Research study · Scientific Reports · 2026
Oleoylethanolamide supplementation improves mood and reduces fatigue in veterans with GWI in a 15-week randomized, double-blind, placebo-controlled exploratory clinical trial
Verified on PubMed Oxford CEBM Level 1B: Randomized Controlled Trial
A 2026 randomized controlled trial in Scientific Reports tested endocannabinoids in fatigue. The results were mixed but encouraging for tiredness and mood. This study suggests that a small group of veterans with Gulf War Illness may feel less fatigued and less low in mood after taking this compound for about three months, and that it.
In plain language
Study overview
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. Half took a daily capsule of a natural fat-based compound called oleoylethanolamide, and half took a look-alike dummy capsule, for about ten weeks, after which everyone could take the real capsule for five more weeks.
Findings
The results were mixed but encouraging for tiredness and mood. Veterans who took the real capsule reported feeling less worn out and a better overall mood, and they also said they had more energy and got along better with others, but their memory tests and pain levels did not change.
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The deeper readScientific analysis
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.
The paper
Citation
Abdullah L, Keegan AP, Hoffmann M, Baraniuk J, Mack W, Sullivan K, et al. Oleoylethanolamide supplementation improves mood and reduces fatigue in veterans with GWI in a 15-week randomized, double-blind, placebo-controlled exploratory clinical trial. Scientific Reports (2026). PubMed 41513981 · DOI
Limitations the authors noted
Small sample size (n=52) and short 15-week duration. Exploratory design; no a priori power calculation. Multiple testing correction not applied to subscale and post-hoc analyses. Single fixed dose precluded dose-response assessment. Non-fasting blood collection. Open-label extension may introduce expectation bias. Pain data missing for first 8 participants due to protocol amendment. Single-site recruitment with predominantly male, White, Florida-based sample.
In practice
Why this matters
This study suggests that a small group of veterans with Gulf War Illness may feel less fatigued and less low in mood after taking this compound for about three months, and that it appeared safe in this group. It does not prove the compound works, because the group was small, the study was short, only one dose was tested, and the main results were not the ones the study set out to test in advance. The open questions are whether the benefit holds in larger and more varied groups, at other doses, and over longer periods.
Frequently asked questions
Clinical Questions & Answers
What were the primary clinical findings regarding Endocannabinoids and Affect?
The results were mixed but encouraging for tiredness and mood. Veterans who took the real capsule reported feeling less worn out and a better overall mood, and they also said they had more energy and got along better with others, but their memory tests and pain levels did not change.
What study limitations or clinical safeguards should patients keep in mind?
Small sample size (n=52) and short 15-week duration. Exploratory design; no a priori power calculation. Multiple testing correction not applied to subscale and post-hoc analyses.
Browse related research
Condition: Affect Condition: Fatigue Condition: Persian gulf syndrome Topic: Endocannabinoids Topic: Oleic acids
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Reviewed by Dr. Caplan on October 20, 2026.
This page is general education about a published study. It is not medical advice and does not create a doctor-patient relationship. For care specific to you, book a consultation.
