The Interplay between Low Dose Naltrexone and Hashimoto’s Thyroiditis

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Hypothyroidism, Low Dose Naltrexone, Apr 17, 2025

Exploring the evidence and clinical relevance of LDN in autoimmune thyroid disease

Hashimoto’s thyroiditis is the most common cause of hypothyroidism in the developed world. As an autoimmune condition, it is driven by chronic inflammation, progressive thyroid tissue destruction, and elevated anti-thyroid antibodies — primarily anti-thyroid peroxidase (TPOAb) and anti-thyroglobulin (TgAb).

While thyroid hormone replacement (typically levothyroxine) remains the standard treatment, many patients continue to experience symptoms like fatigue, weight gain, brain fog, and mood changes — even when lab values appear “normal.” This discrepancy has led practitioners to explore adjunctive therapies that go beyond hormone replacement and target immune dysfunction.

One such emerging therapy is Low Dose Naltrexone (LDN).

What Is Low Dose Naltrexone?

LDN refers to the off-label use of naltrexone hydrochloride at doses between 0.5 mg and 4.5 mg daily, far below the standard 50 mg used to treat opioid or alcohol dependence.

At low doses, LDN doesn’t act primarily as an opioid blocker. Instead, it:

Briefly blocks opioid receptors, triggering a rebound increase in the body’s endorphins and met-enkephalins
Modulates immune function and inflammation
Enhances tissue repair and neuro-immune signaling^1,2

How Hashimoto’s Affects the Immune System

Hashimoto’s thyroiditis involves an overactive immune response that targets the thyroid gland. Hallmarks include:

Th1-dominant immune activity
Elevated inflammatory cytokines (e.g., IL-6, TNF-α)
High levels of TPOAb and TgAb

LDN appears to shift the Th1/Th2 balance, dampen inflammatory signaling, and support regulatory T cell (Treg) function. These immunological effects position it as a compelling therapy for autoimmune diseases like Hashimoto’s.^3,4

What Does the Research Say?

While large randomized controlled trials (RCTs) are still needed, emerging data and clinical reports suggest meaningful benefits of LDN for Hashimoto’s patients:

1. Symptom Relief

LDN may alleviate persistent symptoms including:

Fatigue
Brain fog
Depression
Chronic pain
Mood swings⁵

2. Autoantibody Reduction

Case reports and observational data show LDN may lower TPOAb and TgAb titers by up to 30–50% over 3–6 months.

“We’ve seen patients whose antibody levels dropped significantly after starting LDN,”

notes Dr. Amy Nett, MD.

3. Improved Thyroid Function

In some patients, LDN has correlated with lower TSH and stabilized T3/T4 levels — potentially reducing the need for higher hormone doses.⁷

How Does LDN Work in Autoimmune Thyroiditis?

Mechanisms that may explain LDN’s impact on Hashimoto’s include:

Increased endorphin production – modulates immune responses and reduces inflammation
Reduction of cytokines – including IL-6, TNF-α
Treg/Th17 balance correction – restoring immune tolerance
Improved gut-immune axis – may reduce leaky gut and immune triggers
HPA axis support – by improving mood and sleep

Dosing & Formulation

LDN is typically started at 0.5–1.5 mg at bedtime, titrated to 3.0–4.5 mg as tolerated. Some patients may benefit from microdoses as low as 0.1–0.25 mg.

Preferred timing: Bedtime dosing supports endorphin rhythm
Forms available: Capsules, sublingual, or liquid (compounded)
Alternate dosing: Split doses (e.g., 2 mg twice daily) can be used in some cases

Safety and Considerations

LDN is widely regarded as safe and well tolerated.

Common side effects:

Vivid dreams
Insomnia (usually transient)
Mild nausea or headaches
Temporary symptom flares (Herxheimer-type reactions)

Contraindications:

Opioid use – LDN will block opioid medications
Liver dysfunction – use with caution
Pregnancy – limited data available

LDN is not immunosuppressive and can be safely used alongside thyroid hormone therapy, including levothyroxine and NDT (natural desiccated thyroid).

Integrating LDN into a Hashimoto’s Protocol

LDN works best when integrated into a holistic, functional approach:

Nutrient support: selenium, vitamin D, zinc, iron
Gut healing: addressing dysbiosis and permeability
Dietary triggers: gluten/dairy elimination (case-dependent)
Stress support: adaptogens, lifestyle, and HPA axis regulation

It’s often added after stabilizing thyroid hormone levels and while addressing the root causes of immune dysregulation.

Summary: LDN for Hashimoto’s at a Glance

Benefit	Clinical Impact
Symptom relief	Fatigue, brain fog, mood, pain
Immune modulation	Reduced Th1/Th17 dominance
Antibody reduction	Lower TPOAb/TgAb in many cases
Tolerability	Generally well tolerated, few side effects
Mechanism	Endorphin upregulation, cytokine modulation
Form	Capsule, liquid, sublingual – compounded

Final Thoughts

Low Dose Naltrexone is not a miracle cure — but it is a powerful adjunct for patients struggling with Hashimoto’s symptoms despite “normal” labs. It offers a low-risk, well-tolerated option for rebalancing the immune system and addressing underlying inflammation.

As more clinicians integrate LDN into their protocols, it’s becoming clear: treating autoimmune thyroid disease isn’t just about hormones — it’s about healing the immune system.

If you’re a practitioner and want to learn more about integrating Low Dose Naltrexone into your practice, schedule a FREE training session with one of Harbor Compounding Pharmacy’s Clinical pharmacists now.