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

NCT07644052 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: CAN-004U01DA066079
• Study Type: interventional
• Target: 420
• Locations: 1 country
• Sites: 22

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.
• BMI within 18.0 to 38.0 kg/m2, inclusive.
• Female participants must not be pregnant or lactating. If of childbearing potential - the participant agrees to use an accepted contraceptive regimen.
• Male participants who are fertile and engage in sexual activity must agree to use a double barrier method (e.g., condom and spermicide) during the study and to not donate sperm for 90 days after the last dose of study medication.
• Be seeking and motivated to discontinue cannabis and to minimize withdrawal symptoms.
• 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.
• Meet DSM-5 Cannabis Withdrawal Criteria.
• Report heavy use of daily/near daily cannabis.
• Have a urine drug screen positive for THC/THC metabolite and have a negative result for all other illicit/excluded drugs and alcohol at Screening and Randomization.
• Capable of giving informed consent and stated willingness to comply with all study procedures including inpatient and weekly outpatient visits, daily evening video calls, restrictions, and availability for the duration of the study.
• Willing to be admitted to an inpatient clinic with overnight stays on Days 1 through 6 and return for all outpatient visits.
• Ability to take study drug capsules at approximately the same time each day.
• Have regular access to the internet and access to video/virtual capabilities for video calls by any means.
• Agree to not use any alcohol during the study.

You may not qualify if:

• 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.
• Any clinically important abnormalities on Screening physical examination, assessments, electrocardiogram, or laboratory tests.
• Current or recent history of significant violent or suicidal behavior, risk for suicide or homicide.
• History of clinically significant medical condition that, in the opinion of the Principal Investigator, would jeopardize the safety of the participant or impact on the validity of the study results.
• Participants with risk factors for seizure.
• Known history of allergy, intolerance, or hypersensitivity to nabilone, gabapentin, or pregabalin.
• Prohibited medications at Screening:
• Current use of narcotics, psychedelics, stimulants, opioid agonists and antagonists, kratom, illicit drugs, ketamine, unregulated psychoactive drugs (sometimes known as "gas station drugs"), or products intended to induce a feeling of being high except for cannabis
• Regular benzodiazepine use (more than once per week) and no use within 7 days of Baseline Visit (Day 1)
• Current use (within 7 days of Baseline Visit) of OTC products to help with sleep or anxiety
• Prescription medications to help with sleep or anxiety within 14 days of Screening

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): collaborator
• PleoPharma, Inc.: lead

Study Sites (22)

Woodland International Research Group, LLC

Little Rock, Arkansas, 72211, United States

RECRUITING

Woodland Research Northwest, LLC

Rogers, Arkansas, 72758, United States

RECRUITING

Yale Stress Center

New Haven, Connecticut, 06519, United States

RECRUITING

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

DeLand, Florida, 32720, United States

RECRUITING

Research Centers of America

Hollywood, Florida, 33024, United States

RECRUITING

Sandhill Research, LLC d/b/a Accel Research Sites - St. Pete - Largo Clinical Research Unit

Largo, Florida, 33777, United States

RECRUITING

ForCare Clinical Research

Tampa, Florida, 33613, United States

RECRUITING

Neuroscience Research Institute

West Palm Beach, Florida, 33407, United States

RECRUITING

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

Decatur, Georgia, 30030, United States

RECRUITING

Evergreen Clinical Trials

Norcross, Georgia, 30092, United States

RECRUITING

CenExel iResearch, LLC

Savannah, Georgia, 31405, United States

RECRUITING

AMR Clinical

Lexington, Kentucky, 40509, United States

RECRUITING

Maryland Psychiatric Research Center, University of Maryland School of Medicine

Baltimore, Maryland, 21228, United States

RECRUITING

Oasis Clinical Research

Las Vegas, Nevada, 89121, United States

RECRUITING

Hassman Research Institute, LLC d/b/a CenExel Marlton, NJ

Marlton, New Jersey, 08053, United States

RECRUITING

The Research Foundation for Mental Hygiene/ New York State Psychiatric Institute

New York, New York, 10032, 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

Coastal Carolina Research Center, LLC

North Charleston, South Carolina, 29405, United States

RECRUITING

AMR Clinical

Knoxville, Tennessee, 37920, United States

RECRUITING

Community Clinical Research, Inc.

Austin, Texas, 78754, United States

RECRUITING

Memorial Hermann Village

Houston, Texas, 77043, 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 17, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: September 28, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (22)