Autoimmune diseases are a complex group of conditions in which the immune system mistakenly attacks healthy cells and tissues. While treatment options exist to manage symptoms, there is no known cure for autoimmune diseases. However, recent research has shed light on the potential benefits of Low Dose Naltrexone (LDN) in managing these conditions. In this blog post, we'll explore some of the latest research findings on the use of LDN in autoimmune diseases.

1. The Basics of Low Dose Naltrexone (LDN)

Low Dose Naltrexone (LDN) is an FDA-approved medication typically used in higher doses to treat opioid addiction. However, in low doses (usually 1-4.5 mg per day), it has shown promise in addressing autoimmune diseases. LDN works by modulating the immune system and may help reduce inflammation and promote self-tolerance.

2. Promising Research on Multiple Sclerosis (MS)

Recent studies have examined LDN's potential in treating Multiple Sclerosis (MS), an autoimmune disorder affecting the central nervous system. LDN appears to have a positive impact on MS patients by reducing the frequency and severity of relapses and improving overall quality of life. It may work by inhibiting the activation of microglia cells, which are implicated in neuroinflammation.

3. LDN and Rheumatoid Arthritis

In Rheumatoid Arthritis (RA), LDN has shown potential as an adjunct treatment. A study published in the Journal of Translational Medicine in 2014 suggested that LDN can reduce disease activity and pain levels in RA patients, along with improving sleep quality. LDN's mechanism of action may involve its ability to modulate the immune response and reduce inflammation in the joints.

4. Crohn's Disease and LDN

Crohn's Disease, an inflammatory bowel disease, has also been the focus of LDN research. Several studies have reported that LDN may help reduce disease activity, improve quality of life, and reduce the need for other medications. The anti-inflammatory properties of LDN could be instrumental in providing relief to Crohn's patients.

5. The Immune Modulation Effect

LDN's ability to modulate the immune system is a key feature that makes it relevant for autoimmune diseases. It appears to promote the release of endorphins, which, in turn, influence immune function. By balancing immune responses and reducing inflammation, LDN may be a valuable complementary therapy for a range of autoimmune conditions.

6. Safety and Side Effects

Low Dose Naltrexone is generally well-tolerated, and side effects are typically mild and transient. However, it's essential to work closely with a healthcare provider when considering LDN as part of your treatment plan. Dosage and monitoring should be tailored to individual needs.

Conclusion

While Low Dose Naltrexone is not a guaranteed cure for autoimmune diseases, the recent research findings are promising. LDN's potential to modulate the immune system and reduce inflammation has drawn attention from both patients and healthcare professionals. Nevertheless, it's essential to approach LDN as part of a comprehensive treatment plan, under the guidance of a qualified healthcare provider.

Autoimmune diseases are highly individual, and what works for one person may not work for another. It's crucial to discuss the use of LDN with your doctor to determine whether it's a suitable option for you. With continued research and clinical trials, LDN may play a more significant role in managing autoimmune diseases in the future, offering hope for improved quality of life for those who are affected by these conditions.

Naltrexone is commonly known as an opiate antagonist. This means this drug competes for the same receptors in the body as opioids, like oxycodone or morphine. In doing this, naltrexone makes it so opioid drugs do not work like they normally would. Basically, it reverses their effects and eliminates the feelings of well-being . It is very useful in accidental or intentional overdose and short or long term toxicity. However, these effects are only seen at the higher doses of Naltrexone. High doses include anything 50 mg or higher. At lower doses, Naltrexone has many different effects. Low Dose Naltrexone (LDN) is usually 1 to 5 mg, but can vary slightly. It still keeps its opioid blocking effects, but for a temporary effect. It’s main effect is working on the immune system. This gives LDN the capability to work in a lot of different areas including autoimmune diseases like rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and so much more.

Chemical Structure of Naltrexone

There are two different main types of inflammatory bowel disease; ulcerative colitis and crohn’s disease (as pictured below). Crohn’s disease is complex and mysterious because the cause of it is unknown. It’s thought that many things contribute such as environmental, genetic, infectious, immune, and non-immune factors. What we do know is that it has a distinct characteristic of life-long inflammation that comes and goes most commonly in the colon and last parts of the small intestine. Crohn’s disease is not limited to these areas, it may affect the whole digestive tract in one area or many areas at once. Crohn’s disease is most commonly diagnosed in young adults, before age thirty. Common complications can include extensive bowel wall injury, fistulas, narrowed intestinal lumen, small bowel strictures, and nutritional deficiencies. Some common treatments are medicines, bowel rest, and sometimes surgery. No one treatment regimen will work for everyone with crohn’s disease, but the goal is to decrease the inflammation in the intestines, to prevent flare-ups of symptoms, and to keep the disease in remission.

