A Phase-2 Pilot Study of a Therapeutic Combination of Δ9-Tetrahydracannabinol and Palmitoylethanolamide for Adults With Tourette's Syndrome

J Neuropsychiatry Clin Neurosci. 2021 Fall;33(4):328-336. doi: 10.1176/appi.neuropsych.19080178. Epub 2021 Aug 3.

Abstract

Objective: There are few effective pharmacological treatments for Tourette's syndrome. Many patients with Tourette's syndrome experience impairing tic symptoms despite use of available evidence-based treatments. The investigators conducted a small, uncontrolled trial to examine the safety, tolerability, and dosing of THX-110, a combination of Δ9-tetrahydracannabinol (Δ9-THC) and palmitoylethanolamide (PEA), in Tourette's syndrome.

Methods: A 12-week uncontrolled trial of THX-110 (maximum daily Δ9-THC dose, 10 mg, and a constant 800-mg dose of PEA) in 16 adults with Tourette's syndrome was conducted. The primary outcome was improvement on the Yale Global Tic Severity Scale (YGTSS) total tic score. Secondary outcomes included measures of comorbid conditions and the number of participants who elected to continue treatment in the 24-week extension phase.

Results: Tic symptoms significantly improved over time with THX-110 treatment. Improvement in tic symptoms was statistically significant within 1 week of starting treatment compared with baseline. THX-110 treatment led to an average improvement in tic symptoms of more than 20%, or a 7-point decrease in the YGTSS score. Twelve of the 16 participants elected to continue to the extension phase, and only two participants dropped out early. Side effects were common but were generally managed by decreasing Δ9-THC dosing, slowing the dosing titration, and shifting dosing to nighttime.

Conclusions: Although the initial data from this trial in adults with refractory Tourette's syndrome are promising, future randomized double-blind placebo-controlled trials are necessary to demonstrate efficacy of THX-110 treatment. The challenges raised by the difficulty in blinding trials due to the psychoactive properties of many cannabis-derived compounds need to be further appreciated in these trial designs.

Keywords: Drug/Psychotherapy Treatment of Neuropsychiatric Disorders; Neuropsychology.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Amides / therapeutic use*
  • Cannabinoid Receptor Agonists / therapeutic use*
  • Double-Blind Method
  • Dronabinol / therapeutic use*
  • Ethanolamines / therapeutic use*
  • Female
  • Humans
  • Male
  • Palmitic Acids / therapeutic use*
  • Pilot Projects
  • Psychiatric Status Rating Scales
  • Severity of Illness Index*
  • Tourette Syndrome / drug therapy*
  • Treatment Outcome

Substances

  • Amides
  • Cannabinoid Receptor Agonists
  • Ethanolamines
  • Palmitic Acids
  • palmidrol
  • Dronabinol