Highlight
This double‑blind randomized trial in 80 heterosexual couples (N = 160) integrated repeated intranasal oxytocin, a brief structured partner interaction (Partner Appreciation Task, PAT), and ecological sampling of daily affectionate touch and sexual activity. Intimate physical contact was associated with lower daily cortisol and, when combined with oxytocin, with modestly faster blister wound healing. Effects were small and sensitivity analyses attenuated some findings — suggesting promising but preliminary translational implications.
Background
Close social relationships are robustly associated with better health and longevity in observational studies. Meta-analytic evidence links social integration and supportive relationships to reduced mortality risk, comparable in magnitude to well‑established risk factors such as smoking and alcohol (Holt‑Lunstad et al., 2010). Psychoneuroimmunology offers mechanistic hypotheses: affiliative interactions may buffer the hypothalamic–pituitary–adrenal (HPA) axis and sympathetic arousal, lowering circulating cortisol and systemic inflammation, and thereby improving immune-mediated processes such as wound repair.
Laboratory experiments have shown stress slows wound healing (Kiecolt‑Glaser et al., 1995), and intranasal oxytocin has been proposed as a neurohormonal mediator of social buffering; experimental oxytocin administration can attenuate cortisol responses to psychosocial stress and promote social cognition (Heinrichs et al., 2003). However, there has been limited randomized, controlled data combining neurohormonal modulation with ecologically valid, interpersonal behaviors to test downstream health outcomes such as wound healing in humans.
Study design
This was a double‑blind, randomized, placebo‑controlled trial (ClinicalTrials.gov: NCT01594775) conducted from November 2011 to July 2013 with final analyses in 2023–2025. The sample comprised 80 healthy, heterosexual couples (N = 160; mean age 27.6 ± 5.0 years). On the first laboratory visit, four small suction‑blister wounds were created on each participant’s forearms — a validated human model for studying dermal repair dynamics.
Randomization allocated participants to twice‑daily self‑administered intranasal oxytocin versus placebo for seven days. Separately, couples were randomized to perform a brief structured positive interaction (Partner Appreciation Task, PAT) up to three times during the week or not. Over the 7‑day home period, participants provided 6 daily ecological momentary assessment (EMA) reports (stress, partner interactions, affectionate touch, sexual activity) and collected saliva samples for cortisol across the week (totaling 5,760 EMA time points). Wound healing was assessed visually at 24 hours and again at day 7.
Key findings
Primary wound-healing outcomes
– In the group randomized to the PAT condition, participants who received intranasal oxytocin showed improved wound healing compared with placebo (model coefficient b = −0.125; t286 = −1.983; P = .048). This indicates a small but statistically significant treatment × behavioral interaction in the primary model.
– However, sensitivity analyses attenuated the effect (b = −0.090; t282 = −1.643; P = .10), rendering the primary interaction not robust across analytic choices.
Affectionate touch, sexual activity, and oxytocin
– Daily affectionate touch combined with oxytocin was associated with reduced wound severity (b = −0.038; t137 = −2.091; P = .04). This effect remained significant in sensitivity analyses (b = −0.037; t135 = −2.057; P = .04).
– Daily sexual activity paired with oxytocin was also associated with reduced wound severity (b = −0.145; t137 = −2.122; P = .04). Sensitivity testing showed attenuation to trend level for sexual activity (b = −0.131; t135 = −1.900; P = .06) but the affectionate touch finding was consistent.
Cortisol and stress outcomes
– Greater sexual activity over the week was significantly associated with lower daily cortisol concentrations (b = −373.084; t488 = −2.813; P = .005).
– The trial reports that intimate physical contact broadly attenuated neuroendocrine stress markers, consistent with mechanistic expectations, though detailed cortisol time‑series stratified by oxytocin vs placebo were not described in full in the summary.
Safety and tolerability
– The manuscript does not report major safety signals related to repeated intranasal oxytocin in this young, healthy outpatient sample. No serious adverse events were described in the provided abstract; the full paper should be consulted for comprehensive safety data and adverse event tables.
Effect sizes and clinical interpretation
– Observed effects were modest in magnitude, with small regression coefficients and some instability across sensitivity analyses. The most consistent signal was that daily affectionate touch alongside oxytocin administration related to better wound outcomes.
– These findings suggest biological plausibility and potential additive effects of behavioral and pharmacologic modulation of social neuroendocrine pathways, but do not yet establish clinical utility for oxytocin as an adjunctive treatment in wound care.