For Crohn’s specifically, the mechanism of LDN ties into the distinct life-long inflammation that comes and goes in the gastrointestinal tract. Toll-like receptors (TLR) are a class of proteins in the body that play a key role when dealing with the immune system. Overactivation of TLRs has been linked to various infectious and inflammatory diseases. LDN has been shown to reduce inflammatory response by controlling these TLRs and their signalling. In addition, LDN increases endogenous endorphin signaling through the whole body by short term opioid-receptor blockade. In other words, endogenous (internal) opioid signalling can mimic the effects of opioids because endorphins can cause an analgesic effect. Further, this can promote healing, inhibit cell growth, and reduce inflammation. LDN may even stimulate the body’s own production of endorphins, even after the LDN is no longer in the system. A recommended dosing pattern for LDN in crohn’s disease starts at 1.5 mg per week and can be increased by 1.5 mg per week up to 4.5 mg until symptoms have been reduced.

LDN is unique in the sense that it is not made by a manufacturer like other traditional prescriptions. It is only made in compounding pharmacies, making the dosage and formulation type unique to each prescription. LDN can be compounded into come in liquid, capsules, sublingual drops, cream or tablets. A LDN prescription will require working with both a physician and pharmacist. In almost every recorded trial where LDN is used for the treatment or improvement of crohn’s symptoms, there was a positive effect on the outcome. It has shown to improve crohn’s disease activity index, remission after failing multiple standard regimens, clinical improvement, and reduction in use of anti-inflammatory medications. It is also important to note that the improvement of these outcomes does not come at a price.

LDN very rarely has been associated with side effects during trials and has been well tolerated. Some of the most common side effects reported with its use in trials for inflammatory bowel disease were vivid dreams, drowsiness or insomnia, and headache. These side effects do not affect the effectiveness of LDN. The LDN Research Trust states that in inflammatory bowel disease,

LDN is expected to be successful 78 - 84% of the time according to patient’s reports. The first time LDN was used for inflammatory bowel disease in clinical trials was published in 2007. This refers to a study that used compounded 4.5 mg capsules of LDN daily for three months in addition to their regular medications. LDN was used to determine if it’s use helped enrolled patient’s symptoms related to crohn’s disease. To assess LDN’s effect on disease activity, patients recorded their symptoms in a Crohn’s symptom diary recording things like frequency of diarrhea, abdominal pain, and general well-being. This was used to calculate a Crohn’s disease activity index (CDAI). The index scores can range from 0 to about 600. A CDAI of less than 150 is a marker of remission of Crohn’s disease and a score of greater than 450 is a marker of severe Crohn's disease. Their study results indicated that out of the seventeen patients enrolled, 89% of the patients had a response to the LDN and 67% achieved remission according to their CDAI score.

More recently, in 2018 another study evaluated LDN in patients both not in remission and not responding to the usual therapy for treatment of inflammatory bowel disease. Including more patients than ever before, this study’s goal was to assess LDN’s effects for inflammatory bowel disease treatment of actual patients rather than theoretically or in the lab. Forty-seven patients with inflammatory bowel disease used 4.5 mg of LDN daily for 12 weeks. Clinical improvement was measured by patient self-assessments and outpatient assessments. Of the enrolled patients, 74.5% achieved a clinical response overall. Of those patients who achieved a clinical response, 25.5% of patients had a response of at least 3 months whereas the rest were seen between four and twelve weeks. The biggest difference between this study and the previous study mentioned is this study takes into account both ulcerative colitis and crohn’s disease. However, the results did not show any significant differences between the two types of inflammatory bowel disease. Overall, all studies have shown LDN in crohn’s disease to help in either remission of symptoms or clinical improvement in a well tolerated manner. More and bigger studies are needed to prove it’s place in practice, but it continues to show benefits as a safe add on treatment for the complicated gastrointestinal disease known as crohn’s disease.

The Medicine Center Pharmacy in New Philadelphia specializes in custom compounded medications in custom dosage forms. The pharmacists are trained experts in low dose naltrexone therapy. LDN therapies can be customized across 23 different dosage forms for 15 different disease state protocols. If you would like to learn more about low dose naltrexone or would like to schedule a phone call or video conference please contact us.

Key Articles

★ LDN Rx Consultants (July 2019). Inflammatory bowel disease (IBD) [PDF

file]. Retrieved from: ldnrx.com.

★ Lie MRKL, Giessen JV, Fuhler GM, et al. Low dose Naltrexone for induction

of remission in inflammatory bowel disease patients. J Transl Med

2018;16(55):1-11.

★ Pradeep Chopra (2014). Mechanism of action of low dose naltrexone (ldn)

[PowerPoint slides]. Pain Management Center, RI. Retrieved from:

https://www.ldnresearchtrust.org/sites/default/files/LDN_Mechanism_Of_

Action_Pradeep_Chopra_MD.pdf .

