Table 1A.
Summary of clinical studies investigating palmitoylethanolamide and its correlations to neurocognitive disorders (NCDs).
| References (Country) | Aim of study | Type of study | Population | N | Outcome measure (test name or description) | Summary results | Additional information of interest |
|---|---|---|---|---|---|---|---|
| Paterniti et al. (22) (Italy) | To assess PEA effects on Aβ exposed human neuronal cells | In vitro exposure in humans | 1. CTRL; 2. Aβ; 3. Aβ+PEA(0.27 + 0.027 μM); 4. Aβ+PEA(2.7 + 0.27 μM); 5. Aβ+PEA(27 + 2.7 μM) |
X | 1. Effects on neuronal viability (Vital staining); 2. Effects on brain function (Measurement fo nitrite concentration, Western blot, Alcaline Comet-assay) |
PEA administration restores IκBα level and NFκB nuclear translocation in in vitro neuronal cells after Aβ exposure | / |
| Altamura et al. (23) (Italy) | To assess eCBs/AEs levels modulation in AD patients | Quantitative assessment in humans | 1. AD; 2. CTRL |
71 | 1. eCBs/AEs levels (Blood sample); 2. Carotid atherosclerosis markers (continuous wave Doppler, Color flow B-mode Doppler ultrasound); 3. Memory and cognition (MMSE, Rey Auditory Verbal Learning, oral denomination test, Raven's Colored Progressive Matrices); 4. Neuroradiological evaluation (MRI) |
1. PEA blood levels are not significantly higher in AD patients compared to controls; 2. Higher PEA blood levels are related to lower constructional praxia test score |
1.2-AG blood levels are higher in AD patients compared to controls; 2. 2-AG blood levels are positively related to memory, attention and WMH volume in AD patients; 3. 2-AG blood levels are higher in AD patients with chronic heart ischemic disease; 4. AEA and OEA blood levels are not significantly higher in AD patients compared to controls |
| Caltagirone et al. (24) (Italy) | To assess PEA effects on memory and cognitive function in stroke patients | In vivo exposure in humans | Ischemic stroke patients | 250 | 1. Neurological condition (CNS); 2. Memory and cognition (MMSE) |
1. PEA administration ameliorates neurological status after 30-day treatment in ischemic stroke patients; 2. PEA administration ameliorates cognitive impairment after 30-day treatment in ischemic stroke patients; 3. PEA is well tolerated with no side events all over the time of the study in stroke patients |
PEA administration improves spasticity, pain and independence in daily living after 30-day treatment in ischemic stroke patients |
| Cipriano et al. (25) (Italy) | To assess PEA anti-inflammatory and anti-angiogenic effects on Aβ-exposed HUVEC cells | In vitro exposure in humans | 1. CTRL; 2. Aβ; 3. Aβ+PEA10∧−6; 4. Aβ+PEA10∧−7; 5. Aβ+PEA10∧−8; 6. Aβ+PEA10∧6+GW6471(2.5); 7. Aβ+PEA10∧−6+GW6471(5); 8. Aβ+PEA10∧−6+GW6471(10) |
X | 1. Cell viability (Cell Vitality Assay); 2. Effect on pro-angiogenic factors production and release (Western blot, ELISA); 3. Effect on endothelial cell proliferation (Immunofluorescence, ELISA BrdU assay, ATP Bioluminescence assay) |
1. PEA administration reduces HUVEC cell proliferation; 2. PEA effect is counteracted by GW6471 administration |
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| Brotini et al. (26) (Italy) | To assess PEA effects on non-motor symptoms in PD patients | In vivo exposure in humans | PD patients | 30 | Non-motor Aspects of Experiences of Daily Living (MDS-UPDRS) | 1. PEA add-on to levodopa ameliorates several nM-EDL symptoms in PD patients; 2. PEA is well tolerated with no side events all over the time of the study in PD patients |
PEA add-on to levodopa ameliorates almost all M-EDL symptoms in PD patients |
| Assogna et al. (27) (Italy) | To assess PEA effects on memory, cognitive function and frontal lobe activity in FTD patients | In vivo exposure in humans | FTD patients | 17 | 1. Behavior, memory and cognition (NPI, MMSE, FAB, SAND); 2. Independency (ADL/IADL); 3. Neurological condition (FTLD-CDR); 4. Corticospinal evaluation (TMS); 5. TMS-EEG cortical evaluation |
1. PEA improves frontal lobe functions in FTD patients; 2. PEA reduces behavioral disturbances in FTD patients; 3. PEA restores LICI at ISI 100 in FTD patients; 4. PEA leads to an increase in TMS-evoked frontal lobe activity and high-frequency oscillations in the beta/gamma range; 5. PEA is well tolerated with no side events all over the time of the study in FTD patients |
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| Campolo et al. (28) (Italy) | To assess PEA effects on memory and cognitive function in TBI patients | In vivo exposure in humans | 1. PEA+std; 2. std |
30 | 1. TBI severity (GCS, Marshal Score); 2. Memory and cognition (MMSE, BNCE); 3. Depressive symptoms (BDI); 4. Independency (Barthel Index) |
1. PEA add-on improves memory and cognitive function compared to standard monotherapy in TBI patients; 2. PEA is well tolerated with no side events all over the time of the study in TBI patients |
1. PEA add-on ameliorates independence and mobility in quotidian living activities compared to baseline in TBI patients; 2. PEA add-on does not improve significantly depressive symptoms compared to standard monotherapy in TBI patients |
PEA, palmitoylethanolamide; Aβ, β-amyloid precursor protein; CTRL, control; μM, micromolar; IκBα, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha; NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells; eCBs, endocannabinoids; AEs, acylethanolamines; AD, Alzheimer's disease; MMSE, Mini Mental State Examination; MRI, Magnetic resonance imaging; 2-AG, 2-arachidonoylglycerol; WMH, white matter hyperintensity; AEA, anandamide; OEA, oleoylethanolamide; CNS, Canadian Neurological Scale; HUVEC, Human umbilical vein endothelial cells; GW6471, PPARα antagonist; ELISA, Enzyme-linked immunosorbent assay; BrdU, Bromodeoxyuridine; ATP, Adenosine triphosphate; PD, Parkinson's disease; MDS-UPDRS, Movement Disorder Society/Unified Parkinson's Disease Rating Scale; nM-EDL, Non-motor Aspects of Experiences of Daily Living; M-EDL, Motor Aspects of Experiences of Daily Living; FTD, Frontotemporal dementia; NPI, Neuropsychiatric Inventory; FAB, Frontal Assessment Battery; SAND, Screening for Aphasia in Neurodegeneration; ADL, Activities of Daily Living; IADL, Instrumental Activities of Daily Living; FTLD-CDR, Frontotemporal Lobar Degeneration-modified Clinical Dementia Rating scale; TMS, transcranial magnetic stimulation; TMS-EEG, TMS combined with electroencephalography; LICI, long-interval intracortical inhibition; ISI, inter-stimulus-interval; TBI, traumatic brain injury; std, standard; GCS, Glasgow coma scale; BNCE, brief neuropsychological cognitive examination; BDI, Beck's inventory depression scale.