ArticleNeuropharmacology2023
Buprenorphine and methadone differentially alter early brain development in human cortical organoids.
Article in Neuropharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Cerebral organoids as a platform to model prenatal exposure to drugs of abuse.Neural regeneration research · 2026Article
- Antenatal Opioid Exposure and Cerebral Cortical Maturation in Newborns.JAMA network open · 2026Article
- Prenatal exposure to buprenorphine or methadone and adverse neurodevelopmental outcomes: population based cohort study.BMJ (Clinical research ed.) · 2026Article
- Disrupted Brain Connectivity in Newborns Following Antenatal Opioid Exposure.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2026Observational
- Stem Cell Models for Elucidating Cellular Mechanisms of Substance Use Disorders and Advancing Addiction Pharmacology.Stem cells international · 2026Review
- Bioelectronic Interfaces and Sensors for Neural Organoids.Microsystems & nanoengineering · 2025Review
- Prenatal Opioid Exposure Is Associated with Punctate White Matter Lesions in Term Newborns.The Journal of pediatrics · 2025Observational
- Towards a quality control framework for cerebral cortical organoids.Scientific reports · 2025Article
- Methadone and Buprenorphine as Medication for Addiction Treatment Diversely Affect Inflammation and Craving Depending on Their Doses.Pharmacy (Basel, Switzerland) · 2025Article
- A Comprehensive Review on Utilizing Human Brain Organoids to Study Neuroinflammation in Neurological Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Review
- A human iPSC-derived midbrain neural stem cell model of prenatal opioid exposure and withdrawal: A proof of concept study.PloS one · 2025Article
- Methadone directly impairs central nervous system cells in vitro.Scientific reports · 2024Article
- Brain organoid protocols and limitations.Frontiers in cellular neuroscience · 2024Review
- Investigating the neurobiology of maternal opioid use disorder and prenatal opioid exposure using brain organoid technology.Frontiers in cellular neuroscience · 2024Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Buprenorphine (BUP) and methadone (MTD) are used for medication-assisted treatment (MAT) in opioid use disorder. Although both medications show improved maternal and neonatal outcomes compared with illicit opioid use during pregnancy, BUP has exhibited more favorable outcomes to newborns than MTD. The underlying cellular and molecular mechanisms for the difference between BUP and MTD are largely unknown. Here, we examined the growth and neuronal activity in human cortical organoids (hCOs) exposed to BUP or MTD. We found that the growth of hCOs was significantly restricted in the MTD-treated but not in the BUP-treated hCOs and BUP attenuated the growth-restriction effect of MTD in hCOs. Furthermore, a κ-receptor agonist restricted while an antagonist alleviated the growth-restriction effect of MTD in hCOs. Since BUP is not only a μ-agonist but a κ-antagonist, the prevention of this growth-restriction by BUP is likely due to its κ-receptor-antagonism. In addition, using multielectrode array (MEA) technique, we discovered that both BUP and MTD inhibited neuronal activity in hCOs but BUP showed suppressive effects only at higher concentrations. Furthermore, κ-receptor antagonist nBNI did not prevent the MTD-induced suppression of neuronal activity in hCOs but the NMDA-antagonism of MTD (that BUP lacks) plays a role in the inhibition of neuronal activity. We conclude that, although both MTD and BUP are μ-opioid agonists, a) the additional κ-receptor antagonism of BUP mitigates the MTD-induced growth restriction during neurodevelopment and b) the lack of NMDA antagonism of BUP (in contrast to MTD) induces much less suppressive effect on neural network communications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.