Low Dose Naltrexone (LDN)
Naltrexone is a medication originally approved as a treatment for opioid addiction and alcoholism. It is a mu-opioid antagonist that is a combination of two distinct shapes known as isomers. The research suggests that the L isomer binds to opioid receptors, while the D isomer binds to immune cells.
In 1985, while working at addiction clinics in New York, Bernard Bihari, MD, discovered many novel benefits of using lower doses (4.5 mg) of naltrexone than the standard 50 mg dose used to treat addiction. Dr. Bihari shifted his research and treated patients with HIV/AIDS. Since naltrexone increased the production of endorphins and the immune system is significantly regulated by endorphins, he began using Low Dose Naltrexone (LDN) to help protect what remained of the immune systems of HIV/AIDS patients.
As an opioid antagonist, naltrexone binds to and blocks opioid receptors on cells in the body. Using naltrexone in low doses causes the receptors to be blocked intermittently and the receptor sites rebound with increased production of endorphins. Endorphins are “natural, endogenous opioids” best known for relieving pain, enhancing a sense of well-being, and regulating the immune system.
Increased endorphin release:
- May lessen pain.
- Downregulates inflammatory cytokines, while increasing white blood cells.
- Stimulates mucosal and tissue healing.
- May inhibit tumor growth.
- Reduces death of the cells that produce myelin in the brain, thereby protecting the covering of nerves.
LDN has also been shown to block some non-opioid receptors (toll-like receptors, TLR4) which reduce inflammatory cytokines and suppress the body’s immune response and inflammation. LDN has demonstrated the ability to reduce the severity of symptoms in certain inflammatory conditions such as fibromyalgia, Crohn’s disease, multiple sclerosis and complex regional pain syndrome (CRPS).
Before starting LDN, a full review of medications and supplements should be completed. Modifications of doses for other maintenance medications may need to coincide with the start of LDN. LDN is well tolerated in most patients and side effects tend to be transient. However, care should be taken to slowly titrate the dose avoid side effects.
Some common side effects may include:
- Sleep disturbances/vivid dreams
- Gastrointestinal upset, nausea
- Mild headache
- Mild agitation
Naltrexone is only commercially available as a 50 mg tablet. A prescription for Low Dose Naltrexone must be prepared by a compounding pharmacy. Compounding pharmacists have specialized training and will work with medical professionals to provide guidance for dosing protocols for various conditions. The most common “rule of thumb” is to start with a lower dose and increase slowly.
LDN can be compounded in various dosage forms per prescription:
- Capsules – compounded in appropriate doses for titration and maintenance.
- Liquid – allows for slow titration to optimal dose.
- Sublingual drops – for patients with swallowing difficulties or GI side effects from the liquid. SL drops facilitate more rapid absorption through the oral mucosa.
- Topical Cream – can be helpful when administering to children.
LDN is not commercially available but can be prescribed and compounded by our pharmacy in the best dose and dosage form for each patient. Research involving LDN and its reported uses is constantly expanding. LDN is low cost, has low side effects, and no known abuse potential. Many peer-reviewed studies about the benefits of LDN can be viewed on our site and many more are underway.
Start Low and Go Slow. Doses of LDN need to be titrated and increased slowly over time. Talk to our pharmacist for more information about prescribing LDN.Please contact our compounding pharmacy to discuss your specific needs.
Elsegood, Linda, editor. The LDN Book, Volume Two. Chelsea Green Publishing, 2020.
Altern Ther Health Med. Mar-Apr 2013;19(2):56-65.
Bernard Bihari, MD: Low-Dose Naltrexone for normalizing immune system function
Click here to read the full article.
Clin Rheumatol. 2014; 33(4): 451–459.
The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain
Click here to access the PubMed abstract of this article.
Women's Health ↓
PCOS (polycystic ovary syndrome) has been found to be one of the top causes of infertility. Women with PCOS often struggle to find successful treatment options, however low-dose naltrexone has shown promise in several studies.
PCOS is characterized by increased activity of sympathetic nervous system and has autoimmune characteristics.
Steroids. 2012 Mar 10; 77(4): 306–311.
Medical management of metabolic dysfunction in PCOS
Click here to access the PubMed abstract of this article.
