Cannabis THC Potency, Metabolism, and Cognitive Impairment in Young Adults (THC-YA)

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

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.

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.

Participants will be incentivized to use THC products that are at least 15% less potent than baseline

Participants will be incentivized to use THC products that are at least 35% less potent than baseline

Participants will be incentivized to use THC products that are at least 15% less potent than baseline

Participants will be incentivized to use THC products that are at least 35% less potent than baseline

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

Predisposition to poorly metabolize THC will be measured at baseline using a blood test to identify carriers of the CYP2C9*3 genetic variant. We will then determine whether there are statistically significant differences in baseline and weekly urinary THC levels among CYP2C9*3 carriers compared to non-carriers while controlling for participant reported cannabis use patterns.

Predisposition to poorly metabolize THC will be measured at baseline using a blood test to identify carriers of the CYP2C9*3 genetic variant. We will then determine whether there are statistically significant differences in baseline and 5-week cognitive performance between CYP2C9*3 carriers compared to non-carriers while controlling for participant reported cannabis use patterns. 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, with lower scores indicating more severe cognitive impairment.

Symptoms of a cannabis use disorder will be assessed at baseline using the Cannabis Use Disorder Identification Test (CUDIT). CUDIT scores range from 0 to 32, with a score of 12 or higher indicative of possible cannabis use disorder.

Symptoms of depression will be assessed at baseline and at 5 weeks using the Beck Depression Inventory (BDI). The BDI consists of 21 questions, with scores ranging from 0 to 63; a higher score is indicative of more symptoms of depression. Participant scores at 5 weeks will be compared to their baseline scores.

Participants will complete a baseline survey to determine their pattern of cannabis use one week prior to study enrollment. They will be asked to report the brand, name, and THC concentration of the cannabis product(s) they have been using. They will be able to upload photos of product packaging if available. They will be asked to report frequency of cannabis use by reporting whether they used their cannabis product in the morning, afternoon, and evening of each of the preceding 7 days.

Participants will complete a baseline survey to determine their pattern of cannabis use 7 days after study enrollment. They will be asked to report the brand, name, and THC concentration of the cannabis product(s) they have been using over the 7 preceding days. They will be asked to upload photos of product packaging. They will be asked to report frequency of cannabis use by reporting whether they used their cannabis product in the morning, afternoon, and evening of each of the preceding 7 days. THC concentration and frequency of use will be compared to baseline cannabis use.

Participants will complete a baseline survey to determine their pattern of cannabis use 14 days after study enrollment. They will be asked to report the brand, name, and THC concentration of the cannabis product(s) they have been using over the 7 preceding days. They will be asked to upload photos of product packaging. They will be asked to report frequency of cannabis use by reporting whether they used their cannabis product in the morning, afternoon, and evening of each of the preceding 7 days. THC concentration and frequency of use will be compared to baseline cannabis use.

Participants will complete a baseline survey to determine their pattern of cannabis use 21 days after study enrollment. They will be asked to report the brand, name, and THC concentration of the cannabis product(s) they have been using over the 7 preceding days. They will be asked to upload photos of product packaging. They will be asked to report frequency of cannabis use by reporting whether they used their cannabis product in the morning, afternoon, and evening of each of the preceding 7 days. THC concentration and frequency of use will be compared to baseline cannabis use.

Participants will complete a baseline survey to determine their pattern of cannabis use 28 days after study enrollment. They will be asked to report the brand, name, and THC concentration of the cannabis product(s) they have been using over the 7 preceding days. They will be asked to upload photos of product packaging. They will be asked to report frequency of cannabis use by reporting whether they used their cannabis product in the morning, afternoon, and evening of each of the preceding 7 days. THC concentration and frequency of use will be compared to baseline cannabis use.

Participants will complete a baseline survey to determine their pattern of cannabis use 35 days after study enrollment. They will be asked to report the brand, name, and THC concentration of the cannabis product(s) they have been using over the 7 preceding days. They will be asked to upload photos of product packaging. They will be asked to report frequency of cannabis use by reporting whether they used their cannabis product in the morning, afternoon, and evening of each of the preceding 7 days. THC concentration and frequency of use will be compared to baseline cannabis use.

The relative value of cannabis products used by participants during this trial will be assessed using the adaptive cannabis purchase task. Specifically, participants will be asked to report the largest amount of their preferred cannabis product they would "purchase" at a series of price points using visual analog scales. Participants will respond by placing a mark on the line to indicate their purchase amount, and responses will be anchored by 'none' and 'all of it' and will be coded as values 0-100. Higher values are indicative of higher value attributed to the cannabis product being used.

