The drug is methamphetamine, otherwise known as speed, crystal, crank and by numerous other street names. In a few short years, it has gone from the vice of a few to the drug of choice for millions of Americans.
More than 12 million Americans have tried methamphetamine and 1.5 million are regular users, the US Drug Enforcement Agency says.
They snort, smoke injected the crystalline white powder, which releases a burst of dopamine in the brain. This triggers a euphoric rush of confidence, hyperalertness and sexiness that lasts for hours.
“It makes you feel like you can do anything - and initially you are quicker, smarter and more focused,” says Guy P., a former tilesetter, who is struggling to break his addiction. “But when that first rush wears off you’ll do anything to get it back. Of course you never can.”
The basic ingredient of the drug is as close as the local pharmacy. Pseudoephedrine is a chemical derivative of amphetamine, which is found in many cold and cough medicines. It is brewed with alcohol, lithium and ammonia in thousands of mostly primitive labs that dot the country. Labs have been uncovered in all 50 states; Missouri tops the list, with more than 8,000 labs, equipment caches and toxic dumps seized between 2002 and 2004.
This helps to explain why police nationwide rank the methamphetamine the No. 1 drug they battle today, popular among all socio-economic ranks - from suburban housewives who need a boost to get their chores done to gay men who use it as a stimulant at all- night sex parties.
Policy makers are only now starting to battle the danger. For decades after it was first popularised by motorcycle gangs in the 1960’s, methamphetamine was regarded as “poor-man’s cocaine” popular only in poverty-stricken rural communities.
On Thursday, President George W. Bush’s administration acknowledged that a new initiative was needed. Officials said they were starting a comprehensive approach to battle methamphetamine by devoting more of the country’s 12.4 billion dollar drug control programme to meth and starting the construction of a chain of new substance abuse treatment centres.
“Faces of Meth”
A string of high profile articles in the news media had focused government attention recently. The single most telling effort came from sheriff’s deputy Bret King in Portland, Oregon.
He was struck at how noticeably worse meth users looked every time they were arrested - the pretty mother turned into an old hag within 30 months, her teeth fallen out, her skin already grey with death. The bright-eyed teenager turned sallow and bitter with defeat.
“There were a few cases where the changes that had taken place due to the methamphetamine use were so extreme, that we didn’t realize the person was who they were,” says King.
King launched a programme called “Faces of Meth” to chronicle the ravaged faces of meth users. He took it to schools and it became a media sensation featured in major newspapers and TV shows.
Publication of the photos in The Oregonian newspaper prompted the state to pass legislation in mid-August limiting the cold medicines to prescription sale.
One of the most harrowing images was of Teresa Baxter, 42, a woman now in a drug recovery programme. When she started using the drug two and a half years ago, she was an attractive mother with a sunny smile and neat hair-do. Now her face is so gaunt and wrinkled she can’t even bear to look in the mirror.
“This stuff is powerful, makes people do crazy things,” Baxter said. “I do hate the drug and I wish I had never used it, but I can’t be away from it. It’s hard. It’s really hard for me.”
“My life and my work pretty much fell apart,” said another Faces of Meth graduate, Matthew Cooper. “They all took a back seat to the meth. It may be a matter of months. It may be a matter of years. But it’ll destroy your life.”
Doctors are doling out amphetamines to children as well as adults, but how much to we know about the risks?
GAZING out of a mugshot with an embarrassed half-smile on her face, Theresa Baxter looks younger than her 39 years. The effects of methamphetamine abuse, which had started two years earlier, were yet to show themselves on her face. Three years on, in another police photo, Baxter is virtually unrecognisable. Her face is haggard and covered with sores, fine lines are now crevasses, and her mouth is clamped shut to hide missing teeth. "I can't stand to look at myself," she told a reporter for The Oregonian newspaper, crying during a jailhouse interview.
In the US, the results of amphetamine abuse are all too familiar. The past 10 years has seen an epidemic of addiction, and "crystal" has now overtaken crack cocaine as the nation's number one demon drug. Demand for amphetamine-related addiction treatment rocketed between 1992 and 2002, from 10 admissions per 100,000 people to 52.
