Opioid partial agonist buprenorphine dampens responses to psychosocial stress in humans

Abstract

Preclinical and clinical evidence indicates that opioid drugs have stress-dampening effects. In animal models, opioid analgesics attenuate responses to isolation distress, and in humans, opioids reduce stress related to anticipation of physical pain. The stress-reducing effects of opioid drugs may contribute to their abuse potential. Despite this evidence in laboratory animals, the effects of opioids on responses to psychosocial stress have not been determined in humans. Here we examined the effects of buprenorphine, a μ-opioid partial agonist used to treat opioid dependence and pain, on subjective and physiological responses to a stressful public speaking task in healthy adults. We hypothesized that buprenorphine would reduce subjective and physiological stress responses. Healthy adult volunteers (N = 48) were randomly assigned to receive placebo, 0.2mg sublingual buprenorphine, or 0.4mg sublingual buprenorphine in a two-session study with a stressful speaking task (Trier Social Stress Test; TSST) and a non-stressful control task. During the sessions, the participants reported on their mood states, provided subjective appraisals of the task, and measures of salivary cortisol, heart rate, and blood pressure at regular intervals. Stress produced its expected effects, increasing heart rate, blood pressure, salivary cortisol, and subjective ratings of anxiety and negative mood. In line with our hypothesis, both doses of buprenorphine significantly dampened salivary cortisol responses to stress. On self-report ratings, buprenorphine reduced how threatening participants found the tasks. These results suggest that enhanced opioid signaling dampens responses to social stress in humans, as it does in laboratory animals. This stress-dampening effect of buprenorphine may contribute to the non-medical use of opioid drugs.

Eight-Milligram Single Dose of Buprenorphine as an Expeditious Treatment for Severe Suicidal Ideation: A Case Report

“…Therefore, it is a suitable treatment choice for refractory depression, anxiety, self-injurious behaviors, and suicidal ideation (6,7,(14)(15)(16)(17). In the present report, we observed that 8 mg of buprenorphine had a rapid effect on the reduction and cessation of suicidal thoughts and depression.…”

“…Previously, Striebel and Yovell indicated the antisuicidal potential of low-dose buprenorphine administration in a limited period (6,7). Overall, buprenorphine reduces physiological and subjective responses to social stressors, including social rejection (14). In this regard, Karp et al demonstrated the effectiveness of lowdose buprenorphine for treatment-resistant depression in older adults (17).…”

Opioids and Social Connection

“…Consistent with theorizing, buprenorphine, which stimulates opioids, increased satisfaction with performance to a social stressor (giving a speech; Bershad, Jaffe, Childs, & de Wit, 2015, 2015 and reduced sensitivity to recognizing negative facial expressions (fear; Ipser et al, 2013). OPIOIDS AND SOCIAL CONNECTION 8 However, other findings show inconsistent results.…”

Clinical experimental stress studies: methods and assessment

“…The distance of the slash marks (in centimeters) from the beginning of the line is used to create a numerical value, where a greater number of centimeters indicate the higher levels of stress perception (Aitken, 1969;Bond and Lader, 1974;Hellhammer and Schubert, 2012;Creswell et al, 2014). The POMS questionnaire is developed at 6 points and the questionnaire consists of 72 adjectives, comprising eight subscales: anxiety, dejection, hostility, vigor, fatigue, confusion, friendliness, and elation (McNair et al, 1971;Bershad et al, 2015).…”