A leading medical doctor specializing in diseases of the small intestine, stomach, esophagus, and colon, claims a drug formerly used to treat opioid and alcohol dependence, has become an intriguing choice for managing several gastrointestinal disorders.

In a recent article entitled “Low-Dose Naltrexone in Gastroenterology: A Bonafide ‘Wonder Drug,” Dr. Leonard Weinstock, M.D., a St. Louis-based gastroenterologist and researcher, asserts that naltrexone —  originally used at a dosage of 200 mg daily to treat opioid users and alcoholics — has been found successful in treating intestinal issues when used at just one-tenth of the full dosage.

In my own private practice and here at PROVOKE Health, we have a long history of using low-dose naltrexone (aka, LDN) to treat immune system dysfunction. In fact, a growing body of evidence suggests that LDN is effective in treating conditions such as inflammatory bowel disease (IBD), Crohn’s disease, ulcerative colitis, and irritable bowel syndrome (IBS). It has even shown beneficial implications in several other areas, such as restless legs syndrome (RLS), psoriasis, weight management, and Long COVID, which is characterized by symptoms lasting at least three months after an initial infection.

So what is naltrexone and what do we here at PROVOKE Health think about the potential role of this medication in the battle to overcome chronic illness? Well, that depends. As a functional medicine and integrative healthcare practice committed to motivating patients by providing the healthcare, guidance, and support they need, we believe in providing personalized treatment that addresses the unique health and fitness needs of each patient. We do not promote any single treatment or protocol as a miracle cure or a one-size-fits-all solution.

However, in the context of our clinical practice, we have found naltrexone to be an effective tool in the treatment of a wide range of immune system dysfunctions, such as the following:

• Long COVID
• Psoriasis
• Toxic mold
• Fibromyalgia
• Chronic fatigue syndrome (CFS)
• Rheumatoid arthritis
• Crohn’s disease
• Hashimoto’s thyroiditis
• Scleroderma
• Lupus
• Sjogren’s syndrome
• Multiple sclerosis
• Ulcerative colitis
• Celiac disease

In this post, I share how naltrexone can aid in preventing common issues that are associated with the use of opioids — namely relapse — as well as naltrexone potential benefits, at much lower doses, for temporarily restoring healthy immune function. This can be especially useful while the root causes of immune system dysfunction are being identified and addressed.

Naltrexone in the Treatment of Opioid and Alcohol Use Disorders

Classified as an opioid antagonist, naltrexone has been approved for the treatment of opioid and alcohol addiction since 1984. Opioids encompass a range of substances, including the illegal drug heroin, synthetic opioids such as fentanyl, and prescription painkillers such as oxycodone (OxyContin), hydrocodone (Vicodin), codeine, morphine, and others.

These drugs work by binding to opioid receptors in the body, providing pain relief, slowing down breathing, and inducing a calming effect. However, as you already know, opioids are highly addictive. When taken at the full dose of 200 mg daily (typically four doses of 50 mg), naltrexone blocks opioid receptors to prevent the effects of opiates and reduce cravings.

Think of opioid receptors as locks and opioid molecules as keys. Naltrexone acts as a key that fits into all the locks, so the opioid molecules cannot insert their keys. While on naltrexone, someone using opioids won’t experience the euphoria or intense pleasure because the opioid keys cannot unlock the receptors. As a result, opioids become much less appealing to the user.

Naltrexone isn’t used early in treatment, because it can cause withdrawal symptoms. Other medications may be used during the seven- to 10-day withdrawal period to help reduce cravings. Following detox, naltrexone is prescribed in doses of 50 to 100 mg to suppress the euphoria and other pleasurable sensations of opioids. Naltrexone works similarly to prevent relapse in alcoholics by removing the “reward” for drinking.

The Endorphin-Immune System Connection

Endorphins are natural opiates produced in the body that regulate many biological functions, including immune function. We know that endorphin levels are typically lower in people with autoimmune diseases, and that LDN increases endorphin levels and reduces inflammation, which is common in autoimmune disorders (when the immune system attacks healthy cells in the body).

