Clinical Research Directory

Inclusion Criteria: 1. Healthy non-treatment seeking adults aged 21-70 (inclusive). 2. Use of \> 5 cigarettes per day for \> 2 years. (Use of other tobacco/nicotine products in addition to cigarettes will be acceptable). 3. Biological confirmation of cigarette use: have an expired carbon monoxide (CO) level \> 8 ppm. 4. Alcohol Use: \< 2 drinks/day on average (\< 14 drinks/week). 5. Sleep schedule: No graveyard or third shift work (i.e., participants must report a normal nighttime sleep schedule). 6. 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 and for at least 30 days after the last study drug administration. 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 4. Positive breath alcohol test (\>.01 g/210L) at study admission 5. Have a current physical or mental illness or takes a medication judged by the study team to negatively impact participant safety or scientific integrity 6. Have a resting heart rate \>100, systolic blood pressure \>160mmHg or \<100mmHg, or diastolic blood pressure \>100mmHg or \<50mmHg at screening. 7. Have cold intolerance or a medical condition that might be exacerbated by exposure to cold (e.g. Reynaud's, peripheral neuropathy, trigeminal neuralgia, poorly controlled/uncontrolled hypothyroidism). 8. Are currently pregnant, planning to become pregnant in the next three months, or are currently breastfeeding 9. Have a history of clinically significant cardiac arrhythmias or vasospastic disease (e.g., Prinzmetal's angina, Raynaud's). 10. Have a history of and/or current liver disease, or elevated serum liver transaminase (AST or ALT) above 3 x Upper Limit of Normal (ULN), or elevated bilirubin above 2 x ULN at screening. 11. Are currently enrolled in another clinical trial or have received any drug as part of a research study within 30 days of study participation.