Curr Pharm Des. 2006;12(8):1001-12.
Role of opioid antagonists in the treatment of women with glucoregulation abnormalities.
Click here to access the PubMed abstract of this article.
Fertil Steril. 2009 Jul;92(1):1-12.
The role of the endogenous opioid system in polycystic ovary syndrome.
Click here to access the PubMed abstract of this article.
Mental Health ↓
Naltrexone was associated with improvement in BPD in a dose-dependent manner. The study provided additional evidence that dysregulation of the endogenous opioid system is implicated in the pathophysiology of BPD symptoms.
Hum Psychopharmacol. 2021 Nov;36(6)
Efficacy of naltrexone in borderline personality disorder, a retrospective analysis in inpatients
Click here to access the PubMed abstract of this article.
LDN showed some benefit for major depressive disorder relapse on pro-dopaminergic antidepressant regimens. Larger studies are needed.
J Affect Disord. 2017 Jan 15;208:6-14.
Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants
Click here to access the PubMed abstract of this article.
Treatment with low-dose naltrexone may be a helpful element in the treatment of patients with complex posttraumatic stress disorder. However, it must be realized that the decrease of dissociation may lead patients to a not yet resolvable challenge, in as much as dissociation had previously been a necessary mechanism of self-protection.
Nervenarzt. 2015 Mar;86(3):346-51. (article in German)
[Low dose naltrexone in the treatment of dissociative symptoms]
Click here to access the PubMed abstract of this article.
Accumulating evidence suggests that Low Dose Naltrexone can promote health-supporting immune-modulation which may reduce various oncogenic and inflammatory autoimmune processes. LDN may also play a role in healing and repair of tissues, as well as promoting stress resilience, exercise, social bonding, and emotional well-being, and ameliorating psychiatric problems such as autism and depression.
Med Hypotheses. 2009 Mar;72(3):333-7.
Low-dose naltrexone for disease prevention and quality of life.
Click here to access the PubMed abstract of this article.
Gastrointestinal ↓
Naltrexone directly improves epithelial barrier function by improving wound healing and reducing mucosal endoplasmic reticulum (ER) stress levels. Low dose naltrexone treatment could be considered for the treatment of therapy refractory IBD patients.
J Transl Med. 2018 Mar 9;16(1):55.
Low dose Naltrexone for induction of remission in inflammatory bowel disease patients
Click here to access the PubMed abstract of this article.
Treatment with naltrexone led to improvement in systemic and social quality of life in children with moderate to severe Crohn’s disease.
J Clin Gastroenterol. 2013 Apr;47(4):339-45.
Safety and tolerability of low-dose naltrexone therapy in children with moderate to severe Crohn’s disease: a pilot study
Click here to access the PubMed abstract of this article.
Naltrexone improves clinical and inflammatory activity of subjects with moderate to severe Crohn’s disease compared to placebo-treated controls. Strategies to alter the endogenous opioid system provide promise for the treatment of Crohn’s disease.
Dig Dis Sci. 2011 Jul;56(7):2088-97.
Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn’s disease: a randomized placebo-controlled trial
Click here to access the PubMed abstract of this article.
Low dose naltrexone frequently has side effects but in most is tolerable. It appears to be helpful for many patients with gastrointestinal disorders.
Int J Pharm Compd. Mar-Apr 2010;14(2):171-3.
Low Dose Naltrexone: Side Effects and Efficacy in Gastrointestinal Disorders
Click here to access the PubMed abstract of this article.
Low-dose naltrexone (LDN) therapy appears effective and caused no adverse side effects in subjects with active Crohn’s disease.
Am J Gastroenterol. 2007 Apr;102(4):820-8.
Low-Dose Naltrexone Therapy Improves Active Crohn’s Disease
Click here to access the PubMed abstract of this article.
Dermatology ↓
A summary of current studies of naltrexone used in a dermatologic practice was completed. Data suggest that naltrexone could be helpful in the treatment of a variety of inflammatory and acantholytic skin diseases that are refractory to other treatments.
J Am Acad Dermatol. 2019 Jun;80(6):1746-1752.
