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Research Abstract Human Study

Tetrahydrocannabinol/cannabidiol in the treatment of restless legs syndrome.

Laura Lillo Triguero, Belén Pilo de la Fuente, Judit Díaz Díaz, Cristina López Riolobos, Yolanda Aladro Benito
J Neurol
Jul 1, 2026
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Abstract

BACKGROUND: Dopamine agonists were previously considered the first-line treatment for Restless Legs Syndrome (RLS); however,α2δligands are now recommended to prevent augmentation. As cannabinoids inhibit glutamate release in the striatum, they may represent an effective therapeutic option for RLS. OBJECTIVE: Evaluate the efficacy of 2.7 mgΔ9Tetrahyedrocannabinol/2.5 mg Cannabidiol (2.7mgTHC/2.5mgCBD) in RLS. METHODS: This is an exploratory, prospective, 3-month open-label trial. At baseline, patients underwent blood testing, respiratory polygraphy, and a 14-day actigraphy. Treatment was initiated at baseline, with dose titration at week 4 if required. The Expanded Disability Status Scale (EDSS), Epworth Sleepiness Scale (ESS), International Restless Legs Syndrome Rating Scale (IRLS), Modified Ashworth Scale, and EQ-5D were assessed at baseline and at weeks 4 and 12. The 14-day actigraphy was repeated at week 12. The primary endpoint was improvement in IRLS scores. Sleep parameters were evaluated as secondary endpoints. Primary end point: improvement in IRLS. Sleep parameters were secondary end points. RESULTS: Eighteen patients with RLS were included, of whom 16 had multiple sclerosis (MS). The cohort comprised 55.5% women, with a mean age of 51.87 years, a median EDSS score of 2, and a mean Ashworth score of 1 ± 1.19. Median iron metabolism parameters were within the normal range. At baseline, patients exhibited low daytime sleepiness (ESS: 10.63 ± 3.46) and severe RLS (IRLS: 22.44 ± 8.77). Mean sleep efficiency (SE) was 83.64 ± 6.03%, sleep latency (SL) was 26.71 ± 18.64 min, and wake after sleep onset (WASO) was 40.29 ± 10.03 min. IRLS scores improved significantly after both 1 month and 3 months of treatment (p 

Affiliation

Laura Lillo Triguero

External References

PubMed ID:
42387200

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