Clinical trial NCT05999383: Understanding the Clinical Pharmacology of Marijuana-Tobacco Co-administration
Official title: Understanding the Clinical Pharmacology of Marijuana-Tobacco Co-administration
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: THC
Cannabis
Cannabis Use
Cannabis Smoking
Tobacco Use
Vaping
Keywords: THC
Cannabis
Marijuana
Nicotine
Vape
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
name: National Institutes of Health (NIH)
name: Food and Drug Administration (FDA)
First posted: 2023-08-21
Enrollment: 48
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This is a crossover, randomized, double-blinded clinical pharmacology study enrolling dual cannabis-tobacco smokers to better understand the combined effects of co-administering cannabis and tobacco. The project aims to describe the pharmacokinetics and pharmacodynamics of marijuana-tobacco co-administration by delivering THC and nicotine in various combinations. This foundational study will establish a research program focused on elucidating the public health consequences of marijuana-tobacco co-use.

Detailed description: This is a single-center, within-subject (crossover), randomized, double-blinded clinical pharmacology study of over 8 study visits (days). Participants will be non-treatment-seeking, healthy frequent users of both marijuana and tobacco/nicotine, age 21 to 65 years (21 years because of California tobacco control law). Participants will be marijuana users of any race who smoke or vape marijuana or THC extracts at least three days a week for the past 3 months or more. The study investigators will use positive urine toxicology THC results and self-report of marijuana smoking/vaping to determine eligibility. Participants must also be current users of inhaled forms of tobacco/nicotine (cigarettes, cigars, e-cigarettes) who use the product daily over the past 3 months.

Each study day will consist of a standardized session of 5 puffs of one of 8 study conditions using a PAX-3 vaporizer (PAX Labs, Inc.). Blood will be sampled multiple times for plasma THC, nicotine, and catecholamines, questionnaires administered for sensory and subjective effects, and heart rate, skin blood flow, and skin temperature will be measured. After 6 hours of abstinence, participants will have 60 minutes of ad libitum access to the assigned study condition, during which heart rate and blood pressure will be continuously monitored, blood sampled before and after for THC, nicotine, and platelet aggregation measured, and questionnaires administered.

Studies will be conducted at the Clinical \& Translational Science Institute (CTSI) Clinical Research Services-supported research ward at Zuckerberg San Francisco General.

Eligibility criteria: Inclusion Criteria:

* 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.
* Body Mass Index (BMI) ≤ 38.0 (at investigator's discretion for higher BMI if no other concurrent health issues)
* Current regular user of cannabis who smokes or vapes cannabis or THC extracts at least three days a week for the past 3 months or more
* Test positive for D-9-tetrahydrocannabinol (THC) at screening and self-report of cannabis use
* Current user of inhaled forms of tobacco/nicotine (cigarette, cigars, e-cigarettes) who use the product daily for the past 3 months or more
* Saliva cotinine ≥ 30 ng/mL

Exclusion Criteria:

* Unstable medical conditions:

  * Heart disease
  * Seizures
  * Cancer
  * Thyroid disease (okay if controlled with medication)
  * Diabetes
  * Hepatitis B or C or Liver disease
  * Glaucoma
  * Kidney disease or urinary retention
  * An ulcer in the past year
  * Active use of an inhaler for asthma or Chronic Obstructive Pulmonary Disease (COPD)
* Hypertension if uncontrolled (meaning participant has a diagnosis, but they are not taking medication/under treatment (e.g., diet or exercise plan)
* Drug/Alcohol Dependence

  * Alcohol or illicit drug dependence within the past 12 months (currently in treatment) with the exception of those who recently completed an alcohol/drug treatment program
  * Positive toxicology test at the screening visit (THC \& prescribed medications okay)
  * Opioid replacement therapy (including methadone, buprenorphine, or other)
* Psychiatric conditions

  * Current or past schizophrenia, and/or current or past bipolar disorder
  * Major depression, current or within the past year
  * Major personality disorder
  * Participants with current or past minor or moderate depression and/or anxiety disorders will be reviewed by the PI \[study physician\] and considered for inclusion
  * History of psychiatric hospitalizations are not exclusionary, but study participation will be determined as per PI's \[study physician's\] approval
* 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 PI that the participant is otherwise healthy, stable, and able to participate
* Congenital or acquired immunodeficiency disorders (i.e. HIV, congenital immune deficiency syndrome, chronic diseases)
* Other disorders (i.e. ICU, malnutrition, immunosuppressive therapy)
* Traumatic brain injury
* Recent onset or change (worsening) in cough, fever and/or abdominal symptoms (vomiting or pain) in the past two weeks
* 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
  * Any stimulant medications (ex. Adderall) generally given for attention deficit hyperactivity disorder (ADHD) treatment
* Other/Misc. Chronic Health Problems

