Intranasal Oxytocin Administration Research Articles

Men's sexual response to female partner's intranasal oxytocin administration for hypoactive sexual desire disorder: an open prospective cohort study

To study sexual function, quality of life, and depression in men, whose female partners are undergoing double-blind placebo-controlled randomized treatment for hypoactive sexual desire disorder (HSDD). Open prospective cohort study of 22weeks. Academic medical center. Male partners of 30 premenopausal and postmenopausal women with HSDD. Baseline, 3-month, and 5-month assessment (for 8weeks each) of male response to female partner's use of oxytocin nasal spray (32 IE) and placebo within 50minutes before sexual intercourse. Primary outcome parameters were Sexual Life Quality Questionnaire-Male, Sexual Activity Record, Partner Performance Questionnaire, and Hamilton Depression Scale. Male Sexual Life Quality questionnaire improved significantly from -7.4 ± 9.9 at baseline to 8.2 ± 12 with female partners' treatment with oxytocin nasal spray and to 10.8 ± 13.8 with placebo. Frequency of intercourse improved slightly but not significantly from 6.3 ± 3.9 at baseline to 7.3 ± 4 with female oxytocin therapy, but not with placebo. Male desire and arousal remained stable throughout the study period. Evaluation of female partners' performance by men improved significantly from 8.9 ± 2.8 at baseline to 10.6 ± 2.2 with oxytocin and to 11.2 ± 2.6 with placebo. Female treatment with either oxytocin or placebo for HSDD significantly improves male sexual quality of life and evaluation of female partner's sexual performance with no difference between oxytocin and placebo on any outcome parameters. A nonsignificant improvement was seen in the frequency of intercourse, male arousal, desire, satisfaction, and Hamilton depression scale. NCT02229721.

Bonding With β-Cells-A Role for Oxytocin in Glucose Handling.

The neuropeptide oxytocin is probably best known for its role in social behavior including maternal bonding. It is produced by hypothalamic neurons and plays numerous roles in the central nervous system (CNS) ranging from the establishment of the complex social behaviors over the modulation of neuroendocrine reflexes to the regulation of learning and memory. Over the past decade, oxytocin has also been shown to affect metabolic processes such as food intake and energy homeostasis in animal models (1). More recently, the metabolic effects of oxytocin have been studied in human subjects. Intranasal administration of oxytocin reduces food intake, an effect that seems more pronounced in obese than normal-weight individuals (2,3). Treatment with oxytocin can lead to weight loss and the reversal of weight-related symptoms in obese patients (4). In this issue of Diabetes , Klement et al. (5) present evidence that intranasal oxytocin administration modulates insulin/C-peptide secretion and glucose …

Oxytocin and Aggression.

The neuropeptide oxytocin (OT) has a solid reputation as a facilitator of social interactions such as parental and pair bonding, trust, and empathy. The many results supporting a pro-social role of OT have generated the hypothesis that impairments in the endogenous OT system may lead to antisocial behavior, most notably social withdrawal or pathological aggression. If this is indeed the case, administration of exogenous OT could be the "serenic" treatment that psychiatrists have for decades been searching for.In the present review, we list and discuss the evidence for an endogenous "hypo-oxytocinergic state" underlying aggressive and antisocial behavior, derived from both animal and human studies. We furthermore examine the reported effects of synthetic OT administration on aggression in rodents and humans.Although the scientific findings listed in this review support, in broad lines, the link between a down-regulated or impaired OT system activity and increased aggression, the anti-aggressive effects of synthetic OT are less straightforward and require further research. The rather complex picture that emerges adds to the ongoing debate questioning the unidirectional pro-social role of OT, as well as the strength of the effects of intranasal OT administration in humans.

Overview of Human Oxytocin Research.

