Efficacy of PP-01 in Mitigating Cannabis Withdrawal Symptoms in Adults With Cannabis Use Disorder

NCT07644052 | Recruiting Phase 3 FDA Drug

• 1 other identifier: CAN-004
• Study Type: interventional
• Target: 420
• Locations: 1 country
• Sites: 8

Brief Summary

This study is a randomized, double-blind, placebo and active-controlled, multicenter trial conducted to evaluate whether PP-01 mitigates the withdrawal symptoms associated with discontinuing cannabis in participants with moderate to severe cannabis use disorder (CUD). Study participants will receive PP-01, nabilone, or placebo every day for 34 days. The total study duration will be approximately 78 days, including screening and a one-week inpatient stay. Following the initial inpatient portion of the study, participants will return to the clinic for six clinic visits and complete two telemedicine appointments. Participants will complete daily symptom diaries and other study-related questionnaires. Participants who complete the core study may be eligible to participate in a repeat dosing extension study if they meet required criteria.

Conditions

Cannabis Withdrawal

Keywords

Cannabis Use Disorder; Marijuana Use Disorder

Outcome Measures

Primary Outcomes (2)

• AUCs of the CSCW over Days 2 to 7, inclusive, comparing PP-01 vs Placebo

  Days to 2 to 7

• AUCs of the CSCW over Days 25 to 35, inclusive, comparing PP-01 vs Nabilone to assess rebound

  Days 25 to 35

Secondary Outcomes (7)

• AUCs of CWS-20 Irritability Domain scores over Days 2 to 35 comparing PP-01 vs Placebo

  Days 2 to 35

• AUCs of CWS-20 Irritability Domain scores over Days 25 to 35 comparing PP-01 vs Nabilone

  Days 25 to 35

• AUCs of the CSCW over Days 2 to 35 comparing PP-01 vs Placebo

  Days 2 to 35

• AUCs of CWS-20 Sleep Domain scores over Days 2 to 35 comparing PP-01 vs Placebo

  Days 2 to 35

• AUCs of CWS-20 Sleep Domain scores over Days 2 to 7 comparing PP-01 vs Placebo

  Days 2 to 7

Study Arms (3)

PP-01

EXPERIMENTAL

Oral PP-01 tapered/titrated over 34 days

Combination Product: PP-01

Nabilone

ACTIVE COMPARATOR

Oral Nabilone tapered/titrated over 34 days

Drug: Nabilone

Placebo

PLACEBO COMPARATOR

Oral Placebo given daily for 34 days

Drug: Placebo

Interventions

PP-01 COMBINATION_PRODUCT

Cannabinoid-1 (CB1) partial agonist / GABAergic modulator

PP-01

Nabilone DRUG

CB1 partial agonist

Nabilone

Placebo DRUG

Placebo comparator

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Generally healthy adults between the ages of 18 and 55, inclusive.
• Meet DSM-5 diagnostic criteria for current moderate to severe CUD as confirmed by a licensed physician or psychologist or addiction medicine specialist. An individual with documented experience in the diagnosis of CUD may be qualified upon Sponsor approval.
• BMI within 18.0 to 38.0 kg/m2, inclusive.
• Female participants must not be pregnant or lactating. Nonpregnancy will be confirmed for all females by a urine pregnancy test conducted at Screening and at the Randomization Visit prior to enrollment into the study.
• If of childbearing potential - the participant agrees to use one of the accepted contraceptive regimens from Screening to the first administration of the study medication, during the study, and for at least 30 days after the last dose of the study medication. An acceptable method of contraception includes one of the following:
• Hormonal contraceptives (birth control pills, injectable/implant/insertable hormonal birth control products, transdermal patch)
• Intrauterine device (with or without hormones)
• OR agrees to use a double barrier method (e.g., condom and spermicide) during the study and for at least 30 days after the last dose of the study medication
• The Investigator can use their judgement and familiarity with the participant's preferred and usual lifestyle to understand which form of birth control would be the best and also to determine if abstinence is an option what would achieve 100% effectiveness
• Females of non-childbearing potential - should be surgically sterile (i.e., has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or be postmenopausal (at least 1 year without menses)
• Male participants who are fertile and engage in sexual activity must agree to use a double barrier method (e.g., condom and spermicide) and agree to not donate sperm during the study and for at least 90 days after the last dose of the study medication.
• Be seeking and motivated to discontinue cannabis and to minimize withdrawal symptoms related to cannabis discontinuation.
• Agree to not use cannabis or any product containing CBD, hemp derivatives, terpenes or any THC containing product including delta-8, delta-10, THC-A or any other cannabinoid-like product following Randomization and throughout the study duration.
• Have experienced cravings for cannabis and at least three withdrawal symptoms as defined by DSM-5 Cannabis Withdrawal Syndrome diagnostic criteria within the past year when previously trying to discontinue or reduce use of cannabis
• Meet Criterion C on the DSM-5 Cannabis Withdrawal Diagnostic Criteria

