047”

  • Consistentz = -2.498reported p = .012 · recomputed p = .012

    “Z = −2.498, p = .012”

  • ConsistentF(1, 29) = 9.646reported p = .004 · recomputed p = .004

    “F(1,29) = 9.646, p = .004”

  • ConsistentF(1, 29) = 4.312reported p = .047 · recomputed p = .047

    “F(1,29) = 4.312, p = .047”

  • ConsistentF(1, 29) = 4.515reported p = .042 · recomputed p = .042

    “F(1,29) = 4.515, p = .042”

  • Consistentt(29) = -2.302reported p = .029 · recomputed p = .029

    “t(29) = −2.302, p = .029”

  • Consistentt(29) = -1.21reported p = .236 · recomputed p = .236

    “t(29) = −1.210, p = .236”

  • ConsistentF(1, 29) = 4.485reported p = .043 · recomputed p = .043

    “F(1,29) = 4.485, p = .043”

  • ConsistentF(1, 29) = 5.826reported p = .022 · recomputed p = .022

    “F(1,29) = 5.826, p = .022”

  • ConsistentF(1, 29) = 5.009reported p = .033 · recomputed p = .033

    “F(1,29) = 5.009, p = .033”

  • Consistentt(29) = -2.648reported p = .013 · recomputed p = .013

    “t(29) = −2.648, p = .013”

  • ConsistentF(1, 28) = 13.933reported p < .001 · recomputed p < .001

    “F(1,28) = 13.933, p < .001”

  • Consistentt(12) = -3.739reported p = .003 · recomputed p = .003

    “t(12) = −3.739, p = .003”

  • Consistentt(16) = 0.697reported p = .496 · recomputed p = .496

    “t(16) = 0.697, p = .496”

  • ConsistentF(1, 59) = 10.944reported p = .002 · recomputed p = .002

    “F(1,59) = 10.944, p = .002”

  • ConsistentF(1, 59) = 5.242reported p = .026 · recomputed p = .026

    “F(1, 59) = 5.242, p = .026”

  • ConsistentF(1, 31) = 10.055reported p = .003 · recomputed p = .003

    “F(1,31) = 10.055, p = .003”

  • ConsistentF(1, 28) = 0.079reported p = .781 · recomputed p = .781

    “F(1,28) = 0.079, p = .781”

  • ConsistentF(1, 58) = 5.245reported p = .026 · recomputed p = .026

    “F(1,58) = 5.245, p = .026”

  • ConsistentF(1, 58) = 0.641reported p = .426 · recomputed p = .427

    “F(1,58) = 0.641, p = .426”

  • ConsistentF(1, 57) = 6.8reported p = .012 · recomputed p = .012

    “F(1,57) = 6.800, p = .012”

  • ConsistentF(1, 57) = 4.937reported p = .03 · recomputed p = .030

    “F(1,57) = 4.937, p = .030”

32 of 32

Self-check

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

Self-check results appear here once an independent check has confirmed them.

Cites

Flagged first, then by citations

1 of the 61 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Yan, X., Yong, X., Huang, W., & Ma, Y.
Affiliations
Beijing Normal University (CN)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2018-05-14
Volume
115
Issue
22
Pages
5732-5737
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1800779115
PMC
PMC5984523
OpenAlex
W2804884179
Semantic Scholar
052314896b76450725150f7634aec8ff9b716a49
Cited by
39
References
61
Citations by year
2026: 2 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 10 · 2020: 7 · 2019: 6 · 2018: 3
FWCI
3.84
Type
journal article
Language
en
Open access
Licence
www.pnas.org/site/aboutpnas/licenses.xhtml (vor, 184 d)
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (31722026, 31771204, 91632118, 31661143039)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
placebo effect, social trust, approach behavior, interpersonal distance, social anxiety, oxytocin, pair bonding, social interaction, social well-being, social dysfunction
MeSH terms
Adult, Choice Behavior, Female, Humans, Interpersonal Relations, Male, Oxytocin, Placebos, Social Behavior, Placebo Effect, Trust, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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