Opioid Regulation of Social Homeostasis: Connecting Loneliness to Addiction.

Loneliness heightens the risk of substance use disorder, and a desire to escape this negative feeling motivates drug use. Opioid drugs in particular are believed to target neurobiological circuits involved in social bonding, increasing vulnerability to opioid addiction when social connectedness is lacking. In this narrative review we consider how current understanding of μ-opioid modulation of reward and threat processing across domains sheds light on the mechanisms linking loneliness and substance use.

Hyperalgesia in Patients With a History of Opioid Use Disorder: A Systematic Review and Meta-Analysis.

Importance: Short-term and long-term opioid treatment have been associated with increased pain sensitivity (ie, opioid-induced hyperalgesia). Treatment of opioid use disorder (OUD) mainly involves maintenance with methadone and buprenorphine, and observations of heightened cold pain sensitivity among patients are often considered evidence of opioid-induced hyperalgesia.

Objective: To critically examine the evidence that hyperalgesia in patients with OUD is related to opioid use.

Factors associated with use of opioid rescue medication after surgery.

Background: Opioid exposure after surgery increases risk of persistent opioid use. Here, we characterize at-home use of opioid rescue medication during 1-2 days after outpatient surgery (N=270) in a postoperative opioid-sparing context at a Norwegian hospital.

Methods: The postsurgical pain management plan included non-steroidal anti-inflammatory drugs and up to six pills of 5 mg oxycodone as rescue analgesics.

Children born to women in opioid maintenance treatment: A longitudinal study of child behavioral problems and parenting stress.

In the wake of the "opioid epidemic", there is considerable concern regarding potential harmful long-term effects of prenatal opioid exposure. Opioid misuse and addiction confer increased exposure to lifestyle stressors and health burdens. Accordingly, it is challenging to disentangle effects of prenatal opioid exposure from factors related to maternal stress.

Stress recovery with social support: A dyadic stress and support task.

How does social support bolster resilience? Here, we present a new dyadic paradigm to study causal mechanisms of acute and ecologically valid social support in the laboratory. The Dyadic Stress and Support Task (DSST) consists of a psychosocial stress phase and a recovery phase. During DSST stress, a pair of participants take turns to perform public speaking and mental arithmetic in front of a panel.

Opioid antagonism in humans: a primer on optimal dose and timing for central mu-opioid receptor blockade.

Non-human animal studies outline precise mechanisms of central mu-opioid regulation of pain, stress, affiliation and reward processing. In humans, pharmacological blockade with non-selective opioid antagonists such as naloxone and naltrexone is typically used to assess involvement of the mu-opioid system in such processing. However, robust estimates of the opioid receptor blockade achieved by opioid antagonists are missing.

The Role of Mu-Opioids for Reward and Threat Processing in Humans: Bridging the Gap from Preclinical to Clinical Opioid Drug Studies.

Purpose Of Review: Opioid receptors are widely expressed in the human brain. A number of features commonly associated with drug use disorder, such as difficulties in emotional learning, emotion regulation and anhedonia, have been linked to endogenous opioid signalling. Whereas chronic substance use and misuse are thought to alter the function of the mu-opioid system, the specific mechanisms are not well understood.

A randomized placebo-controlled intranasal oxytocin study on first impressions and reactions to social rejection.

Oxytocin is central to pair-bonding in non-human animals. We assessed effects of intranasal oxytocin on bond formation between two opposite-sex strangers. In a double-blind placebo-controlled design, 50 pairs of one man and one woman received oxytocin or placebo spray intranasally.

'Defrosting' music chills with naltrexone: The role of endogenous opioids for the intensity of musical pleasure.

The endogenous opioid system has been implicated during experiences of pleasure (i.e., from food or sex).

Mental health and use of health care services in opioid-exposed school-aged children compared to foster children.

