Bipolar DepressionPhase 2NCT06229977

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

A Phase 2 study testing Palmitoylethanolamide (PEA) and Treatment as Usual (TAU) in people with Bipolar Depression, run by Rodrigo Machado-Vieira, MD, PhD, MSc at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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 Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Bipolar Depression
What is being tested?: Palmitoylethanolamide (PEA) and Treatment as Usual (TAU)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 34 participants
Where: 1 siteUnited States
Study dates: 17 May 2023to 17 Jul 2025
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 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 9Show fewer

pregnant or nursing women
unstable medical conditions
clinically significant abnormal laboratory tests based on complete blood count, liver and kidney function when available

Trial locations and contacts

1 site in 1 country.

United States1 site

The University of Texas Health Science Center at Houston
Houston, Texas, 77030

Other trials in United States

About this study

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

Conditions: Bipolar Depression
Being tested: Palmitoylethanolamide (PEA), Placebo, Treatment as Usual (TAU)
Keywords: cytokine levels
Medical subject headings: Bipolar Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Palmitoylethanolamide (PEA)Drug
Participants will receive PEA at a dose of 600mg twice daily for 6 weeks.
PlaceboDrug
Participants will receive placebo (a tablet that contains no active ingredient) to be taken twice daily for 6 weeks
Treatment as Usual (TAU)Drug
subjects will receive a mood stabilizer per usual care

Study groups in NCT06229977
Study group	Role	What they receive
PEA plus Treatment as Usual (TAU)	Experimental	Not described Receives: Drug: Palmitoylethanolamide (PEA); Drug: Treatment as Usual (TAU)
Placebo plus Treatment as Usual (TAU)	Placebo comparator	Not described Receives: Drug: Placebo; Drug: Treatment as Usual (TAU)

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Depression as Assessed by the Hamilton Depression Rating Scale (HAM-D)
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.
Measured: Baseline, 6 weeks follow up

Secondary outcomes (4)

Number of Participants That Show a Remission of Depressive Symptoms as Assessed by the HAM-D Scale
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
Measured: from baseline to end of study (6 week follow up)
Number of Participants That Show a Response as Assessed by the HAM-D Scale
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
Measured: from baseline to end of study (6 week follow up)
Change in Depression as Assessed by the Montgomery Äsberg Depression Rating Scale (MADRS)
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.
Measured: Baseline, 6 weeks follow up
Time to Response - HAM-D (≥50% Reduction From Baseline)
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
Measured: Baseline To Week 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 May 202317 Jul 2025

First posted29 Jan 2024
Study start17 May 2023
Primary completion17 Jul 2025
Study completion17 Jul 2025

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.
Other trials for Bipolar DepressionStudies 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 34 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06229977
Sponsor's protocol ID: HSC-MS-21-0989
Status last verified: Jul 2026
First submitted: 19 Jan 2024
Last updated: 13 Aug 2026
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Bipolar Depression trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized Controlled Trial of the Fatty Acid Amide Hydrolase Inhibitor Palmitoylethanolamide in Bipolar Depression
ClinicalTrials.gov ID: NCT06229977
Acronym / sponsor ID: HSC-MS-21-0989
Conditions: Bipolar Depression
Keywords: cytokine levels
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 34 participants (actual)
Lead sponsor: Rodrigo Machado-Vieira, MD, PhD, MScUniversity, hospital or other
Collaborators: Baszucki Brain Research Fund, Milken Institute
Study start: 17 May 2023 (actual)
Primary completion: 17 Jul 2025 (actual)
Study completion: 17 Jul 2025 (actual)
First posted: 29 Jan 2024 (actual)
Results: Posted 13 Aug 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
PEA plus Treatment as Usual (TAU)	Experimental	Drug: Palmitoylethanolamide (PEA), Drug: Treatment as Usual (TAU)
Placebo plus Treatment as Usual (TAU)	Placebo comparator	Drug: Placebo, Drug: Treatment as Usual (TAU)

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (9 listed)

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

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

Primary outcome

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.

4 secondary outcomes

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)
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)
Change in Depression as Assessed by the Montgomery Äsberg Depression Rating Scale (MADRS)
Time frame: Baseline, 6 weeks follow up
Time to Response - HAM-D (≥50% Reduction From Baseline)
Time frame: Baseline To Week 6

Results and safety

Results posted to the registry on 13 Aug 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
PEA Plus Treatment as Usual (TAU)	18	16
Placebo Plus Treatment as Usual (TAU)	16	12

Primary outcome: Change in Depression as Assessed by the Hamilton Depression Rating Scale (HAM-D)

Time frame: Baseline, 6 weeks follow up. Mean (Full Range). Unit: score on a scale

Measure	PEA Plus Treatment as Usual (TAU) n = 16	Placebo Plus Treatment as Usual (TAU) n = 12
Value	-12.38 (-15.93 to -8.83)	-13.03 (-16.78 to -9.28)

Population analysed: Analysis includes participants with both a baseline and a Visit 4 (Week 6) Hamilton Depression Rating Scale (HAM-D) score available. 2 participants from the PEA plus Treatment as Usual (TAU) arm and 4 participants from the Placebo plus Treatment as Usual (TAU) arm discontinued the study prior to Visit 4 or had a missing Visit 4 assessment and were excluded.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: 6 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
PEA Plus Treatment as Usual (TAU)	0 of 18 (0%)	3 of 18 (16.7%)	0 of 18
Placebo Plus Treatment as Usual (TAU)	0 of 16 (0%)	3 of 16 (18.8%)	0 of 16

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Bipolar Depression

Recruiting
Safety and Feasibility of DBS for Bipolar Depression
Bipolar I Disorder, Bipolar Depression
Recruiting
Affective Cognitive Training in Mood Disorders and High-risk Relatives
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RecruitingPhase 3
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Recruiting
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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.

Rodrigo Machado-Vieira, M.D, Ph.D., M.Sc principal investigator

The University of Texas Health Science Center, Houston

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 Palmitoylethanolamide (PEA) and Treatment as Usual (TAU) in people with Bipolar Depression, run by Rodrigo Machado-Vieira, MD, PhD, MSc 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 9 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 13 Aug 2026. 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 13 Aug 2026). 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 Depression as Assessed by the Hamilton Depression Rating Scale (HAM-D) (time frame: Baseline, 6 weeks follow up). 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 NCT06229977.

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 13 Aug 2026.