5. Is opioid liking driven by relief or reward? Evidence from clinical and experimental studies of acute stress

The context or state of an animal can influence the rewarding and aversive effects of drugs. Most human studies focus on what happens after drug-taking, sidestepping the potential influence of how people feel before they take a drug. In two studies, we have turned this approach on its head, directing focus to the pre-drug affective state.

1. By inducing acute social stress before intravenous opioid administration, we test whether acute stress changes drug effects and opioid abuse liability in healthy non-addicted participants. This laboratory approach enables us to compare drug after a stress induction versus a non-stressful task in a double-blind, placebo-controlled manner.

2. In a parallel clinical study, we take advantage of naturally occurring variability in pre-surgery stress by measuring affect and drug effects in a large sample of patients treated with opioid analgesics in the minutes prior to outpatient surgery

1. Preliminary data (86 sessions) indicates a high rate of oxycodone self-administration in healthy volunteers; data on whether self-administration is affected by pre-drug state will be presented in the talk.

2. Preliminary analysis in 269 outpatients indicates no boost in positive mood from remifentanil or oxycodone, but moderate relief of pre-surgery anxiety. Moreover, we find that higher levels of anticipatory negative affect on the day of surgery is associated with more anxiety relief and more mood improvement.

Managing stress is a common reason why chronic pain patients report misusing opioid analgesics. Together, these projects will help us uncover the psychological and physiological underpinnings of how stressors increase opioids’ abuse liability.

Disclosure of interest statement: This work was supported by European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 802885) and by grants to SL and GE by the Norwegian Regional Healthy Authority (Helse Sør-Øst). No pharmaceutical grants were received in the development of these studies.