Cannabis THC Potency, Metabolism, and Cognitive Impairment in Young Adults

Study Overview
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Brief Summary
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The goal of this interventional study is to determine the impact of high potency THC product use on cognitive function of young adults aged 21-25. The main question it aims to answer is: will cannabis users who switch to less potent THC products demonstrate improved cognitive function compared to baseline? Other questions this study aims to answer include: Can researchers accurately assess THC consumption among frequent cannabis users? Can researchers effectively incentivize cannabis users to use less potent THC products? Do genetic variations in THC metabolism impact urinary THC excretion? Do genetic variations in THC metabolism impact cognitive performance in cannabis users? Are quantitative urinary THC values predictive of cognitive impairment? How can researchers use research findings to inform harm reduction practices for people who use cannabis? Participants will submit blood and urine samples and be incentivized to use less potent THC products.

Detailed Description
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The goal of this interventional study is to determine the impact of high potency THC product use on cognitive function of young adults aged 21-25. The aims aims of this study are: Evaluate feasibility of assessing THC consumption, genetic variation in THC metabolism, urinary THC excretion, and cognitive performance in users of high potency cannabis products. Test the effectiveness of an incentivization protocol aimed at encouraging cannabis users to use less potent THC products as a means of harm reduction. Compare group differences between the high and low THC-reduction groups on THC metabolism (urine) and cognitive performance while controlling for any changes in frequency and amount of cannabis used. Identify whether participant predisposition to poorly metabolize THC (i.e., CYP2C9*3 carriers vs. others) impacts urinary THC excretion in the experimental condition relative to baseline in both groups. Identify whether participant predisposition to poorly metabolize THC (i.e., CYP2C9*3 carriers vs. others) impacts cognitive performance in the experimental condition relative to baseline in both groups. Determine whether quantitative urinary THC values correlate with measures of cognitive performance. Communicate basic findings regarding relationships between variables and outcomes in the form of a scorecard to help provide harm reduction strategies for youth who use cannabis. Participants will: Undergo a baseline assessment of cognitive performance and will submit blood and urine samples to assess genetic variation in THC metabolism, and baseline urinary THC excretion. Be randomized to two groups: 1) lower THC reduction group (incentivized to use THC products that are at least 15% less potent than baseline) and 2) higher THC reduction group (incentivized to use THC products that are at least 35% less potent than baseline) . Submit urine samples at baseline and weekly for 5 weeks to measure urinary THC excretion. Complete weekly follow up surveys assessing cannabis use patterns, reinforcing value of the cannabis product(s) used, symptoms of cannabis withdrawal, and presence of positive and negative emotions. Undergo re-assessment of cognitive performance after 5 weeks of intervention. Researchers will compare if participants in each group are able to use less potent THC products and whether the use of less potent THC products results in improved cognitive function.

Official Title
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Impacts of THC Potency of Cannabis Concentrates and THC Metabolism on Cognitive Impairment in Young Adults

Conditions
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Cannabis Use, THC, Marijuana Use, Cognitive Impairment, THC Vaping