Social dysfunction is a core symptom of many psychiatric disorders and current medications have little or no remedial effects on this. Following on from extensive studies on animal models demonstrating that the neuropeptide oxytocin plays an important role in social recognition and bonding, human-based research has explored its therapeutic potential for social dysfunction in psychiatric disorders. Here we outline the historical background of this human-based research and some of the current methodological challenges it is facing. To date, research has primarily attempted to establish functional effects through measuring altered endogenous concentrations, observing effects of exogenous administration and by investigating the effects of polymorphisms and epigenetic modifications of the oxytocin receptor gene. We summarize some of the key findings on behavioral and neural effects that have been reported in healthy subjects in the context of social cognition which have provided encouragement that oxytocin could represent a promising therapeutic target. At the same time, we have identified a number of key areas where we urgently need further information about optimal dosing strategies and interactions with other peptide and transmitter systems. Finally, we have summarized current translational findings, particularly in the context of therapeutic outcomes of intranasal oxytocin administration in autism and schizophrenia. These clinical findings while somewhat varied in outcome do offer increasing cause for optimism that targeting the oxytocin system may provide a successful therapeutic approach for social dysfunction. However, future research needs to focus on the most effective treatment strategy and which types of individuals are likely to benefit most.

Intranasal Oxytocin and Vasopressin Modulate Divergent Brainwide Functional Substrates.

The neuropeptides oxytocin (OXT) and vasopressin (AVP) have been identified as modulators of emotional social behaviors and associated with neuropsychiatric disorders characterized by social dysfunction. Experimental and therapeutic use of OXT and AVP via the intranasal route is the subject of extensive clinical research. However, the large-scale functional substrates directly engaged by these peptides and their functional dynamics remain elusive. By using cerebral blood volume (CBV) weighted fMRI in the mouse, we show that intranasal administration of OXT rapidly elicits the transient activation of cortical regions and a sustained activation of hippocampal and forebrain areas characterized by high oxytocin receptor density. By contrast, intranasal administration of AVP produced a robust and sustained deactivation in cortico-parietal, thalamic and mesolimbic regions. Importantly, intravenous administration of OXT and AVP did not recapitulate the patterns of modulation produced by intranasal dosing, supporting a central origin of the observed functional changes. In keeping with this notion, hippocampal local field potential recordings revealed multi-band power increases upon intranasal OXT administration. We also show that the selective OXT-derivative TGOT reproduced the pattern of activation elicited by OXT and that the deletion of OXT receptors does not affect AVP-mediated deactivation. Collectively, our data document divergent modulation of brainwide neural systems by intranasal administration of OXT and AVP, an effect that involves key substrates of social and emotional behavior. The observed divergence calls for a deeper investigation of the systems-level mechanisms by which exogenous OXT and AVP modulate brain function and exert their putative therapeutic effects.

Intranasal Oxytocin to Prevent Posttraumatic Stress Disorder Symptoms: A Randomized Controlled Trial in Emergency Department Patients

BackgroundThere are currently few preventive interventions available for posttraumatic stress disorder (PTSD). Intranasal oxytocin administration early after trauma may prevent PTSD, because oxytocin administration was previously found to beneficially impact PTSD vulnerability factors, including neural fear responsiveness, peripheral stress reactivity, and socioemotional functioning. Therefore, we investigated the effects of intranasal oxytocin administration early after trauma on subsequent clinician-rated PTSD symptoms. We then assessed whether baseline characteristics moderated the intervention’s effects. MethodsWe performed a multicenter, randomized, double-blind, placebo-controlled clinical trial. Adult emergency department patients with moderate to severe acute distress (n = 120; 85% accident victims) were randomized to intranasal oxytocin (8 days/40 IU twice daily) or placebo (8 days/10 puffs twice daily), initiated within 12 days posttrauma. The Clinician-Administered PTSD Scale (CAPS) was administered at baseline (within 10 days posttrauma) and at 1.5, 3, and 6 months posttrauma. The intention-to-treat sample included 107 participants (oxytocin: n = 53; placebo: n = 54). ResultsWe did not observe a significant group difference in CAPS total score at 1.5 months posttrauma (primary outcome) or across follow-up (secondary outcome). Secondary analyses showed that participants with high baseline CAPS scores receiving oxytocin had significantly lower CAPS scores across follow-up than participants with high baseline CAPS scores receiving placebo. ConclusionsOxytocin administration early after trauma did not attenuate clinician-rated PTSD symptoms in all trauma-exposed participants with acute distress. However, participants with high acute clinician-rated PTSD symptom severity did show beneficial effects of oxytocin. Although replication is warranted, these findings suggest that oxytocin administration is a promising preventive intervention for PTSD for individuals with high acute PTSD symptoms.

