Role of the Serotonin 5-HT2A Receptor in Mescaline-induced Altered States of Consciousness

Visual Analog Scales (VAS) will be repeatedly used to assess subjective alterations in consciousness over time. 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 will be used: "any drug effect", "good drug effect", "bad drug effect", "stimulated", "happy", "anxiety", "nausea", "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 am having insights into connections that previously puzzled me", "open", "talkative", and "trust". Subjects will mark the scale with vertical lines.

Adjective Mood Rating Scale (AMRS) assesses the occurrence and intensity of 60 moods on a 4-point Likert scale ranging from "not at all" to "extremely".

Spiritual Realms Questionnaire (SRQ) assesses the spiritual phenomenons elicited by psychedelic substances through 11 main questions to be answered on a total of 65 sub-ordered visual analog scales (horizontal line, 100 mm, marked with "no, at all" on the left and "yes, very strong" on the right).

States of Consciousness Questionnaire (SCQ) assesses the emergence and intensity of phenomenons occurring in altered states of consciousness on a 6-point Likert scale ranging from 0 ("not at all") to 5 ("extremely").

Mystical-type experience questionnaire (MEQ) assesses with 30 items (embedded into the SCQ) the mystical experiences on a 6-point Likert scale ranging from 0 ("not at all") to 5 ("extremely").

Blood pressure, assessed 20 times during each study session via systolic and diastolic blood pressure.

Heart rate, assessed 20 times during each study session via heart rate, Emax.

Body temperature assessed 20 times during each study session via tympanic body temperature.

Pupil size, assessed 8 times during each study session via pupilometer.

Mescaline and metabolites concentrations measured in the blood plasma, assessed 20 times during each study session via blood samples.

Mescaline and metabolites concentration measured in the urine, assessed in the total amount collected during each study session.

Plasma levels of brain-derived neurotrophic factor (BDNF), assessed 5 times during each study session via blood samples.

Plasma levels of INF-gamma, TNFalpha, Interleukins, assessed 5 times during each study session via blood samples.

Plasma levels of oxytocin, assessed 4 times during each study session via blood samples.

Multifaceted Empathy Test (MET), effects on empathy in computer tests, assessed one time during each study session.

Assessed one time during the screening via the NEO-Five-Factor-Inventory (NEO-FFI). The NEO-FFI assesses 5 personality traits (openness to experience, conscientiousness, extraversion, agreeableness and neuroticism) consisting of of 60 items. Each item is evaluated on a scale from -- "strong disagreement" to ++ "strong agreement".

Assessed one time during the screening via Freiburger Personality Inventory (FPI). The 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").

Assessed one time during the screening via Saarbrücker Personality Questionnaire (SPF). The 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.

Assessed one time during the screening via HEXACO personality inventory (Honesty-Humility, Emotionality, Extraversion, Agreeableness, Conscientiousness, and Openness). The HEXACO consists of 100 items. Each item is evaluated on a scale from 1 "strong disagreement" to 5 "strong agreement".

Assessed one time during the screening via Defense Style Questionnaire (DSQ-40). The 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".

Psychological insight questionnaire (PIQ), assesses painful insights during a psychedelic experience with 14 items (6-point Likert scale ranging from 0 ("not at all") to 5 ("extreme/more than ever before")).

Scale of Positive and Negative Experience (SPANE), assesses life satisfaction regarding the preceding week with12 items (5-point Likert scale ranging from 1 ("very rarely") to 5 ("very often")).

Berner Subjective Well-Being Questionnaire for Adolescents (BFW/E), assesses optimism with 8 items (6-point Likert scale ranging from 1 ("completely wrong") to 6 ("completely right")).

Global Life Satisfaction (GLS), assesses life satisfaction with a single question (ranging from 0 ("not at all satisfied") to 10 ("entirely satisfied")).

Appreciation Scale (AS), assesses appreciation with 57 questions (7-point Likert scale ranging from 1 ("never") to 7 ("several times a day")).

Major adverse events concerning the subject's health during study inclusion (if present) are registered by semi-structured interviews.

List of complaints (LC), which covers the emergence of 66 complaints in a yes/no format, assessed three times during each study session.

Electrocardiogram (ECG) will be recorded twice during the study sessions (baseline and at peak drug effect) as well as on the screening exam to assess potential drug effects on the QTc interval.