Abstract Background: Polyunsaturated fatty acids (PUFAs), particularly Omega-3 (ω-3) and Omega-6 (ω-6) PUFAs, may exert neuroprotective effects via the endocannabinoid system (ECS) and are promoted as brain health supplements. However, despite their potential role in endocannabinoid biosynthesis, the impact of PUFAs on ion channels such as TRPV1 and TRPA1, which are modulated by endocannabinoids, remains incompletely understood.