Intranasal oxytocin administration improves depression-like behaviors in adult rats that experienced neonatal maternal deprivation

Oxytocin (OT), a hypothalamic neuropeptide, has been implicated in the regulation of social behaviors in rodents and humans. This study assessed the effects of intranasal administration of OT on depressive-like behaviors and hippocampal neurogenesis in adult rats following neonatal maternal deprivation (NMD). Here, we show that NMD resulted in significant depression-like behaviors, as indicated by decreases in physical activity and emotional reactivity in a novel environment, in 2-month-old animals. Notably, the OT levels in the plasma, hypothalamus, and hippocampus were decreased in these animals. Intranasal administration of OT reduced the depressive-like behaviors in NMD rats and rescued hippocampal long-term plasticity impaired by NMD stress in rats by promoting hippocampal neurogenesis. These results indicate that OT alleviates the depressive-like behaviors in NMD adult rats, probably mediated by improving adult hippocampal neurogenesis.

Oxytocin is implicated in social memory deficits induced by early sensory deprivation in mice.

Early-life sensory input plays a crucial role in brain development. Although deprivation of orofacial sensory input at perinatal stages disrupts the establishment of the barrel cortex and relevant callosal connections, its long-term effect on adult behavior remains elusive. In this study, we investigated the behavioral phenotypes in adult mice with unilateral transection of the infraorbital nerve (ION) at postnatal day 3 (P3). Although ION-transected mice had normal locomotor activity, motor coordination, olfaction, anxiety-like behaviors, novel object memory, preference for social novelty and sociability, they presented deficits in social memory and spatial memory compared with control mice. In addition, the social memory deficit was associated with reduced oxytocin (OXT) levels in the hypothalamus and could be partially restored by intranasal administration of OXT. Thus, early sensory deprivation does result in behavioral alterations in mice, some of which may be associated with the disruption of oxytocin signaling.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-016-0278-3) contains supplementary material, which is available to authorized users.

The impact of oxytocin administration on brain activity: a systematic review and meta-analysis protocol.

BackgroundConverging evidence demonstrates the important role of the neuropeptide hormone oxytocin (OT) in human behaviour and cognition. Intranasal OT administration has been shown to improve several aspects of social communication, such as the theory of mind performance and gaze to the eye region, and reduce anxiety and related negative cognitive appraisals. While this early research has demonstrated the potential for intranasal OT to treat psychiatric illnesses characterized by social impairments, the neurobiological mechanisms are not well known. Researchers have used functional magnetic resonance imaging (fMRI) to examine the neural correlates of OT response; however, results have been variable and moderating factors are poorly understood. The aim of this meta-analysis is to synthesize data examining the impact of intranasal OT administration on neural activity.Methods/designStudies that report fMRI data after intranasal OT administration will be identified. PubMed, Embase, PsycINFO, and Google Scholar databases will be searched as well as the citation lists of retrieved articles. Eligible articles written in English from 2005 onwards will be included in the meta-analysis, and corresponding authors of these papers will be invited to contribute t-maps. Data will be collected from eligible studies for synthesis using Seed-based d Mapping (SDM) or Multi-Level Kernel Density Analysis (MKDA), depending on the number of usable t-maps received. Additionally, publication bias and risk of bias will be assessed.DiscussionThis systematic review and meta-analysis will be the first pre-registered synthesis of data to identify the neural correlates of OT nasal spray response. The identification of brain regions underlying OT’s observed effects will help guide future research and better identify treatment targets.Systematic review registrationPROSPERO CRD42016038781 Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-016-0386-2) contains supplementary material, which is available to authorized users.

