When methadone was first proposed for the treatment of heroin addiction, it sounded like a pointless gambit — sort of like substituting vodka for gin. That's enabling addicts, critics said, not helping them.
But over the years, maintenance treatment with methadone and other synthetic opiates like buprenorphine has proved successful — more than any other heroin-addiction therapy — in getting people off illicit drugs and lowering HIV transmission rates, crime and death among users. That success, in part, has got researchers wondering whether addiction to other drugs — namely to the stimulants cocaine and methamphetamine — could be curbed in the same way, by substituting a chemically similar alternative.
"It's an idea that really does need to be rigorously evaluated," says Frank Vocci, director of the pharmacotherapy division at the National Institute on Drug Abuse (NIDA). "But right now there is more discussion than data."
The problem of stimulant addiction in the United States has dropped out of the spotlight of late, but it has not disappeared. According to a 2007 government survey, 2.1 million Americans had used cocaine in the month prior to the survey and 1 million had taken other stimulants for non-medical purposes, including more than half a million users of methamphetamine. There are currently no overwhelmingly effective addiction treatments. Abstinence-based rehab therapy for meth and cocaine work about as well as rehab for other drugs — meaning that about one-third of users improve following treatment, but most relapse repeatedly. And despite decades of study of dozens of compounds, there are yet no federally approved medications for cocaine or meth addiction.
Asked whether NIDA thought the concept of stimulant maintenance treatment holds promise, Vocci says, "If putting your money where your mouth is means [that we consider it promising], then, yes, we're funding a fair number of studies."
To date, the research has been mixed, but intriguing. The best studied drugs so far are dexamphetamine, a form of amphetamine contained in the anti-hyperactivity drug Adderall, and modafinil, the wakefulness drug used to treat narcolepsy and shift-work sleep disorder. Most studies have been small and focused on safety rather than efficacy. Some have found no effect — but because of their size, it's difficult to determine whether that's meaningful.
One British study followed 60 stimulant addicts who were treated with dexamphetamine in a Cornwall clinic. Doctors compared how well these patients fared compared with 120 heroin addicts being treated with methadone, and found an equivalent reduction in illicit drug use and drug injection. In both groups, about two-thirds of patients stopped injecting over 10 months.
Another trial in Australia followed 30 cocaine injectors, 16 of whom were treated with dexamphetamine and 14 with a placebo. Cocaine-positive urine tests in the dexamphetamine group fell from 94% to 56%, while the placebo group showed no change after 14 weeks. A similar study of modafinil at the University of Pennsylvania in 2005 found reduced cocaine use in addicts.
But there are reasons that stimulant maintenance treatment was not initially studied more extensively. For one, high doses of amphetamines can cause brain damage, psychosis, heart attack and stroke. (High doses of opioids like methadone, in contrast, can also be dangerous, but once a patient develops a tolerance to it, even very high doses of the drug are not toxic.) The consequences of high-dose use are important, since addicts in treatment often try at least once to use illegal drugs "on top" of their maintenance drug. So far, however, studies of dexamphetamine and similar drugs have not revealed major safety problems. Although a few patients have had psychotic episodes from using "on top," those particular patients turned out to have previously suffered psychosis. "There's pretty consistent evidence that the side effects are generally nominal," says John Grabowski, a professor of psychiatry at the University of Minnesota, who has championed the study of stimulant maintenance treatment in the U.S.
Another problem is that stimulants appear to increase users' desire subjectively, rather than satisfying it. While a heroin high is calming and lasts for several hours, cocaine and amphetamine feel different. As actor Robin Williams, an admitted ex-user, put it, cocaine makes you feel like a new man and the first thing the new man wants is more cocaine. It produces excitement, not relaxation. And the concern is that a maintenance drug would have the same escalating effect.
"That's one argument but the data doesn't seem to support it," says Craig Rush, professor of behavioral science at the University of Kentucky. In a study of seven cocaine-dependent patients, Rush treated them with dexamphetamine maintenance, then gave them cocaine in the lab. The effects of cocaine were blunted. Rush is now looking at what happens when dexamphetamine-maintained patients are given a choice whether or not to take cocaine in the lab — preliminary results suggest they "just say no" more often.
The newer stimulant drug, modafinil, does not carry the same addiction risk as amphetamines, making it a promising alternative as a maintenance drug. But it's also less effective in treating the most severe addictions, according to Grabowski. "In our research, we were able to separate out [the more and less severely addicted patients] and the more severe people were more responsive to the more potent stimulants," says Grabowski, who has conducted two randomized controlled trials involving nearly 200 patients, which found that dexamphetamine treatment reduced cocaine use better than a placebo.
Proponents of stimulant maintenance treatment also note this significant detail: Many stimulant abusers suffer from attention-deficit/hyperactivity disorder (ADHD). While ADHD affects about 1% of the general population, according to Rush, it shows up in about 30% of cocaine and amphetamine addicts. Psychiatrists often hesitate to give hyperactivity drugs to patients with a history of addiction, but some studies suggest that maintenance may be exactly what this group needs — and that their drug abuse is an attempt to self-medicate. The studies that have included ADHD patients (many studies exclude them to avoid confounding) showed positive results. In one pilot study, conducted at Columbia University, maintenance treatment reduced cocaine use and craving in 12 cocaine addicts with ADHD.
None of the researchers believe that stimulant maintenance is a panacea or that it will work for every cocaine or meth addict. But there is no medical treatment that works 100% of the time. "I think we have found something of potential benefit and it should be met with interest and further research, rather than disdain," Grabowski says.
By Maia Szalavitz
Posted on Monday, Dec. 08, 2008