Clinical high-risk (CHR) for psychosis state still lacks effective and safe treatments. Recent evidence supports the anti-neuroinflammatory properties of fatty acid palmitoylethanolamide (PEA) dietary supplementation across the psychosis spectrum. Sixteen subjects at CHR for psychosis with attenuated psychotic symptoms (APS) enrolled in a 12-week, open-label, nonrandomized, single-arm clinical trial of ultramicronized-PEA (um-PEA, 600 mg/day). Biobehavioral assessments were conducted at baseline, 4 weeks, and 12 weeks, particularly using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and quantifying changes in peripheral neuroimmune biomarkers. Linear mixed-effects models showed significant reductions in CAARMS total APS (Delta 12-weeks =-3.8 units,-30.0 %) and Unusual Thought Content (UTC; Delta 12-weeks =-2.0,-52.5 %). No treatment-emergent side effects were reported. In exploratory analyses including neuroimmune biomarkers as covariates and potential moderators, lower baseline Interleukin (IL)-1 beta was associated with greater improvement in UTC, while time-varying IL-10/IL-6 ratio, Interferon (IFN)-gamma, and IL-6 were linked to changes in CAARMS total APS and UTC. A reduction in APS was observed in subjects at CHR for psychosis receiving PEA supplementation, possibly through immune-inflammatory modulation, warranting further research into its therapeutic potential for this condition. Trial registration: ClinicalTrials.gov Identifier NCT06037993.
Effects of palmitoylethanolamide in clinical high-risk for psychosis: A nonrandomized open-label trial
Bortoletto R.;Garzitto M.;Basaldella M.;Scipioni C.;Sepulcri O.;Fabris M.;Curcio F.;Balestrieri M.;Colizzi M.
2025-01-01
Abstract
Clinical high-risk (CHR) for psychosis state still lacks effective and safe treatments. Recent evidence supports the anti-neuroinflammatory properties of fatty acid palmitoylethanolamide (PEA) dietary supplementation across the psychosis spectrum. Sixteen subjects at CHR for psychosis with attenuated psychotic symptoms (APS) enrolled in a 12-week, open-label, nonrandomized, single-arm clinical trial of ultramicronized-PEA (um-PEA, 600 mg/day). Biobehavioral assessments were conducted at baseline, 4 weeks, and 12 weeks, particularly using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and quantifying changes in peripheral neuroimmune biomarkers. Linear mixed-effects models showed significant reductions in CAARMS total APS (Delta 12-weeks =-3.8 units,-30.0 %) and Unusual Thought Content (UTC; Delta 12-weeks =-2.0,-52.5 %). No treatment-emergent side effects were reported. In exploratory analyses including neuroimmune biomarkers as covariates and potential moderators, lower baseline Interleukin (IL)-1 beta was associated with greater improvement in UTC, while time-varying IL-10/IL-6 ratio, Interferon (IFN)-gamma, and IL-6 were linked to changes in CAARMS total APS and UTC. A reduction in APS was observed in subjects at CHR for psychosis receiving PEA supplementation, possibly through immune-inflammatory modulation, warranting further research into its therapeutic potential for this condition. Trial registration: ClinicalTrials.gov Identifier NCT06037993.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
