Low-Dose Naltrexone as an Adjuvant in Combined Anticancer Therapy - adjuvant research review

Sep 21, 2026

Naltrexone (NTX) is a non-selective opioid receptor antagonist, while low-dose naltrexone (LDN) antagonizes the opioid growth factor receptor (OGFr) pathway implicated in cancer cell survival, proliferation, and invasion. The dose- and duration-dependent OGFr blockade can trigger compensatory opioid growth factor (OGF) changes that suppress carcinogenesis. Evidence from in vitro and in vivo models supports LDN’s capacity to inhibit the OGF–OGFr axis without direct cytotoxicity, alongside immunomodulatory effects that support its role as an adjuvant in chemotherapy and immunotherapy.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages23

Reading Time58 min

AccessFree to download

Introduction

Cancer pain and opioid therapy concerns

Opioid receptor expression and antagonist rationale

The µ Receptor and Cancer

Locations and roles of µ-opioid receptors in CNS and immune cells

cancers Review Low-Dose Naltrexone as an Adjuvant in Combined Anticancer Therapy Marianna Ciwun *, Anna Tankiewicz-Kwedlo and Dariusz Pawlak Citation: Ciwun, M.; Tankiewicz-Kwedlo, A.; Pawlak, D. Low-Dose Naltrexone as an Adjuvantin Combined Anticancer Therapy. Cancers 2024, 16, 1240. [https://](https://)[ ](https://)[doi.org/10.3390/cancers16061240](doi.org/10.3390/cancers16061240) Academic Editor: Massimo Broggini Received: 28 February 2024 Revised: 18 March 2024 Accepted: 20 March 2024 Published: 21 March 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . Department of Pharmacodynamics, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, Poland; [anna.tankiewicz-kwedlo@umb.edu.pl](anna.tankiewicz-kwedlo@umb.edu.pl) (A.T.-K.); [dariusz.pawlak@umb.edu.pl](dariusz.pawlak@umb.edu.pl) (D.P.) * [Correspondence: marianna.ciwun@gmail.com](Correspondence: marianna.ciwun@gmail.com); Tel.: +48-85-686-5230 Simple Summary: This review aims to present current evidence on the potential use of low-dose naltrexone (LDN) in cancer therapy. Low-dose naltrexone exhibits an inhibitory effect on cancer cell proliferation by blocking the opioid growth factor–receptor axis and enhancing the immune response against cancer cells. Data from existing studies indicate that low-dose naltrexone has a high anti-cancer potential, especially as an adjuvant in conventional chemotherapy and immunotherapy schemes. Abstract: Naltrexone (NTX) is a non-selective antagonist of opioid receptors, primarily used in the therapy of opioid and alcohol dependence. Low-dose naltrexone (LDN) exhibits antagonistic action against the opioid growth factor receptor (OGFr), whose signaling is associated with the survival, proliferation, and invasion of cancer cells. The mechanism of action of LDN depends on the dose and duration of the OGFr blockade, leading to a compensatory increase in the synthesis of the opioid growth factor (OGF), which has an inhibitory effect on carcinogenesis. Numerous studies on in vitro and in vivo models provide evidence of LDN’s positive impact on inhibiting the OGF–OGFr axis in cancers. LDN’s unique mechanism of action on cancer cells, lack of direct cytotoxic effect, and immunomodulating action form the basis for its use as an adjuvant in chemotherapy and immunotherapy of cancerous lesions. Keywords: naltrexone; low-dose naltrexone; cancer; synergistic therapy; adjuvant 1. Introduction Cancer pain is a serious issue that constitutes a significant barrier to effective therapy and the daily functioning of oncological patients. According to data from 2016, 55% of patients undergoing cancer treatment and 66% of those with advanced cancer suffer from chronic pain, which translates to worse prognoses for the patients and a decrease in the effectiveness of the applied anti-cancer treatment [1] . There are schemes for effective pharmacotherapy of pain using both non-opioid and opioid medications. New literature data suggest that the use of opioids may be associated with a worse response to the applied pharmacotherapy, while simultaneously exacerbating cancer progression [2] . In recent years, it has been discovered that many cancers exhibit overexpression of opioid receptors, which are target points for classical opioid drugs, and stimulating their activity is linked to increased carcinogenesis [3] . Moreover, the discovery of the new ζ-opioid receptor and the OGF–OGFr axis has posed the question to the scientific community of whether the use of opioid receptor antagonists, such as naltrexone and methylnaltrexone, can impact the reversal of the negative effects of using classical opioids in cance

FAQs

What is the proposed mechanism of low-dose naltrexone in cancer therapy?

LDN is proposed to antagonize the opioid growth factor receptor (OGFr) axis, affecting cancer cell survival, proliferation, and invasion. The effect depends on dose and duration of OGFr blockade, leading to compensatory changes in opioid growth factor synthesis with inhibitory impact on carcinogenesis.

Why is LDN considered an adjuvant rather than a direct cytotoxic agent?

The review emphasizes LDN’s lack of direct cytotoxic effect on cancer cells. Instead, it is characterized by immunomodulating actions and inhibition of the OGF–OGFr signaling axis, which supports its use alongside chemotherapy and immunotherapy.

How might opioid receptor antagonists change outcomes compared with classical opioids?

The text notes that classical opioid drugs may be associated with worse responses and can exacerbate cancer progression. It also highlights cancer-associated overexpression of opioid receptors, motivating the question of whether antagonists such as naltrexone and methylnaltrexone can reverse negative effects in cancer therapy.

Sep 21, 2026

Uploaded by Lucas Martin