★ Revia® (naltrexone hydrochloride tablets USP) [package insert]. Pomona,

NY: Duramed Pharmaceuticals, Inc.; issued Oct 2013.

★ Smith JP, Stock H, Bingaman S, et al. Low dose naltrexone therapy

improves active crohn’s disease pilot study. Am J Gastroenterol

2007;102:820-28.

★ Toljan K and Vrooman B. Low-dose naltrexone (ldn)-review of therapeutic

utilization. Med Sci 2018;6(82):1-18.

Low Dose Naltrexone (LDN) is increasingly used by clinicians for management of challenging medical conditions such as chronic pain or autoimmune disorders.  Even though research on LDN as a treatment modality for certain diseases remains sparse, there are several clinical studies conducted to evaluate the effect of LDN for treatment of these conditions and they have shown beneficial effects on symptom improvement.  LDN is known to be extremely safe and well tolerated, especially when compared to the drugs typically used to treat these conditions. That is why LDN is considered as a valuable option for clinicians and is an important focus of ongoing research.

 It has recently been found that the addition of LDN to treatment regimens for mental illness can help reduce symptoms.  However, the evidence showing efficacy of LDN use in treating mental illness is still lacking but the research is ongoing.  I am going to review several clinical trials that focused on LDN and psychological disorders and then discuss the beneficial effects and how LDN can be promising for patients with mental illness.

Naltrexone is a reversible competitive antagonist at the mu and kappa receptors and to a lesser extent is a delta receptor antagonist.  At oral doses of 50–150mg, it can reverse opioid overdoses and treat alcohol addiction.  Paradoxically, LDN enhances the effects of opioid agonists by blocking the opioid receptor transiently which causes a positive feedback mechanism that increases the production of endogenous peptides.  Increased levels of endogenous opioids peptides are known to promote healing, inhibit cell growth, and reduce inflammation.  Naltrexone works by binding to the C-terminal pentapeptide of the scaffolding filamin A with strong affinity. Filamin A is also found on dopaminergic D2 and D3 receptors which might explain the effect of LDN on prevention of desensitization to D2/D3 agonists.  This potential LDN mechanism on dopaminergic receptors led researchers, Bear and Kessler, to propose a study to evaluate for beneficial effects of LDN on restless leg syndrome (RLS)5. The study showed that RLS symptoms had improved with the use of LDN.  RLS is typically treated with D2/D3 agonists such as pramipexole or ropinirole. Thus, the researchers suggested that the LDN use would effective in RLS possibly due to facilitated sensitization of D2/3 agonists.

The pathophysiology of depression is thought to involve abnormal dopaminergic D2 receptor function which is possibly associated with D2 receptor desensitization4.  An observation study has demonstrated that patients had a relapse with depressive symptoms when a D2 antagonist was given following successful treatment with SSRI.  The result was similar in an animal model of depression in which the symptoms were reversed by tricyclic antidepressants4.  Therefore, the prevention of D2 receptor desensitization may be essential to effectively treat depression when combined with antidepressants such as SSRIs or SNRIs.  Antidepressants may foster the sensitization of D2 receptors and LDN may exert antidepressant effects by preventing D2 receptor desensitization and thus enhancing dopaminergic signaling.

In addition, there has been anecdotal evidence in multiple trials showing that LDN has beneficial mood effects in different conditions.  Following the RLS study, a randomized, double blind pilot trial was initiated based on this background information.  The study was conducted to evaluate the hypothesis that patients experiencing depressive breakthroughs would demonstrate greater improvement in their depression when supplementing their current antidepressant regimen with LDN versus placebo, with no significant difference in side effects5. In the study, 12 adults with recurrent major depressive disorder (MDD) on dopaminergic antidepressant regimens (stimulants, dopamine agonists, bupropion, aripiprazole, or sertraline) were randomized to naltrexone 1 mg b.i.d. (n=6) or placebo (n=6) augmentation for 3 weeks. The study found that LDN augmentation reduced the severity of depression symptoms in 12 depressed patients who had relapsed on dopamine-enhancing antidepressants. The key finding of the study is that if a patient has depression and has experienced a relapse while taking a previously effective antidepressant that works primarily by dopaminergic mechanisms, the addition of LDN could potentially reduce the depressive symptoms when combined with the original antidepressant. However, a major limitation with this study is that the patient sample is small.  It may be necessary to reconduct this study with a larger sample size to confirm the significant difference between the LDN and placebo group.  Also, the study included only antidepressants that work by dopaminergic mechanisms.  Thus, additional studies should be conducted to determine how effectively it would work with other types of antidepressants.

