The Use of Low Dose Naltrexone in Dermatology

May 23, 2022

Let’s discuss the use of low dose naltrexone in dermatology.

Low dose naltrexone (LDN) is a competitive opioid receptor antagonist that is safe, non-toxic, and inexpensive. At standard therapeutic dosage, naltrexone blocks the effects of both natural (endorphin) opioids and pharmaceutical opioids. Naltrexone has been applied to several therapeutic scenarios. Primarily, it is used for pain control, including both chronic pain and inflammation control. A low dose of naltrexone typically consists of oral ingestion of 0.5 to 5.0 mg/d.

LDN has been demonstrated to bind to endorphin receptors for approximately 60 to 90 minutes. One consequence of use is that it increases the production of the recipient’s natural endorphins as the body attempts to address the perceived imbalance.

Opioid receptors are found throughout the skin and impact cell proliferation rates, migration, and adhesion. While higher doses of naltrexone result in continuous binding to receptors, low doses result in partial blockade with the outcome of increasing ligand and receptor expression.

Naltrexone is also considered to have anti-inflammatory and immunoregulatory properties through the blockade of macrophage-released tumor necrosis factor (TNF) and the pro-inflammatory cytokines IL-6 and IL-12.

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The Connection Between Autoimmune Diseases and Skin Conditions

Autoimmunity is an immune response against a self-antigen that usually involves T and B lymphocytes. When autoimmunity results in tissue damage or impaired physiological function, the patient enters a disease state.

Autoimmunity relates to skin conditions such as:

Systemic sclerosis
Dermatomyositis
Psoriasis
Vitiligo
Alopecia areata
Pruritus/eczema

Low Dose Naltrexone in Dermatology

Naltroxone’s use in dermatology is linked to its success in treating autoimmune diseases, thanks to its analgesic and anti-inflammatory properties.

Dermatologists regularly face patients with autoimmune diseases that have manifested as skin conditions. Initiating immunosuppression is contraindicated due to the risks of side effects. LDN, however, has few worrying side effects but has been demonstrated to be efficacious in controlling the inflammatory response of the immune system. A systemic review reports that LDN has proved effective in the treatment of several autoimmune conditions.

Additionally, well-founded research that includes randomized clinical trials and case reports demonstrates that LDN can be effective in treating:

Pruritus/eczema
Psoriasis
Prurigo nodularis
Cholestasis
Burn injury
Systemic sclerosis
Hailey-Hailey disease
Lichen planopilaris

Let’s consider some of the conditions that LDN can mitigate in brief.

LDN for Psoriasis

Psoriasis is mainly a dendritic and T-cell–mediated immunologic disease. However, susceptibility to psoriasis involves components of both the adaptive and innate immune systems. In acute psoriasis, both of these immune system components are activated. For chronic plaque phase, adaptive immune responses predominate. In between these extremes lie several clinical subtypes resulting in a spectrum between plaque and pustular psoriasis. This makes psoriasis a particularly challenging disease wherein the treatment must consider both autoimmune and autoinflammatory responses and the balance between the two.

Case study data suggests that psoriasis responds well to LDN, with patients entering remission after only three months of 4.5 mg of daily LDN.

LDN for Eczema

Eczema is a non-infectious cluster of conditions that causes inflamed, irritated, and often itchy skin. There are several types of eczema, including atopic dermatitis (AD), contact dermatitis, nummular eczema, and dyshidrotic eczema. Common to all these variants are the triggers, which include immune system activation, genetics, environmental exposures, and stress.

Evidence suggests that AD may start as an allergic reaction and progress to an autoimmune response. This truth could well explain the success reported in case study data that LDN can be effective against patients’ eczema within a two-week period.

LDN for Alopecia Universalis

Alopecia universalis is an autoimmune system disorder, wherein the immune system attacks the hair follicles. Although the body of available research on LDN in alopecia is only emergent, prescribers are reporting positive outcomes.

LDN for Hailey-Hailey Disease

Hailey-Hailey disease is a rare genetic condition due to a single point mutation, also known as familial benign chronic pemphigus. It causes blisters and erosions, typically around the neck, armpits, skin folds, and genitals. The lesions occur as the skin cells fail to adhere, resulting in the breakdown of affected skin layers. Again, the body of research is emergent, but there is early evidence to support the use of LDN for Hailey-Hailey disease.

In conclusion, it is always a difficult transition period when a drug is applied for off-label use. It can take a long time to collate the evidence required for a reassessment and recategorization. The early studies on LDN, however, are promising and offer hope for a safe, non-toxic systemic treatment for multiple immune-mediated conditions.

VLS Pharmacy and New Drug Loft

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Reach out to our team to learn more about best practices and to partner with our experts on custom compounded medications for your patients.

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