Cannabis DependencePhase 2NCT01618656
Safety and Efficacy of a FAAH-Inhibitor to Treat Cannabis Withdrawal
A Phase 2 study testing PF-04457845 in people with Cannabis Dependence, run by Yale University at 1 site in United States.
Trial summary
Cannabis dependence is associated with changes in the brain's cannabinoid system. When cannabis dependent individuals try to quit using cannabis, some of them experience problems that make it difficult for them to achieve and maintain abstinence. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men only
- Conditions the study is for
- Cannabis Dependence
- What is being tested?
- PF-04457845
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Sep 2012to 11 Mar 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- Male
- Ages 18-55 (inclusive)
- Cannabis Dependence
Who cannot join
- Allergies or intolerance to FAAH-Inhibitors
- Current significant medical or other comorbidities
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale University School of Medicine
New Haven, Connecticut, 06511
About this study
Official title: FAAH-Inhibitor for Cannabis Dependence
Cannabis dependence is associated with changes in the brain's cannabinoid system. When cannabis dependent individuals try to quit using cannabis, some of them experience problems that make it difficult for them to achieve and maintain abstinence. Therefore, reducing the problems related to quitting cannabis may facilitate abstinence. One way to do this is by harnessing the brain's capacity to make its own cannabis-like substances - endocannabinoids. One of the main endocannabinoids is anandamide. The study is based on the hypothesis that the problems related to quitting cannabis use will be reduced by increasing the brain levels of anandamide. Furthermore, by reducing the problems related to quitting cannabis, people will be less likely to relapse. Brain anandamide levels will be increased by blocking the breakdown of anandamide using a fatty acid amide hydrolase inhibitor (FAAH-I). The effects of a novel FAAH-I cannabis withdrawal and relapse in cannabis dependent subjects will be studied in a double-blind, randomized, controlled, proof-of-concept study. Cannabis-dependent subjects will receive placebo or the FAAH-inhibitor PF-04457845 in a 2:1 randomization. The trial consists of a 1 week inpatient stay to achieve abstinence, a 3 week outpatient treatment phase. Cannabis withdrawal will be measured during the inpatient phase. Cannabis use and urinary THC-COOH levels will be measured during the entire study. The treatment phase will be followed by a safety follow up phase of 8 weeks.
- Conditions
- Cannabis Dependence
- Being tested
- PF-04457845, Placebo
- Medical subject headings
- Marijuana Abuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-04457845Drug
Study medication will be administered at 4mg by mouth daily for four weeks.
PlaceboDrug
Sugar pill
| Study group | Role | What they receive |
|---|---|---|
| PF-04457845 | Active comparator | 2/3 of subjects will be randomized to fatty acid amide hydrolase (FAAH) inhibitor 4mg Receives: Drug: PF-04457845 |
| Placebo (sugar pill) | Placebo comparator | 1/3 of subjects will be randomized to placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Marijuana Withdrawal Checklist (MWC)
32-item checklist evaluating potential symptoms of cannabis withdrawal, lower values reflect lesser severity of withdrawal symptoms (lower scores represent a better outcome).
Min: 0 Max: 96
Measured: The MWC was administered on Day 0, Day 1, Day 2, Day 3, and Day 4 (during the inpatient phase when withdrawal peaks) to assess change from baseline (Day 0). The scores from each time point and subject were calculated to report the mean score for each arm.
Change in Self Reported Cannabis Use at the End of 4 Weeks
Subject quantifies and reports frequency of cannabis use prior to study participation and during the 4 week period. Lower scores reflect less cannabis usage, while higher scores reflect more frequent usage.
Min: 0 Max: undeterminable, varies per patient and their usage.
Measured: Administered weekly for 4 weeks to assess change from baseline (Day 0). The scores from each time point and subject were calculated to report the mean score for each arm.
Change in THC-COOH Quantification at the End of 4 Weeks
Subjects provide urine samples to quantify levels of THC.
Measured: Samples obtained weekly for 4 weeks to assess change from baseline (Day 0). The results from each time point and subject were calculated to report the mean score for each arm.
Secondary outcomes (1)
Change in Polysomnography
Polysomnography (PSG) is a comprehensive reading of biophysiological changes that occur during sleep, including identification of sleep stage. A mean and standard deviation of their data points during sleep stages were calculated to determine change from baseline to the end of study treatment.
Measured: Polysomnography was collected two nights prior to baseline visit, for three nights during study treatment and two nights after four weeks of study treatment. A mean was calculated to assess change from baseline (Day 0).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2012 (estimated)
- Study start12 Sep 2012
- Primary completion11 Mar 2016
- Study completion11 Mar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cannabis DependenceStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Deepak C. D'Souza, Yale University
- Investigators
- Deepak C D'Souza, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01618656
- Sponsor's protocol ID
- 1202009714
- Other IDs
- U01DA033267
- Status last verified
- Jan 2023
- First submitted
- 5 Jun 2012
- Last updated
- 23 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
D'Souza DC, Cortes-Briones J, Creatura G, Bluez G, Thurnauer H, Deaso E, Bielen K, Surti T, Radhakrishnan R, Gupta A, Gupta S, Cahill J, Sherif MA, Makriyannis A, Morgan PT, Ranganathan M, Skosnik PD. Efficacy and safety of a fatty acid amide hydrolase inhibitor (PF-04457845) in the treatment of cannabis withdrawal and dependence in men: a double-blind, placebo-controlled, parallel group, phase 2a single-site randomised controlled trial. Lancet Psychiatry. 2019 Jan;6(1):35-45. doi: 10.1016/S2215-0366(18)30427-9. Epub 2018 Dec 6.
