Supplements

THC/CBD combination reduces Restless Legs Syndrome severity in patients with multiple sclerosis and idiopathic RLS

In an exploratory open-label trial, 2.7 mg THC/2.5 mg CBD significantly improved IRLS scores after 1 and 3 months (p<0.001), with sustained improvement at 1 year in 66.66% of patients. Wake after sleep onset was also significantly reduced (p=0.015).

Last updated: Jul 7, 2026โ€ข0 RCTsโ€ข๐Ÿ“– Read as article โ†’

Evidence Score

Evidence Score34/100
Human RCTโ˜†โ˜†โ˜†โ˜†โ˜†
Meta-analysisโ˜†โ˜†โ˜†โ˜†โ˜†
Mechanismโ˜…โ˜…โ˜…โ˜…โ˜…
Safetyโ˜…โ˜…โ˜…โ˜…โ˜†
Confidencelow

Study Evidence

Study 1. Tetrahydrocannabinol/cannabidiol in the treatment of restless legs syndrome.

observational

Lillo Triguero L, Pilo de la Fuente B, D&#xed;az D&#xed;az J, L&#xf3;pez Riolobos C, Aladro Benito Y ยท Journal of neurology (2026)

Participants: N/A
Duration: 3 months (with 1-year follow-up)
Intervention: 2.7 mg ฮ”9-Tetrahydrocannabinol/2.5 mg Cannabidiol (THC/CBD) sublingual or oral formulation, with dose titration at week 4 if required
Outcome: IRLS score (primary), WASO, sleep latency, sleep efficiency (secondary)
Effect Size: N/A (only p-values reported)
Population: 18 patients with RLS (16 with multiple sclerosis, 2 with idiopathic RLS), mean age 51.87 years, 55.5% women

Result:

PubMed: 42387200DOI: 10.1007/s00415-026-13975-y

Mechanism Graph

Cannabinoids inhibit glutamate release in the striatum
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Reduced glutamate release may decrease neuronal hyperexcitability
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This modulation alleviates RLS symptoms
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Result: Reduced RLS severity and improved sleep continuity

Limitations

  • โš Open-label design with no placebo control, limiting causal inference
  • โš Small sample size (n=18) with heterogeneous population (mostly MS patients)
  • โš Short-term follow-up for primary endpoint (3 months), with only 66.66% completing 1-year assessment

Frequently Asked Questions

What dose of THC/CBD was used in this study?โ–ผ

The study used 2.7 mg THC combined with 2.5 mg CBD, with optional dose titration at week 4.

How long did the treatment effects last?โ–ผ

Improvements in RLS severity were observed after 1 and 3 months, and among the 66.66% of patients who continued treatment, benefits were sustained at 1 year.

Did the treatment improve sleep quality?โ–ผ

Wake after sleep onset (WASO) significantly decreased, but sleep latency and sleep efficiency did not show significant changes.

Was this study conducted in patients with multiple sclerosis?โ–ผ

Yes, 16 out of 18 participants had multiple sclerosis; the remaining 2 had idiopathic RLS.

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References

  1. 1.Lillo Triguero L, Pilo de la Fuente B, D&#xed;az D&#xed;az J, L&#xf3;pez Riolobos C, Aladro Benito Y. "Tetrahydrocannabinol/cannabidiol in the treatment of restless legs syndrome.." Journal of neurology, 2026. PMID: 42387200 DOI: 10.1007/s00415-026-13975-y
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.