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Nicotine and the spike protein: the hypothesis and the evidence

8 min read

Some people search for nicotine and the spike protein together, usually after hearing that nicotine might clear the spike protein from the body. This guide follows the idea one step at a time. It shows where the idea started, what each study measured, and which steps have no study at all.

Dr Bryan Ardis has no connection to FMI Patches. He does not endorse or recommend this patch. His statements are described here only so readers can check them against the research.

Where the idea started

In 2020, Jean-Pierre Changeux and colleagues published "A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications" in Comptes Rendus Biologies. The paper contains no new experiments. It combines a literature review with a sequence comparison. The authors matched a short stretch of the spike protein against a neurotoxin-like motif found in snake venom. They wrote that "this observation supports the hypothesis that SARS-CoV-2 virus itself is a nAChR blocker."

The paper's own limits are stated plainly. A sequence match is not a measurement of binding, and the authors wrote that the hypothesis "might be further challenged by additional clinical studies and by experimental observations." The paper also suggests nicotine could be studied as a treatment. That is a proposal for future work, not a finding.

Computer models of binding

The next step was computer modelling. In a 2020 preprint, Oliveira and colleagues modelled a 12-residue stretch of the spike protein docking onto three types of nicotinic receptor. They ran molecular dynamics simulations, three replicates of 300 nanoseconds per complex, and reported favourable binding energy estimates. The authors state that the work is purely computational and that "structural, mutational and single-channel studies will be of interest to test the importance" of the proposed interactions. They also say the snake receptor they used stands in for the human muscle receptor, and that it is unclear whether the peptide acts as an agonist or antagonist at the alpha-7 receptor.

A second group, including Konstantinos Farsalinos as a coauthor, published a docking study in Toxicology Reports in December 2020. It reports a toxin-like sequence in the spike protein and tests several nicotinic agonists, nicotine among them. The authors write that their hypothesis needs to be verified by in vitro and in vivo studies before the findings could have therapeutic implications. A related 2021 paper in Food and Chemical Toxicology by Lagoumintzis and colleagues uses the same kind of model. It says the results "should, however, be viewed cautiously before being experimentally verified," and that "more in vitro and clinical studies are therefore required." Four authors on that paper have a patent application pending, which the paper discloses.

The laboratory test

The most direct test of the binding step is Godellas, Cymes and Grosman, published in PNAS in 2022. They used human alpha-7 nicotinic receptors expressed on living cells. They measured whether spike fragments could displace a labelled toxin that binds the same site. Spike peptides, the S1 domain and an uncleaved S1-S2 construct did not displace it in a sequence-specific way. Scrambled control peptides gave similar results. Electrical recordings showed no clear effect of the S1 domain on the receptor's currents.

The authors conclude that binding of the spike protein to the receptor's acetylcholine-binding sites, and so competition with nicotine, "is unlikely to be a relevant aspect of this complex disease." They also list their own limits. The assay was designed for small molecules and may need longer incubation for peptides. The cells were a simplified stand-in for neurons. The full virus was not tested, and other receptor types were not tested. A negative result for one receptor type, under these conditions, is a narrower finding than a study showing that nicotine clears spike protein from the body.

Which steps have a study

Each step of the idea needs its own evidence. Here is where the sources stand.

The spike protein resembles a snake toxin: a sequence comparison exists, in the 2020 hypothesis paper and the 2021 follow-up. Nothing was tested in the body.

The spike protein binds nicotinic receptors: computer models only, in the 2020 preprint and the 2020 Toxicology Reports paper. One laboratory test of the alpha-7 site was negative.

Nicotine displaces the spike protein at receptors in the body: no study found. The only competition test in the sources above was negative, and it was run in cells, not people.

A patch clears the spike protein from the body: no study found. None of the sources opened for this guide measured spike protein clearance, in people, in animals, or from a patch.

A patch helps people with COVID-19: one randomised trial, NICOVID-REA, in ventilated intensive care patients with severe COVID-19. It found no difference in day-28 deaths, with 30 of 106 patients on nicotine and 31 of 112 on placebo. Its authors wrote: "There is no indication to use nicotine in this situation." The trial could not test prevention, and the authors wrote that they "cannot exclude a preventive effect of nicotine, if administered earlier."

No study is a different finding from a negative study. For the third and fourth steps above, the honest answer is that nobody has tested them.

What trials have not tested

The sources we opened contain no trial that gave nicotine to people after vaccination or infection in order to measure spike protein. The only randomised COVID-19 trial in this guide is the intensive care study above, which tested a different population and a different outcome. None of the studies here was designed around vaccination status.

A missing trial means the question is untested. It does not mean the idea has been tested and failed, and it does not mean the idea is correct.

What Dr Ardis has said

Dr Ardis appears as a featured guest on a Man in America episode streamed on 17 December 2024. The published transcript does not label speakers, so none of its lines can be attributed to him by name. The passages that match his research say that the spike protein would bind to nicotine receptors, that spike proteins are "almost identical to snake venoms" in the host's introduction, and that nicotine could take the place of those venoms at the receptor. In the episode's words, the receptor "will grab nicotine instead of any of the venoms and release them."

That is a claim about displacement at receptors. It is not a claim about clearing spike protein from the body, and the transcript contains no dosing schedule or treatment protocol. The snake venom comparison is stated more strongly in the episode than the 2020 paper states it, and the studies above did not confirm that step. The episode page also carries sales copy for a nicotine patch that is not attributed to him. This guide does not repeat it.

The short version

The idea that nicotine might counter the spike protein comes from a 2020 hypothesis paper and a set of computer models. One laboratory test of the receptor binding step was negative for the receptor type it tested. No source opened for this guide shows that nicotine clears spike protein from the body. The one randomised trial of nicotine in severe COVID-19 found no benefit in ICU patients.

These sources are about nicotine and the spike protein in general. None of them is a study of this patch.

The linked research covers each ingredient on its own and is not a study of this patch. These statements have not been evaluated by the FDA or the TGA. This product is not intended to diagnose, treat, cure, or prevent any disease.

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