Eligibility

Inclusion Criteria

• Ages 18-65
• Good general health based on screening procedures (e.g. physical exam, blood testing, psychiatric evaluation)
• Systolic blood pressure <140 mm Hg, diastolic blood pressure < 90 mm Hg, and heart rate <110 bpm at screening
• Body mass index (BMI) in the range of 18 to 36 kg/m2
• Cannabis use within the past three years but none in the month prior to the first test session
• Negative urine test for illicit substance use and negative breath alcohol test (0% breath alcohol concentration) at screening

Exclusion Criteria

• Use of psychoactive substances (aside from nicotine, caffeine, and alcohol) in the month prior to study initiation

• Current use of over the counter (OTC) drugs, supplements/vitamins, or prescription medications that, in the opinion of the investigator or medical staff, will impact the participant's safety.

• Current use of any prescription or non-prescription medications, including herbal medicines and supplements, that are known to interact with cannabis or pregnenolone

• Self-report or ECG indicating clinically significant cardiovascular conditions, including coronary artery disease, stroke, angina, uncontrolled hypertension, arrhythmias (e.g. atrial fibrillation), heart valve placement, or TIA in the past year.

• History of hormone-sensitive conditions, including but not limited to gynecologic cancers (breast, ovarian, uterine, etc), endometriosis, uterine fibroids, thyroid, pituitary and/or adrenal syndromes, polycystic ovarian syndrome, etc.

• Epilepsy or a history of seizures

• Any of the following laboratory values during screening or upon admission:

  • AST > 165 U/L (normal range 19-55)
  • ALT > 216 U/L (normal range 19-72)
  • Alkaline phosphatase > 1.5x upper limit of normal (ULN)
  • Total bilirubin >1.5 ULN
  • Glomerular filtration rate (EGFR) < 60 ml/min/1.73m2

• Current or past history of meeting DSM-5 criteria for schizophrenia spectrum or other psychotic disorders, or bipolar I or II disorder

• Other unstable and/or compromising medical or psychiatric conditions based on clinical interview and/or MINI results that would interfere with participant safety as determined by study physician, including suicidal ideation and/or attempt, psychosis

• Previous diagnosis and treatment for Cannabis Use Disorder

• Urine drug screen (e.g. Healgen Scientific 14 Panel Rapid Drug Test) indicating the presence of substances including amphetamines, barbiturates, benzodiazepines, cocaine, opioids (including fentanyl), PCP and/or THC at screening.

• Breathalyzer screen indicating presence of alcohol at screening

• Women who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing

• Women who are of childbearing potential and sexually active who are not practicing an effective means of birth control including oral contraceptives, progestin implant, transdermal birth control patch, intrauterine device (IUD) or vaginal ring. Women who report use of condoms or diaphragm must use a "double-barrier" method of contraception (i.e. diaphragm and condoms).

• SBP >/= 140, DBP >/= 90, or pulse >/=110 during screening

• Has donated blood within 30 days of the study

• Allergy to eggs or other food allergies that would make ingestion of brownie mix unsafe.

• Use of concomitant medications, including herbal medicines and botanical supplements, that are strong inhibitors or inducers of CYP3A4 and CYP2C9