Nicotine and Schizophrenia: Dr. Ardis on the Nicotinic Receptor in the Mind

Dr. Bryan Ardis states that schizophrenia is cured with nicotine, and that the research studies behind that statement are collected in his book. He also lists schizophrenia among the conditions he says snake venom is published to cause — part of his wider argument that venom-like toxins and nicotine compete for the same receptors in the body, the nicotinic acetylcholine receptors.

Schizophrenia and nicotine have a long shared history in psychiatric research. People with schizophrenia smoke far more often than almost any other group, and from the early 1990s a research group in Denver, Colorado, traced part of the reason to one receptor — the α7 (alpha-7) nicotinic receptor — and to a brain-wave test of how the brain filters sound. This page sets out what Dr. Ardis says, then walks through that body of research: the smoking studies, the self-medication idea, the P50 “sensory gating” test, the chromosome 15 gene, the post-mortem receptor counts, the nicotine patch studies and the drug trials built on all of it.

Table of Contents

  1. What Dr. Ardis Says
  2. How Often People With Schizophrenia Smoke
  3. The Self-Medication Hypothesis
  4. Sensory Gating and the P50 Brain Wave
  5. The α7 Receptor Gene on Chromosome 15
  6. Fewer Nicotinic Receptors in Post-Mortem Brain Tissue
  7. Nicotine Patch Studies on Attention and Memory
  8. α7 Agonist Trials: DMXB-A (GTS-21)
  9. Safety Notes
  10. Dr. Ardis’s Own Work
  11. Key Research Papers
  12. Connections
  13. Featured Videos

1. What Dr. Ardis Says

Dr. Ardis set this out in a 2025 podcast appearance (Culture Apothecary) and in his book Moving Beyond the COVID-19 Lies: Restoring Health and Hope for Humanity. He makes two statements about schizophrenia.

Nicotine and schizophrenia

Dr. Ardis states that schizophrenia is cured with nicotine. He places it in a list of conditions he describes as targeting, or being helped through, the nicotinic receptors — rabies, HIV, the influenza viruses and the common-cold viruses — and says the research for each is in his book:

What, did you know that schizophrenia is cured with nicotine? … All these I put in the book, by the way. It’s all in there. I’ll show you all the research studies.

He presents himself as the collector of that research rather than its author: “I didn’t prove this, all the scientists that I just collected and gave it to you because it’s so mind-blowing and amazing.” He wants the CDC, NIH and HHS to investigate every condition and virus that targets nicotinic receptors, and whether nicotine — from tobacco products and from the vegetables that carry it in small amounts — is the cure for all of them.

Snake venom and schizophrenia

Later in the same conversation Dr. Ardis lists schizophrenia among the conditions he says snake venom is published to cause:

Did you know snake venom is published to cause miscarriages, infertility, glioblastomas, arthritis, all autoimmune diseases, schizophrenia, Parkinson’s, Alzheimer’s? Did you know it does that? And you know, our government publishes that it does that.

He goes on to say that a 2024 government document lists the new diagnosable long COVID conditions, and that 100% of the roughly 200 long COVID symptoms — which, he says, include schizophrenia, PTSD and psychosis — are also published long-term effects of snake venom in people bitten by snakes. He adds that, even when a bitten person is saved with antivenom in hospital, the venom stays in the body for 14 years. In his view this is the link between schizophrenia, venom and the nicotinic receptor: venom toxins and nicotine bind the same receptor family.

Dr. Ardis does not name a single study for either statement in this appearance; he points readers to his book. The specific studies are not identified here; related published work is listed below.

Back to Table of Contents

2. How Often People With Schizophrenia Smoke

The starting point for nearly all of the research on this page is a plain observation: people with schizophrenia smoke at very high rates, and they tend to smoke heavily.

The largest summary of that observation is a 2005 meta-analysis by Jose de Leon and Francisco Diaz at Eastern State Hospital in Lexington, Kentucky. A meta-analysis pools the results of many separate studies. They gathered 42 studies from 20 countries and found that people with schizophrenia were far more likely to be current smokers than the general population — a weighted average odds ratio of 5.9, meaning the odds of smoking were roughly six times higher. The association was stronger in men (odds ratio 7.2, from 32 studies) than in women (3.3, from 25 studies).

The link held up under stricter comparisons. Against people with other severe mental illnesses, the odds ratio was still 1.9; in three studies that adjusted for other factors, it stayed between 2 and 3. Heavy smoking and high nicotine dependence were more common in smokers with schizophrenia than in smokers in the general population, quit rates were lower, and people with schizophrenia were more likely ever to have smoked. In two studies that adjusted for confounders, people with schizophrenia had a higher risk of starting daily smoking. The authors concluded that “people who are going to develop schizophrenia have risk factors that make them more vulnerable to start smoking.”

