Anti-smoking pill to 'make nicotine feel gross' may be on the way

Want to quit smoking? Scientists are working on a pill that could cut out the nicotine buzz and make smokers feel ‘anxious and gross’ when they have a cigarette

• Nicotine triggers both reward and disgust circuits in the brain  
• Scientists at the University of Toronto have discovered how pleasure overrides aversion in people addicted to nicotine and smoking
• They identified a target for a pill that could block the enjoyable effects and make smoking feel ‘disgusting’ again for those addicted to nicotine

Scientists have discovered the chemical switch that happens in the brain and turns the smell and taste of cigarette smoke from disgusting to delightful for people who get hooked – and say it could lead to a drug to help break the addiction. 

Once someone – or in the study’s case, some animal – becomes addicted, the same neurons that tell the brain to stay away from cigarettes also tell it to keep smoking in order to avoid the pain of withdrawal. 

And at some point the reward for avoiding withdrawal overtakes the aversion to cigarettes, making it difficult to fight off dopamine encouragement to smoke more. 

But the University of Toronto scientists say that knowing what this switch is and how it behaves could help them design a drug – much like those that already exist for alcoholism – that blocks the pleasure of smoking and instead makes it gross again.

Nicotine triggers both disgust and delight circuits in the brain – but for addicts, it becomes more the latter than the former. Now, scientists think they could flip the switch back (file) 

Opioid drugs are a simple and powerful high. They flood the brain with ‘feel good’ chemicals, such as endorphins, which are released when we exercises, that increase feelings of euphoria and dull pain. 

Nicotine is just as addictive, but an addict’s relationship to it is more complicated than that between someone who is opioid dependent and their drug of choice. 

It triggers both the brain’s reward system and an aversion response.   

The latter is clear in a child or non-smoker’s initial reaction to the unpleasant, often described as noxious or smelling toxic.  

At the same time, nicotine also mimics the form and activity of acetylcholine, a neurotransmitter involved in pleasure as well as learning and several forms of addiction. 

Scientists have long known that nicotine behaves in these two seemingly contradictory ways – but not how the pair of pathways play out in the brain, or why addiction so easily seems to overpower aversion.  

The Toronto team discovered that nicotine hits two populations, or groups, of receptors in the same brain region, known as the ventral tegmental area (VTA), which plays an important role in the reward circuit. 

These receptors are one end of the branch-like structure of a neuron that extends to other various areas of the brain and body. 

Some of the receptors from these two populations travel to the same places, others travel to different ones. 

One set of receptors are for dopamine, and the other is for GABA. 

Dopamine is mostly thought of as a chemical for pleasure, but it’s also involved in the version signalling process. 

And dependence upon nicotine seems to mix up how it and nicotine interplay in both of these ways.  

‘Aversion should be there all the time, but the more someone smokes, they’re going to have changes in the amounts of receptors and in the signaling process in the reward system,’ said lead study author Dr Taryn Grieder, who’s been studying nicotine addiction for about a decade. 

‘It is almost like a switch in the brain that gets thrown and there’s almost a breakdown in signalling so that now the aversion that was signaled through dopamine neurons is there, but it’s almost like reward from relieving withdrawal,’ she told DailyMail.com.  

That switch partially explains how nicotine addicts stop feeling bad when they smoke, and only perceive the ‘good’ nicotine seems to do them. 

But that doesn’t really help Dr Grieder and her team come up with treatments to help break the addiction loop for smokers. 

‘You can’t mess with dopamine, because if there’s too much of it it leads to schizophrenia, and too little leads to Parkinson’s and movement problems,’ explains Dr Grieder.  

‘So were were looking for new neurotransmitters that can make nicotine feel gross for everyone. 

‘If we shut down those other neurons [that make smoking feel pleasurable] then only the disgust or aversion will be left.’ 

Those other neurons are related to the neurotransmitter, GABA.

GABA counterbalances neurotransmitters involved in stress, among its myriad other roles. 

Benzodiazepines, a class of drugs that includes Xanax, act on GABA and help treat anxiety. 

In fact, one anti-anxiety drug, Wellbutrin, is already marketed as having the added benefit of being a smoking cessation aid – but it’s unlikely to be prescribed as just a quit-aid, to those without anxiety.    

Now, Dr Grieber and her team have found specific GABA receptors to target, without interfering with the neurotransmitter’s other broad-ranging roles.  

They now where to aim a drug, now they just need to make one. 

‘We would be specifically targeting these receptors on GABA neurons so that no one would feel pleasure from smoking, but it shouldn’t affect anything else – like pleasure from sex or food – except maybe liking alcohol,’ said Dr Greiber. 

An analogue for alcoholism already exists: Antabuse, a drug that triggers severe nausea if combined with alcohol. 

Now, a drug that does something similar for smoking could be on the way.  

Dr Grieder notes that this potential drug is purely theoretical, for now, would likely take years to prepare for humans to take, and would by no means be a ‘cure’ for nicotine addiction, but rather a helpful tool for someone who has made up their mind that they serious about quitting and is changing their behavior, too.   

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