This study investigates whether the anxiolytic effects and anti-inflammatory properties of cannabis vary as a function of the ratio of CBD to THC, with the goal that these effects may shed light on the mixed data linking cannabis use and anxiety. Individuals with mild to moderate anxiety who elect to use cannabis (smoked flower or edible) will complete four weeks of observation. Participants complete cognitive tasks, a substance use history, health questionnaires concerning sleep and physical activity, and a blood draw at four different time points (Baseline, after 2 weeks of cannabis use, and immediately before and after self-administration after 4 weeks of use) with the use of a mobile pharmacology laboratory, which goes to a convenient location for each participant to self-administer their cannabis. Participants are then followed for five months to self-report on cannabis use, anxiety, subjective cognitive functioning, sleep quality, and other mental health symptoms.
Marijuana use is on the rise with the number of adults reporting medical and recreational use doubling in the past decade. Among adult medical marijuana users, 39% report using marijuana for the purposes of self-treating or coping with anxiety. Marijuana is approved for medical use in over half the states and is gaining traction for use as an "off-label" add-on therapy for treatment-resistant anxiety and stress-related disorders. Paradoxically, however, while data suggest that marijuana, in particular ∆9-tetrahydrocannabinol (THC), increases anxiety acutely, cross sectional and longitudinal data suggest associations between marijuana use and lower risk for anxiety disorders. There is some evidence demonstrating that marijuana use is associated with increases in acute anxiety and anxiety disorders. However, other data suggests that marijuana use may be protective for adolescents at-risk for anxiety and decrease the chances of developing an anxiety disorder during college. This finding is consistent with a growing body of evidence from animal models suggesting that marijuana has anxiolytic and anti-inflammatory properties. Clarifying the anxiolytic effects of specific strains that differ in their cannabinoid composition may explain these discrepant findings. Thus, regardless of whether results support or refute the anxiolytic properties of marijuana, findings from this study fill a critical void and can inform public perception. The study goal is to understand the anxiolytic effects of cannabinoids, in particular the effects of THC-based strains vs. CBD-based strains vs strains containing both THC and CBD in different ratios (1:0, 1:1, or 0:1) on inflammation, cognitive functioning, and anxiety/negative affect. This design will capitalize on the novel opportunity to examine the effects of real world marijuana strains on key outcomes.
Study Type
OBSERVATIONAL
Enrollment
361
Self-Directed Use (ad-libitum)
Center for Innovation and Creativity
Boulder, Colorado, United States
Change in Anxiety: Depression Anxiety Stress Scale (DASS21).
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: Circulating Levels of Cytokines (Panel of Inflammatory Markers).
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)
Patient Global Impression of Change: Global Impression of Change Scale (PGIC).
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.
Cognitive Impairment: NIH Toolbox Cognitive Battery, Flanker Inhibitory Control Attention Task (FICA) and International Shopping List Test (ISLT).
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-Reported Affect in the Context of Negative Affect Induction Task
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
Change in Depression: Depression Anxiety Stress Scale (DASS21).
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)
Health and Wellbeing
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 Battery: Balance and Motor Function
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)
Objective Physical Activity/Exercise
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/Exercise
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
Change in Stress: Depression Anxiety Stress Scale (DASS21).
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)
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