Low Dose Naltrexone and Anesthesia

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Over the last 5 years, there has been a HUGE trend towards treating chronic pain patients with what’s called low dose Naltrexone. While some patients find this helpful, it presents a challenge for interventionists like myself, as the increased anesthesia requirements for these patients enhance the risk of procedures. So let’s explore what’s happening and possible solutions.

What Is Low Dose Naltrexone?

About 5 years ago, I began to notice that some of the chronic pain patients that I was seeing for specific regenerative medicine procedures were coming in on low-dose Naltrexone. So what is this and what is the theory? Is it a good thing or a bad thing? Let’s dig in.

Naltrexone is an old drug discovered in 1963 and approved by the FDA in 1984 that was primarily used to help treat addiction. The idea is that it binds to opioid receptors but doesn’t give much of an opioid “high” or euphoria. Hence, it was perfect to trick an addict’s body into believing that it had taken an opioid without being addictive like heroin or prescription narcotics.

Low dose Naltrexone refers to a program that is 1/10th the normal dose (1). At the low dosage level, Naltrexone has unusual properties, including pain relief and anti-inflammatory actions, which are not reported at larger dosages. Because of this, this drug has become a popular treatment used by patients diagnosed with fibromyalgia, ME-CFS, CRPS, and other chronic pain conditions.

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The Problem for Patients, Interventionalists, and Surgeons

A patient from this week gives a sober reminder on how Naltrexone can up anesthesia requirements to dangerous levels. Why? How should we deal with this issue?

First, for perspective, let’s review normal IV anesthesia requirements. For example, this week a patient who was a 170-pound man required 5mg of IV Versed (Valium-like drug) and 100 mcg of Fentanyl (Narcotic) and was unconscious for 30 minutes during the procedure. Then we have my 120-pound female, low-dose Naltrexone patient who was also a THC user. She required 15mg of  Versed and 400 mg of fentanyl and was awake and still speaking to us. Ultimately we had to call in anesthesiology who added Ketamine and Propafol, but that only induced relaxation so we could complete the procedure, not loss of consciousness.

The practical problem of these dose requirements is that they dramatically increase the risk of anesthesia for the patient. To put this is perspective for my non-physician readers if we took 100 patients off the street and gave them the same dose as my female patient without medical monitoring and oxygen/reversal support, about 90-95% would perish due to an inability to breathe. That includes burly 250-pound men. On that same dose, my 120-pound teenager was only slightly sedated!

What’s Happening?

Opioids work by stimulating the Mu narcotic receptor. Naltrexone occupies that same receptor. This is how narcotics exert their effects, by binding to a receptor just like a key to a specific lock. So in my patient, there were fewer open receptors that the Fentanyl could bind to, so despite the crazy high dose, not much of the Fentanyl could do its job. Hence, since the combination of the Versed and the Fentanyl acting together is usually what makes the person fall asleep, she remained awake. In addition, marijuana use also increases anesthesia requirements. So this likely made both the Versed and Fentanyl less effective.

What Are the Recommendations?

This is a tough one, as while stopping a drug like Naltrexone a few days before a procedure will reduce the receptor blocking described above, it won’t reduce receptor upregulation. What’s that? When your body is faced with having a cell receptor flooded, it builds more receptors. So the patient may actually be MORE sensitive to narcotics if the receptors are open since there are more of them. Hence, it’s always going to be a delicate dance with a low-dose Naltrexone patient receiving anesthesia.

The Low Dose Naltrexone Research Trust recommends stopping this drug 2 days before the procedure and then restarting 2 days after the patient has completed taking any oral narcotics prescribed due to the procedure (2). Another case report and review of the literature just states that anesthesia will be harder to administer, citing the same concerns as mine above but gives no concrete recommendations (3). Yet another case report and review discusses that even if Naltrexone is stopped 72 hours before the procedure, there will still likely be higher levels of narcotics required (4). Hence, while the recommendations to stop Naltrexone 2 days before the procedure and then restart after oral narcotics are no longer needed are likely good advice, there still may be much more (or even much less) IV narcotic required during the procedure.

Is This Drug Good or Bad?

My personal opinion is that anytime we can get someone relief with a low dose of an addictive drug, that’s great. However, realize that the drug is still addictive to some degree and that it’s always better to figure out what’s causing the pain and to treat that issue directly. As an example, for the female patient above, she has pain coming from the upper neck, so treating that specific area is always better than starting low-dose Naltrexone.

The upshot? Low-dose Naltrexone will be a challenge when getting patients to sleep during a procedure that requires anesthesia. Given the explosion in use, I wanted to perform a review for patients and physicians on how anesthesia in these patients should be handled. While stopping it before the procedure may help, it’s not a perfect solution to the problem this medication presents. Hence all patients on this drug should realize that it may increase the risks of anesthesia.



(1) Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. 2014;33(4):451-459. doi:10.1007/s10067-014-2517-2

(2) LDN Research Trust. LDN Information Before and After Surgery. https://ldnresearchtrust.org/ldn-information-and-after-surgery Accessed 7/22/21

(3) A&A Case Reports: 1 December 2014 – Volume 3 – Issue 11 – p 142–144 (https://anesthesiaexperts.com/uncategorized/challenges-perioperative-management-patient-receiving-extended-release-naltrexone/ Accessed 7/22/21)

(4) AHRQ. Patient Safety Network. A Painful Medication Reconciliation Mishap. https://psnet.ahrq.gov/web-mm/painful-medication-reconciliation-mishap Accessed 7/22/21

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