Pain Research: Innovative Strategies With Marijuana

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Observational Study of the Effects of Edible Cannabis and Its Constituent Cannabinoids on Pain, Inflammation, and Cognition

Conditions
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Chronic Pain, Chronic Low Back Pain, Cannabis Use

Intervention / Treatment
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* Drug: Cannabis Edible


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Cannabis Edible|Self-Directed Use (ad-libitum)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Interference: Roland Morris Disability Questionnaire (RMDQ) | 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. | 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). | 
| Inflammation: Circulating Levels of Cytokines | 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. | 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). | 
| Flanker Inhibitory Control Attention task (FICA) & International Shopping List Task (ISLT) | 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. | 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). | 
| Functional Assessment of Cancer Therapy Cognitive Scale (FACT-Cog) | Subjective report of cognitive function | 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). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity: Current, Average and Worst pain using NIH Pain intensity scale. | 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. | 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). | 
| Health & Wellbeing | Self-report measure across primary domains of health-related well-being (e.g. exercise and diet). | 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). | 
| Pittsburgh Sleep Quality Assessment (PSQI) | Self-report assessment of sleep quality. | 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). | 
| Motor function | 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. | 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). | 
| Depression and Mood | 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. | 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). | 
| Acute Cognitive impairment: Flanker Inhibitory Control Attention task (FICA) and International Shopping List Task (ISLT). | 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. | 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). | 
| Inflammation: Circulating Levels of Cytokines | 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. | 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). | 
| 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. | Change over six month study, including after 2 week primary exposure period. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cannabis, Pain, Cytokines, Inflammation, Cognition