Nicotine Patch Protocol
Note: Please note, we do not support using a nicotine patch for any longer than 30 days and preferably no longer than 14 days.
Nicotine Patches for Long COVID
Research-Based Insights on Managing Long COVID Symptoms
Are you struggling with persistent symptoms like brain fog, fatigue, or loss of taste and smell after COVID-19?
Emerging research suggests that nicotine patches may provide relief for certain Long COVID symptoms. This page summarizes the latest findings, patient experiences, and expert opinions to help you understand this potential treatment option.
What Nicotine has NOT been demonstrated to do:
Nicotine has not been demonstrated to directly neutralize SARS-CoV-2 spike protein in humans. Computational studies have explored possible interactions involving nicotine, ACE2, and spike protein, but these do not establish a therapeutic effect in patients. They also cannot support the categorical statement that nicotine “does not interact” with spike protein. Computational study, 2020
Nicotine has not been shown to prevent spike protein from binding to ACE2 in humans. A 2026 study reported weak, millimolar-range binding between nicotine and ACE2 in laboratory experiments. The authors emphasized that these findings do not establish physiological effects. Therefore, “nicotine does not bind to ACE2” should be removed. Mallawarachchi et al., Scientific Reports, 2026
Nicotine acts on nicotinic acetylcholine receptors, including α7 receptors, but has not been demonstrated to dislodge spike protein from these receptors in humans. A 2022 experimental study found no appreciable competition by the tested spike preparations at the receptor’s usual neurotransmitter-binding sites. A separate 2023 study reported effects consistent with spike acting at a different, allosteric site. These findings argue against a simple competitive-displacement mechanism; they do not establish that displacement is impossible under every condition. Godellas et al., PNAS, 2022; O’Brien et al., Journal of Biological Chemistry, 2023
Nicotine has not been demonstrated to remove or “flush” spike protein from the body. The frequently cited 2023 report described symptom changes in four people using nicotine patches; it did not demonstrate spike-protein clearance. Symptom improvement alone cannot establish that mechanism. Leitzke, Bioelectronic Medicine, 2023
Nicotine Patches for Long COVID Symptom Management?
Nicotine patches have gained attention as a potential treatment approach for persistent Long COVID symptoms, particularly fatigue, brain fog, autonomic symptoms, and other complaints potentially related to impaired cholinergic signaling.
The Nicotine Patch Protocol is based largely on two publications by Marco Leitzke and colleagues, but the strength of this evidence is limited and should be described accurately.
The first Leitzke paper was an uncontrolled observational report involving only four patients with post-COVID syndrome who used low-dose transdermal nicotine, generally around 7–7.5 mg per day. Improvements in several persistent symptoms were reported, but there was no placebo group, no randomization, and only four participants, so the study cannot establish efficacy. Its primary importance was in proposing a possible therapeutic mechanism involving nicotinic acetylcholine receptors and impaired cholinergic signaling.
The second Leitzke publication was primarily a survey-based study, rather than a controlled treatment trial. Patients reported their experiences with low-dose transdermal nicotine, and many described symptomatic improvement. Because the data were largely self-reported, the findings are vulnerable to selection bias, recall bias, placebo effects, and other confounding factors. The study therefore provides additional hypothesis-generating information but does not establish that nicotine patches are an effective treatment for Long COVID.
These two Leitzke publications are the principal published basis for what has become known as the Nicotine Patch Protocol for Long COVID. At present, however, the protocol is based on a four-patient uncontrolled observational report, subsequent survey data, mechanistic hypotheses, and accumulated patient experience rather than randomized controlled clinical trials.
The proposed rationale includes modulation of nicotinic acetylcholine receptors, restoration of cholinergic nervous-system signaling, and activation of the cholinergic anti-inflammatory pathway.
Interest in the protocol has also been driven substantially by the patient-led Nicotine Patch Test, formerly known as The Nicotine Test, where people with Long COVID share dosing strategies, responses, adverse effects, and individual experiences:
These community reports can generate useful clinical questions and treatment hypotheses, but they remain anecdotal observations rather than controlled scientific evidence.
The nicotine-patch approach has also been discussed in several medical and science-oriented articles. A McGill University Office for Science and Society review, The Strange Story of Nicotine Patches to Treat Long COVID, examines the origins of the nicotinic hypothesis and emphasizes that supporting evidence remains limited and inconsistent. The article notes that some patients report improvement while others report worsening and argues that these experiences should be considered hypothesis-generating rather than proof of efficacy.
