In Niagara Falls, N.Y., it is legally impossible to buy codeine painkillers without a doctor’s approval.

But drive across the border to Niagara Falls, Ont., and you can buy as much codeine as you want. The Toronto Star purchased 1,000 tablets from five pharmacies with barely any questions asked — in little more than an hour.

Codeine is an addictive narcotic and countries like the United States, Sweden and Germany have made the painkiller available by prescription only.

In Canada, however, codeine is widely available without a prescription. In 2013, Canadian pharmacies stocked their shelves with more than $16 million worth of non-prescription codeine, according to estimates by health data company IMS Brogan. This easily translates to hundreds of millions of doses.

These millions of dollars and doses obscure a crucial problem: there is a startling lack of evidence that these drugs work better than household painkillers like Tylenol or Advil.

But their low doses of codeine are addictive — and driving Canadians into hospitals, addiction treatments and years of opioid dependence.

These drugs are “kind of useless,” according to Ross Tsuyuki , editor of the Canadian Pharmacists Journal and a professor of medicine at the University of Alberta. “Every good drug has its risks as well. But a not-so-good drug with risks? It’s pretty hard to justify.”

A Toronto Star investigation has learned of multiple attempts over several decades to ban or restrict non-prescription codeine, by regulators, the Canadian Pharmacists Association and even Ottawa’s own experts, who warned 36 years ago that low doses of codeine can cause addictions despite being ineffective painkillers.

But such recommendations were ignored. Low doses of codeine can be sold without a prescription, as long as the opiate, which is derived from the opium poppy, is cut with two non-narcotic ingredients and stored behind the counter.

This regulatory loophole has made Tylenol No. 1 a household name, but only in Canada, the one country where pharmaceutical giant Johnson & Johnson sells this product.

Its recipe (regular Tylenol, or acetaminophen, combined with caffeine and 8 mg of codeine) has been copied by many generic versions, which now dominate sales. Another formula combines codeine with aspirin — a drug commonly known as “222s,” another only-in-Canada brand that was discontinued by Johnson & Johnson in July.

Proponents of non-prescription codeine say these drugs give people access to pain relief when regular over-the-counter painkillers don’t cut it. According to Johnson & Johnson, Tylenol No. 1 is “safe and effective for treatment of mild to moderate pain” when used as directed, offering an important “lowest effective dose” alternative. Many people take these drugs safely every year and without developing addictions.

But it doesn’t take much to grow addicted; a U.K. parliamentary inquiry in 2009 found that low-dose codeine drugs can cause addiction after just three days.

Many experts agree that for healthy adults, 30 mg is the minimum amount of codeine needed for pain relief. Drugs like Tylenol No. 1 and 222s contain only 8 mg per pill.

“They’re no better than Tylenol, Motrin, Advil — and on the list goes,” said pharmacist Raymond Joubert, registrar of the Saskatchewan College of Pharmacists. “Why have something on the marketplace that doesn’t serve any useful purpose and is used mainly for abuse?”

This question is especially pertinent in light of Canada’s growing opioid epidemic, which is costing the federal government millions to tackle. In Ontario, deaths linked to opioids like morphine, codeine and oxycodone have jumped 242 per cent in two decades.

But while anti-drug strategies are understandably focused on prescription opioids — the primary driver of Canada’s opiate crisis — they ignore non-prescription codeine altogether, even though these drugs have helped Canada become one of the world’s leading codeine consumers.

“There are bigger fish to fry but this is the most accessible problem,” argues pharmacist Mark Barnes, who works with the treatment team at the federally funded Canadian Centre on Substance Abuse . “No one is looking at this.”

These drugs are in effect invisible. Their non-prescription status means doctors and policy-makers have no clue how many Canadians are taking them. Their low-dose formulations also enable a “solitary, hidden addiction” that can last for years or decades — and many addicts likely never seek help.

Barnes said addicts hooked on stronger opioids often resort to non-prescription codeine when trying to stave off withdrawal symptoms. Low-dose codeine can also “unmask a fondness” for opioids, leading people to even stronger drugs, said Dr. David Juurlink , a toxicologist and drug safety researcher with Sunnybrook Health Sciences Centre.

But for many people, non-prescription codeine is the primary problem. In Ontario, more than 500 people have entered methadone treatments over the last three years for addictions to “over-the-counter codeine preparations,” according to a database maintained by the Centre for Addiction and Mental Health (CAMH). Methadone is a substitute drug initially used as a treatment for heroin addicts and often considered a lifetime commitment.

