PK/PD of Vaping THC-containing Liquids vs. Smoked Cannabis

Study Overview
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Brief Summary
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We will conduct a randomized, within-subjects clinical study to compare short-term pharmacokinetic (PK) and pharmacodynamic (PD) effects of Δ9-tetrahydrocannabinol (THC) vaping liquids vs. smoked cannabis containing 6 equivalent standard THC units (5 mg THC=1 Standard THC Unit (STU)) in healthy community members who are current users of both products. While smoking cannabis remains the most common mode of THC use among adults and youth, alternative modes of delivery, such as Electronic Vaping Products (EVPs), are becoming increasingly popular for the delivery of cannabinoids. Declining cannabis risk perceptions, increasing normalization of cannabis, greater legal access and availability to cannabis, ease of administration, and ability to conceal vaped THC use have likely contributed to increasing prevalence of use throughout the population across all age groups. Comparing vaping THC containing liquids with smoking cannabis can serve as an important benchmark for evaluating the delivery and effects of THC vaping products and, their relative safety

Detailed Description
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PRIMARY OBJECTIVE: I. Compare the PK/PD profiles of delta-9 tetrahydrocannabinol (THC) from equivalent standard THC doses (30mg) administered as vaped THC liquid vs. smoked cannabis using a within-subject design. SECONDARY OBJECTIVES: I. Safety PRIMARY OBJECTIVE: I. Compare the PK/PD profiles of delta-9 tetrahydrocannabinol (THC) from equivalent standard THC doses (30mg) administered as vaped THC liquid vs. smoked cannabis using a within-subject design. SECONDARY OBJECTIVES: I. Safety

Official Title
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A Randomized Within-Subject Cross-Over Study to Compare Short-Term PK/PD Effects of Vaping THC-containing Liquids vs. Smoked Cannabis

Conditions
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Cigarette Smoking-Related Carcinoma

Intervention / Treatment
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* Behavioral: Vape device
* Behavioral: Joint
* Drug: Marijuana via vape device
* Drug: Marijuana via joint


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 21 years of age Report concurrent use of commercial (medical or recreational) smoked cannabis and THC vaping cartridges for at least 3 months prior to enrollment Report smoking cannabis and THC- vaping liquid use at the potency level of the study product at least weekly (4x/month) Report of not currently trying to become pregnant (females). Women of childbearing potential must be willing to provide a urine sample and test negative prior to receiving any study-related products/procedures Willing to complete a THC saliva test to check for recent use (NarcoCheck Ref#:NCE-STHC-1) and semi -quantitative urinary tetrahydrocannabinol-carboxylic acid (THCA) rapid test (NarcoCheck® THC PreDosage) during baseline testing, prior to receiving any study-related products Participant must understand the investigational nature of this study and sign an Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: • Illegal or non-prescription drug use within the past 90 days. As detected by NacroCheck® Évolutive® (detection in human urine of the 12 most currently abused drugs) at the first session and prior to receiving any study product Report 2 or more drinking occasions/week with 4 or more drinks/occasion Report of daily nicotine use Current or prior diagnosis of any psychotic disorders Current or prior diagnosis of chronic heart conditions Current or prior diagnosis of any respiratory condition Pregnant or currently trying to become pregnant (females) Detection level 4-5 (>300 ng/mL) from a semi-quantitative urinary THCA rapid test (NarcoCheck® THC PreDosage) Unwilling or unable to follow protocol requirements Any condition which in the Investigator's opinion deems the participant an unsuitable candidate for participation

Ages Eligible for Study
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Minimum Age: 21 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1 (Vape followed by Joint)<br>Patients receive a vape device with THC containing liquid and consume the provided amount in up to 10 minutes. 7 to 14 days later patients receive a cannabis joint and smoke the provided joint in up to 10 minutes. Patients also undergo blood sample collection throughout the study. | Behavioral: Vape device<br>* Consume THC via vape defice<br>* Other names: Behavioral Modification;Drug: Marijuana via joint<br>* Given via joint<br>* Other names: Cannibis;|
| Experimental: Arm II (Joint followed by Vape)<br>Patients receive a cannabis joint and smoke the provided joint in up to 10 minutes. 7 to 14 days later patients receive a vape device with THC containing liquid and consume the provided amount in up to 10 minutes. Patients also undergo blood sample collection throughout the study. | Behavioral: Joint<br>* Consume THC via joint<br>* Other names: Behavior Modification;Drug: Marijuana via vape device<br>* Given via vape device<br>* Other names: Cannibis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) | Blood samples will be collected for plasma levels of THC. All individual pharmacokinetic (PK) parameters will be derived from plasma THC concentrations-versus-time data by non-compartmental analysis using Phoenix WinNonlin, corrected for baseline THC concentrations. Mean differences for each measure will be compared between the experimental (THC vaping) and active control (smoked cannabis) conditions, and by sex | From baseline to 360 minutes after consuming product | 
| Area under the plasma concentration time curve from 0-360 minutes ((AUC^0-360) | Blood samples will be collected for plasma levels of THC. All individual pharmacokinetic (PK) parameters will be derived from plasma THC concentrations-versus-time data by non-compartmental analysis using Phoenix WinNonlin, corrected for baseline THC concentrations. Mean differences for each measure will be compared between the experimental (THC vaping) and active control (smoked cannabis) conditions, and by sex. | From baseline to 360 minutes after consuming product | 
| Time to maximum concentration of THC in plasma (Tmax) | Blood samples will be collected for plasma levels of THC.All individual pharmacokinetic (PK) parameters will be derived from plasma THC concentrations-versus-time data by non-compartmental analysis using Phoenix WinNonlin, corrected for baseline THC concentrations. Mean differences for each measure will be compared between the experimental (THC vaping) and active control (smoked cannabis) conditions, and by sex. | From baseline to 360 minutes after consuming product | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | Number of subjects who experienced an adverse event during the study . | Up to 360 minutes after consuming product | 
| Puffing behaviors | Measure changes in subject puffing behavior by mean number of puffs and duration | Through study completion, an average of 14 days | 
| Short term effects of THC | The Drug Effect Questionnaire (DEQ) rates sixteen component items using a visual analog scale (0-100) to examine drug effects pre- and post-use. | Through Study completion, an average of 14 days | 
| Cognitive Performance as assessed by the Digit Symbol Substitution Task (DSST) | computerized sensitive and valid assessment of cognitive dysfunction that correlates with real-world functional ability to complete daily tasks. The outcome is the total number of correct responses. | Through study completion, an average of 14 days | 
| Paced Auditory Serial Addition Task (PASET) | a validated measure used to assess attention, concentration, working memory, and information processing. | Through study completion , an average of 14 days |