A retrospective case study, performed by the Department of Psychiatry at the UCLA Kern Medical Center in California, had investigated the efficacy of LDN on a comorbid depressive disorder6.  In the report, 5 patients received at least one month of LDN, 2 patients had a diagnosis of MDD, and 2 patients had Bipolar Type II and 1 patient had Bipolar Type I.  The results from this study showed that of these patients, 2 patients with fibromyalgia only had minimal improvement, 1 patient with lumbar discopathy had no improvement, and 1 patient with Lupus had much improvement with liquid LDN.  At the conclusion of this case study, 80% of patients experienced some degree of improvement with LDN at week 4.  Another study conducted by a German Research Group in 2015 found that patients with severe trauma-related dissociative disorders had positive effects after treatment with LDN at doses ranging from 2 - 6 mg daily7.  In this study, 11 out of 15 patients reported immediate positive effects and 7 patients described a lasting beneficial effect.  Although it is not known how LDN positively affects patients with depression or posttraumatic psychotic disorders, it seems that LDN has some association with beneficial effects on depressive or psychotic symptoms in those patients. However, these studies remain limited due to their small sample sizes. These studies need to be replicated with a larger patient population to validate the positive efficacy of LDN on those mental health problems.

As mentioned earlier, it is well known that LDN has beneficial effects on chronic pain and autoimmune disorders.  This knowledge led researchers to conduct clinical studies evaluating the effect of LDN on certain medical conditions such as multiple sclerosis (MS), fibromyalgia, or Crohn’s disease1. LDN has been the subject of many debates and despite there being few clinical studies performed, these studies are key clinical trials demonstrating how LDN results in significant improvement of symptoms.

            Fibromyalgia is a disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, and mood issues. Thus, patients with fibromyalgia are sometimes treated with antidepressants. There is a single-blind crossover pilot study that investigated the effectiveness of LDN in treating fibromyalgia symptoms8.  The study was conducted based on the hypothesis that LDN may reduce fibromyalgia symptoms by inhibiting the activity of microglia and thus reversing central and peripheral inflammation. In this trial, 10 women with fibromyalgia participated and completed daily reports of symptom severity during baseline (2 weeks), placebo (2 weeks), LDN (8 weeks), and washout phases (2 weeks).  In addition, participants visited the lab every 2 weeks for tests of mechanical, heat, and cold pain sensitivity.  This study results showed that LDN reduced fibromyalgia symptoms in the entire cohort with greater than 30% reduction over placebo.  In addition, participants showed improvement in mechanical and heat pain thresholds during the laboratory visits.  Also, participants reported that side effects including insomnia and vivid dreams were rare, or minor and transient. The study concluded that low-dose naltrexone may be an effective, highly tolerable, and inexpensive treatment for fibromyalgia.   The mood changes in fibromyalgia patients may be associated with the severity of pain that the patients are experiencing.  Therefore, it can be suggested that improvement in pain symptoms may contribute to reduction of depressive symptoms in patients with chronic pain.  In other words, LDN may have beneficial effects on mood disorders by exerting positive effects that lower the severity of pain experienced.

            Prescribers are becoming increasingly interested in LDN use for various medical conditions since it is well tolerated, safe, and inexpensive.  Also, several key clinical trials have shown that LDN may be promising for the management of recurrent or hard to treat mental illnesses, but further research is needed to ensure the efficacy of LDN for those medical conditions.  However, researchers emphasize that LDN should not be used alone for the treatment of mental illnesses, but it can be added to enhance the therapeutic effects of existing regimens.  In conclusion, LDN can be effective in treating mood disorders when combined with current regimens but additional studies with larger sample sizes are needed  to generate more reliable data.

The Medicine Center Pharmacy in New Philadelphia specializes in custom compounded medications in custom dosage forms. The pharmacists are trained experts in low dose naltrexone therapy. LDN therapies can be customized across 23 different dosage forms for 15 different disease state protocols. If you would like to learn more about low dose naltrexone or would like to schedule a phone call or video conference please contact us.

 References

1.     Low Dose Naltrexone. Provider Guide.

2.     Chopra, Pradeep. Mechanism of Action of LDN, Low Dose Naltrexone. Provider Guide.

3.     Wang, H.Y., Frankfurt, M., Burns, L.H., 2008. High-affinity naloxone binding to filamin a prevents mu opioid receptor-gs coupling underlying opioid tolerance and dependence. PloS One 3, e1554.

4.     Willner, P., 2002. Dopamine and depression. In: Di Chiara, G. (Ed.), Handbook of Physiology: Dopamine in the CNS. Springer, Berlin, 387–416.

