The purpose of this study is to determine the impact of tetrahydrocannabinol (THC) administration on motivational, subjective, and physiological effects of cigarettes. The study's goals are to test demand for cigarettes, tobacco craving, affect, heart rate, blood pressure, expired breath carbon monoxide, and cognitive performance. Researchers will compare multiple doses of THC and a placebo in participants who smoke cigarettes and either smoke or vape THC in the laboratory.

A full-factorial laboratory study will be conducted to determine the impact of acute THC administration on the dose-related motivational, subjective, and physiological effects of combustible cigarettes. This study will employ a double-blind, placebo-controlled, within-subjects crossover design to examine the dose-effects of THC on combustible tobacco use. The study will use multiple active doses of THC and placebo (0, 5, and 30 mg; corresponding to 0, 1, and 6 standard THC unit doses). Participants will be randomized to either smoked or vaporized THC administration using a between-subjects approach to evaluate the effect of congruent versus incongruent routes of THC and tobacco administration on study outcomes.

Inclusion Criteria:

1. Healthy non-treatment seeking adults aged 21 or older
2. Report daily use of combustible tobacco cigarettes
3. Biological confirmation of cigarette use: have an expired carbon monoxide (CO) level of more than 5 ppm and a positive urine cotinine test at screening
4. Report current use of cannabis (at least 1 occasion per week)
5. Have experience with the inhalation route of administration for cannabis
6. Biological confirmation of cannabis use: have a positive urinary THC drug test at screening.
7. For women of children bearing potential and men with female partners of child-bearing potential, must be willing to use an effective form of contraception during the study.

Exclusion Criteria:

1. Report current intention to reduce or quit cannabis or tobacco use within the next 30 days
2. Meet Diagnostic and Statistical Manual (DSM-5) criteria for a substance use disorder other than alcohol, cannabis, or nicotine
3. Test positive for illicit drugs other than cannabis and tobacco
4. Positive breath alcohol test at study admission
5. Have a current physical or mental illness judged by the study team to negatively impact participant safety or scientific integrity
6. Have a lifetime history of suicidal behavior (i.e. past suicide attempt), or current suicidal behavior or ideation as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)
7. Are currently pregnant, planning to become pregnant in the next three months or are currently breastfeeding
8. Have a history of clinically significant cardiac arrhythmias or vasospastic disease (e.g., Prinzmetal's angina)
9. Are currently enrolled in another clinical trial or have received any drug as part of a research study within 30 days of study participation.