Circulating Oxytocin Changes in Response to MDMA vs. Placebo in Adult Patients With Autism Spectrum Disorder and Matched Healthy Controls

Oxytocin is a hypothalamic neuropeptide released both peripherally and centrally that modulates social behavior, emotional processing, and cognition through receptors in regions such as the amygdala, nucleus accumbens, and prefrontal cortex. Clinical, neurobiological, and genetic studies indicate altered oxytocin signaling in autism spectrum disorder (ASD): meta-analyses show lower peripheral oxytocin levels, reduced receptor binding in some brain areas (especially in females), and correlations between higher peripheral oxytocin receptor expression and better social functioning. Over the past two decades, oxytocin has been evaluated as a therapy for ASD, mainly to target social deficits. While exogenous oxytocin can transiently enhance social cognition and connectivity, long-term trials remain inconclusive. As with other hormone deficiencies, single basal oxytocin measurements are unreliable. An emerging alternative is the use of MDMA, which robustly increases circulating oxytocin concentrations in healthy individuals. Measuring oxytocin release after a standardized MDMA challenge could clarify whether ASD patients retain a functional oxytocinergic response, with a blunted release indicating pathway dysfunction.

The OxySPECTRUM study will address this by administering a single dose of MDMA to high- functioning ASD patients and matched neurotypical controls, comparing plasma neurophysin I (equimolar oxytocin surrogate marker) area under curve (AUC) responses.

• Peak change in plasma oxytocin/neurophysin-I level [Time frame: From baseline (before intake) to 5 hours after a single dose administration of MDMA or placebo]
• Time course of plasma oxytocin/neurophysin-I levels [Time frame: From baseline (before intake) to 5 hours after a single dose administration of MDMA or placebo]
• Time course of plasma MDMA concentration [Time frame: From baseline (before intake) to 5 hours after a single dose administration of MDMA or placebo]
• Time course of pituitary hormone [Time frame: From baseline (before intake) to 5 hours after a single dose administration of MDMA or placebo]
• Change in subjective emotional effects assessed on Subjective effects questionnaire Numeric Analog Scales (NAS) [Time frame: Throughout the treatment visit (timepoint 0, 30, 60, 90, 120, 150, 180, 240, and 300 minutes)]
• EmBody/EmFace Task [Time frame: The test is performed once during each treatment visit and 2-2.5 hours after MDMA administration.]
• Facial emotion recognition task (FERT) [Time frame: The test is performed once during each treatment visit and 2-2.5 hours after MDMA administration.]
• Reading the Mind in the Eyes Test (RMET) [Time frame: The test is administered once during each treatment visit and 2-2.5 hours after MDMA administration.]
• Anxiety level with the State-Trait Anxiety Inventory (STAI) [Time frame: The test requires about 5 minutes.]
• Alexithymia level using the Toronto-Alexithymia-Scale 20 (TAS-20) [Time frame: At the screening visit (about 2 minutes)]
• Depression level using the Beck Depression Inventory II (BDI-II) [Time frame: At the screening visit (about 5 minutes)]
• General physical & mental health using the Patient-Reported Outcomes Measurement Information System (PROMIS) [Time frame: At the screening visit (about 5 minutes)]