Understanding the Clinical Pharmacology of Marijuana-Tobacco Co-administration

NCT ID: NCT05999383

Last Updated: 2026-01-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-01

Study Completion Date

2028-02-01

Brief Summary

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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

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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.

Conditions

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THC Cannabis Cannabis Use Cannabis Smoking Tobacco Use Vaping

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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)

Group Type EXPERIMENTAL

Nicotine

Intervention Type DRUG

Participants will vape Regular and Very Low Nicotine content cigarettes from the PAX device

Pax Loose Leaf Vaporizer

Intervention Type DEVICE

In all arms, participants will be using the PAX Loose Leave Vaporizer.

Placebo Marijuana

Intervention Type OTHER

Participants will vape placebo marijuana from the PAX device

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)

Group Type EXPERIMENTAL

Nicotine

Intervention Type DRUG

Participants will vape Regular and Very Low Nicotine content cigarettes from the PAX device

Pax Loose Leaf Vaporizer

Intervention Type DEVICE

In all arms, participants will be using the PAX Loose Leave Vaporizer.

Placebo Marijuana

Intervention Type OTHER

Participants will vape placebo marijuana from the PAX device

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)

Group Type EXPERIMENTAL

Cannabis

Intervention Type DRUG

Participants will vape marijuana in varying doses from the PAX device

Nicotine

Intervention Type DRUG

Participants will vape Regular and Very Low Nicotine content cigarettes from the PAX device

Pax Loose Leaf Vaporizer

Intervention Type DEVICE

In all arms, participants will be using the PAX Loose Leave Vaporizer.

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)

Group Type EXPERIMENTAL

Cannabis

Intervention Type DRUG

Participants will vape marijuana in varying doses from the PAX device

Nicotine

Intervention Type DRUG

Participants will vape Regular and Very Low Nicotine content cigarettes from the PAX device

Pax Loose Leaf Vaporizer

Intervention Type DEVICE

In all arms, participants will be using the PAX Loose Leave Vaporizer.

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)

Group Type EXPERIMENTAL

Cannabis

Intervention Type DRUG

Participants will vape marijuana in varying doses from the PAX device

Nicotine

Intervention Type DRUG

Participants will vape Regular and Very Low Nicotine content cigarettes from the PAX device

Pax Loose Leaf Vaporizer

Intervention Type DEVICE

In all arms, participants will be using the PAX Loose Leave Vaporizer.

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)

Group Type EXPERIMENTAL

Cannabis

Intervention Type DRUG

Participants will vape marijuana in varying doses from the PAX device

Nicotine

Intervention Type DRUG

Participants will vape Regular and Very Low Nicotine content cigarettes from the PAX device

Pax Loose Leaf Vaporizer

Intervention Type DEVICE

In all arms, participants will be using the PAX Loose Leave Vaporizer.

High marijuana only

Participants will vape high marijuana (\>10% THC)

Group Type EXPERIMENTAL

Cannabis

Intervention Type DRUG

Participants will vape marijuana in varying doses from the PAX device

Pax Loose Leaf Vaporizer

Intervention Type DEVICE

In all arms, participants will be using the PAX Loose Leave Vaporizer.

Regular cigarette only

Participants will vape a regular cigarette (25.94 mg/g nicotine content)

Group Type EXPERIMENTAL

Nicotine

Intervention Type DRUG

Participants will vape Regular and Very Low Nicotine content cigarettes from the PAX device

Pax Loose Leaf Vaporizer

Intervention Type DEVICE

In all arms, participants will be using the PAX Loose Leave Vaporizer.

Interventions

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Cannabis

Participants will vape marijuana in varying doses from the PAX device

Intervention Type DRUG

Nicotine

Participants will vape Regular and Very Low Nicotine content cigarettes from the PAX device

Intervention Type DRUG

Pax Loose Leaf Vaporizer

In all arms, participants will be using the PAX Loose Leave Vaporizer.

Intervention Type DEVICE

Placebo Marijuana

Participants will vape placebo marijuana from the PAX device

Intervention Type OTHER

Other Intervention Names

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Marijuana Nicotine product Electronic vaporizor Placebo for Marijuana

Eligibility Criteria

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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
Minimum Eligible Age

21 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

Food and Drug Administration (FDA)

FED

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gideon St Helen

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

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Zuckerberg San Francisco General Hospital

San Francisco, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Armando Barraza

Role: CONTACT

628-206-4226

Facility Contacts

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Lisa Lawrence

Role: primary

Other Identifiers

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1R01DA056451-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

23-38884

Identifier Type: -

Identifier Source: org_study_id

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