How marijuana (THC) and tobacco interact when used together

Understanding the Clinical Pharmacology of Marijuana-Tobacco Co-administration

Phase 2 Interventional University of California, San Francisco · NCT05999383

This test tries to see if combining marijuana (THC) and tobacco changes blood drug levels and how people feel and respond physically in adults who regularly use both.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment48 (estimated)
Ages21 Years to 65 Years
SexAll
SponsorUniversity of California, San Francisco Academic / other
Locations1 site (San Francisco, California)
Trial IDNCT05999383 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blinded, within-subject (crossover) clinical pharmacology protocol conducted at a single center. Eligible participants are healthy adults aged 21–65 who regularly smoke or vape both marijuana/THC and inhaled tobacco/nicotine. Each of 8 study days delivers 5 puffs from a PAX-3 vaporizer under one of eight THC/nicotine combinations, with multiple timed blood samples for THC, nicotine, and catecholamines, continuous physiological monitoring, and repeated questionnaires. After a period of abstinence, participants have a 60-minute ad libitum access phase with further blood sampling and measures including platelet aggregation, heart rate, blood pressure, and subjective effects.

Who should consider this trial

Good fit: Adults 21–65 who currently smoke or vape cannabis at least three days per week and use inhaled tobacco/nicotine daily for the past three months, who test positive for THC at screening and meet basic vital sign, BMI, and lab criteria, are ideal candidates.

Not a fit: People who do not regularly use both cannabis and inhaled tobacco, those under 21, pregnant people, or those with unstable medical conditions (for example heart disease, seizures, or uncontrolled diabetes) are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the results could clarify the physiological and subjective effects of co-using marijuana and tobacco and help inform public health guidance and clinical counseling.

How similar studies have performed: There is prior pharmacology work characterizing THC or nicotine alone, but rigorous double-blind co-administration pharmacology in regular dual users is relatively novel and limited.

Eligibility criteria

Show full inclusion / exclusion 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

Where this trial is running

San Francisco, California

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions THCCannabisCannabis UseCannabis SmokingTobacco UseVapingMarijuanaNicotine
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.