Background: Parkinson’s disease (PD) is the subject of intense efforts to develop strategies
that slow down or stop disease progression and disability. Substantial evidence points to a prominent
role for neuroinflammation in the underlying dopaminergic cell death. Ultramicronized palmitoylethanolamide
(um-PEA) is well-known for its ability to promote the resolution of neuroinflammation and
exert neuroprotection. This study was designed to assess the efficacy of um-PEA as adjuvant therapy in
patients with advanced PD.
Method: Thirty PD patients receiving levodopa were included in the study. The revised- Movement
Disorder Society/Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) questionnaire was used to
assess motor and non-motor symptoms. Clinical assessments were carried out before and after addition
of um-PEA (600 mg). MDS-UPDRS questionnaire total score for parts I, II, III, and IV was analyzed
using the Generalized Linear Mixed Model, followed by the Wilcoxon signed-rank test to evaluate the
difference of each item’s mean score between baseline and end of um-PEA treatment.
Results: Addition of um-PEA to PD patients receiving levodopa therapy elicited a significant and progressive
reduction in the total MDS-UPDRS score (parts I, II, III and IV). For each item, the mean score
difference between baseline and end of um-PEA treatment showed a significant reduction in most nonmotor
and motor symptoms. The number of patients with symptoms at basal was reduced after one
year of um-PEA treatment. None of the participants reported side effects attributable to the addition of
Conclusion: um-PEA slowed down disease progression and disability in PD patients, suggesting that
um-PEA may be an efficacious adjuvant therapy for PD.