A 2005 review by Veena Kumari and Peggy Postma at the Institute of Psychiatry in London put the smoking rate in schizophrenia at two to four times that of the general population, and noted that patients tend to favour stronger cigarettes and may extract more nicotine from each one than other smokers do.

Back to Table of Contents

3. The Self-Medication Hypothesis

Why would one diagnosis carry such a strong pull toward nicotine? One long-standing answer is the self-medication hypothesis: that many people with schizophrenia smoke because nicotine eases something the illness disturbs, in the way a person might reach for coffee to clear a foggy head.

Kumari and Postma’s review sets out the explanations researchers have offered for the high smoking rate, with particular attention to the theories that tie it to sensory gating (the brain’s ability to filter out repeated, unimportant input) and to the attention and memory difficulties that are part of schizophrenia. They describe those gating and cognitive findings as the main support for the self-medication idea. Other explanations they review include nicotine easing the side effects of antipsychotic drugs and shared social and biological risk factors.

The Denver group that ran the α7 trials described in section 8 framed the question the same way in 2008: patients’ heavy smoking, they wrote, “suggests attempted self-medication” through the α7 nicotinic receptor. The next three sections follow how they arrived there.

Back to Table of Contents

4. Sensory Gating and the P50 Brain Wave

Imagine hearing two clicks half a second apart. In most people the brain responds strongly to the first click and much more weakly to the second — it has already “filed” the sound and turns the volume down on the repeat. This filtering is called sensory gating, and it can be measured with scalp electrodes as a small brain wave that appears about 50 milliseconds after each click, called the P50. A normal result is a much smaller P50 to the second click than to the first.

Most people with schizophrenia do not show that drop: the second click draws nearly as big a response as the first. Researchers link this to the difficulty many patients describe in shutting out background noise and holding attention.

Adler 1993: cigarettes and the P50 test

In 1993 Lawrence Adler, Robert Freedman and colleagues at the Denver VA Medical Center tested whether smoking changes this result. They studied 10 smokers with schizophrenia and 10 smokers without psychiatric illness. Everyone abstained from smoking from 11 p.m. until 8 a.m. the next morning, when their P50 responses to paired clicks were recorded. Then they smoked as much as they wished, and the recordings were repeated twice.

The patients with schizophrenia showed what the authors called “a marked but brief improvement” in P50 gating immediately after smoking. In the smokers without psychiatric illness, gating was slightly impaired. The authors concluded that cigarette smoking “can transiently normalize” the gating deficit in schizophrenia. The word transiently mattered to the group’s later work: the effect faded quickly, which they connected to the way nicotine switches the α7 receptor on and then leaves it unresponsive for a time.

Back to Table of Contents

5. The α7 Receptor Gene on Chromosome 15

Nicotinic receptors come in many subtypes, built from different protein subunits. The α7 subtype is made of five identical α7 subunits, is common in the hippocampus (a memory and filtering centre of the brain) and is encoded by a gene called CHRNA7.

Freedman 1997: a family study points to 15q13–14

The P50 gating deficit runs in families: it appears in most people with schizophrenia and also in many of their relatives who do not have the illness. In a 1997 study in the Proceedings of the National Academy of Sciences, Robert Freedman and a large team from the University of Colorado studied nine families with multiple cases of schizophrenia. Earlier work in people and animals had suggested that weaker α7 receptor function could underlie the gating defect.

Using a genome-wide linkage analysis — a scan for stretches of DNA that travel through families together with a trait — they found that the P50 deficit was linked to a marker at chromosome 15q13–14, the location of the α7 nicotinic receptor gene, with a maximum lod score of 5.3 (a lod score above 3 is the usual threshold for meaningful linkage). The authors noted that, despite patients’ “extremely heavy nicotine use,” nicotinic receptors had not previously been thought to be involved in schizophrenia, and concluded that the α7 gene “may be responsible for the inheritance of a pathophysiological aspect of the illness.”

Leonard 2002: variants in the gene’s switch region

In 2002 Sherry Leonard and colleagues at the University of Colorado sequenced the core promoter of CHRNA7 — the stretch of DNA that acts as the gene’s on-switch — in people from 166 families with schizophrenia and in 165 controls. They found several promoter variants and showed in laboratory tests that the functional ones reduced how much of the gene was transcribed. These functional variants were significantly more common in the schizophrenia group, and controls who carried one were more likely to fail the P50 gating test. The authors cautioned that other nearby genetic changes could not be ruled out, and concluded that the promoter variants “may contribute to a common pathophysiologic feature of schizophrenia.”

Back to Table of Contents

6. Fewer Nicotinic Receptors in Post-Mortem Brain Tissue

If the α7 receptor matters to gating, people with schizophrenia might have fewer of those receptors. Counting them requires a molecule that sticks to the receptor and nothing else — and the standard tool for the α7 receptor comes from snake venom.

α-Bungarotoxin: a venom toxin used as a receptor tag

α-Bungarotoxin is a toxin from the venom of the many-banded krait, an Asian snake. It binds tightly to the α7 nicotinic receptor (and to the muscle-type nicotinic receptor) and blocks it. Because it binds so tightly, researchers attach a radioactive label to it and use it to map where α7 receptors sit in brain tissue. This is the same receptor family that Dr. Ardis points to when he links venom toxins and nicotine.

Freedman 1995: the hippocampus

Freedman, Hall, Adler and Leonard published the receptor count in 1995. Their reasoning, as stated in the paper: α-bungarotoxin produces a defect in auditory gating in laboratory animals that resembles the gating defect seen in schizophrenia, and nicotine transiently normalises that defect in patients.

They obtained post-mortem hippocampus tissue from eight people with schizophrenia and eight age-matched people without it. Sections were labelled with radioactive α-bungarotoxin and imaged; binding of a second nicotinic compound, cytisine, was also measured. The toxin labelled a population of probable inhibitory interneurons — nerve cells whose job is to quiet other nerve cells — mainly in the dentate gyrus and the CA3 region. That labelling was significantly lower in the schizophrenia tissue, with seven of the eight patients below the range of the comparison group, and cytisine binding was also significantly lower. The differences were not explained by general cell loss, drug exposure at the time of death, or smoking history.

The authors suggested that fewer nicotinic receptors could mean the brain’s own acetylcholine fails to switch on these quieting interneurons, which would show up clinically as poor gating of sensory input — the P50 finding in section 4.

Back to Table of Contents

7. Nicotine Patch Studies on Attention and Memory

Studies of smokers are hard to read: a smoker who has gone without nicotine overnight is in withdrawal, and part of any “improvement” after a cigarette may simply be relief of that withdrawal. To get around this, a group at Massachusetts General Hospital in Boston gave nicotine patches to people who did not smoke at all.

Barr 2008: attention

Ruth Barr, A. Eden Evins and colleagues studied 28 non-smoking adults with schizophrenia and 32 non-smoking healthy controls. Each person wore a 14 mg nicotine patch on one visit and an identical placebo patch on another, in random order, and took a battery of thinking tests before and three hours after each patch. The main test was the Continuous Performance Test, Identical Pairs version, a sustained-attention task in which the person presses a button whenever two identical items appear in a row.

Nicotine significantly improved reaction time, made reaction times more consistent and reduced random errors in both groups. It reduced commission errors (pressing when one should not) and improved performance on a Stroop task (naming the ink colour of a printed colour word) to a greater extent in the schizophrenia group than in the controls. The authors summarised that a single dose of nicotine improved attention in both groups and was linked to greater gains in the inhibition of impulsive responses in people with schizophrenia.

Jubelt 2008: memory

A companion study from the same group, led by Lindsay Jubelt, tested episodic memory in 10 non-smoking adults with schizophrenia and 12 non-smoking controls, again with a 14 mg patch against placebo, with testing before and four hours after application. Nicotine was associated with faster and more accurate recognition of new items, and there was a trend toward a stronger reduction in mistaken “seen it before” answers to new items in the schizophrenia group. Nicotine had no effect on accuracy or speed for items the person had already seen. The authors suggested that the effect of longer-term nicotinic treatment on novelty detection deserved study.

Both studies tested a single patch on a single day, in adults; neither was designed to measure the symptoms of schizophrenia over time.

Back to Table of Contents

8. α7 Agonist Trials: DMXB-A (GTS-21)

Nicotine is what pharmacologists call a low-potency agonist at the α7 receptor: it switches the receptor on weakly and then leaves it unresponsive for a while. The Denver group wanted a compound that would switch α7 on more selectively. They chose DMXB-A (3-(2,4-dimethoxybenzylidene) anabaseine, also known as GTS-21), a derivative of anabaseine, a natural alkaloid related to nicotine. DMXB-A is a partial α7 agonist and can be taken by mouth.

Olincy 2006: the proof-of-concept trial

Ann Olincy, Robert Freedman, William Kem and colleagues ran a randomised, double-blind crossover trial of two doses of DMXB-A and a placebo in 12 non-smokers with schizophrenia who continued their usual antipsychotic medicine. One person was withdrawn because of a temporary drop in white blood cell count. The main measures were the total score on the Repeatable Battery for the Assessment of Neuropsychological Status (a standard set of memory, attention and language tests) and P50 gating.

The trial found significant improvement in the total thinking-test score, particularly at the lower DMXB-A dose compared with placebo, and the authors reported that the effects were greater than those of nicotine in a similar study. P50 gating also improved significantly. Patients generally tolerated the drug well. The authors called for longer trials to establish clinical usefulness.

Freedman 2008: the first phase 2 trial

The follow-up trial, published in the American Journal of Psychiatry in 2008, gave 31 non-smoking people with schizophrenia two doses of DMXB-A and a placebo for four weeks each, in a three-arm, double-blind crossover design at two sites, alongside their usual antipsychotic. Thinking was measured with the MATRICS Consensus Cognitive Battery; symptoms with the Scale for the Assessment of Negative Symptoms (SANS) and the Brief Psychiatric Rating Scale (BPRS).

Across all three arms there was no significant difference between DMXB-A and placebo on the MATRICS thinking measures. At the higher dose, patients showed significant improvement on the SANS total score and nearly significant improvement on the BPRS total score, most clearly in anhedonia (loss of pleasure) and alogia (poverty of speech) — the so-called negative symptoms. In the first treatment period alone, DMXB-A was associated with improvement in attention/vigilance and working memory compared with baseline. Five people developed a mild tremor and nearly half had mild nausea. The authors concluded that DMXB-A improved ratings of negative symptoms “that are generally resistant to treatment” with standard antipsychotics, and that its clinical usefulness was not yet determined.

Back to Table of Contents

9. Safety Notes

Back to Table of Contents

10. Dr. Ardis’s Own Work

Dr. Ardis says the research studies behind his statements on schizophrenia are collected in his 2024 book, described on this site at Moving Beyond the COVID-19 Lies. His nicotine hypothesis, his snake-venom argument and the rest of his work are gathered on the Dr. Bryan Ardis hub.

Back to Table of Contents

Key Research Papers

  1. de Leon J, Diaz FJ (2005). A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors. Schizophr Res. — PubMed PMID: 15949648
  2. Kumari V, Postma P (2005). Nicotine use in schizophrenia: the self medication hypotheses. Neurosci Biobehav Rev. — PubMed PMID: 15964073
  3. Adler LE, Hoffer LD, Wiser A, Freedman R (1993). Normalization of auditory physiology by cigarette smoking in schizophrenic patients. Am J Psychiatry. — PubMed PMID: 8238642
  4. Freedman R, Coon H, Myles-Worsley M, Orr-Urtreger A, et al. (1997). Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proc Natl Acad Sci U S A. — PubMed PMID: 9012828
  5. Leonard S, Gault J, Hopkins J, Logel J, et al. (2002). Association of promoter variants in the alpha7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia. Arch Gen Psychiatry. — PubMed PMID: 12470124
  6. Freedman R, Hall M, Adler LE, Leonard S (1995). Evidence in postmortem brain tissue for decreased numbers of hippocampal nicotinic receptors in schizophrenia. Biol Psychiatry. — PubMed PMID: 7548469
  7. Barr RS, Culhane MA, Jubelt LE, Mufti RS, et al. (2008). The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia and nonpsychiatric controls. Neuropsychopharmacology. — PubMed PMID: 17443126
  8. Jubelt LE, Barr RS, Goff DC, Logvinenko T, et al. (2008). Effects of transdermal nicotine on episodic memory in non-smokers with and without schizophrenia. Psychopharmacology (Berl). — PubMed PMID: 18548234
  9. Olincy A, Harris JG, Johnson LL, Pender V, et al. (2006). Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia. Arch Gen Psychiatry. — PubMed PMID: 16754836
  10. Freedman R, Olincy A, Buchanan RW, Harris JG, et al. (2008). Initial phase 2 trial of a nicotinic agonist in schizophrenia. Am J Psychiatry. — PubMed PMID: 18381905

PubMed Topic Searches

  1. PubMed: Schizophrenia, nicotine and self-medication
  2. PubMed: P50 sensory gating and nicotine in schizophrenia
  3. PubMed: CHRNA7 and schizophrenia
  4. PubMed: α7 nicotinic agonist trials in schizophrenia

Back to Table of Contents

Connections

Back to Table of Contents