Tramadol: The Opioid Crisis for the Rest of the World – Wall Street Journal

GAROUA, Cameroon—Not long ago, a Dutch neurobiologist announced a surprising discovery: A root used by rural West African healers to treat pain contains an apparently natural version of a man-made opioid.
The root from northern Cameroon had such high levels of a painkiller called tramadol that mice given an extract and placed on a hot plate didn’t feel their feet burning at first.
A year later, German rivals came up with a different explanation for the unusual plant. Inexpensive, imported tramadol is so heavily abused in northern Cameroon that it seeps from human and animal waste into the groundwater and soil, where vegetation absorbs it, wrote Michael Spiteller and Souvik Kusari, chemists at the University of Dortmund.
Farmers in Northern Cameroon told the researchers that they take double or triple the safe dosage, and feed tramadol to cattle to help them pull plows through the scorching afternoon sun.
“I have to use it,” says Mamadou, a 35-year-old cotton-factory worker in Garoua. He pulled a red pill from his pocket and washed it down with warm pineapple soda. He started using tramadol five years ago, and says he now takes about 675 milligrams daily—more than double the recommended short-term dosage. “Everyone consumes it here,” he says. His mother, his brother, “even the old people.”
Fueled by cut-rate Indian exports and inaction by world narcotics regulators, tramadol dependency extends across Africa, the Middle East and into parts of Asia and Eastern Europe. Tramadol is abused in Guangzhou, Chinese researchers found. The Egyptian government is waging a crackdown within communities including Cairo’s cabdrivers. Saudi officials in May confiscated several thousand pills smuggled in a shipment of frozen meat—one of dozens of busts around the Persian Gulf. A documentary by Pittsburgh filmmakers last year showed tramadol abuse among street children in Ukraine.
It is also hitting the developed world. In the U.S., which is already struggling with addiction to the synthetic narcotic fentanyl, the federal Substance Abuse and Mental Health Services Administration last year reported emergency-room visits related to tramadol misuse more than tripled in 2011 from 2005, to 21,649. In Northern Ireland, tramadol is killing more people than heroin.
For some poor countries, it is an opioid crisis that may be as pervasive as America’s, and more complicated to combat.
“These are the truths,” says Jacques Mems, the police commissioner in Ngaoundere, a Cameroon transit hub where the local jail is over capacity from tramadol arrests. “The problem is too big, and we just don’t have the means.”
Opioids are chemicals derived from, or designed to mimic, substances found naturally in the opium poppy. Tramadol isn’t the strongest, and it isn’t the most addictive. Its widespread abuse stems not so much from its chemical properties as from the international regulations governing the drug.
For five decades, an intergovernmental agency called the International Narcotics Control Board has regulated trade in nearly every opioid. It publishes quotas for how much a country can produce, export or import, and the treaty underpinning the INCB requires registration and documentation for companies that send and receive shipments. It covers natural substances such as raw opium and dried waste from poppy-seed production, as well as lab-made chemicals such as fentanyl and methadone.
The agency doesn’t regulate tramadol, initially the result of long-ago assumptions that the drug isn’t prone to abuse. That turned out to be a misconception rooted in tramadol’s strange chemistry, independent scientists say. Early testing was done via injection, which for most drugs has a stronger effect than oral doses. But recent research shows that tramadol taken orally can have a stronger impact on users than morphine.
International regulators say they now realize tramadol is heavily abused in some places. They still decline to control it due to what some of them say is a weakness in their systems: When a drug comes under INCB regulation, it can become difficult for doctors in poor countries with disorganized health systems to obtain for legitimate use.
Since tramadol isn’t INCB-controlled, it is the only opioid available in parts of Cameroon and other developing nations for people with cancer and post-surgical pain. Doctors Without Borders considers it an “essential drug.” Afraid of limiting legitimate access to tramadol, the World Health Organization expert committee that recommends which drugs the INCB should control has decided repeatedly to leave tramadol “unscheduled,” meaning unregulated.
“We have to be careful not to deprive people who really need those medicines by scheduling it,” says Gilles Forte, the committee’s Switzerland-based secretary.
