Palmitoylethanolamide, an antidepressant with (barely) any side effects

Palmitoylethanolamide, an antidepressant with (barely) any side effects

In the shelves of a few supplements stores, you can find palmitoylethanolamide, usually abbreviated as PEA. It is especially popular among people suffering from chronic pain and who would rather not use regular painkillers. Palmitoylethanolamide is a body-based substance, an excellent analgesic, and barely has any side effects so far. That same substance is likely also an antidepressant, according to an animal study published by Chinese researchers in the Pharmacological Reports.



Palmitoylethanolamide (find the structural formula below) is an endocannabinoid, which is created by the body itself. The substance has depicted significant anti-inflammatory effect in several test tube studies.




The researchers experimented with 5 groups of mice. During a week they either did not give the mice anything, gave them 20 mg fluoxetine per kilo body weight, or gave them 10, 20, or 40 mg palmitoylethanolamide per kilo body weight. You can calculate the human equivalent of those doses by dividing the doses by 10. Fluoxetine (find the structural formula on the right) is an antidepressant. It is the active substance in Prozac.

Subsequently, the researchers subjected the mice to some tests, so that the pharmacologists could detect the antidepressant activity of the substances. The tests conducted were the forced swimming test and the tail suspension test.

In the forced swimming test, the mice are allowed to swim around in an aquarium from which they cannot escape for a particular period. The measurements are carried out by estimating the minutes that a mouse has spent without searching a way out, floating around motionless. Shorter time is the indication of stronger antidepressant activity of the dosed substance.

In the tail suspension test, the mice are suspended upside down on their tail. Afterward, readings are obtained by measuring the duration in which the mice tried to escape, hanging passively. Shorter time depicts stronger antidepressant activity of the dosed substance.



According to the forced swimming test (first chart below) and the tail suspension test (second chart), palmitoylethanolamide had an antidepressant effect which was similar to the effect of fluoxetine.





The researchers concluded that:

  • The results provide evidence that palmitoylethanolamide possesses an antidepressant-like effect comparable to the reference drug – fluoxetine.”
  • Palmitoylethanolamide deserves more attention as a potential antidepressant.”
  • “Endogenous cannabinoid compounds may play an important role in the near future for treating depression.”