Anxiety, Inflammation, Stress, and Cannabinoids

The DASS21 is a 21-item scale that measures self-reported change in anxiety, depression, and stress symptoms. Participants are asked to use 4-point severity/frequency scales (higher values indicate greater severity) to rate the extent to which they have experienced each state. Scores for Depression, Anxiety and Stress are calculated by summing the scores for the relevant items. Changes in DASS subscale self-report will be tested in relation to THC and CBD blood levels. For this aim, only the Anxiety subscale was used. Anxiety subscale score range 0-42 Normal 0-6; Mild 7-9; Moderate 10-14; Severe 15-19; Extremely severe 20-42

Time frame: Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration)

Change in inflammation from before to after cannabis use will be tested in relation to THC and CBD blood levels. The sum concentration of the cytokines IL-1a, IL-1b, IL-6, IL-8, IL-12, and TNFα, which are generally regarded as pro-inflammatory, will be utilized. The range for these values can be from 0 to infinity. Higher values indicate higher (worse) levels of inflammation.

Time frame: Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration)

Population: Participants were included in inflammatory marker analyses if they had biomarkers available for both timepoints (baseline and 4 weeks). Thus, sample size here is not the same as sample size for self-report based outcomes.

Patient Global Impression of Change Scale (PGIC) measures self-reported change on a 1-7 scale (i.e. from 1 (very much worse) to 7 (very much improved) in anxiety. Changes in this measure will be tested in relation to THC and CBD blood levels. Scale possible score range 0-7, with higher scores indicating the largest amount of possible change.

Time frame: This was administered only once, at the 4 week timepoint, asking participants to reflect on how much change they had experienced over the past 4 weeks.

The DASS21 is a 21-item scale that measures self-reported change in anxiety, depression, and stress symptoms. Participants are asked to use 4-point severity/frequency scales (higher values indicate greater severity) to rate the extent to which they have experienced each state. For this aim, only the Depression subscale was used. Depression subscale score range 0-21 Normal (0 to 4), Mild (5 to 6), Moderate, (7 to 10), Severe (11 to 13), Extremely Severe (14 and above)

Time frame: Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration)

The DASS21 is a 21-item scale that measures self-reported change in anxiety, depression, and stress symptoms. Participants are asked to use 4-point severity/frequency scales (higher values indicate greater severity) to rate the extent to which they have experienced each state. For this aim, only the Stress subscale was used. Stress subscale score range 0-33 Normal (0 to 14), Mild (15 to 18), Moderate, (19 to 25), Severe (26 to 33)

Time frame: Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration)

Co-outcomes testing multiple domains of thinking, memory, and perception (NIH Toolbox), cognitive impairment in the domains of immediate and delayed recall (ISLT), attention and inhibitory control (FICA). Cognitive outcomes are measured in standard scores (e.g. Range of \>70 to \>140 (Mean of 100 and SD of 15) with higher scores indicating better performance) and can be averaged to reflect a Standard score of overall cognitive function.

Time frame: Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration)

Self-report measure across primary domains of diet, assessment of sleep quality, and health-related well-being. Each domain was assessed with the following single items: Diet: In general, how healthy is your overall diet? Would you say (response options 0- excellent; 1- very good; 2- good; 3- fair; 4- poor) Sleep Quality: During the past 2 weeks, how would you rate your sleep quality overall? (response options 0- very good; 1- fairly good; 2- fairly bad; 3- very bad) Health Related Wellbeing: In general, how would you describe your health? (response options 0- excellent; 1- very good; 2- good; 3- fair; 4- poor)

Time frame: Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration)

Motor control assessed via dynamic sway, proprioception, and finger tapping rate. Motor outcomes can be aggregated via Z-score to reflect a Z-score of overall motor function. We calculated the sum of Motor Battery Balance (Eyes Open, Eyes Closed, and Head Back) z-scores. A score of 0 means a participant's balance is at the mean for the sample. Higher scores (scores greater than 0) correspond to worse balance compared to the sample. Scores lower than 0 indicate better balance compared to the sample.

Time frame: Change from baseline to 4 weeks: Baseline (before 4 weeks of cannabis use) and Post-Administration (after 4 weeks of use and after acute self-administration)

Physical activity via objective daily data on wearable watch as measured by average minutes of moderate to vigorous physical activity (MVPA).

Time frame: 4 weeks

Physical activity via subjective self-report data using the Stanford Leisure-Time Activity Categorical item with 6 item responses (L-CAT; 1-6). Scores are reported as a mean between 1 and 6, larger numbers correspond to higher levels of activity.

Time frame: 4 weeks

Participants reported levels of negative affect on a novel scale from -50 (worst) to +50 (best) while undergoing a guided rumination to induce negative affect.

Time frame: Acute change in affect from before the negative affect induction task to post-breathing

Brief self-report from participants on anxiety and sleep in the past 24 hours. These are all 1-item novel questions in a daily, text based survey. Anxiety and sleep are on a scale of 1-10, with higher numbers being more anxiety or better sleep. Score is an average rating over 30 days.

Time frame: One survey per day for 30 days (at the start of the 4 week study)

Self-report from participants on anxiety (DASS anxiety subscale), sleep (novel sleep quality question ranging from 1-10 and 10 being best sleep), subjective cognitive functioning (perceived cognitive ability from the Functional Assessment of Cancer Therapy-Cognitive Function scale as was already reported in secondary measures- see for full description), and general health health (novel health question as was also reported in secondary measures- see for full description).

Time frame: 5 months (post-study completion)