Expert commentary and mechanistic considerations
Biological plausibility
– Oxytocin modulates social behavior and has centrally mediated inhibitory effects on the HPA axis; prior experimental work demonstrates reductions in cortisol responses to psychosocial stress after intranasal oxytocin, especially in contexts of social support (Heinrichs et al., 2003). Lower cortisol and reduced sympathetic tone can favor wound repair through improved local immune responses, angiogenesis, and collagen deposition.
– Peripheral oxytocin receptors are present on some immune cells and vascular endothelium, raising the possibility of direct trophic or anti‑inflammatory effects on tissue repair; however, translational evidence in humans remains limited.
Strengths
– Rigorous double‑blind randomized design integrating pharmacologic manipulation with an ecologically valid behavioral microintervention and dense repeated physiological and EMA sampling.
– Use of an experimental human wound model allows mechanistic inference about healing dynamics.
Limitations
– Sample composition: young, healthy, heterosexual couples limit external validity to older adults, single individuals, same‑sex couples, clinically ill or immunocompromised populations, and patients with chronic wounds.
– Statistical robustness: several primary associations were borderline significant and attenuated in sensitivity analyses, raising concerns about false positives, multiple testing, and model dependence.
– Oxytocin administration: intranasal dosing regimens, central penetration, and pharmacokinetics remain areas of debate; peripheral vs central effects cannot be separated in this design.
– Behavioral measurement: affectionate touch and sexual activity were self‑reported via EMA, which may reduce recall bias but remains subject to social desirability and reporting variability.
Context with prior literature
– This trial builds on observational and experimental literature linking social support to improved health and the stress‑buffering role of oxytocin, and aligns with classic psychoneuroimmunology findings that stress slows wound healing (Kiecolt‑Glaser et al., 1995). It advances the field by testing combined behavioral and neurohormonal interventions in a randomized framework.
Clinical implications and future directions
Translational potential
– Findings are hypothesis‑generating rather than practice‑changing. They suggest that promoting positive, affectionate interactions and sexual health in partnered patients may have measurable physiological benefits, and that adjunctive neurohormonal modulation could amplify these effects.
Research priorities
– Replication in larger, more diverse samples and in clinical populations with impaired healing (e.g., diabetic foot ulcers, elderly) is essential before clinical adoption.
– Dose–response and pharmacokinetic studies of intranasal oxytocin, and exploration of timing relative to wound creation and to partner interactions, are needed.
– Mechanistic endpoints (local inflammatory markers, cytokine profiling, histologic assessments) could clarify whether benefits are mediated centrally via HPA modulation, by peripheral oxytocin receptor action, or by behaviorally mediated stress reduction.
– Ethical, social, and safety considerations around chronic oxytocin administration and the boundary between behavioral interventions and pharmacologic augmentation of social bonds warrant careful study.
Conclusion
This randomized trial provides intriguing evidence that intimate physical contact is associated with lower daily cortisol and, when combined with intranasal oxytocin, with modest improvements in experimental dermal wound healing. The strongest and most consistent signal was for affectionate touch together with oxytocin. Results are preliminary: effect sizes were small, some findings were sensitive to analytic choices, and generalizability is limited. Nonetheless, the study meaningfully integrates psychosocial behavior and neurohormonal modulation in a rigorous experimental paradigm and offers a foundation for targeted translational research on social interventions to improve recovery and resilience.
Funding and trial registration
Trial registration: ClinicalTrials.gov Identifier: NCT01594775. Funding and conflicts of interest are reported in the original manuscript (Schneider et al., JAMA Psychiatry, 2025); readers should consult the published paper for full disclosures.
Selected references
– Schneider E, Hernández C, Brock R, et al. Intranasal Oxytocin and Physical Intimacy for Dermatological Wound Healing and Neuroendocrine Stress: A Randomized Clinical Trial. JAMA Psychiatry. 2025 Nov 12:e253705. doi:10.1001/jamapsychiatry.2025.3705. PMID: 41222549; PMCID: PMC12613093.
– Holt‑Lunstad J, Smith TB, Layton JB. Social Relationships and Mortality Risk: A Meta‑analytic Review. PLoS Med. 2010;7(7):e1000316.
– Kiecolt‑Glaser JK, Marucha PT, Malarkey WB, et al. Slowing of wound healing by psychological stress. Lancet. 1995;346(8984):1194‑1196.
– Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U. Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry. 2003;54(12):1389‑1398.
