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

September 1, 2026 updated by: PleoPharma, Inc.

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo and Active-Controlled Clinical Trial of Titrating Doses of PP-01 for the Mitigation of Cannabis Withdrawal Symptoms in Adults With Cannabis Use Disorder: Core Study With Safety Extension Phase

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
420

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72211
        • Recruiting
        • Woodland International Research Group, LLC
        • Principal Investigator:
          • George Konis, MD
      • Rogers, Arkansas, United States, 72758
        • Recruiting
        • Woodland Research Northwest, LLC
        • Principal Investigator:
          • Ryan Mahelona, MD
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Recruiting
        • Yale Stress Center
        • Principal Investigator:
          • Rajita Sinha, PhD
    • Florida
      • DeLand, Florida, United States, 32720
        • Recruiting
        • University Clinical Research-DeLand, LLC d/b/a Accel Research Sites - DeLand Clinical Research Unit
        • Principal Investigator:
          • Bruce G. Rankin, DO
      • Hollywood, Florida, United States, 33024
        • Recruiting
        • Research Centers of America
        • Principal Investigator:
          • Edwin A. Gomez, MD
      • Largo, Florida, United States, 33777
        • Recruiting
        • Sandhill Research, LLC d/b/a Accel Research Sites - St. Pete - Largo Clinical Research Unit
        • Principal Investigator:
          • Rosario B. Hidalgo, MD
      • Tampa, Florida, United States, 33613
        • Recruiting
        • ForCare Clinical Research
        • Principal Investigator:
          • Marlene P. Hart, MD
      • West Palm Beach, Florida, United States, 33407
        • Recruiting
        • Neuroscience Research Institute
        • Principal Investigator:
          • Danesh Alam, MD
    • Georgia
      • Decatur, Georgia, United States, 30030
        • Recruiting
        • Sandhill Research, LLC d/b/a Accel Research Sites - NeuroStudies Clinical Research Unit 755
        • Principal Investigator:
          • Marshall L. Nash, MD, FAHA, CPI, FAPCR
      • Norcross, Georgia, United States, 30092
        • Recruiting
        • Evergreen Clinical Trials
        • Principal Investigator:
          • Dmitriy Pelishev, DO
      • Savannah, Georgia, United States, 31405
        • Recruiting
        • CenExel iResearch, LLC
        • Principal Investigator:
          • Nancy E. Backus, MD
    • Kentucky
      • Lexington, Kentucky, United States, 40509
        • Recruiting
        • AMR Clinical
        • Principal Investigator:
          • Peter Akpunonu, MD
    • Maryland
      • Baltimore, Maryland, United States, 21228
        • Recruiting
        • Maryland Psychiatric Research Center, University of Maryland School of Medicine
        • Principal Investigator:
          • David A Gorelick, MD, PhD
    • Nevada
      • Las Vegas, Nevada, United States, 89121
        • Recruiting
        • Oasis Clinical Research
        • Principal Investigator:
          • Stephen Tam, MD
    • New Jersey
      • Marlton, New Jersey, United States, 08053
        • Recruiting
        • Hassman Research Institute, LLC d/b/a CenExel Marlton, NJ
        • Principal Investigator:
          • Elan A. Cohen, PhD
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • The Research Foundation for Mental Hygiene/ New York State Psychiatric Institute
        • Principal Investigator:
          • John Mariani, MD
      • Staten Island, New York, United States, 10314
        • Recruiting
        • Richmond Behavioral Associates
        • Principal Investigator:
          • Romana Kulikova, MD
    • Ohio
      • North Canton, Ohio, United States, 44720
        • Recruiting
        • Neuro-Behavioral Clinical Research, Inc.
        • Principal Investigator:
          • Shishuka Malhotra, MD
    • South Carolina
      • North Charleston, South Carolina, United States, 29405
        • Recruiting
        • Coastal Carolina Research Center, LLC
        • Principal Investigator:
          • Elizabeth Perkins, MD
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • Recruiting
        • AMR Clinical
        • Principal Investigator:
          • Jerry L. Punch, MD
    • Texas
      • Austin, Texas, United States, 78754
        • Recruiting
        • Community Clinical Research, Inc.
        • Principal Investigator:
          • David Brown, MD
      • Houston, Texas, United States, 77043
        • Recruiting
        • Memorial Hermann Village
        • Principal Investigator:
          • Dominick Stevan D'Aunno, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Generally healthy adults between the ages of 18 and 55, inclusive.
  2. Meet DSM-5 diagnostic criteria for current moderate to severe CUD as confirmed by a licensed physician or psychologist or addiction medicine specialist.
  3. BMI within 18.0 to 38.0 kg/m2, inclusive.
  4. Female participants must not be pregnant or lactating. If of childbearing potential - the participant agrees to use an accepted contraceptive regimen.
  5. 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.
  6. Be seeking and motivated to discontinue cannabis and to minimize withdrawal symptoms.
  7. 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.
  8. Meet DSM-5 Cannabis Withdrawal Criteria.
  9. Report heavy use of daily/near daily cannabis.
  10. 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.
  11. 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.
  12. Willing to be admitted to an inpatient clinic with overnight stays on Days 1 through 6 and return for all outpatient visits.
  13. Ability to take study drug capsules at approximately the same time each day.
  14. Have regular access to the internet and access to video/virtual capabilities for video calls by any means.
  15. Agree to not use any alcohol during the study.
  16. No plan to change current nicotine use.
  17. Ability to read, understand, and complete daily diaries.