Intervention / Treatment
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* Behavioral: 15% THC Potency Reduction
* Behavioral: 35% THC Potency Reduction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between the ages of 21-25 Resides in San Francisco Self-report cannabis concentrate use as their primary method of cannabis use Self-report using cannabis daily or almost daily (i.e., at least 6 out of 7 days during each of the last 4 weeks) Self-report only purchasing cannabis from regulated retail stores in California. Exclusion Criteria: Pregnant Regularly uses other drugs (other than nicotine)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 15% THC Potency Reduction Group<br>Participants will be incentivized to use THC products that are at least 15% less potent than baseline | Behavioral: 15% THC Potency Reduction<br>* Participants will be incentivized to use THC products that are at least 15% less potent than baseline<br>|
| Experimental: 35% THC Potency Reduction Group<br>Participants will be incentivized to use THC products that are at least 35% less potent than baseline | Behavioral: 35% THC Potency Reduction<br>* Participants will be incentivized to use THC products that are at least 35% less potent than baseline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Rapid Visual Information Processing Score | Cognitive performance will be assessed using the CANTAB, a computer-based cognitive assessment system. Participants in this study will complete a battery of seven neuropsychological tests. CANTAB is administered to subjects using a touch screen computer and is language- and culture- independent. Participants scores at 5 weeks will be compared to their baseline scores. The Rapid Visual Information Processing test takes 9 minutes to complete and is scored on a scale of 0-54, with a higher score indicative of better cognitive performance. | Baseline and 5 weeks | 
| Change in Paired Associates Learning score | Cognitive performance will be assessed using the CANTAB, a computer-based cognitive assessment system. Participants in this study will complete a battery of seven neuropsychological tests. CANTAB is administered to subjects using a touch screen computer and is language- and culture- independent. Participants scores at 5 weeks will be compared to their baseline scores. The Paired Associates Learning test takes 8 minutes to complete and is scored on a scale of 0-100%, with a higher percentage indicative of better cognitive performance. | Baseline and 5 weeks | 
| Change in Delayed Matching-to-Sample Score | Cognitive performance will be assessed using the CANTAB, a computer-based cognitive assessment system. Participants in this study will complete a battery of seven neuropsychological tests. CANTAB is administered to subjects using a touch screen computer and is language- and culture- independent. Participants scores at 5 weeks will be compared to their baseline scores. The Delayed Matching-to-Sample test takes 7 minutes to complete and is scored on a scale of 0-100%, with a higher percentage indicative of better cognitive performance. | Baseline and 5 weeks | 
| Change in Verbal Recognition Memory score | Cognitive performance will be assessed using the CANTAB, a computer-based cognitive assessment system. Participants in this study will complete a battery of seven neuropsychological tests. CANTAB is administered to subjects using a touch screen computer and is language- and culture- independent. Participants scores at 5 weeks will be compared to their baseline scores. The Verbal Recognition Memory test takes 6 minutes to complete and is scored on a scale of 0-36, with a higher score indicative of better cognitive performance | Baseline and 5 weeks | 
| Change in Spatial Working Memory score | Cognitive performance will be assessed using the CANTAB, a computer-based cognitive assessment system. Participants in this study will complete a battery of seven neuropsychological tests. CANTAB is administered to subjects using a touch screen computer and is language- and culture- independent. Participants scores at 5 weeks will be compared to their baseline scores. The Spatial Working Memory test takes 4 minutes to complete and is scored on a scale of 0-306, with a lower score indicative of fewer errors and better cognitive performance. | Baseline and 5 weeks | 
| Change in One-Touch Stockings of Cambridge score | Cognitive performance will be assessed using the CANTAB, a computer-based cognitive assessment system. Participants in this study will complete a battery of seven neuropsychological tests. CANTAB is administered to subjects using a touch screen computer and is language- and culture- independent. Participants scores at 5 weeks will be compared to their baseline scores. The One-Touch Stockings of Cambridge test takes 10 minutes to complete and scores are based on the time it takes for a participant to solve 20 problems. Shorter time to solve a problem is indicative of better cognitive performance. | Baseline and 5 weeks | 
| Change in Stop Signal Task score | Cognitive performance will be assessed using the CANTAB, a computer-based cognitive assessment system. Participants in this study will complete a battery of seven neuropsychological tests. CANTAB is administered to subjects using a touch screen computer and is language- and culture- independent. Participants scores at 5 weeks will be compared to their baseline scores. The Stop Signal Task test takes 14 minutes to complete and is scored on a scale of 1-1000 milliseconds, with a shorter time indicative of better cognitive performance. | Baseline and 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Urinary THC Excretion | Urinary THC excretion will be measured using liquid chromatography mass spectroscopy (LC/MS/MS). THC levels will be corrected/standardized for level of hydration by dividing total THC by total urine creatinine. Results range from <5 ng/mL to 5,000 ng/mL, with higher values indicative of more THC in the urine. | Baseline | 
| Week 1 Urinary THC Excretion | Urinary THC excretion will be measured using liquid chromatography mass spectroscopy (LC/MS/MS). THC levels will be corrected/standardized for level of hydration by dividing total THC by total urine creatinine. Results range from <5 ng/mL to 5,000 ng/mL, with higher values indicative of more THC in the urine. Week 1 THC levels will be compared to baseline urine THC levels. | 7-10 days after study enrollment. | 
| Week 2 Urinary THC Excretion | Urinary THC excretion will be measured using liquid chromatography mass spectroscopy (LC/MS/MS). THC levels will be corrected/standardized for level of hydration by dividing total THC by total urine creatinine. Results range from <5 ng/mL to 5,000 ng/mL, with higher values indicative of more THC in the urine. Week 2 THC levels will be compared to baseline THC levels. | 14-17 days after study enrollment. | 
| Week 3 Urinary THC Excretion | Urinary THC excretion will be measured using liquid chromatography mass spectroscopy (LC/MS/MS). THC levels will be corrected/standardized for level of hydration by dividing total THC by total urine creatinine. Results range from <5 ng/mL to 5,000 ng/mL, with higher values indicative of more THC in the urine. Week 3 THC levels will be compared to baseline THC levels. | 21-24 days after study enrollment. | 
| Week 4 Urinary THC Excretion | Urinary THC excretion will be measured using liquid chromatography mass spectroscopy (LC/MS/MS). THC levels will be corrected/standardized for level of hydration by dividing total THC by total urine creatinine. Results range from <5 ng/mL to 5,000 ng/mL, with higher values indicative of more THC in the urine. Week 4 THC levels will be compared to baseline THC levels. | 28-30 days after study enrollment. | 
| Week 5 Urinary THC Excretion | Urinary THC excretion will be measured using liquid chromatography mass spectroscopy (LC/MS/MS). THC levels will be corrected/standardized for level of hydration by dividing total THC by total urine creatinine. Results range from <5 ng/mL to 5,000 ng/mL, with higher values indicative of more THC in the urine. Week 5 THC levels will be compared to baseline THC levels. | 35-38 days after study enrollment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dabs, Wax, Cannabis, Marijuana, High Potency THC, Young Adult, Youth