THC/CBD combination shows promise for treating restless legs syndrome

Dopamine agonists were previously considered the first-line treatment for Restless Legs Syndrome (RLS); however, &#x3b1;2&#x3b4; ligands are now recommended to prevent augmentation. As cannabinoids inhibit glutamate release in the striatum, they may represent an effective therapeutic option for RLS. Evaluate the efficacy of 2.7&#xa0;mg &#x394;9Tetrahyedrocannabinol/2.5&#xa0;mg Cannabidiol (2.7mgTHC/2.5mgCBD) in RLS. 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. 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&#xa0;years, a median EDSS score of 2, and a mean Ashworth score of 1&#x2009;&#xb1;&#x2009;1.19. Median iron metabolism parameters were within the normal range. At baseline, patients exhibited low daytime sleepiness (ESS: 10.63&#x2009;&#xb1;&#x2009;3.46) and severe RLS (IRLS: 22.44&#x2009;&#xb1;&#x2009;8.77). Mean sleep efficiency (SE) was 83.64&#x2009;&#xb1;&#x2009;6.03%, sleep latency (SL) was 26.71&#x2009;&#xb1;&#x2009;18.64&#xa0;min, and wake after sleep onset (WASO) was 40.29&#x2009;&#xb1;&#x2009;10.03&#xa0;min. IRLS scores improved significantly after both 1 month and 3 months of treatment (p&#x2009;<&#x2009;0.001). WASO was significantly reduced (p&#x2009;=&#x2009;0.015), whereas no significant changes were observed in SL or SE. After 1&#xa0;year, 66.66% of patients remained on treatment and continued to show sustained improvement in IRLS scores (p&#x2009;=&#x2009;0.000). In this exploratory open-label study, treatment with 2.7&#xa0;mg THC/2.5&#xa0;mg CBD was effective in reducing RLS severity, as measured by the IRLS scale, in patients with MS and-associated idiopathic RLS. Improvements were observed after 1 and 3 months of treatment and were maintained after 1&#xa0;year among patients who continued therapy.