Is Naltrexone (opioid receptor antagonist) effective for treating long Covid?

Low-Dose Naltrexone for Long COVID

Low-dose naltrexone (LDN) shows promising results for treating long COVID symptoms, particularly fatigue, pain, and neurological symptoms, and should be considered as a treatment option for patients with persistent symptoms. 1

Evidence for LDN in Long COVID

Low-dose naltrexone has emerged as a potential therapeutic option for long COVID based on several lines of evidence:

• LDN has been shown to improve quality of life and reduce symptomatology in patients with Post-COVID-19 Syndrome (PCS) 2
• A clinical study demonstrated significant improvements in 6 of 7 measured parameters including:
  • Recovery from COVID-19
  • Activities of daily living
  • Energy levels
  • Pain levels
  • Concentration
  • Sleep disturbance (All with p ≤ 0.001) 2

Mechanism of Action

Recent research provides insight into how LDN may work in long COVID:

• LDN restores Transient Receptor Potential Melastatin 3 (TRPM3) ion channel function in natural killer cells from long COVID patients 3
• This restoration reestablishes adequate calcium influx necessary for homeostatic cellular processes 3
• Dysfunctional TRPM3 ion channels are associated with the pathophysiology of long COVID 3

Dosing and Administration

Based on available evidence, the following dosing approach is recommended:

1. Start with 1 mg daily for the first month 2
2. Increase to 2 mg daily for the second month 2
3. May further titrate up to 4.5 mg daily as tolerated 4

Safety Profile

LDN appears to be generally safe in long COVID patients:

• In a study of 38 participants who commenced LDN, only 2 (5.3%) discontinued due to adverse effects 2
• Reported side effects include diarrhea and fatigue 2
• Other mild adverse events previously reported for LDN can typically be managed with dose adjustments 4

Combination Therapy

Some evidence suggests potential benefits from combining LDN with other treatments:

• LDN combined with NAD+ supplementation showed significant improvement in quality of life scores and reduced fatigue in patients with persistent fatigue after COVID-19 4
• 52% of patients were considered responders after 12 weeks of this combined treatment 4

Important Considerations

When prescribing LDN for long COVID, be aware of:

• LDN should not be used in patients taking opioid medications due to potential interactions 5
• Patients with significant liver disease may not be suitable candidates 5
• The optimal duration of treatment is still being investigated, with current studies examining effects over 12-16 weeks 4, 5

Ongoing Research

A double-blind, randomized controlled trial is currently underway to further evaluate LDN for post-COVID fatigue syndrome, which will provide more definitive evidence on its efficacy 5.

Alternative Approaches

For patients who cannot take LDN or have inadequate response, consider:

• Mitochondrial support with Coenzyme Q10 and D-ribose 1
• Antihistamines for mast cell activation symptoms 1
• Non-pharmacological options like cognitive pacing and energy conservation strategies 1
• Avoid recommending exercise for patients with post-exertional malaise, as physical activity worsened the condition in 75% of long COVID patients 1