Effects of Intranasal Oxytocin on Emotion Regulation in Insecure Adolescents: Study Protocol for a Double-Blind, Randomized Controlled Trial.

BackgroundEmotional dysregulation and impaired attachment are potential contributors to the development of psychopathology in adolescence. This raises the question of whether oxytocin (OT), the paradigmatic “attachment hormone,” may be beneficial in such contexts. Recent evidence suggests that intranasal administration of OT increases affiliative behavior, including trust and empathy. OT may also facilitate social reciprocity by attenuating the stress response to interpersonal conflict. To date, few studies have investigated the effects of intranasal oxytocin (IN-OT) on neurophysiological emotion regulation strategies in healthy adolescents, particularly during parent-adolescent interaction. To understand these mechanisms, our study will examine the effects of IN-OT on emotion regulation in adolescents during parent-adolescent stressful interactions, and on each adolescent’s visual and neurophysiological strategies when visualizing attachment-related pictures. We hypothesize that IN-OT will influence psychophysiological outcomes under conditions of stress. We predict that IN-OT will momentarily increase feelings of safety and attenuate stress and hostile behavior during conflict situations. OT may also enhance attachment security by increasing comfort and proximity-seeking, and reducing neurophysiological hyperactivation.ObjectiveThe objective of this study is to evaluate the effects of IN-OT on insecure adolescents by studying their behavior and discourse during a disagreement with one of their parents. Their neurophysiological responses to pictures eliciting attachment-related emotions and their visual exploration strategies will also be investigated.MethodsIn this randomized, double-blind, placebo-controlled parallel-group design, 60 healthy male adolescents classified as insecurely attached will receive 24 international units (IU) of IN-OT versus placebo (PB), 45 minutes before the experimental tasks. Each adolescent will then be invited to engage in an experimental conflict discussion with one of his parents. The conflict session will be videotaped and coded for verbal and non-verbal interaction behavior, using the Goal-Corrected Partnership in Adolescence Coding System (GPACS). Each adolescent will then be asked to visualize attachment-related pictures on a screen. Eye-tracking (ET) and neurophysiological responses, including electrodermal activity (EDA) and heart rate (HR), will be recorded simultaneously and continuously during attachment-related picture viewing (Besançon Affective Picture Set-Adolescents, BAPS-Ado).ResultsEnrollment for the study was completed in May 2016. Data analysis commenced in July 2016. Study results will be submitted for publication in the winter of 2017.ConclusionsOT is a complex molecule with many facets that are not yet fully understood. This experimental protocol will increase scientific and clinical knowledge of emotion regulation skills in insecure adolescents by assessing the impact of IN-OT on parent-adolescent interaction and on the visual processing of attachment-related emotions. Positive results could lead to therapeutic uses of IN-OT to treat emotion dysregulation in adolescence.

EFFECTS OF INTRANASAL OXYTOCIN ON PERCEPTIONS OF TRUSTWORTHINESS IN AGING

Perceptions of trustworthiness in others influence thought and behavior during social interactions. Growing evidence suggests that intranasal administration of the neuropeptide oxytocin increases p ...

Intranasal oxytocin increases neural responses to social reward in post-traumatic stress disorder.

