Pain Research: Innovative Strategies With Marijuana (PRISM)

• ClinicalTrials.gov Identifier: NCT03522324
• Recruitment Status: Recruiting
• First Posted: May 11, 2018
• Last Update Posted: April 27, 2021
• Sponsor: University of Colorado, Boulder
• Collaborators: University of Colorado, Denver; Colorado State University
• Information provided by (Responsible Party): L. Cinnamon Bidwell, University of Colorado, Boulder

Tracking Information

• First Submitted Date: April 17, 2018
• First Posted Date: May 11, 2018
• Last Update Posted Date: April 27, 2021
• Actual Study Start Date: June 1, 2018
• Estimated Primary Completion Date: October 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 9, 2018)

• Pain Interference: Roland Morris Disability Questionnaire (RMDQ) [ Time Frame: Change over two time points over 2 weeks: Baseline (before 2 weeks of edible use), Pre-Administration (after 2 weeks of use and before acute administration). ]
  Measure of pain interference (RMDQ), using the total RMDQ score (0-24). THC and CBD blood levels will be tested in relation to all outcomes.
• Inflammation: Circulating Levels of Cytokines [ Time Frame: Change over two time points over 2 weeks: Baseline (before 2 weeks of edible use), Pre-Administration (after 2 weeks of use and before acute administration). ]
  Tests levels of recent inflammation (panel of inflammatory markers) before and after cannabis use. THC and CBD blood levels will be tested in relation to all outcomes.
• Flanker Inhibitory Control Attention task (FICA) & International Shopping List Task (ISLT) [ Time Frame: Change over two time points over 2 weeks: Baseline (before 2 weeks of edible use), Pre-Administration (after 2 weeks of use and before acute administration). ]
  Co-outcomes testing cognitive impairment in the domains of immediate and delayed recall (ISLT) and 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.
• Functional Assessment of Cancer Therapy Cognitive Scale (FACT-Cog) [ Time Frame: Change over two time points over 2 weeks: Baseline (before 2 weeks of edible use), Pre-Administration (after 2 weeks of use and before acute administration). ]
  Subjective report of cognitive function

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 9, 2018)

• Pain Intensity: Current, Average and Worst pain using NIH Pain intensity scale. [ Time Frame: Change over four time points over 2 weeks: Baseline (before start of edible use), Pre-Administration (after 2 weeks of edible use and post-acute administration), and Post-Administration (1 and 2 hours post-use. acute measure of edible cannabis effects). ]
  Test effects of cannabinoids on pain using the "current pain", "average pain", and "worst pain" versions of the Pain Intensity scale (on a scale from 0-10). THC and CBD blood levels will be tested in relation to all outcomes.
• Health & Wellbeing [ Time Frame: Change over four time points over 2 weeks: Baseline (before start of edible use), Pre-Administration (after 2 weeks of edible use and post-acute administration), and Post-Administration (1 and 2 hours post-use. acute measure of edible cannabis effects). ]
  Self-report measure across primary domains of health-related well-being (e.g. exercise and diet).
• Pittsburgh Sleep Quality Assessment (PSQI) [ Time Frame: Change over four time points over 2 weeks: Baseline (before start of edible use), Pre-Administration (after 2 weeks of edible use and post-acute administration), and Post-Administration (1 and 2 hours post-use. acute measure of edible cannabis effects). ]
  Self-report assessment of sleep quality.
• Motor function [ Time Frame: Change over four time points over 2 weeks: Baseline (before start of edible use), Pre-Administration (after 2 weeks of edible use and post-acute administration), and Post-Administration (1 and 2 hours post-use. acute measure of edible cannabis effects). ]
  Physical function assessment of motor flexibility and control. Motor outcomes can be aggregated via Z-score to reflect a Z-score of overall motor function.
• Depression and Mood [ Time Frame: Change over four time points over 2 weeks: Baseline (before start of edible use), Pre-Administration (after 2 weeks of edible use and post-acute administration), and Post-Administration (1 and 2 hours post-use. acute measure of edible cannabis effects). ]
  Self-report measures of depression, anxiety, and stress. 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.
• Acute Cognitive impairment: Flanker Inhibitory Control Attention task (FICA) and International Shopping List Task (ISLT). [ Time Frame: Acute changes in three time points over 2 hours: Pre-Administration (after 2 weeks of use, before acute administration), Post-Administration 1-hr & 2-hr (after 2 weeks of use, 1 and 2 hours after acute administration). ]
  Co-outcomes testing cognitive impairment after acute use of cannabis in the domains of immediate and delayed recall (ISLT) and and 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.
• Inflammation: Circulating Levels of Cytokines [ Time Frame: Acute changes in three time points over 2 hours: Pre-Administration (after 2 weeks of use, before acute administration), Post-Administration 1-hr & 2-hr (after 2 weeks of use, 1 and 2 hours after acute administration). ]
  Acute changes in inflammation (panel of inflammatory markers) immediately before and after cannabis use. THC and CBD blood levels will be tested in relation to all outcomes.
• Patient Global Impression of Change: Global Impression of Change Scale (PGIC). [ Time Frame: Change over six month study, including after 2 week primary exposure period. ]
  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.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: May 9, 2018)