Excluding tramadol from INCB oversight means there’s no cap on production and no limit or tracking for exports. So each day, 40-foot containers of red pills, green capsules and blue barrels of raw tramadol powder leave India, one of the world’s largest generic-drug producers, for ports including Lagos, La Paz, Taipei and Tobruk.
“All we know is that it’s a gray market,” says Gopal Agarwal, who ships tramadol to Benin from his factory, Pharmalink Laboratories, in an office park in a Mumbai suburb. On a recent afternoon the CCTV monitor in his office showed the production area downstairs; women in hair nets were stuffing capsules into blister packs while four men on their lunch break napped on the floor of another room.
Bertha Madras, a Harvard professor and former U.S. antidrug official who has advised the WHO expert committee, has another name for the tramadol market: “international chaos.”
The framework for regulating addictive drugs took shape in early 1961, when representatives from 73 countries met over two months at United Nations headquarters. The Single Convention on Narcotic Drugs declared that narcotics are “indispensable for the relief of pain and suffering” and set out twin goals: to “ensure the availability” of opioids for pain relief and to “prevent and combat” the “serious evil” of addiction.
It listed dozens of chemicals that would come under its mandate, and outlined a system of quotas and tracking. The treaty established the INCB to enforce those rules.
A year after the treaty was signed, Kurt Flick, a chemist at German drugmaker Grünenthal GMBH, set out to make a cough suppressant by simplifying the structure of poppy derivative codeine.
At the time, says the 91-year-old Dr. Flick, many German scientists were trying to create synthetic drugs that didn’t carry the normal opioid side effects, which include addiction.
Dr. Flick says he developed a molecule that seemed promising. But just when he was finishing tramadol’s development, Grünenthal was overtaken by a crisis: Its popular drug thalidomide was causing catastrophic birth defects.
“For 15 years nothing happened,” Dr. Flick says.
That changed after a Grünenthal scientist, Ernst-Günther Schenck, started testing the drug. Dr. Schenck, a former Waffen SS official who conducted nutrition experiments that killed prisoners during World War II, found tramadol effective for different types of pain. And it appeared to be less addictive than other opioids. He published several papers on its efficacy, and in 1977, Germany approved tramadol for sale. Dr. Schenck died in 1998.
Tramadol quickly gained popularity as a painkiller. “On the one hand I’m happy that I was able to help people that are in pain with my invention,” says Dr. Flick, who still uses a coffee pot and mugs with the brand name “Tramal 100” his old company gave him in the 1980s. “But I wouldn’t have expected that it would have such a world-wide reach.”
At first there was little, if any, evidence of abuse. The WHO drug-control committee didn’t review tramadol until 1992. It cited research saying tramadol didn’t have the same addictive properties as other opioids and concluded in a report it shouldn’t be subject to regulation “on the basis of its low abuse liability.”
In 1994, patients world-wide consumed less than 25,000 kilograms of tramadol, according to figures Grünenthal published using data from research firm IMS Health. The U.S. approved tramadol for sale a year later, and world-wide consumption began rising.
By the time the WHO committee reassessed tramadol in 2000, global shipments were 148,000 kilograms. Tramadol “has been associated with craving, drug-seeking behavior,” the committee wrote, citing cases of abuse, harsh withdrawal symptoms and “the potential to produce dependence of the morphine-type.” After further review, the committee in 2003 raised additional concerns: “larger numbers of case reports of abuse, dependence and withdrawal syndrome for tramadol than for any other analgesic” aside from butorphanol, a potent and tightly controlled painkiller. Still the committee decided not to recommend regulation.
In 2006 researchers for the U.S. National Institute on Drug Abuse and Johns Hopkins University published a paper showing that injected tramadol is a weaker opioid than tramadol taken orally, due to the way the liver processes it.
The WHO committee that year again declined to recommend regulating the drug, saying “studies in animals indicated that tramadol may have a low abuse potential.”
300 miles
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As tramadol lost its patent protection in some areas, India’s large generic pharmaceutical industry sensed an opportunity. Raju Sharma, 50 years old, runs Aaron Healthcare and Export Pvt. in Mumbai. Like many Indian drug exporters, it’s a family firm that started in an unrelated industry; Mr. Sharma’s father made construction materials before buying a medicine factory in the 1970s. In the mid-2000s, Mr. Sharma saw a new market taking shape in Nigeria’s burgeoning cities. He cultivated contacts, and began exporting there around 2005.
