Co-Ultramicronized Palmitoylethanolamide/Luteolin normalizes GABAB-ergic activity and cortical plasticity in long COVID-19 syndrome

Abstract:

Objective: Transcranial magnetic stimulation (TMS) studies showed that patients with cognitive dysfunction and fatigue after COVID-19 exhibit impaired cortical GABAB-ergic activity, as revealed by reduced long-interval intracortical inhibition (LICI).

Aim of this study was to test the effects of co-ultramicronized palmitoylethanolamide/luteolin (PEA-LUT), an endocannabinoid-like mediator able to enhance GABA-ergic transmission and to reduce neuroinflammation, on LICI.

Methods: Thirty-nine patients (26 females, mean age 49.9 ± 11.4 years, mean time from infection 296.7 ± 112.3 days) suffering from persistent cognitive difficulties and fatigue after mild COVID-19 were randomly assigned to receive either PEA-LUT 700mg + 70mg or PLACEBO, administered orally bid for eight weeks. The day before (PRE) and at the end of the treatment (POST), they underwent TMS protocols to assess LICI. We further evaluate short-latency afferent inhibition (SAI) and long-term potentiation (LTP)-like cortical plasticity.

Results: Patients treated with PEA-LUT but not with PLACEBO showed a significant increase of LICI and LTP-like cortical plasticity. SAI remained unaffected.

Conclusions: Eight weeks of treatment with PEA-LUT restore GABAB activity and cortical plasticity in long Covid patients.

Significance: This study confirms altered physiology of the motor cortex in long Covid and indicates PEA-LUT as a candidate for the treatment of this post-viral condition.

Source: Viviana Versace, Paola Ortelli, Sabrina Dezi, Davide Ferrazzoli, Alessia Alibardi, Ilenia Bonini, Michael Engl, Roberto Maestri, Martina Assogna, Valentina Ajello, Elke Pucks-Faes, Leopold Saltuari, Luca Sebastianelli, Markus Kofler, Giacomo Koch. Co-Ultramicronized Palmitoylethanolamide/Luteolin normalizes GABAB-ergic activity and cortical plasticity in long COVID-19 syndrome. Clinical Neurophysiology, 2022, ISSN 1388-2457, https://doi.org/10.1016/j.clinph.2022.10.017. https://www.sciencedirect.com/science/article/pii/S1388245722009385 (Full text)