Dr. Laviolette is an assistant professor of anatomy and cell biology at the University of Western Ontario in London who is conducting extensive research on the addictive properties of nicotine. He works with other scientists to develop more effective drugs to help people butt out permanently.

Many scientists now believe smokers are more likely to quit for good when they combine counselling and therapy with pharmacological aids.

In January, Laviolette and his colleagues announced they had developed a treatment that would target nicotine addiction at both the neurobiological and molecular levels.

What they did was alter the nicotine receptors in the brains of lab rats so that instead of producing a rewarding or pleasurable feeling when injected with nicotine, the rat brains interpreted the nicotine infusion as a negative or aversive phenomenon, thus eliminating the desire for more nicotine.

“The next stage is obviously to develop some sort of a pharmacological compound that can target that receptor,” Laviolette says. “Hopefully then the effect would be, if you smoked a cigarette, instead of finding the cigarette rewarding, you’re going to find it very unpleasant and you would either no longer have the urge to continue smoking cigarettes.”

The drug Laviolette and his colleagues tested was a compound called MLA, short for methylycaconitine – a modified neurotoxin derived from snake venom. While it’s a long way away from clinical testing on humans, MLA is designed to modify the alpha seven nicotine receptor in the brain. The receptor alters the way the brain interprets the nicotine changing the reaction from a rewarding one, to an averse one.

Pharmaceutical answers for smokers

Pharmaceutical companies have pills for almost everything. There are pills to cure erectile dysfunction, pills that can help you lose weight and there are even pills which treat a condition called RLS – restless leg syndrome.

Smoking cessation drugs have been available in Canada since the late 1990s. In 1998, Biovail Pharmaceuticals announced the release of Zyban – a dopamine and norepinephrine reuptake inhibitor – as one of the first pharmacological stop-smoking aids. Despite a success rate of less than 30 per cent, doctors continue to write thousands of prescriptions for Zyban every year.

Zyban has been available in Canada, with a prescription, since 1998.

Earlier this year Health Canada approved the drug Champix, another dopamine-blocking smoking pill, developed by Pfizer. It too is now available by prescription.

Laviolette says there are a few new smoking cessation drugs in the pipeline designed to compete with Zyban which should be available in Canada within the next six months. However, he says it could be up to 10 years before an anti-smoking drug made with MLA is available by prescription in Canada. 

“It’s hard to say how long,” he says. “First they have to do all the chemistry, then they have to get the approval from Health Canada to do clinical trials. So I’d say we’re five to 10 years away from marketing a drug like this.”

Smokers develop psychological compulsions towards nicotine as well as physiological dependencies to the stimulant, but nicotine addiction is more complex than that, Laviolette says. According to Laviolette, there is a social component to nicotine addiction and that it has been proven that cigarettes are habit forming. He says it is difficult to treat these aspects of nicotine addiction pharmacologically.

Laviolette says he would even recommend smoking cessation drugs to his friends if they were having trouble quitting cold turkey.

“I don’t think the nicotine gums and patches are all that effective,” he says. “It’s just a temporary solution. You can’t be on that patch the rest of your life. People usually relapse after weaning themselves off the patch.”

“I would say in the interim the drugs like Zyban are working,” he says. “But we need to develop better treatments, we want to see 100 per cent success rates, we don’t want to see 15 or 20 per cent.”

But those low success rates are spurring a number of Canadian scientists to set out to develop more effective drugs in the battle against nicotine addiction.

Rising demand for stop-smoking drugs

It’s not like there isn’t a market for products – pharmacological or not – that help people quit smoking. More than 4.5 million Canadians are habitual smokers and this year alone, more than 45,000 people will die from tobacco use. That’s like losing the entire population of a small town the size of Cornwall, Ontario to smoking-related deaths every year.

Millions of dollars are spent every year on various smoking cessation therapies, from nicotine patches to nicotine gum. But as pharmaceutical options become more advanced and effective, more and more Canadians are opting to quit smoking with the help of medication.

Even the Canadian Cancer Society's “One Step at a Time” guide to quitting smoking puts a heavy emphasis on the importance of medication.

"Nicotine replacement therapy and/or Buproprion (Zyban) may just give you the edge you need to quit," the guide says. There are more than a dozen mentions of available medical smoking cessations products, but it fails to mention any specific brands.

