From nicotine gum and patches for smoking cessation to buprenorphine and methadone for opioid use disorders, medication-assisted treatment (MAT) using “replacement” therapy in the form of medications that are similar to the substance being abused is a proven treatment method — it works. So it’s not surprising that prescription stimulants can help people with addictions to stimulants, such as cocaine and methamphetamine. However, there are no approved medications to treat either cocaine or methamphetamine dependence. The National Institute on Drug Abuse (NIDA) is not enthusiastic about pursuing any such research.
The reason may have more to do with politics than science, according to John Grabowski, Ph.D., professor in the Department of Psychiatry at the University of Minnesota, Minneapolis. “The notion of harm reduction is not well loved by NIDA itself, and they have been resistant to the whole concept of stimulant replacement therapy,” Grabowski, a pioneering researcher in the area of treating cocaine addiction with prescription stimulants and a current NIDA grantee, told ADAW last week. “I was once castigated by somebody from NIDA who said, ‘Do you expect me to go up to Congress to talk about giving stimulants to stimulant abusers?’” Grabowski’s answer was, he said, “Yes, that’s your job.”
In one respect, the reticence to provide research funds on replacement therapy is difficult to understand, given NIDA’s strong support for buprenorphine, which it helped to develop, and to methadone, which is a proven medication. In another, as Grabowski himself pointed out, even methadone and buprenorphine are controversial in some circles these days. “It’s almost a reversion to the principle of the past, of wanting to punish drug users,” said Grabowski of the popular sentiment against agonist therapy.
Although most of Grabowski’s work has been with cocaine addiction, methamphetamine and cocaine are “quite similar,” he said. “We would like to find the best candidate stimulant for use for both.”
More studies are needed, said David A. Gorelick, M.D., Ph.D., professor of psychiatry at the University of Maryland. Noting that Grabowski’s work has shown that long-acting stimulants are better than short-acting for the treatment of cocaine dependence, Gorelick told ADAW. Other studies that showed limited effectiveness, including some by Grabowski, might have been affected by doses that were too low, resulting in craving. “The limited evidence we have would say it’s more important to use the long-acting stimulants, and at the higher end of the dose range,” said Gorelick. “We need many more studies to flesh out the optimum dose.”
As for the barriers to using a stimulant to treat stimulant dependence, it’s “the same issue we faced with methadone and buprenorphine,” said Gorelick. “The bottom line is, it works.”
Using stimulants to treat methamphetamine use disorders is analogous to using methadone or buprenorphine to treat opioid use disorders, said Grabowski. “And in much of the work that has been done, there has been some success,” he said.
Charles P. O’Brien, M.D., Ph.D., professor in the Department of Psychiatry at the University of Pennsylvania, told ADAW that there might be increases in craving if patients with stimulant use disorders are given stimulants.
But Grabowski disagreed with this, saying that this would not occur if adequate doses are given. The same problem — craving — occurs in new medication-assisted treatment patients who are started on doses of methadone that are too low.
“The main shortcoming of many studies — and the likely reason why the evidence is not as conclusive for stimulant replacement therapies as it is for opioid replacement therapies like methadone or diacetylmorphine (prescription heroin) — is inadequate dosing,” said Daniel Robelo, research coordinator for the Drug Policy Alliance. “Some of the existing studies employed doses that were way too low, especially for long-term, treatment-refractory, stimulant-dependent subjects.”
Patients and the research community would benefit from controlled trials using “more robust doses that more closely approximate the effects of recreational stimulants,” said Robelo. “Nevertheless, the emerging evidence is quite promising, if not uniformly so.”
Most recently, Grabowski published a paper in Drug and Alcohol Dependence on the use of lisdexamfetamine (Vyvanse) to treat cocaine use disorders. In that safety study, conducted with lead author Mark E. Mooney and colleagues, he found the slower onset and longer duration of action make Vyvanse work well for stimulant dependence, he said.
Toby Clark Pickens, executive director of the Austin Harm Reduction Coalition, found that many methamphetamine clients use stimulants like Ritalin, Adderall or — especially — Vyvanse to help them quit. “They tell me when they try to quit, they get too tired and they can’t go to work — so when they take the Adderall, they are able to get to work,” she said. Interestingly, many of these clients also say they have attention deficit hyperactivity disorder. “These people are more functional methamphetamine users — they’re not homeless,” she said.
The harm-reduction community has been more supportive of replacement therapies than the mainstream research community — and, in fact, “harm reduction” may be a misnomer. If treatment works, isn’t it treatment?
Meanwhile, NIDA is heading in other directions, including vaccines.
“NIDA is dedicated to our mission of reducing the burden of substance use disorders and fully considers all scientifically sound proposals to achieve this goal,” said a NIDA spokesperson. “To date, treatment of methamphetamine with stimulants has shown mixed results in various patient populations and thus has not been approved to treat methamphetamine addiction.”
The ‘paper of ill repute’
In 2009, Grabowski found that giving stable doses of prescription-grade methamphetamine to cocaine users was found to be highly effective. “This is something nobody likes to talk about,” said Grabowski, who referred sardonically to the study, published in Drug and Alcohol Dependence, as the “paper of ill repute.”
“Perhaps someone will discover the magic pill, but I expect that harm reduction will be the most promising strategy for the foreseeable future,” said Grabowski. So far, despite a decade of work, vaccines have not shown great promise. Behavioral interventions have shown some efficacy and are used as a baseline for any medication study.
As for Grabowski’s paper comparing immediate-release and sustained-release methamphetamine for the treatment of cocaine dependence, only the latter produced a great benefit. “If you think they cringe at d-amphetamine, they go over the top with methamphetamine as treatment,” he said. Grabowski noted that the manufacturer stopped producing the sustained-release preparation of methamphetamine “in the great war on methamphetamine,” but continued producing the immediate-release version.
For abstracts of cited papers, go to:
Using stimulants to treat cocaine dependence has been found to be effective if the dose is adequate, and could work for methamphetamine dependence as well, but more research is needed.