Given the concerns raised regarding the effects of prenatal exposure to methadone and buprenorphine on the developmental outcomes of the children, this study assessed mental health and use of services in a national sample of school-aged children (N = 78) born to women enrolled in opioid maintenance treatment during pregnancy, compared with a group of foster children (N = 140). The majority of the opioid-exposed children lived with their birth parent(s) at the time of assessment (N = 62), while 16 lived in foster homes. Caregivers completed the Strengths and Difficulties Questionnaire (SDQ) and the Reactive Attachment Disorder scale.

Assessment of Anhedonia in Adults With and Without Mental Illness: A Systematic Review and Meta-analysis.

Importance: Anhedonia, a reduced capacity for pleasure, is described for many psychiatric and neurologic conditions. However, a decade after the Research Domain Criteria launch, whether anhedonia severity differs between diagnoses is still unclear. Reference values for hedonic capacity in healthy humans are also needed.

Anhedonia in chronic pain and prescription opioid misuse.

Background: Both acute and chronic pain can disrupt reward processing. Moreover, prolonged prescription opioid use and depressed mood are common in chronic pain samples. Despite the prevalence of these risk factors for anhedonia, little is known about anhedonia in chronic pain populations.

The role of the opioid system in decision making and cognitive control: A review.

The opioid system regulates affective processing, including pain, pleasure, and reward. Restricting the role of this system to hedonic modulation may be an underestimation, however. Opioid receptors are distributed widely in the human brain, including the more "cognitive" regions in the frontal and parietal lobes.

Effects of opioid receptor stimulation and blockade on touch pleasantness: a double-blind randomised trial.

The μ-opioid receptor (MOR) system has long been thought to underpin the rewarding properties of pleasant touch. Numerous non-human animal studies implicate MORs in social behaviours involving touch, but little is currently known about MOR involvement in human touch reward. Here, we employed a bi-directional pharmacological double-blind crossover design to assess the role of the human MOR system for touch pleasantness and motivation.

Intact responses to non-drug rewards in long-term opioid maintenance treatment.

Disruption of non-drug reward processing in addiction could stem from long-term drug use, addiction-related psychosocial stress, or a combination of these. It remains unclear whether long-term opioid maintenance treatment (OMT) disrupts reward processing. Here, we measured subjective and objective reward responsiveness in 26 previously heroin-addicted mothers in >7 years stable OMT with minimal psychosocial stress and illicit drug use.

Morphine reduced perceived anger from neutral and implicit emotional expressions.

The μ-opioid system modulates responses to pain and psychosocial stress and mediates non-social and social reward. In humans, the μ-opioid agonist morphine can increase overt attention to the eye-region and visual exploration of faces with neutral expressions. However, little is known about how the human μ-opioid system influences sensitivity to and appraisal of subtle and explicit cues of social threats and reward.

Opioid Modulation of Value-Based Decision-Making in Healthy Humans.

Modifying behavior to maximize reward is integral to adaptive decision-making. In rodents, the μ-opioid receptor (MOR) system encodes motivation and preference for high-value rewards. Yet it remains unclear whether and how human MORs contribute to value-based decision-making.

Sweet taste pleasantness is modulated by morphine and naltrexone.

Background: Rodent models highlight the key role of μ-opioid receptor (MOR) signaling in palatable food consumption. In humans, however, the effects of MOR stimulation on eating and food liking remain unclear.

Objectives: Here, we tested sweet pleasantness experience in humans following MOR drug manipulations.

The µ-opioid system promotes visual attention to faces and eyes.

Paying attention to others' faces and eyes is a cornerstone of human social behavior. The µ-opioid receptor (MOR) system, central to social reward-processing in rodents and primates, has been proposed to mediate the capacity for affiliative reward in humans. We assessed the role of the human MOR system in visual exploration of faces and eyes of conspecifics.

Placebo improves pleasure and pain through opposite modulation of sensory processing.

Placebo analgesia is often conceptualized as a reward mechanism. However, by targeting only negative experiences, such as pain, placebo research may tell only half the story. We compared placebo improvement of painful touch (analgesia) with placebo improvement of pleasant touch (hyperhedonia) using functional MRI and a crossover design.