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

Cannabis Cannabinoid Res. 2023 Apr;8(2):374-378. doi: 10.1089/can.2021.0158. Epub 2022 Jun 24.


Background: Cannabidiol (CBD) is one of the main nonpsychoactive components of Cannabis sativa and may represent an alternative treatment for Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) in patients with Parkinson's disease (PD) and REM (Rapid Eye Movement) sleep behavior disorder (RBD). Objective: Our purpose was a post hoc exploratory analysis to evaluate the CBD's efficacy to improve the severity of RLS/WED symptoms in patients with PD and RBD. Methods: A post hoc exploratory analysis of a phase II/III, a parallel, double-blind, placebo-controlled clinical trial was conducted in 18 patients with RLS/WED and PD plus RBD associated. Six patients were randomized to the CBD group in doses of 75-300 mg, and twelve received placebo capsules. They were followed up for 14 weeks. The primary outcome was the severity of RLS/WED by Restless Legs Syndrome Rating Scale of the International Restless Legs Syndrome Study Group (IRLSSG). Results: CBD showed no difference in relationship to placebo for primary and secondary outcomes. Conclusion: CBD showed no reduction in the severity of RLS/WED manifestation in patients with PD and RBD.

Keywords: Parkinson's disease; Willis-Ekbom disease; cannabidiol; restless legs syndrome; sleep.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cannabidiol* / pharmacology
  • Cannabidiol* / therapeutic use
  • Cannabis*
  • Humans
  • Parkinson Disease* / complications
  • Parkinson Disease* / drug therapy
  • REM Sleep Behavior Disorder* / complications
  • REM Sleep Behavior Disorder* / drug therapy
  • Restless Legs Syndrome* / complications
  • Restless Legs Syndrome* / diagnosis
  • Restless Legs Syndrome* / drug therapy


  • Cannabidiol