# Oleoylethanolamide supplementation improves mood and reduces fatigue in veterans with GWI in a 15-week randomized, double-blind, placebo-controlled exploratory clinical trial

> **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637)
> **Publisher:** CED Clinic (https://cedclinic.com)
> **Canonical URL:** https://cedclinic.com/research/endocannabinoids-for-fatigue-randomized-controlled-trial/
> **Published:** 2026-10-20T16:49:41-04:00 | **Last Modified / Clinically Audited:** 2026-10-20T16:49:42-04:00
> **Clinical Summary:** This study looked at 52 military veterans who had been sick since the 1991 Gulf War with long-lasting tiredness, low mood, pain and memory problems.

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Gulf War Illness (GWI) affects 32% of Veterans from the 1990–1991 Gulf War. It is characterized by fatigue, mood disturbances, pain and cognitive decrements, with no FDA-approved treatment. This exploratory randomized, double-blind, placebo-controlled trial evaluated the safety and efficacy of oleoylethanolamide (OEA) supplementation in 52 Veterans with GWI (mean age 59 ± 5 SD, 94% males and 79% White). Participants received 200 mg of OEA twice daily or a matching placebo for 10 weeks, followed by a 5-week open-label OEA extension. Outcomes included the Multidimensional Fatigue Inventory (MFI-20), abbreviated Profile of Mood States (POMS), Short-Form McGill Pain Questionnaire, Veterans RAND 36-Item Health Survey (SF-36 V), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and CNS Vital Signs Test, administered at baseline and 10- and 15-weeks. A main effect of OEA for reducing fatigue (MFI-20, p ≤ 0.05) and improving the total mood disturbances score (POMS, p ≤ 0.05) was observed. Participants on OEA reported increased energy, emotional well-being, and social functioning (SF-36 V, p ≤ 0.05). No changes were seen in cognitive performance or pain. Oleoylethanolamide was well-tolerated with no serious adverse events. In summary, OEA was safe and improved fatigue and mood in Veterans with GWI. Larger trials are needed to confirm these benefits.

 

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### Verification & Medical Governance

- **Lead Clinical Author:** Benjamin Caplan, MD
- **Credentials:** Board Certified in Family Medicine (ABFM), Former CMO Canna Care Docs (250,000+ patients supervised), Founder & CMO CED Clinic & CED Foundation, Author of *The Doctor-Approved Cannabis Handbook* (Penguin Random House).
- **Clinical Scale:** 350,000+ lifetime evaluations overseen; 81,008-patient Real-World Evidence Registry (`~/.ced_rwe_vault.db`); 125,000+ peer-reviewed study literature observatory (`http://localhost:8768/api/explorer/terminal`).
- **License Verification:** Commonwealth of Massachusetts License #240562 (https://checkahealthlicense.mass.gov/).
- **NPI Registry:** 1962722637 (https://npiregistry.cms.hhs.gov/provider-view/1962722637).
- **Ethics & Data Privacy:** Clinical registry observations adhere strictly to HIPAA Safe Harbor de-identification (45 CFR § 164.514(b)) and criteria for secondary research exemption under 45 CFR § 46.104(d)(4).