Opioid system and human emotions

Nummenmaa, Lauri; Tuominen, Lauri

doi:10.1111/bph.13812

Cited by 133 publications

(106 citation statements)

References 138 publications

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“…In both sexes, MORs were widely expressed in the brain (Figure 1), consistent with previous studies 37 .…”

Section: Resultssupporting

confidence: 91%

Interindividual variability and lateralization of µ-opioid receptors in the human brain

Kantonen

Karjalainen

Isojärvi

et al. 2019

Preprint

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AbstractThe brain’s µ-opioid receptors (MORs) are involved in analgesia, reward and mood regulation. Several neuropsychiatric diseases have been associated with dysfunctional MOR system, and there is also considerable variation in receptor density among healthy individuals. Sex, age, body mass and smoking have been proposed to influence the MOR system, but due to small sample sizes the magnitude of their influence remains inconclusive. Here we quantified in vivo MOR availability in the brains of 204 individuals with no neurologic or psychiatric disorders using positron emission tomography (PET) with tracer [11C]carfentanil. We then used Bayesian hierarchical modeling to estimate the effects of sex, age, body mass index (BMI) and smoking on [11C]carfentanil binding potential. We also examined hemispheric lateralization of MOR availability. Age had regionally specific effects on MOR availability, with age-dependent increase in frontotemporal areas but decrease in amygdala, thalamus, and nucleus accumbens. The age-dependent increase was stronger in males. MOR availability was globally lowered in smokers but independent of BMI. Finally, MOR availability was higher in the right versus the left hemisphere. The presently observed variation in MOR availability may explain why some individuals are prone to develop MOR-linked pathological states, such as chronic pain or psychiatric disorders.

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“…In both sexes, MORs were widely expressed in the brain (Figure 1), consistent with previous studies 37 .…”

Section: Resultssupporting

confidence: 91%

Interindividual variability and lateralization of µ-opioid receptors in the human brain

Kantonen

Karjalainen

Isojärvi

et al. 2019

Preprint

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“…Opioid receptors and peptides are expressed throughout the human reward and reinforcement circuit (Le Merrer, Becker, Befort, & Kieffer, ; Nummenmaa & Tuominen, ) and opioidergic action is involved in hedonic and motivational processing of food (Mendez, Ostlund, Maidment, & Murphy, ; Peciña & Smith, ). We previously found evidence for opioid modulation in physical exercise.…”

Section: Discussionmentioning

confidence: 99%

“…Despite progress in understanding the effects of exercise on hedonic processing of food, the underlying neurochemical mechanisms remain unrevealed. The endogenous mesolimbic opioid system and particularly the μ‐opioid receptors (MOR) are linked to both incentive motivation and hedonic functions, and are involved in generating pleasurable sensations of consuming palatable foods (Nummenmaa & Tuominen, ; Peciña & Smith, ). Animal studies have shown that MOR agonist administration increases food intake (Gosnell & Levine, ; Peciña & Smith, ) and may specifically increase the preference for high‐fat diet (Taha, ).…”

Section: Introductionmentioning

confidence: 99%

Aerobic exercise modulates anticipatory reward processing via the μ‐opioid receptor system

Saanijoki

Nummenmaa

Tuulari

et al. 2018

Human Brain Mapping

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Physical exercise modulates food reward and helps control body weight. The endogenous µ-opioid receptor (MOR) system is involved in rewarding aspects of both food and physical exercise, yet interaction between endogenous opioid release following exercise and anticipatory food reward remains unresolved. Here we tested whether exercise-induced opioid release correlates with increased anticipatory reward processing in humans. We scanned 24 healthy lean men after rest and after a 1 h session of aerobic exercise with positron emission tomography (PET) using MOR-selective radioligand [ C]carfentanil. After both PET scans, the subjects underwent a functional magnetic resonance imaging (fMRI) experiment where they viewed pictures of palatable versus nonpalatable foods to trigger anticipatory food reward responses. Exercise-induced changes in MOR binding in key regions of reward circuit (amygdala, thalamus, ventral and dorsal striatum, and orbitofrontal and cingulate cortices) were used to predict the changes in anticipatory reward responses in fMRI. Exercise-induced changes in MOR binding correlated negatively with the exercise-induced changes in neural anticipatory food reward responses in orbitofrontal and cingulate cortices, insula, ventral striatum, amygdala, and thalamus: higher exercise-induced opioid release predicted higher brain responses to palatable versus nonpalatable foods. We conclude that MOR activation following exercise may contribute to the considerable interindividual variation in food craving and consumption after exercise, which might promote compensatory eating and compromise weight control.

