What to Avoid When Taking Low-Dose Naltrexone (LDN)

LDN warnings graded by evidence

Three grades. Avoid or plan ahead: a known mechanism plus a label warning or published cases. Ask first: indirect evidence, or a 50 mg warning never tested at low doses. No evidence of a problem: a common warning, but no published study shows a problem with LDN (searches under how we checked).

No evidence of a problem is not proof of safety. LDN trials have been small, and many combinations have never been tested.³ Bring your full medicine and supplement list to the prescriber.

Opioids are the one interaction with a clear mechanism

Naltrexone blocks opioid receptors. At 50 mg, its label rules it out for people taking opioid pain medicines, people who depend on opioids (including methadone or buprenorphine) and people in opioid withdrawal. Before starting, people need an opioid-free period, "including tramadol."⁴

For low doses the evidence is thinner. Researchers who ran early LDN trials thought even a low dose might block enough receptors to make opioid painkillers less effective. They excluded everyone taking opioids, and as of 2014 knew of no study testing the two together.³

An LDN case report points the other way. A man taking LDN for multiple sclerosis was given a single 5 mg dose of oxycodone and became unresponsive to painful stimuli. He needed naloxone and a night in intensive care. The authors propose that LDN may make some people more sensitive to opioids; drug-interaction software flags the pair only as a withdrawal risk.⁵ A single case shows the combination can be unpredictable but cannot show how often it happens.

If you need an opioid for an injury or a dental procedure, tell whoever prescribes it that you take naltrexone. After full-dose naltrexone wears off, a previously tolerated opioid dose can cause an overdose (overdose warning).⁴ Whether the same happens after stopping LDN is not known.⁶

Opioids also turn up in cough, diarrhea and kratom products

Cough and cold medicines. The 50 mg label warns that opioid-containing cough and cold preparations, antidiarrheal preparations and painkillers may not help people on naltrexone.⁴ Codeine is one such opioid; check the ingredients or ask a pharmacist.⁷

Loperamide (Imodium). The prescribing label for Imodium capsules calls loperamide "a mu-opioid agonist" and says it "binds to the opiate receptor in the gut wall."¹¹ Opioid antidiarrheals are on the same list of medicines that may not help.⁴ Whether that holds at low doses is untested; PubMed lists no study of loperamide with LDN. If it seems not to work, ask before taking more: higher-than-recommended doses can cause serious heart rhythm problems.¹¹

Kratom. The FDA says kratom is not lawfully marketed in the US as a drug or a dietary supplement. Its main compounds, mitragynine and 7-hydroxymitragynine (7-OH), bind to the same brain receptors as opioid drugs.⁷ Case reports describe sudden withdrawal after naltrexone in regular kratom users. In one, a man with daily, high-dose kratom use took his first 50 mg tablet, prescribed off-label for weight loss, and within 30 minutes was restless and sweating with a fast heartbeat.⁸ Another followed an intramuscular naltrexone injection.⁹ Both involved full-dose naltrexone; PubMed lists no case on LDN. If you use kratom, tell the prescriber before starting LDN.

Surgery and procedures: agree on a stop date with the team

There is little data on how LDN affects pain relief and anesthesia. In a 2023 review, two Australian anaesthetists report that, in their experience, people who keep taking 1 to 6 mg a day through surgery need much more opioid. On that basis they suggest withholding LDN for 24 to 72 hours beforehand; their hospital uses 72 hours for every form of naltrexone. General patient advice ranges from 24 hours to 7 days, and no guidance exists on when to restart.⁶

Before a planned procedure:

1. Tell the surgeon, anesthesiologist or dentist that you take low-dose naltrexone, and the dose.
2. Ask whether to hold it and for how long. Staying on LDN and using higher opioid doses may be possible, as an individual risk-benefit decision.⁶
3. Agree on the stop and restart dates with them and with the doctor who prescribes your LDN. Don't stop on your own.

Timing for the 50 mg tablet and Vivitrol is on stopping naltrexone before surgery.

