Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (816 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Trexan; EN-1639A; EN1639A; EN 1639A; Antaxone; Celupan; ReVia; Nalorex.
Where it fits in the MeSH classification
- Broader topics
- Naloxone
Related concepts
Research landscape
PubMed indexes 9,302 records tagged with the MeSH heading “Naltrexone” (counts retrieved 2026-10-31). 1,403 of them (15.1%) were published from 2020 onward, and the busiest period so far is through 1999 with 3,424 records.
Reviews account for 934 records (10.0%) and meta-analyses for 135. Randomized controlled trials number 1,018 (10.9%) as a share of all records on the topic. Randomized trials make up a comparatively large share of this literature, which means many treatment questions have been tested directly.
Show the data
| Period | Records |
|---|---|
| through 1999 | 3,424 |
| 2000-2009 | 2,199 |
| 2010-2019 | 2,276 |
| 2020 onward | 1,403 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 934 | 10.0% |
| Meta-analyses | 135 | 1.5% |
| Randomized controlled trials | 1,018 | 10.9% |
Method: PubMed query "Naltrexone"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
Opioid system modulation with buprenorphine/samidorphan combination for major depressive disorder: two randomized controlled studies [1]
Abstract reading summary — source excerpts
- Opening excerpt
- The endogenous opioid system is thought to play an important role in the regulation of mood.
- Closing excerpt
- This report describes adjunctive BUP/SAM 2 mg/2 mg combination, a therapy with a novel opioidergic mechanism of action, as a potential new treatment option for patients with MDD who have an inadequate response to currently available ADT.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (350 words)
The endogenous opioid system is thought to play an important role in the regulation of mood. Buprenorphine/samidorphan (BUP/SAM) combination is an investigational opioid system modulator for adjunctive treatment of major depressive disorder (MDD). To confirm results from early studies, we report the efficacy and safety of BUP/SAM as adjunctive treatment in patients with MDD and an inadequate response to antidepressant therapy (ADT) in FORWARD-4 and FORWARD-5: two phase 3, randomized, double-blind, placebo-controlled studies that utilized the same sequential parallel-comparison design. Efficacy was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS). FORWARD-5 achieved the primary endpoint and demonstrated that adjunctive BUP/SAM 2 mg/2 mg was superior to placebo (average difference change from baseline to week 3 through end of treatment [EOT] in MADRS-6 and -10 versus placebo: -1.5, P = 0.018; -1.9, P = 0.026, respectively). FORWARD-4 did not achieve the primary endpoint (change from baseline in MADRS-10 at week 5 versus placebo: -1.8, P = 0.109), although separate analyses showed significant treatment differences at other timepoints using traditional, regulatory-accepted endpoints such as reduction in MADRS-10 at EOT. The pooled analysis of the two studies demonstrated consistently greater reduction in MADRS-10 scores from baseline for BUP/SAM 2 mg/2 mg versus placebo at multiple timepoints including EOT and average change from baseline to week 3 through EOT (-1.8, P = 0.010; -1.8, P = 0.004, respectively). The overall effect size (Hedges' g) in the pooled analyses for MADRS-10 change from baseline to EOT was 0.22. Overall, BUP/SAM was generally well tolerated, with most adverse events (AEs) being mild or moderate in severity. The most common AEs, occurring in ≥5% of patients in the BUP/SAM 2 mg/2 mg treatment group, which was more frequently than the placebo group, included nausea, constipation, dizziness, vomiting, somnolence, fatigue, and sedation. There was minimal evidence of abuse, and no evidence of dependence or opioid withdrawal by AEs or objective measures. This report describes adjunctive BUP/SAM 2 mg/2 mg combination, a therapy with a novel opioidergic mechanism of action, as a potential new treatment option for patients with MDD who have an inadequate response to currently available ADT.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 30374191 · DOI · PMC7303008
Activation of TRPM7 by naltriben enhances migration and invasion of glioblastoma cells [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Glioblastoma (GBM), the most common and aggressive brain tumor in the central nervous system, remains a lethal diagnosis with a median survival of < 15 months.
- Closing excerpt
- Therefore, potentiated TRPM7 activity contributes to the devastating migratory and invasive characteristics of GBM.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (162 words)
Glioblastoma (GBM), the most common and aggressive brain tumor in the central nervous system, remains a lethal diagnosis with a median survival of < 15 months. Aberrant expression of the TRPM7 channel has been linked to GBM functions. In this study, using the human GBM cell line U87, we evaluated the TRPM7 activator naltriben on GBM viability, migration, and invasiveness. First, using the whole-cell patch-clamp technique, we showed that naltriben enhanced the endogenous TRPM7-like current in U87 cells. In addition, with Fura-2 Ca2+ imaging, we observed robust Ca2+ influx following naltriben application. Naltriben significantly enhanced U87 cell migration and invasion (assessed with scratch wound assays, Matrigel invasion experiments, and MMP-2 protein expression), but not viability and proliferation (evaluated with MTT assays). Using Western immunoblots, we also detected the protein levels of p-Akt/t-Akt, and p-ERK1|2/t-ERK1|2. We found that naltriben enhanced the MAPK/ERK signaling pathway, but not the PI3k/Akt pathway. Therefore, potentiated TRPM7 activity contributes to the devastating migratory and invasive characteristics of GBM.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 28061441 · DOI · PMC5355261
Dopaminergic and opioidergic regulation during anticipation and consumption of social and nonsocial rewards [3]
Abstract reading summary — source excerpts
- Opening excerpt
- The observation of animal orofacial and behavioral reactions has played a fundamental role in research on reward but is seldom assessed in humans.
