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The orexin neurotransmitter system as a target for medication development for opioid use disorder

Neuropsychopharmacology volume 49, pages 329–330 (2024)Cite this article

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While medications for opioid use disorder (MOUD) such as buprenorphine and methadone are frontline, highly effective treatments for opioid use disorder (OUD), the OUD treatment continuum can be improved. Patients and families identify craving as one of the most troubling symptoms during active opioid use, and anxiety and insomnia as the most troubling symptoms during opioid abstinence, and these remain significant challenges for OUD treatments.

The orexin (also known as hypocretin) system is broadly involved in arousal, stress response, sleep, and reward-seeking/consumption behaviors. A recent randomized study (N = 38) compared the dual-orexin receptor antagonist (DORA) suvorexant (20 mg, 40 mg; approved in 2014 for insomnia), to placebo in persons with OUD undergoing a brief buprenorphine taper [1]. Suvorexant was selected because it induces sleep via suppression of the awake network [2], whereas other sleep aids promote sleep via sedation and thus face challenges for adoption in MOUD settings. Suvorexant taken at bedtime produced clinically-significant improvements in self-reported and electroencephalography-determined insomnia. Collateral improvements in opioid craving were also observed [1], which were surprising because they were derived from a non-opioid medication and within patients already receiving a gold-standard MOUD.

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References

  1. Huhn AS, Finan PH, Gamaldo CE, Hammond AS, Umbricht A, Bergeria CL, et al. Suvorexant ameliorated sleep disturbance, opioid withdrawal, and craving during a buprenorphine taper. Sci Transl Med. 2022;14:eabn8238.

    Article  CAS  PubMed  Google Scholar 

  2. Singh R, Biswas DA. Physiological role of orexin/hypocretin in the human body in motivated behavior: a comprehensive review. Cureus. 2023;15:e34009.

    PubMed  PubMed Central  Google Scholar 

  3. Georgescu D, Zachariou V, Barrot M, Mieda M, Willie JT, Eisch AJ, et al. Involvement of the lateral hypothalamic peptide orexin in morphine dependence and withdrawal. J Neurosci. 2003;23:3106–3111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. James MH, Aston-Jones G. Orexin reserve: a mechanistic framework for the role of orexins (hypocretins) in addiction. Biol Psychiatry. 2022;92:836–844. https://doi.org/10.1016/j.biopsych.2022.06.027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD, 21224, USA

    A. S. Huhn & K. E. Dunn

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  1. A. S. Huhn
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  2. K. E. Dunn
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Both authors contributed to the conceptualization, drafting, and final revision of this work and agree to be held accountable for all aspects of the work.

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Correspondence to K. E. Dunn.

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Competing interests

In the past 3 years, KED has consulted or served as an advisor to study protocols with companies Mind Med, Inc. DemeRx, Cessation Therapeutics, and Indivior and has received funding through her university from the National Institute on Drug Abuse and Cure Addiction Now. ASH has consulted for Gilgamesh and received research funding from Indivior through his University.

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Huhn, A.S., Dunn, K.E. The orexin neurotransmitter system as a target for medication development for opioid use disorder. Neuropsychopharmacol. 49, 329–330 (2024). https://doi.org/10.1038/s41386-023-01679-0

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  • DOI: https://doi.org/10.1038/s41386-023-01679-0

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