Understanding the Clinical Pharmacology of Marijuana-Tobacco Co-administration (CANNIC)

January 5, 2026 updated by: University of California, San Francisco
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

48

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94110
        • Recruiting
        • Zuckerberg San Francisco General Hospital
        • Contact:
        • Principal Investigator:
          • Gideon St. Helen, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Placebo marijuana and regular cigarette
Participants will vape a 50/50 mixture of placebo marijuana (0% THC) and regular cigarette (25.94 mg/g nicotine content)
Device: Pax Loose Leaf Vaporizer
In all arms, participants will be using the PAX Loose Leave Vaporizer.
Other Names:
  • Electronic vaporizor
Drug: Nicotine
Participants will vape Regular and Very Low Nicotine content cigarettes from the PAX device
Other Names:
  • Nicotine product
Other: Placebo Marijuana
Participants will vape placebo marijuana from the PAX device
Other Names:
  • Placebo for Marijuana
Experimental: Placebo marijuana and Very Low Nicotine Content cigarette
Participants will vape a 50/50 mixture of placebo marijuana (0% THC) and Very Low Nicotine Content cigarette (0.42 mg/g nicotine content)
Device: Pax Loose Leaf Vaporizer
In all arms, participants will be using the PAX Loose Leave Vaporizer.
Other Names:
  • Electronic vaporizor
Drug: Nicotine
Participants will vape Regular and Very Low Nicotine content cigarettes from the PAX device
Other Names:
  • Nicotine product
Other: Placebo Marijuana
Participants will vape placebo marijuana from the PAX device
Other Names:
  • Placebo for Marijuana
Experimental: Medium marijuana and regular cigarette
Participants will vape a 50/50 mixture of medium marijuana (<5% THC) and regular cigarette (25.94 mg/g nicotine content)
Drug: Cannabis
Participants will vape marijuana in varying doses from the PAX device
Other Names:
  • Marijuana
Device: Pax Loose Leaf Vaporizer
In all arms, participants will be using the PAX Loose Leave Vaporizer.
Other Names:
  • Electronic vaporizor
Drug: Nicotine
Participants will vape Regular and Very Low Nicotine content cigarettes from the PAX device
Other Names:
  • Nicotine product
Experimental: Medium marijuana and Very Low Nicotine Content cigarette
Participants will vape a 50/50 mixture of medium marijuana (<5% THC) and Very Low Nicotine Content cigarette (0.42 mg/g nicotine content)
Drug: Cannabis
Participants will vape marijuana in varying doses from the PAX device
Other Names:
  • Marijuana
Device: Pax Loose Leaf Vaporizer
In all arms, participants will be using the PAX Loose Leave Vaporizer.
Other Names:
  • Electronic vaporizor
Drug: Nicotine
Participants will vape Regular and Very Low Nicotine content cigarettes from the PAX device
Other Names:
  • Nicotine product
Experimental: High marijuana and regular cigarette
Participants will vape a 50/50 mixture of high marijuana (>10% THC) and regular cigarette (25.94 mg/g nicotine content)
Drug: Cannabis
Participants will vape marijuana in varying doses from the PAX device
Other Names:
  • Marijuana
Device: Pax Loose Leaf Vaporizer
In all arms, participants will be using the PAX Loose Leave Vaporizer.
Other Names:
  • Electronic vaporizor
Drug: Nicotine
Participants will vape Regular and Very Low Nicotine content cigarettes from the PAX device
Other Names:
  • Nicotine product
Experimental: High marijuana and Very Low Nicotine Content cigarette
Participants will vape a 50/50 mixture of high marijuana (>10% THC) and Very Low Nicotine Content cigarette (0.42 mg/g nicotine content)
Drug: Cannabis
Participants will vape marijuana in varying doses from the PAX device
Other Names:
  • Marijuana
Device: Pax Loose Leaf Vaporizer
In all arms, participants will be using the PAX Loose Leave Vaporizer.
Other Names:
  • Electronic vaporizor
Drug: Nicotine
Participants will vape Regular and Very Low Nicotine content cigarettes from the PAX device
Other Names:
  • Nicotine product
Experimental: High marijuana only
Participants will vape high marijuana (>10% THC)
Drug: Cannabis
Participants will vape marijuana in varying doses from the PAX device
Other Names:
  • Marijuana
Device: Pax Loose Leaf Vaporizer
In all arms, participants will be using the PAX Loose Leave Vaporizer.
Other Names:
  • Electronic vaporizor
Experimental: Regular cigarette only
Participants will vape a regular cigarette (25.94 mg/g nicotine content)
Device: Pax Loose Leaf Vaporizer
In all arms, participants will be using the PAX Loose Leave Vaporizer.
Other Names:
  • Electronic vaporizor
Drug: Nicotine
Participants will vape Regular and Very Low Nicotine content cigarettes from the PAX device
Other Names:
  • Nicotine product

