Anxiety, Inflammation, Stress, and Cannabinoids

NCT03491384 | Completed Results

• 1 other identifier: R01DA04413
• Study Type: observational
• Target: 361
• Locations: 1 country
• Sites: 1

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.

Conditions

Anxiety; Anxiety Disorders; Anxiety Generalized; Anxiety Chronic; Inflammation; Inflammatory Response

Keywords

anxiety; inflammation; cannabis; marijuana; stress

Outcome Measures

Primary Outcomes (3)

• 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

  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.

  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.

  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.

Secondary Outcomes (8)

• Cognitive Impairment: NIH Toolbox Cognitive Battery, Flanker Inhibitory Control Attention Task (FICA) and International Shopping List Test (ISLT).

  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

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

• Change in Depression: 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)

• 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)

• 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)

Other Outcomes (2)

• Exploratory: Daily Follow-Up Messages

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

• Exploratory: Monthly Follow-Up Surveys

  5 months (post-study completion)

Interventions

Cannabis (smoked flower, ingested edible) DRUG

Self-Directed Use (ad-libitum)

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Community Sample

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Colorado, Boulder: lead
• University of Colorado, Denver: collaborator

Study Sites (1)

Center for Innovation and Creativity

Boulder, Colorado, 80304, United States

Location

Related Publications (3)

• Martin-Willett R, Skrzynski CJ, Bryan AD, Bidwell LC. Effects of Cannabinoids on Emotional States and Alcohol Use Among Underrepresented Groups: Moderation by Perceived Discrimination. Hum Psychopharmacol. 2025 Sep;40(5):e70016. doi: 10.1002/hup.70016.

  PMID: 40916181 DERIVED

• Skrzynski CJ, Rosa L, Drake A, Bryan AD, Bidwell LC. Experimental study on cannabis use and affect: Effects on reactivity to and recovery from negative stimuli. J Psychopathol Clin Sci. 2025 Aug;134(6):639-650. doi: 10.1037/abn0001023. Epub 2025 Jun 16.

  PMID: 40522823 DERIVED

• Bidwell LC, Martin-Willett R, Skrzynski C, Lisano J, Ortiz Torres M, Giordano G, Hutchison KE, Bryan AD. Acute and Extended Anxiolytic Effects of Cannabidiol in Cannabis Flower: A Quasi-Experimental ad libitum Use Study. Cannabis Cannabinoid Res. 2024 Aug;9(4):1015-1027. doi: 10.1089/can.2023.0187. Epub 2024 Jan 22.

  PMID: 38252547 DERIVED

Related Links

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

Biospecimen

Retention: SAMPLES WITH DNA

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

MeSH Terms

Conditions

Anxiety Disorders; Generalized Anxiety Disorder; Inflammation; Marijuana Abuse

Interventions

nabiximols

Condition Hierarchy (Ancestors)

Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Substance-Related Disorders; Chemically-Induced Disorders

Results Point of Contact

• Title: Dr. L. Cinnamon Bidwell
• Organization: University of Colorado Boulder

CUChange@Colorado.edu

3037355180

Study Officials

• Cinnamon Bidwell, PhD

  University of Colorado, Boulder

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Research Professor

Study Record Dates

• First Submitted: February 28, 2018
• First Posted: April 9, 2018
• Study Start: April 1, 2018
• Primary Completion: December 30, 2022
• Study Completion: May 17, 2023
• Last Updated: August 27, 2025
• Results First Posted: December 9, 2024

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)