At PROVOKE Health, we may prescribe naltrexone for patients experiencing immune dysfunction. Depending on the situation, we may start with naltrexone to alleviate symptoms or introduce it later if progress with other treatments has stalled. However, we always combine naltrexone with supportive and motivating care to tackle the underlying causes, such as heavy metal toxicity, mold exposure, hormone imbalances, infections, or other conditions contributing to the autoimmune disorder.

Naltrexone appears to be more effective for certain patients. The patients who tend to benefit the most report symptoms such as muscle aches, joint pains, restless sleep, mold exposure, and Hashimoto’s thyroiditis. For those who do experience improvement, the positive effects can be quite significant.

How Naltrexone Works

Numerous biological systems in the human body contain opiate receptors, which, together with natural opiates (endorphins and other chemical messengers), regulate a wide range of biological functions, including the immune response. Additionally, a class of proteins called toll-like receptors (TLRs), which are part of the immune system, can recognize and be activated by invading microbes as well as endogenous signaling molecules such as endorphins.

LDN functions as an antagonist in both of these areas, giving it the ability to modify the biological functions of these two receptor groups by suppressing undesirable immune reactions and stimulating immune activity that is suppressed by disease.

LDN’s ability to both suppress and stimulate immune activity is largely due to the chiral nature of the naltrexone molecule and the different effects of its Levo and Dextro isomers.

The term chiral refers to the asymmetrical structure of the two molecules produced when the medication is synthesized. The two molecules (isomers) are identical in chemical composition but differ in shape, with half being left-handed (Levo) and half being right-handed (Dextro). This difference in shape enables them to interact with different groups of receptors in the body.

The Levo isomer interacts with the commonly understood opiate (endorphin) receptors group and the Dextro isomer interacts with the TLR group, as follows:

Levo Naltrexone

• Blocks (antagonizes) opiate receptors for several hours
• Increases natural production of anti-inflammatory endorphins
• Upregulates opiate receptors
• Has direct effect on some cell proliferation rates

Dextro Naltrexone

• Blocks (antagonizes) some TLR receptors
• Reduces production of pro-inflammatory cytokines
• Suppresses cascade inflammation
• Produces central and system effects as TLR receptors are present on microglial cells, mast cells, and macrophages

Specifically, when used in the treatment of autoimmune disorders, LDN has the following effects:

• Acts as a glial modulator (glial cells are specialized brain cells that protect neurons, provide nutrition, and help to repair inflammation within the brain). Overactive glial cells can lead to increased brain inflammation and ultimately degeneration and dysfunction of brain cells contributing to a variety of brain disorders including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Parkinson’s disease, pain syndromes, Alzheimer’s disease, encephalitis, glioblastoma, and multiple sclerosis (MS).
• Blocks endorphin receptors for about four to six hours, initiating increased production of endogenous opioids and opioid receptors.
• Blocks the opioid growth factor (OGF) receptor, resulting in increased production of endogenous OGF (also known as Met 5-Enkephalin) and OGF receptors, thereby increasing signaling. OGF is a naturally occurring peptide in the body that plays a crucial role in regulating the immune system, managing pain, and promoting overall well-being. As the neuropeptide Met 5-Enkephalin, it influences the central and peripheral nervous system and impacts other targets throughout the body, resulting in downstream effects on immune modulation.
• LDN has become a widespread therapeutic used to safely inhibit inflammatory processes by inhibiting proliferation of T-lymphocytes and B-lymphocytes following a peripheral autoimmune trigger, and to inhibit T-cell infiltration into the central nervous system (CNS). The end result is reduced flare up of self-attack by the immune system. Without a reduction of B-lymphocyte and T-cell infiltration, the autoimmune response can persist, uncontrolled, attacking various tissue types, which may include (most commonly) cartilage/joints, thyroid, gastrointestinal mucosal tissue, neuronal tissue, and skin.

