Cerebrospinal fluid levels of the endocannabinoid anandamide are reduced in patients with untreated newly diagnosed temporal lobe epilepsy

Abstract

SUMMARYPurpose: The endocannabinoid system is involved in excitatory/inhibitory balance mechanisms within the central nervous system (CNS). Growing evidence shows that its perturbation leads to development of epileptic seizures in experimental models, thus indicating that endocannabinoids play an intrinsic protective role in suppressing pathologic neuronal excitability. Experimental data also demonstrate that the endocannabinoid anandamide (AEA) can antagonize epileptic discharges in hippocampal tissue. The objective of our study was to measure endocannabinoids levels in the cerebrospinal fluid (CSF) of drug-naive patients affected by temporal lobe epilepsy (TLE). Methods: We measured the levels of both AEA and the other endocannabinoid, 2-arachidonoylglycerol (2-AG), in the CSF of drug-naive patients with TLE.Results: A significant reduction of AEA was found in the CSF of patients with compared with healthy controls (epileptic patients = 2.55 ± 1.78 pmol/ml; healthy controls = 11.65 ± 7.53 pmol/ml; n = 9 for both groups, p < 0.01). 2-AG levels, however, were not affected (epileptic patients = 209.5 ± 146.56; healthy controls = 159.6 ± 110.2) (n = 6 for both groups, p = 0.48). Discussion: Our findings seem to be consistent with experimental evidence demonstrating a significant prevention of epileptic seizures induced by endocannabinoids in models of epilepsy. Furthermore, they support the hypothesis that AEA may be involved in its pathogenesis, suggesting a hypothetical primary impairment of the endocannabinoid system in untreated TLE. The actual role of this in vivo dysregulation still remains unclear.

Targeting brain and peripheral plasticity of the lipidome in acute kainic acid-induced epileptic seizures in mice via quantitative mass spectrometry

“…7) is in agreement with previous studies demonstrating such a regulation under certain conditions, e.g., acute stress [76,77]. The AEA levels were found to be decreased in cerebrospinal fluid in drug-naive patients suffering from TLE, indicating a dysregulation of the eCB system in pathogenesis of TLE [78].…”

Cannabinoids and Epilepsy

“…CBDV potentiated the effects of phenobarbital, ethosuximide, and valproate in 2 seizure models [181]. These studies suggest that both Δ9-THC and CBD provide significant protection from seizures [147,[154][155][156][157][158][159][160][161][162][163][164][165][166]. GABA = γ-aminobutryic acid in preclinical animal trials, presenting potential targets for human studies.…”

“…3, light green trace) [159]. Furthermore, compared with healthy controls, patients with temporal lobe epilepsy have reduced levels of anandamide in cerebrospinal fluid samples [160]. These findings suggest that seizure activity induces a homeostatic upregulation of excitatory terminal CB 1 Rs, which may reduce excitatory neurotransmitter release via DSE (see "The Endocannabinoid System").…”

Quantitative profiling of endocannabinoids and related N-acylethanolamines in human CSF using nano LC-MS/MS

“…However, limited information is currently available on endocannabinoid and NAE levels in the CSF from healthy humans or patients. Previous studies have quantified the endocannabinoids, 2-AG and AEA (18)(19)(20)(21), and two NAEs (OEA and PEA) (22)(23)(24), but not the related lipid messengers.…”