Plasma Oxytocin Changes in Response to Low-dose MDMA vs. Placebo in Patients With Arginine Vasopressin Deficiency and Healthy Controls

Area under the concentration-time curve in plasma oxytocin level from baseline oxytocin measurement (before MDMA intake) to 5 hours after a single administration of 25 mg or 50 mg MDMA in patients with Arginine Vasopressin deficiency as compared to healthy controls.

Peak change in oxytocin plasma level assessed for MDMA and placebo between patients and healthy controls

The outcome will be descriptive. The p-value for the treatment effect will be adjusted for multiple testing using the Bonferroni-Holm procedure.

The time course of plasma and urine measures after intake of MDMA or placebo will be visualized by means of line plots and box-plots for patients and healthy controls.

The outcome will be descriptive. The p-value for the treatment effect will be adjusted for multiple testing using the Bonferroni-Holm procedure.

The time course of plasma and urine measures after intake of MDMA or placebo will be visualized by means of line plots and box-plots for patients and healthy controls.

NAS (e.g.,any drug effect, good drug effect, bad drug effect, trust, etc., 0-10) will be repeatedly used to assess subjective alterations in consciousness over time. NAS will be presented as a range from 0 to 10 marked with "not at all" on the left and "extremely" on the right. The following NAS will be used: "any effect", "good effect", "bad effect", "liking", "high", "happy", "fear", "stimulated", "feeling close to others", "concentration", "thinking", "open", "trust", "want to be with other people", "loss of sense of time", and "the boundaries between myself and my surroundings seemed to blur". Scales will be administered before and repeatedly after substance administration and will take 2 minutes to answer.

The EmBody and EmFace subtasks comprise each of 42 stimuli showing body or facial expressions of angry, happy, or neutral affect. Stimuli last 1.5 seconds at 24 frames per second and are geometrically and optically standardized to prevent biases induced by ethnic cues (e.g., hair or skin tone) or clothing. The test is performed once during each treatment visit and 2-2.5 h after MDMA administration.

At timepoint 150 min during the expected peak concentration of MDMA participants will perform FERT. 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.

Anxiety level assessed for MDMA and placebo between patients and healthy controls with STAI.

The state score (STAI-S) evaluates the current state of anxiety, asking how respondents feel "right now," using items that measure subjective feelings of apprehension, tension, nervousness, worry, and activation/arousal of the autonomic nervous system.

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 state score (STAI-S) evaluates the current state of anxiety, asking how respondents feel "right now," using items that measure subjective feelings of apprehension, tension, nervousness, worry, and activation/arousal of the autonomic nervous system.

Anxiety level assessed for MDMA and placebo between patients and healthy controls with STAI.

This is a questionnaire given to adults to determine the general anxiety levels. 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 STAI-T evaluates relatively stable aspects of "anxiety proneness," including general states of calmness, confidence, and security. A score above 45/80 indicating clinically significant anxiety symptoms.

Documenting list of complaints (LC)

Documenting all adverse effects

Samples will be taken for analysis and collected during the study days

Samples will be taken for analysis and collected during the study days

Samples will be taken for analysis and collected during the study days

Samples will be taken for analysis and collected during the study days

Samples will be taken for analysis and collected during the study days

Alexithymia is described as a trait to identify and describe emotions experienced by oneself or others. It is characterized by a marked difficulty in consciously experiencing, identifying, and describing emotions, as well as reduced introspection. 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 is one of the most used self-reported scales for measuring depression. It uses 21 items ranked from 0 (symptom absent) to 3 (severe symptoms) to measure the severity of depression.

The self-administered form takes about 5-10 minutes for the participant. 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).

PROMIS measures are relevant across all conditions to assess clinical symptoms, functioning, and quality of life. This questionnaire will consist of 29 items. In addition, cognitive functions consisting of 4 items and sociodemographic core data will be asked. PROMIS measures have been developed and validated with state-of-the-science methods to be psychometrically sound and to transform how life domains are measured. They have greater precision than most conventional measures. Greater precision (less error) enhances power in a less costly way than increasing sample size. PROMIS measures are relevant across all conditions to assess clinical symptoms, functioning, and quality of life.

The PROMIS is a set of person-centred measures that evaluates and monitors physical, mental, and social health in adults and children. PROMIS measures can be used with the general population and with individuals living with chronic conditions.PROMIS measures are relevant across all conditions to assess clinical symptoms, functioning, and quality of life. This questionnaire will consist of 29 items. In addition, cognitive functions consisting of 4 items and sociodemographic core data will be asked. PROMIS measures have been developed and validated with state-of-the-science methods to be psychometrically sound and to transform how life domains are measured. They have greater precision than most conventional measures. Greater precision (less error) enhances power in a less costly way than increasing sample size. PROMIS measures are relevant across all conditions to assess clinical symptoms, functioning, and quality of life.

This questionnaire is a diagnostic test designed to measure the expression of Autism Spectrum Disorder (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 TFEQ-R18 developed by Karlsson et al.118, assesses three dimensions of eating behavior: cognitive restraint, uncontrolled eating, and emotional eating. It consists of 18 items rated on a 4- point Likert scale and includes six items for cognitive restraint, nine for uncontrolled eating, and three for emotional eating. Higher scores in the respective scales are indicative of greater cognitive restraint, uncontrolled, or emotional eating. The reliability of each scale was computed using Cronbach's alphas. The overall reliability was acceptable (Cronbach's alpha = 0.82).

Indirect calorimetry for measurement of REE will be assessed after the expected plasma peak concentration of MDMA at 180min. Participant will be in an air-conditioned room with a room temperature between 22-24° C and wearing light clothing. To avoid activation of cold-induced thermogenesis and ensure a comfortably warm body surface temperature the patient will be covered by a blanket during the measurement of REE. Energy expenditure will then be measured with the ventilated hood technique using a Cosmed Quark Resting metabolic rate (RMR) for 30 minutes. Furthermore, participants will be asked to only perform a maximum of 30 minutes of medium exercise during the preceding 24 h.The unit of REE is kcal per 24 hours. It is assessed by volume of oxygen uptake (VO2) and expelled volume of carbon dioxide (VO2) in ml/min and calculated by the Weir Equation REE = [3.9 * (VO2) + 1.1 (VCO2)] * 1.44. The respiratory quotient (RQ) is calculated by dividing VCO2 by VO2.

Samples will be taken for analysis and collected during the study days

Samples will be taken for analysis and collected during the study days

Samples will be taken for analysis and collected during the study days

Assessed on a 10-point Numeric Analog Scale (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. The following NAS will be used: "any effect", "good effect", "bad effect", "liking", "high", "happy", "fear", "stimulated", "feeling close to others", "concentration", "thinking", "open", "trust", "want to be with other people", "loss of sense of time", and "the boundaries between myself and my surroundings seemed to blur".

Assessment of blood pressure

Assessment of heart rate

Assessment of body temperature

Assessment of plasma sodium

Assessment of potassium