  * Oral thrush
  * Fainting
  * Other "life threatening illnesses" as per study physician's discretion
* Pregnancy

  * Pregnancy (self-reported and urine pregnancy test)
  * Breastfeeding (determined by self-report)
* Concurrent participation in another clinical trial
* Inability to communicate in English
* History of marijuana-induced psychosis or paranoia after smoking marijuana
* Scoring a 7 or higher on the Severity of Dependence Scale (SDS) for cannabis use
* Planning to quit smoking or vaping within the next 60 days
* Planning to quit cannabis use within the next 60 days
* Uncomfortable with getting blood drawn
* Willingness to abstain from tobacco smoking and all combustible products for 13 hours before admission
* Willingness to abstain from smoking/ingestion of cannabis 13 hours before
* Willingness to abstain from nicotine products 13 hours before each admission

Primary outcomes:
measure: Change in peak plasma concentration of THC
timeFrame: From Baseline to Day 1
measure: Change in peak plasma concentration of THC
timeFrame: From Day 1 to Day 2
measure: Change in peak plasma concentration of THC
timeFrame: From Day 2 to Day 3
measure: Change in peak plasma concentration of THC
timeFrame: From Day 3 to Day 4
measure: Change in peak plasma concentration of THC
timeFrame: From Day 4 to Day 5
measure: Change in peak plasma concentration of THC
timeFrame: From Day 5 to Day 6
measure: Change in peak plasma concentration of THC
timeFrame: From Day 6 to Day 7
measure: Change in peak plasma concentration of THC
timeFrame: From Day 7 to Day 8
measure: Change in Peak plasma concentration of nicotine
timeFrame: From Baseline to Day 1
measure: Change in Peak plasma concentration of nicotine
timeFrame: From Day 1 to Day 2
measure: Change in Peak plasma concentration of nicotine
timeFrame: From Day 2 to Day 3
measure: Change in Peak plasma concentration of nicotine
timeFrame: From Day 3 to Day 4
measure: Change in Peak plasma concentration of nicotine
timeFrame: From Day 4 to Day 5
measure: Change in Peak plasma concentration of nicotine
timeFrame: From Day 5 to Day 6
measure: Change in Peak plasma concentration of nicotine
timeFrame: From Day 6 to Day 7
measure: Change in Peak plasma concentration of nicotine
timeFrame: From Day 7 to Day 8
Secondary outcomes:
measure: Cardiovascular effects among dosages using heart rate as a measure
timeFrame: From Baseline to Day 1
measure: Cardiovascular effects among dosages using heart rate as a measure
timeFrame: From Day 1 to Day 2
measure: Cardiovascular effects among dosages using heart rate as a measure
timeFrame: From Day 2 to Day 3
measure: Cardiovascular effects among dosages using heart rate as a measure
timeFrame: From Day 3 to Day 4
measure: Cardiovascular effects among dosages using heart rate as a measure
timeFrame: From Day 4 to Day 5
measure: Cardiovascular effects among dosages using heart rate as a measure
timeFrame: From Day 5 to Day 6
measure: Cardiovascular effects among dosages using heart rate as a measure
timeFrame: From Day 6 to Day 7
measure: Cardiovascular effects among dosages using heart rate as a measure
timeFrame: From Day 7 to Day 8
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: From Baseline to Day 1
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: From Day 1 to Day 2
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: From Day 2 to Day 3
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: From Day 3 to Day 4
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: From Day 4 to Day 5
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: From Day 5 to Day 6
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: From Day 6 to Day 7
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: From Day 7 to Day 8
measure: Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
timeFrame: From Baseline to Day 1
measure: Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
timeFrame: From Day 1 to Day 2
measure: Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
timeFrame: From Day 2 to Day 3
measure: Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
timeFrame: From Day 3 to Day 4
measure: Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
timeFrame: From Day 4 to Day 5
measure: Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
timeFrame: From Day 5 to Day 6
measure: Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
timeFrame: From Day 6 to Day 7
measure: Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
timeFrame: From Day 7 to Day 8
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital
state: California
Study officials:
affiliation: University of California, San Francisco
name: Gideon St Helen
role: PRINCIPAL_INVESTIGATOR
References: