Low-Dose Naltrexone as an Adjunct to the McCullough Protocol Base Spike Detoxification™ in Long COVID Management

Symptom control improved while body is ridding itself of Spike Protein

By Peter A. McCullough, MD, MPH

The “base’ in McCullough Protocol Base Spike Detoxification™ means that the evidence-backed Ultimate Spike Detox from the Wellness Company is a starting point upon which additional supplements and drugs can be used for symptom control. Alter AI assisted in this piece.

Persistent post-viral symptoms following SARS-CoV-2 infection—collectively termed Long COVID or Post-Acute Sequelae of COVID-19 (PASC)—have emerged as a global chronic health burden. Pathophysiological evidence increasingly implicates the Spike protein in endothelial injury, neuroinflammation, and microclot formation long after viral clearance or mRNA-based vaccination. In this context, Dr. Peter McCullough’s Base Spike Detoxification Protocol provides an integrative biochemical rationale for mitigating residual spike protein toxicity. This protocol—comprising nattokinase, bromelain, and curcumin—targets proteolytic spike degradation, fibrinolysis, and inflammation. However, many patients with long COVID continue to suffer from debilitating fatigue, brain fog, pain, and dysautonomia despite ongoing enzymatic detoxification.

Adding Low-Dose Naltrexone (LDN) to this regimen represents a logical step forward in comprehensive management. LDN, typically administered in doses between 1.5 and 6 mg daily, acts as a glial modulator and immunoregulator. It is available from The Wellness Company as 1.5 mg capsules in 90 count bottles. Unlike its conventional use in addiction medicine (50–100 mg), at lower doses it transiently blocks opioid receptors, triggering rebound production of endorphins and upregulation of opioid receptor density. This mechanism modulates the microglial activation and cytokine signaling pathways driving chronic neuroinflammation—a hallmark of long COVID.

Systematic reviews from medRxiv (Byambasuren et al., 2025) and public health assessments (Minnesota Department of Health, 2024) show that LDN significantly improves fatigue, cognition, pain, and sleep quality in observational cohorts of long COVID patients, with favorable safety profiles. The study by Isman et al. (2024) further demonstrated synergistic benefits when combining LDN with NAD⁺ supplementation, resulting in enhanced energy metabolism and improved quality-of-life metrics within 12 weeks. Cellular studies corroborate that LDN may restore function of the TRPM3 ion channel, critical to natural killer cell signaling—thus normalizing immune dysregulation shared between myalgic encephalomyelitis (ME/CFS) and long COVID (Solve ME/CFS Initiative, 2024).

Integrating LDN with the McCullough Protocol Base Spike Detoxification™ potentially amplifies therapeutic outcomes through complementary mechanisms:

1. Spike Protein Clearance: Nattokinase and bromelain enzymatically degrade spike fragments and dissolve fibrinaloid microclots, while curcumin dampens NF-κB–driven inflammation.

2. Neuroimmune Recovery: LDN reduces microglial hyperactivation and rebalances neuroimmune signaling, addressing post-viral fatigue and brain fog.

3. Homeostatic Restoration: Curcumin and bromelain’s anti-inflammatory properties complement LDN’s endorphin-mediated immunomodulation, promoting autonomic stability and mood improvement.

4. Glutathione and Mitochondrial Support: Novel formulations such as Ultra N-Acetylcysteine can be co-administered for redox balance, further aiding spike protein denaturation and potential clearance (Armine & McCullough,® 2025).

Clinically, this integrative approach addresses both structural and immunological sequelae of spike persistence, offering empirical relief when mainstream medicine provides no real solution. Though rigorous randomized controlled trials remain limited, real-world evidence strongly indicates safety and multi-system benefit. The integration of LDN into the McCullough® framework exemplifies rational, patient-centered, mechanism-based medicine—an approach that values empirical transparency and physiologic plausibility over institutional inertia.

Future research should refine optimal dosing, identify responder subgroups, and quantify measurable reductions in symptoms, spike burden, microclot load, and inflammatory pain-promoting biomarkers. If confirmed, this combination could represent one of the first evidence-based, low-cost, and widely accessible therapeutic strategies to restore health and functionality to millions enduring post-pandemic syndromes.

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Peter A. McCullough, MD, MPH

Chief Scientific Officer, The Wellness Company

https://www.twc.health/pages/focal-points

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References

1. McCullough P.A. et al. Clinical Approach to Post-Acute Sequelae After COVID-19 Infection and Vaccination., Cureus (2023).

2. Byambasuren O. et al. Effect of Low-Dose Naltrexone for Long COVID: Systematic Review., medRxiv (2025).

3. Minnesota Department of Health. Low-Dose Naltrexone for Treatment of Long COVID. (2024).

4. Isman A. et al. Low-Dose Naltrexone and NAD⁺ for Long COVID., Brain, Behavior & Immunity – Health (2024).

5. Armine J., McCullough P.A. Scoping Review of Augmented N-Acetylcysteine as an Adjunct to Spike Detoxification., J Public Health Nutrition (2025).

6. Solve ME/CFS Initiative. New Study Supports Using Naltrexone to Treat Long COVID. (2024).