A single dose of a drug that boosts endocannabinoid levels significantly reduced tics and premonitory urges in Tourette syndrome patients in a Phase 1 crossover trial.
People with Tourette syndrome, neurologists, movement disorder specialists
Significant tic reduction from a single dose
What the researchers found
A single 40 mg dose of Lu AG06466 (a MAGL inhibitor that raises 2-AG endocannabinoid levels) showed an overall trend of tic reduction across all scales, with 2 of 3 tic scales (including the Yale Global Tic Severity Score) showing significant improvement versus placebo at various timepoints. Premonitory urges were also significantly reduced.
Why it matters
Tourette syndrome lacks consistently effective treatment. This is the first trial of a MAGL inhibitor (which works by boosting the body's own endocannabinoids rather than introducing external cannabinoids) in TS patients.
The numbers in context
20 patients; 40 mg single dose; 2/3 tic scales showed significant improvement; premonitory urges significantly reduced; common side effects: headache, somnolence, fatigue
How the study worked
Phase 1b double-blind crossover study in 20 adult Tourette syndrome patients on standard medications. Single fasted dose of Lu AG06466 (40 mg) or placebo in each period, with tic assessments at multiple timepoints.
What this study cannot tell us
Only 20 patients. Single-dose study cannot assess long-term efficacy or safety. Phase 1b exploratory trial, not a definitive efficacy study.
How to read the evidence
Small Phase 1b crossover trial providing proof-of-concept, but larger and longer trials are needed.
When this study was published
Published in 2022
The bigger picture
Rather than using cannabis directly, this approach leverages the body's own endocannabinoid system by preventing breakdown of 2-AG. If confirmed in larger trials, it could provide tic relief without cannabis-related side effects.
Questions still open
- Would repeated dosing maintain or increase the tic-reducing effect? Could MAGL inhibitors work for other conditions where endocannabinoid deficiency is suspected?
Common questions
Can endocannabinoid drugs help Tourette syndrome?
How is this different from using cannabis for tics?
Read the original research
Endocannabinoid Modulation Using Monoacylglycerol Lipase Inhibition in Tourette Syndrome: A Phase 1 Randomized, Placebo-Controlled Study.
Pharmacopsychiatry, 55(3), 148-156
Citation
Müller-Vahl, Kirsten R; Fremer, Carolin; Beals, Chan; Ivkovic, Jelena; Loft, Henrik; Schindler, Christoph. (2022). Endocannabinoid Modulation Using Monoacylglycerol Lipase Inhibition in Tourette Syndrome: A Phase 1 Randomized, Placebo-Controlled Study.. Pharmacopsychiatry, 55(3), 148-156. https://doi.org/10.1055/a-1675-3494
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