THC Crossover Study

Nicotine Dependence Clinical Trial

— TRDRP  

Official title:

Cardiovascular Effects of Cannabis Compared to Tobacco Use

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04429568
• Other study ID #: 17-24117
• Status: Recruiting
• Phase: N/A
• Start date: October 30, 2020
• Est. completion date: June 30, 2024

Study information

• Verified date: April 2024
• Source: University of California, San Francisco
• Contact: Lisa Lawrence
• Phone: (415) 608-4864
• Email: Lisa.Lawrence[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Experienced dual cannabis-tobacco smokers will participate in a within-subject crossover study with three blocks: smoked cannabis (purchased by participants from a local dispensary), dry herb cannabis vaporizer, and usual brand tobacco cigarette. Each block will consist of 2 consecutive days on an inpatient research ward. The first inpatient day of each block will comprise of two sessions: (1) The first session will be a standardized bout to compare pharmacokinetic, physiologic, and subjective effects of cannabis and tobacco use; (2) after 6 hours of abstinence, the second session will be ad libitum access to the assigned product for 2 hours to compare subjective effects (reward, satisfaction, craving reduction) and use patterns. The second inpatient day will consist of ad libitum use of the assigned product from 8:00 in the morning to midnight. An abstinence day will be added after the second day of the last block to assess exposure and effects biomarkers during a period of abstinence from cannabis (smoked/vaped) or tobacco.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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:

Current or past schizophrenia, and/or current or past bipolar disorder; Adult onset attention deficit hyperactivity disorder (ADHD); Participants with current or past depression and/or anxiety disorders will be reviewed by the study physician and considered for inclusion; History of psychiatric hospitalizations are not exclusionary, but study participation will be determined as per study physician's approval

• 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
• Scoring a 2 or higher on the Severity of Dependence Scale for cannabis use
• Planning to quit smoking or vaping within the next 60 days

Related Conditions & MeSH terms

• Cannabis
• Cannabis Smoking
• Cannabis Use, Unspecified
• Cardiovascular Risk Factor
• Cigarette Smoking
• Marijuana Abuse
• Nicotine Dependence
• Nicotine Withdrawal
• THC
• Tobacco Use
• Tobacco Use Disorder

Intervention

Other:
• Smoked Cannabis
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.
• Vaped Cannabis
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.
• Tobacco Cigarette
Tobacco cigarettes of participants' choice (usual brand) will be provided by research staff for use on the study.

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California
United States	Zuckerberg San Francisco General Hospital	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Tobacco Related Disease Research Program

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Toxicant exposure between smoked tobacco and cannabis using expired carbon monoxide as the measure	We will examine differences in expired carbon monoxide (CO) from day 1 (both max change and integrated AUC of expired CO) between smoked tobacco and cannabis.	Day 1 of each arm
Secondary	Toxicant exposure between smoked tobacco and cannabis using mercapturic acid as the measure	We will examine differences in 12-hour urine mercapturic acid metabolites of volatile organic compounds (VOCs) (from day 2) between smoked tobacco and cannabis.	Day 2 of each arm
Secondary	Toxicant exposure between smoked tobacco and cannabis using use as a measure	We will also examine how measures of use (number of puffs, amount use, number of use episodes) correlate with biomarker concentrations between smoked tobacco and cannabis.	Days 1-2 of each arm
Secondary	Cardiovascular effects between smoked tobacco and cannabis 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 tobacco and cannabis.	Day 1 of each arm
Secondary	Cardiovascular effects between smoked tobacco and cannabis using epinephrine as a measure	Urine catecholamine excretion, particularly epinephrine, will be examined in 12-hour urines.	Day 2 of each arm
Secondary	Cardiovascular effects between smoked tobacco and cannabis using platelet activation as a measure	We will examine differences in blood and urine biomarkers of platelet activation between smoked tobacco and cannabis.	Day 2 of each arm
Secondary	Cardiovascular effects between smoked tobacco and cannabis using oxidant stress as a measure	We will examine differences in blood and urine biomarkers of oxidant stress between smoked tobacco and cannabis.	Day 2 of each arm
Secondary	Cardiovascular effects between smoked tobacco and cannabis using endothelial dysfunction as a measure	We will examine differences in blood and urine biomarkers of endothelial dysfunction and inflammation between smoked tobacco and cannabis.	Day 2 of each arm
Secondary	Puffing behaviors across all products	We will examine how puffing behaviors are different between all products (smoked and vaped cannabis, as well as with smoked tobacco cigarettes) and how they correlate with toxicant biomarker concentrations. Vaping topography measures will be obtained from frame by frame analysis of high definition videos.	Days 1-2 of each arm