Fatima Hamade, PharmD, BCACP
Keywords: Low-dose naltrexone; Autoimmune; Chronic Inflammation; Compounding Pharmacy
This case report explores the use of compounded low-dose naltrexone (LDN) as an adjunctive therapy for persistent autoimmune symptoms, highlighting its proposed immunomodulatory mechanisms, individualized dosing strategies, and the collaborative role of naturopathic physicians and compounding pharmacists.
Could low-dose naltrexone offer additional symptom relief for patients with autoimmune disease? This case report examines the use of individualized compounded LDN in a patient with Hashimoto’s thyroiditis, reviewing its proposed mechanisms of action, dosing considerations, clinical outcomes, and the value of interdisciplinary collaboration in personalized care.
Introduction
Autoimmune diseases affect nearly 8% of the population and continue to rise in prevalence worldwide.1 Despite their diverse clinical presentations, these disorders share a common pathophysiology of immune dysregulation that drives chronic inflammation and subsequent tissue injury. Conventional therapies often include corticosteroids, immunosuppressive medications, targeted biologics and disease-modifying agents (DMARDs). While these therapies significantly enhance patient outcomes, many individuals continue to experience persistent fatigue, chronic pain, cognitive impairment, and a diminished quality of life despite receiving standard clinical care.
Low-dose naltrexone (LDN) has emerged as an adjunctive therapy of growing clinical interest. Administered in doses ranging from approximately 0.5 mg to 4.5 mg daily, LDN appears to exert immunomodulatory rather than immunosuppressive effects.2 Endorphins are endogenous opioid peptides produced by the body that play important roles in pain modulation, stress response, and immune regulation. One proposed mechanism suggests LDN transiently blocks opioid receptors, resulting in a compensatory increase in endogenous endorphin production. In addition, LDN appears to modulate Toll-like receptor 4 (TLR4) signaling on activated microglia and other immune cells, reducing the production of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α).3,4 Together, these mechanisms may contribute to reduced neuroinflammation and modulation of the dysregulated immune response observed in certain autoimmune and chronic inflammatory conditions.
Because commercially manufactured formulations of LDN are not available, compounding pharmacies play an essential role in individualized patient care. LDN can be compounded in a variety of dosage forms, including capsules, liquids, creams and tablets.
Case Presentation
Patient Information
A 48-year-old female presented with Hashimoto’s thyroiditis, chronic fatigue, musculoskeletal pain, and intermittent cognitive complaints, despite stable thyroid replacement therapy and nutritional support.
Presenting Concern
Persistent fatigue, widespread pain, poor sleep quality, and declining exercise tolerance for the past 9 -12 months.
Clinical History and Context
Past medical history (PMH) was significant for Hashimoto’s thyroiditis diagnosed 6 years earlier. Prior therapy included levothyroxine, selenium, vitamin D, omega-3 fatty acids, dietary modification, and stress management. Following discussion between the naturopathic physician and compounding pharmacist, individualized LDN therapy was recommended.
Diagnostic Assessment
TSH 1.8 mIU/L; Free T4 and Free T3 within reference range; thyroid peroxidase antibodies remained elevated; CRP mildly elevated.
Clinical Assessment
Persistent symptoms were believed to be related to chronic autoimmune inflammation despite biochemical control of thyroid disease.
Therapeutic Intervention
The patient initiated compounded low-dose naltrexone (LDN) capsules at 0.5 mg nightly, which was titrated to a target dose of 4.5 mg over 12 weeks. Clinical counseling covered treatment expectations, the necessity of a gradual titration schedule, and standard adverse effects, including vivid dreams, sleep disturbances, headaches, and mild gastrointestinal upset. Crucially, the patient was educated on strict opioid precautions.
Follow-up and Outcomes
After 12 weeks, the patient reported improved fatigue, sleep quality, and cognitive function. Pain improved from 7/10 to approximately 3-4/10 with no serious adverse events.
Safety and Tolerability
Transient vivid dreams resolved without intervention.
