INTERVENTIONALCOMPLETEDNCT06229977

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

Locally preserved from ClinicalTrials.govOpen ClinicalTrials.govlast source update 2026-08-13

What this record can show

Registry results are available

Results are reported by the registry submitter and preserved exactly. They are not independent verification or a treatment recommendation.

Registry facts

Study at a glance

Phase: PHASE2
Enrollment: 34 (ACTUAL)
Start date: 2023-05-17
Sponsor: Rodrigo Machado-Vieira, MD, PhD, MSc
Design: RANDOMIZED · PARALLEL · TREATMENT
Locations: 1
Results record: Present in registry snapshot

Linked local records

Related local records

Local links use governed condition terms or exact source-reported intervention names. They are navigation candidates, not efficacy claims.

Conditions

No published condition report matched.

Cannabinoids and active compounds

palmitoyl ethanolamide

Medicines

No exact medicine-name link was found.

Interventions

What was registered

DRUG

Palmitoylethanolamide (PEA)

Participants will receive PEA at a dose of 600mg twice daily for 6 weeks.

DRUG

Placebo

Participants will receive placebo (a tablet that contains no active ingredient) to be taken twice daily for 6 weeks

DRUG

Treatment as Usual (TAU)

subjects will receive a mood stabilizer per usual care

Source-reported results

Results posted to the registry

5 outcomes

Results are reported by the registry submitter and preserved exactly. They are not independent verification or a treatment recommendation.

Primary outcomes: 1
Secondary outcomes: 4
Statistical analyses: 0
Adverse-event terms: 6

PRIMARYChange in Depression as Assessed by the Hamilton Depression Rating Scale (HAM-D)

Time frame: Baseline, 6 weeks follow up
Measure: MEAN · score on a scale
Reporting status: POSTED

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.

Population: 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.

Group	N	Value	Spread / interval
PEA Plus Treatment as Usual (TAU)	16	-12.38	-15.93 to -8.83
Placebo Plus Treatment as Usual (TAU)	12	-13.03	-16.78 to -9.28

SECONDARYNumber 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)
Measure: COUNT_OF_PARTICIPANTS · Participants
Reporting status: POSTED

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

Eligibility

Population and criteria

Sex: ALL
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Not accepted

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

primary outcomes

primary measures

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

Time frame: Baseline, 6 weeks follow up

secondary outcomes

secondary measures

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)

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

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.

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

Publications

Locally readable linked articles

No exact PMID-linked public article is currently readable locally.

Snapshot provenance

Snapshot: 83279213-0bb3-4300-81d8-6b567876aae7
Retrieved: 11/09/2026, 14:14:52
SHA-256: f495f145916d62f6880729cfcc1a0a0ad876c28cab905a4e1c1b947c8212a675

Event	System	Groups: affected / at risk
Headache	Nervous system disorders	PEA Plus Treatment as Usual (TAU): 1 / 18 · Placebo Plus Treatment as Usual (TAU): 1 / 16
Vertigo	Nervous system disorders	PEA Plus Treatment as Usual (TAU): 1 / 18 · Placebo Plus Treatment as Usual (TAU): 0 / 16
Dry Mouth	Immune system disorders	PEA Plus Treatment as Usual (TAU): 1 / 18 · Placebo Plus Treatment as Usual (TAU): 1 / 16
Arthralgia (Aching Joints)	Musculoskeletal and connective tissue disorders	PEA Plus Treatment as Usual (TAU): 1 / 18 · Placebo Plus Treatment as Usual (TAU): 0 / 16
Decreased Appetite	Endocrine disorders	PEA Plus Treatment as Usual (TAU): 1 / 18 · Placebo Plus Treatment as Usual (TAU): 0 / 16
Skin Rash	Skin and subcutaneous tissue disorders	PEA Plus Treatment as Usual (TAU): 0 / 18 · Placebo Plus Treatment as Usual (TAU): 1 / 16

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

Registry results are available

Study at a glance

Related local records

Conditions

Cannabinoids and active compounds

Medicines

What was registered

Palmitoylethanolamide (PEA)

Placebo

Treatment as Usual (TAU)

Results posted to the registry

Population and criteria

Inclusion criteria

Exclusion criteria

primary measures

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

secondary measures

Number of Participants That Show a Remission of Depressive Symptoms as Assessed by the HAM-D Scale

Number of Participants That Show a Response as Assessed by the HAM-D Scale

Change in Depression as Assessed by the Montgomery Äsberg Depression Rating Scale (MADRS)

Time to Response - HAM-D (≥50% Reduction From Baseline)

Locally readable linked articles

Overall Study

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

Region of Enrollment

Montgomery Äsberg Depression Rating Scale Score

Hamilton Depression Rating Scale Score

Columbia Suicide Severity Rating Scale (C-SSRS) Risk Score

PEA Plus Treatment as Usual (TAU)

Placebo Plus Treatment as Usual (TAU)

Group	N	Value	Spread / interval
PEA Plus Treatment as Usual (TAU)	15	-15.97	-22.48 to -9.46
Placebo Plus Treatment as Usual (TAU)	12	-18.22	-25.14 to -11.30

Group	N	Value	Spread / interval
PEA Plus Treatment as Usual (TAU)	17	4	2 to 6
Placebo Plus Treatment as Usual (TAU)	14	2	2 to 4