The uses of naltrexone in dermatologic conditions
Click here to access the PubMed abstract of this article.
“Off label LDN has been shown to improve dermatologic conditions such as systemic sclerosis, Hailey-Hailey Disease, lichen planopilaris, and guttate psoriasis… “
“Atopic dermatitis (AD) is one of the most common chronic skin disorders, affecting up to 20% of children and 10% of adults in the industrialized world… A trial of a topical formulation of 1% naltrexone [cream] in 40 patients with severe atopic dermatitis revealed a 29% improvement after just 2 weeks of use.”
J Drugs Dermatol. 2019 Mar 1;18(3):235-238.
Low Dose Naltrexone in Dermatology
Click here to access the PubMed abstract of this article.
Dermatology is encountering increasing rates of autoimmune disease manifesting in primary skin conditions that are difficult to treat without risk of immunosuppression. The ability of low doses of naltrexone (LDN), 1.5 to 4.0 mg/day orally, to influence a variety of systemic pathways, including the immune system.
A review of the literature from 1971 until April 2018 shows that LDN was effective in treating pruritus attributable to atopic dermatitis, prurigo nodularis, cholestasis, burn injury, systemic sclerosis, Hailey-Hailey disease, and lichen planopilaris. Serious side effects were not reported. They concluded that LDN has the potential for the treatment of chronic inflammatory skin conditions; however, additional evidence is needed for dosing and long-term treatment guidelines.
JAMA Dermatol. 2019 Feb 1;155(2):229-236.
Utility of Naltrexone Treatment for Chronic Inflammatory Dermatologic Conditions: A Systematic Review
Click here to access the PubMed abstract of this article.
Low-Dose Naltrexone Therapy for Psoriasis
Low-dose naltrexone regulates lymphocyte responses, reduces cytokine production, and likely reduces mast cell activity. Two recent reports suggested that low-dose naltrexone is a beneficial and convenient therapy for psoriasis. Patients included 13 females, 2 males; mean age 57 years; mean psoriasis duration 16 years. Of the patients, 8 had psoriatic arthritis. In the past, 5 had completely failed and 10 had partially responded to =1 topical therapy. Patients used a self-assessed Likert scale and the response to 4.5 mg of oral naltrexone was as follows: 8/15 marked improvement; 2/15 somewhat improved, and 5/15 unchanged. Three adverse events included insomnia, diarrhea, and self-limited headache. In conclusion, marked improvement was seen by 53% of the 15 patients.
Int J Pharm Compd. Mar-Apr 2020;24(2):94-96.
Low-dose Naltrexone Therapy for Psoriasis
Click here to access the PubMed abstract of this article.
Prurigo Excoriée Treated with LDN
A 53-year-old woman presented with a 25-year history of acne excoriée and prurigo excoriée. The pruritus affected her quality of life and disturbed her sleep. She had scarring on her face and body resulting from persistent scratching. The pruritus proved refractory to treatment despite a multi-modal treatment approach including multiple topicals, phototherapy, and systemic agents such as isotretinoin, antibiotics, anxiolytic agents, and neuromodulators. She was extremely frustrated that various treatments had been ineffective at controlling the itch-scratch cycle. After treatment with LDN, 3mg at bedtime, she became itch-free within a few weeks. She reported that the LDN had a beneficial impact on her quality of life.
BMJ Case Rep. 2021 Nov 19;14(11):e243773.
Prurigo excoriée treated with low dose naltrexone
Click here to access the PubMed abstract of this article.
Autoimmune Conditions ↓
LDN in Rheumatoid and Seropositive Arthritis
While studies indicate beneficial effects of LDN in autoimmune diseases, clinical research on LDN in rheumatic disease is limited. Using a pharmaco-epidemiological approach, Norwegian researchers tested the hypothesis that LDN use leads to reduced dispensing of other drugs (NSAIDs, opioids, TNF-α antagonists and DMARDs) used in the treatment of rheumatic disease. Patients (n = 360) were stratified into three groups based on LDN exposure. In persistent LDN users, there was a 13% relative reduction in cumulative defined daily doses (DDD) of all medicines examined and 23% reduction of analgesics. There was no significant DDD change in patients with less LDN exposure. There was a decrease in the number of NSAID users among patients with the least LDN exposure. The results support the hypothesis that persistent use of LDN reduces the need for other medications used in the treatment of rheumatic and seropositive arthritis. Randomized clinical trials of LDN in rheumatic disease are warranted.