The number of deaths is unknown, however. An analysis of Ontario coroners’ reports by the Ontario Drug Policy Research Network showed codeine played a role in 1,870 fatalities between 1991 and 2010 — but there is no way of knowing how many might be linked to non-prescription codeine.

Deaths or overdoses caused by acetaminophen or aspirin — the other painkillers mixed into non-prescription codeine pills — are even harder to track.

“They get hooked on the codeine but more often than not, they get into acute medical trouble from the aspirin and acetaminophen,” said Juurlink, who treats a few of these cases every year, some life-threatening.

For Juurlink, anyone with pain serious enough to require an opiate should get a doctor’s advice. Non-prescription codeine allows people to bypass that step.

Pharmacists become the only gatekeepers. But while regulators have leaned on pharmacists to police this painkiller, they haven’t given them the tools.

In most provinces, including Ontario, pharmacists have no way of tracking customers’ purchasing histories; they have no idea if a customer bought 200 pills from another store five minutes ago. Addicts can easily travel from pharmacy to pharmacy, collecting as they go.

For Rob, a 34-year-old Toronto man, this access enabled a Tylenol No. 1 addiction that lasted half his life. He asked for his surname not to be used, citing fears over stigma and job consequences.

He first tried the drug at 16, when he and his friends popped the pills in their parents’ basements. In his 20s, Rob was getting high every day, extracting codeine from up to 80 pills and dissolving it into a bitter, cloudy drink.

He couldn't even endure a friend’s wedding without his “pill juice.” “I had my drink ready to take at just the right times, waiting for it to kick in so I would feel good,” he said quietly.

After abusing this drug on and off for more than a decade, Rob sought help. He had landed in the hospital, lost a long-term girlfriend and isolated himself from friends and family. Today, he is taking methadone — maybe for the rest of his life.

Rob never had to get a prescription or do anything illegal. He just needed $10 or $15 and access to one of Ontario’s 4,000 pharmacies.

“No pharmacist ever said no.”

CANADA’S CODEINE problem is not new. Health professionals sounded the alarm in the 1930s, when codeine was being sold “holus-bolus over the counter to every man, woman or child who wants to purchase it,” according to Dr. David Hartigan , a Liberal MP from 1935 to 1940.

In 1936, Hartigan pointed out that an opium committee with the League of Nations — the UN’s predecessor — had called out Canada for having the highest codeine consumption in the world.

“If the government wants to do anything to elevate the people and to improve social conditions, it should begin with the prohibition of the promiscuous use of the drug,” Hartigan said according to Hansard , which transcribes debates in the House of Commons.

Almost eight decades later, there are 105 products on the Canadian market that contain codeine. Just over half are sold without a prescription, exempted by the Narcotic Control Regulations , which impose the following conditions:

That codeine doses be limited to 8 mg (or 20 mg per 30 mL in a liquid).

The codeine is combined with at least two other non-narcotic ingredients.

The drug is properly labelled and pharmacists refuse sales when there are “reasonable grounds” to believe it will be misused.

But why sell the drug at all? This is something Advit Shah is struggling to understand.

Shortly after Shah became a pharmacist in Manitoba, he was troubled that colleagues were selling non-prescription codeine without asking any questions. He wondered why he should recommend this drug for dental pain, lower back pain and migraines, common reasons given by people who ask for the painkiller. So he combed through the literature, looking for hard evidence that these drugs provide any added benefit.

“There’s nothing,” Shah said.

What research he did find only evaluated stronger codeine doses. When combined with other painkillers like acetaminophen, codeine does seem to boost pain relief — but only slightly, while also increasing side effects. A 2006 analysis in the Canadian Medical Association Journal found that “weak” opioids — including codeine doses of 20 to 180 mg — failed to “significantly outperform” certain antidepressants and NSAIDs, a painkiller category that includes aspirin and ibuprofen. Another study from South Africa described non-prescription codeine formulations as “irrational.”

Pain researchers at the University of Oxford have published a table evaluating the efficacy of dozens of common painkillers, placing 60 mg of codeine at the bottom. This analysis — which has its flaws but is the “best available comparative information” according to a paper in the journal Australian Prescriber — found that only 15 per cent of people who took 60 mg of codeine (more than seven times the codeine found in Canada’s non-prescription drugs) achieved at least 50 per cent pain relief. By comparison, 18 per cent achieved the same pain relief taking a placebo.

“A sugar pill outperformed 60 mg of codeine,” Shah said. “So what does that tell you? It’s a useless product.”

