NCT07216690

Pregnenolone as a Treatment for Cannabis Intoxication

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Johns Hopkins University · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

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

Interventions

Type	Name	Description
DRUG	Cannabis	Cannabis brownie, 25mg THC
DRUG	Pregnenolone 250 mg	Pregnenolone, low dose, one 250mg pregnenolone capsule and one 0 mg pregnenolone capsule
DRUG	Pregnenolone 500 mg	Pregnenolone, high dose, two 250 mg pregnenolone capsules
DRUG	Placebo	Placebo capsule, 0mg
DRUG	Placebo brownie	Placebo brownie, 0mg THC

Timeline

• Start date: 2026-05-01
• Primary completion: 2028-01-01
• Completion: 2029-01-01
• First posted: 2025-10-14
• Last updated: 2026-03-31

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study