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New Advances in Opioid Research
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New Advances in Opioid Research

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 20 October 2025 | Viewed by 1679

Special Issue Editor

Dr. Matthew E. Layton

E-Mail Website
Guest Editor
Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99202, USA
Interests: addictions; opioids; pain; hyperbaric oxygen treatment; natural products and drug interactions

Special Issue Information

Dear Colleagues,

Opioid addiction has tripled in the last 25 years, now affecting over 35 million people worldwide. Recurrence rates remain high, and opioid research has been largely limited by stigma, social disparities, and regulatory barriers. This Special Issue invites cutting-edge research from across the continuum from molecular mechanisms to translational clinical approaches. Relevant topics include the use of hyperbaric oxygen for opioid withdrawal in animal and human experiments, as well as findings from complementary, alternative, and integrative research projects. While molecular level research is a priority, mixed-methods patient research findings are also welcome.

This Special Issue is supervised by Dr. Matthew E. Layton, assisted by our Guest Editor’s Assistant Editor Dr. Poppy Gardiner (Washington State University, https://medicine.wsu.edu/directory/wsu-profile/poppymay.gardiner/).

Dr. Matthew E. Layton
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • methadone
  • buprenorphine
  • hyperbaric oxygen
  • complementary/alternative/integrative treatments
  • patient-centered outcomes

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Published Papers (3 papers)

