Understanding the Clinical Pharmacology of Marijuana-Tobacco Co-administration

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