Therapeutic alliance and perceived social support are important predictors of treatment response for post-traumatic stress disorder (PTSD). Intranasal oxytocin administration may enhance treatment response by increasing sensitivity for social reward and thereby therapeutic alliance and perceived social support. As a first step to investigate this therapeutical potential, we investigated whether intranasal oxytocin enhances neural sensitivity to social reward in PTSD patients. Male and female police officers with (n = 35) and without PTSD (n = 37) were included in a double-blind, randomized, placebo-controlled cross-over fMRI study. After intranasal oxytocin (40 IU) and placebo administration, a social incentive delay task was conducted to investigate neural responses during social reward and punishment anticipation and feedback. Under placebo, PTSD patients showed reduced left anterior insula (AI) responses to social rewards (i.e. happy faces) compared with controls. Oxytocin administration increased left AI responses during social reward in PTSD patients, such that PTSD patients no longer differed from controls under placebo. Furthermore, in PTSD patients, oxytocin increased responses to social reward in the right putamen. By normalizing abberant insula responses and increasing putamen responses to social reward, oxytocin administration may enhance sensitivity for social support and therapeutic alliance in PTSD patients. Future studies are needed to investigate clinical effects of oxytocin.

S.12.06 - Repeated intranasal oxytocin administration as early preventive intervention for PTSD: a randomized controlled trial

S.12.06 - Repeated intranasal oxytocin administration as early preventive intervention for PTSD: a randomized controlled trial

Notice of Retraction and Replacement: Hofmann et al. Effect of intranasal oxytocin administration on psychiatric symptoms: A meta-analysis of placebo-controlled studies. Psychiatry Research. 2015;228:708-714

Notice of Retraction and Replacement: Hofmann et al. Effect of intranasal oxytocin administration on psychiatric symptoms: A meta-analysis of placebo-controlled studies. Psychiatry Research. 2015;228:708-714

Variation in the Oxytocin Receptor Gene Is Associated with Face Recognition and its Neural Correlates.

The ability to recognize faces is crucial for daily social interactions. Recent studies suggest that intranasal oxytocin administration improves social recognition in humans. Oxytocin signaling in the amygdala plays an essential role for social recognition in mice, and oxytocin administration has been shown to influence amygdala activity in humans. It is therefore possible that the effects of oxytocin on human social recognition depend on mechanisms that take place in the amygdala—a central region for memory processing also in humans. Variation in the gene encoding the oxytocin receptor (OXTR) has been associated with several aspects of social behavior. The present study examined the potential associations between nine OXTR polymorphisms, distributed across the gene, and the ability to recognize faces, as well as face-elicited amygdala activity measured by functional magnetic resonance imaging (fMRI) during incidental encoding of faces. The OXTR 3′ polymorphism rs7632287, previously related to social bonding behavior and autism risk, was associated with participants’ ability to recognize faces. Carriers of the GA genotype, associated with enhanced memory, displayed higher amygdala activity during face encoding compared to carriers of the GG genotype. In line with work in rodents, these findings suggest that, in humans, naturally occurring endogenous modulation of OXTR function affects social recognition through an amygdala-dependent mechanism. These findings contribute to the understanding of how oxytocin regulates human social behaviors.

Differential effects of oxytocin on social sensitivity in two distinct breeds of dogs (Canis familiaris)

Dogs have been proven to show several human-analogue social behaviors, and recent research raises the possibility that the oxytocin system is related to these. However, despite dogs’ general tendency to excel in the domain of social cognition, there is increasing evidence that dogs’ ability to utilize human signals may vary with breed. Moreover, breeds may show differences not only in their ‘inborn’ communicative abilities, but also in their learning skills related to these. The aim of the present study was to explore breed differences and breed-specific effects of oxytocin administration on different aspects of social responsiveness. Dogs from two markedly different breeds, Border Collies (cooperative workers) and Siberian Huskies (independent workers) were tested. After having received intranasal administration of oxytocin or placebo, subjects participated in three behavioral tests measuring social responsiveness. Our results show that there are several behavioral differences between the two breeds and also that there are differential effects of the oxytocin treatment. Border Collies were in general more susceptible to the ‘social’ effects of oxytocin compared to Siberian Huskies: after oxytocin administration they (1) looked more at the experimenter in the ‘Unreachable food’ situation, (2) looked more at the owner and shifted their gaze more between the sound source and the owner in a potentially dangerous situation, and (3) looked longer at the experimenter’s eyes in the ‘Tolerance of prolonged eye contact’ test. These findings suggest that selection for enhanced cooperative abilities, possibly complemented by the effect of different social environments the two breeds experience, affects dogs’ performance in several behavioral tests and that the neurohormonal background differently modulates social behavior in different working breeds.

