A double-blind, randomized, cross-over, placebo-controlled, pilot trial with Sativex in Huntington's disease

J Neurol. 2016 Jul;263(7):1390-400. doi: 10.1007/s00415-016-8145-9. Epub 2016 May 9.


Huntington's disease (HD) is a neurodegenerative disease for which there is no curative treatment available. Given that the endocannabinoid system is involved in the pathogenesis of HD mouse models, stimulation of specific targets within this signaling system has been investigated as a promising therapeutic agent in HD. We conducted a double-blind, randomized, placebo-controlled, cross-over pilot clinical trial with Sativex(®), a botanical extract with an equimolecular combination of delta-9-tetrahydrocannabinol and cannabidiol. Both Sativex(®) and placebo were dispensed as an oral spray, to be administered up to 12 sprays/day for 12 weeks. The primary objective was safety, assessed by the absence of more severe adverse events (SAE) and no greater deterioration of motor, cognitive, behavioral and functional scales during the phase of active treatment. Secondary objectives were clinical improvement of Unified Huntington Disease Rating Scale scores. Twenty-six patients were randomized and 24 completed the trial. After ruling-out period and sequence effects, safety and tolerability were confirmed. No differences on motor (p = 0.286), cognitive (p = 0.824), behavioral (p = 1.0) and functional (p = 0.581) scores were detected during treatment with Sativex(®) as compared to placebo. No significant molecular effects were detected on the biomarker analysis. Sativex(®) is safe and well tolerated in patients with HD, with no SAE or clinical worsening. No significant symptomatic effects were detected at the prescribed dosage and for a 12-week period. Also, no significant molecular changes were observed on the biomarkers. Future study designs should consider higher doses, longer treatment periods and/or alternative cannabinoid combinations.Clincaltrals.gov identifier: NCT01502046.

Keywords: Cannabinoid; Clinical trial; Huntington’s disease; Sativex.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Amino Acids / pharmacology
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biogenic Monoamines / cerebrospinal fluid
  • Cannabidiol
  • Cross-Over Studies
  • Dronabinol
  • Drug Combinations
  • Endocannabinoids / genetics
  • Endocannabinoids / metabolism
  • Female
  • Fibroblasts / drug effects
  • Follow-Up Studies
  • Gene Expression Regulation / drug effects
  • Humans
  • Huntington Disease / blood
  • Huntington Disease / cerebrospinal fluid
  • Huntington Disease / drug therapy*
  • Male
  • Mental Status Schedule
  • MicroRNAs / blood
  • Middle Aged
  • Outcome Assessment, Health Care
  • Peptide Fragments / cerebrospinal fluid
  • Pilot Projects
  • Plant Extracts / therapeutic use*
  • Plant Structures*
  • Severity of Illness Index
  • tau Proteins / cerebrospinal fluid


  • Amino Acids
  • Amyloid beta-Peptides
  • Biogenic Monoamines
  • Drug Combinations
  • Endocannabinoids
  • MIRN34 microRNA, human
  • MicroRNAs
  • Peptide Fragments
  • Plant Extracts
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Cannabidiol
  • Dronabinol
  • nabiximols

Associated data

  • ClinicalTrials.gov/NCT01502046