Pregnenolone as a Treatment for Cannabis Intoxication

NCT ID: NCT07216690

Last Updated: 2026-01-30

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-03-01
• Study Completion Date: 2029-01-01

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.

Detailed Description

This human laboratory study will characterize the ability of pregnenolone to reverse the acute cannabis intoxication using measures of subjective drug effects, cardiovascular responses, and cognitive performance. Participants (n=16) will complete four double-blind, randomized, outpatient sessions. In each session, participants will self-administer cannabis containing either 0 mg THC (placebo) or 25 mg THC (active) via an oral route of administration. Ninety minutes after cannabis administration, participants will self-administer two oral capsules containing either 0 mg pregnenolone or 250 mg pregnenolone for a total of either 0 mg, 250 mg, or 500mg pregnenolone. Assessments will include subjective drug effect instruments, a battery of cognitive and psychomotor performance tasks, and physiological measures. Sessions will be conducted at a target rate of once per week. Results from this study of pregnenolone could have far-reaching clinical implications: not only would results provide conceptual support for NAMs as treatments for cannabis intoxication but may posit pregnenolone itself as a novel pharmacotherapeutic that could reduce the burden of ineffective and potentially harmful medications currently used in the treatment of cannabis intoxication in emergency settings. If pregnenolone is shown to be effective, additional drug development can be done to determine the best formulation, dose, and route of administration for maximal clinical benefit. Should pregnenolone not reverse THC intoxication completely, development of analogs with greater efficacy can be explored.

Conditions

Cannabis Intoxication

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo Brownie and Capsules

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsule, 0mg

Placebo brownie

Intervention Type: DRUG

Placebo brownie, 0mg THC

Cannabis/THC brownie and Placebo Capsules

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

Group Type: PLACEBO_COMPARATOR

Cannabis

Intervention Type: DRUG

Cannabis brownie, 25mg THC

Placebo

Intervention Type: DRUG

Placebo capsule, 0mg

Cannabis/THC Brownie and Pregnenolone, low dose

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

Group Type: EXPERIMENTAL

Cannabis

Intervention Type: DRUG

Cannabis brownie, 25mg THC

Pregnenolone 250 mg

Intervention Type: DRUG

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

Cannabis/THC Brownie and Pregnenolone, high dose

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

Group Type: EXPERIMENTAL

Cannabis

Intervention Type: DRUG

Cannabis brownie, 25mg THC

Pregnenolone 500 mg

Intervention Type: DRUG

Pregnenolone, high dose, two 250 mg pregnenolone capsules

Interventions

Cannabis

Cannabis brownie, 25mg THC

Intervention Type: DRUG

Pregnenolone 250 mg

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

Intervention Type: DRUG

Pregnenolone 500 mg

Pregnenolone, high dose, two 250 mg pregnenolone capsules

Intervention Type: DRUG

Placebo

Placebo capsule, 0mg

Intervention Type: DRUG

Placebo brownie

Placebo brownie, 0mg THC

Intervention Type: DRUG

Other Intervention Names

delta-9-tetrahydrocannabinol; THC; delta-9-THC; Pregnenolone; Pregnenolone

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Wolinsky, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins University School of Medicine, Behavioral Pharmacology Research Unit

Baltimore, Maryland, United States

Countries

United States

Central Contacts

David Wolinsky, MD

Role: CONTACT

dwolins2@jhmi.edu

(646) 572-6959

Facility Contacts

David Wolinsky, MD

Role: primary

dwolins2@jhmi.edu

646-572-6959

Other Identifiers

R21DA063854

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00526530

Identifier Type: -

Identifier Source: org_study_id