Understanding the Factors Driving the Increased Prevalence of Autoimmunity

The prevalence of autoimmunity is increasing. Consider the following statistics from the National Health Council:

• Among test subjects, the prevalence of antinuclear antibodies (ANA), the most common biomarker of autoimmunity, nearly doubled between 1988 and 2012. In the same study, the prevalence of ANA among adolescents aged 12 to 19 years old increased nearly 300 percent.
• The prevalence of type 1 diabetes has nearly doubled in the past 40 years in the adult population.
• Over the past 30 years, the prevalence of celiac disease in the U.S. has increased five-fold, doubling approximately every 15 years.
• The estimated number of people with multiple sclerosis worldwide increased 30 percent from 2013 to 2022.
• Between 2006 to 2021, the prevalence of inflammatory bowel disease (IBD) increased 46 percent.

There is no single cause. There are many. Due to the many causes of autoimmunity, patients and doctors can be easily frustrated and confused on the subject, as the trigger for and management of the condition can be elusive.

Why has autoimmunity been increasing? Plenty of research and clearly stated hypotheses have been articulated to begin to answer this question. Here are a few of the main explanations:

• Hygiene hypothesis: This is the notion that by living in a cleaner environment, the immune system lacks the exposure to infectious agents (bacteria, viruses, fungi, and parasites) it needs to develop properly. Generally, growing up in a more rural environment with increased exposure to germs is better for immune system development than growing up in a comparatively sterile urban environment with access to clean food and water, antibacterial soaps and detergents, and proper hygiene.
• Altered food supply/diet: This is the notion that the modern food supply and diet negatively impact the immune system. Compared to the more natural whole foods that early humans consumed, many of us now consume a diet high in sugar and processed foods. By some estimates, 70 percent or more of the immune system is located in the gut. Diet plays a key role in gut health, protecting the lining of the gut, which serves as a protective barrier, and feeding the community of microorganisms that reside in the gut. Unhealthy foods can damage the lining of the gut, causing substances that are supposed to remain in the digestive tract to leak out into the bloodstream and trigger an immune response. Unhealthy foods can also cause imbalances in the community of microorganisms, allowing unhealthy bacteria, viruses, or fungi (yeast) to grow unchecked. Either of these conditions (damaged gut lining or microbial imbalances) can cause or contribute to the development of autoimmunity.
• Increases in certain infections: The flip side of the hygiene hypothesis is that certain infections can increase a person’s susceptibility to an autoimmune condition, such as rheumatoid arthritis, MS, IBD, and thyroid disease. This happens when bacteria have antigens that trigger a massive immune response and trick the body into attacking itself after the bacteria is gone.
• Increased exposure to environmental triggers: Environmental triggers includes mold, fungi, and bacteria in homes, schools, and workplaces. Exposure to these triggers can all lead to alterations in immune function.
• Increased exposure to emerging viruses such as COVID 19 and associated vaccines: Evidence suggests a connection between COVID-19 (and vaccines used to protect against it) and an increase in autoimmunity. No surprise here, as novel and virulent infections and vaccines can wreak havoc on an immune system that has never been exposed to anything like these highly engineered infectious agents and vaccines. Susceptibility is further exacerbated by vitamin deficiencies and unhealthy lifestyle factors that are common in our chronically ill society.

How to Take Low Dose Naltrexone (LDN)

The Food & Drug Administration has not approved Low-Dose Naltrexone for autoimmune conditions, so it is not available at standard pharmacies in the United States. If we determine that LDN is appropriate for your PROVOKE plan of care, we will use a compounding pharmacy to prepare your prescription.

Once prescribed, LDN is best taken at night, around 9 p.m. This timing allows the medication to bind to your opioid receptors before your endorphin levels peak between 3 a.m. and 4 a.m. By taking LDN at 9 p.m., your brain is tricked into thinking that endorphin levels are too low, prompting the production of more endorphins. This increase in endorphins helps to regulate immune system function.

How PROVOKE Health Addresses the Root Causes of Autoimmunity

At PROVOKE Health, we prescribe LDN as an adjunct component in a broader plan of care focused on restoring healthy immune function. LDN provides short-term relief, while we work closely with the patient to implement a long-term solution that addresses the root cause(s) of the patient’s immune dysfunction. By addressing the root cause(s), we seek to restore health instead of merely suppressing symptoms.

