Recruiting
Phase 2

Pregnenolone

Sponsor:

Johns Hopkins University

Code:

NCT07216690

Conditions

Cannabis Intoxication

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

Interventions

Cannabis

Pregnenolone 250 mg

Pregnenolone 500 mg

Placebo

Placebo brownie

Study Details

Brief summary:

The present study will characterize the ability of pregnenolone to reverse the acute intoxication and associated symptoms of cannabis. Healthy adults with a history of cannabis use will be recruited to participate in a placebo-controlled, within-subject crossover study at Johns Hopkins Behavioral Pharmacology Research Unit (BPRU). By clarifying the ability of pregnenolone to reverse cannabis intoxication symptoms, this study will pave the way for larger clinical studies that provide a foundation for the development of future CB1-receptor NAM medications that could be applied in emergency situations and potentially validate pregnenolone as a treatment for cannabis intoxication.

Conditions

Cannabis Intoxication

Study ID

NCT07216690

Start date

Apr 24, 2026

Status verified date

Jul, 2026

Completion date

Jan 1, 2029

Anticipated

Primary completion date

Jan 1, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

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 and at baseline for dosing session
  • 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 and before study sessions

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 THC at screening and prior to study sessions
  • Breathalyzer screen indicating presence of alcohol at screening and prior to study sessions
  • 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 >/=100 during screening and/or prior to dosing session
  • 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

Study Design

Enrollment

20 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

placebo comparator: Placebo Brownie and Capsules

Placebo brownie, 0mg THC; two 0 mg pregnenolone capsules

placebo comparator: Cannabis/THC brownie and Placebo Capsules

25mg Cannabis/THC Brownie; two 0 mg pregnenolone capsules

experimental: Cannabis/THC Brownie and Pregnenolone, low dose

25mg Cannabis/THC Brownie; one 250 mg pregnenolone capsule and one 0 mg pregnenolone capsule

experimental: Cannabis/THC Brownie and Pregnenolone, high dose

25mg Cannabis/THC Brownie and two 250 mg pregnenolone capsules

Interventions

Cannabis

Cannabis brownie, 25mg THC

Pregnenolone 250 mg

Pregnenolone, low dose, one 250mg pregnenolone capsule and one 0 mg pregnenolone capsule

Pregnenolone 500 mg

Pregnenolone, high dose, two 250 mg pregnenolone capsules

Placebo

Placebo capsule, 0mg

Placebo brownie

Placebo brownie, 0mg THC

Primary outcome measure

  • Mean Peak Change From Baseline Drug Effect as Assessed by the Drug Effect Questionnaire (DEQ) [ Time Frame: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing ]
  • Mean peak change from baseline psychomotor performance as assessed by the Digit Symbol Substitution Task (DSST) [ Time Frame: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing ]
  • Mean peak change from baseline working memory performance as assessed by the Paced Auditory Serial Addition Task (PASAT) [ Time Frame: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing ]
  • Mean Peak Levels of Blood Pregnenolone, THC, and THC metabolites (11-OH-THC, and THCCOOH. ) [ Time Frame: baseline and 1.5, 2, 3, 4, and 6 hours post-dosing ]
  • Mean Peak Change from Baseline Psychotomimetic effects as assessed by the Psychotomimetic States Inventory (PSI) [ Time Frame: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing ]
  • Mean Peak Change From Baseline Heart Rate [ Time Frame: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing ]
  • Mean Peak Change From Baseline Blood Pressure (mmHg) [ Time Frame: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing ]

Central Contacts and Locations

Central contacts

David Wolinsky, MD

(646) 572-6959dwolins2@jhmi.edu

Locations

Johns Hopkins University School of Medicine, Behavioral Pharmacology Research Unit

Recruiting

Baltimore, Maryland, United States, 21224

Contacts

David Wolinsky, MD

646-572-6959dwolins2@jhmi.edu

Principal Investigator:

David Wolinsky, MD

More Information

Sponsor

Johns Hopkins University

Last update posted

Jul 10, 2026

Last verified

Jul, 2026

Keywords

  • cannabis
  • pregenolone
  • cannabis intoxication
  • THC
  • delta-9-thc
  • CB1 receptor

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Johns Hopkins University on 2026-07-10.