Opioid effects on sleep: Review of the literature and consideration of the hypothalamic-pituitary-adrenal axis as a relevant mechanism

Sleep difficulties are pervasive among individuals chronically exposed to opioids, such as those with opioid use disorder (OUD) and/ or individuals with chronic pain receiving long-term opioid therapy. This chapter reviews the comorbidity between chronic opioid exposure and sleep disturbance, including emphasis on the effects of opioids on sleep in persons with opioid physical dependence and/ or chronic pain, and the neurotransmitter systems that are associated with those effects. We then synthesize a large literature suggesting that alteration of the hypothalamic-pituitary-adrenal (HPA) axis following chronic exposure to opioids may be a mechanism by which sleep difficulties persist among patients receiving long-term opioid therapy for chronic pain and/ or patients with OUD. This section focuses on HPA function in the context of opioid use, opioids and circadian functioning, opioids and stress response, the role of the HPA axis in sleep, and the combined effects of opioids, HPA function, stress, and sleep. Finally, we outline the clinical impact of chronic opioid exposure on sleep and stress reactivity and recommend that providers treating individuals chronically exposed to opioids (1) routinely assess sleep disturbance and stress, and (2) consider adjunctive interventions that address sleep disturbance and stress, when appropriate.