Anxiety, Inflammation, and Stress

• ClinicalTrials.gov Identifier: NCT03491384
• Recruitment Status: Recruiting
• First Posted: April 9, 2018
• Last Update Posted: March 24, 2020
• Sponsor: University of Colorado, Boulder
• Collaborator: University of Colorado, Denver
• Information provided by (Responsible Party): L. Cinnamon Bidwell, University of Colorado, Boulder

Study Description

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.

Condition or disease	Intervention/treatment
Anxiety; Anxiety Disorders; Anxiety Generalized; Anxiety Chronic; Inflammation; Inflammatory Response	Drug: Cannabis (smoked flower, ingested edible)

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.

Study Design

• Study Type: Observational
• Estimated Enrollment: 210 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Novel Approaches to Understanding the Role of Cannabinoids and Inflammation in Anxiety
• Actual Study Start Date: April 1, 2018
• Estimated Primary Completion Date: January 30, 2022
• Estimated Study Completion Date: June 30, 2022

Groups and Cohorts

Intervention Details:

• Drug: Cannabis (smoked flower, ingested edible)
  Self-Directed Use (ad-libitum)

Outcome Measures

Primary Outcome Measures :

1. Change in Anxiety/Negative Affect: Depression Anxiety Stress Scale (DASS21). [ Time Frame: Change over three time points over 4 weeks: Baseline (before 4 weeks of cannabis use), Pre-Administration (after 4 weeks of use, but before acute self-administration), 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. Subjects 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 self-report will be tested in relation to THC and CBD blood levels.
2. Change in Inflammation: Circulating Levels of cytokines (panel of inflammatory markers). [ Time Frame: Change over three time points over 4 weeks: Baseline (before 4 weeks of cannabis use), Pre-Administration (after 4 weeks of use, but before acute self-administration), 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.
3. Patient Global Impression of Change: Global Impression of Change Scale (PGIC). [ Time Frame: Change over three time points over 4 weeks: Baseline (before 4 weeks of cannabis use), Pre-Administration (after 4 weeks of use, but before acute self-administration), and Post-Administration (after 4 weeks of use and after acute self-administration) ]
   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.

Secondary Outcome Measures :

1. 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). [ Time Frame: Change over three time points over 4 weeks: Baseline (before 4 weeks of cannabis use), Pre-Administration (after 4 weeks of use, but before acute self-administration), 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.
2. Stress reactivity induction [ Time Frame: Change over three time points over 4 weeks: Baseline (before 4 weeks of cannabis use), Pre-Administration (after 4 weeks of use, but before acute self-administration), and Post-Administration (after 4 weeks of use and after acute self-administration). ]
   Measure affective and stress reactivity responses through lab paradigm assessing attention to affective/stress inducing cues.
3. Depression and Mood [ Time Frame: Change over three time points over 4 weeks: Baseline (before 4 weeks of cannabis use), Pre-Administration (after 4 weeks of use, but before acute self-administration), 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.
4. Health and Wellbeing [ Time Frame: Change over three time points over 4 weeks: Baseline (before 4 weeks of cannabis use), Pre-Administration (after 4 weeks of use, but before acute self-administration), 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.
5. Motor Battery: Balance and Motor Function [ Time Frame: Change over three time points over 4 weeks. ]
   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.
6. Objective physical activity/exercise [ Time Frame: Change over 2 weeks. ]
   Physical activity via objective daily data on wearable watch.
7. Physical activity/exercise [ Time Frame: Change over 4 weeks. ]
   Physical activity via subjective self-report data.

Other Outcome Measures:

1. Exploratory: Daily Follow-Up Messages [ Time Frame: One survey per day for 30 days (at the start of the 4 week study) ]
   Brief self-report from participants on anxiety, cannabis use, and sleep in the past 24 hours.
2. Exploratory: Monthly Follow-Up Surveys [ Time Frame: One survey per month for 5 months (at the end of the 4 week study) ]
   Self-report from participants on anxiety, drug use, sleep, subjective cognitive functioning, and mental health.

Biospecimen Retention:   Samples With DNA

Blood samples (including DNA analysis) gut microbiome samples (including microbial DNA analysis)

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Community Sample

Criteria

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.

Contacts and Locations

Contacts

Contact: Leah Hitchcock, PhD; 303-492-0288; OASIS.CUstudy@gmail.com

Locations

United States, Colorado

Center for Innovation and Creativity; Recruiting

Boulder, Colorado, United States, 80304

Contact: Leah Hitchcock, PhD

Sponsors and Collaborators

University of Colorado, Boulder

University of Colorado, Denver

Investigators

• Principal Investigator: Cinnamon Bidwell, PhD; University of Colorado, Boulder

More Information

Additional Information:

OASIS Website, CU Change Lab, University of Colorado-Boulder 

• Responsible Party: L. Cinnamon Bidwell, Assistant Research Professor, University of Colorado, Boulder
• ClinicalTrials.gov Identifier: NCT03491384
• Other Study ID Numbers: R01DA04413
• First Posted: April 9, 2018
• Last Update Posted: March 24, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by L. Cinnamon Bidwell, University of Colorado, Boulder:

anxiety; inflammation; cannabis; marijuana; stress

Additional relevant MeSH terms:

Inflammation; Anxiety Disorders; Mental Disorders; Pathologic Processes