Background: The cannabinoid system may be involved in the humoral mechanisms at the
neuromuscular junction. Ultramicronized-palmythoylethanolamide (μm-PEA) has recently been
shown to reduce the desensitization of Acetylcholine (ACh)-evoked currents in denervated patients
modifying the stability of ACh receptor (AChR) function.
Objective: To analyze the possible beneficial effects of μm-PEA in patients with myasthenia gravis
(MG) on muscular fatigue and neurophysiological changes.
Method: The duration of this open pilot study, which included an intra-individual control, was three
weeks. Each patient was assigned to a 1-week treatment period with μm-PEA 600 mg twice a day. A
neurophysiological examination based on repetitive nerve stimulation (RNS) of the masseteric and the
axillary nerves was performed, and the quantitative MG (QMG) score was calculated in 22 MG patients
every week in a three-week follow-up period. AChR antibody titer was investigated to analyze a
possible immunomodulatory effect of PEA in MG patients.
Results: PEA had a significant effect on the QMG score (p=0.03418) and on RNS of the masseteric
nerve (p=0.01763), thus indicating that PEA reduces the level of disability and decremental muscle response.
Antibody titers did not change significantly after treatment.
Conclusion: According to our observations, μm-PEA as an add-on therapy could improve muscular
response to fatigue in MG. The possible modulation of AChR currents as a means of eliciting a direct
effect from PEA on the conformation of ACh receptors should be investigated. The co-role of cytokines
also warrants an analysis. Given the rapidity and reversibility of the response, we suppose that
PEA acts directly on AChR, though further studies are needed to confirm this hypothesis.