Anxiety, Inflammation, and Stress

Completed

Conditions: Anxiety Generalized
Inflammation
Inflammatory Response
Anxiety Disorders
Anxiety Chronic
Anxiety

Registration Number: NCT03491384

Lead Sponsor: University of Colorado, Boulder

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 361

Inclusion Criteria

Non-users of cannabis must have been a non-user of cannabis for at least six months
If a user of cannabis, at least one episode of lifetime cannabis use and a desire to use cannabis to cope with anxiety.
Reports at least mild to moderate anxiety (≥5 on GAD-7)

Exclusion Criteria

Seeking treatment for a substance use disorder
Current use of other drugs (e.g., cocaine, methamphetamine)
Current use psychotropic or steroid-based medications
Has an immune-relevant disease (e.g. HIV)
Daily tobacco user
Currently pregnant or trying to become pregnant
In treatment for psychotic disorder, bipolar disorder or major depression disorder with suicidal ideation; or a history with these disorders.

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change in Anxiety: Depression Anxiety Stress Scale (DASS21).	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. 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
Change in Inflammation: Circulating Levels of Cytokines (Panel of Inflammatory Markers).	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.
Patient Global Impression of Change: Global Impression of Change Scale (PGIC).	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.	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.

Secondary Outcome Measures

Name	Time	Method
Cognitive Impairment: NIH Toolbox Cognitive Battery, Flanker Inhibitory Control Attention Task (FICA), International Shopping List Test (ISLT), and Functional Assessment of Cancer Therapy Cognitive Scale (FACT-Cog).	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), and a subjective report of cognitive complaint (FACT-Cog). 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.
Stress Reactivity Induction	Acute change in affect from before the stress induction task to post-breathing	Measure change in affect in response to a stress reactivity task through lab paradigm assessing attention to affective/stress inducing cues
Depression and Mood	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 of depression and mood states will be assessed at baseline and the four-week appointment. Given the observational nature of the study, co-outcomes are appropriate to comprehensively assess change in depression/negative affect over the course of the study.
Health and Wellbeing	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 health-related well-being, diet, and assessment of sleep quality.
Motor Battery: Balance and Motor Function	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.
Objective Physical Activity/Exercise	Change over 2 weeks	Physical activity via objective daily data on wearable watch.
Physical Activity/Exercise	Change over 4 weeks.	Physical activity via subjective self-report data.