5.     Mischoulon D, Hylek L, Yeung AS, Clain AJ, Baer L, Cusin C, Ionescu DF, Alpert JE, Soskin DP, Fava M. Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants. J Affect Disord. 2017 Jan 15;208:6-14. doi: 10.1016/j.jad.2016.08.029. Epub 2016 Oct 1. Erratum in: J Affect Disord. 2017 Oct 27;227:198.

6.     The 15th Pacific Rim College of Psychiatrists Scientific Meeting. (https://onlinelibrary.wiley.com/doi/pdf/10.1111/appy.12002)

7.     Pape, W., Wöller, W. Low dose naltrexone in the treatment of dissociative symptoms Nervenarzt 86, 346–351 (2015). https://doi.org/10.1007/s00115-014-4015-9

8.     Younger J, Mackey S. Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study. Pain Med. 2009 May-Jun;10(4):663-72. doi: 10.1111/j.1526-4637.2009.00613.x. Epub 2009 Apr 22. PMID: 19453963; PMCID: PMC2891387.

Epilepsy is a broad term used to describe people who suffer multiple seizures in their life time.  Seizures are defined as sudden, uncontrolled electrical brain activity.  Depending on how the brain looks at these electrical currents a person may change behavior, display abnormal movement or even lose consciousness.

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The LDN Book Edited by Linda Elsegood

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As of 2015 about 3.4 million people suffer from epilepsy.1 Most people with epilepsy take one or more medications to prevent seizure activity. However, an estimated 30% of people worldwide do not respond to current FDA approved medications.2 With the rise in popularity of medical marijuana for treatment of epilepsy, scientists have begun to look at opioids again for new uses.  Ultra-low doses of naltrexone along with morphine or cannabis are being studied.

What is low and ultra-low dose naltrexone?

            Naltrexone is currently FDA approved as treatment for opioid and alcohol abuse. Available in pill or as an injection, treatment for opioid and alcohol abuse uses doses from 50mg to 380mg.  Low dose naltrexone broadly refers to dosages below the 50mg mark for opioid and alcohol abuse treatment.3 specifically 0.5mg to 10mg is the studied range when talking about low dose naltrexone. 

Ultra-low dose refers to even smaller doses ranging from 1/1000000000 of a milligram to 1/1000000 of a milligram. To picture how small ultra-low dose naltrexone is think of opioid treatment doses as a swimming pool.  Low doses are a couple of buckets.  Ultra-low doses would be drops.

There is no recommended dose of naltrexone for epilepsy or seizures in humans. The ultra-low doses have only been studied in mice as add-on to opioids and cannabis products.  These doses were administered in injection form.

How does low dose naltrexone work to prevent seizures?

            Ultra-low doses of naltrexone alone do not stop or prevent seizures.  Morphine and cannabis like products work to raise the amount of electrical activity in the brain needed to cause a seizure.  The exact way ultra-low doses of naltrexone works with opioids and cannabis in epilepsy is unknown.  Scientists think ultra-low naltrexone works either to increase the effects of the morphine and cannabis or helps to decrease tolerance.4-6

What are the studies saying about ultra-low dose naltrexone for epilepsy?

            Trials in mice using ultra-low dose naltrexone have been promising.  Data favors further study of ultra-low dose naltrexone with either opioids or cannabis like products.  However, no data yet suggests any safety for trials in humans.  Further animal study is needed to evaluate long term use.  Current trials in mice only looked at one seizure per mouse.4-6 

What are the risks of using low dose naltrexone for seizure control?

            As stated in the above section, current trial data is only for mice after one incident.  The effects of treatment long term have not been evaluated.  Seizure activity may develop again after time on the medications.  Doses tested in mice may not work in humans.

The Medicine Center Pharmacy in New Philadelphia specializes in custom compounded medications in custom dosage forms. The pharmacists are trained experts in low dose naltrexone therapy. LDN therapies can be customized across 23 different dosage forms for 15 different disease state protocols. If you would like to learn more about low dose naltrexone or would like to schedule a phone call or video conference please contact us.

Resources

1.     CDC [Internet]. Epilepsy Fast Facts. Center for disease control: Atlanta (GA); last updated 18 July 2018, accessed 18 April 2020. Available from: https://www.cdc.gov/epilepsy/about/fast-facts.htm

2.     Wahab A. Difficulties in Treatment and Management of Epilepsy and Challenges in New Drug Development. Pharmaceuticals (Basel). 2010 Jul; 3(7): 2090–2110.Published online 2010 Jul 5. Accessed April 2020.

3.     SAMHSA. Naltrexone. Substance Abuse and Mental Health Services Administration. Last updated  September 2019, accessed April 2020. Available from: https://www.samhsa.gov/medication-assisted-treatment/treatment/naltrexone

4.     Honar H, Riazi K, Homayoun H, Sadeghipour H, Rashidi N, Ebrahimkhani MR, et al. Ultra-low dose naltrexone potentiates the anticonvulsant effect of low dose morphine on clonic seizures. Neuroscience. 2004;129(3):733-42.