It turns out brokering was simpler than manufacturing, so Mr. Sharma sold the factory. His 10-person staff now arranges purchases from factories and sales to African buyers from an air-conditioned, glass-walled Mumbai office.
As tramadol shipments from India rose, African and Middle Eastern governments struggled to control the trade. In Nigeria, where it is illegal to distribute the narcotic without a license, authorities confiscated shipments that weren’t approved by the government’s drug-control agency.
Exporters say they responded by sending tramadol to middlemen in Benin, a tiny West African country with lax drug restriction. Benin is “the second-largest recipient of registered commercial freight shipments from India of the prescription drug tramadol,” the U.S. State Department wrote in March.
Mr. Sharma and a half-dozen other drug exporters in Mumbai say they ship drugs to Benin for their clients to distribute across the region, through Nigeria and into Cameroon.
“We don’t know how they are distributing to other countries, to Nigeria,” said the head of Aveo Pharmaceuticals Pvt., Arvind Sharma, who isn’t related to Raju Sharma. On his desk was a box of tramadol marked “Super Royal X-225.”
He and a colleague, Anand Mandlia, say complying with local African laws is the responsibility of their customers. “We are not doing any hanky-panky business,” Mr. Mandlia says.
Tramadol that goes from India to Benin makes its way to places like Garoua, a smoky city in northern Cameroon where vultures circle over the edge of town. Men in caftans buy boxes labeled “Super Royal X-225” from curbside vendors for a few cents a pill. The potent red tablets are known as “tomates” because the little red apples printed on their boxes remind locals of tomatoes. Coffee sellers with outdoor stands will empty a couple of tramadol capsules into a customer’s Nescafe for 10 cents.
Omarou Aziz, a skinny 35-year-old with a thin mustache and bulging eyes, works in a barber shop he built from corrugated aluminum south of Garoua in Ngaoundere. He began taking tramadol in 2008. “It made me very strong,” he says. He could work longer hours, which helped since a haircut there costs only about 40 cents.
He kept upping his dosage to get the same effect, settling on 1000 mg daily. He grew cantankerous, he says, and would start fights, sometimes while shaving a client’s head. “It was difficult because you were always inflaming customers,” he says. He overdosed multiple times, collapsing in seizures. But he kept taking it. Stopping made him sick.
Further north, where Cameroon narrows to a thin spit between Nigeria and Chad, the drug is popular with the terrorist group Boko Haram. “We find tramadol packets in the pockets of those we kill,” says a Cameroon army commander who oversees antiterror missions.
At Garoua’s hospital, physician Ibrahima Amadou says about four years ago he began noticing motorcycle-taxi drivers waiting for customers outside the hospital gate convulsing in the dirt street.
Dr. Amadou asked colleagues what was wrong; a nurse at the hospital who moonlights as a motorcycle driver told him they used tramadol. Overdoses cause seizures. Dr. Amadou surveyed emergency-room visitors, and found that about 80% of the traffic accidents that resulted in emergency-room visits involved a driver on tramadol. Each week, he says, he sees patients who have overdosed, sometimes fatally.
Since then the situation in Garoua has gotten worse, he says: “Almost everybody now is dependent on tramadol. It’s beyond just motorbike riders.”
A tramadol overdose looks different from most opioid overdoses, in which a person slowly stops breathing. Excess tramadol intake tends to cause seizures and a fast collapse. The hospital doesn’t have the resources to perform routine blood tests for drugs, and emergency-room patients often refuse to say what they were taking, Dr. Amadou says.
In the U.S., Shanna Babalonis, a professor who studies drug addiction at the University of Kentucky, was doing her own research. She says she heard about rising tramadol abuse and noticed the drug wasn’t controlled at the federal level. “Everybody said ‘How is that possible? It’s an opioid,’ ” she recalls.
She tested it on opioid users, and found it produced opioid effects similar to those of oxycodone, the narcotic in OxyContin, which is stronger than morphine and tightly controlled. She published the research in 2012, and in 2013 the DEA classified tramadol as a ‘Schedule IV” narcotic. The move tightened restrictions on how many refills a doctor may prescribe a patient and created federal penalties for illegal sales.
