Your Guide to Low Dose Naltrexone for Fibromyalgia

In recent years, researchers, clinical experience and case reports, as well as anecdotal experiences from people living with fibromyalgia shared in online forums have discovered that  Low Dose Naltrexone (LDN) in doses ranging from 1 to 4.5mg per day1, can be a helpful treatment for fibromyalgia. While there are a number of medications commonly prescribed for fibromyalgia, they can have unwanted side effects, LDN provides a potential alternative. This guide will outline the benefit of LDN for fibromyalgia, how it works, current research outcomes, side effects, how and where to access it.

Here at MoreGoodDays®, we believe medication is a therapy enabler rather than a pain killer. This is because they are unlikely to be a long term solution but may help with a short term solution - enabling you to better engage in pain management approaches that will reshape your pain system over time.

What is Low Dose Naltrexone?

Naltrexone has a biphasic dose response, which simply means at high doses it does one thing and at a low dose it does the opposite.

To understand this more, strap yourselves in because we need to dive into some biochemistry. Let’s start with a few necessary definitions:

Receptor: Receptors are protein molecules embedded in cell walls that act as locks. For them to work, they need a specific key – such as drugs, hormones or chemical messengers in your nervous system (neurotransmitters). In the case of LDN, we are talking about opioid receptors in the brain who control the production of the body's own opioids.

Medications can be the key to unlocking how receptors work in two ways:

  1. They fit in the lock and activate a biochemical or electrical reaction to happen (Agonists)
  2. They fit in the lock but stop a biochemical or electrical reaction from happening and prevent other molecules from activating it (Antagonists)

At higher doses, naltrexone has been used for decades to help people avoid relapse after detoxifying from drug and alcohol dependencies. Acting as an antagonist it blocks opioid receptors sites, therefore reducing pleasure gained from them and lowers motivation to use them again2.

At lower doses, naltrexone acts as a weak agonist - it takes up the opioid receptor sites but activates the production of more endorphins, therefore increasing our body’s own pain-relief. It also plays a role in immune balancing.

When you are doing your own research, it is important to remember that there are significant differences in the action, effect and use of naltrexone at different dosages - for fibromyalgia (and in the rest of this article), we are only talking about low dose (between 1.5 and 4.5 mg/day).

Does Low Dose Naltrexone work for fibromyalgia?

Let's unpack a bit more how and why LDN works for fibromyalgia.

At a low dose, naltrexone impacts fibromyalgia via two main action pathways:

  1. Analgesic effect. Evidence from animal studies suggests that LDN increases levels of endorphin and enkephalin (the body's natural painkillers) and therefore increases levels of the body’s own painkillers. These chemicals interact with receptors in your brain to help you feel focused, less impacted by pain and improve mood. Yes please!
  1. Anti- inflammatory effect. We know that people living with fibromyalgia can have a sensitised central nervous system (CNS) and immune systems. LDN binds to receptors in the immune system and has an antagonistic effect stopping the production certain molecules that trigger or increase inflammation (you may have heard of these bad guys already - pro-inflammatory cytokines3). Less immune activity - less pain.  
A diagram showing how low dose naltrexone for fibromyalgia works - with two main effects  1. Analgesic (activating the body's natural pain relief) and 2. anti-inflammatory effect (reducing pro-inflammatory cytokines in immune system (more detail in text above)
The two main action pathways for Low Dose Naltrexone for fibromyalgia

It’s important to note that the use of LDN for people living with fibromyalgia is to address pain and inflammation as suggested above and should not be interpreted as a suggestion that they might have a drug dependency regardless of drugs they may have previously taken.

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There have been a number of studies investigating the effect of LDN on fibromyalgia with many showing positive effects on pain, improved sleep and overall well being4,5. Smaller trials and case studies have shown improvements in quality of life and mood measures6 as well as a reduction in inflammatory markers7. One small study indicated that around three quarters of patients with painful conditions (not just fibromyalgia) reported pain relief within a time frame between one and three months8.

While emerging (and ongoing) research has shown LDL to be safe and effective for a reduction in pain symptoms, a systematic review of evidence suggests that future well-designed trials with large sample sizes are required9.

