Enkephalins

What are Enkephalins?

Enkephalins are endogenous opioid peptides—small signaling molecules the body makes itself. They act as neurotransmitters and neuromodulators, helping regulate pain, stress responses and reward.

The two main forms are methionine-enkephalin (Met-enkephalin) and leucine-enkephalin (Leu-enkephalin). Both act at opioid receptors, including delta and mu receptors; their affinities differ.

Enkephalins and endorphins both belong to the body’s opioid-peptide systems, but the names do not identify the same molecules. Met-enkephalin and Leu-enkephalin differ from beta-endorphin.

How they work

Enkephalins can reduce pain signaling by activating opioid receptors in the nervous system. Among their effects is inhibition of the release of substance P, a neuropeptide involved in transmitting pain signals.

They also participate in stress responses, gastrointestinal activity and reward processing. The effect depends on the peptide, receptor and site of action.

Why researchers study them

Enkephalin signaling is being investigated in chronic pain, addiction and depression. One proposed approach is to slow the breakdown of enkephalins so that their effects last longer. These are research directions, not established enkephalin treatments for mood disorders.

A review by Fricker and colleagues (2020) describes what is known about opioid peptides and the questions that remain. A review by Peciña and colleagues (2019) examines the endogenous opioid system in depression and possible therapeutic approaches. Effects produced by a drug or an animal experiment still need to be distinguished from the function of a particular peptide in humans.