At Nervana Medical, we are excited to offer Low Dose Naltrexone therapy as a potential solution for various health conditions.

What is Low-dose Naltrexone?

Naltrexone was first approved by the FDA in 1984 to treat opioid addiction. Later on, it was discovered that low-dose naltrexone (LDN)---low dose being one-tenth of naltrexone’s usual dose---has anti-inflammatory and immune-modulating effects. LDN appears to be safe with few side effects and no abuse potential. It is also cost-effective because only a small amount is needed. Research on LDN also demonstrated improvements in other diseases.   

Weight Loss:

LDN appears to contribute to weight loss by a number of mechanisms. Studies have shown that LDN may help curb your appetite by reducing the appeal of food. As a result, you start losing your cravings for food. LDN may also aid in increasing the body’s growth hormone levels. Growth hormone helps in weight loss by facilitating the building of lean muscles and burning of fats. Insulin resistance is another issue. It contributes to weight gain, obesity, and a number of other diseases like diabetes, heart attacks, and strokes. LDN helps reduce insulin resistance therefore, not only does it have the potential to help with weight loss, but it may also address other potential diseases!  

The FDA approved weight loss medication naltrexone HCL to treat overweight and obese patients.  Low dose Naltrexone works to suppress your appetite. Combination weight loss medications like these may improve your mood and suppress your sugar and carb cravings to stop overeating once and for all.

Take low dose naltrexone to:

• Regulate appetite: Naltrexone helps normalize your metabolism, matching your appetite to resting energy expenditures.

• Reduce insulin resistance: Naltrexone modulates cellular resistance to insulin, which may lead to weight loss.

• Improve sleep: Lack of sleep has negative effects on your body’s hormonal system, which can lead to weight gain. Naltrexone combats this unhealthy cycle.

• Improve mood: Combination LDN weight loss medications trigger an increase in serotonin and dopamine production, which decreases anxiety and stress and reduces emotional eating.

Depressive Disorders:

Patients with depressive disorders are constantly seeking information regarding various treatment modalities that might help ameliorate symptomatology and improve their mood. The use of low-dose naltrexone (LDN), as based on the plausible hypothesis that depression is associated with central nervous system (CNS) inflammation while LDN can decrease inflammatory responses.

Proposed mechanism of action: LDN, as referenced by naltrexone doses between 1 mg and 5 mg daily, binds non-selectively to all opioid receptors antagonistically but extremely transiently. Short duration of this receptor-ligand interaction leads to a paradoxical downstream increase in endogenous endorphins and enkephalins. These in turn exert regulatory control on a subset of opioid receptors-the zeta, or opioid growth factor receptors-which are mainly expressed on immune cells. When intermittently activated, they inhibit cell proliferation.

Additionally, LDN was found to block toll-like receptor-4 expressed on immune cells in the CNS which are responsible for triggering inflammatory responses. Blockade leads to a shift from production of pro-inflammatory cytokines to anti-inflammatory cytokines.

There is limited studies and literature review regarding LDN and depressive disorders and fibromyalgia but the reviews currently available did demonstrate improvement in depressive and pain score surveys. It is not clear whether the benefit was associated with the reduction in inflammation or an indirect increase in dopamine through the increase in endorphins.

Chronic Pain:

Low-dose naltrexone (LDN) has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn’s disease, multiple sclerosis, and complex regional pain syndrome. There is 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 doses of naltrexone and appear to be entirely independent from naltrexone’s better-known activity on opioid receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated. Despite the initial promise of efficacy, the use of LDN for chronic disorders is still highly experimental. Published trials have low sample sizes, and few replications have been performed. We cover the typical usage of LDN in clinical trials, caveats to using the medication, and recommendations for future research and clinical work. LDN may represent one of the first glial cell modulators to be used for the management of chronic pain disorders.