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in peak plasma concentration of THC
Time Frame: From Baseline to Day 1
To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
From Baseline to Day 1
Change in peak plasma concentration of THC
Time Frame: From Day 1 to Day 2
To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
From Day 1 to Day 2
Change in peak plasma concentration of THC
Time Frame: From Day 2 to Day 3
To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
From Day 2 to Day 3
Change in peak plasma concentration of THC
Time Frame: From Day 3 to Day 4
To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
From Day 3 to Day 4
Change in peak plasma concentration of THC
Time Frame: From Day 4 to Day 5
To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
From Day 4 to Day 5
Change in peak plasma concentration of THC
Time Frame: From Day 5 to Day 6
To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
From Day 5 to Day 6
Change in peak plasma concentration of THC
Time Frame: From Day 6 to Day 7
To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
From Day 6 to Day 7
Change in peak plasma concentration of THC
Time Frame: From Day 7 to Day 8
To assess the differences between THC dosages, the study investigators will determine maximum plasma THC concentration (Cmax) using plasma THC concentrations from the standardized sessions.
From Day 7 to Day 8
Change in Peak plasma concentration of nicotine
Time Frame: From Baseline to Day 1
To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
From Baseline to Day 1
Change in Peak plasma concentration of nicotine
Time Frame: From Day 1 to Day 2
To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
From Day 1 to Day 2
Change in Peak plasma concentration of nicotine
Time Frame: From Day 2 to Day 3
To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
From Day 2 to Day 3
Change in Peak plasma concentration of nicotine
Time Frame: From Day 3 to Day 4
To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
From Day 3 to Day 4
Change in Peak plasma concentration of nicotine
Time Frame: From Day 4 to Day 5
To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
From Day 4 to Day 5
Change in Peak plasma concentration of nicotine
Time Frame: From Day 5 to Day 6
To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
From Day 5 to Day 6
Change in Peak plasma concentration of nicotine
Time Frame: From Day 6 to Day 7
To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
From Day 6 to Day 7
Change in Peak plasma concentration of nicotine
Time Frame: From Day 7 to Day 8
To assess the differences between nicotine dosages, the study investigators will determine maximum plasma nicotine concentration (Cmax) using plasma nicotine concentrations from the standardized sessions.
From Day 7 to Day 8

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiovascular effects among dosages using heart rate as a measure
Time Frame: From Baseline to Day 1
The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.
From Baseline to Day 1
Cardiovascular effects among dosages using heart rate as a measure
Time Frame: From Day 1 to Day 2
The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.
From Day 1 to Day 2
Cardiovascular effects among dosages using heart rate as a measure
Time Frame: From Day 2 to Day 3
The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.
From Day 2 to Day 3
Cardiovascular effects among dosages using heart rate as a measure
Time Frame: From Day 3 to Day 4
The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.
From Day 3 to Day 4
Cardiovascular effects among dosages using heart rate as a measure
Time Frame: From Day 4 to Day 5
The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.
From Day 4 to Day 5
Cardiovascular effects among dosages using heart rate as a measure
Time Frame: From Day 5 to Day 6
The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.
From Day 5 to Day 6
Cardiovascular effects among dosages using heart rate as a measure
Time Frame: From Day 6 to Day 7
The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.
From Day 6 to Day 7
Cardiovascular effects among dosages using heart rate as a measure
Time Frame: From Day 7 to Day 8
The investigators will compare maximum change in heart rate as well as an integrated measure of heart rate over the first 180 minutes after the standardized session among dosages.
From Day 7 to Day 8
Area under the plasma concentration versus time curve (AUC)
Time Frame: From Baseline to Day 1
To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.
From Baseline to Day 1
Area under the plasma concentration versus time curve (AUC)
Time Frame: From Day 1 to Day 2
To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.
From Day 1 to Day 2
Area under the plasma concentration versus time curve (AUC)
Time Frame: From Day 2 to Day 3
To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.
From Day 2 to Day 3
Area under the plasma concentration versus time curve (AUC)
Time Frame: From Day 3 to Day 4
To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.
From Day 3 to Day 4
Area under the plasma concentration versus time curve (AUC)
Time Frame: From Day 4 to Day 5
To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.
From Day 4 to Day 5
Area under the plasma concentration versus time curve (AUC)
Time Frame: From Day 5 to Day 6
To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.
From Day 5 to Day 6
Area under the plasma concentration versus time curve (AUC)
Time Frame: From Day 6 to Day 7
To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.
From Day 6 to Day 7
Area under the plasma concentration versus time curve (AUC)
Time Frame: From Day 7 to Day 8
To assess the differences of absorption among dosages, the study investigators will determine the AUC using plasma nicotine and THC concentrations from the standardized sessions.
From Day 7 to Day 8
Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
Time Frame: From Baseline to Day 1
Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.
From Baseline to Day 1
Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
Time Frame: From Day 1 to Day 2
Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased craving of marijuana.
From Day 1 to Day 2
Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
Time Frame: From Day 2 to Day 3
Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.
From Day 2 to Day 3
Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
Time Frame: From Day 3 to Day 4
Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.
From Day 3 to Day 4
Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
Time Frame: From Day 4 to Day 5
Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.
From Day 4 to Day 5
Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
Time Frame: From Day 5 to Day 6
Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.
From Day 5 to Day 6
Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
Time Frame: From Day 6 to Day 7
Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.
From Day 6 to Day 7
Change in subjective effects scores using the Marijuana Cravings Questionnaire (MCQ)
Time Frame: From Day 7 to Day 8
Self-assessed cravings will be measured using the MCQ. Questions on the MCQ are scored on a 7 point scale of 1 = Strongly Disagree and 7 = Strongly Disagree, with higher scores indicating increased cravings.
From Day 7 to Day 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

National Institute on Drug Abuse (NIDA)
National Institutes of Health (NIH)
Food and Drug Administration (FDA)

Investigators

  • Principal Investigator: Gideon St Helen, University of California, San Francisco

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2025

Primary Completion (Estimated)

February 1, 2028

Study Completion (Estimated)

February 1, 2028

Study Registration Dates

First Submitted

August 11, 2023

First Submitted That Met QC Criteria

August 11, 2023

First Posted (Actual)

August 21, 2023

Study Record Updates

Last Update Posted (Actual)

January 7, 2026

Last Update Submitted That Met QC Criteria

January 5, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23-38884
  • 1R01DA056451-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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