Discussion
Low-dose naltrexone offers a different therapeutic approach from conventional immunosuppressive therapies by supporting immune modulation rather than broad immune suppression. This case highlights the potential role of low-dose naltrexone (LDN) as an adjunctive therapy for patients with persistent autoimmune symptoms despite conventional treatment. Following initiation of LDN, the patient experienced improvements in fatigue, pain, sleep, and cognitive function with minimal adverse effects, suggesting that LDN may provide additional symptomatic benefit in selected patients.2-6
The patient’s response is consistent with the proposed mechanisms of LDN, including transient opioid receptor blockade with increased endogenous endorphin production and modulation of Toll-like receptor 4 (TLR4), resulting in reduced production of pro-inflammatory cytokines such as TNF-α and IL-6.3,4 Similar clinical improvements have been reported in previous studies; however, larger randomized controlled trials are needed to better define the role of LDN in autoimmune and chronic inflammatory conditions.2-7
In addition, this case highlights the value of collaboration between naturopathic physicians and compounding pharmacists. Individualized dosing, careful excipient selection and dosage form, patient education and close follow-up may contribute to successful clinical outcomes. Because patients vary in both sensitivity and clinical response, a gradual titration schedule is generally recommended to optimize tolerability and identify the lowest effective dose. A common approach and the approach used in this case is to initiate therapy at 0.5 mg -1 mg once daily and increase the dose by 0.5 mg-1 mg every 14 days, depending on the patient’s response and any adverse effects experienced. This gradual titration allows patients to adjust to therapy while minimizing side effects. Although many patients ultimately achieve therapeutic benefit at doses between 3 mg and 4.5 mg daily, others experience meaningful improvement at lower doses, and some may need higher doses. For this reason, dosing should always be individualized based on clinical response rather than targeting a universal maintenance dose.
Optimizing timing of dosing may increase patient adherence. LDN is commonly administered at bedtime, and many patients tolerate nighttime dosing well. However, dosing time should be individualized based on patient response. Some patients may experience vivid dreams, insomnia or sleep disturbances after initiating therapy or during dose escalation. In these cases, morning administration may improve tolerability while maintaining clinical benefit. Ultimately the optimal dosing schedule is what works best for the patient. Patients should be encouraged to communicate any changes in sleep or other adverse effects to their healthcare provider so that the dosing schedule can be adjusted accordingly. Collaboration between the prescribing clinician and compounding pharmacist can help optimize both adherence and therapeutic outcomes through individualized dosing strategies and ongoing patient education.
Conclusion
This case highlights the value of collaboration between naturopathic physicians and compounding pharmacists, as individualized dosing, gradual titration, dosage-form selection, patient education, and close follow-up may improve tolerability and therapeutic outcomes. Because patients vary in clinical response, LDN dosing and administration time should be individualized, with dose adjustments and timing based on patient tolerability and preference.
References
- Office of Research on Women’s Health. Autoimmune Diseases Research. National Institutes of Health. Accessed July 25, 2026. https://orwh.od.nih.gov/OADR-ORWH
- Plank JR, Glover SC, Moloney BD, et al. A randomized, double-blind, placebo-controlled, hybrid parallel-arm study of low-dose naltrexone as an adjunctive anti-inflammatory treatment for major depressive disorder. Trials. 2022;23(1):822. doi:10.1186/s13063-022-06738-3
- 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. doi:10.1007/s10067-014-2517-2
- Parkitny L, Younger J. Reduced pro-inflammatory cytokines after eight weeks of low-dose naltrexone for fibromyalgia. Biomedicines. 2017;5(2):16. doi:10.3390/biomedicines5020016
- Management of patients on low-dose naltrexone: A clinical review for urgent care providers. J Urgent Care Med. Published February 20, 2024. Accessed July 25, 2026.
6.Toljan K, Vrooman B. Low-dose naltrexone (LDN)—review of therapeutic utilization. Med Sci (Basel). 2018;6(4):82. doi:10.3390/medsci6040082
- Raknes G, Småbrekke L. Low dose naltrexone in multiple sclerosis: Effects on medication use. A quasi-experimental study. PLoS One. 2017;12(11):e0187423. doi:10.1371/journal.pone.0187423
8.Smith JP, Bingaman SI, Ruggiero F, Mauger DT, Mukherjee A, McGovern CO, Zagon IS. Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn’s disease: A randomized placebo-controlled trial. Dig Dis Sci. 2011;56(7):2088-2097. doi:10.1007/s10620-011-1653-7.
9.McDermott MT. Low-Dose Naltrexone Treatment of Hashimoto’s Thyroiditis. In: Hennessey JV, ed. Management of Patients With Pseudo-Endocrine Disorders. Springer; 2019:317-326. doi:10.1007/978-3-030-22720-3_24.
Author Bio
Fatima Hamade, PharmD, BCACP is the owner and head pharmacist of Rancho Compounding Pharmacy in San Diego, California. She has more than 25 years of pharmacy experience and specializes in personalized compounded medications, with clinical interests in low-dose naltrexone (LDN), hormone replacement therapy, dermatology, and pain management. She works closely with naturopathic physicians and other healthcare providers to create individualized, evidence-informed treatment plans that optimize patient care.
Fatima Hamade, PharmD, BCACP
Rancho Compounding Pharmacy, San Diego, California
info@myranchopharmacy.com
(P) 619-303-7771
Conflicts of Interest
None declared.
Funding and Support
None.
