First study finds elevated endocannabinoid levels in the spinal fluid of Tourette syndrome patients

What the researchers found

In the first study measuring CSF endocannabinoids in Tourette syndrome, both AEA (anandamide, p=0.0018) and 2-AG (p=0.0003) were significantly elevated in 20 TS patients compared to 19 controls. PEA and arachidonic acid were also elevated. 2-AG levels correlated with ADHD symptom severity (p<0.01).

Why it matters

Cannabis-based medicines have been reported to improve tics in Tourette syndrome, but the biological basis was unknown. This first-ever CSF study confirms endocannabinoid system involvement in TS pathophysiology.

The numbers in context

20 TS patients vs 19 controls; AEA elevated (p=0.0018); 2-AG elevated (p=0.0003); PEA elevated (p=0.02); AA elevated (p<0.0001); 2-AG correlated with ADHD severity (p<0.01).

How the study worked

Case-control study comparing CSF levels of endocannabinoids (AEA, 2-AG), PEA, and arachidonic acid in 20 adult Tourette syndrome patients vs. 19 controls using LC/MRM quantification.

What this study cannot tell us

Small sample; cross-sectional design; cannot determine if elevated levels are cause or consequence; CSF may not perfectly reflect brain-regional endocannabinoid activity; adult patients only.

How to read the evidence

Moderate: first-of-its-kind study with significant findings, but small sample and cross-sectional.

When this study was published

Published 2020.

The bigger picture

The elevated endocannabinoid levels could represent either a compensatory response to tic-related neural dysfunction or a primary pathological mechanism. Either way, it validates the endocannabinoid system as a therapeutic target for Tourette syndrome.

Questions still open

• Are endocannabinoid levels in CSF responsive to treatment with cannabinoid medications? Would measuring CSF endocannabinoids help predict who responds to cannabis-based therapy?

Common questions

Read the original research

Cerebrospinal fluid endocannabinoid levels in Gilles de la Tourette syndrome.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 45(8), 1323-1329

Citation

Müller-Vahl, Kirsten R; Bindila, Laura; Lutz, Beat; Musshoff, Frank; Skripuletz, Thomas; Baumgaertel, Charlotte; Sühs, Kurt-Wolfram. (2020). Cerebrospinal fluid endocannabinoid levels in Gilles de la Tourette syndrome.. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 45(8), 1323-1329. https://doi.org/10.1038/s41386-020-0671-6

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