Smoking Cessation, Part II: Crafting an Ideal Solution

Introduction

Last week, we covered the various options for smoking cessation, and discovered that most of them had serious flaws. Although use of nicotine replacement therapies (NRTs) is cited to be 2X more effective than quitting cold turkey, it’s worth remembering cold turkey only works less than 5% of the time in keeping patients off cigarettes after 6 months.

If we want a healthier population, then we need to do much better than that.

So what do we think a successful smoking cessation product should look like?

Minimize withdrawal effect through gradual nicotine reduction:

Withdrawal symptoms are an important contributor to smoking relapse, and if we want to effectively minimize withdrawal effects, we need to understand what happens inside the body when a person starts and quits smoking:

Where Does Smoking Addiction Come From at a Molecular Level?

Smoking addiction primarily stems from the interaction between nicotine and the brain's reward system. Nicotine binds to nicotinic acetylcholine receptors (nAChRs) in the brain, and this binding triggers the release of neurotransmitters, including dopamine, which creates feelings of pleasure and reward. Over time, repeated nicotine exposure leads to changes in the brain, increasing the number of nicotine receptors and altering the brain’s chemistry to become dependent on nicotine for dopamine release.

Nicotine's Molecular Pathway During Quitting: Down-Regulation of Receptors

When nicotine intake stops, the brain begins the process of down-regulation, gradually decreasing the number of nicotine receptors to return to their normal state. This down-regulation process, however, takes time and contributes to the prolonged nature of withdrawal symptoms.

Why Do Molecular Level Changes Manifest into Physical Symptoms?

The molecular changes in the brain, such as the drop in dopamine levels and the high activity of unoccupied receptors, lead to various physical and psychological symptoms. These include:

• Headaches: When nicotine use stops abruptly, changes in blood flow and pressure within the brain can trigger headaches. Nicotine has a vasoconstrictive effect, meaning it narrows blood vessels, so when nicotine is suddenly removed, blood vessels may widen too quickly, causing pain. This sudden shift can lead to tension headaches or even migraines in some individuals.

• Fatigue: Fatigue is a common withdrawal symptom due to the brain’s decreased dopamine levels. Dopamine is crucial for regulating motivation and energy levels, and without the regular stimulation from nicotine, the brain struggles to maintain these functions. This can result in feelings of exhaustion and lethargy, making daily activities more challenging.

• Irritability and Anxiety: The absence of nicotine disrupts the brain's chemical balance, leading to heightened irritability and anxiety. Nicotine often serves as a coping mechanism for stress, and without it, the stress response can become more intense.

• Cravings: Cravings are the brain's way of signaling the need to restore its previous state of dopamine balance. These intense urges to smoke are driven by the brain’s desire to regain the pleasurable feelings associated with nicotine use. Cravings can be triggered by environmental cues, stress, or even routine activities that were once associated with smoking.

• Sleep Disturbances: Nicotine withdrawal can significantly disrupt sleep patterns, leading to insomnia or disturbed sleep. Nicotine affects neurotransmitters that regulate sleep, so its absence can cause difficulty falling asleep, staying asleep, or experiencing restful sleep. This can exacerbate other withdrawal symptoms, such as fatigue and irritability.

The key takeaway is that a sudden drop in nicotine levels causes various unwanted physical symptoms.

Gradual Nicotine Reduction: The Most Direct and Obvious Way

To effectively minimize withdrawal effects, the most direct method is to satisfy the craving immediately, but slowly decrease the amount of nicotine consumed. This gradual reduction allows the brain to adjust over time, easing the intensity of withdrawal symptoms. By providing a steady, reduced amount of nicotine, these products support the down-regulation of receptors without causing the shock of sudden nicotine absence, making the quitting process more manageable and increasing the likelihood of success.

A successful product would thus have to deliver nicotine to the bloodstream as quickly as cigarettes do, yet can be controlled to slowly decrease the amount of nicotine over time based on the user’s withdrawal symptom severity, which current NRTs are not capable of.

Gentle Behavior Modification

Smoking isn’t just about nicotine addiction:

Smoking is not just a pharmacological issue; it’s also a deeply ingrained behavior. The act of smoking is often tied to routines, social interactions, and coping mechanisms for stress and boredom. This complexity makes smoking a multifaceted addiction that is challenging to overcome. For instance, people often smoke during specific activities, such as drinking coffee, driving, or taking breaks at work, which reinforces the habit through repetition and association.

Minimizing Disruption is Key:

To encourage people to start quitting, it’s crucial to disrupt their routines and habits as little as possible initially. This approach can be likened to a Trojan Horse method, where the introduction of cessation tools is subtle and integrated into the smoker’s existing habits.

A successful product would mimic the hand-to-mouth action and inhalation sensation of smoking, providing a familiar experience while gradually reducing nicotine intake. This method allows users to maintain their routines and habits, making the transition smoother and less jarring.

While e-cigarettes seem to satisfy this criteria, their heat-based technology and potential for carcinogenic byproducts make it unsuitable as a therapeutic product and unlikely to ever get FDA approval as a smoking cessation product.

Structured Smoking Cessation Support:

Counseling Programs are effective…

Counseling has been proven to be highly effective in smoking cessation efforts. It provides structure for the psychological aspect of smoking addiction by offering accountability and support. Through counseling, individuals receive guidance on coping strategies, stress management, and behavioral changes, all of which are essential in overcoming the mental hurdles of quitting smoking.

… But extending Structure to the pharmacological and physical challenge of smoking cessation is critical as well.

However, effective smoking cessation treatment requires structure that extends beyond psychological support to the pharmacological and physical aspects as well. Proper use of nicotine replacement therapies (NRTs) is crucial, as incorrect usage can lead to quitting failures.

As highlighted in the previous article, underdosing and overdosing on NRTs are common issues that hinder the quitting process. Users are supposed to start with a high dosage and gradually reduce it over time. Cutting down too quickly can lead to underdosing, causing intense cravings and a higher risk of smoking relapse. Conversely, staying on NRTs for too long can lead to continued nicotine dependence and side effects like sleep disturbances, headaches, and nausea. Therefore, structured support systems that guide users on the correct dosage and usage of NRTs are essential for successful smoking cessation.

A successful product would therefore need to be able to automatically adjust the delivered nicotine level according to treatment plan without relying on patient input and track usage, while allowing for additional supportive services such as behavior modification and mental health programs to be delivered to the patient as they quit smoking.

Conclusion:

To summarize, we believe a success smoking cessation product needs to have the following characteristics:

1. Rapid delivery of nicotine to the bloodstream to quickly satisfy cravings along the cessation journey to minimize withdrawal symptoms;

2. Automatic step down of delivered nicotine concentration to ensure adherence to quitting regimen.

3. Digital tools to monitor smoking cessation progress, and deliver mental health programs to address both pharmacological and behavioral challenges of smoking cessation.

Integrating behavioral support with pharmacological guidance ensures that individuals receive comprehensive care. Digital products and tools can help monitor NRT usage, provide reminders, and adjust dosages based on individual needs, thereby preventing underdosing or overdosing. This holistic approach addresses both the psychological and physical dimensions of addiction, making it more likely for smokers to quit successfully and maintain their smoke-free status in the long term.

If you find that smokers having single digit quit success rates is a ridiculous notion and want to see better solutions on the market, please join us at The Healthcare Syndicate on AngelList to invest in companies that are tackling this massive health challenge in cigarette smoking.

And that’s a wrap on this series on smoking cessation! Please subscribe to our newsletter if you haven’t, and share our newsletter with a friend. Stay tuned to our newsletter for more insights into healthcare innovation!