THC Crossover Study

NCT04429568 | Completed DMC

• 1 other identifier: 17-24117
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

This is a randomized, crossover study enrolling experienced dual cannabis-tobacco smokers (N=18) to describe the differences in THC and toxicant exposure, examining pharmacokinetic, subjective, and cardiovascular effects from smoking and vaping dry herb cannabis. This study will also examine the differences in toxicant exposure and cardiovascular disease risk between smoking cannabis and smoking tobacco cigarettes.

Conditions

THC; Cannabis; Cannabis Smoking; Cannabis Use, Unspecified; Cigarette Smoking; Tobacco Use; Nicotine Dependence; Nicotine Withdrawal; Cardiovascular Risk Factor

Keywords

vape; cannabis; tobacco cigarette; thc; marijuana; smoking

Outcome Measures

Primary Outcomes (15)

• Peak plasma concentration

  To assess the differences between smoked and vaped cannabis, we will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.

  Day 1 of each arm

• Time to peak plasma concentration

  To assess the differences of these variables between smoked and vaped cannabis, we will determine the time to max concentration (Tmax) using plasma THC concentrations from the standardized sessions.

  Day 1 of each arm

• Area under the plasma concentration versus time curve (AUC)

  To assess the differences of these variables between smoked and vaped cannabis, we will determine the AUC using plasma THC concentrations from the standardized sessions.

  Day 1 of each arm

• Subjective effects between cannabis products using the Marijuana Cravings Questionnaire

  We will assess measures from the Marijuana Cravings Questionnaire (MCQ) and compare them between smoked and vaped cannabis.

  Days 1-2 of each arm

• Subjective effects between cannabis products using the Visual Analog Scale

  We will assess measures from the Visual Analog Scale (VAS) and compare them between smoked and vaped cannabis.

  Days 1-2 of each arm

• Subjective effects between cannabis products using the Drug Effects Questionnaire

  We will assess measures from the Drug Effects Questionnaire (DEQ) and compare them between smoked and vaped cannabis.

  Days 1-2 of each arm

• Max change of expired carbon monoxide

  We will examine differences in max change of expired carbon monoxide (CO) from day 1 between smoked and vaped cannabis.

  Days 1-2 of the cannabis arms

• Area under the expired carbon monoxide (CO) curve (AUC)

  We will examine differences in integrated AUC of expired carbon monoxide from day 1 between smoked and vaped cannabis.

  Days 1-2 of the cannabis arms

• Differences in metabolites of volatile organic compounds (VOCs)

  We will examine differences in 12-hour urine mercapturic acid metabolites of volatile organic compounds (from day 2) between smoked and vaped cannabis.

  Days 1-2 of the cannabis arms

• Exposure to toxicants between cannabis products

  We will also examine how measures of use (number of puss, amount use, number of use episodes) correlate with biomarker concentrations between smoked and vaped cannabis.

  Days 1-2 of the cannabis arms

• Cardiovascular effects between cannabis products using heart rate as a measure

  We will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 30 minutes after the standardized session (day 1) between smoked and vaped cannabis.

  Day 1 of each arm

• Cardiovascular effects between cannabis products using epinephrine as a measure

  Urine catecholamine excretion, particularly epinephrine, will be examined in 12-hour urines and compared between smoked and vaped cannabis.

  Day 2 of each cannabis arm

• Cardiovascular effects between cannabis products using platelet activation as a measure

  We will examine differences in blood and urine biomarkers of platelet activation between smoked and vaped cannabis.

  Day 2 of each cannabis arm

• Cardiovascular effects between cannabis products using oxidant stress as a measure

  We will examine differences in blood and urine biomarkers of oxidant stress between smoked and vaped cannabis.

  Day 2 of each cannabis arm

• Cardiovascular effects between cannabis products using endothelial dysfunction as a measure

  We will examine differences in blood and urine biomarkers of endothelial dysfunction and inflammation between smoked and vaped cannabis.

  Day 2 of each cannabis arm

Secondary Outcomes (9)

• Toxicant exposure between smoked tobacco and cannabis using expired carbon monoxide as the measure

  Day 1 of each arm

• Toxicant exposure between smoked tobacco and cannabis using mercapturic acid as the measure

  Day 2 of each arm

• Toxicant exposure between smoked tobacco and cannabis using use as a measure

  Days 1-2 of each arm

• Cardiovascular effects between smoked tobacco and cannabis using heart rate as a measure

  Day 1 of each arm

• Cardiovascular effects between smoked tobacco and cannabis using epinephrine as a measure

  Day 2 of each arm

Study Arms (3)

Smoked Cannabis, Vaped Cannabis, or Tobacco Cigarette

OTHER

* Abstinence from any product night before hospital admission * Standardized Session of assigned product: smoked cannabis, vaped cannabis, or tobacco cigarette * 6-hr abstinence and blood draws (PK) * 2 hr Free use session w/ video monitoring * Free use of assigned product * 12-hr cardiovascular (CV) monitoring * Circadian blood draws * 12-hr urine collection