Oxytocin modulates hemodynamic responses to monetary incentives in humans.

Oxytocin is a neuropeptide widely recognized for its role in regulating social and reproductive behavior. Increasing evidence from animal models suggests that oxytocin also modulates reward circuitry in non-social contexts, but evidence in humans is lacking. We examined the effects of oxytocin administration on reward circuit function in 18 healthy men as they performed a monetary incentive task. The blood oxygenation level-dependent (BOLD) signal was measured using functional magnetic resonance imaging in the context of a randomized, double-blind, placebo-controlled, crossover trial of intranasal oxytocin. We found that oxytocin increases the BOLD signal in the midbrain (substantia nigra and ventral tegmental area) during the late phase of the hemodynamic response to incentive stimuli. Oxytocin's effects on midbrain responses correlated positively with its effects on positive emotional state. We did not detect an effect of oxytocin on responses in the nucleus accumbens. Whole-brain analyses revealed that oxytocin attenuated medial prefrontal cortical deactivation specifically during anticipation of loss. Our findings demonstrate that intranasal administration of oxytocin modulates human midbrain and medial prefrontal function during motivated behavior. These findings suggest that endogenous oxytocin is a neurochemical mediator of reward behaviors in humans-even in a non-social context-and that the oxytocinergic system is a potential target of pharmacotherapy for psychiatric disorders that involve dysfunction of reward circuitry.

Effects of chronic oxytocin on attention to dynamic facial expressions in infant macaques

Studies in a variety of species have reported enhanced prosocial effects after an acute administration of the neuromodulating hormone, oxytocin (OT). Although the exact mechanisms underlying these effects are not fully understood, there is broad interest in developing OT into a treatment for social deficits. Only a few studies, however, have examined the effects of OT if given repeatedly during early development, the period when early intervention is likely to have the greatest benefits for reversing the progression towards social impairment. Those studies, exclusively in rodents, report mixed results. Some have shown enhancement of prosocial behavior, including increased social exploration, but others have shown anti-social effects, including increased aggression. In the present study, infant rhesus macaques were treated with a high-frequency (3× per week) or low-frequency (1× per week) dose of intranasal oxytocin (IN-OT) or placebo (IN-saline) between two and six months of age, after which their reactions to dynamic facial expressions (neutral, lipsmacking and threats) were measured. Results showed that IN-OT, compared to placebo, increased the time monkeys spent viewing the expression videos, but selectively reduced attention to the eyes in neutral faces in a dose dependent manner. The mechanism for this non-prosocial effect may be that repeated IN-OT administration down-regulates the expression of OT receptors in brain regions important for regulating social attention. Consequently, our results raise questions about the efficacy of implementing chronic IN-OT as a pharmacotherapy for the treatment of social deficits, particularly if given early in development. More work is needed, not only to identify optimal treatment schedules, but also to understand how IN-OT exerts its influences on the brain and behavior.

Promising effects of oxytocin on social and food-related behaviour in young children with Prader-Willi syndrome: a randomized, double-blind, controlled crossover trial.

