Clinical Study to Evaluate the Effects of Oral Delta-9-tetrahydrocannabinol (Δ9-THC) With and Without Alcohol on Perception and Driving Performance in Healthy Adults

Inclusion criteria

• Subject signs an IRB approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act authorization) before any study related procedures are performed.
• Subject is a healthy, non-smoking man or woman, 21 to 55 years of age, inclusive, who weighs at least 50 kg (110 lbs) and has a body mass index of 18.5 to 33.0 kg/m2, inclusive, at Screening and check-in (Day -1).
• Subject possesses a valid U.S. driver's license and has driven a minimum of 600 miles per year for the previous 3 years.
• During screening subjects will be assessed using a driving simulation test. Subject must not demonstrate any motion sickness as determined by the investigator and defined in the driving simulation operations manual and subject must not have erratic driving as defined in the Screening Visit Driving Practice Assessment Operational Manual.
• Subject has normal medical history findings, clinical laboratory results, vital sign measurements, 12-lead ECG results, and physical examination findings at screening and check-ins or, if abnormal, the abnormality is not considered clinically significant (as determined and documented by the investigator or designee). Out of range tests may be repeated once for confirmation at screening and/or check-ins at investigator's discretion.
• Subject is an occasional user of cannabis, defined as having at least one cannabis exposure within the last 6 months, but no daily use pattern and no cannabis exposure within the past month.
• Subject has consumed alcohol equivalent to achieving approximately 0.10% BAC (approximately 3-4 standard drinks for females and 4-5 drinks for males over 1-2 hours) within the past year without experiencing significant adverse reactions. (Note: 1 standard drink = 12 ounces of beer \[5% alcohol by volume\], 5 ounces of wine \[12% alcohol by volume\], or 1.5 ounce of distilled spirits \[40% alcohol\]).
• Subject must report at least 1 instance of simultaneous alcohol and cannabis use over the past one year without experiencing significant adverse reactions based on investigator discretion.
• Participants must agree to refrain from using any of the following for the duration of the study: alcohol, nicotine containing products, marijuana (except for provided study drug) or marijuana-derived products, hemp or hemp-derived products, including CBD, and illicit drugs of any kind. Only THC and alcohol administered at the study site will be permitted.
• Subject must test negative for severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) by a rapid antigen test at check-in. If a subject's test comes back as invalid, the test can be repeated.
• Female subjects must be of non-childbearing potential (non-childbearing potential includes post-menopausal females defined as spontaneous amenorrhea for at least 12 months with FSH in the post-menopausal range or females who have undergone a surgical procedure that prevents pregnancy (e.g., hysterectomy, bilateral tubal ligation, occlusion, or salpingo-oophorectomy) or, if they are of childbearing potential, they must have negative serum HCG at screening and check-in and be practicing 2 effective methods of birth control (as determined by the investigator or designee; only one of the methods, but not both, may be a barrier technique) from Screening until at least 3 months after the end of the study. They must agree not to donate eggs for 30 days until after study completion.
• Male subjects must agree to practice 2 effective methods of birth control (as determined by the investigator or designee) beginning at check-in (Day -1) until at least 3 months after the last dose of study drug. Subject must also agree to inform female partner(s) about participation in the study and ensure they are using a highly effective form of contraception (e.g., hormonal birth control or copper IUD). Male subjects may not donate sperm for 90 days after the end of the study.
• Subject agrees to and is highly likely (as determined by the investigator) to comply with the protocol defined procedures and to complete the study.

Exclusion criteria

• A history of cannabis use disorder or use of any psychoactive drug in the last month.
• Any reported history of alcohol intolerance.
• Alcohol intolerance as detected by ethanol patch testing.
• Subject has a dry mouth or history of salivary gland disfunction or surgery.
• A history of any psychiatric diagnosis, including mood, anxiety, and psychotic disorders.
• Any family history of schizophrenia or other psychotic illness.
• Any history of seizures, epilepsy, or traumatic brain injury.
• History of syncope within 3 months prior to screening or any history of recurrent and/or unexplained episodes of syncope.
• A positive test result for alcohol and drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, alcohol, opiates, phencyclidine, propoxyphene, methadone, ) at screening and check-in (Day -1).
• Use or intend to use any medications other than birth control, including prescription, OTC, herbal or recreational products (excluding cannabis) in the 14 days prior to check-in (Day -1), unless deemed acceptable by the investigator.
• Currently participating in another clinical study of an investigational drug or has been treated with any investigational drug within 30 days or 5 half-lives (whichever is longer) of dosing for this study.
• Subject has used nicotine-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff, electronic cigarettes) within 6 weeks of Screening. Subjects must refrain from using these throughout the study.
• Subject is unable to tolerate a controlled, quiet study conduct environment, including avoidance of music, television, movies, games, and activities that may cause excitement, emotional tension, or arousal during the prespecified time points.
• Subject has known or suspected allergies or sensitivities to the study drug, delta 9-THC or sesame seeds/oil.
• Subject has a history of consuming more than 14 units of alcoholic beverages per week within 6 months before Screening, has a history of alcohol use disorder or drug/chemical/substance abuse within 2 years before Screening (Note: 1 unit = 12 ounces of beer, 5 ounces of wine, or 1.5 ounce of spirits/hard liquor).
• Subject tests positive for potential active alcohol use disorder (as determined by a score of 3 or greater on the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C).
• Subject has a history of suicidal ideation or previous suicide attempts.
• Subject has a history or evidence of a clinically significant disorder, condition, or disease (e.g., cancer, human immunodeficiency virus \[HIV\], hepatic or renal impairment) that, in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
• Subject has a diagnosis of COVID-19 or any signs or symptoms that are consistent with COVID-19 per CDC recommendations at screening or check-in (Day -1). These include subjects with fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, diarrhea, or other symptoms indicative of likely COVID-19 in the opinion of the investigator.
• Subject has any condition possibly affecting study drug absorption (e.g., gastrectomy, Crohn's disease, irritable bowel syndrome).
• Subject has clinical laboratory test results (hematology, serum chemistry and urinalysis) at screening or check-ins that are outside the reference ranges provided by the clinical laboratory and considered clinically significant by the investigator. Out of range tests may be repeated once for confirmation at screening and/or check-ins at investigator's discretion.
• Subject has a mean systolic blood pressure \<90 or \>140 mmHg or a mean diastolic blood pressure \<50 or \>90 mmHg at either screening or check-ins, unless determined not clinically significant per investigator. Blood pressure will be measured after the subject has been resting in a sitting position for approximately 5 minutes. Two blood pressure repeats will be permitted in instances where initial measures out of normal range.
• Subject has a positive test result at screening for HIV 1 or 2 antibody, hepatitis C virus antibodies, or hepatitis B surface antigen.
• Subject is unable or unwilling to undergo multiple venipunctures for blood sample collection because of poor tolerability or is unlikely to complete the study due to poor venous access.
• Subject has had any significant blood loss, donated 1 unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days, or donated plasma within 7 days before check-in.
• Subject with any visual or hearing impairment that will prevent accurate completion of study assessments (as determined by the investigator).
• Subject has any other condition that precludes his or her participation in the study (as determined by the investigator).