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

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: Bipolar Depression
• Intervention / Treatment: Drug: Palmitoylethanolamide (PEA); Drug: Treatment as Usual (TAU); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

2

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)	This is a 13 item questionnaire and each is scored from 0-2 for a maximum score of 26 , a higher score indicating worse outcome	Baseline, 6 weeks follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants that show a remission of depressive symptoms as assessed by the HAM-D scale.	Remission of depressive symptoms are defined by a score of ≤7 on the HAM-D. This is a 13 item questionnaire and each is scored from 0-2 for a maximum score of 26 , a higher score indicating worse outcome	from baseline to end of study (6 week follow up)
Percentage of participants that show a response as assessed by the HAM-D scale	Response rate is defined by ≥ 50 % reduction in depression score(HAM-D). This is a 13 item questionnaire and each is scored from 0-2 for a maximum score of 26 , a higher score indicating worse outcome	from baseline to end of study (6 week follow up)
Number of participants that show early improvement as defined by >20% improvement in HAM-D depression score	This is a 13 item questionnaire and each is scored from 0-2 for a maximum score of 26 , a higher score indicating worse outcome	From baseline to week 2 visit
Change in depression as assessed by the Montgomery Äsberg Depression Rating Scale (MADRS)	This is a 10 item questionnaire and each is scored from 0 -6 for a maximum score of 60, higher score indicating worse outcome	Baseline, 6 weeks follow up

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: 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

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 (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 28, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: cytokine levels
• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Mental Disorders; Mood Disorders; Bipolar Disorder; Anti-Infective Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antirheumatic Agents; Sensory System Agents; Antiviral Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Anti-Inflammatory Agents, Non-Steroidal; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Therapeutics; palmidrol
• 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