Endocannabinoids, Stress, Craving And Pain Effects Study (ESCAPE)

October 16, 2025 updated by: Primavera A. Spagnolo, MD, PhD, Brigham and Women's Hospital

Investigating the Effects of Palmitoylethanolamide (PEA) on Stress, Craving and Pain in Opioid Use Disorder

Opioid use disorder (OUD) represents one of the most severe public health crises, with more than 2 million individuals affected in the United States. Existing treatments do not target and restore several key alterations triggering opioid craving and relapse, including increased response to stress, mood disturbances and greater sensitivity to pain, which are caused by prolonged exposure to opioids. This double-blind, randomized, placebo-controlled study will investigate the effects that palmitoylethanolamide (PEA), an endogenous molecule part of the endocannabinoid system available as a dietary supplement, exerts on these alterations and their underlying mechanisms, with the goal of identifying a novel therapeutic approach to reduce craving and prevent relapse in patients with OUD.

Study Overview

Status

Status

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

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 (Actual)

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.
12

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.
  • Early Phase 1

Contacts and Locations

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

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital

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

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18 to 65
  • DSM-5 diagnosis of OUD
  • English speaking
  • Receiving either buprenorphine or methadone for treatment of opioid use disorder for at least 3 consecutive months prior to enrollment
  • Receiving a stable dose of buprenorphine or methadone for the duration of the study
  • Agreeable to abstaining from using any cannabis or CBD products two weeks prior to enrollment in the study, and for the duration of the trial

  • For women of childbearing potential: agreeable to use one of the following:

    • hormonal methods, such as birth control pills, patches, injections, vaginal rings, or implants
    • barrier methods (such as a condom or diaphragm) used with a spermicide (a foam, cream, or gel that kills sperm)
    • intrauterine device (IUD)
    • abstinence (no sex)

Exclusion Criteria:

  • DSM-5 diagnosis of moderate-to-severe cannabis use disorder, alcohol use disorder, and/or psychostimulant use disorder [medical record review and health history form]
  • Active, recurrent substance use within the last 3 months that will interfere with study participation and completion of study procedures [medical record review and health history form]
  • History of psychotic, bipolar and schizoaffective disorders [medical record review and health history form]
  • Lifetime psychiatric hospitalization or suicide attempt, as assessed by the health history form
  • Recent history (within 2 years) of major depressive disorder [health history form and clinical interview]
  • Currently pregnant or breastfeeding (female only) [pregnancy test/ self-reported]
  • History of autoimmune or chronic inflammatory diseases [health history form] Current use of medications known to alter inflammatory and immune response [health history form] Raynaud's disease [health history form]
  • BMI >45
  • Hepatic liver enzymes greater than 3x upper normal limit
  • Vital signs: HR ≤60 or ≥100, SBP ≤90 or ≥160, DBP ≤50 or ≥100, RR < 12 or > 20
  • Recent history of clinically significant medical conditions including, but not limited to, malignancy (and treatment for malignancy), HIV, immunological, endocrine (including uncontrolled diabetes or thyroid disease), renal, GI, or hematological abnormalities that are uncontrolled* [health history form and medical record review]

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.
Active Comparator: PEA 600 mg
PEA capsules (600 mg twice a day) will be administered for 21 days
Drug: Palmitoylethanolamide
Palmitoyethanolamide (PEA) s a dietary supplement with anti-inflammatory and analgesic properties. Subjects will receive PEA (Levagen+) 600 capsules mg twice daily (BID) orally from Day 1 to Day 21
Other Names:
  • Levagen+
Placebo Comparator: Placebo
Placebo capsules (600 mg twice a day) will be administered for 21 days
Other: Placebo
Participants will receive placebo matched to 600 mg PEA (Levagen+) capsules BID orally from Day 1 to Day 21

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
Measure Description
Time Frame
stress-induced opioid craving visual analog scale (VAS)
Time Frame: day 21
decrease from baseline in experimentally-provoked stress-induced craving ratings as measured via the visual analog scale (0= no craving to 100= extremely strong craving). Lower scores indicate reduced craving
day 21

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.
Brigham and Women's Hospital

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.
November 1, 2022

Primary Completion (Actual)

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.
January 14, 2025

Study Completion (Actual)

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.
January 14, 2025

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).
July 27, 2022

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.
July 27, 2022

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.
July 29, 2022

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.
October 20, 2025

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.
October 16, 2025

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, 2025

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.
  • 2022P001440

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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