Have you heard of Low Dose Naltrexone, or LDN? Since the beginning of my Hashimoto’s journey, this medication hasbeen on my radar, and in recent years, I have learned so much more about it.
In 2015, I conducted a survey of over 2000 readers with Hashimoto’s, asking for the most helpful interventions in their health journeys.
One reader wrote: “Low Dose Naltrexone changed my life for the better. If I had not added that to my regimen, I would still be suffering from nerve pain and uncontrollable allergy symptoms, in addition to the problems I have from Hashimoto’s.”
While only 38 percent of those that tried Low Dose Naltrexone reported feeling better, those who did see benefits, had some spectacular results. Forty-eight percent were able to reduce their thyroid antibodies, 61 percent saw an improvement in mood, 66 percent had more energy, and 40 percent saw a reduction in pain.
I have personally seen this medication change people’s lives and wanted to share some more information on it, in case you have hit a plateau in your healing journey.
In this article, you will learn:
- What Low Dose naltrexone, or LDN is
- How LDN benefits Hashimoto’s
- Potential side effects
- The Root Cause Approach vs. conventional treatment
- Where to find LDN and how to take it
What is LDN?
You may be familiar with Naltrexone, which is an FDA-approved medication that has been used since the 1980s for opioid withdrawal. It is used at a higher, standard dose of 50 mg per day. However, low doses of this medication (hence, Low Dose Naltrexone or LDN), have been found to modulate the immune system and have shown promise in improving cases of autoimmune disease. These include Crohn’s, MS, and Hashimoto’s, as well as other immune system-related conditions such as cancer and HIV/AIDS. Dr. Bernard Bihari is credited with making these discoveries about using Naltrexone, off-label at lower doses.
LDN is truly an intriguing drug. It can be incredibly helpful for quite a few symptoms that are common for people with Hashimoto’s. I have seen people be able to get rid of pain. I have seen people be able to lower their thyroid antibodies significantly. I’ve seen some people be able to lower their thyroid medications. In speaking with other practitioners in the space, including Dr. Mark Mandel, I have heard about people with MS, who were in wheelchairs, that are now walking (these were not personal clients). Other people with food addictions have been able to overcome their addictions. People with cancer have been able to shrink tumors. The websites dedicated to sharing research are Low Dose Naltrexone (LDN) and LDN Research Trust. They are full of testimonials about ulcers, tumors, and lesions disappearing within months of initiating LDN.
Sounds pretty incredible, right? You might be wondering how it works.
Doses of 1.5 – 4.5 mg per day are usually recommended and have been reported to enhance immune function by increasing the body’s production of endorphins, also known as endogenous endorphin production. This is important for autoimmunity because the increased endorphins help to modulate and regulate the immune system. LDN also reportedly works by reducing inflammation, promoting DNA synthesis, and slowing down motility in the GI tract, to facilitate healing.
To get a little more technical, LDN balances the immune system by increasing the amount of T-regulatory cytokines and modulating TGF-B, leading to a reduction of Th-17, the promoter of autoimmunity. This means that it turns off the cells that cause autoimmunity!
How does LDN benefit Hashimoto’s?
Research on LDN is sparse, although there seems to be increasing interest in it. The first article was published in 2007, and it showed LDN as an effective and safe therapy for Crohn’s disease (1). Since that time, I’ve seen articles showing positive results with LDN for multiple sclerosis (2), fibromyalgia (3), and other immune issues such as cancer (4). It seems to be particularly beneficial for symptoms of chronic pain, too (5).
There haven’t been any research studies or clinical trials looking specifically at LDN and Hashimoto’s. I think this is more a reflection of the lack of financial gain involved with LDN, as opposed to its promise for autoimmune thyroid conditions. What I mean is that, since LDN is relatively inexpensive and available in generic form, the drug companies don’t have a lot to gain from funding this type of research.
Even with the lack of scientific data, there is a lot of clinical data from my friends and colleagues who use low-dose naltrexone in their practices. Personally, I have seen people going into complete remissions with LDN. Where thyroid antibodies were once in the 1000+ IU/mL range, they went under 100 IU/mL with LDN. I have seen a large reduction in TPO antibodies and TG antibodies, as well as autoimmune symptoms, in about 40 percent of clients with Hashimoto’s who have tried LDN. Many times, people have been able to eliminate their symptoms and reduce their dosages of medications. Some people have even been able to get completely off their medications.
