In humans, the δ-opioid receptor is most heavily expressed in the basal ganglia and neocortical regions of the brain.

[14] These antidepressant effects have been linked to endogenous opioid peptides acting at δ- and μ-opioid receptors,[15] and so can also be produced by enkephalinase inhibitors such as RB-101.

In the 2008 Phase 2 clinical trial by Astra Zeneca, NCT00759395, 15 patients were treated with the selective delta agonist AZD 2327.

Relying on RET, Javitch and coworkers showed that RET signals were more characteristic of random proximity between receptors, rather than an actual bond formation between receptors, suggesting that discrepancies in binding profiles may be the result of downstream interactions, rather than novel effects due to oligomerization.

Recent work indicates that exogenous ligands that activate the delta receptors mimic the phenomenon known as ischemic preconditioning.

[21] Experimentally, if short periods of transient ischemia are induced the downstream tissues are robustly protected if longer-duration interruption of the blood supply is then affected.

As a consequence, our understanding of their function is much more limited than those of the other opioid receptors for which selective ligands have long been available.