“The role of LDN and ultra-low dose naltrexone (ULDN, microgram dosing of naltrexone) for chronic pain have been described recently in medical literature. A review from the University of Kansas Medical School evaluates the existing evidence for using LDN for treating pain and its microgram dosing in the potentiation of opioid medication while reducing side effects. “It has been proposed that LDN halts inflammatory cascades via glial cell inactivation. In addition, the role of microgram dosing of naltrexone has shown promise as a method to increase analgesia and decrease tolerance to opioid medications.”

J Pain Manage Ther. 2019; 3(1):1-5.

Treating chronic pain with low dose naltrexone and ultralow dose naltrexone: a review paper.

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The use of oral low dose naltrexone (1 mg to 4.5 mg) for the treatment of chronic pain is novel because it is a nonopioid alternative. Low dose naltrexone (LDN) use is “off-label” and has been used successfully to manage chronic pain, autoimmune disorders, and dermatologic conditions. LDN could be a viable treatment option for chronic pain because other agents for chronic pain, such as nonsteroidal agents (NSAIDs), have adverse effects of gastrointestinal bleeding, renal injury, and increase a patient’s risk of myocardial infarction or stroke. Additionally, LDN has minimal adverse effects, no drug-drug interactions, and is relatively inexpensive compared with other options for chronic pain.

Sr Care Pharm. 2019 Jan 1;34(1):43-46.

The Use of Low-Dose Naltrexone for Chronic Pain

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LDN for Chronic Regional Pain Syndrome

A systematic qualitative review found that Low-Dose Naltrexone (LDN) treatment was positively associated with symptom relief in patients experiencing chronic pain, dystonia, and sleep disturbances. Complex regional pain syndrome (CRPS) is a rare, neuropathic disorder that affects fewer than 200,000 individuals in the United States annually. Current treatments often focus on pain management and fall short of relieving symptoms of pain and dystonia in patients. Due to the limited number of available articles focusing on the treatment of complex regional pain syndrome with LDN, the majority of studies analyzed focused on other chronic pain syndromes. There is a need for additional prospective and interventional studies addressing the use of LDN in the treatment of complex regional pain syndrome symptoms.

Pain Physician. 2021 Jul;24(4):E393-E406.

Low-Dose Naltrexone Use for Patients with Chronic Regional Pain Syndrome: A Systematic Literature Review

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LDN for Chronic, Nonmalignant Pain Syndromes

Pain can have a devastating effect on the quality of life of patients in palliative medicine. To date, most research has been centered on opioid-based pain management in palliative care. However, opioid and nonopioid medications such as nonsteroidal anti-inflammatory drugs have limitations in clinical use. Low-dose naltrexone has gained popularity as an off-label treatment for several autoimmune diseases as well as chronic pain disorders including fibromyalgia, complex regional pain syndrome, and diabetic neuropathy.

Am J Hosp Palliat Care. 2019 Oct;36(10):907-912.

Pharmacology Update: Low-Dose Naltrexone as a Possible Nonopioid Modality for Some Chronic, Nonmalignant Pain Syndromes

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The authors completed a comprehensive literature review to evaluate the efficacy of LDN in the management of chronic pain conditions and determine its potential for the treatment of orofacial pain.

They determined that LDN provides an alternative method to manage chronic pain disorders. Since orofacial pain conditions share characteristics with other chronic pain disorders, LDN may offer additional management options for these patients.

J Am Dent Assoc. 2020 Dec;151(12):891-902.e1.

Use of low-dose naltrexone in the management of chronic pain conditions: A systematic review

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Click here to read the review.

Many patients suffering from fibromyalgia do not adequately respond to traditional therapies. Studies have shown low dose naltrexone to be well tolerated, inexpensive and likely an effective treatment option.

Curr Rheumatol Rev. 2018;14(2):177-180.

Low Dose Naltrexone in the Treatment of Fibromyalgia

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Biomedicines. 2017 Apr 18;5(2):16.

Reduced Pro-Inflammatory Cytokines after Eight Weeks of Low-Dose Naltrexone for Fibromyalgia

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Arthritis Rheum. 2013 Feb;65(2):529-38.

Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels

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Pain Med. May-Jun 2009;10(4):663-72.

Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study

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Chronic inflammatory diseases are complex to treat and have an impact on a large number of patients. Since the 1990s, opioid prescriptions have been increasing in prevalence in chronic inflammatory and neuropathic conditions. However, most opioids are considered less effective or have unproven efficacy in chronic conditions such as multiple sclerosis, fibromyalgia, and Crohn’s disease.

Fibromyalgia is not considered a classic inflammatory disease, but rather a disorder of the central nervous system that has a neuroimmune component. The effect of LDN as an immune-modulator may be beneficial for treating fibromyalgia, and pilot studies have started to evaluate its impact. Participants reported significantly less pain and symptoms associated with their fibromyalgia, and no moderate or major adverse effects were reported.

A notable effect of LDN in fibromyalgia has been increased pain tolerance. The participants reported not only a reduction in daily pain but also significantly increased quality of life and mood.

Pharmacotherapy. 2018 Mar;38(3):382-389.

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

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Low-dose naltrexone (LDN) has been shown to be a promising treatment in chronic pain conditions that involve inflammatory processes such as fibromyalgia, Crohn’s disease, multiple sclerosis, and complex regional pain syndrome (CRPS).

Clin Rheumatol. 2014; 33(4): 451–459.

The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain

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Additional review was completed to evaluate the clinical use of low-dose naltrexone in the treatment of chronic pain. LDN showed more promise and it was concluded that LDN should be investigated further in clinical practice.

Curr Pain Headache Rep. 2020 Aug 26;24(10):64.

Low-Dose Naltrexone for Chronic Pain: Update and Systemic Review

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Sixty-seven participants with painful diabetic neuropathy were randomized to receive either 2mg naltrexone or 10mg amitriptyline daily following a 2-week run-in period. Low-dose naltrexone exhibited similar efficacy and a superior safety profile compared with amitriptyline in painful diabetic neuropathy.

J Diabetes. 2021 Oct;13(10):770-778.

Efficacy and safety of low-dose naltrexone in painful diabetic neuropathy: A randomized, double-blind, active-control, crossover clinical trial

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LDN for Burning Mouth Syndrome

Burning mouth syndrome is a chronic pain condition characterized by a burning sensation of the oropharynx. The pathophysiology of burning mouth syndrome includes peripheral and central sensitization. Treatment is generally aimed at symptom reduction. A case report described a woman in her 60s with burning mouth syndrome that had been refractory to treatment for nearly a decade. Low-dose naltrexone (LDN) has been reported to provide analgesia in central sensitization states and was successful in reducing pain severity in this patient. The report concluded that LDN may be a therapeutic option for patients with burning mouth syndrome who are refractory to conventional therapies.

A A Pract. 2021 May 17;15(5):e01475.

Utilization of Low-Dose Naltrexone for Burning Mouth Syndrome: A Case Report

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