The totality of the basic and clinical research to date suggests that LDN is a promising treatment approach for chronic pain conditions thought to involve inflammatory processes. The clinical data supporting its use are very preliminary, and more research is needed before the treatment approach can be widely recommended. Critical parameters such as dosing still need to be refined. LDN may emerge as the first of many glial cell modulators that could be used to treat chronic conditions, with more specifically targeted medications developed in the future. As conventional anti-inflammatories have poor blood brain-barrier permeability, we expect centrally active immune modulators to be an area of interest in the future.

Naltrexone belongs to a class of drugs known as opioid antagonists. Naltrexone blocks opiate drugs from binding to the opioid receptors, which can result in increased endorphin and enkephalin release. Therefore, this results in reduced signaling and release of inflammatory substances, nerve cell inflammation and autoimmune mediators.

When taken at bedtime, the short acting LDN binds to the receptors which leads to a brief blockade of opioid receptors between 2 am and 4 am. This blockade is believed to up-regulate vital elements of the immune system by causing an increase in endorphin and enkephalin production.

Chronic Fatigue:

Naltrexone is used as an off-label treatment in low doses for several chronic immune-modulated disorders in many countries. Although only small-scale clinical trials have been performed, these suggest efficacy in several diseases including Crohn’s disease, fibromyalgia and Gulf War Illness. Despite numerous internet reports of response to low-dose naltrexone (LDN), no clinical trials exist in people with chronic fatigue syndrome. This condition is characterized by chronic profound fatigue, post exertional malaise, pain and autonomic and neurocognitive disturbances. This series of three case reports compiled by people with long-term ill-health due to chronic fatigue syndrome shows the range of responses they observed when taking LDN, from life changing to a reduction in some symptoms only. Treatment doses ranged from 4 to 12mg. Clinical trials may be warranted to explore the potential use of naltrexone in people with these debilitating illnesses which currently have no licensed treatments available.

The mechanism of action for naltrexone at low dose in this disease group is unknown. It is possibly due to rebound of endorphins following short-term suppression or to direct action suppressing inflammation induced by microglia. There have been no formal dosing studies of naltrexone at low dose in any disorder. Therefore, although the dose of 3–4.5 mg is established in clinical practice, some practitioners use 9 mg (Klimas, personal communication, 2017) or higher in chronic fatigue syndrome. Causality and dosing need further studies..

Overall Conclusion:

LDN brings about potential benefits regarding its anti-inflammatory effects, the immune system and its involvement in chronic fatigue, chronic pain, mood disorders,including depression and weight loss. More robust studies are needed however, as naltrexone is out of patent, funding for such studies is problematic, despite the drug itself being relatively cheap. Most large studies are funded by large pharmaceutical companies, and there is no incentive for them to continue research of drugs once they are off-patent. 

LDN does appear to have some benefit in certain patients and Nervana has clinically witnessed this in some of their own patients. We find this to be intriguing; and its side effect/safety profile is quite promising. 

Patient Drug Information

• We advise taking LDN in the evening before bed but not too late into the night-

• Low Dose Naltrexone (LDN) refers to prescribed doses below 10mg per day (4.5mg/daily is most common)

• At low doses of 10mg per day or less, LDN is shown to reduce chronic inflammation, autoimmunity, obesity, fatigue, and chronic pain

• Used successfully for over 40 years with an outstanding safety record

Most Common LDN Side Effects

• Vivid dreams

• Mild anxiety

• Insomnia

• Headache

During the first three to five days of taking LDN, you may experience mild to moderate levels of the above side effects. Side effects typically diminish on their own by day five. If you experience side effects, you may reduce them by reducing your dose by half (typical dosing is 4.5 mg, therefore ½ a tab would be 2.25 mg) for the first two weeks with a gradual increase to the 4.5mg dose.

Note: Please stop taking any dosage of Naltrexone a minimum of 48 hours before any surgical procedure or medical diagnostic requiring sedation, such as surgery or a colonoscopy. If you are not sure if you need to stop Naltrexone, please ask your doctor ordering the test or procedure. Additionally, Naltrexone cannot be taken in conjunction with opioids(narcotics)/painkillers. If you need to stop taking Naltrexone for a surgery, and accompanying painkillers are prescribed, you may resume LDN only 48 hours after you take your last painkiller.

