Could the cure to smoking be found in SMOKE
Researchers diving into way addiction works to solve woes, writes Jamie Morton
Could the very chemical compounds found in tobacco smoke be used to help people stub out the harmful habit? That’s the big question of a new million-dollar study, which might also yield better ways to treat depression and anxiety.
At the core of the major research programme, led by Massey University’s Dr Penny Truman, are compounds in tobacco smoke that are thought to enhance nicotine’s addictiveness.
The MAO mystery
The compounds work by inhibiting a family of enzymes called monoamine oxidase, or MAO, which help us by cleaning out unwanted chemicals throughout our bodies and clearing neurotransmitters from our brains.
But MAO inhibitors influence how long these neurotransmitters — notably dopamine, seratonin and epinephrine, which are important for addiction, mood and stress respectively — linger.
In recent times, scientists have been working to understand how MAO inhibitors found in tobacco smoke itself affects our mental functioning.
Smokers and some researchers say smoking helps with mood. Others have suggested this is simply because smoking deals with the stress and anxiety caused by nicotine withdrawal.
So far, Truman said, there had been no way decide between those theories; it was possible both were true.
Smokers have also claimed the habit helps with Parkinson’s Disease, Alzheimer’s and schizophrenia.
On the flipside, MAO inhibitors in smoke have the potential to worsen nicotine and other addiction problems, by stopping dopamine from being cleared from the brain quickly, thereby making its reward signal bigger.
“This is another aspect of smoking which is theorised, but never directly proved.”
It’s from within this complex interplay that Truman and her colleagues have shed new light, by untangling about half the MAO inhibiting activity in the smoke. “Previously we could only explain 5 to 10 per cent of the activity we could see.
“Finding these inhibitors gives us a way of answering a variety of questions. How much of the inhibition we see from tobacco smoke can we now explain? Do they affect addictive responses to nicotine? Do they affect anxiety and depression? These are the first questions we want to ask.”
The big potential was that they might have struck upon a type of inhibitor that acted differently from the inhibitor-based drugs we had today.
“These known drugs can help with such things as depression and Parkinson’s . . . but have a problem in that they only have a clinical effect when MAO levels are very strongly reduced — around 90 per cent.”
At this level, people became dangerously unable to metabolise other chemicals in the body — so all of the known MAO inhibitors had significant side effects, pushing them somewhat out of favour with clinicians.
But if we believed what smokers told us, they might be experiencing beneficial effects at around 30 to 40 per cent general MAO inhibition.
If so, we could have a clinically effective drug with much reduced side effects. “I know this is counterintuitive,” said Truman. “How can anything good come out of a cigarette?
How can something be better if it has a smaller effect? But it is a possibility that deserves exploration.”
A new therapy?
The first step of her programme, funded by the Government’s Endeavour Fund, would be to confirm just which of the compounds affected how addictive nicotine is.
“To do that we have to get rats addicted to nicotine, or to nicotine with MAO inhibitors, and then ask, how much work will you do to get this drug? This is the gold standard method of testing how addictive drugs are.”
They’d also take a closer look at whether the inhibiting activity was equivalent to that seen in smokers.
Then they’d test ways to use these chemicals to make an improved version of nicotine replacement therapy, either as an inhaler or as a vaping device.
“We aim . . . to prove whether or not these inhibitors can enhance nicotine addiction and to know enough about their effects that we can devise a ‘tobacco replacement therapy’, which will be better at weaning smokers off tobacco than straight nicotine replacement is,” she said.
“Once we have that . . . we will go into pharmaceutical development mode — and where that takes us depends on who is interested in developing it and funding it.
“More research [will be] needed to take the drug from something that has the desired effect in a rat to something that can be used safely on people.”
Opening the ‘trapdoor’
Truman wants the concept to become a reality, because she sees smoking as a trap with horrible long-term effects.
“We want to see that trapdoor opened. There is a lot more to tobacco dependence than we have known up until now — and that means there is a lot of potential for people to get better help to quit smoking in the future.”
She also favours a paradigm shift, in which the focus could move from forcing smokers to quit, to helping them quit more easily.
Although tobacco control measures had brought down smoking — just 13 per cent of Kiwis smoke each day now, compared with a quarter of the population in the mid-1990s — she was concerned that pressure had now reached “uncharted waters”.
“What we seem to be seeing is that the people this pressure works least well for are the most disadvantaged.
“They are the ones who are also most severely impacted by such things as tax increases . . . anecdotally we are seeing severe financial and emotional hardship among disadvantaged smokers and their families, with more thefts of cigarettes and more people growing their own tobacco plants.”
A recent report on tax increases concluded they were working, but also pointed to a potential “tipping point” where the hardships induced might outweigh the benefits.
“We need to be looking hard for better ways to do things,” she said.
“Tobacco smoking is very addictive. As things are at the moment, some people who want to quit just cannot.
“As a chemist, I think in terms of ‘ratelimiting steps’. The rate-limiting step for smoking cessation is the huge barrier heavily addicted smokers have to climb over to stop smoking.
“If we can make the barrier lower — or give them an easy ramp to climb up — then they will be able to quit more easily. They will be given a way they can respond to the pressure they are under by actually stopping smoking.
“After all, that’s what we all want them to do, and what — for the most part — they themselves want to do.”
And just as tantalising: we might be able to use the same compounds to treat anxiety, depression and Parkinson’s Disease.
“If there is potential to harness the ‘good effects’ of smoking without the killer chemicals that go with it at the moment, that will also be a game changer.”