Worldwide, amphetamines are the second most popular illicit drug after cannabis. The UN estimates that some 26 million people use them illegally each year. The dramatic increases of the 1990s have slowed, but many regions, particularly the US and Australia, still report record numbers of users. And with the surge in illegal use has come a slew of research on amphetamines' devastating health effects.
So it seems surprising, on the face of it, that amphetamines are increasingly being prescribed as therapeutic drugs, not just for adults but also for children as young as 2. In 2001 doctors wrote 20 million prescriptions a month for amphetamines and related drugs in the US alone, according to drug industry monitor IMS Health. That represents an increase of over 500 per cent during the 1990s. A similar pattern is evident around the world.
Prescribed primarily for attention-deficit hyperactivity disorder (ADHD), which affects around 6 per cent of children and about 8 per cent of adults at some time in their lives, amphetamines are also used to treat narcolepsy and have been used experimentally to help people to recover from a stroke. Some researchers are now suggesting that amphetamines should be used as maintenance therapy for meth addicts, in the same way that methadone maintenance is used to help heroin addicts (see "Off the streets").
But if amphetamines are so damaging, is it really a good idea to be dishing them out therapeutically, especially to children? "This is what I've been interested in all along, trying to understand how and under what conditions these drugs are safe and when are they useful," says Nora Volkow, director of the National Institute on Drug Abuse (NIDA) in Bethesda, Maryland. Now she and other researchers are starting to get some answers.
The amphetamines are a class of stimulant drugs often known as speed. The best known are methamphetamine and dexamphetamine, which are both used recreationally and therapeutically. The most commonly prescribed form is methylphenidate (Ritalin), an amphetamine derivative that has a somewhat different chemical structure but similar behavioural effects. All affect the brain by boosting levels of the neurotransmitters dopamine and noradrenalin, and in some cases, serotonin and glutamate. This produces heightened alertness, energy, euphoria and focus, while cutting appetite for food and sleep. Hence their appeal as recreational drugs.
Abusing amphetamines is risky. The drugs can be highly addictive, and Volkow's research and that of other groups has consistently shown that addicts can suffer brain damage that may be irreversible. In one study from 2001, Volkow imaged the brains of abstinent amphetamine addicts and control subjects using positron emission tomography. The scans showed that addicts' brains had fewer dopamine transporter proteins in regions linked to positive emotions and planning. They were also worse at memorising lists of words and did poorly on motor tests. In a follow-up study nine months later, Volkow found significant recovery in the brains of addicts who had remained abstinent, although there was no improvement in memory and motor tests (The Journal of Neuroscience, vol 21, p 9414).
It is impossible to know, of course, whether the drug caused the damage, or whether these people would have performed badly even before they became addicts. But animal research shows that high doses of amphetamine can do long-lasting damage to brain cells. Curiously, however, far less damage is seen in humans than in animals. One explanation may be that many addicts also smoke. In rodents, nicotine is known to have a protective effect against such damage.
The question of whether therapeutic doses are similarly harmful, however, has received much less attention. "For many of these medications, we don't have good knowledge of the risks," says Volkow. Although it is hard to say for sure how much addicts take - quality control is not a priority of illegal manufacture - researchers think it is at least 10 times the doses used for treatment. But even if the amounts were reliably known, you can't draw any conclusions from the data on illicit use. "The really tricky thing is back-extrapolating," says Frank Vocci, director of the division of pharmacotherapy and the medical consequences of drug abuse at NIDA. "If you take 1000 grams and it produces brain damage, will 1 gram produce a thousandth of the amount of brain damage?"
For some toxins, the relationship between dose and damage is linear. But others, such as morphine, have a therapeutic range over which the drug is harmless. Whether the same is true for amphetamine is not yet known.
The route of administration and even the context in which a drug is taken can also alter the user's response. "The same drug in one condition is reinforcing and rewarding, and in another, it's not," says Volkow. Rats, for example, seem much more susceptible to the pleasurable effects of amphetamines if they are given them in a novel situation. A similar effect has been observed in humans, prompting some to suspect that a therapeutic context might make the drugs safer.
The speed at which the drugs reach the brain is another critical factor. Therapeutic doses are administered orally, whereas abusers tend to favour more harmful routes such as smoking and injecting. The latter get larger doses of the drug to the brain faster, reducing the brain's ability to compensate. A dose that might be innocuous when taken orally could cause brain damage when injected.
