Low-Dose Naltrexone (LDN): A Surprisingly Versatile Therapy for Pain, Autoimmunity, Mood, and Chronic Fatigue

Low-Dose Naltrexone (LDN) has rapidly become one of the most talked-about emerging therapies in integrative medicine. Originally developed as a 50 mg medication for opioid and alcohol dependence, naltrexone behaves very differently at low doses (typically 1–6 mg). At these lower levels, LDN exhibits unique anti-inflammatory, immunomodulatory, and neuroregulatory effects that can benefit a wide range of chronic conditions—including autoimmune diseases, chronic pain syndromes, pruritic skin disorders, depression, and chronic fatigue.

Because LDN is not commercially produced in low-dose form, many clinicians rely on compounding pharmacies. However, a clever and inexpensive preparation method—validated in a published clinical pearl—allows patients to compound LDN safely at home using FDA-approved 50 mg tablets. This makes LDN accessible, affordable, and easy to dose.

What LDN Is and How It Works

At low doses, LDN temporarily blocks opioid receptors for just a few hours. This short blockade creates a “rebound” effect, leading to:

• Increased production of endorphins, the body’s natural pain-modulating chemicals
• Modulation of microglial activity, reducing central inflammation
• Improved regulation of the immune system
• Potential normalization of inflammatory signaling pathways involved in mood disorders and fatigue

This mechanism explains why LDN is used across such diverse clinical conditions.

Conditions That May Benefit From LDN

Research, clinical experience, and patient-reported outcomes support the use of LDN for:

Autoimmune and Inflammatory Conditions

• Hashimoto’s thyroiditis
• Crohn’s disease & ulcerative colitis
• Psoriasis, lichen planopilaris, Hailey-Hailey disease
• Rheumatoid arthritis and other inflammatory arthritides

Chronic Pain & Neurologic Conditions

• Fibromyalgia
• Neuropathic pain
• Complex regional pain syndrome
• Migraine adjunctive therapy

Chronic Pruritus & Dermatologic Disorders

• Chronic itching disorders
• Pruritic inflammatory dermatoses

Mood Conditions (Adjunctive Therapy)

• Depression (via microglial modulation, anti-inflammatory effects, and endorphin upregulation)

Energy & Motivation Disorders

• Chronic fatigue (improves inflammatory signaling and neural energy regulation)

LDN is not a cure, but many patients report significant symptom reduction within 4–12 weeks of consistent dosing.

How to Prepare LDN at Home 

A method published in the Journal of the American Academy of Dermatology describes a stable, inexpensive way to compound LDN using commercially available tablets mixed with orange juice. This technique significantly improves taste, reduces grittiness, and maintains stability for up to 90 days.

bronfenbrener2021

Ingredients

• Ten 50 mg naltrexone tablets (total of 500 mg)
• 500 mL (16.9 oz) of orange juice or preferred juice
• Clean storage container with lid
• Dosing syringe or dropper

Instructions

1. Crush ten 50 mg naltrexone tablets into fine powder.
2. Mix thoroughly into 500 mL of juice.
3. Shake vigorously.
4. Refrigerate after preparation.
5. Shake before each use to evenly distribute the medication.

This creates a 1 mg/mL LDN solution, allowing simple and precise titration.

How to Dose LDN: A Practical Titration Strategy

Week 1:

1 mg nightly (1 mL of solution)

Week 2:

2 mg nightly

Week 3:

3 mg nightly

Week 4:

Increase only if needed:

• 4–4.5 mg nightly (most common therapeutic dose)

Alternative Options

• Ultra-slow titration: Increase by 0.5 mg every 1–2 weeks
• Low-dose responders: Some stabilize at 1–3 mg
• Higher-dose trials: Rarely up to 5–6 mg if symptoms persist

Timing

• Most take LDN at night, as endorphin rebound appears to be beneficial the following day.
• If insomnia or vivid dreams occur, shift dosing to morning.

What to Expect

Many patients notice benefits such as reduced inflammation, improved pain tolerance, better mood stability, and increased energy. Improvements often appear within 4–12 weeks, although autoimmune conditions may require a longer trial.

Side effects are typically mild and transient:

• Vivid dreams
• Initial insomnia
• Headache
• Mild nausea
• Temporary irritability or anxiety

LDN must not be used with opioid medications, as even low doses can precipitate withdrawal.

Why LDN Is Becoming So Popular

LDN is:

• Safe
• Cost-effective
• Well-tolerated
• Supported by growing clinical evidence
• Useful across many chronic, difficult-to-treat conditions

Patients appreciate a therapy that works at the level of immune regulation, inflammation, and central nervous system balance—especially when standard therapies have failed.

References

1. Bronfenbrener, R. Inexpensive compounding of low dose naltrexone (LDN) with orange juice. Journal of the American Academy of Dermatology. 2019. (Manuscript accepted; describes 1 mg/mL preparation and 90-day stability). bronfenbrener2021
2. Fawcett JP, Morgan NC, Woods DJ. Formulation and Stability of Naltrexone Oral Liquid for Rapid Withdrawal from Methadone. Ann Pharmacother. 1997;31(11):1291–1295.
3. GoodRx. Naltrexone Prices and Naltrexone Coupons. Available at: https://www.goodrx.com/naltrexone (Pricing referenced in Bronfenbrener 2019).
4. 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.
5. Toljan K, Vrooman B. Low-dose naltrexone (LDN)—Review of therapeutic utilization. Med Sci. 2018;6(4):82.
6. Patten DK, Schultz BG, Berlau DJ. The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation. Front Pharmacol. 2018;9:963.
7. Raison CL, Miller AH. Role of inflammation in depression: implications for psychosomatic medicine. Psychosom Med. 2011;73(2):113–122. (Mechanistic support for LDN in depression.)
8. Montoya JG, et al. Inflammatory cytokines in chronic fatigue syndrome. PNAS. 2017;114(34):E7150–E7158. (Supports LDN’s theoretical role in chronic fatigue through immune modulation.)