The relative value of cannabis products used by participants during this trial will be assessed using the adaptive cannabis purchase task. Specifically, participants will be asked to report the largest amount of their preferred cannabis product they would "purchase" at a series of price points using visual analog scales. Participants will respond by placing a mark on the line to indicate their purchase amount, and responses will be anchored by 'none' and 'all of it' and will be coded as values 0-100. Higher values are indicative of higher value attributed to the cannabis product being used.

The relative value of cannabis products used by participants during this trial will be assessed using the adaptive cannabis purchase task. Specifically, participants will be asked to report the largest amount of their preferred cannabis product they would "purchase" at a series of price points using visual analog scales. Participants will respond by placing a mark on the line to indicate their purchase amount, and responses will be anchored by 'none' and 'all of it' and will be coded as values 0-100. Higher values are indicative of higher value attributed to the cannabis product being used.

The relative value of cannabis products used by participants during this trial will be assessed using the adaptive cannabis purchase task. Specifically, participants will be asked to report the largest amount of their preferred cannabis product they would "purchase" at a series of price points using visual analog scales. Participants will respond by placing a mark on the line to indicate their purchase amount, and responses will be anchored by 'none' and 'all of it' and will be coded as values 0-100. Higher values are indicative of higher value attributed to the cannabis product being used.

The relative value of cannabis products used by participants during this trial will be assessed using the adaptive cannabis purchase task. Specifically, participants will be asked to report the largest amount of their preferred cannabis product they would "purchase" at a series of price points using visual analog scales. Participants will respond by placing a mark on the line to indicate their purchase amount, and responses will be anchored by 'none' and 'all of it' and will be coded as values 0-100. Higher values are indicative of higher value attributed to the cannabis product being used.

The relative value of cannabis products used by participants during this trial will be assessed using the adaptive cannabis purchase task. Specifically, participants will be asked to report the largest amount of their preferred cannabis product they would "purchase" at a series of price points using visual analog scales. Participants will respond by placing a mark on the line to indicate their purchase amount, and responses will be anchored by 'none' and 'all of it' and will be coded as values 0-100. Higher values are indicative of higher value attributed to the cannabis product being used.

Symptoms of cannabis withdrawal will be assessed using the Cannabis Withdrawal Scale (CWS). The CWS consists of 19 questions and assesses withdrawal symptoms as well as the impact of the symptoms on daily activities. The personal experience score ranges from 0-190, with a higher score indicative of more withdrawal symptoms. The negative experience score ranges from 0-190, with a higher number indicative of more negative impact on daily activities.

Symptoms of cannabis withdrawal will be assessed using the Cannabis Withdrawal Scale (CWS). The CWS consists of 19 questions and assesses withdrawal symptoms as well as the impact of the symptoms on daily activities. The personal experience score ranges from 0-190, with a higher score indicative of more withdrawal symptoms. The negative experience score ranges from 0-190, with a higher number indicative of more negative impact on daily activities.

Positive and negative emotions will be assessed using the Positive and Negative Affect Scale (PANAS), which consists of 20 questions, 10 questions assessing positive emotions, and 10 questions assessing negative emotions. Each set of questions is scored on a scale of 10-50, with a higher score indicative of more positive or negative emotions, respectively.

Positive and negative emotions will be assessed using the Positive and Negative Affect Scale (PANAS), which consists of 20 questions, 10 questions assessing positive emotions, and 10 questions assessing negative emotions. Each set of questions is scored on a scale of 10-50, with a higher score indicative of more positive or negative emotions, respectively.

Positive and negative emotions will be assessed using the Positive and Negative Affect Scale (PANAS), which consists of 20 questions, 10 questions assessing positive emotions, and 10 questions assessing negative emotions. Each set of questions is scored on a scale of 10-50, with a higher score indicative of more positive or negative emotions, respectively.

Positive and negative emotions will be assessed using the Positive and Negative Affect Scale (PANAS), which consists of 20 questions, 10 questions assessing positive emotions, and 10 questions assessing negative emotions. Each set of questions is scored on a scale of 10-50, with a higher score indicative of more positive or negative emotions, respectively.

Positive and negative emotions will be assessed using the Positive and Negative Affect Scale (PANAS), which consists of 20 questions, 10 questions assessing positive emotions, and 10 questions assessing negative emotions. Each set of questions is scored on a scale of 10-50, with a higher score indicative of more positive or negative emotions, respectively.

Positive and negative emotions will be assessed using the Positive and Negative Affect Scale (PANAS), which consists of 20 questions, 10 questions assessing positive emotions, and 10 questions assessing negative emotions. Each set of questions is scored on a scale of 10-50, with a higher score indicative of more positive or negative emotions, respectively.

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)

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