Does Low-Dose Oral Naltrexone Alleviate Symptoms of Long COVID? A Systematic Review and Meta-Analysis

Long COVID, a condition marked by persistent symptoms following COVID-19 infection, poses significant challenges in regard to clinical management. While emerging pharmacological treatments have demonstrated limited benefits in isolated studies, clinical experience and the literature suggest that low-dose naltrexone (LDN) may be a promising therapeutic option. Therefore, in this systematic review, we aim to synthesise findings from the available literature and evaluate the overall safety and efficacy of LDN as a potential treatment for long COVID. A literature search was conducted using a combination of key terms—‘COVID’, ‘COVID-19’, ‘SARS-COV-2’, and ‘Naltrexone’— and the following databases: MEDLINE, Web of Science (Clavirate), Embase, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Cumulative Index in Nursing and Allied Health Literature (CINAHL). The methodology is available on the PROSPERO database (CRD42025630362). Screening identified five eligible articles. Four studies were included, but only two provided comparable data suitable for meta-analysis. Meta-analysis demonstrated statistically significant improvements in fatigue, brain fog, and headaches. Preliminary evidence suggests LDN has potential benefits in the treatment of long COVID, particularly with respect to fatigue, brain fog, and headaches, but more robust studies, such as randomised controlled trials, are urgently needed to confirm LDN’s safety and efficacy.