A Phase 2 interventional study of Cannabis and Pregnenolone 250 mg in Cannabis Intoxication, sponsored by Johns Hopkins University. Recruiting at 1 site in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-29.
Sponsored by Johns Hopkins University · Phase 2, Interventional, and Treatment
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.
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.
Exclusion Criteria
Any of the following laboratory values during screening or upon admission:
Placebo brownie, 0mg THC; two 0 mg pregnenolone capsules
Drug: Placebo · Drug: Placebo brownie
25mg Cannabis/THC Brownie; two 0 mg pregnenolone capsules
Drug: Cannabis · Drug: Placebo
25mg Cannabis/THC Brownie; one 250 mg pregnenolone capsule and one 0 mg pregnenolone capsule
Drug: Cannabis · Drug: Pregnenolone 250 mg
25mg Cannabis/THC Brownie and two 250 mg pregnenolone capsules
Drug: Cannabis · Drug: Pregnenolone 500 mg
Cannabis brownie, 25mg THC
Also known as: delta-9-tetrahydrocannabinol, THC, delta-9-THC
Pregnenolone, low dose, one 250mg pregnenolone capsule and one 0 mg pregnenolone capsule
Also known as: Pregnenolone
Pregnenolone, high dose, two 250 mg pregnenolone capsules
Also known as: Pregnenolone
Placebo capsule, 0mg
Placebo brownie, 0mg THC
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.
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)
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).
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)
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).
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. )
Mean peak levels of pregnenolone, THC, and the THC metabolites 11-OH-THC, and THCCOOH in the blood of participants.
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)
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.
Time frame: 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)
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)
Mean Peak change from baseline blood pressure (systolic and diastolic)
Time frame: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing
Mean peak change from baseline psychomotor performance (attempted and percentage correct) 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 number attempted and percentage correct trials in 90-seconds. Minimum score of 0 but no maximum score (higher scores indicate better performance).
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 (reaction time) 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 reaction time on correct trials out of 90 recorded is secondary outcome (faster reaction times indicate better performance).
Time frame: 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)
Mean Peak change from baseline rating (0-100) of "positive" Drug Effect items (e.g., "like"; "want more) on the DEQ, a visual analog scale (VAS) self-report questionnaire, with 0 being no effect and 100 being maximum effect.
Time frame: 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)
Mean Peak change from baseline rating (0-100) of negative Drug Effect items (e.g., "dislike") on the DEQ, a visual analog scale (VAS) self-report questionnaire, with 0 being no effect and 100 being maximum effect.
Time frame: 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)
Mean Peak change from baseline rating (0-100) of cannabis-specific Drug Effect items (e.g., "paranoid"; "munchies") on the DEQ, a visual analog scale (VAS) self-report questionnaire, with 0 being no effect and 100 being maximum effect.
Time frame: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing
Mean Peak Changes from Baseline in ratios of blood pregnenolone levels to blood levels of THC and 11-OH-THC
Peak blood levels of pregnenolone will be compared to peak blood levels of THC and 11-OH-THC across the timepoints throughout the study.
Time frame: baseline and 1.5, 2, 3, 4, and 6 hours post-dosing
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