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How Does Zyban (Bupropion) Work?


More than 1 billion people worldwide smoke tobacco, placing increased pressure on both health and economic services. So, effective cessation aids are needed to lower these numbers and alleviate the strain. One popular aid is Zyban, a prescription-only tablet designed to help you quit smoking for good.

How Zyban Works - The Mechanism of Action

Zyban contains the active ingredient bupropion. It was first developed to treat depression, so the Zyban mechanism of action for quitting smoking isn’t fully understood. However, it is known to change the levels of some chemicals (neurotransmitters) in the brain.

Bupropion is a weak inhibitor of dopamine and noradrenaline reuptake, chemicals in the brain that are associated with addictive behaviour. When you smoke, your body absorbs nicotine from the cigarette into the bloodstream which crosses the blood-brain barrier. This causes dopamine to be released from the pleasure-seeking pathways in the brain. When nicotine intake is reduced, dopamine reuptake occurs.

Bupropion works by stopping dopamine reuptake, reducing the effect of dopamine deficiency experienced when you withdraw from nicotine. Bupropion also works by inhibiting noradrenaline reuptake. Although this mechanism of action is not well understood, the release of noradrenaline from the brain has been seen in many addictive behaviours.

When you take Zyban to quit smoking, it works by reducing the withdrawal symptoms experienced when you stop using nicotine. It does this by mimicking the effects of nicotine on the neurotransmitters and acts as an antagonist for the nicotine receptors in the brain, preventing nicotine withdrawal symptoms.

Image Source: Psych Scene Hub

Bupropion and the Brain

Bupropion is the active ingredient in Zyban and helps you give up smoking. It works by reducing the cravings you can experience when you quit smoking, caused by the addictive substance nicotine. Some research also shows that it can also reduce withdrawal symptoms.

Bupropion is most effective when it is used alongside a stop-smoking program. Zyban is also an antidepressant so it can have a positive effect on your overall mood. Bupropion acts on the brain by preventing the reuptake of specific neurotransmitters:

  • Dopamine
  • Serotonin
  • Noradrenaline

Doing so helps to balance any imbalance in these chemicals that are associated with depression but also addictive behaviour.

Metabolism of Zyban

After being absorbed in the gut, bupropion metabolism occurs mainly in the liver. It has a half-life of 21 hours which means it takes this time for bupropion to reduce by half in the body.

Bupropion is metabolised in the liver into the active metabolites:

  • Hydroxybupropion
  • Threohydrobupropion
  • Erythrobupropion

These metabolites are further metabolised and then excreted via the kidneys in urine. Research shows that bupropion is metabolised into its most active metabolite, hydroxybupropion, by the enzyme CYP2B6.

That means that bupropion metabolism may be affected by CYP2B6 inhibitors. The following medicines may reduce the level of active metabolites in the body:

  • Clopidogrel
  • Diazepam
  • Norfluoxetine
  • Orphenadrine
  • Paroxetine
  • Sertraline

These medicines will likely increase bupropion but reduce the blood concentration of its active metabolite, hydroxybupropion.

The opposite may occur if you take CYP2B6 inducers with Zyban. This includes medicines and herbal remedies, such as:

  • Carbamazepine
  • Clotrimazole
  • Phenobarbital
  • Rifampicin
  • St John’s Wort

Effectiveness and Considerations

Zyban is licensed as a smoking cessation aid in the UK and USA. Research shows that 20% of smokers who use bupropion therapy, quit and remain non-smoking after one year. A Cochrane Review published in 2004 found that bupropion treatments doubled the chances of quitting smoking compared to placebo.

Stapleton et al., (2013) found that bupropion was associated with slightly better abstinence rates compared to nicotine replacement therapy.


Zyban contains the active ingredient bupropion and was first developed to treat depression but has since been licensed as a smoking cessation therapy. It works by inhibiting the enzymes involved in dopamine and noradrenaline reuptake. By inhibiting the reuptake of dopamine, the reward pathways associated with nicotine are stopped and cravings subside.

Always consult healthcare providers for personalised medical advice and treatment plans for weight loss. Go to our dedicated Zyban page to find out how you can purchase this treatment directly from Prescription Doctor.


  • Addiction, (2013) Randomized trial of nicotine replacement therapy (NRT), bupropion and NRT plus bupropion for smoking cessation: effectiveness in clinical practice.
  • Cochrane Library, (2004) Antidepressants for smoking cessation.
  • NIH, (2005) How does bupropion work as a smoking cessation aid?
  • NIH, (2008) The Use of Bupropion SR in Cigarette Smoking Cessation.
  • Psych Scene Hub, (2021) Bupropion - Mechanism of Action.
  • The Lancet, (2021) Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990–2019: a systematic analysis from the Global Burden of Disease Study 2019.
  • NIH, (2008) The Use of Bupropion SR in Cigarette Smoking Cessation.

Authored By

Leanne Edermaniger

Medical Content Writer
Leanne is a science and health content writer focusing on human health and biology while utilising her solid academic background.

Published on: 27/03/2024

Reviewed By

Mohamed Imran Lakhi

MPharm - Lead Pharmacist
Imran Lakhi is the superintendent pharmacist and founder at Prescription Doctor. He has been at the core of our team.

Reviewed on: 27/03/2024
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