Other: Smoked Cannabis; Other: Vaped Cannabis; Other: Tobacco Cigarette

Either of the 2 remaining products

OTHER

* Abstinence from any product night before hospital admission * Standardized Session of assigned product: smoked cannabis, vaped cannabis, or tobacco cigarette * 6-hr abstinence and blood draws (PK) * 2 hr Free use session w/ video monitoring * Free use of assigned product * 12-hr CV monitoring * Circadian blood draws * 12-hr urine collection

Other: Smoked Cannabis; Other: Vaped Cannabis; Other: Tobacco Cigarette

Remaining product

OTHER

* Abstinence from any product night before hospital admission * Standardized Session of assigned product: smoked cannabis, vaped cannabis, or tobacco cigarette * 6-hr abstinence and blood draws (PK) * 2 hr Free use session w/ video monitoring * Free use of assigned product * 12-hr CV monitoring * Circadian blood draws * 12-hr urine collection

Other: Smoked Cannabis; Other: Vaped Cannabis; Other: Tobacco Cigarette

Interventions

Smoked Cannabis OTHER

Cannabis will be purchased by the participants and reimbursed the full cost by the study. Participants will be asked to purchase enough to last 2 full days of use. To reduce variability between products, participants will be asked to purchase cannabis from one dispensary near the research facility (Purple Star MD at 2520 Mission St., San Francisco). Receipt must be provided to study staff.

Either of the 2 remaining products; Remaining product; Smoked Cannabis, Vaped Cannabis, or Tobacco Cigarette

Vaped Cannabis OTHER

Cannabis will be purchased by the participants and reimbursed the full cost by the study. Participants will be asked to purchase enough to last 2 full days of use. To reduce variability between products, participants will be asked to purchase cannabis from one dispensary near the research facility (Purple Star MD at 2520 Mission St., San Francisco). Receipt must be provided to study staff. All participants will use the study-provided PAX® (PAX 2) dry herb vaporizer, one of the most popular handheld vaporizers.

Either of the 2 remaining products; Remaining product; Smoked Cannabis, Vaped Cannabis, or Tobacco Cigarette

Tobacco Cigarette OTHER

Tobacco cigarettes of participants' choice (usual brand) will be provided by research staff for use on the study.

Either of the 2 remaining products; Remaining product; Smoked Cannabis, Vaped Cannabis, or Tobacco Cigarette

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy on the basis of medical history and limited physical examination, as described below:
• Heart rate \< 105 beats per minute (BPM); Systolic Blood Pressure \< 160 and \> 90\*; Diastolic Blood Pressure \< 100 and \> 50\*
• \*Considered out of range if both machine and manual readings are above/below these thresholds.
• Current regular user of cannabis who smokes cannabis as joint or blunt at least 3 times a week for past 3 months
• History of cannabis vaporizer use or willingness to use the vaporizer in the study
• Current tobacco cigarette use who smokes ≥ 5 cigarettes per day
• Saliva cotinine ≥ 50 ng/ml
• Test positive for D-9-tetrahydrocannabinol (THC) at screening and self-report of cannabis use

You may not qualify if:

• Unstable medical conditions:
• Heart disease; Uncontrolled hypertension; Thyroid disease (okay if controlled with medication); Diabetes; Hepatitis B or C or Liver disease; Glaucoma; Prostatic hypertrophy
• Psychiatric conditions:
• Concurrent regular use of smokeless tobacco or pipes \[occasional users of these products may be enrolled if they agree to abstain from their use during the period of the study\]
• Medications:
• Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6 (Example: rifampicin, dexamethasone, phenobarbital, and other anticonvulsant drugs).; Concurrent use of nicotine-containing medications; Psychiatric medications: current regular use of any psychiatric medications with the exception of Selective Serotonin Reuptake Inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) and current evaluation by the study physician that the participant is otherwise healthy, stable, and able to participate.
• Other/Misc. Chronic Health Conditions:
• Oral thrush; Fainting; Untreated thyroid disease; Other "life threatening illnesses" as per study physician's discretion
• Pregnancy:
• Pregnancy (self-reported and urine pregnancy test); Breastfeeding (determined by self-report)
• Drug/Alcohol Dependence:
• Alcohol or illicit drug dependence within the past 12 months with the exception of those who have recently completed an alcohol/drug treatment program; Positive toxicology test at the screening visit (THC \& prescribed medications okay); Methadone replacement therapy
• Concurrent participation in another clinical trial
• Inability to communicate in English
• History of marijuana-induced psychosis or paranoia after smoking marijuana

Sponsors & Collaborators

• University of California, San Francisco: lead
• Tobacco Related Disease Research Program: collaborator

Study Sites (2)

Zuckerberg San Francisco General Hospital

San Francisco, California, 94110, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Marijuana Abuse; Marijuana Smoking; Cigarette Smoking; Tobacco Use; Tobacco Use Disorder; Vaping; Wiskott-Aldrich Syndrome; Smoking

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Marijuana Use; Behavior; Smoking, Non-Tobacco Products; Tobacco Smoking; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphopenia; Leukopenia; Cytopenia; Hemorrhagic Disorders; Leukocyte Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked; Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Gideon St. Helen, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2019
• First Posted: June 12, 2020
• Study Start: October 30, 2020
• Primary Completion: June 25, 2024
• Study Completion: June 25, 2024
• Last Updated: July 1, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)