THC Crossover Study

Experienced dual cannabis-tobacco smokers will participate in a within-subject crossover study with three blocks: smoked cannabis (purchased by participants from a local dispensary), dry herb cannabis vaporizer, and usual brand tobacco cigarette. Each block will consist of 2 consecutive days on an inpatient research ward. The first inpatient day of each block will comprise of two sessions: (1) The first session will be a standardized bout to compare pharmacokinetic, physiologic, and subjective effects of cannabis and tobacco use; (2) after 6 hours of abstinence, the second session will be ad libitum access to the assigned product for 2 hours to compare subjective effects (reward, satisfaction, craving reduction) and use patterns. The second inpatient day will consist of ad libitum use of the assigned product from 8:00 in the morning to midnight. An abstinence day will be added after the second day of the last block to assess exposure and effects biomarkers during a period of abstinence from cannabis (smoked/vaped) or tobacco.

Inclusion criteria

• Healthy on the basis of medical history and limited physical examination, as described below:

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.

• Current regular user of cannabis who smokes cannabis as joint or blunt at least 3 times a week for past 3 months
• History of cannabis vaporizer use or willingness to use the vaporizer in the study
• Current tobacco cigarette use who smokes ≥ 5 cigarettes per day
• Saliva cotinine ≥ 50 ng/ml
• Test positive for D-9-tetrahydrocannabinol (THC) at screening and self-report of cannabis use

Exclusion criteria

• Unstable medical conditions:

Heart disease; Uncontrolled hypertension; Thyroid disease (okay if controlled with medication); Diabetes; Hepatitis B or C or Liver disease; Glaucoma; Prostatic hypertrophy

• Psychiatric conditions:

Current or past schizophrenia, and/or current or past bipolar disorder; Adult onset attention deficit hyperactivity disorder (ADHD); Participants with current or past depression and/or anxiety disorders will be reviewed by the study physician and considered for inclusion; History of psychiatric hospitalizations are not exclusionary, but study participation will be determined as per study physician's approval

• Concurrent regular use of smokeless tobacco or pipes [occasional users of these products may be enrolled if they agree to abstain from their use during the period of the study]
• 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; Psychiatric medications: 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 study physician that the participant is otherwise healthy, stable, and able to participate.

• Other/Misc. Chronic Health Conditions:

Oral thrush; Fainting; Untreated thyroid disease; Other "life threatening illnesses" as per study physician's discretion

• Pregnancy:

Pregnancy (self-reported and urine pregnancy test); Breastfeeding (determined by self-report)

• Drug/Alcohol Dependence:

Alcohol or illicit drug dependence within the past 12 months with the exception of those who have recently completed an alcohol/drug treatment program; Positive toxicology test at the screening visit (THC & prescribed medications okay); Methadone replacement therapy

• Concurrent participation in another clinical trial
• Inability to communicate in English
• History of marijuana-induced psychosis or paranoia after smoking marijuana
• Scoring a 2 or higher on the Severity of Dependence Scale for cannabis use
• Planning to quit smoking or vaping within the next 60 days