Study Finds Low-Dose Naltrexone Works No Better than Placebo

By Pat Anson, PNN Editor

In recent years, low-dose naltrexone (LDN) has grown in popularity as a treatment for fibromyalgia and other chronic pain conditions. Although naltrexone is only FDA-approved for the treatment of substance use disorders, a growing number of patients and providers say low doses of naltrexone prescribed off-label can be effective in relieving pain.

A new study by Danish researchers is casting doubt on the some of those claims, finding that LDN works no better than a placebo in reducing pain for women with fibromyalgia. In their double-blind, placebo-controlled study, 99 adult women with fibromyalgia were randomly assigned to receive either an LDN pill or an identical-looking placebo daily for 12 weeks.

The study findings, recently published The Lancet Rheumatology, found a minor improvement in pain intensity for the LDN group, with a similar pain reduction in the placebo group. There were no serious adverse events in either group.

“This study did not show that treatment with low-dose naltrexone was superior to placebo in relieving pain. Our results indicate that low-dose naltrexone might improve memory problems associated with fibromyalgia, and we suggest that future trials investigate this further,” wrote lead author Karin Due Bruun, MD, a researcher in the Pain Center at Odense University Hospital in Denmark.

The Danish study is notable, because placebo-controlled, double-blind studies are considered the gold standard in medical research. Until now, much of the evidence about LDN has been anecdotal or low quality.

In a 2020 review of nearly 800 LDN studies, another research team could find only eight that were high quality enough to meet their criteria for evaluation. Nevertheless, they found that LDN “provides an alternative in medical management of chronic pain disorders.”

A 2019 review by British researchers also found that LDN is safe to use, but recommended that more clinical studies be conducted.

How naltrexone works is not exactly clear. LDN supporters believe the drug modulates the immune system, reduces inflammation and stimulates the production of endorphins, the body's natural painkiller.

In 50mg doses, naltrexone blocks opioid receptors in the brain and decreases the desire to take opiates or alcohol. But in smaller doses of 5mg or less, patients have found LDN to be an effective pain reliever. PNN columnists have shared their positive experiences using LDN to treat everything from interstitial cystitis to Ehlers-Danlos syndrome to fibromyalgia.  

A woman with fibromyalgia tried all sorts of FDA-approved medications to relieve her leg pain, brain fog and depression. None worked, until she tried LDN.   

“After about seven days, my pain lessened,” said Janice Hollander. “[LDN] has completely changed my life. I don’t know that I would be here today if it wasn’t for it. I don’t think I could go for another year in the misery I was in.” 

Naltrexone does cause minor side effects, such as nausea and dizziness, and because it is an opioid antagonist it should not be taken with opioid medication.

Patients interested in trying LDN often encounter doctors who won’t prescribe it off-label. The LDN Research Trust includes a list of LDN-friendly doctors and pharmacies on its website.

Low Dose Naltrexone Emerging as Treatment for Intractable Pain

By Forest Tennant, PNN Columnist

A major advance in pain management is the discovery of low-dose naltrexone (LDN), a non-opioid medication used to treat substance abuse. When prescribed off-label, LDN not only relieves pain, but has anti-inflammatory and immune boosting properties on brain and spinal cord tissues. It is now the preferred, first drug of choice for people living with constant, intractable pain.

Only those persons who are not currently on daily opioids should take LDN. A major purpose of LDN is to prevent the necessity of daily opioids, including buprenorphine/Suboxone.

A starting dosage of LDN is usually 0.5 – 1.0 milligrams taken twice a day. The average maintenance dose is about 3 – 5mg given twice a day. The maximum dose is about 7mg taken twice a day.

LDN should ideally be a part of a multi-drug program. A nerve conduction blocker (neuropathic) agent such as gabapentin or diazepam will almost always boost pain relief. A dopamine surrogate such as Adderall, Ritalin or mucuna, is also very helpful.  Routinely recommended are standard anti-inflammatory (e.g., Ketorolac) and tissue healing anabolic agents (e.g., DHEA).

A pain flare medication should also be handy and ready. Some patients taking LDN can occasionally take a low dose of tramadol, codeine or hydrocodone for pain flares. Other flare medications include ketamine, CBD, medical marijuana, ibuprofen (800mg), oxytocin, kratom and ketorolac.

Caution and Warning

Persons who currently take daily opioids must withdraw from opioids before starting LDN. In our studies, patients sometimes became deathly ill if they took LDN while still on opioids. Severe withdrawal may set in, pain relief will diminish and, at worst, a cardiac-adrenal crisis may be precipitated.

If one has Intractable Pain Syndrome and is currently on a regimen including opioids that satisfactorily reduces pain, there is no medical reason to switch to LDN.

Forest Tennant is retired from clinical practice but continues his research on intractable pain and arachnoiditis. This column is adapted from newsletters recently issued by the IPS Research and Education Project of the Tennant Foundation. Readers interested in subscribing to the newsletter can sign up by clicking here.

The Tennant Foundation has given financial support to Pain News Network and sponsors PNN’s Patient Resources section.  

How Low Dose Naltrexone Relieved My Chronic Pain

By Marelle Reid, Guest Columnist

For the past eight years I've been dealing with Interstitial Cystitis (IC), a chronic pain condition that feels like a bladder infection that never ends. No one really knows what causes IC and there is no cure.

I've tried everything from surgery and homeopathy to narcotics and antidepressants, but nothing seemed to work until I discovered Low Dose Naltrexone (LDN). A hormone specialist suggested I use LDN as a way to combat the nerve pain that had plagued me for years. I figured I might as well try it since the only side effects from LDN are trouble sleeping and vivid dreams.

MARELLE REID

After a couple of weeks I found the strange dreams stopped, and a few months later I realized I was able to eat foods I normally would avoid because they made my IC pain worse. In fact, I was able to resume a completely normal diet, including foods and drinks that would have previously sent me into terrible flare.

For the past year I've been taking 4.5mg naltrexone at night just before bed. Although it has not cured me, I've been thrilled to find that it has reduced my pain to the point where I no longer feel held back from doing anything I would have done before I was diagnosed with IC. 

Naltrexone is the same drug used to treat alcoholism and opioid addiction. In larger doses (50mg) it blocks opioid receptors in the brain and decreases the desire to take opiates or alcohol.  It's believed that taking naltrexone in smaller doses stimulates the immune system and the production of endorphins, the body's natural painkiller.

LDN is prescribed "off label" for many conditions, but it isn't well known as a treatment for chronic pain because it's not marketed by any drug company for that purpose. The patent on naltrexone expired years ago and there's little money to be made from it or to conduct clinical trials.

However, a review of anecdotal information online and in social media suggests many people suffering from Crohn's disease, multiple sclerosis, fibromyalgia and other chronic illnesses believe they have benefited from taking LDN. (See "Naltrexone Changed Life of Fibromyalgia Patient").

I hope others can find the same relief that I have. 

Marelle Reid lives in Vancouver, British Columbia.

Pain News Network invites other readers to share their stories with us. Send them to editor@painnewsnetwork.org.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.