You may not qualify if:

• Participants with history or significant presence of any of the following criteria should be excluded from enrollment into the study:
• Lifetime history of DSM-5 diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder.
• Current DSM-5 criteria for a psychiatric disorder that in the Investigator's judgment is unstable, would be disrupted by the study medication, or is likely to require new pharmacotherapy or psychotherapy during the study period. Individuals who are currently stable on psychotropic medication for at least 3 months may be included at the discretion of the Investigator's judgement.
• Participants who meet DSM-5 criteria for any history of or current drug use disorder within the previous 2 years, other than cannabis, nicotine, or caffeine use disorders.
• Participants who consume alcohol on a regular or frequent basis and who do not agree or are deemed by the Investigator to be unable to discontinue alcohol for the duration of the study.
• Participants using cannabis for a physician directed medical condition requiring use such as epilepsy.
• Unstable medical conditions, such as AIDS, cancer, uncontrolled hypertension, Type 1 diabetes or uncontrolled or multi-dose insulin treated Type 2 diabetes, pulmonary hypertension, or heart disease.
• Positive test results for HIV-1/HIV-2 Ag/Ab, HBsAg, or HCVAb unless previously treated and successfully cleared of Hepatitis C virus.
• Current or recent history of significant violent or suicidal behavior, risk for suicide or homicide:
• \- Participants with any suicidal behavior or answering "yes" to Question 4 or 5 on suicidal ideation within the past 1 year based on the Screening version of the C-SSRS
• History of clinically significant hepatic, renal, cardiovascular, pulmonary, hematologic, neurological, psychiatric, gastrointestinal, endocrine, oncologic, immunologic, dermatologic disease of any etiology (including infections), or any other condition that, in the opinion of the Principal Investigator, would jeopardize the safety of the participant or impact the validity of the study results.
• Presence or history of clinically significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability, with the exception that cholecystectomy is permitted at the discretion of the Investigator.
• Any clinically important abnormalities on Screening PE, assessments, ECG, or laboratory tests, including but not limited to:
• Hemoglobin \< 10.0 g/dL
• Serum creatinine:

Sponsors & Collaborators

• PleoPharma, Inc.: lead

Study Sites (8)

University Clinical Research-DeLand, LLC d/b/a Accel Research Sites - DeLand Clinical Research Unit

DeLand, Florida, 32720, United States

RECRUITING

Sandhill Research, LLC d/b/a Accel Research Sites - NeuroStudies Clinical Research Unit 755

Largo, Florida, 33777, United States

RECRUITING

ForCare Clinical Research

Tampa, Florida, 33613, United States

RECRUITING

Sandhill Research, LLC d/b/a Accel Research Sites - NeuroStudies Clinical Research Unit 755

Decatur, Georgia, 30030, United States

RECRUITING

CenExel iResearch, LLC

Savannah, Georgia, 31405, United States

RECRUITING

Richmond Behavioral Associates

Staten Island, New York, 10314, United States

RECRUITING

Neuro-Behavioral Clinical Research, Inc.

North Canton, Ohio, 44720, United States

RECRUITING

AMR Clinical

Knoxville, Tennessee, 37920, United States

RECRUITING

MeSH Terms

Interventions

nabilone

Study Officials

• Jay Constantine, MD

  PleoPharma, Inc.

  STUDY DIRECTOR

Central Study Contacts

LBR Regulatory

CONTACT

859-426-5035; lois.rosenberger@lbria.com

PleoPharma, Inc.

CONTACT

610-937-2882; jcon@pleopharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2026
• First Posted: June 12, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: June 12, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)