Characterization of Endocannabinoid and Endogenous Opioid Levels in Adolescents With Cannabis Use Disorder

Study Overview
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Brief Summary
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This project seeks to learn more about the effects of cannabis use on the endocannabinoid system and endogenous opioid systems in adolescents to address a fundamental gap in knowledge and identify biomarkers that may help distinguish youth who relapse from youth who remain sober.

Detailed Description
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Learning the effects of cannabis use on the endocannabinoid system and endogenous opioid systems in adolescents addresses a fundamental gap in knowledge and may identify biomarkers that help distinguish youth who relapse from youth who remain sober. The specific aims of the project are to: Measure endocannabinoid (eCB) and endogenous opioid (endorphin) levels in the blood of adolescents who use cannabis regularly and adolescents who never use cannabis. We expect eCB and endorphin levels to differ significantly in adolescents who use cannabis regularly compared to adolescents who do not. Characterize circulating eCB and endorphin levels at baseline, during abstinence, and after natural resumption of cannabis use. Collect data to evaluate cannabis craving and to test for association of craving with eCB and endorphin levels in adolescents who use cannabis regularly. We expect that larger changes in eCB and endorphin levels will be associated with higher craving scores.

Official Title
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Characterization of Endocannabinoid and Endogenous Opioid Levels in Adolescents

Conditions
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Cannabis Use

Intervention / Treatment
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* Behavioral: Contingency Management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 14 to 25 years of age. Use cannabis at least twice a week for the past month. Exclusion Criteria: Refusal of valid written consent, Current psychosis, Obvious intoxication, Current risk of suicide, Violence sufficiently great to interfere with evaluation or to endanger evaluators, Obvious intellectual deficiency as noted during the informed consent process, or inability of patient or family to comply with the study protocol. Use of other illicit drugs in the past 90 days by self-report or detected by urine drug test. Use of opioid medications for medical or recreational purposes currently or within the past 90 days. Does not have access to an Internet connected devise or cannot use Zoom.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 25 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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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: The contingency management (CM) procedure will consist of a four-week abstinence-based incentive program. At the initial visit, participants will be instructed to refrain from using cannabis for the next month and abstinence will be monitored by urine and saliva drug tests. Participants will be paid at each study visit for attendance and abstinence. CM payment rates for abstinence will revert to the initial payment level following a missed study visit or if THC levels rise or are detected by saliva drug screen, respectively.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Contingency Management<br>Abstinence will be rewarded following a contingency management (CM) payment scale. | Behavioral: Contingency Management<br>* Participants will be paid for abstinence at each study visit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cannabinoid levels in blood | Cannabinoid levels in blood: Our primary measure will be 11-nor-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) concentrations in whole blood, which have been demonstrated to be a reliable quantitative measure of cannabis use over the past few weeks35. We will measure an additional 10 cannabinoids [THC, 11-hydroxy-THC, THC-glucuronide, cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), cannabidivarin (CBDV), tetrahydro-cannabivarin (THCV), and THCV-COOH]34, which will be visually inspected to identify potential secondary outcomes. | Collected at Baseline | 
| Cannabinoid levels in blood | Cannabinoid levels in blood: Our primary measure will be 11-nor-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) concentrations in whole blood, which have been demonstrated to be a reliable quantitative measure of cannabis use over the past few weeks35. We will measure an additional 10 cannabinoids [THC, 11-hydroxy-THC, THC-glucuronide, cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), cannabidivarin (CBDV), tetrahydro-cannabivarin (THCV), and THCV-COOH]34, which will be visually inspected to identify potential secondary outcomes. | Collected at Week 2 | 
| Cannabinoid levels in blood | Cannabinoid levels in blood: Our primary measure will be 11-nor-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) concentrations in whole blood, which have been demonstrated to be a reliable quantitative measure of cannabis use over the past few weeks35. We will measure an additional 10 cannabinoids [THC, 11-hydroxy-THC, THC-glucuronide, cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), cannabidivarin (CBDV), tetrahydro-cannabivarin (THCV), and THCV-COOH]34, which will be visually inspected to identify potential secondary outcomes. | Collected at Week 4 | 
| Cannabinoid levels in blood | Cannabinoid levels in blood: Our primary measure will be 11-nor-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) concentrations in whole blood, which have been demonstrated to be a reliable quantitative measure of cannabis use over the past few weeks35. We will measure an additional 10 cannabinoids [THC, 11-hydroxy-THC, THC-glucuronide, cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), cannabidivarin (CBDV), tetrahydro-cannabivarin (THCV), and THCV-COOH]34, which will be visually inspected to identify potential secondary outcomes. | Collected at Week 8 | 
| Endocannabinoid levels in blood | We will measure endocannabinoid (eCB) levels AEA and 2-AG, the primary eCBs, in whole blood. | Collected at Baseline | 
| Endocannabinoid levels in blood | We will measure endocannabinoid (eCB) levels AEA and 2-AG, the primary eCBs, in whole blood. | Collected at Week 2 | 
| Endocannabinoid levels in blood | We will measure endocannabinoid (eCB) levels AEA and 2-AG, the primary eCBs, in whole blood. | Collected at Week 4 | 
| Endocannabinoid levels in blood | We will measure endocannabinoid (eCB) levels AEA and 2-AG, the primary eCBs, in whole blood. | Collected at Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endorphin levels in blood | Endorphin levels in blood: Circulating beta Endorphin (b-EP) levels will be quantified using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. | Collected at Baseline | 
| Endorphin levels in blood | Endorphin levels in blood: Circulating beta Endorphin (b-EP) levels will be quantified using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. | Collected at Week 2 | 
| Endorphin levels in blood | Endorphin levels in blood: Circulating beta Endorphin (b-EP) levels will be quantified using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. | Collected at Week 4 | 
| Endorphin levels in blood | Endorphin levels in blood: Circulating beta Endorphin (b-EP) levels will be quantified using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. | Collected at Week 8 | 
| Cannabis Craving | Cannabis craving: The Marijuana Craving Questionnaire (MCQ) will be used to assess cannabis craving. | Collected at Baseline | 
| Cannabis Craving | Cannabis craving: The Marijuana Craving Questionnaire (MCQ) will be used to assess cannabis craving. | Collected at Week 2 | 
| Cannabis Craving | Cannabis craving: The Marijuana Craving Questionnaire (MCQ) will be used to assess cannabis craving. | Collected at Week 4 | 
| Cannabis Craving | Cannabis craving: The Marijuana Craving Questionnaire (MCQ) will be used to assess cannabis craving. | Collected at Week 8 |