←Restless Legs Syndrome
Study register · detail Fallserie · Restless Legs Syndrome · 2026

Palmitoylethanolamide (PEA) in the treatment of restless legs syndrome: Rationale and case report.

Bugnicourt et al. ·Neurological sciences Impact 1.9
Mixed GRADE Very low 0 citations
Samplen = 1 Pat.
Durationunclear
EndpointPain intensity
Blindingn.a.
DesignFallserie
Routeoral
Key finding

In a case series with one gabapentin-treated patient, reduced painful RLS symptoms were shown after PEA supplementation, with no adverse events reported; the exact duration and magnitude of the effect remain unclear.

Summary

Case report of a gabapentin-treated RLS patient (n=1), in whom oral PEA supplementation (palmitoylethanolamide, an endocannabinoid lipid mediator) led to a subjective decrease in pain symptoms. No adverse events reported. Anecdotal evidence, no controlled intervention.

P
PopulationPatient with restless legs syndrome (RLS) under gabapentin base therapy, n=1
I
InterventionOral palmitoylethanolamide (PEA) as supplementation (dose not specified), add-on to gabapentin
O
OutcomeReduction in painful RLS symptom intensity after PEA initiation; no adverse events reported
Confidence in the evidence
Very low

The lowest GRADE level, the effect estimate remains uncertain.

Downgraded for
Imprecision
Quality profile
Sample size ★★★★★
Blinding —
Effect size Mixed
Citations / year ★★★★★
Authors
Bugnicourt JM
DOI 10.1007/s10072-025-08677-8↗
Design: Fallserie
Share
Abstract
Restless legs syndrome (RLS) is a common, sleep-related, neurological disorder. Various treatments are available but some have side effects. Therefore, alternative treatment options with minimal side effects are being actively sought. Palmitoylethanolamide (PEA) is an endogenous lipid signalling molecule known to have anti-inflammatory and analgesic properties. According to the literature, oral PEA supplementation can decrease the levels of pain associated with central and peripheral neurological conditions, such as migraine and peripheral neuropathy. For the first time, we report of a gabapentin-treated patient whose painful symptoms of RLS decreased in intensity following the initiation of supplementation with PEA. No adverse events were reported.
Indication
Further studies on Restless Legs Syndrome
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10.1016/j.smrv.2020.101339 View study →
C de Almeida et al. · 2023 · Cannabis and cannabinoid research
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The Effect of Cannabidiol for Restless Legs Syndrome/Willis-Ekbom Disease in Parkinson's Disease Patients with REM Sleep Behavior Disorder: A Post Hoc Exploratory Analysis of Phase 2/3 Clinical Trial.
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Post-hoc-Analyse einer Phase-II/III-RCT bei n=18 Patienten mit RLS/WED und Parkinson plus RBD; CBD 75–300 mg (n=6) vs. Placebo (n=12) über 14 Wochen. CBD zeigte keine signifikante Reduktion der RLS-Schwere (IRLSSG-Skala) im Vergleich zu Placebo. Negativer Befund, klinisch informativ aber methodisch limitiert durch kleine Stichprobe und post-hoc-Charakter.

10.1089/can.2021.0158 View study →

The impediment to action advances action. — Marcus Aurelius