Role of the Serotonin 2A Receptor in Psilocybin-induced Altered States of Consciousness

VAS will be presented as 100 mm long horizontal lines marked with "not at all" on the left and "extremely" on the right. The following VAS items will be used: "any drug effect", "good drug effect", "bad drug effect", "drug high", "anxiety", "nausea", "feeling depressed", "alteration of vision", "alterations of hearing", "sounds seem to influence what I see", "alteration of sense of time", "the boundaries between myself and my surroundings seem to blur", "I gain insights into contexts that were previously were inscrutable to me", "talkative", "open", "trust" and "the context of my thought is personal/impersonal". Subjects will mark the scale with vertical lines.

The adjective mood rating scale (AMRS or EWL60S) is a 60-item Likert scale that allows repeated assessment of mood in 6 dimensions: activation, inactivation, well-being, anxiety/depressed mood, extroversion and introversion, and emotional excitability.The AMRS consists of subscales measuring "activation", "positive mood", "extroversion", "introversion", "inactivation", and "emotional excitability.

This 100-item questionnaire is rated on a six-point scale. Forty-three items embedded into this questionnaire comprise the Mystical Experience Questionnaire (MEQ). which is sensitive to the effects of psilocybin. The 43 items provide scale scores for each of seven domains of mystical experiences: internal unity (pure awareness, a merging with ultimate reality), external unity (unity of all things, all things are alive, all is one), sense of sacredness (reverence, sacred), noetic quality (encounter with ultimate reality, more real than everyday reality), transcendence of time and space, deeply felt positive mood (joy, peace, love), paradoxicality/ineffability (claim of difficulty in describing the experience in words). The investigators will also derived the four scale scores of the newly validated revised 30-item MEQ: mystical, positive mood, transcendence of time and space, and ineffability.

This questionnaire rates psychedelic experiences with a focus on phenomenological, autobiographical, and existential psychedelic experiences. The scale includes 12 main questions to be answered on a total of 78 sub-ordered visual rating scales (sub-ordered visual rating scales mostly only need to be answered when the answer to the main question is "yes"). The last major question with eight sub-ordered visual rating scales of the PAE-PS is on worldview/beliefs.

Blood pressure (systolic and diastolic) will be measured with an automatic oscillometric device.

Heart rate will be measured with an automatic oscillometric device.

Body temperature will be measured with an ear thermometer.

Personality traits are known to affect subjective responses to psychoactive substances and are assessed for explorative future analysis of pooled data. The NEO Five Factor Inventory (NEO-FFI) is a self-description questionnaire with 60 items for the measurement of the "big five": neuroticism, extraversion, openness, agreeableness, and consciousness. It uses a 5-point Likert scale ranging from "completely disagree" to "fully agree".

Personality traits are known to affect subjective responses to psychoactive substances and are assessed for explorative future analysis of pooled data. The Freiburger Personality Inventory (FPI-R) version comprises 138 items and covers 12 dimensions of personality: life satisfaction, social orientation, performance orientation, inhibition, excitability, aggressiveness, stress, physical complaints, health concerns, openness, as well as the secondary factors according to Eysenck's Extraversion and Emotionality (Neuroticism). It uses a 2-point scale ("true" and "not true").

Personality traits are known to affect subjective responses to psychoactive substances and are assessed for explorative future analysis of pooled data. The Saarbrücker Persönlichkeitsfragebogen (SPF) defines empathy as the "reactions of one individual to the observed experiences of another." It assesses 28-items on a 5-point Likert scale ranging from "Does not describe me well" to "Describes me very well". The measure has 4 subscales (Perspective Taking, Fantasy, Empathic Concern, Personal Distress) each made up of 7 different items.

Personality traits are known to affect subjective responses to psychoactive substances and are assessed for explorative future analysis of pooled data. The HEXACO personality inventory is a six-dimensional model of human personality with 100 items.The six factors are: Honesty-Humility, Emotionality, Extraversion, Agreeableness, Conscientiousness and Openness to Experience.

Personality traits are known to affect subjective responses to psychoactive substances and are assessed for explorative future analysis of pooled data. The Defense Style Questionnaire (DSQ-40) can provide scores for 20 individual defenses, and scores for the three factors "mature", "neurotic", and "immature". Each item is evaluated on a scale from 1 to 9, where "1" indicates "completely disagree" and "9" indicates "fully agree".

Assesses the degree of psychological insight caused by a psychedelic experience through 14-items to be answered on a 6-point Likert scale ranging from 0 ("not at all") to 5 ("extremely").

Corrected QT time (QTc) will be measured twice on the study days (baseline and at peak drug effect) to examine possible drug-induced changes in the ECG as well as a safety measure (millisecond scale).

The 2011 revised Beschwerden-Liste (B-LR) 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".

140 items are rated on a six-point scale and include attitudes about life (13 positive and 13 negative items), attitudes about self (11 positive and 11 negative items), mood changes (nine positive and nine negative items), behavioral changes (one positive and one negative item), spirituality (22 positive and 21 negative items). Three additional questions are included

Cognitive assessment will be conducted using established tasks from the CANTAB battery. The tasks are administered in a computerized format.

Maximal Plasma concentration of Psilocybin and Metabolites Cmax after substance administration. Calculated via blood samples.

Time until Psilocybin and Metabolites concentration peak in plasma after substance administration. Calculatet via blood samples after substance administration.

Area under the plasma concentration versus time curve for psilocybin and metaboliteswill be calculated up to 24h using blood sampels colected during the study visits after substance administration.

The elimination half life values of Psilocybin and metabolites will be calculated using blood samples collected during study visits after substance administration.

Sleep phases will be scored in every study session using an automated sleep stage classification algorithm of the SomnoArt® armband. The SomnoArt® armband will record, acceleration (3D accelerometer), and heart rate (red-infrared pulse oximeter) activity. Variables of %REM sleep is calculated as REM sleep duration divided by total sleep duration).

Sleep phases will be scored in every study session using an automated sleep stage classification algorithm of the SomnoArt® armband. The SomnoArt® armband will record, acceleration (3D accelerometer), and heart rate (red-infrared pulse oximeter) activity. REM Latency is calculated as duration of non-REM sleep before the first REM phase.

Sleep phases will be scored in every study session using an automated sleep stage classification algorithm of the SomnoArt® armband. The SomnoArt® armband will record, acceleration (3D accelerometer), and heart rate (red-infrared pulse oximeter) activity. REM Efficiency is calculated as REM sleep duration divided by the total REM episode duration