Table 3 Primary and secondary measures
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. |
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. |