• Exploratory: Daily Follow-up Messages [ Time Frame: 2 weeks (daily) ]
  Brief self-report from participants on cannabis use, pain, and sleep in the past 24 hours.
• Exploratory: Monthly Follow-up Surveys [ Time Frame: 6 months (monthly) ]
  Self-report from participants on all drug use, subjective cognitive function, pain, sleep, and mental health
• Objective physical activity/exercise [ Time Frame: 2 weeks ]
  Physical activity and sleep via objective daily data on wearable watch.
• Physical activity/exercise [ Time Frame: 2 weeks ]
  Physical activity via subjective self-report data

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Pain Research: Innovative Strategies With Marijuana
• Official Title: An Observational Study of the Effects of Edible Cannabis and Its Constituent Cannabinoids on Pain, Inflammation, and Cognition
• Brief Summary: This study tests the effects of cannabinoid levels in blood on pain relief, inflammation, and cognitive dysfunction in chronic pain patients who choose to use edible cannabis. Over a two-week period, participants use an edible product of their choice. Blood levels of 9-delta-tetrahydrocannabinol (THC) and cannabidiol (CBD) will be measured before, during, and after the two-week exposure period to determine whether there are associations with pain, inflammation, sleep, physical activity, anxiety/depression, and cognitive dysfunction. After the two-week self-administration period, participants will be followed for six months to collect self-report data on cannabis use, pain levels, sleep quality, and mental health symptoms.

Detailed Description

The National Center for Health Statistics reports that approximately 76 million Americans suffer from chronic pain, affecting the lives of more Americans than cancer, diabetes, and heart disease combined. Perhaps because of its ubiquity and the challenge to its treatment, relief from chronic pain is by far the most commonly cited condition by patients for use of marijuana, with 87%-94% of medical marijuana users reporting using for relief of a pain condition.

Although the mechanisms are still unclear, marijuana and its constituent cannabinoids, including 9-delta-tetrahydrocannabinol (THC), are thought to be involved in reducing pain and associated inflammation. However, THC is also associated with harm in the form of cognitive dysfunction. Synergistic interactions of multiple cannabinoids are believed to produce different effects on both pain relief and cognitive function as compared to THC alone. For example, cannabidiol (CBD) is another primary cannabinoid that may work synergistically with THC in a multi-target analgesic approach.

This study examines the effects of cannabinoids in edible form on pain relief, inflammation, and cognitive dysfunction in chronic pain patients who choose to use marijuana in the context of a short-term (2 weeks), patient-oriented, observational design and a mobile pharmacology and phlebotomy lab.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

Blood samples collected for cytokine and cannabinoid quantitation.

• Sampling Method: Non-Probability Sample
• Study Population: Community Sample

Condition

• Chronic Pain
• Chronic Low Back Pain
• Cannabis Use

Intervention

Drug: Cannabis Edible

Self-Directed Use (ad-libitum)

• Study Groups/Cohorts: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 9, 2018): 283
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 31, 2022
• Estimated Primary Completion Date: October 31, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Intent to initiate use of marijuana to treat chronic pain
• At least one episode of lifetime marijuana use, but infrequent marijuana use for prior six months
• Self-reported non-specific chronic low back pain for at least three months
• Health eligibility approved by study physician
• At least mild to moderate pain intensity OR pain interferes with important life functions

Exclusion Criteria:

• Other drug use (cocaine, methamphetamine, etc.) in the past 3 days and/or actively seeking or in treatment for any substance use disorder
• Use of marijuana to treat pain at any time in lives
• Current use of psychotropic medications (other than SSRIs and ADHD meds), or use of antivirals, steroids, or regular use of maximal doses of NSAIDS
• A daily tobacco user
• Are currently pregnant or trying to become pregnant
• Acute illness (other than chronic pain) or any immune-related disease (e.g., HIV)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Leah Hitchcock, PhD; 303-492-0288; prism.custudy@gmail.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03522324
• Other Study ID Numbers: R01AT009541( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: L. Cinnamon Bidwell, University of Colorado, Boulder
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Colorado, Boulder
• Original Study Sponsor: Same as current

Collaborators

• University of Colorado, Denver
• Colorado State University

Investigators

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

• PRS Account: University of Colorado, Boulder
• Verification Date: April 2021