PubMed 30528676
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FAAH-Inhibitor for Cannabis Dependence
- ClinicalTrials.gov ID
- NCT01618656
- Acronym / sponsor ID
- 1202009714
- Conditions
- Cannabis Dependence
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 12 Sep 2012 (actual)
- Primary completion
- 11 Mar 2016 (actual)
- Study completion
- 11 Mar 2016 (actual)
- First posted
- 13 Jun 2012 (estimated)
- Results
- Posted 23 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cannabis dependence is associated with changes in the brain's cannabinoid system. When cannabis dependent individuals try to quit using cannabis, some of them experience problems that make it difficult for them to achieve and maintain abstinence. Therefore, reducing the problems related to quitting cannabis may facilitate abstinence. One way to do this is by harnessing the brain's capacity to make its own cannabis-like substances - endocannabinoids. One of the main endocannabinoids is anandamide. The study is based on the hypothesis that the problems related to quitting cannabis use will be reduced by increasing the brain levels of anandamide. Furthermore, by reducing the problems related to quitting cannabis, people will be less likely to relapse. Brain anandamide levels will be increased by blocking the breakdown of anandamide using a fatty acid amide hydrolase inhibitor (FAAH-I). The effects of a novel FAAH-I cannabis withdrawal and relapse in cannabis dependent subjects will be studied in a double-blind, randomized, controlled, proof-of-concept study. Cannabis-dependent subjects will receive placebo or the FAAH-inhibitor PF-04457845 in a 2:1 randomization. The trial consists of a 1 week inpatient stay to achieve abstinence, a 3 week outpatient treatment phase. Cannabis withdrawal will be measured during the inpatient phase. Cannabis use and urinary THC-COOH levels will be measured during the entire study. The treatment phase will be followed by a safety follow up phase of 8 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PF-04457845 | Active comparator | Drug: PF-044578452/3 of subjects will be randomized to fatty acid amide hydrolase (FAAH) inhibitor 4mg |
| Placebo (sugar pill) | Placebo comparator | Drug: Placebo1/3 of subjects will be randomized to placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Male
- Ages 18-55 (inclusive)
- Cannabis Dependence
Key exclusion criteria (2 listed)
- Allergies or intolerance to FAAH-Inhibitors
- Current significant medical or other comorbidities
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 |
|---|---|---|
| PF-04457845Study medication will be administered at 4mg by mouth daily for four weeks. | Drug | PF-04457845 |
| PlaceboSugar pill | Drug | Placebo (sugar pill) |
Primary outcome
Change in Marijuana Withdrawal Checklist (MWC)
Time frame: The MWC was administered on Day 0, Day 1, Day 2, Day 3, and Day 4 (during the inpatient phase when withdrawal peaks) to assess change from baseline (Day 0). The scores from each time point and subject were calculated to report the mean score for each arm.
32-item checklist evaluating potential symptoms of cannabis withdrawal, lower values reflect lesser severity of withdrawal symptoms (lower scores represent a better outcome). Min: 0 Max: 96
Change in Self Reported Cannabis Use at the End of 4 Weeks
Time frame: Administered weekly for 4 weeks to assess change from baseline (Day 0). The scores from each time point and subject were calculated to report the mean score for each arm.
Subject quantifies and reports frequency of cannabis use prior to study participation and during the 4 week period. Lower scores reflect less cannabis usage, while higher scores reflect more frequent usage. Min: 0 Max: undeterminable, varies per patient and their usage.
Change in THC-COOH Quantification at the End of 4 Weeks
Time frame: Samples obtained weekly for 4 weeks to assess change from baseline (Day 0). The results from each time point and subject were calculated to report the mean score for each arm.
Subjects provide urine samples to quantify levels of THC.
1 secondary outcome
Change in Polysomnography
Time frame: Polysomnography was collected two nights prior to baseline visit, for three nights during study treatment and two nights after four weeks of study treatment. A mean was calculated to assess change from baseline (Day 0).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30528676D'Souza DC, Cortes-Briones J, Creatura G, Bluez G, Thurnauer H, Deaso E, Bielen K, Surti T, Radhakrishnan R, Gupta A, Gupta S, Cahill J, Sherif MA, Makriyannis A, Morgan PT, Ranganathan M, Skosnik PD. Efficacy and safety of a fatty acid amide hydrolase inhibitor (PF-04457845) in the treatment of cannabis withdrawal and dependence in men: a double-blind, placebo-controlled, parallel group, phase 2a single-site randomised controlled trial. Lancet Psychiatry. 2019 Jan;6(1):35-45. doi: 10.1016/S2215-0366(18)30427-9. Epub 2018 Dec 6.
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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. This study is not recruiting at the moment.
Deepak C D'Souza, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PF-04457845 in people with Cannabis Dependence, run by Yale University at 1 site 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 3 inclusion and 2 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: finished, as of the sponsor's last update on 23 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Marijuana Withdrawal Checklist (MWC) (time frame: The MWC was administered on Day 0, Day 1, Day 2, Day 3, and Day 4 (during the inpatient phase when withdrawal peaks) to assess change from baseline (Day 0). The scores from each time point and subject were calculated to report the mean score for each arm.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01618656, which also lists 1 linked publication.
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 23 Feb 2023.