Ask CLYR: In LDN trials, side effects were usually mild. Vivid dreams, sleep changes and nausea were reported most often, and serious side effects were not more common than with placebo. LDN is not appropriate with liver disease, a naltrexone allergy, or certain medicines, so a provider screens you first.
Low-dose naltrexone (LDN) is a compounded capsule, not FDA-approved at this dose, and prescribed off-label. Because it is used off-label, the best information on side effects comes from the clinical trials that tested it, mostly in fibromyalgia, plus larger reviews of oral naltrexone. This article sets out what those studies recorded, how it compared with placebo, and the cautions that matter before anyone takes it. For an overview of LDN itself, see what low-dose naltrexone is.
The short answer
In trials, LDN side effects were usually mild and often temporary. Vivid dreams, sleep changes and nausea came up most often. Serious side effects were not more common than with placebo. That does not mean LDN has no side effects: one meta-analysis found adverse events were somewhat more frequent with LDN than with placebo overall. And some people should not take naltrexone at any dose.
What trials recorded
Vivid dreams and sleep changes
The earliest fibromyalgia pilot, by Younger and Mackey (2009), reported that side effects including insomnia and vivid dreams were rare, minor and transient. A 2024 meta-analysis by Vatvani and colleagues pooled four randomized trials with 222 people with fibromyalgia and found more vivid dreams and nausea with LDN than with placebo, with no difference in headache, diarrhea or dizziness.
How often, compared with placebo
Placebo comparisons matter, because people in trials report symptoms whether or not they take the active medicine.
| Study | Design | What it found |
|---|---|---|
| Rodríguez-Freire et al., 2026 | 12-month randomized trial, 4.5 mg | Adverse events in 68.8% on LDN vs 72% on placebo, mostly mild and transient; no treatment-related serious events |
| Due Bruun et al., 2024 | Randomized trial, 99 people, 6 mg | Stopped for adverse events: 4 of 49 (8%) on naltrexone vs 3 of 50 (6%) on placebo |
| Hegde et al., 2025 | Meta-analysis of chronic pain trials | Adverse events more frequent with LDN than placebo (incidence rate ratio 1.4) |
| Vatvani et al., 2024 | Meta-analysis, 4 trials, 222 people | More vivid dreams and nausea with LDN; serious adverse events no different |
Put together, most side effects were mild, and the overall rate was close to placebo in the longest trial, but at least one pooled analysis found more adverse events with LDN. A fair summary is "generally well tolerated", not "no side effects".
Serious adverse events
Serious adverse events were not more common with LDN than placebo in the fibromyalgia meta-analysis (Vatvani, 2024). More broadly, a 2019 meta-analysis by Bolton and colleagues of 89 placebo-controlled trials of oral naltrexone across many uses, with 11,194 participants, found no increase in serious adverse events. Those trials looked at oral naltrexone in general, not LDN specifically; the difference between the two is covered in LDN vs the standard 50 mg tablet.
Who should not take LDN
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.
Pregnancy and breastfeeding
LDN has not been studied enough in pregnancy or breastfeeding. Tell your provider if you are pregnant, breastfeeding or planning a pregnancy, so they can weigh that in their decision.
When to contact a provider
- Yellowing of the skin or eyes, or dark urine
- Severe or lasting stomach pain
- Signs of an allergic reaction, such as rash, swelling or trouble breathing
- Sleep changes or dreams that bother you
- Anything else that worries you
In an emergency, call 911.
How CLYR screens
At CLYR, the intake checks your medicines and health conditions before a licensed provider reviews anything. The provider then decides whether LDN is appropriate for you. If it is prescribed, a licensed compounding pharmacy prepares 4.5 mg capsules. 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. You can read more and start a screening on the LDN page.
Frequently asked questions
What are the most common LDN side effects?
Studies most often reported vivid dreams, sleep changes and nausea. They were usually mild and often eased with time.
Is LDN safe?
In trials, serious side effects were not more common than with placebo. It is still a prescription medicine, and some health conditions and medicines rule it out.
Who should not take LDN?
People with liver disease, hepatitis or abnormal liver tests, a known allergy to naltrexone, or who take medicines that cannot be combined with it. The full list is in the Important Safety Information.
What if LDN affects my sleep?
Tell your provider. They may change the timing, and they decide whether LDN is still appropriate for you. Timing is covered in LDN dosing: why 4.5 mg.
Does LDN interact with other medicines?
Yes, some medicines cannot be combined with naltrexone. Tell your provider about everything you take, including supplements.