A Trial of the Fatty Acid Amide Hydrolase Inhibitor Palmitoylethanolamide in Bipolar Depression

August 10, 2026 updated by: Rodrigo Machado-Vieira, MD, PhD, MSc

A Randomized Controlled Trial of the Fatty Acid Amide Hydrolase Inhibitor Palmitoylethanolamide in Bipolar Depression

The purpose of this study is to o evaluate the antidepressant efficacy of the PEA in Bipolar Depression and the association between antidepressant response with endogenous cannabinoids and cytokine levels

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Phase 2

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
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas Health Science Center at Houston

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • diagnosis of Bipolar Disorder according to the Diagnostic and Statistical Manual of Mental Disorders (Structured Clinical Interview), Fifth Edition, (DSM5), with a score of ≥16 on the 17-item HAM-D
  • currently in use of at least one FDA approved mood stabilizer with or without antidepressant
  • medically and neurologically healthy on the basis of medical history, physical examination

Exclusion Criteria:

  • Cannabis misuse according to clinical judgement
  • unstable medical condition or uncontrolled medical problem with known central nervous system (CNS) effects
  • active DSM-5 substance use disorder in past three months (other than alcohol or nicotine use disorder)
  • acute high suicidal risk
  • in a manic episode
  • current psychotic features or cognitive impairment that would preclude understanding of the consenting process or tests/examination
  • pregnant or nursing women
  • unstable medical conditions
  • clinically significant abnormal laboratory tests based on complete blood count, liver and kidney function when available

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: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PEA plus Treatment as Usual (TAU)
Drug: Palmitoylethanolamide (PEA)
Participants will receive PEA at a dose of 600mg twice daily for 6 weeks.
Drug: Treatment as Usual (TAU)
subjects will receive a mood stabilizer per usual care
Placebo Comparator: Placebo plus Treatment as Usual (TAU)
Drug: Treatment as Usual (TAU)
subjects will receive a mood stabilizer per usual care
Drug: Placebo
Participants will receive placebo (a tablet that contains no active ingredient) to be taken twice daily for 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Depression as Assessed by the Hamilton Depression Rating Scale (HAM-D)
Time Frame: Baseline, 6 weeks follow up
The Hamilton Depression Rating Scale measures severity of depression. The total score ranges from 0 to 26, higher score indicating greater depression severity. The change in score will be reported. The change in score will be reported as the [(Score at 6 weeks follow up) - (Score at Baseline)] - A negative value indicates improvement of depression severity.
Baseline, 6 weeks follow up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants That Show a Remission of Depressive Symptoms as Assessed by the HAM-D Scale
Time Frame: from baseline to end of study (6 week follow up)
Remission of depressive symptoms is defined by a HAM-D score of ≤7. The Hamilton Depression Rating Scale (HAM-D) measures severity of depression. The total score ranges from 0 to 26, higher score indicating greater depression severity
from baseline to end of study (6 week follow up)
Number of Participants That Show a Response as Assessed by the HAM-D Scale
Time Frame: from baseline to end of study (6 week follow up)
Response rate is defined by ≥ 50 % reduction in HAM-D Score from baseline. The Hamilton Depression Rating Scale (HAM-D) measures severity of depression. The total score ranges from 0 to 26, higher score indicating greater depression severity
from baseline to end of study (6 week follow up)
Change in Depression as Assessed by the Montgomery Äsberg Depression Rating Scale (MADRS)
Time Frame: Baseline, 6 weeks follow up
The Montgomery Äsberg Depression Rating Scale measures severity in depression. The total score ranges from 0 to 60, a higher score indicating greater depression. The change in score will be reported. The change in score will be reported as the [(Score at 6 weeks follow up) - (Score at Baseline)] - A negative value indicates improvement of depression severity.
Baseline, 6 weeks follow up
Time to Response - HAM-D (≥50% Reduction From Baseline)
Time Frame: Baseline To Week 6
Time to first study visit at which a participant achieved ≥50% reduction from baseline HAM-D total score. The Hamilton Depression Rating Scale (HAM-D) measures severity of depression. The total score ranges from 0 to 26, higher score indicating greater depression severity
Baseline To Week 6

Collaborators and Investigators

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

Sponsor

Rodrigo Machado-Vieira, MD, PhD, MSc

Collaborators

Milken Institute
Baszucki Brain Research Fund

Investigators

  • Principal Investigator: Rodrigo Machado-Vieira, M.D, Ph.D., M.Sc, The University of Texas Health Science Center, Houston

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)

May 17, 2023

Primary Completion (Actual)

July 17, 2025

Study Completion (Actual)

July 17, 2025

Study Registration Dates

First Submitted

January 19, 2024

First Submitted That Met QC Criteria

January 19, 2024

First Posted (Actual)

January 29, 2024

Study Record Updates

Last Update Posted (Actual)

August 13, 2026

Last Update Submitted That Met QC Criteria

August 10, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HSC-MS-21-0989

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

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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