The Cholinergic System as a Treatment Target for Opioid Use Disorder
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LEADING ARTICLE
The Cholinergic System as a Treatment Target for Opioid Use Disorder Kevin P. Jensen1 · Elise E. DeVito1 · Sarah Yip1 · Kathleen M. Carroll1 · Mehmet Sofuoglu1
© Springer Nature Switzerland AG 2018
Abstract Opioid overdoses recently became the leading cause of accidental death in the US, marking an increase in the severity of the opioid use disorder (OUD) epidemic that is impacting global health. Current treatment protocols for OUD are limited to opioid medications, including methadone, buprenorphine, and naltrexone. While these medications are effective in many cases, new treatments are required to more effectively address the rising societal and interpersonal costs associated with OUD. In this article, we review the opioid and cholinergic systems, and examine the potential of acetylcholine (ACh) as a treatment target for OUD. The cholinergic system includes enzymes that synthesize and degrade ACh and receptors that mediate the effects of ACh. ACh is involved in many central nervous system functions that are critical to the development and maintenance of OUD, such as reward and cognition. Medications that target the cholinergic system have been approved for the treatment of Alzheimer’s disease, tobacco use disorder, and nausea. Clinical and preclinical studies suggest that medications such as cholinesterase inhibitors and scopolamine, which target components of the cholinergic system, show promise for the treatment of OUD and further investigations are warranted.
Key Points Opioid use disorder (OUD) is increasing in the population and new medications could help reduce the negative impact to global health. Medications that target the brain cholinergic system show promise in clinical and preclinical studies of OUD. Further studies on cholinergic medications for OUD are warranted.
1 Introduction The US is currently facing an opioid use disorder (OUD) epidemic, which started with large increases in opioid prescriptions in 1990 and expanded by the widespread availability of heroin and synthetic opioids [1, 2]. In addition to affecting the US, OUD is problematic in several other * Mehmet Sofuoglu [email protected] 1
Department of Psychiatry and VA Connecticut Healthcare System, Yale University, School of Medicine, 950 Campbell Ave, Bldg 36/116A4, West Haven, CT 06516, USA
countries and significantly contributes to global disease burden [3]. The current epidemic has resulted in an estimated 2.1 million individuals in the US with OUD in 2016 [4, 5]. In 2016, over 42,000 people died from opioid overdose, making it the leading cause of accidental death in the US [6]. Medication-assisted treatment (MAT), including methadone, buprenorphine, and naltrexone, is effective in reducing opioid use, rate of OUD-associated infections, and psychosocial consequences of OUD [7–9]. However, high rates of attrition limit the effectiveness of MAT, underscoring the need to develop novel primary or adjunct treatments for OUD [7, 8]. As discussed in this review, among potential treatment targets for OUD, th
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