5.     Bahremand A, Shafaroodi H, Ghasemi M, Nasrabady SE, Gholizadeh S, and Dehpour AR. The cannabinoid anticonvulsant effect on pentylenetetrazole-induced seizure is potentiated by ultra-low dose naltrexone in mice. Epilepsy Res. 2008 Sep;81(1):44-51.

6.     Roshanpour M, Ghasemi M, Riazi K, Rafiei-Tabatabaei N, Ghahremani MH, and Dehpour AR. Tolerance to the anticonvulsant effect of morphine in mice: blockage by ultra-low dose naltrexone. Epilepsy Res. 2009 Feb;83(2-3):261-4.

Physiology of the Disease

Cancer is a condition in which cells within your body divide at an uncontrolled rate. Our body's natural defense against these cells are known as tumor suppressor genes. However, mutations can occur leading to the formation of oncogenes that promote cell growth and reproduction, or suppression of tumor suppressor genes. When this occurs, the cells divide rapidly leading to tumors or large masses and cause your bodies other healthy cells to die. These cancerous cells can then travel to other parts of your body through the bloodstream via a process known as metastasis. When this occurs, the cancer can continue to grow in these areas making it much more difficult to treat.

LDN – How it Works

At its intended doses of 50-100 mg, naltrexone is an opioid antagonist used in the treatment of addiction. However, when used at much lower doses, naltrexone is known to act as an anti-inflammatory agent. As we used LDN more and more, and involve it in animal and human studies, we have found it to be useful in many other conditions such as cancer. Although we do not know the full mechanism of action for benefit in cancer patients, here are some proposed mechanisms:

●      Intermittent dosing significantly reduced cancer cell development, in contrast to a constant blockade that accelerated tumor growth

●      May enhance natural killer cells, T-Cell, IL-2, and TH-2 activity via the mu receptor and also by binding to receptors on cancer cells themselves. These cells are the major players in our body’s natural immune system

●      LDN causes increased cell death in certain cancers and potentially increases patient response to chemotherapy agents

●      Cells that are treated with LDN up-regulate BAD and BIK1 genes that aid in cell death

●      Some cancer patients treated with intermittent LDN, experienced greater benefit by chemotherapy drugs

o   Example: Priming HCT116 with LDN before treatment with oxaliplatin significantly increased cell ki

Effectiveness

            Naltrexone’s potential for cancer prevention and treatment began mainly from the work of Penn State investigators Ian Zagon and his colleagues. They initially studied and published evidence that a dose of 0.1mg/kg in mice reduced neuroblastoma tumor incidence by 66%, slowed tumor growth by 98% and increased survival by 36% over controls.

            More recent publications include that from Liu et al in 2016 who published that cells treated with LDN followed by chemotherapy always resulted in a greater reduction in cell number and viability when compared to cells cultured with LDN after chemotherapy treatment. However, in cells treated with standard NTX, treatment with any of the cytotoxic drugs did not generally result in dramatic reductions in cell number or viability.

            Another researcher, Dr.Bernard Bihari has reported he has treated about 450 cancer patients with LDN, and he reports that over 270 patients had significant benefits from LDN. Of those patients, 86 of them had shown objective signs of decreased tumor size of at least 75%. Another 125 patients were stabilizing or on a path toward remission.

Dosing

Starting doses can be anywhere from 0.5 mg to 1.5 mg, and is increased up to 4.5 mg; which is the maximum dose for Low Dose Naltrexone. Specifically for cancer patients, the dose should be a goal daily for at least 7 days before starting an "on/off cycle"

●      An "on/off cycle" consists of 3 days on and 3 days off LDN

●      The 3 days off should fall directly before chemotherapy treatment. Although there are no known contraindications with chemotherapy, it is recommended to avoid use together until further research is completed

It has been seen in some cancer patients, that taking a CBD product on the 3 days off increases the anti-tumor effect of LDN

Side Effects

LDN is well tolerated in most patients and limited further when a patient is started on a start low and go-slow method. This means the patient should be started at a low dose and titrated up slowly. When side effects occur, they are usually mild and include:

●      Sleep disturbances

●      Mild headache

●      Mild agitation

●      Nausea/GI effects - consider switching to liquid sublingual LDN to bypass GI tract

It has been found in patients that experienced side effects, that they can be stopped by decreasing the dose by half for 2-3 days, and then continuing with titration again.

