Moreover, as mentioned above, the selective [248] synthetic KOR-agonist difelikefalin (0.25–1 mg twice daily; p.o.)significantly suppressed pruritus of AD patients, and it was well tolerated in a multicenter, double-blind, placebo-controlled, randomized, phase 2 clinical trial (NCT04018027) [249]. Here, OPRK1 is linked to Alzheimer disease.