Possible Drug Interactions: Tell your doctor and pharmacist if you are allergic to naltrexone, any of the ingredients of LDN tablets, as well as any other medications. Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking. Be sure to mention any of the following: amiloride (Midamor); angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin, in Lotrel), captopril, enalapril (Vasotec, in Vaseretic), fosinopril, lisinopril (in Zestoretic), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), and trandolapril (Mavik); beta-blockers such as atenolol (Tenormin), labetalol (Trandate), metoprolol (Lopressor, Toprol XL), nadolol (Corgard, in Corzide), and propranolol (Hemangeol, Inderal, InnoPran); calcium channel blockers such as amlodipine (Norvasc), diltiazem (Cardizem, Cartia, Diltzac, others), felodipine, isradipine, nicardipine (Cardene), nifedipine (Adalat, Afeditab CR, Procardia), nimodipine (Nymalize), nisoldipine (Sular), and verapamil (Calan, Covera, Verelan, in Tarka); cimetidine (Tagamet); digoxin (Lanoxin); diuretics (‘water pills’); furosemide (Lasix); hormone replacement therapy; insulin or other medications for diabetes; isoniazid (Laniazid, in Rifamate, in Rifater); medications for asthma and colds; medications for mental illness and nausea; medications for thyroid disease; morphine (MS Contin, others); niacin; oral contraceptives (‘birth control pills’); oral steroids such as dexamethasone, methylprednisolone (Medrol), and prednisone (Rayos); phenytoin (Dilantin, Phenytek); procainamide; quinidine (in Nuedexta); quinine; ranitidine (Zantac); triamterene (Dyrenium, in Maxzide, others); trimethoprim (Primsol); or vancomycin (Vancocin). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.

Note: The above statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

Individualized Treatment: Our experienced medical professionals will work closely with you to develop a personalized LDN treatment plan tailored to your specific needs and health goals. We take into account your unique medical history, current health condition, and any other medications you may be taking.

Holistic Approach: we believe in a holistic approach to healthcare. LDN therapy can be an integral part of a comprehensive treatment plan that may include lifestyle modifications, dietary adjustments, and other therapies to enhance your overall well-being.

Ongoing Support: Our dedicated team is committed to supporting you throughout your LDN journey. We provide regular follow-up appointments to monitor your progress, address any concerns or questions, and make adjustments to your treatment plan as needed.

Evidence-Based Medicine: LDN has gained attention in recent years, and numerous studies have shown its potential benefits in various health conditions. We stay up to date with the latest research and incorporate evidence-based practices into our treatment protocols.

*We often add low dose naltrexone therapy to a variety of our programs at no additional cost; such as our weight loss program!

Resources:

Bolton MJ, Chapman BP, Van Marwijk HLow-dose naltrexone as a treatment for chronic fatigue syndromeBMJ Case Reports CP 2020;13:e232502.

Felger JC. Role of Inflammation in Depression and Treatment Implications. Handb Exp Pharmacol. 2019;250:255-286. doi: 10.1007/164_2018_166. PMID: 30368652.

Kulak-Bejda A, Bejda G, Waszkiewicz N. Safety and efficacy of naltrexone for weight loss in adult patients - a systematic review. Arch Med Sci. 2020 Sep 10;17(4):940-953. doi: 10.5114/aoms.2020.96908. PMID: 34336024; PMCID: PMC8314402.

Patten DK, Schultz BG, Berlau DJ. The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn's Disease, and Other Chronic Pain Disorders. Pharmacotherapy. 2018 Mar;38(3):382-389. doi: 10.1002/phar.2086. Epub 2018 Feb 23. PMID: 29377216.

Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. 2014 Apr;33(4):451-9. doi: 10.1007/s10067-014-2517-2. Epub 2014 Feb 15. PMID: 24526250; PMCID: PMC3962576.

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