- Closing excerpt
- Results suggest that facial reactions during anticipated and experienced pleasure rely on partly different neurochemical systems, and also that the neurochemical bases for food and touch rewards are not identical.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (144 words)
The observation of animal orofacial and behavioral reactions has played a fundamental role in research on reward but is seldom assessed in humans. Healthy volunteers (N = 131) received 400 mg of the dopaminergic antagonist amisulpride, 50 mg of the opioidergic antagonist naltrexone, or placebo. Subjective ratings, physical effort, and facial reactions to matched primary social (affective touch) and nonsocial (food) rewards were assessed. Both drugs resulted in lower physical effort and greater negative facial reactions during reward anticipation, especially of food rewards. Only opioidergic manipulation through naltrexone led to a reduction in positive facial reactions to liked rewards during reward consumption. Subjective ratings of wanting and liking were not modulated by either drug. Results suggest that facial reactions during anticipated and experienced pleasure rely on partly different neurochemical systems, and also that the neurochemical bases for food and touch rewards are not identical.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33046213 · DOI · PMC7553773
Effect of naltrexone pretreatment on ketamine-induced glutamatergic activity and symptoms of depression: a randomized crossover study [4]
Abstract reading summary — source excerpts
- Opening excerpt
- We investigated the potential role of the opioid system in modulating glutamatergic effects of ketamine administration in major depressive disorder.
- Closing excerpt
- gov registration: NCT04977674 .
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (160 words)
We investigated the potential role of the opioid system in modulating glutamatergic effects of ketamine administration in major depressive disorder. Twenty-six adults with major depressive disorder participated in a double-blind crossover study, receiving oral placebo or 50 mg naltrexone before an intravenous infusion of 0.5 mg per kg ketamine. Brain glutamatergic activity in the anterior cingulate cortex was measured using functional magnetic resonance spectroscopy and depressive symptoms were assessed with the Montgomery-Åsberg Depression Rating Scale. Naltrexone attenuated the increase in glutamate + glutamine to total N-acetylaspartate ratio during ketamine infusion compared to placebo (F1,253 = 4.83, P = 0.029) and also attenuated the reduction in Montgomery-Åsberg Depression Rating Scale scores on day 1 (condition-by-time interaction, F1,74 = 5.39, P = 0.023). These findings demonstrate that the opioid system modulates the acute response to ketamine and subsequent antidepressant effects. Interactions between the glutamate and opioid systems may have implications for the development of new depression treatment strategies. ClinicalTrials.gov registration: NCT04977674 .
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40707608 · DOI · PMC12443602
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful? [5]
- Research article Efficacy of naltrexone and acamprosate for alcoholism treatment: a meta-analysis [6]
- Research article Pharmacotherapy of addictions [7]
- Research article Opioid antagonists for alcohol dependence [8]
- Research article Pharmacotherapy for Alcohol Use Disorder: A Systematic Review and Meta-Analysis [9]
- Research article Long-term course of opioid addiction [10]
References
- Fava M, Thase ME, Trivedi MH, Ehrich E, Martin WF, Memisoglu A, et al.. Opioid system modulation with buprenorphine/samidorphan combination for major depressive disorder: two randomized controlled studies. . 2020. PMID 30374191 · DOI · PMC7303008
- Wong R, Turlova E, Feng ZP, Rutka JT, Sun HS. Activation of TRPM7 by naltriben enhances migration and invasion of glioblastoma cells. . 2017. PMID 28061441 · DOI · PMC5355261
- Korb S, Götzendorfer SJ, Massaccesi C, Sezen P, Graf I, Willeit M, et al.. Dopaminergic and opioidergic regulation during anticipation and consumption of social and nonsocial rewards. . 2020. PMID 33046213 · DOI · PMC7553773
- Jelen LA, Lythgoe DJ, Stone JM, Young AH, Mehta MA. Effect of naltrexone pretreatment on ketamine-induced glutamatergic activity and symptoms of depression: a randomized crossover study. . 2025. PMID 40707608 · DOI · PMC12443602
- Maisel NC, Blodgett JC, Wilbourne PL, Humphreys K, Finney JW. Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful?. Addiction. 2013. PMID 23075288 · DOI · PMC3970823
- Kranzler HR, Van Kirk J. Efficacy of naltrexone and acamprosate for alcoholism treatment: a meta-analysis. Alcohol Clin Exp Res. 2001. PMID 11584154 · DOI
- Kreek MJ, LaForge KS, Butelman E. Pharmacotherapy of addictions. Nat Rev Drug Discov. 2002. PMID 12209151 · DOI
- Rösner S, Hackl-Herrwerth A, Leucht S, Vecchi S, Srisurapanont M, Soyka M. Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev. 2010. PMID 21154349 · DOI · PMC13590218
- McPheeters M, O'Connor EA, Riley S, Kennedy SM, Voisin C, Kuznacic K, et al.. Pharmacotherapy for Alcohol Use Disorder: A Systematic Review and Meta-Analysis. JAMA. 2023. PMID 37934220 · DOI · PMC10630900
- Hser YI, Evans E, Grella C, Ling W, Anglin D. Long-term course of opioid addiction. Harv Rev Psychiatry. 2015. PMID 25747921 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.