It's worth noting that LDN has shown improvement in symptoms when used to treat a number of other conditions, including common co-occurring conditions10,11,12, with fibromyalgia and conditions associated with immune systems that are out of whack such as:

  • myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
  • long-COVID
  • Crohn's disease
  • multiple sclerosis
  • complex regional pain syndrome (CPRS)
  • arthritis.

In summary, LDN helps by:

  • boosting the body’s natural painkillers = less pain
  • reducing inflammation = less pain.  

How long does it take for Low Dose Naltrexone to work for fibromyalgia?

Like any new medication, it can take a few weeks before you would notice any change in symptoms from taking Low Dose Naltrexone (LDN) for fibromyalgia. If LDN is prescribed you are likely to have a slow dosage increase over initial few weeks (for example, beginning with a 1.5 mg daily for the first week and increasing to 4.5 over 3 weeks if well tolerated13). As a result, any possible benefits from the treatment are likely to not be noticed until the full dosage is reached.

So taking into account the slow increase to full dose and the time it might take for the medication to take effect - it could be up to a few months before any benefits are noticed.

Side effects of Low Dose Naltrexone

While LDN is usually very well tolerated at these low doses, it does come with few side effects. The known side effects of LDN include:

  • dizziness
  • headache
  • difficulty sleeping (insomnia)
  • vivid dreams
  • nausea
  • vomiting
  • decreased appetite
  • joint pain
  • muscle cramps
  • tooth pain
  • anxiety.

All of these short term side effects are predominantly based on the experiences of people using it at higher doses in the addiction management field. So when taken at low doses for fibromyalgia management, these effects are milder. A recent trial showed stomach issues to be the most common side effect but these were mild and tolerable14.

The long term use of LDN has not sufficiently been researched although the drug has been safely used for its primary purpose (in addictions recovery) for many years.

What should I avoid when taking Low Dose Naltrexone?

Even at low doses, naltrexone blocks opioid receptors and so should not be taken with certain medications (including opioids) or alcohol. This also includes people who might be withdrawing from opioids or have symptoms of opioid withdrawal. Waiting a while after reducing opioid based medication ensures that the LDN does not produce unwanted withdrawal symptoms.

So it's crucial to consult with a healthcare professional experienced in LDN therapy before considering it as a treatment option. They can assess your individual circumstances, any other medications you might be taking and determine if LDN is appropriate for you.

Should I take Low Dose Naltrexone in the morning or at night?

People sometimes ask if they should take low dose naltrexone in the morning or at night. This can be individual but often night time is recommended unless it is causing any disruptions to your sleep, then it might be better taken in the morning.

How to get Low Dose Naltrexone & what does it cost?

If LDN is something you might be willing to try, begin by having a frank discussion with your health provider about whether LDN may be appropriate for you. It is important to be clear that LDN is a prescription-only drug, so you will need to obtain a prescription for its use. There are some helpful resources available about important considerations about buying medication online.

Typically, you will pay less than $100 AUD for a single box of 100 capsules at 1.5mg so depending on your dosage, around $2-3/day.

In the US, Naltrexone is only FDA approved for drug and alcohol abuse. LDN is compounded and there is no approval process for compounded medications and is likely to cost around $1-2 USD per day and may or may not be covered by your insurance.

Why won't my doctor prescribe Low Dose Naltrexone for fibromyalgia?

Due to its relatively recent use and emerging research on its efficacy and safety, some doctors may not be aware of the potential benefits of LDN for fibromyalgia. If you want to have a frank and open discussion with your doctor, you may like to bring some information along to your next appointment for you and your doctor to discuss.

Three possible resources to share with your medical team:

  • LDN Research Trust. This is a British website for LDN. While it is not specific to Fibro, the trust works to raise funds for research trials and the website contains heaps of information including resources and interviews of people using LDN for fibromyalgia symptom management.
  • Low-dose naltrexone in the treatment of fibromyalgia.  A recent systematic review and narrative synthesis in the Australian Journal of General Practice
  • Or…why not print and take this blog with you, including the references below!

What else should I consider?

Medication is not a stand alone treatment for fibromyalgia. It is important to work closely with your healthcare team and ensure that you are still attending to those other management options for your fibromyalgia such as  education, lifestyle changes and support.

Our MoreGoodDays® app includes information on how to navigate different medications for fibromyalgia, how to know when it is or isn’t working for you, and how to advocate yourself in health care appointments to get what you need. Let's have a chat!