Pregnenolone to treat cannabis intoxication
Pregnenolone as a Treatment for Cannabis Intoxication
This trial tests whether oral pregnenolone can quickly reverse cannabis intoxication symptoms in healthy adults with prior cannabis use.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 20 (estimated) |
| Ages | 18 Years to 65 Years |
| Sex | All |
| Sponsor | Johns Hopkins University Academic / other |
| Locations | 1 site (Baltimore, Maryland) |
| Trial ID | NCT07216690 on ClinicalTrials.gov |
What this trial studies
This double-blind, randomized, within-subject crossover Phase 2 study will enroll 16 healthy adults with prior cannabis use to measure whether pregnenolone can reverse acute cannabis effects. In four outpatient sessions participants will self-administer oral cannabis containing 0 or 25 mg THC, then 90 minutes later receive 0 mg, 250 mg, or 500 mg pregnenolone under blinded conditions. Outcomes include subjective drug-effect ratings, cognitive and psychomotor performance tasks, and cardiovascular measures collected across sessions. Sessions are spaced about one week apart to compare responses within each participant and inform future development of CB1-receptor NAM medications.
Who should consider this trial
Good fit: Ideal candidates are healthy adults aged 18–65 with a history of cannabis use within the past three years, who meet blood pressure, heart rate, BMI, and medication-screening requirements and can abstain from cannabis for one month before sessions.
Not a fit: People with significant medical or psychiatric conditions, current use of psychoactive prescription medications, recent illicit substance use, or those outside the trial’s age/BMI limits are unlikely to benefit from this study.
Why it matters
Potential benefit: If effective, pregnenolone could provide a fast-acting medication to reduce acute cannabis intoxication symptoms and decrease reliance on less effective or harmful treatments in emergency settings.
How similar studies have performed: Preclinical work and limited human laboratory data suggest pregnenolone or other CB1 negative allosteric modulators can blunt THC effects, but efficacy for treating intoxication in clinical/emergency settings remains unproven.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
Baltimore, Maryland
- Johns Hopkins University School of Medicine, Behavioral Pharmacology Research Unit — Baltimore, Maryland, United States (Recruiting)
Study contacts
- Principal investigator: David Wolinsky, MD — Johns Hopkins University
- Study coordinator: David Wolinsky, MD
- Email: dwolins2@jhmi.edu
- Phone: (646) 572-6959
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.