Prader-Willi syndrome (PWS) is known for hyperphagia with impaired satiety and a specific behavioural phenotype with stubbornness, temper tantrums, manipulative and controlling behaviour and obsessive-compulsive features. PWS is associated with hypothalamic and oxytocinergic dysfunction. In humans without PWS, intranasal oxytocin administration had positive effects on social and eating behaviour, and weight balance. To evaluate the effects of intranasal oxytocin compared to placebo administration on social behaviour and hyperphagia in children with PWS. Randomized, double-blind, placebo-controlled, crossover study in a PWS Reference Center in the Netherlands. Crossover intervention with twice daily intranasal oxytocin (dose range 24-48 IU/day) and placebo administration, both during 4 weeks, in 25 children with PWS (aged 6 to 14 years). In the total group, no significant effects of oxytocin on social behaviour or hyperphagia were found, but in the 17 children younger than 11 years, parents reported significantly less anger (P = 0·001), sadness (P = 0·005), conflicts (P = 0·010) and food-related behaviour (P = 0·011), and improvement of social behaviour (P = 0·018) during oxytocin treatment compared with placebo. In the eight children older than 11 years, the items happiness (P = 0·039), anger (P = 0·042) and sadness (P = 0·042) were negatively influenced by oxytocin treatment compared to placebo. There were no side effects or adverse events. This randomized, double-blind, placebo-controlled study suggests that intranasal oxytocin administration has beneficial effects on social behaviour and food-related behaviour in children with PWS younger than 11 years of age, but not in those older than 11 years of age.

Urinary and plasma oxytocin changes in response to MDMA or intranasal oxytocin administration

BackgroundThe neuropeptide oxytocin (OT) has received increased experimental attention for its putative role in both normal social functioning and several psychiatric disorders that are partially characterized by social dysfunction (e.g., autism spectrum disorders: ASD). Many human experimental studies measure circulating plasma levels of OT in order to examine the relationship between the hormone and behavior. Urinary OT (uOT) assays offer a simple, easy, and non-invasive method to measure peripheral hormone levels, but the correspondence between uOT and plasma OT (pOT) levels is unclear. Here, we conducted two within-subjects, double-blind studies exploring changes in uOT and pOT levels following administration of two drugs: MDMA, an oxytocin-releasing drug (Study 1), and intranasal oxytocin (INOT: Study 1 and 2). MethodsIn Study 1, 14 adult participants (2 females) were each administered either oral 1.5mg/kg MDMA or 40IU INOT across two different study sessions. In Study 2, 10 male participants (adolescents and young adults) diagnosed with ASD received either 40IU INOT or placebo across two different sessions. In both studies, blood and urine samples were collected before and after drug administration at each study session. For Study 1, 10 participants provided valid plasma and urine samples for the MDMA session, and 8 provided valid samples for the INOT session. For Study 2, all 10 participants provided valid samples for both INOT and placebo sessions. Pre- and post-administration levels of pOT and uOT were compared. Additionally, correlations between percent change from baseline uOT and pOT levels were examined. ResultsStudy 1: Plasma OT and uOT levels significantly increased after administration of MDMA and INOT. Furthermore, uOT levels were positively correlated with pOT levels following administration of MDMA (r=0.57, p=0.042) but not INOT (r=0.51, p=0.097). Study 2: There was a significant increase in uOT levels after administration of INOT, but not after administration of placebo. Under both conditions, INOT and placebo, significant increases in pOT levels were not observed. Additionally, change from baseline uOT and pOT levels were positively correlated (r=0.57, p=0.021). There was no significant correlation between uOT and pOT levels following placebo administration. ConclusionOur results show a measurable and significant increase in pOT and uOT levels after the administration of MDMA (Study 1) and INOT (Study 1 and Study 2). Additionally, a positive correlation between uOT and pOT levels was observed in both samples (healthy adults and ASD patients) in at least one condition. However, uOT and pOT levels were not correlated under all conditions, suggesting that uOT levels do not fully correspond to pOT levels in the time windows we measured. Future studies should further examine the relationship between levels of pOT and uOT in healthy and clinical populations on measures of social behavior because uOT may serve as an additional non-invasive method to measure peripheral OT changes.