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“…Since MDD is a complex syndrome that includes debilitating emotional, physical, and psychologic symptoms, impaired ability to cope with stress, and significant social dysfunction, which all contribute to diminished well-being [10][11][12][13], new agents with novel mechanisms of action are urgently needed [14]. The endogenous opioid system is a fundamental regulator of mood in humans and is thought to play a critical role in various functional and social processes affected by depression, including motivation, social functioning/ attachment, and resiliency [15][16][17][18]. There is some evidence to support opioid modulation as a potential treatment target for MDD.…”

Section: Introductionmentioning

confidence: 99%

Opioid system modulation with buprenorphine/samidorphan combination for major depressive disorder: two randomized controlled studies

et al. 2018

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The endogenous opioid system is thought to play an important role in the regulation of mood. Buprenorphine/samidorphan (BUP/SAM) combination is an investigational opioid system modulator for adjunctive treatment of major depressive disorder (MDD). To confirm results from early studies, we report the efficacy and safety of BUP/SAM as adjunctive treatment in patients with MDD and an inadequate response to antidepressant therapy (ADT) in FORWARD-4 and FORWARD-5: two phase 3, randomized, double-blind, placebo-controlled studies that utilized the same sequential parallelcomparison design. Efficacy was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS). FORWARD-5 achieved the primary endpoint and demonstrated that adjunctive BUP/SAM 2 mg/2 mg was superior to placebo (average difference change from baseline to week 3 through end of treatment [EOT] in MADRS-6 and −10 versus placebo: −1.5, P = 0.018; −1.9, P = 0.026, respectively). FORWARD-4 did not achieve the primary endpoint (change from baseline in MADRS-10 at week 5 versus placebo: -1.8, P = 0.109), although separate analyses showed significant treatment differences at other timepoints using traditional, regulatory-accepted endpoints such as reduction in MADRS-10 at EOT. The pooled analysis of the two studies demonstrated consistently greater reduction in MADRS-10 scores from baseline for BUP/ SAM 2 mg/2 mg versus placebo at multiple timepoints including EOT and average change from baseline to week 3 through EOT (-1.8, P = 0.010; -1.8, P = 0.004, respectively). The overall effect size (Hedges' g) in the pooled analyses for MADRS-10 change from baseline to EOT was 0.22. Overall, BUP/SAM was generally well tolerated, with most adverse events (AEs) being mild or moderate in severity. The most common AEs, occurring in ≥5% of patients in the BUP/SAM 2 mg/2 mg treatment group, which was more frequently than the placebo group, included nausea, constipation, dizziness, vomiting, somnolence, fatigue, and sedation. There was minimal evidence of abuse, and no evidence of dependence or opioid withdrawal by AEs or objective measures. This report describes adjunctive BUP/SAM 2 mg/2 mg combination, a therapy with a novel opioidergic mechanism of action, as a potential new treatment option for patients with MDD who have an inadequate response to currently available ADT.

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Opioid system and human emotions

Abstract: This article is part of a themed section on Emerging Areas of Opioid Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc.

Cited by 133 publications

References 138 publications

Interindividual variability and lateralization of µ-opioid receptors in the human brain

Interindividual variability and lateralization of µ-opioid receptors in the human brain

Aerobic exercise modulates anticipatory reward processing via the μ‐opioid receptor system

Opioid system modulation with buprenorphine/samidorphan combination for major depressive disorder: two randomized controlled studies

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