CNS Drugs

, Volume 28, Issue 8, pp 713–730 | Cite as

Orexin/Hypocretin Based Pharmacotherapies for the Treatment of Addiction: DORA or SORA?

  • Shaun Yon-Seng Khoo
  • Robyn Mary BrownEmail author
Review Article


Addiction is a chronic relapsing disorder which presents a significant global health burden and unmet medical need. The orexin/hypocretin system is an attractive potential therapeutic target as demonstrated by the successful clinical trials of antagonist medications like Suvorexant for insomnia. It is composed of two neuropeptides, orexin-A and orexin-B and two excitatory and promiscuous G-protein coupled receptors, OX1 and OX2. Orexins are known to have a variety of functions, most notably in regulating arousal, appetite and reward. The orexins have been shown to have a role in mediating the effects of several drugs of abuse, such as cocaine, morphine and alcohol via projections to key brain regions such as the ventral tegmental area, nucleus accumbens and prefrontal cortex. However, it has not yet been demonstrated whether the dual orexin receptor antagonists (DORAs) under development for insomnia are ideal drugs for the treatment of addiction. The question of whether to use a DORA or single orexin receptor antagonist (SORA) for the treatment of addiction is a key question that will need to be answered in order to maximize the clinical utility of orexin receptor antagonists. This review will examine the role of the orexin/hypocretin system in addiction, orexin-based pharmacotherapies under development and factors affecting the selection of one or both orexin receptors as drug targets for the treatment of addiction.


Cocaine Ventral Tegmental Area Progressive Ratio Acamprosate Orexin Neuron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



RMB and SYK are supported by the National Health and Medical Research Council of Australia. SYK is supported by an Australian Postgraduate Award; RMB is supported by a Peter Doherty Fellowship. The authors declare that they have no conflicts of interest.


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.School of PsychologyUniversity of New South WalesSydneyAustralia
  2. 2.Florey Institute of Neuroscience and Mental HealthUniversity of MelbourneParkvilleAustralia

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