Use of experimental medicine approaches for the development of novel psychiatric treatments based on orexin receptor modulation

Beckenstrom, Amy C.; Coloma, Preciosa; Dawson, Gerard R.; Finlayson, Ailidh K.; Malik, Asad; Post, Anke; Steiner, Michel; Potenza, Marc N.

doi:10.1016/j.neubiorev.2023.105107

Cited by 4 publications

(3 citation statements)

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“…Similarly, risky decision-making is not a usual measure of therapeutic success. Nonetheless, it has been argued that approaches aiming to investigate efficacy of interventions consider the use of such experimental medicine measures ( Beckenstrom et al, 2023 ). Considering these factors, the positive results of the study may be limited in determining the success of the intervention, in turn potentially limiting the transferability of findings to other contexts.…”

Section: Discussionmentioning

confidence: 99%

The effects of emotional working memory training on internet use, impulsivity, risky decision-making, and cognitive emotion regulation strategies in young adults with problematic use of the internet: A preliminary randomized controlled trial study into possible mechanisms

Emadi Chashmi,

Shahrajabian,

Hasani

et al. 2023

JBA

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IntroductionConsidering adverse correlates of problematic use of internet use (PUI), the present study evaluated an intervention aimed at PUI and several putative underpinnings.MethodsA randomized controlled trial study investigated the efficacy of emotional working memory training (eWMT) in improving impulsivity, risky decision-making, and cognitive emotion-regulation (CER) strategies among individuals with PUI in comparison with a placebo group. Young adults (N = 36) with PUI were either trained for 20 sessions in an n-back dual emotional task (eWMT; n = 18) or a feature-matching task (placebo; n = 18).ResultsTwenty continuous sessions of eWMT significantly improved participants' impulsivity, risky decision-making, CER, internet use and PUI symptoms in the short term, compared to the placebo condition.DiscussionThese preliminary results suggest that eWMT may constitute a promising intervention for PUI and improving cognitive and emotional functioning, and larger, longer studies are warranted.

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Section: Discussionmentioning

confidence: 99%

The effects of emotional working memory training on internet use, impulsivity, risky decision-making, and cognitive emotion regulation strategies in young adults with problematic use of the internet: A preliminary randomized controlled trial study into possible mechanisms

Emadi Chashmi,

Shahrajabian,

Hasani

et al. 2023

JBA

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“…Other neuropeptides, including orexin, oxytocin, and melanocortin 4 (MC4) receptors, have also been linked to nicotine addiction and/or stress-induced nicotine relapse. Orexin, a neuropeptide that has been linked to emotion, sleep, and stress response [132][133][134][135], may be a potential therapeutic target for controlling nicotine use [136,137]. Intra-cerebroventricular injection of orexin-1 could reinstate extinguished nicotine-seeking behavior, suggesting that orexin-1 might be involved in nicotine relapse [56].…”

Section: Other Peptide Systemsmentioning

confidence: 99%

Neurobiology of Stress-Induced Nicotine Relapse

Wang,

Chen,

Dong

et al. 2024

IJMS

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Tobacco smoking is the leading cause of preventable death and disease. Although there are some FAD-approved medicines for controlling smoking, the relapse rate remains very high. Among the factors that could induce nicotine relapse, stress might be the most important one. In the last decades, preclinical studies have generated many new findings that lead to a better understanding of stress-induced relapse of nicotine-seeking. Several molecules such as α3β4 nicotinic acetylcholine receptor, α2-adrenergic receptors, cannabinoid receptor 1, trace amine-associated receptor 1, and neuropeptide systems (corticotropin-releasing factor and its receptors, dynorphine and kappa opioid receptor) have been linked to stress-induced nicotine relapse. In this review, we discuss recent advances in the neurobiology, treatment targets, and potential therapeutics of stress-induced nicotine relapse. We also discuss some factors that may influence stress-induced nicotine relapse and that should be considered in future studies. In the final section, a perspective on some research directions is provided. Further investigation on the neurobiology of stress-induced nicotine relapse will shed light on the development of new medicines for controlling smoking and will help us understand the interactions between the stress and reward systems in the brain.

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“…Orexins are excitatory neuropeptides, produced by a small number of neurons in the hypothalamus, that project to (and receive input from) many areas of the brain including well‐characterized centers of natural (food) and synthetic (drugs) reward signal processing/integration. Not surprisingly, the orexin system has emerged as an important new drug target for neuropsychiatric conditions due to its role in diverse brain functions (Beckenstrom et al, 2023). Preclinical studies suggest that orexin neuropeptides regulate intake of highly palatable food and compulsive behavior, stress processing, and the motivation for obtaining rewards mainly through activation of orexin 1 receptor (OX1R), as well as sleep and wakefulness mainly through orexin 2 receptor (OX2R) (Merlo Pich & Melotto, 2014; Tsujino & Sakurai, 2013).…”

Section: Introductionmentioning

confidence: 99%

Efficacy, safety, and tolerability of nivasorexant in adults with binge‐eating disorder: A randomized, Phase II proof of concept trial

McElroy

Coloma

Berger

et al. 2023

Intl J Eating Disorders

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ObjectiveThis Phase II, placebo‐controlled, double‐blind study investigated the efficacy, safety, and tolerability of nivasorexant in the treatment of adults with moderate to severe binge‐eating disorder (BED).MethodsAdults meeting the DSM‐5 BED criteria were randomized 1:1 to placebo or nivasorexant (100 mg b.i.d.). The primary endpoint was the change from baseline to Week 12 in the number of binge eating (BE) days per week. Exploratory efficacy endpoints included cessation of BE in the last 4 weeks of treatment; and change from baseline to Week 12 in the number of BE episodes/week, the clinician global impression (CGI) of change, the Yale‐Brown Obsessive‐Compulsive Scale modified for BE, and the Hamilton rating scale for depression (HAMD‐17). Key safety outcomes included treatment‐emergent adverse events (TEAEs) and adverse events of special interest (i.e., somnolence and fatigue).ResultsSixty‐eight participants were randomized to each treatment arm. The change from baseline to Week 12 in the number of BE days/week was the same for placebo (least squares mean [LSM]: −2.93) and nivasorexant (LSM: −2.93), with no difference between the treatment groups (LSM difference = .000 [95% confidence interval (CI): −.69, .69], p = .9992). Furthermore, no differences between treatment groups were observed in the exploratory efficacy endpoints. Nivasorexant was well tolerated; the overall incidence of TEAEs was balanced between treatment groups, and the frequency of somnolence and fatigue in the nivasorexant group were similar to placebo.DiscussionIn this proof‐of‐concept study, 100 mg b.i.d. nivasorexant did not improve BE in adults with moderate to severe BED.Public SignificanceThe results of this Phase II study indicate that nivasorexant was well tolerated in adults with BED, but did not improve binge eating behavior over placebo. Further research is needed to improve our understanding of the role of the orexin‐1 receptor in BED.

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Use of experimental medicine approaches for the development of novel psychiatric treatments based on orexin receptor modulation

Cited by 4 publications

References 290 publications

The effects of emotional working memory training on internet use, impulsivity, risky decision-making, and cognitive emotion regulation strategies in young adults with problematic use of the internet: A preliminary randomized controlled trial study into possible mechanisms

The effects of emotional working memory training on internet use, impulsivity, risky decision-making, and cognitive emotion regulation strategies in young adults with problematic use of the internet: A preliminary randomized controlled trial study into possible mechanisms

Neurobiology of Stress-Induced Nicotine Relapse

Efficacy, safety, and tolerability of nivasorexant in adults with binge‐eating disorder: A randomized, Phase II proof of concept trial

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