Effects of SERT Inhibition on the Subjective Response to LSD in Healthy Subjects

Visual analog scale consisting of 94 items. Constructed of five scales and allows assessing mood, anxiety, derealization, depersonalization, changes in perception, auditory alterations, and reduced vigilance. Scales will be presented as 100 mm long horizontal lines marked with vertical lines by the participant.

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). We 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 has recently been developed by linguist and psychologist K. Stocker, Swiss Federal Institute of Technology Zürich and University of Zürich, to rate psychedelic (entheogenic) experiences with a focus on spiritual aspects insufficiently covered by the 5D-ASC and SCQ. The scale includes 11 main questions to be answered on a total of 65 sub-ordered visual rating scales. Results will be used to validate the scale and will be analyzed similar to the 5D-ASC using paired t-tests and comparing the constructs defined by the 11 main questions contained within the four main dimensions religious-psychological spirituality spectrum of humanity, human condition and life meaningfulness, dealing with personal problems, and worldview/belief.

This is a newly developed instrument to assess the degree to which an event has facilitated acute insight and gained awareness into emotions, behaviors, beliefs, memories, or relationships. The 14 items resulting from a recent validation process are to be rated on a 6-point Likert scale ranging from 0 = "No; not at all" to 5 = "Extremely (more than ever before in my life)".

Repeatedly measured using blood pressure / pulse apparatus (mmHg scale)

Repeatedly measured using blood pressure / pulse apparatus (beats per minute scale)

Repeatedly measured using ear thermometer (degree Celsius scale)

Paroxetine plasma concentrations will be measured repeatedly over time using LC-MS/MS techniques (nanogram per milliliter scale)

LSD plasma concentrations will be measured repeatedly over time using LC-MS/MS techniques (nanogram per milliliter scale)

Messenger ribonucleic acid (mRNA) expression levels in whole blood as a peripheral marker of spiny neuronal gene (CNS) expression will be used to measure expression of HTR genes as well as expression of the SERT gene.

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).