Ask CLYR: No randomized trial of LDN for long COVID had reported results in the sources we reviewed. Small uncontrolled studies reported improvements in fatigue and pain, but a 2026 review rated that evidence as low certainty. LDN is prescribed off-label for this use, and a provider decides if it is appropriate.
Long COVID has few proven options, so it is not surprising that low-dose naltrexone (LDN) gets attention. LDN is a compounded capsule, not FDA-approved at this dose, and any use for long COVID is off-label. The research so far is early: small studies without placebo groups, and one 2026 review that rated the certainty of the evidence as low. This article explains what was studied and what those studies can and cannot tell us. For background, see what low-dose naltrexone is.
The short answer
As of October 2026, we found no published randomized trial results for LDN in long COVID. Small uncontrolled studies reported improvements, and a 2026 systematic review by Byambasuren and colleagues rated the certainty of that evidence as low. Whether LDN helps long COVID is not known.
What has been studied
| Study | Design | What it found |
|---|---|---|
| O'Kelly et al., 2022 | Pre-post study, 52 people (36 completed follow-up), 1 mg then 2 mg | Self-reported improvement on 6 of 7 measures; 2 stopped because of diarrhea |
| Bonilla et al., 2023 | Retrospective review, 59 people, one center | Associated with fewer symptoms and better function |
| Tamariz et al., 2024 | Retrospective cohort, 108 people | Higher chance of improvement vs physical therapy alone (hazard ratio 5.04, wide range 1.22 to 20.77) |
| Isman et al., 2024 | Open-label, LDN plus NAD+ | Authors described it as safe and possibly beneficial for a subset; the authors were employees of the telehealth company that sponsored the work |
| Byambasuren et al., 2026 | Systematic review and meta-analysis | No randomized trials found; 4 pre-post studies, 155 people; improvements in fatigue, pain, sleep and function; certainty low |
The wide range in the Tamariz study means the true effect could be anywhere from small to large, which is typical of a small retrospective study.
Why pre-post studies cannot prove a benefit
A pre-post study measures symptoms before and after a treatment, with no comparison group. That design cannot separate the effect of the medicine from other explanations:
- Placebo effect. People often feel better when they start something new and expect it to help.
- Improvement over time. Many long COVID symptoms change on their own over months.
- No comparison group. Without a group taking placebo, there is nothing to measure the change against.
- Self-report. Symptom scores reported by participants who know what they are taking are easily influenced.
Fibromyalgia shows why this matters: early small LDN studies looked positive, and larger placebo-controlled trials did not. See LDN and fibromyalgia: what the trials found.
Trials in progress
A randomized, placebo-controlled trial protocol from British Columbia was published in 2024 (Naik and colleagues). We did not find published results as of October 2026. This article will be updated when randomized results appear.
Talking to a provider
If you are considering LDN, a provider can talk through this low-certainty evidence, check your medicines and health history, and help you decide what to track, such as fatigue, sleep and daily activity. There is no promise of improvement. Doses in these studies ranged from 1 to 6 mg; how CLYR's 4.5 mg compares is covered in LDN dosing: why 4.5 mg, and side effects in LDN side effects.
If you and your provider decide to try it
At CLYR, a licensed provider reviews your screening and decides whether LDN is appropriate for you. At CLYR, low-dose naltrexone 4.5 mg is $119 for 30 capsules or $169 for 90 capsules. Each order is billed once and nothing renews. Provider review and shipping are included, and your provider sets the days of supply. See the LDN page.
Frequently asked questions
Does LDN work for long COVID?
It is not known yet. Small studies without a placebo group reported improvements, but a 2026 review rated the certainty of that evidence as low, and randomized trials are still needed.
Is LDN approved for long COVID?
No. LDN is compounded and not FDA-approved. Any use for long COVID is off-label and decided by a licensed provider.
What dose was used in long COVID studies?
Doses ranged from 1 to 6 mg a day across the studies in the 2026 review. Your provider sets your dose.
Are there randomized trials underway?
Yes, at least one randomized trial protocol has been published. Check back, as this article will be updated when results appear.
Important safety information
Compounded low-dose naltrexone is a prescription capsule dispensed only after a licensed provider independently reviews your intake and determines it is appropriate for you. Do not take naltrexone if you take any opioid medicine or have taken one in the last 14 days, including tramadol, codeine, methadone or buprenorphine, because naltrexone blocks them and can cause sudden withdrawal; do not take it if you currently take or need opioid medicines, have liver disease, hepatitis or abnormal liver tests, or are allergic to naltrexone. Tell your provider about kidney disease, pregnancy, breastfeeding or plans for pregnancy, and about every medication and supplement you take. Side effects may include vivid dreams, trouble sleeping, headache, nausea, dizziness or anxiety. Carry a note that you take naltrexone, because opioid pain medicines may not work normally while it is in your system. Compounded medications are made by a licensed U.S. 503A pharmacy to a provider's prescription; they are not FDA-approved and have not been reviewed by the FDA for safety or effectiveness. Individual results vary. Not everyone qualifies. This page is informational and is not medical advice. Call 911 in an emergency.
The same text appears in the Important Safety Information on the LDN page.