Pregnenolone for Cannabis Intoxication

Overseen By David Wolinsky, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: Psychoactive substances, OTC drugs

Disqualifiers: Cardiovascular conditions, Hormone-sensitive conditions, Epilepsy, Schizophrenia, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether pregnenolone, a naturally occurring steroid hormone, can reverse the effects of cannabis intoxication. The goal is to determine if pregnenolone can reduce symptoms such as confusion or feeling too "high" after cannabis use. Participants will receive either a placebo or varying doses of pregnenolone after consuming cannabis. This study is suitable for healthy adults who have previously used cannabis but not within the last month. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important early-stage findings.

Will I have to stop taking my current medications?

Yes, you may need to stop taking your current medications. The trial excludes participants who use over-the-counter drugs, supplements, or prescription medications that could impact safety, according to the investigator's opinion.

Is there any evidence suggesting that pregnenolone is likely to be safe for humans?

Research shows that pregnenolone might help mitigate the effects of cannabis use. Earlier studies suggest that pregnenolone can protect the brain from cannabis, indicating it could be a safe option for cannabis users.

Early studies have tested pregnenolone to see if it can reduce the effects of marijuana use. These studies generally found it well-tolerated, with few side effects reported.

While these early results are promising, it's important to note that this research is still in its early stages. Although pregnenolone appears safe so far, further research is needed to confirm these findings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using pregnenolone for cannabis intoxication because it offers a novel approach by potentially modulating the effects of THC, the active component in cannabis. Unlike standard treatments that might focus on symptomatic relief, pregnenolone is a naturally occurring steroid hormone that could directly influence the brain's response to THC, potentially reducing its intoxicating effects. This unique mechanism of action, targeting the brain's cannabinoid receptors differently, sets pregnenolone apart from existing options and opens up new possibilities for effectively managing cannabis intoxication.

What evidence suggests that pregnenolone might be an effective treatment for cannabis intoxication?

Research suggests that pregnenolone might help counteract the effects of cannabis use. Pregnenolone, a natural substance in the body, has been shown in early studies to block marijuana's effects. In animal studies, pregnenolone reduced symptoms like anxiety and confusion caused by cannabis. These findings suggest it could help treat cannabis intoxication in humans. This trial will evaluate pregnenolone's effects at different doses, with some participants receiving a low dose and others a high dose, alongside a cannabis/THC brownie. Other participants will receive a placebo for comparison. While more research is needed, initial results are promising for managing cannabis-related symptoms. ^{1 4 5 6 7}

Who Is on the Research Team?

David Wolinsky, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for healthy adults who have used cannabis before. It's designed to see if pregnenolone, a hormone, can help with the effects of being high on cannabis. Participants will try different treatments in a controlled setting at Johns Hopkins.

Inclusion Criteria

Cannabis use within the past three years but none in the month prior to the first test session

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

Exclusion Criteria

Use of psychoactive substances (aside from nicotine, caffeine, and alcohol) in the month prior to study initiation

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 > 378 U/L (normal range 38-126), Total bilirubin >2.5 mg/dl (normal values=0.3-1.0 mg/dL), Glomerular filtration rate (EGFR) < 45 (normal values >60)

Current or past history of meeting DSM-5 criteria for schizophrenia spectrum or other psychotic disorders, or bipolar I or II disorder

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants complete four double-blind, randomized, outpatient sessions to assess the effects of pregnenolone on cannabis intoxication.

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pregnenolone

Trial Overview The study tests two doses of pregnenolone (250 mg and 500 mg) against placebos (inactive substances), including a placebo brownie, to see which is better at reducing the symptoms of cannabis intoxication.

How Is the Trial Designed?

Group I: Cannabis/THC Brownie and Pregnenolone, low dose Experimental Treatment 2 Interventions

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

Group II: Cannabis/THC Brownie and Pregnenolone, high dose Experimental Treatment 2 Interventions

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

Group III: Placebo Brownie and Capsules Placebo Group 2 Interventions

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

Group IV: Cannabis/THC brownie and Placebo Capsules Placebo Group 2 Interventions

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

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07216690?term=heart+disease

Pregnenolone as a Treatment for Cannabis Intoxication The present study will characterize the ability of pregnenolone to reverse the acute intoxication and associated symptoms of cannabis.

2. ctv.veeva.com ctv.veeva.com/study/pregnenolone-as-a-treatment-for-cannabis-intoxication

Pregnenolone as a Treatment for Cannabis Intoxication The present study will characterize the ability of pregnenolone to reverse the acute intoxication and associated symptoms of cannabis.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02439814

NCT02439814 | Pregnenolone and Marijuana Dependence Pregnenolone is a steroid that occurs naturally in the body, and early studies have shown that pregnenolone may block the effects of marijuana intoxication.

4. withpower.com withpower.com/trial/phase-2-cannabis-intoxication-11-2025-8951f

Pregnenolone for Cannabis Intoxication · Info for Participants The present study will characterize the ability of pregnenolone to reverse the acute intoxication and associated symptoms of cannabis.

5. researchgate.net researchgate.net/publication/313880867_Pregnenolone_blocks_cannabinoid-induced_acute_psychotic-like_states_in_mice

Pregnenolone blocks cannabinoid-induced acute ... These findings indicate that CB1-biased signaling mediated by pregnenolone may be useful for the treatment of Cannabis intoxication and to ...

6. nature.com nature.com/articles/s41591-023-02381-w

Signaling-specific inhibition of the CB1 receptor for ... ... toxicity and (3) formulation and bioavailability issues, each ... Pregnenolone can protect the brain from cannabis intoxication.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12034656/

Acute cannabis intoxication among the paediatric population Abstract. This narrative review synthesizes the toxicological, clinical and medico-legal aspects of paediatric cannabis intoxication.