Shah now refuses to sell non-prescription codeine at his pharmacy. In an article published by the Canadian Healthcare Network, he urged other pharmacists to do the same.

But the Canadian government was warned more than three decades ago about the ineffectiveness and addictive potential of low-dose codeine — by its own appointed experts.

In 1979, the same year the Narcotic Control Regulations came into force, a committee struck by Ottawa’s health protection branch recommended codeine be phased out of non-prescription drugs. The federal “bureau of drugs” director, Dr. Ian Henderson, said small doses of codeine are ineffective for pain relief, The Canadian Press reported. He also warned that animal studies had shown that even low doses of narcotics can cause dependence.

Thirteen years later, concerns were raised by the Canadian Pharmacists Association , which passed a resolution to investigate whether regulatory changes are needed to rein in the overconsumption of non-prescription codeine. The association also gave drug manufacturers two years to provide justification for these drugs, according to an article in the Canadian Pharmacists Journal .

In 2000, the Manitoba Pharmaceutical Association (now the College of Pharmacists of Manitoba ) passed a resolution to ban non-prescription codeine, which it sent to Health Canada. It also asked the National Association of Pharmaceutical Regulatory Authorities (NAPRA) to review this drug too. NAPRA sets national guidelines for pharmacists and can recommend prescription requirements on low-dose codeine, which it currently categorizes as “ Schedule II ” (meaning no prescription required but the drug is stored behind the counter).

NAPRA ultimately decided not to pursue a ban.

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There’s a certain point where you have to cut your losses and say this isn’t a good product, it’s never been a good product and you’re setting people up for tragedy,” said Phil Emberley, the Canadian Pharmacists Association’s director of pharmacy innovation.

In emailed statements, Health Canada and NAPRA stood behind Canada’s current rules. Both emphasized that non-prescription codeine can only be sold by a pharmacist.

“These products can only be accessed by a pharmacist who has the opportunity to interact with the patient and provide them with advice,” Health Canada spokesperson Sylwia Krzyszton wrote in an email.

But former addicts who bought thousands of codeine pills “behind the counter” for more than a decade say pharmacists rarely if ever asked questions or provided advice.

Brampton resident Rick Foster, 53, began taking Tylenol No. 1 in his mid-30s for chronic neck pain. He started with four pills a day; two decades later, he was taking as many as 20 — enough acetaminophen to seriously risk his liver.

A few years ago, Foster had neck surgery and was finally referred to a pain specialist. To his surprise, the specialist urged him to stop using Tylenol 1 and take a liver test. (Foster stopped but didn’t get tested.)

After 20 years of buying Tylenol No. 1 from pharmacists, this was the first thorough consultation he received on this drug.

“Very, very rarely were any questions asked. I would say next to none at all,” said Foster, who believes he “dodged a bullet” and now takes a prescription opioid called Nucynta.

In November, the Star visited five Ontario pharmacies to try to buy non-prescription codeine.

At three of them, employees asked no questions before selling 200 pills. The others asked just one — “Have you used this before?” — and only one offered a 22-second explanation that codeine can cause drowsiness and constipation. Nobody asked why the drug was being bought.

Several pharmacists told the Star that non-prescription codeine is a source of frustration in the profession. There is a patchwork of monitoring systems across the country, ranging from Alberta — where pharmacists can voluntarily record sales in a central database — to Ontario, where pharmacists are not required to document a customer’s purchasing history even in their own stores.

“A lot of pharmacists just don’t bother” asking questions, said John Greiss, a Toronto pharmacist and health policy blogger concerned about low-dose codeine. “Potential abusers know how to get through the system and you’re busy with people who do actually need time and attention.”

Refusing to sell can also be “very, very difficult,” said Shah in Manitoba — especially when other pharmacists are selling the drug, no questions asked.

“(Customers) were going, ‘Well, why are you asking me this and other pharmacists aren’t asking me?’ ” he said. “They feel like it’s a personal attack … they become literally belligerent.”

FOR DRUG COMPANIES , there is at least one good reason to sell non-prescription codeine.

“It was always, by far and away, one of the top-selling (non-prescription) medications,” said Tony Nickonchuk, a pharmacist in Alberta.

In 2013, pharmacies spent an estimated $16.3 million buying non-prescription codeine from wholesalers, according to IMS Brogan (No figure for dosages was available.) These drugs are then sold at a huge markup — up to 200 or 300 per cent, according to pharmacists Nickonchuk and Shah.

