CSF Levels of the Endocannabinoid Anandamide are Reduced in Patients with Untreated Narcolepsy Type 1: A Pilot Study

Author(s): Andrea Romigi*, Monica Bari, Claudio Liguori, Francesca Izzi, Cinzia Rapino, Marzia Nuccetelli, Natalia Battista, Sergio Bernardini, Diego Centonze, Nicola Biagio Mercuri, Fabio Placidi, Mauro Maccarrone

Journal Name: CNS & Neurological Disorders - Drug Targets
Formerly Current Drug Targets - CNS & Neurological Disorders

Volume 19 , Issue 2 , 2020


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Graphical Abstract:


Abstract:

Background: Endocannabinoids (ECs) modulate both excitatory and inhibitory components in the CNS. There is a growing body of evidence that shows ECs influence both hypothalamic orexinergic and histaminergic neurons involved in narcolepsy physiopathology. Therefore, ECs may influence sleep and sleep-wake cycle.

Objective: To evaluate EC levels in the CSF of untreated narcoleptic patients to test whether ECs are dysregulated in Narcolepsy Type 1 (NT1) and Type 2 (NT2).

Methods: We compared CSF Anandamide (AEA), 2-Arachidonoylglycerol (2-AG) and orexin in narcoleptic drug-naïve patients and in a sample of healthy subjects.

Results: We compared NT1 (n=6), NT2 (n=6), and healthy controls (n=6). We found significantly reduced AEA levels in NT1 patients compared to both NT2 and controls. No differences were found between AEA levels in NT2 versus controls and between 2-AG levels in all groups, although a trend toward a decrease in NT1 was evident. Finally, the CSF AEA level was related to CSF orexin levels in all subjects.

Conclusion: We demonstrated that the EC system is dysregulated in NT1.

Keywords: Endocannabinoid, narcolepsy type 1, narcolepsy type 2, anandamide, 2-arachidonoylglycerol, cerebrospinal fluid.

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VOLUME: 19
ISSUE: 2
Year: 2020
Page: [142 - 147]
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DOI: 10.2174/1871527319666200309115602
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