The Pharmacodynamics of Cannabinoid-Caffeine Combinations

Exclusion Criteria

• •1. Person has a known history of significant allergic condition or significant hypersensitivity to cannabis, cannabinoid medications, hemp products, or excipients of the investigational product.
• •2. Person has a known history of significant allergic condition or significant hypersensitivity to caffeine or caffeine products.
• •3. Person has been exposed to any investigational drug or device \< 30 days prior to randomization or plans to take an investigational drug during the study.
• •4. Person has used cannabis, cannabinoid analogue (e.g., dronabinol, nabilone), and/or any CBD- or delta-9-tetrahydrocannabinol (THC)-containing product within 30 days of screening or during the study.
• •5. Person has history of use of any synthetic cannabinoid receptor agonist (e.g., spice, K2) within the past year.
• •6. Person consumes more than 400 mg/day of coffee or other caffeine products (approximately 4 cups of coffee per day) on average within 30 days of screening.
• •7. Person has used illicit substances (e.g., amphetamine, cocaine, methamphetamine, 3,4-Methyl enedioxy methamphetamine \[MDMA\], lysergic acid diethylamide \[LSD\], ketamine, heroin, psilocybin, salvia, prescription medications not prescribed to the person) within 30 days of screening or during the study.
• •8. Person tests positive for any substance, including THC, at screening.
• •9. Person is currently using products or medications that may interact with one or more of the ingredients in the investigational product, including the following drugs or supplements: warfarin, clobazam, valproic acid, phenobarbital, mechanistic target of rapamycin \[mTOR\] inhibitors, oral tacrolimus, St. John's wort, Epidiolex, over the counter stimulants (e.g., phentermine), prescribed stimulants (e.g., Ritalin, Vyvanse), antihypertensive drugs (e.g., captopril, valsartan).
• •10. Person endorses current suicidal intent as indexed via items 4 and 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS).
• •11. Person has a history or family history of psychosis or schizophrenia.
• •12. Person has a diagnosis of cardiac disease or significant cardiac condition.
• •13. Person has a diagnosis of hypertension and/or a blood pressure reading with systolic pressure \> 150 mm Hg or diastolic pressure \> 90 mm Hg.
• •14. Person has an acute or progressive disease or disorder that is likely to interfere with the objectives of the study or the ability to adhere to protocol requirements.
• •15. Person is currently pregnant, breastfeeding, or is planning to become pregnant within 30 days of completing the study.
• •16. Woman of childbearing potential, unless she has not engaged in vaginal intercourse, or she has used effective contraception when doing so (for example, double barrier), for at least 30 days prior to the study (however, a male condom should not be used in conjunction with a female condom).
• •17. Woman of childbearing potential, unless willing to ensure that she or her partner use effective contraception (for example, double barrier) during the study and for 30 days thereafter (however, a male condom should not be used in conjunction with a female condom).
• •18. Man whose partner is of childbearing potential, unless willing to ensure that he or his partner use effective contraception (for example, double barrier) during the study and for 30 days thereafter (however, a male condom should not be used in conjunction with a female condom).
• •19. Person has history of diagnosis related to hepatic function and/or significantly impaired hepatic function (alanine aminotransferase \[ALT\] \>5 ⋅ upper limit of normal or total bilirubin \[TBL\] \>2 ⋅ upper limit of normal) OR the ALT or aspartate aminotransferase (AST) \>3 ⋅ upper limit of normal and TBL \>2 ⋅ upper limit of normal (or international normalized ratio \[INR\] \>1.5).
• •20. Person demonstrates behavior indicating unreliability or inability to comply with the requirements of the protocol.