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Cannabis IntoxicationPhase 2NCT07216690

Pregnenolone as a Treatment for Cannabis Intoxication

A Phase 2 study testing Cannabis, Pregnenolone 250 mg and Pregnenolone 500 mg in people with Cannabis Intoxication, run by Johns Hopkins University at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Cannabis Intoxication
What is being tested?
Cannabis, Pregnenolone 250 mg and Pregnenolone 500 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
20 participants
Where
1 siteUnited States
Study dates
24 Apr 2026to 1 Jan 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
  • 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

Who cannot join

  • 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
Show all 23Show fewer
  • 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/or THC at screening.
  • Breathalyzer screen indicating presence of alcohol at screening
  • 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 >/=110 during screening
  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

David Wolinsky, MD contact

(646) 572-6959

dwolins2@jhmi.edu

United States1 site, 1 recruiting

  • Johns Hopkins University School of Medicine, Behavioral Pharmacology Research Unit

    Baltimore, Maryland, 21224

    David Wolinsky, MD, 646-572-6959, dwolins2@jhmi.edu

    David Wolinsky, MD

    Recruiting

Other trials in United States

About this study

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.

Read the 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.

Being tested
Cannabis, Pregnenolone 250 mg, Pregnenolone 500 mg, Placebo, Placebo brownie
Keywords
cannabis, pregenolone, cannabis intoxication, THC, delta-9-thc, CB1 receptor
Medical subject headings
Marijuana Abuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CannabisDrug

    Also called delta-9-tetrahydrocannabinol, THC, delta-9-THC

    Cannabis brownie, 25mg THC

  • Pregnenolone 250 mgDrug

    Also called Pregnenolone

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

  • Pregnenolone 500 mgDrug

    Also called Pregnenolone

    Pregnenolone, high dose, two 250 mg pregnenolone capsules

  • PlaceboDrug

    Placebo capsule, 0mg

  • Placebo brownieDrug

    Placebo brownie, 0mg THC

Study groups in NCT07216690
Study groupRoleWhat they receive
Placebo Brownie and CapsulesPlacebo comparatorPlacebo brownie, 0mg THC; two 0 mg pregnenolone capsules
Receives: Drug: Placebo; Drug: Placebo brownie
Cannabis/THC brownie and Placebo CapsulesPlacebo comparator25mg Cannabis/THC Brownie; two 0 mg pregnenolone capsules
Receives: Drug: Cannabis; Drug: Placebo
Cannabis/THC Brownie and Pregnenolone, low doseExperimental25mg Cannabis/THC Brownie; one 250 mg pregnenolone capsule and one 0 mg pregnenolone capsule
Receives: Drug: Cannabis; Drug: Pregnenolone 250 mg
Cannabis/THC Brownie and Pregnenolone, high doseExperimental25mg Cannabis/THC Brownie and two 250 mg pregnenolone capsules
Receives: Drug: Cannabis; Drug: Pregnenolone 500 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

  2. 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).

    Measured: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

  3. 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).

    Measured: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

  4. 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.

    Measured: baseline and 1.5, 2, 3, 4, and 6 hours post-dosing

  5. 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.

    Measured: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

  6. Mean Peak Change From Baseline Heart Rate

    Mean Peak change from baseline heart rate (as measured by beats per minute)

    Measured: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

  7. Mean Peak Change From Baseline Blood Pressure (mmHg)

    Mean Peak change from baseline blood pressure (systolic and diastolic)

    Measured: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

Secondary outcomes (6)

  1. 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).

    Measured: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

  2. 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).

    Measured: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

  3. 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.

    Measured: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

  4. 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.

    Measured: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

  5. 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.

    Measured: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing

  6. 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.

    Measured: baseline and 1.5, 2, 3, 4, and 6 hours post-dosing

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Oct 2025
  2. Study start24 Apr 2026
  3. Primary completion1 Jan 2028 (estimated)
  4. Study completion1 Jan 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
Randomized, controlled, within subjects
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07216690
Sponsor's protocol ID
IRB00526530
Other IDs
R21DA063854
Status last verified
Sep 2026
First submitted
6 Oct 2025
Last updated
29 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cannabis, Pregnenolone 250 mg and Pregnenolone 500 mg in people with Cannabis Intoxication, run by Johns Hopkins University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact David Wolinsky, MD ((646) 572-6959, dwolins2@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Peak Change From Baseline Drug Effect as Assessed by the Drug Effect Questionnaire (DEQ) (time frame: baseline and 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dosing). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07216690.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2026; AzTrials last refreshed its copy on 6 Nov 2026.

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