Nevertheless, there are hints that therapeutic use is not risk-free. In June, the US Food and Drug Administration announced that it was planning to change the labelling on amphetamines to highlight known side effects such as psychotic behaviour and aggression. And the Canadian government has suspended sales of one form of the ADHD drug Adderall, which contains dexamphetamine. The authorities say it was linked with 20 unexplained deaths due to cardiovascular problems, although both manufacturer Shire Pharmaceuticals and many psychiatrists dispute any connection.
“For many of these medications we don't have good knowledge of the risks”
Research on rats has also led to concerns over how these drugs may affect brain development. When William Carlezon of Harvard University and his colleagues exposed young rats to therapeutic doses of Ritalin and observed them as they grew, they found that the mature rats found cocaine unrewarding, were less interested in sex and less likely to prefer sweetened water to plain water. This might sound like the recipe for the perfect teen: one who eschews sex, drugs and sugar. What it really is, however, is a prescription for depression. "Ritalin is essentially breaking the reward system," says Carlezon.
These results may not be relevant to humans, however. The rats received Ritalin by injection, while people take it orally. And the treated rats did not have a rat equivalent of ADHD. In one rat model of the disorder, Ritalin releases less dopamine than it does in normal rats. If this occurred in humans, Ritalin would normalise dopamine levels, instead of leading to the elevated levels Carlezon found.
In any case, existing human studies don't point to a problem. "There is no data supporting the notion that stimulants result in depression," says Timothy Wilens, a psychiatrist at Harvard Medical School.
It is also emerging that, contrary to what has been assumed, Ritalin may not have quite the same effects on the brain as amphetamines. In fact, it may have a protective effect. Last year, Glen Hanson of the University of Utah in Salt Lake City showed that methamphetamine damages cells by interfering with a protein, VMAT2, that is involved in dopamine storage. If dopamine is not sequestered properly, it can cause oxidative damage to the cell. Ritalin, however, increases levels of VMAT2 and can even protect against methamphetamine damage in rats, if administered afterwards.
So while Ritalin and amphetamines have similar effects on behaviour, the same does not apply to brain cells. In fact, Hanson suggests that Ritalin could help prevent the degeneration of dopamine neurons seen in Parkinson's disease. This also raises the question of whether Ritalin could be used in detoxification of meth addicts to minimise brain damage, and whether it would be a good drug to use for long-term maintenance.
Volkow isn't ready to give Ritalin a clean bill of health just yet. She has asked NIDA researchers who carry out population surveys on drugs and mental health to start looking at the long-term effects of prescription drugs. These surveys might uncover problematic relationships if, for example, children given Ritalin were more prone to adult depression.
Considering how widely they are prescribed, very little is known about the effects of therapeutic amphetamines and Ritalin. And that seems rather odd, even irresponsible. After all, if doctors were prescribing cocaine, heroin or ecstasy to children, you'd want to be sure they knew what they were doing.
From issue 2509 of New Scientist magazine, 23 July 2005, page 37
Off the streets
THE most effective treatment for heroin addiction is methadone maintenance. And now researchers want to try something similar for amphetamines, even though many specialists believe it will never work.
Methadone works by satisfying addicts' craving. Amphetamine addiction, however, involves "reverse tolerance": addicts become more sensitive to certain effects of the drug, not less as happens with opiates. So maintenance might actually increase cravings.
In the 1960s, doctors in the UK regularly used amphetamine maintenance, and although little proper research was done, the consensus was that it didn't work. In the past few years, however, interest in maintenance has been revived.
A trial in Sydney, Australia, in 2001 found that amphetamine addicts were more likely to stay in counselling if they were maintained on dexamphetamine. Another study showed that more than half of a group of 148 addicts maintained on dexamphetamine stopped injecting the drug.
"When we first presented our results, we were called cowboys," says John Grabowski, a psychiatrist at the University of Texas in Houston who is studying stimulant maintenance. "I have friends who thought I was completely wrong, but now they're saying, 'Hey, the data looks good.'"
Whether such treatment proves socially acceptable is another question. "Many people are uncomfortable with the notion of addicts getting the drug they want," says Alex Wodak of St Vincent's Hospital in Sydney, who carried out the 2001 trial. The US National Institute on Drug Abuse is reviewing the research and Volkow promises more funding if the data holds up.