Low-Dose Naltrexone (LDN)

Potential benefits may include but are not limited to:

1. Chronic Pain Conditions

• Fibromyalgia
• Complex Regional Pain Syndrome (CRPS)
• Chronic back pain / neuropathic pain

2. Autoimmune Disorders

• Hashimoto’s thyroiditis
• Rheumatoid arthritis
• Lupus (SLE)
• Multiple sclerosis (MS)

3. Neurological Conditions

• Multiple sclerosis (MS)
• Parkinson’s disease
• ALS (Amyotrophic Lateral Sclerosis)

4. Inflammatory Bowel Diseases

• Crohn’s disease
• Ulcerative colitis

5. Mental Health & Mood Disorders

• Depression (especially treatment-resistant)
• PTSD
• Autism

6. Weight Loss

Potential Side Effects

• Vivid dreams, usually within the first few weeks of therapy
• Fatigue
• Insomnia
• Flu-like symptoms
• Decreased appetite
• Anxiety
• Headache
• Dizziness

Warnings

• Do not use LDN treatment in patients who are receiving opioid analgesics, are dependent on opioids, and those individuals who have failed the naloxone challenge test or who have a positive urine screen for opioids.
• Patients should stop taking LDN 48 hours prior to surgery using anesthesia as the LDN could affect the efficacy.

Naltrexone is a reversible, competitive antagonist primarily opposing β-endorphin action at the μ-opioid receptor. At standard doses, it blocks these receptors to treat substance use disorders. However, when used at much lower doses, the transient receptor blockade triggers a compensatory release of natural endorphins. This boost in endogenous endorphins has a cascade of pharmacological effects that underpin the versatility of LDN:

• Modulatates the immune response
• Antagonizes Toll-Like-Receptors 4 (TLR4): suppressing cytokine modulated immune reactivity
• Antagonizes TLR4-mediated production of NF-kB: reducing inflammation, potentially down regulating oncogenes
• Reverses hyperinsulinemia mediated Sirtuin1 repression, decreasing inflammatory mediators in macrophages, and reinstating insulin sensitivity
• Reins in microglia cell hyperactivity, affording neuroprotective effects and alleviation of centralized pain syndromes

The antagonism of the μ-opioid receptor also prevents autoinhibition of proopiomelanocortic (POMC) neurons. POMC cells produce α-melanocyte stimulating hormone (α-MSH), an MC4R agonist. Stimulation of the MC4R by α-MSH produces an anorexic effect, increasing energy expenditure and decreasing appetite in both animals and humans. 

Q. How do LDN Flex-Dose Tablets Work?

A. The LDN flex-dose tablet is designed for easy and precise dosing:

• The tablet is scored into quarters (1⁄4). It does not require a pill cutter. Place the tablet on a solid surface and firmly press down on the middle of the tablet, scored side up, and it will easily break into quarters.

Q. What are the ingredients in LDN Flex-Dose Tablets?

A. Active ingredient: naltrexone

• Prebiotic filler
• That’s it! They are suitable for vegetarians and vegans. The tablets do not contain common allergenic ingredients like lactose, magnesium stearate, artificial colors, or preservatives.

Q. What are the advantages of Flex-Dose Tablets Over Capsules

A. The flex-dose tablet allows patients to titrate up their dose with just one prescription, instead of needing multiple Prescriptions for different strengths. Cost savings with only one prescription needed. Providers only need to write for one prescription versus multiple strengths.

Q. What do you advise in case of a missed dose?

A. There is no need to make up a missed dose of LDN.

Q. Should LDN be cycled?

A. There is no need to cycle LDN. LDN has a short half-life of 4 to 6 hours so taking it once a day would afford a significant drug free period.

Q. May LDN be stopped abruptly?

A. There is no harm in stopping LDN abruptly and stopping it does not cause withdrawal effects. It does not need to be tapered down.

Q. How should LDN be titrated?

A. LDN is titrated to minimize side effects like vivid dreams which typically present in the early stages of therapy. Most patients can start LDN at a 1.125 mg dose which is 1⁄4 of the standard 4.5 mg dose and slowly work up by adding 1⁄4 tablet each week. Most patients will settle on a maintenance dose of about 4.5mg for autoimmune conditions.

Q. What is the best time to take LDN?

A. LDN is typically taken at night to better align circadian patterns when endorphin levels are naturally higher.

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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.

de Carvalho JF, Skare T. Low-Dose Naltrexone in Rheumatological Diseases. Mediterr J Rheumatol. 2023 Mar 31;34(1):1-6. doi: 10.31138/mjr.34.1.1.PMID: 37223594; PMCID: PMC10201089.

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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;33(4):451-459.

Smith JP, Field D, Bingaman SI, Evans R, Mauger DT. Safety and tolerability of low-dose naltrexone therapy in children with moderate to severe Crohn’s disease: a pilot study. J Clin Gastroenterol. 2013;47(4):339-345. doi:10.1097/MCG.0b013e3182702f2b