Clinical trial NCT06334016: Evaluating the Delivery and Effects of THC Vaping Liquids in the Bloodstream
Official title: Acute Effects of Sequential Nicotine Vaping on the Pharmacokinetic and Pharmacodynamic Properties of Vaped THC: A Double-Blind, Placebo-Controlled, Randomized Within-Subject Crossover Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Cannabis Dependence
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2024-03-27
Enrollment: 60
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Within-subject crossover study
Primary purpose: BASIC_SCIENCE

Brief summary: This clinical trial assesses differences in the delivery of THC to the bloodstream depending on whether nicotine vapes are used before or after THC. While there has been much recent publicity about vaping products and concern about their safety considering their increasing use for THC administration, the THC delivery profile associated with THC liquid vaping products in human subjects is currently unknown. Importantly, how the delivery to the bloodstream of THC vaping liquids compare to delivery from smoked cannabis, which is the most used method of cannabis delivery, will serve as an important benchmark for evaluating the delivery and effects of THC vaping products, and their relative safety.

Detailed description: PRIMARY OBJECTIVES:

I. Assess pharmacokinetic (PK)/pharmacodynamic (PD) profiles of THC vaping liquids administered with co-use of vaped nicotine.

II. Outcomes of interest will be assessed overall, and according to biological sex.

SECONDARY OBJECTIVES:

I. Safety. II. Assessment of differences in puffing behaviors. III. Short-term subjective drug effects, and cognitive performance following THC use without nicotine versus (vs.) THC use with pre-nicotine use vs. THC use with post-nicotine use in current consumers of both vaped cannabis and vaped nicotine products.

OUTLINE: Participants are randomized to 1 of 3 arms.

ARM A: Participants complete 3 vaping sessions separated by 7-14 days on study:

* VISIT 1: Participants vape placebo nicotine for 10 minutes, followed by THC for 10 minutes, and then placebo nicotine again for 10 minutes.
* VISIT 2: Participants vape nicotine for 10 minutes, followed by THC for 10 minutes, and then placebo nicotine for 10 minutes.
* VISIT 3: Participants vape placebo nicotine for 10 minutes, followed by THC for 10 minutes, and then nicotine for 10 minutes.

ARM B: Participants complete 3 vaping sessions separated by 7-14 days on study:

* VISIT 1: Participants vape nicotine for 10 minutes, followed by THC for 10 minutes, and then placebo nicotine for 10 minutes.
* VISIT 2: Participants vape placebo nicotine for 10 minutes, followed by THC for 10 minutes, and then nicotine for 10 minutes.
* VISIT 3: Participants vape placebo nicotine for 10 minutes, followed by THC for 10 minutes, and then placebo nicotine again for 10 minutes.

ARM C: Participants complete 3 vaping sessions separated by 7-14 days on study:

* VISIT 1: Participants vape placebo nicotine for 10 minutes, followed by THC for 10 minutes, and then nicotine for 10 minutes.
* VISIT 2: Participants vape placebo nicotine for 10 minutes, followed by THC for 10 minutes, and then placebo nicotine again for 10 minutes.
* VISIT 3: Participants vape nicotine for 10 minutes, followed by THC for 10 minutes, and then placebo nicotine for 10 minutes.

All participants also undergo blood sample collection throughout the trial.

After completion of study intervention, participants are followed up at 30 days.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 21 years of age; (self-reported on screening, verified at study visit).
* Report use of commercial THC vaping cartridges for at least 3 months prior to enrollment; (self-reported).
* Experience with THC potency at or above the study product AND experience with chasing THC with nicotine (at least monthly); (self-reported).
* Report use of THC vaping liquids at least weekly (4x/month); (self-reported).
* Daily use of nicotine vaping products containing 5% nicotine for at least 3 months prior to enrollment; (self-reported).
* 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), semi-quantitative urinary THCA rapid test (NarcoCheck® THC Pre Dosage), and an illicit drug urine test (NarcoCheck® Évolutive®) during baseline testing, prior to receiving any study-related products.
* Negative THC saliva test (NarcoCheck Ref#: NCE-S-THC-1), detection level 1-3 on urinary THCA rapid test (NarcoCheck® THC PreDosage), and illicit drug screen negative for all drugs except THC (NarcoCheck® Évolutive®).
* Willing to abstain from nicotine use for 8 hours prior to each study session and abstain from cannabis use 7 days prior to each session.
* 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:

* Detection level 4-5 (\> 300 ng/mL) on urinary THCA rapid test (NarcoCheck® THC PreDosage Ref#: DOA-M03-9B) and a positive result on THC saliva test (NarcoCheck Ref#: NCE-S-THC-1).
* Illegal or non-prescription drug use within the past 90 days. As detected by NarcoCheck® Évolutive® (detection in human urine of the 12 most currently abused drugs) at the first session and prior to receiving any study product. THC use detected by NarcoCheck® Évolutive® is permitted
* Illegal or non-prescription drug use/alcohol substance use disorder (SUD) within the past year; (self-reported).
* Report 2 or more drinking occasions/week with 4 or more drinks/occasion; (self-reported).
* Report of daily cigarette use; (self-reported).
* Current or prior diagnosis of schizophrenia, bipolar disorder, or other severe psychotic mental illness; (self-reported).
* Current or prior diagnosis of myocardial infarction, arrhythmia, or congestive heart failure (self-reported).
* Current or prior cancer diagnosis.
* Pregnant, currently trying to become pregnant, or breastfeeding (females); (self-reported; pregnancy validated on study visit by urine test).
* Regular use of medications that contain nicotine, induce CYP2A6, stimulants, or sympatholytics (e.g., beta-blockers); (self-reported).
* Unwilling or unable to follow protocol requirements.
* Any condition which in the Investigator's opinion deems the participant an unsuitable candidate for participation.
* The following special populations will be excluded:

  * Cognitively impaired adults/adults with impaired decision-making capacity
  * Individuals who are not yet adults (infants, children, teenagers)
  * Pregnant women
  * Prisoners
* No children or person under the age of 21 will be involved in the study. While those under 21 may use cannabis smoked or vaping products, the legal age of purchasing and using those products in New York State is 21. The current legal age to purchase and use tobacco products in New York State (NYS) is 21. Thus, our provision of study product to adults aged 21 and older is in line with current NYS law.

Primary outcomes:
measure: Maximum concentration of THC in plasma (Cmax)
timeFrame: Up to 21 days
measure: Area under the plasma concentration-time curve from 0-360 minutes (AUC0-360)
timeFrame: Up to 21 days
measure: Time to maximum concentration of THC in plasma (Tmax)
timeFrame: Up to 21 days
Secondary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: Up to 30 days after completion of study intervention
measure: Puffing behaviors
timeFrame: Up to 21 days
measure: Puffing behaviors
timeFrame: Up to 21 days
measure: Short-term drug effects
timeFrame: Up to 21 days
measure: Marijuana Withdrawal Checklist [MWC)
timeFrame: Up to 21 days
measure: Digit Symbol Substitution Task (DSST)
timeFrame: Up to 21 days
measure: Paced Auditory Serial Addition Task (PASET)
timeFrame: Up to 21 days
measure: Tobacco Craving Questionnaire (Short Form)
timeFrame: Up to 21 days
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Danielle M Smith
role: PRINCIPAL_INVESTIGATOR
References: