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.
PMID 38539570 38539570 DOI 10.3390/cancers16061240 10.3390/cancers16061240 Ciwun et al. 2024, Ciwun 2024
Cite this article
Ciwun, M., Tankiewicz-Kwedlo, A., & Pawlak, D. (2024). Low-Dose Naltrexone as an Adjuvant in Combined Anticancer Therapy. Cancers, 16(6), 1240. https://doi.org/10.3390/cancers16061240
Ciwun M, Tankiewicz-Kwedlo A, Pawlak D. Low-Dose Naltrexone as an Adjuvant in Combined Anticancer Therapy. Cancers (Basel). 2024;16(6):1240. doi:10.3390/cancers16061240
Ciwun, Marianna, et al. "Low-Dose Naltrexone as an Adjuvant in Combined Anticancer Therapy." Cancers, vol. 16, no. 6, 2024, pp. 1240.
[OBJECTIVE] The role of intrauterine PRP infusion in managing recurrent implantation failure (RIF) remains controversial despite its emerging clinical use. This systematic review aims to evaluate its therapeutic potential in RIF patients and further to investigate variations in outcomes based on transfer cycle type, embryo developmental stage, RIF diagnostic criteria, and endometrial thickness. [METHODS] We systematically searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for randomized controlled trials (RCTs) investigating PRP treatment for RIF patients from the beginning of the database to May 2025. [RESULTS] This meta-analysis showed that PRP administration significantly improved clinical pregnancy rate (CPR) [OR = 3.18, 95%CI (2.45, 4.14), I2 = 3%], biochemical pregnancy rate (BPR) [OR = 2.84, 95%CI (2.22, 3.63), I2 = 0%], ongoing pregnancy rate (OPR) [OR = 3.41, 95%CI (2.08, 5.60), I2 = 30%] and live birth rate (LBR) [OR=5.10, 95%CI (1.95, 13.37), I2 = 75%] in women with RIF. However, PRP intrauterine infusion did not reduce miscarriage rate (MR). Notably, the preterm birth rate was significantly higher in the PRP group compared to controls [OR = 8.24, 95%CI (2.09, 32.41), I2 = 0%]. Subgroup analysis demonstrated that PRP improved CPR, BPR and LBR in both the fresh and frozen embryo transfer cycles. Additionally, while PRP increased CPR, LBR and reduced MR in blastocyst transfers [CPR OR = 3.84, 95%CI (2.82, 5.23), I2 = 0%; LBR OR = 7.32, 95%CI (3.17, 16.90), I2 = 63%; MR OR = 0.27, 95%CI (0.07, 0.96), I2 = 54%], these effects were not observed in cleavage-stage embryo transfers. Moreover, PRP administration associated with a higher CPR [OR = 3.84, 95%CI (2.82, 5.23), I2 = 0%], OPR[OR = 4.13, 95%CI (1.79, 9.56), I2 = 48%], LBR [OR = 7.32, 95%CI (3.17, 16.90), I2 = 63%] and a lower MR [OR = 0.27, 95%CI (0.07, 0.96), I2 = 54%] in women with ≥3 prior implantation failure, it did not confer the same benefit to those with a history of ≥2 failed cycles. [CONCLUSION] These findings suggest a possible beneficial role for PRP on pregnancy outcomes to some extent in women with RIF, particularly in cases with ≥3 prior failed transfers, and blastocyst transfer may increase LBR and reduce miscarriage risk. However, further investigation is warranted to determine whether this treatment may pose an increased risk of preterm birth. [SYSTEMATIC REVIEW REGISTRATION] https://www.crd.york.ac.uk/prospero/, identifier CRD420251061511.
therapeutics/prescribing-safety/off-label-prescribingpcos/treatment/ovulation-inductionreproductive-endocrinology/ovarian-hormones/estrogen
Open Access
Zhang D et al., 2026·International journal of women's health
Tamoxifen, clomiphene, and letrozole are primary pharmacological options for inducing ovulation in polycystic ovary syndrome (PCOS). Given the high clinical prevalence of PCOS, a comprehensive characterization of the adverse drug event (ADE) profiles associated with these treatments is essential. We performed disproportionality analyses using FAERS data to detect ADE signals at the Preferred Term (PT) and System Organ Class (SOC) levels via four established algorithms (ROR, PRR, BCPNN, and EBGM). A drug-ADE network was constructed to visualize these associations. Of 21,730 identified PCOS-related reports, letrozole predominated (n=17,185), followed by tamoxifen (n=4465) and clomiphene (n=80). Most cases involved women aged 18-65 years (weight: 50-100 kg), primarily from the United States. Letrozole-related reports increased steadily, peaking at 2323 cases in 2021, while tamoxifen and clomiphene counts remained comparatively low. At the PT level, fatigue was a common signal for both tamoxifen and letrozole. Notably, malignant tumor progression, fatigue, and arthralgia emerged as shared signals across all three agents. At the SOC level, ADEs for tamoxifen and letrozole were frequently categorized under neoplasms; letrozole was specifically linked to hematological disorders (e.g, neutropenia). In contrast, clomiphene exhibited stronger associations with psychiatric and gastrointestinal events. Distinct safety signals characterize these three primary PCOS treatments. These pharmacological variations underscore the necessity of personalized medicine; treatment selection must be tailored to the patient's specific risk profile, with targeted clinical monitoring for relevant ADEs to optimize therapeutic outcomes.
therapeutics/prescribing-safety/off-label-prescribing
Open Access
Despite the availability of a wide variety of analgesics, many patients with chronic pain often experience suboptimal pain relief in part related to the absence of any medication to address the nociplastic component of common pain syndromes. Low-dose naltrexone has been used for the treatment of chronic pain, typically at 4.5 mg per day, even though it is also noted that effective doses of naltrexone for chronic pain presentations range from 0.1 to 4.5 mg per day. We performed an observational analysis to determine the range of effective naltrexone daily dosing in 41 patients with chronic musculoskeletal pain. Charts of 385 patients, 115 males, 270 females, ages 18-92, were reviewed. Two hundred and sixty patients with chronic diffuse, symmetrical pain were prescribed a titrating dose of naltrexone to determine a maximally effective dose established by self-report of 1) reduction of diffuse/generalized and/or severity level of pain and/or 2) positive effects on mood, energy, and mental clarity. Brief Pain Inventory and PROMIS scales were given pre- and post-determining a maximally effective naltrexone dose. Forty-one patients met all criteria for inclusion, successfully attained a maximally effective dose, and completed a pre- and post-outcome questionnaire. Hormesis was demonstrated during the determination of the maximally effective dosing, which varied over a wide range, with statistically significant improvement in BPI. The maximally effective dose of low-dose naltrexone for the treatment of chronic pain is idiosyncratic, suggesting the need for 1) dosage titration to establish a maximally effective dose and 2) the possibility of re-introduction of low-dose naltrexone to patients who had failed initial trials on a fixed dose of naltrexone.
Naltrexone is a mu-opioid receptor antagonist with a long half-life compared with naloxone. Both of these drugs, along with others, were developed with the intention of reversing the effects of opioid abuse or toxicity. Evidence has also shown that naltrexone has a benefit in preventing relapse by reducing opioid cravings and reducing symptoms of opioid withdrawal. The benefits of this drug were not only shown with opioid abuse. In 1984 this drug was also approved for alcohol abuse. Naltrexone has been proven to decrease alcohol relapse by decreasing the craving. Apart from these approved indications for the use of naltrexone, with time, it has been seen that this drug has a benefit in treating chronic pain. A number of studies have shown the benefits of this drug with inflammatory bowel disease, fibromyalgia, multiple sclerosis, diabetic neuropathy, and complex regional pain syndrome, among others. More studies are needed to approve this medication for specific chronic pain conditions.