Formulations

●      Oral liquid: 1 mg/1 mL daily

●      Capsules or tablets

●      Sublingual drops

o   Drops are placed under the tongue from a dropper bottle

●      Creams: 0.5 mg/mL

o   Useful for children who you have difficulty administering the other formulations, or those who are allergic to additives in other formulations of LDN

Key Resources

Boundless. Overview of Cancer [Internet]. Lumen: Boundless Anatomy and Physiology. Available from: https://courses.lumenlearning.com/boundless-ap/chapter/overview-of-cancer/

Brown N, Panksepp J. Low-dose naltrexone for disease prevention and quality of life. Medical Hypotheses. 2009;72(3):333–7.

How Low Dose Naltrexone Works [Internet]. How does Low Dose Naltrexone Work | LDN Research Trust - Low Dose Naltrexone. Available from: https://www.ldnresearchtrust.org/how-naltrexone-works

Low Dose Naltrexone [Internet]. The Low Dose Naltrexone Homepage. Available from: http://www.ldninfo.org/

Toljan K, Vrooman B. Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization. Medical Sciences. 2018;6(4):82.

written by Jordan Hughes, PharmD Candidate Ohio Northern University

Coronaviruses are one of the largest groups of viruses that we know about in medicine, and it has an extensive range of natural hosts. Recently, newly evolved Coronaviruses have posed a massive threat to public health causing a worldwide pandemic.  The novel coronavirus that causes COVID-19 sparks an inflammatory immune response that is essential to control and eliminate the infection, however, certain immune responses can cause a decrease of gas exchange in the lungs. This causes a huge problem because oxygenation of the blood is essential for human life and is the basis for maintaining function of all major organs. So, will low dose naltrexone target certain immunological markers to ensure that the body does not injure itself during the fight against coronavirus?

Naltrexone is a pure opioid antagonist with activity and many opioid and non-opioid receptors. It is currently used for alcohol use disorders, opioid addictions and obesity. Naltrexone can be used for several different disorders depending on the dosage that is used, and the effects might differ when the doses are changed. Higher doses of naltrexone can be used for impulse control disorders and several other addictions. However, Low Dose Naltrexone (LDN), has been studied and shown promise in the treatment of many diseases such as Crohn’s disease, multiple sclerosis, and chronic fatigue syndrome. Dr. Bernard Bihari, known to some as the father of Low Dose Naltrexone, completed research that showed LDN was used to boost endorphin levels in patients by 3X. These endorphins levels can improve immune function and might be used to help at-risk patients to fight off the Novel Coronavirus infection.

To understand how medications attack and destroy the virus, we need to understand how the virus gets inside the body, how it infects the host, and how it is transmitted to others. Like many other infectious diseases, Coronavirus enters the body through direct contact with direct mucous membranes such as eyes, mouth, or nose. When the virus gets into the body, it will use the body’s own cells to replicate and spread. When the body recognizes the foreign virus, it will send in many natural defenses. These natural defenses will cause a fever, cough, inflammation, possible mucous production, and other symptoms. The virus can then spread from an infected person to others through droplets from a cough, sneeze, or contact with another person. That is why it is essential to follow social distancing guidelines, wash your hands regularly, disinfect areas high touch areas, stay home if you are sick, and wear a mask when you need to go out in public.

The next issue that we need to tackle is clarifying the process of the virus replication and the triggering of the important immune responses. To understand this process, we need look at the shape of the coronavirus.

The coronavirus uses its membrane to protect itself from attack. The spike coming from the outside of the membrane is used to connect to the body’s cells and insert replicating data into the cells to continue to make more of the virus.

The body will recognize the infection and send a variety of immune responses to attack the invader. The body has several natural defenses that are activated by Coronavirus. Some of the defenses are toll-like receptors, IL-6, transforming growth factor beta, and many other pro-inflammatory defenses in the body. These defenses will attack the virus by using complicated pathways and mechanisms. These mechanisms will trigger fever, irritation and inflammation in the lungs, and cough which are the main symptoms of the COVID-19 disease.

Toll Like Receptors (TLR) have several downstream effects when they become activated by an agonist like coronavirus. The downstream products include tumor necrosis factor alpha, IL-6, and inflammatory factor nitric oxide (NO). When low dose naltrexone blocks these TLRs, it inhibits the production of these inflammatory cytokines and acts as an immunomodulator through the suppression of innate immune cells.

Low Dose Naltrexone (LDN) has been proven to reduce several pro-inflammatory cytokines in the treatment of other diseases, but due to the recent discovery of this novel virus, we are unsure of the effectiveness of LDN on this virus. In one study where LDN was used to decrease fibromyalgia pain, the treatment group found reduced plasma levels of many inflammatory cytokines that are also released during immune response to COVID-19. These people found 18% reduction in overall symptoms, and the study suggests that that LDN plays a key role in the reduction of several key pro-inflammatory cytokines and symptoms.