LDN is something I recommend for people who have a lot of different challenges, including high antibodies, as well as women who want to get pregnant, and those with multiple autoimmune conditions. LDN can even be an alternative treatment for Graves’ disease, and used instead of thyroid-toxic drugs.
Interview with Dr. Mark Mandel
To learn more, I decided to interview Dr. Mark Mandel, PharmD, compounding pharmacist, LDN expert, and fellow Midwestern University Chicago College of Pharmacy grad, on the effects of LDN in people with Hashimoto’s and autoimmunity. Dr. Mandel was kind enough to share his knowledge with me, and I want to share an excerpt from our interview with you here.
IW: What types of people benefit from LDN?
MM: We have seen amazing results in people with autoimmune conditions, cancers, and neuropathic pain.
IW: How is LDN thought to work for autoimmune conditions?
MM: The exact mechanism has not been determined, but the theory is that LDN increases endorphin activity two to three fold. Additionally, it may increase the numbers of endorphin receptors and/or the sensitivity of the receptors. The increased endorphin activity results in better modulation of the immune system.
IW: How is LDN taken?
MM: The typical starting dose for people with Hashimoto’s, fibromyalgia, and MS is 1.5 mg every night at bedtime, but may be even lower depending on the individual. The target dose will come down to the individual patient, and we often need to titrate it. At times, the condition may be dynamic, and we may need to change the dose of LDN just as you would with other medications such as thyroid drugs. (Note: To help you even further, I’ve created an eBook, Optimizing Thyroid Medications, that you can download for free.)
LDN can be taken in the form of a compounded tablet, capsule, liquid, or transdermal formulation. We often find that the transdermal (skin) or sublingual formulations work best for those with liver issues. The transdermal formulation is recommended for children with autism.
For people who are new to LDN or for those with swallowing issues (dysphagia), I will usually recommend starting with a liquid formulation. That allows us to figure out the correct dose for each person.
IW: What are some of the more common adverse reactions that people have to LDN?
MM: Sleep disturbances, nausea, and irritability are some of the issues that people report.
For those that have nausea, we have found that using a sublingual dose seems to help. In cases of sleep disturbances, we recommend adjusting the dose to a morning time instead.
For those who have become irritable after taking LDN, I would recommend reducing the dose. While 1.5 mg is a typical starting dose for Hashimoto’s, some may do better with a starting dose of 0.5 to 1 mg. This is where the liquid LDN allows us to get a minute dose and gradually progress to a target dose. I like to use the old pharmacy adage that applies to most medications: “Start low and go slow.”
Liver toxicity has been reported with the full dose naltrexone, but I have not encountered this with the low dose naltrexone. However, we always recommend liver function tests while taking this medication.
IW: What types of benefits can be seen with LDN for thyroid disorders?
MM: Once you have been titrated to the correct dose, you will start feeling better. This will usually be followed by an improvement in labs, such as improved markers in TSH, T4, T3, and TPO levels. The time to start feeling better will, of course, vary per person. Once you start to feel better, maintain the dose for 2–3 months, and follow-up with your physician to see if your laboratory markers have improved. I recently had a patient with hyperthyroidism who struggled with trying to get pregnant for many years, and was finally able to get pregnant after starting LDN.
IW: Speaking of pregnancy, is LDN considered to be safe during pregnancy?
MM: Yes, all of the literature does seem to indicate that LDN is safe during pregnancy. (Dr. Wentz’ note: I have found studies that have used full dose naltrexone during pregnancy for opiate-addicted mothers. Results of the studies demonstrated that there were no negative outcomes associated with the use of naltrexone, and the newborn infants did not experience any symptoms of opioid withdrawal at birth.)
IW: Is LDN a life-long drug?
MM: Not necessarily. We have experienced patients with chronic neuropathic pain who had used LDN for a limited time period and were able to stop it; and if you are a young person with Hashimoto’s, you can go into remission through modulating your immune system with LDN. The medication will help you move towards an appropriate immune status, and once the immune system is in balance again, you may be able to get off the LDN.
