Selective Antiepileptic Effects of N ‐Palmitoylethanolamide, a Putative Endocannabinoid

Summary:  Purpose: The purpose of this study was to determine whether N ‐palmitoylethanolamide (PEA), a putative endocannabinoid, would be effective against kindled amygdaloid seizures. For a comparison with earlier work, we also tested the effectiveness of PEA against pentylenetetrazol (PTZ)‐induced convulsions. Methods: Kindling electrodes were implanted bilaterally in the amygdala in 32 Long‐Evans rats. After the kindling of generalized (stage 5) seizures, the effects of PEA administration [i.p.; 1, 10, 100 mg/kg in dimethylsulfoxide (DMSO)] were evaluated for anticonvulsant activity. PEA (40 mg/kg, i.p. in DMSO) also was tested for anticonvulsant activity against PTZ‐induced convulsions (75 mg/kg, i.p.). Results: After i.p. administration of PEA, kindled rats displayed an increased latency to clonus at the 1‐mg/kg dose. No other dose‐dependent effects were noted. When tested against PTZ‐induced convulsions, PEA protected against tonic convulsions and prolonged the latency between convulsive episodes. Conclusions: PEA produces antiepileptic effects, but does not completely suppress seizures. The mechanism of action of PEA remains to be defined.