Our approach to restoring healthy immune function lives within our five-phase protocol to care:

• Phase 1 — Assessment by Comprehensive Evaluation: Your journey begins with an in-depth new-patient intake process. Unlike many healthcare practices, our new-patient forms aren’t photocopied. They don’t skimp on space to provide detailed answers to the questions we ask, and they are designed from the ground up by our doctors and healthcare team members to ensure we’re asking the right questions at the right time. (For existing patients, we’re highly intentional about updating your patient questionnaire responses throughout your healthcare journey.

• Phase 2 — Repair Through Personalized Plans of Care: Once we have a detailed understanding of your health, we create a customized plan of care that is tailored to your specific situation. This plan is based on our integrative approach to care, which combines the best of functional medicine and conventional healthcare (also known as allopathic medicine) with complementary therapies. By considering and applying the best of both approaches, we save you time and money. Our plans of care often address diet and nutrition and stress management, and may include hormone and cortisol balancing, and IV and peptide therapies.

• Phase 3 — Motivate with Ongoing Support: This phase emphasizes empowering you with the tools and knowledge needed to maintain and optimize your health. It includes continuous support, education, and preventive care to ensure lasting health improvements and make you feel your best.

• Phase 4 — Adjust by Tailored Modification: In this phase, fueled by your well-timed follow-up appointments, we review your progress and make necessary adjustments to your personalized plan of care. These follow-up appointments and re-evaluations help us ensure that your health plan remains effective and responsive to your evolving needs. Adjustments might include reassessing health markers, tweaking nutrition plans, and modifying additional treatment protocols.

• Phase 5 — Sustain with Optimization: After we have addressed your immediate health concerns and repaired the foundations of your health, we focus on sustaining and optimizing your overall well-being. This phase may include new or enhanced modalities such as emerging peptides, hormone balancing and replacement therapies, and medical-grade vitamin and dietary supplements, just to name a few.

At PROVOKE Health, our doctors, healthcare providers, and staff are committed to being your partners in health, providing a supportive and empathetic environment where your unique health and fitness needs are met with personalized care. Our approach is designed to motivate and empower you, thereby helping you achieve a state of health that enables you to live your life to the fullest.

Don’t just mask your symptoms with temporary relief, which can let the underlying issues worsen over time. At PROVOKE Health, we focus on identifying and addressing the root causes of your ailments. We work closely with you to restore and maintain your optimal health.

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Disclaimer: The information in this blog post  about Low-Dose Naltrexone (LDN) is provided for general informational purposes only and may not reflect current medical thinking or practices. No information contained in this blog post should be construed as medical advice from Dr. Matthew Lewis, Functional Healthcare Group, PLLC, or PROVOKE Health, nor is this blog post intended to be a substitute for medical counsel on any subject matter. No reader of this blog post should act or refrain from acting on the basis of any information included in, or accessible through, this blog post without seeking the appropriate medical advice on the particular facts and circumstances at issue from a licensed medical professional in the recipient’s state, country or other appropriate licensing jurisdiction.

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About the Author: Dr. Matt Lewis, D.C., DACBN, CFMP^® specializes in diagnosing and treating the underlying causes of the symptoms related to chronic and unexplained illness through nutrition, lifestyle, chiropractic, and other natural approaches to whole-health healing at PROVOKE Health in Tampa, Fla. Dr. Lewis has 20 years of experience practicing nutritional and holistic medicine. He earned his B.S. in Biology from Shenandoah University, his Doctorate in Chiropractic from Life University, his Diplomate status in Clinical Nutrition from the American Clinical Board of Nutrition, his CFMP from Functional Medicine University, and his certification as a Digestive Health Specialist (DHS) through the Food Enzyme Institute. Dr. Lewis’ passion for health and wellness stems from his own personal experience. With a family history of autoimmune conditions and diabetes, and his own lab tests showing his genetic susceptibility to Hashimoto’s thyroiditis (autoimmune thyroid), Dr. Lewis has learned how to restore his own health and vigor to prevent the onset of these and other illnesses and live an incredibly active life. Through this process, he acquired a deeper understanding of health and wellness, which he now offers his patients in Tampa and elsewhere.