For the past eight years Adam Cook has been trying, unsuccessfully, to quit smoking. The 25-year-old Waterloo, Ontario landscaper says he started smoking at the age of 17 when he was still in high school.

“I guess I just got in with a group of people who were smoking and that’s how it started,” he says.

Cook says that over those eight years, he’s tried to quit smoking on three different occasions. But each time he found himself buying a fresh pack after a few months of going without his Belmont Milds.

“I tried chewing the gum but it didn’t really help with the cravings,” he says. “Plus, chewing gum just isn’t as much fun as the whole act of smoking. Taking the wrapper off the pack, taking the first soft one out, the whole act of lighting it – the whole process is addictive.”

Cold turkey is hard to do if your friends smoke, Cook says. He tried to quit abruptly, but soon found himself bumming smokes from his friends, and eventually he was back to buying his own packs of cigarettes again.

“I think I’d be open to taking a pill if it meant I would be more likely to quit,” he says. “I guess it would also depend on the side effects though.”

Squirrel monkeys and nicotine

According to Dr. Bernard Le Foll, a clinical scientist with the Nicotine Dependence Clinic at the Canadian Centre for Addiction and Mental Health (CAMH) with the University of Toronto, scientists need to develop better smoking cessation drugs because of their potential for success and because smokers need help quitting.

“The medications that are available right now are not successful in a lot of patients,” Le Foll says. “We need to find better medications to address the problem.”

Le Foll and his colleagues believe they have developed a new experiment model which will allow scientists to better study the addictive properties of nicotine in monkeys with an eye on designing new anti-nicotine drugs for humans. Previous studies involving primates and these kinds of tests had been plagued with problems and their findings were difficult to reproduce.

Le Foll and his co-authors believed these problems stemmed from the conditioning the monkeys had endured prior to the testing. The results of their study were published at the online, peer-reviewed publication from the Public Library of Science (PLoS) at www.plosone.org.

The study, a joint venture with the U.S. National Institutes of Health (NIH), revealed that nicotine use is highly addictive in primates. 

The researchers wanted to create a test which would allow scientists to mimic the reinforcing effects of nicotine in primates. A chamber was constructed with two levers, each with a series of lights above them. A squirrel monkey would be placed in the chamber and would start pressing the levers. When the monkey pressed the active lever, a light would go on and then the monkey would receive an automatic injection of nicotine, essentially self-administering it. When the inactive lever was pressed, the light came on, but there was no injection.

After about a week, the monkeys being tested began to pay more attention to the active lever than the inactive lever, showing a preference for the nicotine.

“They were actively motivated to get an injection of nicotine,” Le Foll says.

In one experiment, the number of times the monkey would be required to press the lever in order to administer an injection of nicotine was progressively increased. One monkey pressed the active lever 600 times just to administer a single injection of nicotine.

“It is shown in humans that smokers are very reactive to these types of cues that are associated with tobacco smoking,” Le Foll says. “So we use that to mimic that aspect of the behaviour”

Le Foll says previous studies had found evidence that one of the actions of nicotine is to enforce a motivational value of some cues, something akin to Pavlovian conditioning. For example when the light goes off, the monkey associated the stimulus with the pleasurable feeling from the nicotine, thereby associating the light with the pleasure derived from the nicotine.

“A smoker that is used to smoking in a particular environment, when he comes back to that environment, just the presentation of the stimuli that is associated with tobacco consumption can cause a relapse. So we use the lights to mimic those stimuli.”

Although there has been extensive research into the role nicotine plays in reinforcing smoking in humans, this is the first study of its kind to evaluate the same motivational value of nicotine in experimentally naïve monkeys – meaning they have never been tested on before or conditioned for experiments. It helps to support earlier findings that identify biological reasons for cigarette addiction.

And while Le Foll and Laviolette continue to make strides on the neurobiological and pharmacological fronts of the battle against tobacco dependency, both say that looking into how a person’s genetics affect their nicotine reception is the next frontier in smoking cessation research.

“Nicotine and tobacco dependence are very complex phenomenon which rely on multiple factors, and clearly there are individual factors.”

While there is no sure fire cure for smoking, scientists continue to improve the tools available to help people who are serious about quitting, do so for good.