Indeed, the number of orexin-immunoreactive neurons was found to be increased by 54% in the post-mortem brains of persons with opioid use disorder (Thannickal et al., 2018), a phenomenon that is mimicked in laboratory animals across a broad range of species and drugs of abuse (Collier et al., 2019; Collier et al., 2020; Collier et al., 2021; Fragale, James & Aston-Jones, 2021; James et al., 2019; Matzeu & Martin-Fardon, 2021), except for alcohol use disorder, where there is a decrease in the number and size of orexin neurons in mice and humans (McGregor et al., 2023; Olney et al., 2015). Here, HCRT is linked to opioid use disorder.