Restless Leg Syndrome (RLS) is a neurological disorder characterized by an uncontrollable urge to move the legs, particularly during periods of rest, leading to significant sleep disturbances and impaired quality of life. Current treatments, while effective for some, often come with limitations, such as side effects or inadequate symptom relief. This study explored the use of a proprietary topical cream containing magnesium-infused cannabidiolic acid (CBDA) as a novel approach to targeting peripheral mechanosensitive channels involved in RLS pathophysiology.

In an open-label trial, ten participants applied the CBDA cream nightly for two weeks and were evaluated using the International Restless Leg Syndrome Rating Scale (IRLS) and the Patient’s Global Impression of Change (PGIC) questionnaire. Statistical analyses revealed a significant reduction in IRLS scores from baseline (M = 25.80) to post-intervention (M = 8.00; p < 0.001), alongside improvements in secondary outcomes, including sleep disturbances and daytime drowsiness. PGIC results indicated enhanced quality of life, with participants reporting substantial symptom relief. Four participants experienced complete resolution of symptoms, and no adverse effects were reported.

These findings suggest that CBDA’s unique formulation, combining amphiphilicity, TRPA1 modulation, and divalent cation activity, effectively targets mechanosensitive channels, such as Piezo and TRPA1, within the dermis. The cream’s membrane-penetrating properties likely enhance its therapeutic action, offering a promising peripheral-focused treatment option for RLS.

While these results are encouraging, limitations such as the small sample size and lack of a control group highlight the need for further randomized, double-blind, placebo-controlled trials. Mechanistic studies to explore the interaction of CBDA with mechanoreceptors would also be valuable. This pilot trial provides a foundation for a novel, safe, and potentially effective alternative for individuals with RLS, particularly those unresponsive to conventional therapies.

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