Abstract

Opioid use disorder is a chronic relapsing condition that affects millions of people world-wide and that often has major detrimental effects on the individual’s well-being. The condition is primarily characterized by prioritization of opioid drugs over other important and rewarding aspects of life. However, co-occurring mental and somatic health problems such as depression and chronic pain are common. Opioids have a long history as analgesics and recreational drugs. Consequently, endogenous opioids are expected to naturally regulate experiences of pain and reward. Opioid use disorder is primarily managed with medications that target opioid receptors. These include opioid agonists such as methadone and buprenorphine that stimulates the receptor, and the opioid antagonist naltrexone which blocks the receptors. This dissertation addresses concerns that these medications interfere with endogenous opioid-regulation of pain and reward experiences and thereby cause, maintain or exacerbate patients’ symptoms of depression and pain. A review of the existing literature on experiences of pain and reward in individuals with opioid use disorder, and the regulation of such experiences by the endogenous opioid system, is first presented. This is followed by a presentation of novel results from three scientific papers. First, a systematic review and meta-analysis demonstrates that studies to date have consistently found clinically significant cold pain hypersensitivity in patients maintained on opioid agonists for their opioid use disorder, but that evidence for this hyperalgesia being related to long-term use of such medications is limited. Next, two sets of analyses of data from an observational study conducted in parallel with two clinical trials of extended-release naltrexone for opioid use disorder in Norway are reported. These show comparably high levels of anhedonia, depression, chronic pain and cold pain sensitivity in patients receiving opioid agonists and naltrexone. Overall, the results presented in this dissertation are consistent with reduced well-being in patients undergoing opioid substitution treatment, regardless of medication choice. The current work adds to a growing literature indicating that many patients have unmet needs for additional support to manage mental and somatic health problems despite receiving treatment for their opioid use disorder.