There are other countries where non-prescription codeine is available, including Australia and the U.K., which sells it over the counter. But both countries seem to be awakening to addiction issues with the drug and are moving towards tighter rules, like smaller pack sizes (a maximum 32 pills in the U.K.) and label warnings about addiction (which are not on bottles in Canada).

Beth Sproule, a clinician-scientist with CAMH and the University of Toronto, would like to see these drugs become prescription-only. But she suspects sales would plummet. “It probably wouldn’t be prescribed,” she said.

Pharmacists agree there would be significant pushback from customers, many of whom swear by these drugs. They question, however, whether some people are just getting pain relief from the acetaminophen or aspirin mixed into the pills — or even a placebo effect.

There are also worries that the drug’s weak effects encourage people to take more and more. And some people who complain that their headaches come back after stopping the drug could also be experiencing “rebound headaches,” which are actually a withdrawal symptom.

“I have trouble concluding that it’s really helping people,” Nickonchuk said. “If we’re going to argue that it’s not dangerous — and that it’s not dangerous enough to warrant it being prescription — show me the evidence.”

The Star asked Health Canada, NAPRA and leading drug manufacturers for such evidence. None was provided.

Health Canada spokesperson Eric Morrissette said “the current benefit to risk profile of codeine 8 mg products continues to support their market approval.” The health agency also pointed out that the UN Single Convention on Narcotic Drugs from 1961 categorizes these drugs as requiring fewer controls than pure codeine.

But Health Canada would not provide any scientific evidence of the drug’s therapeutic efficacy. The health regulator also said it has never done a risk-benefit analysis of non-prescription codeine, which would have to be triggered by a “safety signal” from its surveillance systems. Health Canada says it continually monitors the safety of all drugs.

Johnson & Johnson said that products like Tylenol No. 1 were evaluated when Health Canada last updated its labelling rules for acetaminophen products in 2009. Labelling standards are developed for non-prescription drugs with a “well characterized safety and efficacy profile,” company spokeswoman Shelley Kohut wrote in an email. “Additional company sponsored efficacy studies have not been conducted and are not required for approval of products with a labelling standard.”

Generic drug giant Teva (which makes Ratio-Lenoltec No. 1, Canada’s bestselling generic of Tylenol No. 1, according to IMS Brogan) refused to answer any questions from the Star.

As for NAPRA, its meeting minutes from 2002 refer to documents that evaluated the drug’s risks and benefits, but spokesperson Lisa Gall said they were not available to the public.

When asked why this drug is still around, many experts arrived at the same answer: inertia. Codeine has been used for more than 200 years and many people grew up with these pills in their medicine cabinets.

But scientists continue to learn new things about codeine.

Codeine is technically a “prodrug” because it only works after the liver converts it to morphine. But emerging evidence shows that people metabolize codeine differently. For example, studies have shown about 40 per cent of North Africans have the gene variant associated with “ultra-fast metabolizers,” thus making them more susceptible to overdose; in Europe, it’s only 3 per cent.

Five years ago, the Canadian Medical Association Journal questioned whether codeine should be phased out altogether. After a number of child deaths were linked to the ultra-fast metabolizer gene, Health Canada in 2013 recommended against giving codeine to children under 12.

Non-prescription codeine also carries an extra risk: the painkillers that have been mixed into the drug.

Acetaminophen, for example, is a growing concern in both Canada and the U.S. , where it is the leading cause of acute liver failure. For addicts of non-prescription codeine, they may be popping these pills for the opiate but they are also getting dangerous amounts of acetaminophen.

But perhaps the greatest consequences are the social harms that come with addiction, said Dr. Lindy Lee with the Addictions Foundation of Manitoba , who spoke to the Star in July. Lee, who recently died of colon cancer, was considered one of Manitoba’s top addiction experts.

She said her patients often experienced depression and social isolation for years or even decades before turning up at her treatment centre. These included aboriginals and women of all income levels. Lee also recalled a businessman who bought chemistry sets to extract the codeine from his pills.

It makes them feel “like a better, more confident version of themselves,” she told the Star.

For Rob, the 34-year-old Toronto man, he was a smart but “extremely tense” teenager when he discovered codeine. “I had found something that just spoke to me,” he said. “I felt a way that I’d never felt before. I felt good and relaxed.”

He accepts responsibility for his addiction but believes he would have never got hooked on this drug if it were not so widely available. Clean-cut and intelligent, Rob once dreamed of becoming a writer. Today, he yearns for just the basic things in life.

“I would love to have a family. I would just love to just have a career,” he said. “I’m just trying to survive.”

jyang@thestar.ca