Nicotine is the main active chemical ingredient in tobacco. While nicotine can be found in multiple products such as e-cigarettes and chewing tobacco, smoking cigarettes is still the most common method of intake. It affects the brain activity by altering the levels of mood-related chemicals such as dopamine and serotonin.¹ These chemicals make you feel good, and with frequent use, your brain starts to rely on nicotine to feel that way. 

The relationship between quitting nicotine and depression is complex and interconnected, where one can influence the other. Individuals with depression often use nicotine as a coping mechanism for stress and therefore tend to smoke at higher rates than the general population. However, smoking itself can worsen depression. After a while, nicotine changes how the brain responds to its own chemicals. Thereby increasing the risk of developing depressive symptoms and possibly requiring long-term antidepressant use.²

Depression can make it harder to quit smoking, especially for those who experience stronger depressive symptoms even when attempting to quit.³ Developing tolerance for temporary mood and emotional fluctuations is an important part of maintaining abstinence. Although quitting nicotine can cause withdrawal symptoms such as sadness or irritability, these effects are usually temporary. Upon stopping successfully, you can experience lasting improvements in overall mental well-being.⁴ 

Why quitting nicotine isn’t just physical

There is a common misconception that nicotine improves mental health by relieving anxiety and stress. Many individuals use nicotine as a form of “self-medication” to cope with negative emotions.¹ Although smoking may provide temporary relief from withdrawal symptoms—such as irritability, restlessness, and mood swings—this short-term improvement is often misinterpreted as improved mental health.⁵ In reality, regular intake of nicotine changes the usual brain functioning and can eventually lead to mood swings as part of withdrawal effects.⁶

These neurochemical changes can lead to nicotine dependance,which is associated with an increased risk of severe depression.² Because smoking is closely linked to mental health and emotions, quitting can be a real challenge. When nicotine intake stops, the brain must adapt to the absence of chemicals released by it. During this adjustment period, individuals may experience anxiety, irritability, difficulty concentrating and low mood. These emotional and mental challenges are part of nicotine withdrawal and can typically last longer. 

Therefore, just by understanding that quitting involves both body and mind, individuals can better manage withdrawal symptoms and improve their likelihood of successfully quitting.¹

How nicotine affects the brain and mood

Nicotine acts on special centres of the brain through various pathways, changing the way certain brain chemicals work.

• Nicotinic acetylcholine receptors: These receptors help brain cells communicate by regulating the release of key neurotransmitters. Nicotine changes how these receptors work, and such changes have been linked to the development of depressive symptoms. With regular nicotine use, the brain adjusts to these changes, leading to poor mental health outcomes^1,2
• Antidepressant-like effects: Nicotine triggers the release of neurotransmitters such as dopamine and serotonin in the brain, which causes happiness and relaxation. However, prolonged nicotine use can worsen depressive symptoms because the brain becomes accustomed to the elevated levels, and fails to stabilise mood naturally¹
• Dopamine system: Nicotine stimulates dopamine release, creating rewarding sensations such as pleasure, which makes it addictive. Over time, the brain undergoes changes that require increasingly higher amounts of nicotine to achieve the same pleasurable effects. This cycle reinforces addiction and can contribute to behavioral and emotional difficulties¹

Besides dopamine, the release of chemicals – serotonin and acetylcholine – also play important roles in stabilising mood. Nicotine use triggers the release of all three chemicals.¹ However, with long-term use, certain receptors become less responsive to nicotine, and increase in number as the brain attempts to compensate. These changes interfere with how the brain controls mood, possibly leading to depression over time.²

What happens during nicotine withdrawal

Nicotine withdrawal causes many behavioural symptoms, which can make it difficult to quit. These effects show up when the brain’s chemistry is disrupted after cutting back on nicotine. Such changes can strongly affect our motivation and ability to quit successfully. 

Common symptoms

Nicotine withdrawal is mostly associated with mood changes, including nervousness, irritability, restlessness, and sadness. These symptoms can greatly affect how well someone manages to quit smoking completely.⁶

Two hypothesis for withdrawal-induced negative effects

There are two main explanations for why people feel low or anxious when they quit smoking:

• Existing mental health theory: This suggests that withdrawal can unmask pre-existing mental health conditions. Individuals with a history of depression or anxiety are more likely to feel worse when they quit nicotine and may begin to feel depressed or anxious again⁶
• Nicotine withdrawal effects: According to this theory, the negative symptoms, such as anxiety or sadness, are direct consequences of nicotine withdrawal itself. These symptoms tend to be more intense in individuals with higher levels of nicotine dependence, even if they had no prior history of mood disorders⁶

Emotional barriers to quitting smoking

Feeling depressed or anxious during the withdrawal process can make it harder to discontinue completely. This emotional stress can reduce motivation and the chances of success in quitting.⁶

Brain’s recovery journey after quitting nicotine

The brain changes caused by long-term nicotine use can begin to reverse after stopping its consumption. Most withdrawal symptoms disappear within a few weeks of quitting because the brain’s chemistry starts returning to normal. However, some changes may take longer to fully recover, which explains why maintaining abstinence becomes easier after the first few weeks of quitting.⁴

How to cope with depression following quitting

Coping with depression after quitting nicotine often requires a combination of medication and counseling, particularly for individuals with a history of mental health conditions.