The following year, the WHO committee recommended again not to regulate tramadol. The committee struggled with a “complete lack of data from some countries that recently have reported tramadol abuse and dependence,” it wrote in its annual report.
“There was anecdotal information that abuse was a problem in some places, but those countries didn’t come forward” with data the committee would need to determine whether to recommend regulation, says committee member Jason White.
Also weighing in its decision was a presentation by Grünenthal. “Tramadol has a well-characterized low abuse potential,” the company wrote to the committee. Grünenthal acknowledged that “a limited number of countries, particularly Egypt as well as the African and Middle East regions, face illicit trafficking and abuse of tramadol,” but argued abuse occurs in the context of “political and social instabilities” best addressed by individual countries.
Frank Laschewski, a medical affairs executive for Grünenthal, which still accounts for about 7% of world tramadol shipments, said he’s aware of the reports of abuse, and finds them puzzling. “It’s very difficult to explain why in these countries tramadol is abused, because the abuse potential is low,” he says.
Cameroon’s experience would argue otherwise. Police in the villages and cities like Ngaoundere and Garoua have been arresting tramadol sellers recently. But dealers are still in business. Last spring, wholesalers in downtown Garoua waited for customers behind shuttered storefronts, and curbside medicine sellers started making buyers use a code word (“bouton rouge”) for the drug.
Tramadol has all but taken over the life of Ibrahim, a blank-eyed 36-year-old in a green embroidered caftan and matching round hat. He lives in Ngaoundere, a largely Muslim transit hub where Cameroon’s inland railway ends and trucks pick up cargo bound for the Sahara’s southern edge.
Ibrahim worked 12 bone-rattling hours a day as a motorcycle driver, weaving through traffic on Ngaoundere’s potholed streets. His body hurt, and a relative recovering from surgery gave him a couple of tramadol pills. They eased the aches, took his angry edge off and helped him stay awake, because, unlike most opioids, tramadol acts as a stimulant.
Soon, Ibrahim says he began buying tramadol from curbside vendors for a few cents for a 100 mg capsule, taking one or two each morning and evening with lime or Nescafe. If Ibrahim didn’t take tramadol at all, he got sick. It was “like all your stomach is boiling, he says. “It feels like you have malaria,” Like others, he sought out stronger pills.
Indian exporters like Raju Sharma adjusted their products to meet the changing demand. He initially sent 50 mg and 100 mg tramadol capsules to West Africa. After it “started being abused” in the late 2000s, he says, “people started requesting far higher doses.” First 120 mg, then 200 and 225. Dosages above 100 mg aren’t legal in Nigeria, the purported end market for many shipments. “I don’t know the logic of 225,” Mr. Sharma says. “Medically it doesn’t make sense.”
At a cafe one day in 2011, one of Ibrahim’s friends emptied ten 100 mg tramadol capsules into a cup of coffee to prove he could handle such a high dose. “The minute this guy finished drinking he collapsed,” Ibrahim says. He died soon after in a hospital.
Ibrahim was losing control. His temper grew short, and his mind scattered. During a recent interview, he needed to consult his government ID card to determine his birthday and age. Ibrahim’s son’s teacher summoned him to school “to explain why I beat the children,” he says. “I was not washing the children and dressing them well.”
He says he managed to cut his intake from about 1,000 mg daily to about 400. Off the high doses of tramadol, he says, “I’m a changed person, because I know that beating the child is not correct.”
Late last year he got a job chauffeuring a local dignitary—a position that, after close to 20 years, let him trade the hot and dusty motorcycle job for an air-conditioned car.
One morning in February, he said with an embarrassed smile, he took five 120 mg pills and went to work. He drove his boss to an event in the desert and drank some honey wine. The drugs and the wine sent him into a blur, he says. Driving back, he didn’t notice there was something wrong with the car’s engine until it went up in flames. By spring, he was back riding the bike, with a pocket full of tramadol pills.
—Mackenzie Knowles-Coursin in Cameroon and Ulrike Dauer and Natascha Divac in Frankfurt contributed to this article.
Write to Justin Scheck at
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