IW: What advice do you have for those considering the use of LDN?
MM: LDN should be used as part of an arsenal to help you overcome your autoimmune condition. Appropriate levels of vitamin D, full spectrum light exposure, and food sensitivities all play a role in autoimmunity and need to be considered as well. It’s also best to work with a compounding pharmacy that can help you titrate your dose correctly.
Learn more about LDN and download the full transcript of my interview with Dr. Mark Mandel below!
Interview with Shannon Garrett
I also interviewed Shannon Garrett, RN, who is a Functional Nurse Nutritionist, LDN Nurse Educator, and founder of Holistic Thyroid Care for The Thyroid Secret docuseries. She works with clients with Hashimoto’s, and helps them use LDN as a tool. She also shares my root-cause philosophy, and I want to share with you some of the pearls I learned from our conversation.
Shannon has had her own journey with Hashimoto’s and saw 9 doctors before getting a diagnosis… and spent many more years exploring her own root causes. When she added LDN to her protocol, she reported an improvement in her quality of life. And now, she helps others to do the same.
The most important point I learned from Shannon is that LDN won’t work unless certain underlying issues are also addressed. It is not a stand-alone treatment. You will need to address gut imbalances, follow an anti-inflammatory diet, address nutrient deficiencies, and support the adrenals. She explained to me that Candida is the most important factor that will block LDN from working, and that Candida is always an issue with LDN because it is a natural part of the immune system. LDN can have a down regulating effect on the immune system and cause yeast and other opportunistic pathogens to thrive, if they are not addressed. Shannon recommends getting stool testing, treating Candida and avoiding sugar, if you are considering using LDN.
I know about this first-hand. LDN was one of the first interventions that I tried on my thyroid journey back in 2009. As a pharmacist, I was looking for the magic immune system pill, but I found that it made me somewhat irritable after a few nights of taking it, so I gave up on it and moved on to something else. From Shannon, I now know that gut imbalances, primarily Candida, can lead to anxiety while taking LDN. It can also disrupt sleep for the first couple of weeks.
With Hashimoto’s, the typical medical treatment (thyroid hormone replacement) does not address the immune component. LDN alone cannot be the autoimmune support that is needed, without the other nutrition and lifestyle pieces in place. Shannon cautions that LDN requires a commitment and monitoring since, while taking LDN, your body can increase its thyroid hormone production and, along with thyroid medication, it can become too much. Shannon has her clients keep a journal to track one’s heart rate and blood pressure, in order to identify any signs that thyroid hormone needs to be decreased. She also has her clients start on a very low LDN dose and titrate up slowly, saying that this works best for Hashimoto’s versus other autoimmune conditions who might readily tolerate a slightly higher dose off the bat.
Shannon told me,“all things considered, it is a wonderful and safe drug.” When it works, the benefits include improved energy, improved quality of life, weight loss, better mood, a reduction of thyroid antibodies, improved fertility, and reduced pain.
How LDN Differs from Conventional Treatment
As you may have experienced, conventional treatment for Hashimoto’s involves thyroid replacement hormone (once it is diagnosed, that is), but doesn’t often address this important immune modulation piece that we’ve been discussing. That’s where uncovering your root cause is so important, and where LDN can play a role.
When it comes to a root cause approach, exploring food sensitivities, infections, gut health and toxins can play an important piece. I talk about this more in my books, Hashimoto’s Thyroiditis: The Root Cause and Hashimoto’s Protocol.
I want to stress that LDN is not a cure, but rather an immune modulator that can be used to prevent further damage to the thyroid while one is looking for their root cause; or to rebalance the immune system when the root cause cannot be found.
Where to find LDN and How to Take It
LDN is not a commonly prescribed medication and is only available as a prescription. It needs to be compounded into lower doses by a professional compounding pharmacy. Luckily, even without insurance coverage, this medication is available in generic form and is very affordable, usually costing between $15-$40 per month.
It may not always be possible to convince your doctor to prescribe LDN. On my quest to try LDN, I talked to my local compounding pharmacist to figure out which doctors in my area were knowledgeable about prescribing LDN. Now, I recommend for physicians to speak with an LDN-trained compounding pharmacist to learn more.
