Cannabis WithdrawalPhase 3NCT07644052
Efficacy of PP-01 in Mitigating Cannabis Withdrawal Symptoms in Adults With Cannabis Use Disorder
A Phase 3 study testing PP-01 and Nabilone in people with Cannabis Withdrawal, run by PleoPharma, Inc. at 22 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Cannabis Withdrawal
- What is being tested?
- PP-01 and Nabilone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 420 participants
- Where
- 22 sitesUnited States
- Study dates
- 17 Jun 2026to Sep 2027
- Phase
- Phase 3
- 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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
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- 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.
- No plan to change current nicotine use.
- Ability to read, understand, and complete daily diaries.
Who cannot join
- 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.
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- 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
- Current use of nabilone, dronabinol, Sativex, Epidiolex, synthetic cannabinoids
- Gabapentin or pregabalin or use within 30 days of Screening
- Heavy users of alcohol within 60 days of Screening or binge drinkers of alcohol within 30 days of Screening.
- 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.
- Use of an investigational drug or biologic within 30 days or 5 times the half-life (whichever is longer) prior to the Screening Visit.
- Active influenza or COVID-19 infection or planned vaccination.
- Prior participation in any PleoPharma clinical study.
Trial locations and contacts
22 sites in 1 country. Contact the study team or a site near you to ask about taking part.
22 sites in 1 country
United States22 sites, 22 recruiting
- Recruiting
Community Clinical Research, Inc.
Austin, Texas, 78754
David Brown, MD
- Recruiting
Maryland Psychiatric Research Center, University of Maryland School of Medicine
Baltimore, Maryland, 21228
David A Gorelick, MD, PhD
- Recruiting
Sandhill Research, LLC d/b/a Accel Research Sites - NeuroStudies Clinical Research Unit 755
Decatur, Georgia, 30030
Marshall L. Nash, MD, FAHA, CPI, FAPCR
- Recruiting
University Clinical Research-DeLand, LLC d/b/a Accel Research Sites - DeLand Clinical Research Unit
DeLand, Florida, 32720
Bruce G. Rankin, DO
- Recruiting
Research Centers of America
Hollywood, Florida, 33024
Edwin A. Gomez, MD
- Recruiting
Memorial Hermann Village
Houston, Texas, 77043
Dominick Stevan D'Aunno, MD
- Recruiting
AMR Clinical
Knoxville, Tennessee, 37920
Jano John Yanoyan, DO, MBA, CPE
- Recruiting
Sandhill Research, LLC d/b/a Accel Research Sites - St. Pete - Largo Clinical Research Unit
Largo, Florida, 33777
Rosario B. Hidalgo, MD
- Recruiting
Oasis Clinical Research
Las Vegas, Nevada, 89121
Stephen Tam, MD
- Recruiting
AMR Clinical
Lexington, Kentucky, 40509
Peter Akpunonu, MD
- Recruiting
Woodland International Research Group, LLC
Little Rock, Arkansas, 72211
George Konis, MD
- Recruiting
Hassman Research Institute, LLC d/b/a CenExel Marlton, NJ
Marlton, New Jersey, 08053
Elan A. Cohen, PhD
- Recruiting
Yale Stress Center
New Haven, Connecticut, 06519
Rajita Sinha, PhD
- Recruiting
The Research Foundation for Mental Hygiene/ New York State Psychiatric Institute
New York, New York, 10032
John Mariani, MD
- Recruiting
Evergreen Clinical Trials
Norcross, Georgia, 30092
Dmitriy Pelishev, DO
- Recruiting
Neuro-Behavioral Clinical Research, Inc.
North Canton, Ohio, 44720
Shishuka Malhotra, MD
- Recruiting
Coastal Carolina Research Center, LLC
North Charleston, South Carolina, 29405
Elizabeth Perkins, MD
- Recruiting
Woodland Research Northwest, LLC
Rogers, Arkansas, 72758
Ryan Mahelona, MD
- Recruiting
CenExel iResearch, LLC
Savannah, Georgia, 31405
Nancy E. Backus, MD
- Recruiting
Richmond Behavioral Associates
Staten Island, New York, 10314
Romana Kulikova, MD
- Recruiting
ForCare Clinical Research
Tampa, Florida, 33613
Marlene P. Hart, MD
- Recruiting
Neuroscience Research Institute
West Palm Beach, Florida, 33407
Danesh Alam, MD
About this study
Official title: 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.
