The role of orexin receptor antagonists in inhibiting the development of drug addiction: A review of past studies

Document Type : Review Article(s)


1 1. Department of Addiction Studies, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran 2. Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Addiction Studies, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran

3 Department of Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran

4 Department of Biology and Health Sciences, Meredith College, Raleigh, North Carolina, USA

5 Department of Physical Therapy, Faculty of Paramedical and Rehabilitation Science, Mashhad University of Medical Sciences, Mashhad, Iran



The orexinergic system and its receptors are involved in many physiological processes. Their functions in energy homeostasis, 
arousal, cognition, stress processing, endocrine functions, and pain modulation have been investigated. Many studies have shown
that the orexinergic system cooperates with the dopaminergic system in the addiction process. Emerging evidence suggests that the 
orexinergic system can be effective in the induction of drug dependence and tolerance. Therefore, several researches have been 
conducted on the effect of orexin receptor (OXR) antagonists on reducing tolerance and dependence caused by drug abuse. Due 
to the significant growth of the studies on the orexinergic system, the current literature was conducted to collect the findings of 
previous studies on orexin and its receptors in the induction of drug addiction. In addition, cellular and molecular mechanisms
of the possible role of orexin in drug tolerance and dependence are discussed. The findings indicate that the administration of
OXR antagonists reduces drug dependence. OXR blockers seem to counteract the addictive effects of drugs through multiple 
mechanisms, such as preventing neuronal adaptation. This review proposes the potential clinical use of OXR antagonists in the 
treatment of drug dependence.


Peyman Esmaili-Shahzade-Ali-Akbari: (Google Scholar) (PubMed)

Amir - Ghaderi: (Google Scholar) (PubMed)

Atena Sadeghi: (Google Scholar) (PubMed)

Fatemeh Nejat: (Google Scholar) (PubMed)

Alireza Mehramiz: (Google Scholar) (PubMed)


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