Pregnenolone as a Treatment for Cannabis Intoxication

Johns Hopkins University

Status and phase: Begins enrollment this month; Phase 2

Conditions: Cannabis Intoxication

Treatments: Drug: Placebo; Drug: Pregnenolone 500 mg; Drug: Pregnenolone 250 mg; Drug: Cannabis; Drug: Placebo brownie

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07216690

R21DA063854 (U.S. NIH Grant/Contract)

IRB00526530

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

• Self-report 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 > 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

• 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 indicating the presence of substances including amphetamines, barbiturates, benzodiazepines, cocaine, opioids (including fentanyl), PCP, and THC at screening and prior to study sessions

• Breath 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), vaginal ring, and/or regular use of condoms or diaphragm.

• Breath alcohol screens indicating presence of alcohol at screening and prior to study sessions

• SBP >/= 140, DBP >/= 90, or pulse >/=100 during screening and/or prior to dosing session

• Has donated blood within 30 days of the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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40 participants in 4 patient groups, including a placebo group

Placebo Brownie and Capsules

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo brownie

Drug: Placebo

Cannabis/THC brownie and Placebo Capsules

Placebo Comparator group

Description:

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

Treatment:

Drug: Cannabis

Drug: Placebo

Cannabis/THC Brownie and Pregnenolone, low dose

Experimental group

Description:

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

Treatment:

Drug: Cannabis

Drug: Pregnenolone 250 mg

Cannabis/THC Brownie and Pregnenolone, high dose

Experimental group

Description:

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

Treatment:

Drug: Cannabis

Drug: Pregnenolone 500 mg