From the Guidelines
Low dose naltrexone (LDN) is recommended for inflammation at a dose of 1.5-4.5 mg daily, taken at bedtime, due to its ability to reduce pro-inflammatory cytokines and modulate microglial activity, as shown in a study published in Ophthalmology in 2017 1. The standard protocol for LDN often starts at 1.5 mg daily for 1-2 weeks, then increases to 3 mg for another 1-2 weeks, before reaching the target dose of 4.5 mg daily. Some key points to consider when using LDN for inflammation include:
- LDN should be taken consistently, as benefits may take 2-3 months to become noticeable, and patients should continue treatment for at least 6 months to properly evaluate effectiveness.
- The medication works by temporarily blocking opioid receptors, which triggers increased production of endorphins and enkephalins, resulting in reduced inflammation and modulated immune system function, as noted in the study published in Ophthalmology in 2017 1.
- LDN is generally well-tolerated with minimal side effects, which may include vivid dreams, sleep disturbances, or headaches that typically resolve within the first few weeks.
- It's essential to use compounded LDN from a reputable pharmacy since commercial naltrexone tablets (50 mg) cannot be accurately divided into the required low doses.
- Patients should discuss this treatment with their healthcare provider, especially if they take opioid medications, as naltrexone blocks opioid effects and could precipitate withdrawal in opioid-dependent individuals, highlighting the importance of careful consideration and monitoring when using LDN for inflammation, as supported by the evidence from the study published in Ophthalmology in 2017 1.
From the Research
Mechanism of Action
- Low-dose naltrexone (LDN) is hypothesized to inhibit cellular proliferation of T and B cells and block Toll-like receptor 4, resulting in an analgesic and anti-inflammatory effect 2.
- LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells, with effects unique to low dosages of naltrexone and independent from its better-known activity on opioid receptors 3.
- When used in low doses, naltrexone acts as a glial modulator with a neuroprotective effect via inhibition of microglial activation, and binds to Toll-like receptor 4, inhibiting downstream cellular signaling pathways that lead to pro-inflammatory cytokines 4.
Efficacy in Chronic Pain and Inflammation
- Evidence supports the safety and tolerability of LDN in multiple sclerosis, fibromyalgia, and Crohn's disease, with subjective benefits over placebo, but limited evidence for more objective measures 2.
- LDN has been shown to reduce symptom severity in conditions such as fibromyalgia, Crohn's disease, multiple sclerosis, and complex regional pain syndrome 3.
- A pilot trial found that LDN treatment in fibromyalgia was associated with a reduction of several key pro-inflammatory cytokines and symptoms, including a 15% reduction of FM-associated pain and an 18% reduction in overall symptoms 5.
Clinical Use and Future Research
- LDN may represent one of the first glial cell modulators to be used for the management of chronic pain disorders, but its use is still highly experimental and requires further research 3.
- A systematic review found that LDN has shown promise in reducing symptoms related to chronic pain conditions, and its mechanism appears to be modulation of neuro-inflammation, specifically the modulation of glial cells and release of inflammatory chemicals in the central nervous system 6.
- Further randomized controlled trials are needed to determine the efficacy of LDN due to insufficient evidence supporting its use in chronic pain and inflammatory conditions 2, 6.