A feature in The Sick Times, Nicotine patches help relieve symptoms in some people with Long COVID. Can the science behind it lead to future therapies?, reviews patient experiences with transdermal nicotine and explores the possible scientific mechanisms behind these reports, including nicotinic acetylcholine receptor signaling and its potential relevance to future therapeutic development.
Gordon Medical Associates has also published How Nicotine Is Changing the Game for Long COVID, which discusses nicotine patches from a more favorable clinical perspective and describes proposed mechanisms and reported patient responses.
https://gordonmedical.com/how-nicotine-is-changing-the-game-for-long-covid/
Together, these articles illustrate both the interest surrounding nicotine patches and the substantial uncertainty that remains. They should not be interpreted as additional clinical-trial evidence; rather, they provide commentary, patient experiences, and differing interpretations of the same early scientific literature.
Nicotine patches are not FDA-approved for the treatment of Long COVID, and no randomized controlled trial has yet established their efficacy for Long COVID. The available clinical evidence consists primarily of a four-patient uncontrolled observational report, a subsequent survey-based study, mechanistic hypotheses, and patient-reported experience. The Nicotine Patch Protocol should therefore be considered an experimental approach supported by preliminary, hypothesis-generating evidence rather than established clinical-trial evidence.
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How Nicotine Patches Support Post-COVID Recovery
Nicotine interacts with nicotinic acetylcholine receptors (nAChRs), which play a crucial role in communication between nerve cells and regulating inflammation. Emerging research suggests the following mechanisms may contribute to its effects on Long COVID symptoms:
- Activation of nAChRs: These receptors are involved in almost all synaptic nerve signals. Nicotine may help restore their function, which could be disrupted by the SARS-CoV-2 virus.
- Cholinergic Anti-Inflammatory Pathway: Nicotine binds to α7-nAChRs on macrophages and nerve cells, activating a pathway known to reduce inflammation.
- Increased ACE2 Expression: Nicotine may upregulate the production of ACE2 receptors, which play a role in modulating inflammation and blood pressure.
- Vagus Nerve Activity: Nicotine has been shown to increase vagus nerve activity, which is critical for autonomic nervous system balance.
- Reduction of Chronic Inflammation: By activating nAChRs, nicotine may decrease systemic inflammation often observed in Long COVID.
From the current available research
A typical approach is based on findings from early studies and patient reports. The papers report:
- Starting with a Low Dose: Begin with a 7mg nicotine patch, commonly used for smoking cessation.
- Short-Term Application: Use for 14–30 days while monitoring symptoms.
- Consult a Healthcare Provider: Tailor the dosage and duration to your needs with professional guidance.
Note: This protocol is derived from existing studies and is not a one-size-fits-all solution. Individual responses may vary.
While some healthcare professionals are cautiously optimistic about nicotine patches for Long COVID, they emphasize the need for further research, including larger clinical trials to confirm efficacy, investigations into long-term safety, and studies to identify which patient groups may benefit the most. Experts agree that patients should approach this treatment under medical supervision and in conjunction with other care options.
“Nicotine’s interaction with acetylcholine receptors shows promise, but the complexity of Long COVID requires more comprehensive studies to confirm its role.”
If the protocol is not working for you
The nicotine patch helps some people with Long COVID and does nothing for others. That difference usually comes down to which mechanism is driving your symptoms. Fatigue from mitochondrial dysfunction responds to different treatment than fatigue from dysautonomia, and neither one shows up on a standard blood panel. If you have run the protocol and nothing has shifted, the question worth answering is which mechanism you are actually dealing with.
Dr. Groysman evaluates patients for the six mechanisms behind most Long COVID symptoms and treats the one driving your case. You can read how that assessment works on the treatments page.
Getting started
Telemedicine consultation: initial evaluation available remotely if you are not local to Texas
In-person assessment: full evaluation with diagnostic testing at the Plano clinic
Treatment planning: based on your symptoms, your triggers, and whether you are a candidate
Contact
Phone: 214-390-7557 (click to call)
Online booking: schedule through our patient portal
Location: Plano, Texas, serving greater Dallas Fort Worth and telehealth patients nationwide