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Table 3 Primary and secondary measures

From: MDLSD: study protocol for a randomised, double-masked, placebo-controlled trial of repeated microdoses of LSD in healthy volunteers

Measure Domain Scale
Primary measures
 Alternate Uses Test (AUT) [35] Creativity: divergent thinking 3 items; participants are given the name of a household item and are given 2 min to produce possible uses; responses are marked for fluency (number of responses), flexibility (number of different categories of responses), elaboration (number of elaborative details), and originality (uniqueness of response).
 Big Five Inventory-2 (BFI-2) [50] Personality: open-mindedness, agreeableness, conscientiousness, extraversion, negative emotionality 60 items on a 5-point scale (1–5) from “disagree strongly” to “agree strongly” with 5 scales reported as the mean response. Open-mindedness scale evaluated as a primary measure and all others as secondary measures.
 Visual Long-Term Potentiation Paradigm (EEG LTP) [55] Plasticity: Hebbian plasticity Participants are presented with visual stimuli which is “tetanised” with high-frequency stimulation, assessed as the amplitude of visual-evoked ERP response to tetanised stimuli vs non-tetanised stimuli.
 Roving Mismatch Negativity Paradigm (EEG MMN) [56] Plasticity: predictive coding Participants are presented with a series of tones followed by a series of deviant tones, assessed as the amplitude of auditory-evoked ERP response to deviant tone and rate of subsequent habituation to tone.
 Modified Tellegen Absorption Scale (MODTAS) [28, 51] Personality: absorption 34 items rated on a 5-point scale (0–4) reported as the sum of scores (0–136).
 Remote Associates Task (RAT) [52] Creativity: convergent thinking 20 items; participants are given 3 words and need to produce a word that all 3 have in common, assessed as number correct and number attempted.
 Resting-State fMRI Connectivity 9-min continual recording on 3-T Siemens scanner with a 32-channel head coil.
Secondary measures
 5-Dimensional Altered States of Consciousness Questionnaire (5D-ASC) [57, 58] Drug effects: psychological 91 items rated on VAS (1–100) with 5 scales and 11 subscales reported as % of the maximum score.
 Adverse events Unwanted health effects Participants are asked daily to report any “unpleasant health issues” and to rate them as mild, moderate, or serious.
 Consensual Assessment Technique (CAT) [59] Creativity: non-specific Participants are given 15 min to complete a paper collage; the result is rated by independent assessors on VAS (0–100) from low to high on (1) creativity and (2) technical goodness, reported as mean rater response.
 Detail and Flexibility Questionnaire (DFlex) [60] Attention to detail and cognitive rigidity 24 items on a 6-point scale (1–6) with 2 subscales reported as the sum of scores (total 24–144; subscales 12–72).
 Daily questionnaire Mood: well, sad, happy, stressed, creative, anxious, focused, tired, calm, connected, angry, energy, irritable, motivated, craving 15 items rated on VAS (0–100) reported as individual scores.
 Depression, Anxiety, and Stress Scale (DASS) [61] Mood: depression, anxiety, stress 42 items on a 4-point scale (0–3) with 3 subscales reported as the sum of scores (0–42).
 Drug Effects Visual Analogue Scale (VAS) Drug effects: psychological 16 items rated on VAS (0–100) reported as individual and mean scores.
 Electrocardiogram (ECG) Drug effects: physiological QT interval, heart rate variability.
 Everyday Problem-Solving Questionnaire Creativity: problem solving 4 items rated on a VAS (0–100) reported as individual and mean scores.
 Expectancy questionnaire Expectancy 18 items rated on VAS (0–100; see Table 4).
 Five Facets of Mindfulness Questionnaire (FFMQ) [62] Mindfulness: observe, act with awareness, non-judgement, describe, non-reacting 39 items rated on a 5-point scale (1–5) with 5 subscales reported as the mean of scores.
 Fitbit Charge 4, Activity and Sleep Tracker, manufactured by Fitbit, San Francisco, CA, USA Drug effects: physiological Activity reported as steps per day and sleep reported as minutes asleep per day.
 Genetic biomarkers Genetic BDNF Val66Met.
 Inflammatory cytokines Immune modulation Plasma concentration of inflammatory cytokines analysed reported in pg/ml.
 NIH Toolbox Picture Vocabulary Test, Flanker Inhibitory Control and Attention Test, Picture Sequence Memory Test, List Sorting Working Memory Test, Dimensional Change Card Sort Test, Pattern Comparison Processing Speed Test [63] Cognition: language, attention, executive function, episodic memory, working memory, processing speed Reported as individual scores and NIH Fluid Cognition Composite Score Uncorrected Standard Score [64].
 NIH Toolbox Anger-Affect, Anger-Hostility, Anger-Physical Aggression, Positive Affect, General Life Satisfaction, Meaning and Purpose, Emotional Support, Instrumental Support, Loneliness, Friendship, Perceived Hostility, Perceived Rejection, Self-Efficacy [65] Mood: anger, positive affect, general life satisfaction, meaning and purpose, social support, companionship, social distress, self-efficacy Reported as individual scores and NIH Psychological Well-being Summary, Social Satisfaction Summary [64].
 Pharmacokinetic/pharmacodynamic (PKPD) measures Drug metabolism Plasma concentration of drug in pg/ml.
 Peripheral mononuclear blood cell (PMBC) biomarkers Physiology 5HT2A receptor mRNA expression in PMBC cells.
 Profile of Mood States (POMS) [66] Mood: fatigue, tension, depression, anger, vigour, confusion 65 items on a 5-point scale (0–4) with 6 subscales reported as the sum of scores.
 Perceived Stress Scale (PSS) [67] Mood: stress 10 items on a 5-point scale (0–5) reported as the sum of scores.
 Self-Assessment Manikins (SAM) [68] Drug effects: valence, arousal, dominance 3 items on a 9-point scale (1–9) reported as individual scores.
 Semi-structured audio interview Open-ended ~ 30-min interview with open-ended questions about the experience of microdosing trial for qualitative analysis.
 Subject release interview Open-ended Brief discussion of participant’s experience of first dose and assessment of safety to discharge.
 State of Surrender (SoS) [69] Mindset: surrender 10 items on a 6-point scale (1–6) reported as the mean of scores.
 State of Preoccupation (SoP) [69] Mindset: preoccupation 4 items on a 6-point scale (1–6) reported as the mean of scores.
 Vital signs Physiology Systolic and diastolic blood pressure in mmHg and heart rate in bpm.