Clinical trial NCT04429568: THC Crossover Study
Official title: Cardiovascular Effects of Cannabis Compared to Tobacco Use
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
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
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Tobacco Related Disease Research Program
First posted: 2020-06-12
Enrollment: 14
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Peak plasma concentration
timeFrame: Day 1 of each arm
measure: Time to peak plasma concentration
timeFrame: Day 1 of each arm
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: Day 1 of each arm
measure: Subjective effects between cannabis products using the Marijuana Cravings Questionnaire
timeFrame: Days 1-2 of each arm
measure: Subjective effects between cannabis products using the Visual Analog Scale
timeFrame: Days 1-2 of each arm
measure: Subjective effects between cannabis products using the Drug Effects Questionnaire
timeFrame: Days 1-2 of each arm
measure: Max change of expired carbon monoxide
timeFrame: Days 1-2 of the cannabis arms
measure: Area under the expired carbon monoxide (CO) curve (AUC)
timeFrame: Days 1-2 of the cannabis arms
measure: Differences in metabolites of volatile organic compounds (VOCs)
timeFrame: Days 1-2 of the cannabis arms
measure: Exposure to toxicants between cannabis products
timeFrame: Days 1-2 of the cannabis arms
measure: Cardiovascular effects between cannabis products using heart rate as a measure
timeFrame: Day 1 of each arm
measure: Cardiovascular effects between cannabis products using epinephrine as a measure
timeFrame: Day 2 of each cannabis arm
measure: Cardiovascular effects between cannabis products using platelet activation as a measure
timeFrame: Day 2 of each cannabis arm
measure: Cardiovascular effects between cannabis products using oxidant stress as a measure
timeFrame: Day 2 of each cannabis arm
measure: Cardiovascular effects between cannabis products using endothelial dysfunction as a measure
timeFrame: Day 2 of each cannabis arm
Secondary outcomes:
measure: Toxicant exposure between smoked tobacco and cannabis using expired carbon monoxide as the measure
timeFrame: Day 1 of each arm
measure: Toxicant exposure between smoked tobacco and cannabis using mercapturic acid as the measure
timeFrame: Day 2 of each arm
measure: Toxicant exposure between smoked tobacco and cannabis using use as a measure
timeFrame: Days 1-2 of each arm
measure: Cardiovascular effects between smoked tobacco and cannabis using heart rate as a measure
timeFrame: Day 1 of each arm
measure: Cardiovascular effects between smoked tobacco and cannabis using epinephrine as a measure
timeFrame: Day 2 of each arm
measure: Cardiovascular effects between smoked tobacco and cannabis using platelet activation as a measure
timeFrame: Day 2 of each arm
measure: Cardiovascular effects between smoked tobacco and cannabis using oxidant stress as a measure
timeFrame: Day 2 of each arm
measure: Cardiovascular effects between smoked tobacco and cannabis using endothelial dysfunction as a measure
timeFrame: Day 2 of each arm
measure: Puffing behaviors across all products
timeFrame: Days 1-2 of each arm
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Gideon St. Helen, PhD
role: PRINCIPAL_INVESTIGATOR
References: