Exploring Nicotine Therapy for Long COVID Brain Fog: Potential, Risks, and the Need for Evidence

Could Nicotine Be a Relief for Long COVID Brain Fog?

Long COVID, a condition characterized by lingering symptoms that persist long after an initial SARS-CoV-2 infection, continues to puzzle both researchers and healthcare providers. One of the most debilitating symptoms affecting millions worldwide is 'brain fog'—a term describing cognitive difficulties such as memory lapses, poor concentration, and mental fatigue. In the quest for innovative treatments, a surprising candidate has entered the spotlight: nicotine, commonly known for its use in smoking cessation products like gum and patches.

How Nicotine Entered the Long COVID Conversation

Nicotine has traditionally been used in controlled forms to aid people in quitting smoking. Recently, however, anecdotal reports and early-stage research have suggested it might offer relief for neurological symptoms related to long COVID, particularly brain fog and fatigue. A notable personal account, highlighted in Slate, tells the story of a woman whose persistent cognitive difficulties improved significantly after she began chewing low-dose nicotine gum. While individual anecdotes cannot serve as proof of effectiveness, her experience aligns with findings from an intriguing small-scale study in Germany.

The German Pilot Study: Early Signs of Promise

In this preliminary German study, four individuals suffering from long COVID symptoms received daily low-dose nicotine patches. Remarkably, all exhibited noticeable improvements in symptoms such as tiredness, weakness, shortness of breath, and exercise intolerance within six days. Those who had lost their sense of taste or smell also reported full recovery of those senses within 16 days. Given the limited size and scope of the study, researchers caution against drawing broad conclusions, but the results suggest a potential avenue for further investigation through larger clinical trials.

Understanding Long COVID and the Neurological Link

Long COVID affects a significant proportion of people following COVID-19 infection. Some recover fully within weeks, while an estimated 3% to 5%—over 2.8% of the UK population—continue to experience symptoms for months or even years. Brain fog, along with fatigue and mood disturbances, are among the most commonly reported neurological complaints.

Current research suggests these symptoms may arise due to a combination of factors, including persistent inflammation, reduced oxygen supply to the brain, vascular (blood vessel) damage, and disruption of the blood-brain barrier. However, the exact mechanisms driving long COVID's cognitive effects remain under active investigation.

The Acetylcholine Hypothesis

One leading theory explored by the German research team involves acetylcholine, a key neurotransmitter necessary for memory, attention, and mood regulation. Acetylcholine communicates via specialized receptors (nicotinic acetylcholine receptors) found throughout the nervous system. The hypothesis posits that the COVID-19 virus may disrupt the functioning of these receptors, either by direct interference or altering their signaling efficiency. Such disruption could explain many of the cognitive and mood-related symptoms observed in long COVID patients.

Why Might Nicotine Help? Mechanisms and Delivery Methods

Nicotine, the primary compound in tobacco products, also binds to nicotinic acetylcholine receptors. This raises the possibility that nicotine could restore normal receptor function—at least partially—counteracting the interference thought to be caused by the virus. While the notion that nicotine directly displaces the virus is highly speculative and not established, its role in regulating these neural pathways is a topic of scientific interest.

Nicotine replacement therapies are available in various forms including patches, gum, lozenges, and nasal sprays. Patches deliver nicotine steadily through the skin, minimizing spikes in blood nicotine concentration and, in some studies, lowering the risk of chemical dependency. Gum and lozenges, in contrast, enable users to control dosage but can lead to rapid increases in blood nicotine levels.

Evaluating Nicotine's Cognitive Effects

Research on nicotine's influence on cognitive performance yields mixed results. While some studies show marginal improvement in attention and alertness, findings on memory and concentration are inconsistent. Importantly, the body of evidence specific to long COVID remains limited, underscoring the urgent need for large-scale, targeted research.

Risks and Safety Considerations

Nicotine, even in non-combustible forms such as patches or gum, is not without health risks. Common side effects include nausea, dizziness, increased heart rate, and elevated blood pressure. For people with long COVID symptoms like exercise intolerance, certain stimulant effects on heart rate may even provide some benefit—though this must be closely monitored in a medical setting. Long-term use, particularly among never-smokers, raises important concerns about the potential for addiction and adverse cardiovascular impacts.

Expert Caution and Alternative Approaches

Medical professionals strongly advise against self-medicating with nicotine products for long COVID brain fog or related symptoms. The absence of standardized dosing guidelines, the risk of dependency, and the long-unknown effects make unsupervised use a risky proposition. Instead, experts recommend evidence-based lifestyle strategies: gradual increases in physical activity, balanced nutrition, avoiding alcohol and tobacco, ensuring adequate sleep, practicing mindfulness, and engaging in cognitive stimulation are all believed to support neurological recovery.

Investigational medications, such as guanfacine (sometimes combined with N-acetylcysteine), are also being explored for their potential to ameliorate brain fog in small patient cohorts. Additionally, a clinical trial has tested nicotine for mild cognitive impairment in older adults, though this research was not focused on long COVID. Given increasing anecdotal interest and preliminary results, more rigorous clinical trials looking at nicotine’s safety and efficacy for long COVID symptoms are likely in development.

Conclusion

The emergence of nicotine replacement therapies as a possible intervention for long COVID brain fog underscores the complexity of both the condition and its treatment landscape. While early anecdotes and small studies hint at potential benefit, much remains unknown about efficacy, safety, and the underlying neurological mechanisms. For now, the use of nicotine-based therapies should be reserved for supervised clinical research settings. The pressing global challenge of long COVID demands continued research into both pharmaceutical and lifestyle-based therapies, ensuring that any new treatments are both safe and effective for those still battling the long-term effects of COVID-19.