Using medicines to help quit

Drugs like varenicline help reduce depression symptoms linked to nicotine withdrawal. It also increases the chances of quitting smoking, especially for people who have already been dealing with depressive symptoms.⁷

Bupropion (sustained-release) can help more smokers quit, regardless of their history of depression. It works by modulating neurotransmitters—particularly dopamine—which can enhance mood and partially replicate the rewarding effects of nicotine.¹

If someone has been successfully treated for depression and is stable, it is important to consult a doctor before attempting to quit smoking. Clinicians often recommend continuing the use of antidepressants for at least 6 months or longer when trying to quit smoking. Smoking cessation therapy can be added to their antidepressant treatment to prevent worsening of depressive symptoms. Quitting smoking may also slow the metabolism of certain antidepressants, which could potentially increase their blood levels and the chances of side effects.¹

Behavioral support

Cognitive-behavioural therapy (CBT) is useful for smokers who experience frequent episodes of depression during cessation. However, adding CBT for depression to a smoking cessation treatment may not help smokers who have low depression scores. Supportive strategies—such as reinforcing the benefits of quitting and helping individuals manage challenges that arise after cessation—can further improve the likelihood of remaining smoke-free.¹

When to seek professional help

Since quitting nicotine affects both mind and body, it is advisable to seek professional help, especially in the following situations:

History of mental illness

People with a history of depression, anxiety or other mental health issues are more likely to develop strong depressive symptoms. Getting professional help is very important for them to manage their mental health during the quitting phase.⁶

Severe or constant depressive symptoms

If depressive symptoms are severe, last a long time, or interfere with daily life after quitting smoking, then it is important to see a doctor or mental health professional. Up to 24% of individuals with a history of major depression may experience a new episode soon after quitting. Close monitoring of symptoms and timely intervention are essential to ensure safety and support successful long-term abstinence.¹

Considering medication

The decision to use medicines like varenicline or bupropion, or to adjust antidepressant doses, should always be made with a healthcare professional.¹

Suicidal thoughts

Antidepressants, especially in children and teens, may increase the risk of suicidal thoughts. Any signs of self-harm or suicide need urgent professional help. Close monitoring during the first months of treatment is necessary to catch any warning signs immediately.¹

Initial assessment

At the start of quitting smoking, a doctor will assess the individual’s mood and level of nicotine dependence. This comprehensive initial evaluation helps guide the selection of the most appropriate treatment plan.¹

Long-term mental health benefits of quitting nicotine

Cutting back on nicotine can cause short-term mood changes but studies show it eventually contributes to lasting mental health benefits. People who discontinue nicotine tend to feel less anxious, stressed, and depressed over time, along with improved overall well-being and mood stability.

• Reduced anxiety and depression: In the long run, people who quit smoking experience lower levels of anxiety and depression compared to those who continue to smoke⁴
• Improved stress response and positive mood: Upon successful cessation, people experience less stress and more positive emotions⁴
• Lower risk of developing mental health disorders: People with a past history are less likely to develop new episodes of anxiety or depression after successful quitting⁴
• Long-term mood stability: People who quit smoking often see lasting improvements in their mental health regardless of whether they have a mental health condition or not⁴
• Clinically meaningful improvements: The mental health benefits of quitting smoking are comparable to those achieved with antidepressant medications used to treat anxiety disorders⁴

Benefits for those with previous mental illness

A study involving more than 4,000 people—both with and without pre-existing mental health conditions—found that quitting smoking for at least 15 weeks resulted in significant improvements in mental health. Participants showed lower anxiety and depression scores, with even greater benefits observed in those with a history of mental illness. This proves quitting nicotine benefits mental health, especially for those with previous mental health issues.⁷

Summary

Nicotine is the main active substance of tobacco that interferes with normal brain function. It works by binding with special structures on your brain cells called receptors, making them release neurotransmitters such as dopamine and serotonin. Because of the high level of these neurotransmitters, smoking can seem enjoyable for a while. But over time, your brain requires more nicotine to feel the same pleasurable effects, leading to addiction. When you attempt to quit smoking, your body will go through nicotine withdrawal, which can trigger strong emotional changes. Such symptoms can be really difficult to deal with, especially for those who have previously experienced depression or anxiety. 

Depression itself is a mental health condition marked by continuous low mood, trouble sleeping and loss of interest in activities. Soon after cessation, many people notice a worsening of mood because the brain has to adjust to the absence of nicotine. However, if you succeed with quitting, you can notice drastic improvements in anxiety and depression over time. Even if a quit attempt is not successful, it usually does not cause lasting harm to your mental health, so just trying to quit is not harmful. Moreover, both nicotine addiction and depression can be addressed simultaneously to achieve more favourable results.