- Conditions
- Cannabis Withdrawal
- Being tested
- PP-01, Nabilone, Placebo
- Keywords
- Cannabis Use Disorder, Marijuana Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PP-01Combination product
Cannabinoid-1 (CB1) partial agonist / GABAergic modulator
NabiloneDrug
CB1 partial agonist
PlaceboDrug
Placebo comparator
| Study group | Role | What they receive |
|---|---|---|
| PP-01 | Experimental | Oral PP-01 tapered/titrated over 34 days Receives: Combination Product: PP-01 |
| Nabilone | Active comparator | Oral Nabilone tapered/titrated over 34 days Receives: Drug: Nabilone |
| Placebo | Placebo comparator | Oral Placebo given daily for 34 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUCs of the CSCW over Days 2 to 7, inclusive, comparing PP-01 vs Placebo
Measured: Days to 2 to 7
AUCs of the CSCW over Days 25 to 35, inclusive, comparing PP-01 vs Nabilone to assess rebound
Measured: Days 25 to 35
Secondary outcomes (7)
AUCs of CWS-20 Irritability Domain scores over Days 2 to 35 comparing PP-01 vs Placebo
Measured: Days 2 to 35
AUCs of CWS-20 Irritability Domain scores over Days 25 to 35 comparing PP-01 vs Nabilone
Measured: Days 25 to 35
AUCs of the CSCW over Days 2 to 35 comparing PP-01 vs Placebo
Measured: Days 2 to 35
AUCs of CWS-20 Sleep Domain scores over Days 2 to 35 comparing PP-01 vs Placebo
Measured: Days 2 to 35
AUCs of CWS-20 Sleep Domain scores over Days 2 to 7 comparing PP-01 vs Placebo
Measured: Days 2 to 7
AUCs of CWS-20 Craving Domain scores over Days 2 to 35 comparing PP-01 vs Placebo
Measured: Days 2 to 35
AUCs of CWS-20 Craving Domain scores over Days 2 to 7 comparing PP-01 vs Placebo
Measured: Days 2 to 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2026
- Study start17 Jun 2026
- Primary completionJun 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cannabis WithdrawalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 420 participants (estimated)
Sponsor and investigators
- Lead sponsor
- PleoPharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Jay Constantine, MD, Study director, PleoPharma, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07644052
- Sponsor's protocol ID
- CAN-004
- Other IDs
- U01DA066079
- Status last verified
- Sep 2026
- First submitted
- 8 Jun 2026
- Last updated
- 27 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07644052
- Acronym / sponsor ID
- CAN-004
- Conditions
- Cannabis Withdrawal
- Keywords
- Cannabis Use Disorder, Marijuana Use Disorder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 420 participants (estimated)
- Lead sponsor
- PleoPharma, Inc.Industry (pharma, biotech, devices)
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 17 Jun 2026 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 12 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| PP-01 | Experimental | Combination Product: PP-01Oral PP-01 tapered/titrated over 34 days |
| Nabilone | Active comparator | Drug: NabiloneOral Nabilone tapered/titrated over 34 days |
| Placebo | Placebo comparator | Drug: PlaceboOral Placebo given daily for 34 days |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (17 listed)
- 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.
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PP-01Cannabinoid-1 (CB1) partial agonist / GABAergic modulator | Combination product | PP-01 |
| NabiloneCB1 partial agonist | Drug | Nabilone |
| PlaceboPlacebo comparator | Drug | Placebo |
Primary outcome
AUCs of the CSCW over Days 2 to 7, inclusive, comparing PP-01 vs Placebo
Time frame: 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
7 secondary outcomes
AUCs of CWS-20 Irritability Domain scores over Days 2 to 35 comparing PP-01 vs Placebo
Time frame: 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
AUCs of the CSCW over Days 2 to 35 comparing PP-01 vs Placebo
Time frame: 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
AUCs of CWS-20 Sleep Domain scores over Days 2 to 7 comparing PP-01 vs Placebo
Time frame: 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
AUCs of CWS-20 Craving Domain scores over Days 2 to 7 comparing PP-01 vs Placebo
Time frame: Days 2 to 7
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jay Constantine, MD study director
PleoPharma, Inc.
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PP-01 and Nabilone in people with Cannabis Withdrawal, run by PleoPharma, Inc. at 22 sites 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 17 inclusion and 22 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 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 LBR Regulatory (859-426-5035, lois.rosenberger@lbria.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUCs of the CSCW over Days 2 to 7, inclusive, comparing PP-01 vs Placebo (time frame: Days to 2 to 7). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Oct 2026.