Alcohol: no known interaction, and LDN is not an alcohol treatment

No published study has tested alcohol with LDN. At full dose, the 50 mg label says naltrexone does not cause a disulfiram-like reaction with alcohol, the flushing and sickness that disulfiram (Antabuse) causes.⁴ Your prescriber may still advise limits because of your condition or your other medicines.

LDN is not a treatment for alcohol or opioid use disorder; the approved alcohol dose is 50 mg a day.⁴ One small trial gave LDN to 45 people with HIV and chronic pain in St. Petersburg, Russia, 15 per group, who had drunk heavily in the past year; at the start they averaged about 2 heavy drinking days a month. LDN did not reduce heavy drinking days compared with placebo, a secondary outcome.¹³ See LDN has no evidence for alcohol use disorder and naltrexone for alcohol use disorder.

Don't take LDN with other naltrexone products

Contrave pairs 8 mg of naltrexone with bupropion in each tablet, and its label says combining it with other naltrexone-containing products is not recommended.¹⁰ The 50 mg tablet and the Vivitrol shot are full-dose naltrexone, so an LDN prescription on top adds more of the same drug. If two doctors prescribe naltrexone in different forms, make sure each knows about the other. Dose differences are on naltrexone dosage.

Five common warnings with no published evidence of a problem

Benzodiazepines. The 50 mg label lists no interaction with benzodiazepines, and its suggested emergency pain plan for people on full-dose naltrexone includes "conscious sedation with a benzodiazepine."⁴ No LDN study has found a problem.

Dextromethorphan. The FDA label for Auvelity, a prescription tablet that contains this cough suppressant, describes dextromethorphan as an NMDA receptor antagonist and sigma-1 receptor agonist, and does not describe it as an opioid.¹⁴ No published study has tested it with LDN. Check combination cold products for other ingredients.

Immunosuppressants and transplant drugs. LDN is sometimes said to work against them; no published study in people has tested the combination. If you take these drugs, tell your transplant or specialist team about LDN anyway.

Thyroid medicine. In a Norwegian prescription-database study of 898 people with hypothyroidism, followed for a year before and after their first LDN prescription, starting LDN was not linked to any change in thyroid hormone dispensing; "if anything," use of levothyroxine tended to rise with more LDN use.¹⁵ The study counted prescriptions filled, not thyroid blood tests.

Herbal supplements. We found no evidence of a problem with St John's wort, ginkgo or echinacea. A PubMed search on October 17, 2026 (St John's wort, hypericum, ginkgo, echinacea or herbal) found only an unrelated case report. Kratom is the exception, because it acts on opioid receptors (see above).

Pregnancy, liver and kidney disease are untested at low doses

At 50 mg, naltrexone carries a liver warning, and patients are asked to tell their doctor if they are pregnant, plan to be or are breastfeeding.⁴ A 2026 review found no evidence on whether the 50 mg concerns about pregnancy and liver or kidney disease apply at low doses.² The liver warning, and the one registry case at 4.5 mg, are covered on naltrexone and your liver.

Tell the lab you take naltrexone before a drug test

Naltrexone may or may not interfere with enzyme-based urine tests for opioids, depending on the test. Chromatography methods are not affected.⁴ Mention LDN before any drug screen. See will naltrexone show up on a drug test?

Stopping or changing your dose. Talk to your prescriber first. What early LDN studies saw after people stopped is on stopping LDN.

Your experience: If you take LDN, you can share your story on our naltrexone reviews page. LDN stories will be labeled off-label.

How we checked

• Labels read on October 17, 2026: the 50 mg naltrexone tablet, Contrave, Imodium (Janssen, 2016), Auvelity and ProvayBlue, plus the FDA's kratom page.
• PubMed searches the same day paired "low dose naltrexone" with each item in the table; apart from Raknes 2020 and the Leonard case report, none found a study of a combination.
• Read in full: Whately and Stead, Raknes and Jarka. Abstracts only: Leonard 2017 and Jensen 2021.