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

Subjective emotional effects will be assessed repeatedly using the subjective/emotional effects questionnaire assessed with NAS. NAS will be presented as a range from 0 to 10 marked with "not at all" on the left and "extremely" on the right.

During the expected peak concentration of MDMA, participants will perform the EmBody/EmFace Task. Each of 42 stimuli showing body or facial expressions of angry, happy, or neutral affect (14 clips per emotion, half in front view and half in half-profile side view from the left). Stimuli last 1.5 seconds at 24 frames per second and are geometrically and optically standardized. Item order is pseudorandom to prevent sequence effects and was determined using the following constraints: the same emotion is shown no more than twice in a row; the same view per emotion is not shown consecutively (i.e., no angry-front, angry-front).

The FERT is used to assess recognition of basic emotions. The task includes 10 neutral faces and 160 faces that express one of four basic emotions (i.e., happiness, sadness, anger, and fear), with pictures morphed between 0% (neutral) and 100% in 10% steps. Two female and two male pictures are used for each of the four emotions. The outcome measure is accuracy (proportion correct).

The RMET is used to assess theory of mind and emotion recognition from subtle facial cues. The task consists of 36 photographs showing only the eye region of male and female faces. For each photograph, four mental state descriptors (e.g., "anxious," "thoughtful," "playful," "serious") are presented, and participants are asked to choose the word that best matches what the person is feeling or thinking. Stimuli are displayed in random order without time restriction. The primary outcome measure is accuracy (proportion correct), with higher scores reflecting better social-cognitive performance.

Based on responses to 20 items, with scores ranging from 1 ("almost never") to 4 ("almost always"), a total score is calculated. The total trait score (STAI-T) ranges from 20 to 80, with higher scores indicating more pronounced anxiety and scores.

The TAS 20 has a three-factor structure: difficulty identifying feelings, difficulty describing feelings and externally oriented thinking. It includes 20 questions with scores ranging from 1 (strongly disagree) to 5 (strongly agree).

The BDI II uses 21 items ranked from 0 (symptom absent) to 3 (severe symptoms) to measure the severity of depression. The minimum score is 0 and maximum score is 63. In non-clinical populations, scores above 20 indicate depression. In those diagnosed with depression, scores of 0-13 indicate minimal depression, 14-19 (mild depression), 20-28 (moderate depression) and 29-63 (severe depression).

The PROMIS is a set of person-centred measures that evaluate and monitor physical, mental, and social health. This questionnaire will consist of 29 items. In addition, cognitive functions consisting of 4 items and sociodemographic core data will be asked.

This questionnaire is a diagnostic test designed to measure the expression of ASD traits in an individual by his or her subjective self-assessment. The AQ consists of 50 items, with four choices for each item from "definitely agree" to "definitely disagree" and a total score from 0 to 50. A score above the proposed cut-off of 29 highlights significant traits of autism.

The CATI is a validated 42-item self-report questionnaire measuring autistic traits across six domains: Social Interactions, Communication, Social Camouflage, Repetitive Behaviours, Cognitive Rigidity, and Sensory Sensitivity.