Exclusion Criteria:

  1. Lifetime history of DSM-5 diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder.
  2. 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.
  3. 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.
  4. 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.
  5. Participants using cannabis for a physician directed medical condition requiring use such as epilepsy.
  6. Any clinically important abnormalities on Screening physical examination, assessments, electrocardiogram, or laboratory tests.
  7. Current or recent history of significant violent or suicidal behavior, risk for suicide or homicide.
  8. 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.
  9. Participants with risk factors for seizure.
  10. Known history of allergy, intolerance, or hypersensitivity to nabilone, gabapentin, or pregabalin.

  11. 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
    • Current use of nabilone, dronabinol, Sativex, Epidiolex, synthetic cannabinoids
    • Gabapentin or pregabalin or use within 30 days of Screening
  12. Heavy users of alcohol within 60 days of Screening or binge drinkers of alcohol within 30 days of Screening.
  13. A positive urine drug/alcohol test at Screening or Randomization for narcotics and/or illicit drugs other than cannabis. If the test is positive for benzodiazepines or alcohol at Screening, and if it is reported that they are only occasional users, a repeat urine drug screen can be performed at the discretion of the Medical Monitor and must be negative at the time of Randomization.
  14. Use of an investigational drug or biologic within 30 days or 5 times the half-life (whichever is longer) prior to the Screening Visit.
  15. Active influenza or COVID-19 infection or planned vaccination.
  16. Prior participation in any PleoPharma clinical study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: PP-01
Oral PP-01 tapered/titrated over 34 days
Combination product: PP-01
Cannabinoid-1 (CB1) partial agonist / GABAergic modulator
Active Comparator: Nabilone
Oral Nabilone tapered/titrated over 34 days
Drug: Nabilone
CB1 partial agonist
Placebo Comparator: Placebo
Oral Placebo given daily for 34 days
Drug: Placebo
Placebo comparator

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
AUCs of the CSCW over Days 2 to 7, inclusive, comparing PP-01 vs Placebo
Time Frame: Days to 2 to 7
Days to 2 to 7
AUCs of the CSCW over Days 25 to 35, inclusive, comparing PP-01 vs Nabilone to assess rebound
Time Frame: Days 25 to 35
Days 25 to 35

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
AUCs of CWS-20 Irritability Domain scores over Days 2 to 35 comparing PP-01 vs Placebo
Time Frame: Days 2 to 35
Days 2 to 35
AUCs of CWS-20 Irritability Domain scores over Days 25 to 35 comparing PP-01 vs Nabilone
Time Frame: Days 25 to 35
Days 25 to 35
AUCs of the CSCW over Days 2 to 35 comparing PP-01 vs Placebo
Time Frame: Days 2 to 35
Days 2 to 35
AUCs of CWS-20 Sleep Domain scores over Days 2 to 35 comparing PP-01 vs Placebo
Time Frame: Days 2 to 35
Days 2 to 35
AUCs of CWS-20 Sleep Domain scores over Days 2 to 7 comparing PP-01 vs Placebo
Time Frame: Days 2 to 7
Days 2 to 7
AUCs of CWS-20 Craving Domain scores over Days 2 to 35 comparing PP-01 vs Placebo
Time Frame: Days 2 to 35
Days 2 to 35
AUCs of CWS-20 Craving Domain scores over Days 2 to 7 comparing PP-01 vs Placebo
Time Frame: Days 2 to 7
Days 2 to 7

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
PleoPharma, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Jay Constantine, MD, PleoPharma, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 17, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 8, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 8, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 12, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 2, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 1, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CAN-004

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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