Antidepressant Response of DMT Masked With Propofol

Changes in depressive symptoms will be assessed using Montgomery-Asberg-Depression Rating Scale (MADRS). The MADRS is a ten-item questionnaire widely used to measure severity of depressive symptoms during the last week. Total score (range 0-60); higher scores indicate greater depression severity.

Changes in depressive symptoms will be assessed using Beck Depression Inventory (BDI) questionnaire. Total score (range 0-63); higher scores indicate more severe depressive symptoms.

Changes in anxiety will be assessed using the self-reported State-Trait Anxiety Inventory (STAI) questionnaire. Separate total scores for State Anxiety (S-Anxiety) and Trait Anxiety (T-Anxiety) (each range 20-80); higher scores indicate greater anxiety.

The clinical global impression (CGI) is an instrument for the assessment of the patient's overall functioning both before and after starting the treatment.

Severity of Illness (CGI-S): Rated on a 7-point scale (1 = normal, 7 = among the most extremely ill).

The clinical global impression (CGI) is an instrument for the assessment of the patient's overall functioning both before and after starting the treatment.

Improvement (CGI-I): Rated on a 7-point scale (1 = very much improved, 7 = very much worse).

Changes in quality of life will be assessed by World Health Organization Quality of life scale (WHOQOL-bref). The WHOQOL-bref is one of the most commonly used self-rating instruments for the assessment of the quality of life and covers different domains of quality of life (physical, psychological, level of independence, social relationships, and environment, and spirituality). Domain scores (Physical, Psychological, Social, Environmental), scaled from 0 to 100; higher scores indicate better quality of life.

Psychedelics have been shown to produce persisting effects on well-being and appreciation of social relationships on the PEQ.This questionnaire will be used at the EOS visit to assess similar persisting effects of the DMT experience in addition to any effects on depressive symptomatology. Subscale scores (e.g., positive attitudes, mood changes, spirituality), typically rated 0-5 or 0-6; higher scores indicate stronger persisting effects.

The 5 Dimensions of Altered States of Consciousness (5D-ASC) Scale is a questionnaire containing visual analog scales for 94 items. The instrument contains five scales assessing mood, anxiety, derealization, depersonalization, changes in perception, auditory alterations, and reduced vigilance. Each item of the scale is scored on a 0-100 mm VAS. Scores for 5 dimensions (e.g., Oceanic Boundlessness, Anxious Ego Dissolution), range typically 0-100%; higher scores indicate more intense altered states.

Participants will be asked by the investigator to repeatedly rate their subjective effects verbally on a Likert scale from 0 to 10 for: "any drug effect", "good drug effect", "bad drug effect", and "fear". Ratings will be performed before and repeatedly after substance administration and will take approximately 30 sec to complete. The time course and maximal ratings (Emax, 0-10) are defined for each rating and Emax values compared between treatments using analysis of variance (ANOVAs). Total and subscale scores (range and subscales vary by implementation); higher scores indicate more intense subjective effects.

In the PES, 100-items are rated on a six-point scale. The PES represents a revalidation of the original 100-item States of Consciousness Questionnaire (SOCQ)

The Emotional breakthrough inventory (EBI) is a validated instrument with 6 items to assess the degree of emotional breakthrough as a distinct component of the acute psychedelic experience. Total score (range varies); higher scores indicate stronger emotional breakthrough experiences.

Acute adverse effects wil be assessed by the List of complaints (LC). LC is a self-reporting tool to assess physical and general discomfort. A revised version is used which consists of a 40-item list covering a wide variety of symptoms and complaints that are answered with a four-point intensity-scoring ranging from "not at all" to "strong". Total number or severity of reported somatic and psychological complaints will be evaluated.

Adverse events will be assessed over the whole study period.

brain-derived neurotrophic factor (BDNF), a biomarker for neurogenesis will be quantified in blood samples collected before and 14 days after intervention

Interleukin-1 beta (IL-1β) an immunological factor linked to depression will be quantified in blood samples collected before and 14 days after intervention

Plasma levels of DMT will be measured once shortly before the end of the perfusion

Expectancy will be assessed before the first drug administration. Thus, patients will know at this timepoint whether they get the treatment with or without propofol. To measure expectancy, a modified 2-item version of the Credibility / Expectancy Questionnaire (CEQ) is used. Credibility score (range 3-27).

The Stanford Expectations of Treatment Scale (SETS) will evaluate positive and negative expectancies. Expectancy score (range 3-27 or expressed as a probability %).

The Adjective Mood Rating Scale (AMRS) is a self-rating scale assessing current mood states. The AMRS will be used to assess mood before the DMT experience. Positive mood and greater acute well-being is expected to positively enhance the acute DMT effects as similarly shown for other psychedelics. Scores for multiple mood dimensions (e.g., energy, mood, agitation); higher scores reflect greater expression of that dimension.

Personality traits are known to affect subjective responses to psychoactive substances. The NEO Five Factor Inventory (NEO-FFI) will be used during screening to self-assess personality traits. Scores for five domains (Neuroticism, Extraversion, Openness, Agreeableness, Conscientiousness); raw or standardized T-scores.

Personality traits are known to affect subjective responses to psychoactive substances. The Tellegen Absorption Scale (TAS) will be used during screening to self-assess personality traits. Total score (range 0-34 or 0-136, depending on version); higher scores indicate greater trait absorption.

Level of sedation will be assessed during propofol session after each administration using the validated Richmond Agitation-Sedation Scale (RASS). The RASS is an observer-rated clinical scale used to assess level of agitation and sedation in the intensive care unit. The scale ranges from "+4" (combative) through "0" (alert and calm) to "-5" (unarousable). Intermediate scores include "+3" (very agitation), "+2" (agitated), "+1" (restless), "-1" (drowsy), "-2" (light sedation), "-3" (moderate sedation), and "-4" (deep sedation).