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Co-ultramicronized palmitoylethanolamide/luteolin normalizes GABAB-ergic activity and cortical plasticity in long COVID-19 syndrome

Versace V, Ortelli P, Dezi S, Ferrazzoli D, Alibardi A, Bonini I, Engl M, Maestri R, Assogna M, Ajello V, Pucks-Faes E, Saltuari L, Sebastianelli L, Kofler M, Koch G. Clin Neurophysiol. 2023;145:81-88.

Randomised controlled trialHumansWith luteolin

This study tested palmitoylethanolamide together with luteolin. Its results cannot be assigned to palmitoylethanolamide alone. More combination studies.

Design
Randomised controlled trial
Subjects
39 adults with persistent fatigue and cognitive complaints after mild COVID-19 enrolled; 34 completed (17 per group). Mean age 50, 26 women, about 10 months after infection
Dose used in the study
700 mg ultramicronised PEA plus 70 mg luteolin (Glialia, Epitech Group) as sublingual microgranules, twice daily, versus inert placebo granules
Duration
8 weeks
What was measured
Transcranial magnetic stimulation of the motor cortex before and after treatment: long-interval intracortical inhibition (LICI, primary outcome, a marker of GABA-B activity), short-latency afferent inhibition (SAI), and LTP-like plasticity after theta-burst stimulation, plus cognitive screening with MoCA and FAB

What the authors reported

The trial found:

  • LICI increased in the PEA-luteolin group (conditioned response fell from 67 to 32 percent of test amplitude) but not with placebo (67 to 71 percent); interaction p = 0.034.
  • LTP-like plasticity was restored at 1 and 10 minutes after theta-burst in the treated group only.
  • SAI did not change.
  • MoCA and FAB scores did not differ between groups.
  • No side effects reported.

Limits of this study

Small trial (17 per group after 5 withdrawals). Outcomes are neurophysiological markers, not symptoms; fatigue and cognition scores were not reported as outcomes and the cognitive tests showed a ceiling effect. Allocation was pseudo-randomised to balance groups. Single centre, 8 weeks, no follow-up. Product and placebo supplied free by Epitech Group; no external funding. Registered after the study started (NCT05311852).

Source

PubMed 36455453 · doi:10.1016/j.clinph.2022.10.017

Entry checked against the abstract on PubMed, and the full text, supplied by Devlin from Clinical Neurophysiology (ScienceDirect) on 2026-10-19. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.