Insights into the mechanisms underlying opioid use disorder and potential treatment strategies

Abstract

Opioid use disorder is a worldwide societal problem and public health burden. Strategies for treating opioid use disorder can be divided into those that target the opioid receptor system and those that target non‐opioid receptor systems, including the dopamine and glutamate receptor systems. Currently, the clinical drugs used to treat opioid use disorder include the opioid receptor agonists methadone and buprenorphine, which are limited by their abuse liability, and the opioid receptor antagonist naltrexone, which is limited by poor compliance. Therefore, the development of effective medications with lower abuse liability and better potential for compliance is urgently needed. Based on recent advances in the understanding of the neurobiological mechanisms underlying opioid use disorder, potential treatment strategies and targets have emerged. This review focuses on the progress made in identifying potential targets and developing medications to treat opioid use disorder, including progress made by our laboratory, and provides insights for future medication development. LINKED ARTICLES This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc

TIDAL: Topology-Inferred Drug Addiction Learning

“…For example, the United States (U.S.) recorded 70630 drug abuse-related deaths in 2019, and that number exceeded 100,000 in 2021, up 15% from 2020, becoming the leading cause of accidental deaths in the U.S. The current approaches to treating drug addiction can be classified into two categories, one directly targeting the drug receptor system and the other indirectly targeting nondrug receptor systems, like the dopamine and glutamate receptors . For psychostimulant drugs, like cocaine, the main mechanism for the treatment is to inhibit dopamine reuptake via blockading the dopamine transporter (DAT) .…”

Mice with High FGF21 Serum Levels Had a Reduced Preference for Morphine and an Attenuated Development of Acute Antinociceptive Tolerance and Physical Dependence

“…The psychological dependence of craving opioids is associated with opioid misuse. Increases in dopamine levels in certain brain regions mediate the reinforcing effects of opioids (Cao et al, 2021; Nisell et al, 1994; Wiss et al, 2018). In addition to opioids, sucrose, saccharin and alcohol, as well as other drugs of abuse, increase dopamine release in the nucleus accumbens (NAc) and this increase in dopamine levels has been correlated to development of preference in mice (Ma and Zhu, 2014; Yoshimoto et al, 1992).…”

Opioid research in the time of the opioid crisis

“…The approved therapies for OUD, namely, methadone, the buprenorphine‐naloxone combination and naltrexone are reviewed by Cao et al (2023). They point out that in OUD neuroadaptations also occur in dopaminergic, glutamatergic and GABAergic circuits.…”

“…There is evidence for sex differences in treatment outcomes and complications of translation from animal models to human patients (Cao et al, 2023). The standard method to examine drugs for abuse liability and to evaluate treatments for substance use disorders including OUD is intravenous self‐administration in rats or non‐human primates, usually allowing the animals continuous access to the drug under study for a set time.…”

“…There is evidence for sex differences in treatment outcomes and complications of translation from animal models to human patients (Cao et al, 2023). The standard method to examine drugs for abuse Many people with OUD start off being treated chronically with opioid medications for pain.…”