The proposed mechanism by which LDN would work to effectively inhibit the coronavirus from causing severe illness is complicated and theorized. This means that the lungs would become less inflamed and have a larger amount of useful surface area in which oxygen could be passed from the lungs into the blood. When considering the mechanism of the Coronavirus, and the inhibitory effects of LDN, we are proposing the use of LDN to promote treatment and prophylaxis of this new infectious virus. Dr. Phil Boyle, an Irish physician has also proposed the immune enhancing effects of LDN for COVID-19 prophylaxis at doses of 3 mg to 4.5 mg nightly. He claims that daily LDN acts to normalize one’s immune system and could perhaps downregulate an overactive immune system in a time of infection.

When considering the possible benefits in contrast with the risks of using LDN, we should consider prior research to evaluate the likelihood of LDN causing severe adverse reactions. A meta-analysis was conducted analyzing the adverse effects of LDN compared to placebo. This study analyzed 11,194 patients and concluded that LDN does not increase the risk of serious adverse effects over placebo. These studies confirm the overall safety profile of oral LDN in the treatment of patients with varying doses and disease groups. This shows that the use of LDN in patients who are at-risk of contracting COVID-19 safe and highly advantageous.

A vaccine for the novel coronavirus is underway but could take months to years to finally hit the market. However, LDN is available now. With limited treatment options for the Novel Coronavirus and the severity of the disease, it is imperative to search for therapeutic options to improve immune health and reduce the spread of COVID-19. Low Dose Naltrexone could be used as an immune boosting agent for those who are at high risk of contracting the COVID-19 disease. Those who should be considered for this Low Dose Naltrexone therapy include the elderly, those who are immunocompromised, and those who have structural lung disease.

The LDN Research Trust released a documentary earlier this month that provides education for patients that are suffering from chronic pain and are dependent on opioid prescription medication.

At the Medicine Center Pharmacy we strive to help educate patients and the medical profession to use an alternative, inexpensive, effective treatment. Watch Pain Specialists talk about using Ultra and Low Dose Naltrexone to treat their patients with Chronic Pain. Our thanks to the speakers in alphabetical order: Asher Goldstein MD, John Kim MD, Neel Mehta MD, Norman Marcus MD, Pradeep Chopra MD, Samyadev Datta MD. This program is not sponsored by any pharmaceutical manufacturer, it is funded by donations to the LDN Research Trust which has been a driving force in providing LDN education and research around the world.

You can learn more about low dose naltrexone at one of our monthly patient education seminars or by contacting the pharmacy. You can register here for the next seminar: Register Here

Recently, NBC News released a report by Dr. Rudi Tanzi, from Massachusetts General Hospital. He has discovered inflammation kills millions of nerve cells, shutting down the area responsible for thinking and memory. Could this be link be a between nervous system inflammation and memory play a factor in Alzheimer’s Disease? If it is true, then treating inflammation could lead to a viable approach to addressing the symptoms of Alzheimer’s. 

This link to neuroinflammation could lead to many new treatment options for patients that suffer from autoimmune diseases like alzheimer’s.

If you would like to learn more about how the mechanism of action of low-dose naltrexone mechanism may affect inflammation in the central nervous system through action on the microglial cells.

“We review the evidence that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone’s better-known activity on opioid receptors.”

— Jarred Younger & Luke Parkitny & David McLain Clin Rheumatol (2014) 33:451–459

Learn more about low dose naltrexone and at our next public seminar.

A recent article published by NPR does a fantastic job of providing legitimacy to a therapy that has been very popular at our compounding pharmacy, low dose naltrexone (LDN). The volume of scientific information is expanding at an enormous pace, and as a result it is challenge to be aware of all the cutting edge therapies, so it is great when the press helps to raise awareness.

The good news is that the research is there, but often takes time to trickle into the mainstream standard of care. This NPR article relays the experience of living with chronic pain from the “other side" of the story, the non-research side, from the point of view of patients.

The article tells the history of LDN, why it's so promising, and the fact that ONLY compounding pharmacies have the ability to prepare this medication in custom dosage forms to meet patients needs.

Patients and providers can quickly read (or listen) to this news story and understand now low dose naltrexone works and it provides legitimacy in coming from a national news source such as NRP

Dr. Bruce Vrooman, an associate professor at Dartmouth's Geisel School of Medicine, was an author of a recent review of low-dose naltrexone research.

The full text of the NPR News story can be found here: In Tiny Doses, An Addiction Medication Moonlights As A Treatment For Chronic Pain

The compounding pharmacists can assist you with your questions about LDN, for more information contact the pharmacy here or call us at 330-339-4466.

Our next public information session on LDN will be October 3rd, 2019 at 6:30pm at the Hampton Inn Meeting Room 1299 West High Avenue New Philadelphia, Ohio 44663.

Do you have experience with LDN you would like to share?