There have been concerns about compounding medications not being accurate throughout, so I always make sure people use pharmacies that have PCCA starting materials. They dilute the ingredients, which makes it much harder to make an error with the dose. The key is to start out low and adjust according to what your body needs. Doses of 1.5–4.5 mg per day are usually recommended.
You’ll need to work with your doctor regarding LDN, since each person is unique and has individual needs that should be addressed. Keep in mind, what works for one person might not have the same benefit for another. The medication can be taken a number of ways (most notably at night, but some may take it in the morning if sleep is disrupted too much), so talk to your doctor about what’s best for you. Try not to get discouraged when something doesn’t pan out; instead, think of it as a puzzle. You fit the pieces together to complete the puzzle. Sometimes, something might look like a fit, but it’s not quite the right one. It’s a process and a journey, but it’s definitely worth it. LDN can be a wonderful and safe tool in the Hashimoto’s toolkit for some.
LDN Side Effects, Precautions and Interactions
The main side effect of low-dose naltrexone is vivid dreams. I experienced this myself. The first few nights that I used LDN, I had romance novel-type dreams where my husband, Michael, was a Fabio-like character riding around on a white horse without his shirt and sunbathing on yachts (LOL)! Shannon Garrett, RN shared with me in our interview that she dreamed about her dogs holding pink umbrellas and flying!
LDN can disrupt sleep as the body releases endorphins overnight, but the frequent waking usually passes after the first two weeks. The vivid dreaming may last longer, however, depending on the person. This may be a good or bad thing, depending on your dreams. 🙂
Other than the vivid dreams and initial sleep disruption, the side effect profile is very minimal. As a pharmacist, this is something I don’t often get to say and makes me really excited about the power of this medication.
Much of the research and information available concerning naltrexone precautions pertains to the higher doses of naltrexone used for opiate withdrawal, rather than low dose naltrexone. However, the following risk factors and interactions should be taken into consideration and discussed with a knowledgeable practitioner, before beginning LDN.
Naltrexone (in full dose) may not be appropriate for those who have hepatic or renal dysfunction. There is some risk of hepatotoxicity with naltrexone, and this risk is increased in individuals with acute liver failure. This is mainly a concern when using higher doses of naltrexone, and one study has shown that LDN does not change liver enzyme status/liver function in those with autoimmune conditions. However, elevated liver enzymes in acute liver failure and/or acute renal failure can also lead to decreased effectiveness of certain drugs, including LDN.
Generally, it is not recommended to use LDN when taking opiates, as naltrexone can counteract the effects of opiates, and can increase the risk of abuse and overdose. Some sources have suggested that LDN can be safely taken with opiates if the two are spaced apart by at least several hours, however, this must be done at the discretion and approval of one’s healthcare practitioner due to the high risk of interaction.
Other known medications that can interact with LDN include: buprenorphine, Cymbalta (duloxetine), and Wellbutrin XL (bupropion). While buprenorphine has been safely used in combination with naltrexone, naltrexone can block the effects of buprenorphine. Not much research is available on whether the interactions with Cymbalta and Wellbutrin XL apply specifically to high dose naltrexone, or to LDN as well. Speaking with a practitioner is advised before starting LDN, if taking any of the above medications.
Additionally, calcium carbonate supplements should not be taken while using LDN, as the calcium carbonate can bind to naltrexone, turning it into a “slow release” that prevents the rebound effect (the mechanism that makes it effective) of LDN.
As with any intervention, I also recommend monitoring thyroid hormone closely while taking LDN, and testing thyroid hormone levels every 30-90 days, as LDN can improve thyroid function and a medication adjustment may be needed.
Next Steps
As those of you that have read my book will know, the immune system can be thrown off balance by a variety of factors. Some of those factors include food sensitivities, infections, or an imbalance in gut bacteria. Thus, I always recommend using LDN as a part of a whole person approach, and not as a standalone therapy.
