Pregnenolone as a Treatment for Cannabis Intoxication

NCT07216690 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: IRB00526530R21DA063854
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Keywords

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

Outcome Measures

Primary Outcomes (7)

• Mean Peak Change From Baseline Drug Effect as Assessed by the Drug Effect Questionnaire (DEQ)

  Mean Peak change from baseline rating (0-100) of Drug Effect items related to stimulation (e.g., alertness) and sedation (e.g., sleepy/tired) on the DEQ, a visual analog scale (VAS) self-report questionnaire, with 0 being no effect and 100 being maximum effect.

  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)

  Computerized version of Digit Symbol Substitution Task will be administered to assess psychomotor performance. Mean peak change from baseline total correct trials in 90-seconds. Minimum score of 0 but no maximum score (higher scores indicate better performance).

  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)

  Computerized version of Paced Auditory Serial Addition Task administered to assess working memory performance. Mean peak change from baseline total correct trials out of 90 recorded is primary outcome (higher scores indicate better performance).

  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. )

  Mean peak levels of pregnenolone, THC, and the THC metabolites 11-OH-THC, and THCCOOH in the blood of participants.

  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)

  Mean Peak change from baseline rating of PSI, a 48-item scale designed to measure psychotomimetic effects resulting from psychoactive substance use. Participants rate each item on a four-point visual analog scale, 0 (not at all), 1 (slightly), 2 (moderately), or 3 (strongly). Higher score worse effects.

  baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

• Mean Peak Change From Baseline Heart Rate

  Mean Peak change from baseline heart rate (as measured by beats per minute)

  baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

• Mean Peak Change From Baseline Blood Pressure (mmHg)

  Mean Peak change from baseline blood pressure (systolic and diastolic)

  baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

Secondary Outcomes (6)

• Mean peak change from baseline psychomotor performance (attempted and percentage correct) as assessed by the Digit Symbol Substitution Task (DSST)

  baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

• Mean peak change from baseline working memory performance (reaction time) as assessed by the Paced Auditory Serial Addition Task (PASAT)

  baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

• Mean Peak Change From Baseline Drug Effect (positive effect) as Assessed by the Drug Effect Questionnaire (DEQ)

  baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

• Mean Peak Change From Baseline Drug Effect (negative effect) as Assessed by the Drug Effect Questionnaire (DEQ)

  baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

• Mean Peak Change From Baseline Drug Effect (cannabis specific) as Assessed by the Drug Effect Questionnaire (DEQ)

  baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

Study Arms (4)

Placebo Brownie and Capsules

PLACEBO COMPARATOR

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

Drug: Placebo; Drug: Placebo brownie

Cannabis/THC brownie and Placebo Capsules

PLACEBO COMPARATOR

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

Drug: Cannabis; Drug: Placebo

Cannabis/THC Brownie and Pregnenolone, low dose

EXPERIMENTAL

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

Drug: Cannabis; Drug: Pregnenolone 250 mg

Cannabis/THC Brownie and Pregnenolone, high dose

EXPERIMENTAL

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

Drug: Cannabis; Drug: Pregnenolone 500 mg

Interventions

Pregnenolone 500 mg DRUG

Pregnenolone, high dose, two 250 mg pregnenolone capsules

Also known as: Pregnenolone

Cannabis/THC Brownie and Pregnenolone, high dose

Cannabis DRUG

Cannabis brownie, 25mg THC

Also known as: delta-9-tetrahydrocannabinol, THC, delta-9-THC

Cannabis/THC Brownie and Pregnenolone, high dose; Cannabis/THC Brownie and Pregnenolone, low dose; Cannabis/THC brownie and Placebo Capsules

Pregnenolone 250 mg DRUG

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

Also known as: Pregnenolone

Cannabis/THC Brownie and Pregnenolone, low dose

Placebo DRUG

Placebo capsule, 0mg

Cannabis/THC brownie and Placebo Capsules; Placebo Brownie and Capsules

Placebo brownie DRUG

Placebo brownie, 0mg THC

Placebo Brownie and Capsules

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Johns Hopkins University School of Medicine, Behavioral Pharmacology Research Unit

Baltimore, Maryland, 21224, United States

RECRUITING

MeSH Terms

Conditions

Marijuana Abuse

Interventions

nabiximols; Dronabinol; Pregnenolone

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Study Officials

• David Wolinsky, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Wolinsky, MD

CONTACT

(646) 572-6959; dwolins2@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Double blind, double dummy
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, controlled, within subjects

Study Record Dates

• First Submitted: October 6, 2025
• First Posted: October 14, 2025
• Study Start: April 24, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: May 1, 2026

Record last verified: 2026-04

Locations

US (1)