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Phospholipid-Based Delivery System Optimizes the Solubility and Systemic Exposure of Palmitoylethanolamide and Supports Clinical Benefits in Chronic Neuropathic Low Back Pain

Amjad Khan, Fazle Rabbani, Ayesha Kanwal, Areaba Shafiq, Ikram Ujjan, Anna Vellaccio, Massimo Ronchi, Giovanna Petrangolini, Eric De Combarieu, Silvia Turroni, Gabriele Conti. Biomedicines. 2026 Feb 6;14(2):380.

Randomised controlled trialHumans

Design
Randomised controlled trial
Subjects
120 adults with chronic neuropathic low back pain (40 per group: PEA-PL 600 to 300 mg, PEA-PL 450 mg, placebo), plus a separate healthy-volunteer pharmacokinetic group
Dose used in the study
Phospholipid-formulated PEA (Cronilief, Phytosome delivery) 600 mg tapering to 300 mg/day, or 450 mg/day, versus placebo, added to standard of care
Duration
8 weeks (clinical trial); 2 weeks in the pharmacokinetic sub-study
What was measured
PEA solubility in simulated intestinal fluid; plasma PEA levels after supplementation; neuropathic pain (DN4, NPRS), functional disability (ODI), sleep quality (PSQI), quality of life (SF-12), and analgesic use.

What the authors reported

The trial found:

  • The phospholipid formulation increased PEA solubility about eight-fold and produced higher plasma PEA levels than unformulated PEA.
  • Both dose regimens significantly improved pain, disability, sleep and quality-of-life scores versus placebo (all p<0.0001), with larger effects for the 600 to 300 mg regimen.
  • Analgesic use was discontinued more often in the PEA-PL groups (65 to 70%).

Limits of this study

Four authors are employees of Indena S.p.A., which supplied the phospholipid PEA formulation, unformulated PEA and placebo; the remaining authors declare no conflicts.

Source

PubMed 41751279 · doi:10.3390/biomedicines14020380

Entry checked against the abstract on PubMed on 2026-09-22. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.