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Research

16 pages, 2024 KiB  
Article
Opioid-Induced Regulation of Cortical Circular-Grin2b_011731 Is Associated with Regulation of circGrin2b Sponge Target miR-26b-3p
by Aria Gillespie and Stephanie E. Daws
Int. J. Mol. Sci. 2025, 26(11), 5010; https://doi.org/10.3390/ijms26115010 - 22 May 2025
Viewed by 269
Abstract
Opioid use induces neurobiological adaptations throughout mesolimbic brain regions, such as the orbitofrontal cortex (OFC), which mediates decision-making and emotional–cognitive regulation. Previously, we showed that a circular RNA (circRNA) species, rno_circGrin2b_011731 (circGrin2b), is upregulated in the OFC of rats [...] Read more.
Opioid use induces neurobiological adaptations throughout mesolimbic brain regions, such as the orbitofrontal cortex (OFC), which mediates decision-making and emotional–cognitive regulation. Previously, we showed that a circular RNA (circRNA) species, rno_circGrin2b_011731 (circGrin2b), is upregulated in the OFC of rats following chronic self-administration (SA) of the opioid heroin. circGrin2b is derived from Grin2b, which encodes the regulatory subunit of the glutamate ionotropic NMDA receptor, GluN2B. However, the upstream regulatory mechanisms of circGrin2b biogenesis and the downstream consequences of circGrin2b dysregulation remain unknown. We hypothesized that opioid-induced elevation of circGrin2b is accompanied by regulation of circRNA biogenesis enzymes, and that circGrin2b may sponge microRNAs (miRNAs), as miRNA sponging is a well-described characteristic of circRNAs. To test these hypotheses, we established an in vitro primary cortical cell culture model to examine alterations in circGrin2b expression following exposure to the opioid morphine. We measured mRNA expression of known circRNA splicing factors and observed significant downregulation of Fused in Sarcoma (Fus), a negative regulator of circRNA biogenesis, following 90 min or 24 h of morphine exposure. Downregulation of Fus at 24 h post-morphine was accompanied by upregulation of circGrin2b and downregulation of miR-26b-3p, a predicted miRNA target of circGrin2b. Luciferase reporter assays confirmed interaction of miR-26b-3p with circGrin2b. Finally, we report a significant negative relationship between circGrin2b and miR-26b-3p expression in the OFC of rats following heroin SA. We conclude that regulation of circGrin2b is an opioid-induced neuroadaptation that may impact downstream signaling of miRNA pathways in the frontal cortex. Full article
(This article belongs to the Special Issue New Advances in Opioid Research)
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16 pages, 2771 KiB  
Article
An Investigation of the RNA Modification m6A and Its Regulatory Enzymes in Rat Brains Affected by Chronic Morphine Treatment and Withdrawal
by Anna Hronova, Eliska Pritulova, Lucie Hejnova and Jiri Novotny
Int. J. Mol. Sci. 2025, 26(9), 4371; https://doi.org/10.3390/ijms26094371 - 4 May 2025
Viewed by 367
Abstract
N6-methyladenosine (m6A) is one of the most prevalent methylated modifications of mRNA in eukaryotes. This reversible alteration can directly or indirectly influence biological functions, including RNA degradation, translation, and splicing. This study investigates the impact of chronic morphine administration and varying [...] Read more.
N6-methyladenosine (m6A) is one of the most prevalent methylated modifications of mRNA in eukaryotes. This reversible alteration can directly or indirectly influence biological functions, including RNA degradation, translation, and splicing. This study investigates the impact of chronic morphine administration and varying withdrawal durations (1 day, 1 week, 4 weeks, and 12 weeks) on the m6A modification levels in brain regions critical to addiction development and persistence. Our findings indicate that in the prefrontal cortex, the m6A levels and METTL3 expression decrease, accompanied by an increase in FTO and ALKBH5 expression, followed by fluctuating, but statistically insignificant changes in methylation-regulating enzymes over prolonged withdrawal. In the striatum, reductions in m6A levels and METTL3 expression are observed at 4 weeks of withdrawal, preceded by non-significant fluctuations in enzyme expression and the m6A modification levels. In contrast, no changes in the m6A modification levels or the expression of related enzymes are detected in the hippocampus and the cerebellum. Our data suggest that m6A modification and its regulatory enzymes undergo region-specific and time-dependent changes in response to chronic morphine exposure and subsequent withdrawal. Full article
(This article belongs to the Special Issue New Advances in Opioid Research)
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20 pages, 5879 KiB  
Article
Drug-Checking and Monitoring New Psychoactive Substances: Identification of the U-48800 Synthetic Opioid Using Mass Spectrometry, Nuclear Magnetic Resonance Spectroscopy, and Bioinformatic Tools
by Maria Beatriz Pereira, Carlos Família, Daniel Martins, Mar Cunha, Mário Dias, Nuno R. Neng, Helena Gaspar and Alexandre Quintas
Int. J. Mol. Sci. 2025, 26(5), 2219; https://doi.org/10.3390/ijms26052219 - 28 Feb 2025
Viewed by 683
Abstract
The misuse of opioids and opiates has remained a persistent issue since the 19th century. The recent resurgence of non-fentanyl synthetic opioids, such as U-type opioids and nitazenes, has further exacerbated the ongoing crisis. Identifying these synthetic opioids presents many challenges, including the [...] Read more.
The misuse of opioids and opiates has remained a persistent issue since the 19th century. The recent resurgence of non-fentanyl synthetic opioids, such as U-type opioids and nitazenes, has further exacerbated the ongoing crisis. Identifying these synthetic opioids presents many challenges, including the emergence of new substances, the lack of standards, and the presence of structural isomers. This highlights the need for a robust structural characterisation strategy in forensic laboratories. To address these challenges, we developed a methodology to identify a U-type opioid sample received by Kosmicare from the European Union-funded SCANNER project, which was suspected to be either U-48800 or U-51754. Our innovative approach combined gas chromatography coupled with mass spectrometry (GC-MS), nuclear magnetic resonance spectroscopy (NMR), and molecular dynamics to characterise the questioned sample unequivocally. While the GC-MS analysis suggested a potential match with the mass spectrum of U-51754 and its structural isomer U-48800, NMR analysis confirmed the presence of U-48800 in the sample, which was further validated through molecular dynamics experiments. These experiments provided additional insights, confirming the structural features underlying the obtained NMR profile. The presented methodology offers a valuable solution for cases involving the identification of isomers, which are currently one of the most significant challenges in identifying new psychoactive substances. Full article
(This article belongs to the Special Issue New Advances in Opioid Research)
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