Clinical trial NCT06077292: Cannabis THC Potency, Metabolism, and Cognitive Impairment in Young Adults
Official title: Impacts of THC Potency of Cannabis Concentrates and THC Metabolism on Cognitive Impairment in Young Adults
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cannabis Use
THC
Marijuana Use
Cognitive Impairment
THC Vaping
Keywords: Cannabis
Marijuana
High Potency THC
Dabs
Wax
Young Adult
Youth
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Cannabis Public Policy Consulting
First posted: 2023-10-11
Enrollment: 110
Sex: ALL
Minimum age (years): 21
Maximum age (years): 25
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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: 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:

1. Evaluate feasibility of assessing THC consumption, genetic variation in THC metabolism, urinary THC excretion, and cognitive performance in users of high potency cannabis products.
2. Test the effectiveness of an incentivization protocol aimed at encouraging cannabis users to use less potent THC products as a means of harm reduction.
3. 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.
4. 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.
5. 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.
6. Determine whether quantitative urinary THC values correlate with measures of cognitive performance.
7. 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change in Rapid Visual Information Processing Score
timeFrame: Baseline and 5 weeks
measure: Change in Paired Associates Learning score
timeFrame: Baseline and 5 weeks
measure: Change in Delayed Matching-to-Sample Score
timeFrame: Baseline and 5 weeks
measure: Change in Verbal Recognition Memory score
timeFrame: Baseline and 5 weeks
measure: Change in Spatial Working Memory score
timeFrame: Baseline and 5 weeks
measure: Change in One-Touch Stockings of Cambridge score
timeFrame: Baseline and 5 weeks
measure: Change in Stop Signal Task score
timeFrame: Baseline and 5 weeks
Secondary outcomes:
measure: Baseline Urinary THC Excretion
timeFrame: Baseline
measure: Week 1 Urinary THC Excretion
timeFrame: 7-10 days after study enrollment.
measure: Week 2 Urinary THC Excretion
timeFrame: 14-17 days after study enrollment.
measure: Week 3 Urinary THC Excretion
timeFrame: 21-24 days after study enrollment.
measure: Week 4 Urinary THC Excretion
timeFrame: 28-30 days after study enrollment.
measure: Week 5 Urinary THC Excretion
timeFrame: 35-38 days after study enrollment.
Other outcomes:
measure: Urinary THC Excretion in CYP2C9*3 carriers
timeFrame: Baseline
measure: Cognitive Performance in CYP2C9*3 carriers
timeFrame: Baseline
measure: Change in Cannabis Use Disorder Identification Identification Test (CUDIT) score
timeFrame: Baseline and 5 weeks
measure: Change in participant reported depression symptoms
timeFrame: Baseline and 5 weeks
measure: Baseline Participant Reported Cannabis Use
timeFrame: Baseline
measure: Week 1 Participant Reported Cannabis Use
timeFrame: 7 days after study enrollment
measure: Week 2 Participant Reported Cannabis Use
timeFrame: 14 days after study enrollment
measure: Week 3 Participant Reported Cannabis Use
timeFrame: 21 days after study enrollment
measure: Week 4 Participant Reported Cannabis Use
timeFrame: 28 days after study enrollment
measure: Week 5 Participant Reported Cannabis Use
timeFrame: 35 days after study enrollment
measure: Baseline Adapted Cannabis Purchase Task
timeFrame: Baseline
measure: Week 1 Adaptive Cannabis Purchase Task
timeFrame: 7 days after study enrollment
measure: Week 2 Adaptive Cannabis Purchase Task
timeFrame: 14 days after study enrollment
measure: Week 3 Adaptive Cannabis Purchase Task
timeFrame: 21 days after study enrollment
measure: Week 4 Adaptive Cannabis Purchase Task
timeFrame: 28 days after study enrollment
measure: Week 5 Adaptive Cannabis Purchase Task
timeFrame: 35 days after study enrollment
measure: Baseline Participant Reported Cannabis Withdrawal Symptoms
timeFrame: Baseline
measure: Week 5 Participant Reported Cannabis Withdrawal Symptoms
timeFrame: 35 days after study enrollment
measure: Baseline Participant Reported Affect
timeFrame: Baseline
measure: Week 1 Participant Reported Affect
timeFrame: 7 days after study enrollment
measure: Week 2 Participant Reported Affect
timeFrame: 14 days after study enrollment
measure: Week 3 Participant Reported Affect
timeFrame: 21 days after study enrollment
measure: Week 4 Participant Reported Affect
timeFrame: 28 days after study enrollment
measure: Week 5 Participant Reported Affect
timeFrame: 35 days after study enrollment
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Veronika Mesheriakova, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cannabis Public Policy Consulting
name: Michael Sofis, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sachse-Seeboth C, Pfeil J, Sehrt D, Meineke I, Tzvetkov M, Bruns E, Poser W, Vormfelde SV, Brockmoller J. Interindividual variation in the pharmacokinetics of Delta9-tetrahydrocannabinol as related to genetic polymorphisms in CYP2C9. Clin Pharmacol Ther. 2009 Mar;85(3):273-6. doi: 10.1038/clpt.2008.213. Epub 2008 Nov 12.
citation: Murray RM, Quigley H, Quattrone D, Englund A, Di Forti M. Traditional marijuana, high-potency cannabis and synthetic cannabinoids: increasing risk for psychosis. World Psychiatry. 2016 Oct;15(3):195-204. doi: 10.1002/wps.20341.
citation: Ramaekers JG, Kauert G, van Ruitenbeek P, Theunissen EL, Schneider E, Moeller MR. High-potency marijuana impairs executive function and inhibitory motor control. Neuropsychopharmacology. 2006 Oct;31(10):2296-303. doi: 10.1038/sj.npp.1301068. Epub 2006 Mar 29.
citation: D'Souza DC, Ganesh S, Cortes-Briones J, Campbell MH, Emmanuel MK. Characterizing psychosis-relevant phenomena and cognitive function in a unique population with isolated, chronic and very heavy cannabis exposure. Psychol Med. 2020 Oct;50(14):2452-2459. doi: 10.1017/S0033291719002721. Epub 2019 Oct 16.
citation: Bidwell LC, Martin-Willett R, Karoly HC. Advancing the science on cannabis concentrates and behavioural health. Drug Alcohol Rev. 2021 Sep;40(6):900-913. doi: 10.1111/dar.13281. Epub 2021 Mar 30.
citation: Bourque J, Potvin S. Cannabis and Cognitive Functioning: From Acute to Residual Effects, From Randomized Controlled Trials to Prospective Designs. Front Psychiatry. 2021 Jun 10;12:596601. doi: 10.3389/fpsyt.2021.596601. eCollection 2021.