As I mentioned in Hashimotos: Root Cause, I also used LDN before I started working on my diet. Had I worked with a knowledgeable professional, I would have learned that LDN works best when used alongside a leaky gut diet. Additionally, according to Shannon Garrett, LDN may not work if someone has a Candida overgrowth. For improved tolerability, titrating the dose is also necessary.
It’s important to work with your functional medicine doctor and compounding pharmacist to ensure LDN will be right for you, and that you get the right dose.
Here are the LDN Pharmacies I recommend (they ship US-wide):
To learn more about LDN, check out the Low Dose Naltrexone and LDN Research Trust sites. You can be sure that I will be following any new research pertaining to Hashimoto’s and will update you here.
It took me over three years to get myself in remission. I hope that with the information I share in my book and on this blog, you will be able to get yourself into remission more quickly and efficiently.
P.S. For continued updates and interaction, please become a part of our Facebook community and sign up for my newsletter to get a free book chapter from my first book, recipes, a Thyroid Diet start guide, and notifications about my latest research.
References
- Smith JP, Stock H, Bingaman S, Mauger D, Rogosnitzky M, Zagon IS. Low-dose naltrexone therapy improves active Crohn’s disease. American Journal of Gastroenterology. 2007;102(4):820-8.
- Ludwig MD, Zagon IS, McLaughlin PJ. Serum [Met5]-enkephalin levels are reduced in multiple sclerosis and restored by low-dose naltrexone. Experimental Biology and Medicine. 2017;242(15):1524-1533. doi: 10.1177/1535370217724791
- Metyas S, Chen CL, Yeter K, Solyman J, Arkfeld DG. Low dose naltrexone in the treatment of fibromyalgia. Current Rheumatology Reviews. 2018;14(2):177-180. doi: 10.2174/157339711366617321120329
- Li Z, You Y, Griffin N, Feng J, Shan F. Low-dose naltrexone (LDN): A promising treatment in immune-related disease and cancer therapy. International Immunopharmacology. 2018;61:178-184. doi: 10.1016/j.intimp.2018.05.020
- Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clinical Rheumatology. 2014;33(4):451-9. doi: 10.1007/s10067-014-2517-2.
- Towers CV, Katz E, Weitz B, Visconti K. Use of naltrexone in treating opioid use disorder in pregnancy. Am J Obstet Gynecol. 2019 Jul 31. pii: S0002-9378(19)30944-5. doi: 10.1016/j.ajog.2019.07.037.
- Dickson, Stephen J. Pharmacokinetic and Pharmacodynamic interactions, formulation, preparation, stability and considerations for practical prescribing of Low Dose Naltrexone. LDN Research Trust Conference, 2013.
- Naltrexone Interactions. Drugs.com. https://www.drugs.com/drug-interactions/naltrexone.html. Accessed January, 2022.
- Low Dose Naltrexone. Fibromyalgia Trust. http://fibrotrust.org/low-dose-naltrexone/. Accessed January, 2022.
- Ludwig MD, Turel AP, Zagon IS, McLaughlin PJ. Long-term treatment with low dose naltrexone maintains stable health in patients with multiple sclerosis. Mult Scler J Exp Transl Clin. 2016;2:2055217316672242. Published 2016 Sep 29. doi:10.1177/2055217316672242
- Boendermaker, A.E. et al. Elevated liver enzymes and renal failure, with a surprising outcome. Two similar cases. Neth J Crit. Care. 2013;17(1):33-36. https://nvic.nl/sites/nvic.nl/files/pdf/case-report-4.pdf. Accessed January 25, 2022.
- Q & A: Taking LDN and Other Substances/Treatments. LDN Science. https://www.ldnscience.org/patients/qa/taking-ldn-and-other-substances-treatments. Accessed January, 2022.
- McDonough M. Naltrexone and liver disease. Aust Prescr. 2015;38(5):151. doi:10.18773/austprescr.2015.063
- Farahmand S, Ahmadi O, Dehpour A, Khashayar P. Does adding low doses of oral naltrexone to morphine alter the subsequent opioid requirements and side effects in trauma patients?. Am J Emerg Med. 2012;30(1):75-78. doi:10.1016/j.ajem.2010.09.031
Note: Originally published in February 2015, this article has been revised and updated for accuracy and thoroughness.