PLoS One. 2019 Feb 14;14(2):e0212460.
Low dose naltrexone: Effects on medication in rheumatoid and seropositive arthritis. A nationwide register-based controlled quasi-experimental before-after study
Click here to access the PubMed abstract of this article.
Treatment of Autoimmune Disease with LDN
Zagon and McLaughlin of the Department of Neural and Behavioral Sciences, Penn State University College of Medicine, explained the intermittent blockade of the opioid growth factor (OGF) – OGF receptor (OGFr) axis by low dose naltrexone (LDN), and the role of enkephalin (i.e., OGF) in autoimmune disorders, specifically multiple sclerosis, Crohn’s disease, and fibromyalgia. “Clinical reports on subjects taking LDN have documented reduced fatigue, few side-effects, and improved overall health… Intermittent OGFr blockade with LDN restores serum enkephalin levels… The interplay between LDN, and the onset and treatment of autoimmune diseases, chronic pain, and other addictive behaviors requires further investigation, but highlights a central role for enkephalins and intermittent blockade of the OGF-OGFr pathway in pathogenesis and treatment of these disorders.”
Exp Biol Med (Maywood). 2018 Dec;243(17-18):1323-1330.
Intermittent blockade of OGFr and treatment of autoimmune disorders
Click here to access the PubMed abstract of this article.
LDN for Multiple Sclerosis
The review focused on 215 MS patients who were provided a prescription for oral LDN. The study reports that a significant number of patients found combination therapy of an immunomodulating agent and LDN to be tolerable and possibly beneficial. Some patients preferred LDN alone. LDN did not cause any unexpected side effects.
J Clin Psychopharmacol. 2015 Oct;35(5):609-11.
Low Dose Naltrexone for Treatment of Multiple Sclerosis: A Retrospective Chart Review of Safety and Tolerability
Click here to access the PubMed abstract of this article.
Clinical Benefits of Low-Dose Naltrexone for Sjogren’s
Sjogren’s Syndrome is a chronic autoimmune disorder that causes inflammation of the lacrimal and salivary glands, resulting in dryness of the eyes and mouth. In addition, fatigue and musculoskeletal pain, often described as aching, is very common. Treatment directed toward alleviating the fatigue and pain associated with Sjogren’s is currently very limited. Since Low-Dose Naltrexone (LDN) has pain-relieving and anti-inflammatory properties, case reports on patients with suspected Sjogren’s based on long-standing dry eyes, dry mouth, joint pain, fatigue and elevated measures of inflammation showed clinical improvement with LDN.
Cureus. 2019 Mar 11;11(3):e4225.
Sjogren’s Syndrome: Clinical Benefits of Low-dose Naltrexone Therapy
Click here to access the PubMed abstract of this article.
Cureus. 2020 Jul 1;12(7):e8948.
Sjogren’s Syndrome and Clinical Benefits of Low-Dose Naltrexone Therapy: Additional Case Reports
Click here to access the PubMed abstract of this article.
Chronic Pain ↓
“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.
Click here to read the review.
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
Click here to access the PubMed abstract of this article.
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
Click here to access the PubMed abstract of this article.
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
Click here to access the PubMed abstract of this article.
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
Click here to access the PubMed abstract of this article.
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
Click here to access the PubMed abstract of this article.
Biomedicines. 2017 Apr 18;5(2):16.
Reduced Pro-Inflammatory Cytokines after Eight Weeks of Low-Dose Naltrexone for Fibromyalgia
Click here to access the PubMed abstract of this article.
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
Click here to access the PubMed abstract of this article.
Pain Med. May-Jun 2009;10(4):663-72.
Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study
Click here to access the PubMed abstract of this article.
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
Click here to access the PubMed abstract of this article.
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
Click here to access the PubMed abstract of this article.
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
Click here to access the PubMed abstract of this article.
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
Click here to access the PubMed abstract of this article.
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
Click here to access the PubMed abstract of this article.