Inside the Addiction Drug Pipeline
(page 2)Owens is currently in the race for a methamphetamine vaccine, with one of his anti-meth shots already in human tests for safety. Owens’ innovative approach is very different from Taffe’s more traditional one, however. Owens is synthesizing methamphetamine-primed antibodies in the lab and then injecting them into patients. Rather than waiting to see if your body produces its own antibodies, “we can give you enough antibody and we can do it fast and at the right dose, just like any other medication," Owen says.
A major problem with all addiction vaccines is that their effect is short-lived. A decent immune response typically requires a series of injections over a month or so, but the response may fade in a matter of weeks. But to overcome addiction, many people need long-term, even lifetime, treatment. The costs and complications of a vaccine that must be administered every few months would probably be prohibitive for both patients and health insurance companies.
Ironically, Scripps' most significant contribution to addiction treatment is not a vaccine at all but a pill that has been around for years. Researchers have shown that gabapentin (Neurontin), originally approved to treat seizures, has modest effectiveness against alcoholism during acute withdrawal and early abstinence. While vaccines prevent the substance from entering the brain, conventional drugs like gabapentin are chemicals that “block the brain effect, not just the substance effect," Koob says.
The Center for Studies of Addiction (CSA), at the University of Pennsylvania’s School of Medicine, may be our best hope for getting effective treatments into addicts’ bodies in the near term. Because CSA not only researches new treatment options but actually works with people with substance abuse problems, they have established a unique program of clinical trials of psychoactive drugs already approved for other conditions to see if they can help curb addiction. This is one of the most economical ways to bring an addiction treatment to market. Most of these drugs have been around for years, so their safety issues are well known; they can go directly into human trials.
No one expects any of these drugs to be a game-changer. Because each will likely offer, at best, only modest benefits, CSA is banking on the “cocktail” model of treatment: Use two or three partially effective drugs together to target different receptors and pathways at the same time.
"The money for research would usually come from pharma companies," Kroob says. “But there's a stigma associated with working with drug addiction.”
CSA's program includes testing two medications for alcohol abuse: naltrexone, an old anti-craving drug, and Seroquel, a bipolar treatment. Trials are up and running for the dual addiction of alcohol and cocaine with a combination of naltrexone and modafinil, a non-amphetamine stimulant that has not exactly won raves in previous anti-cocaine studies. Nonetheless, CSA is doing its own modafinil-for-coke-addiction trial, adding the anti-nicotine drug Chantix. The program has a certain throw-it-against-the-wall-and-see-if-it-sticks rationale, but some of these drugs will likely stick for some addicts.
Kyle Kampman, MD, medical director of CSA's Addiction Treatment and Medication Development Division and principal investigator of a project in the Cocaine Medication Development Center, reports that his lab just completed a trial of a cocaine vaccine (the data are still being analyzed). Substance abuse vaccines fit the “cocktail” model perfectly. Because vaccines do not affect the brain, a cocaine addict could take both the vaccine and psychoactive drugs that do target the brain; a heroin addict could do a vaccine-Suboxone cocktail. Pile on the pills!
Progress in basic research and clinical trials is slow and expensive—witness the ongoing failures of Scripps’ many experimental vaccines. Both Scripps and CSA are funded mainly by the federal government and pharmaceutical companies. But money is tight. Scripps’ Kroob says that their promising heroin vaccine is in limbo until he finds financial backers to pay for more animal studies. "This kind of money would usually come from pharma companies," he says. “But there's a stigma associated with working with drug addiction.”
The drug industry has calculated that the market for addiction treatments, especially vaccines, is too small to be profitable. A large number of clinicians would have to prescribe the treatment. But only some 3,500 physicians in the US specialize in addiction. Many physicians do not see addiction as a legitimate medical condition and have no interest in treating addicts. Others look at the high failure rate of all addiction therapies and recoil.
Obamacare might somewhat improve the situation. Many poor and uninsured people with substance abuse will become eligible for Medicaid. The Affordable Care Act mandates that Medicaid and all health insurance for newly eligible adults starting in 2014 must include services for substance use disorders. Yet whether the coverage offered by Medicaid and the exchanges will prove adequate remains to be seen. Medicaid has a lifetime cap for methadone and Suboxone that covers only five months of treatment. Yet controlling substance abuse with long-term medication is cost-effective. “Look at any emergency room,” Koob says. “Half of the patients are there because of addiction-related issues.”
By default, the financial burden of addiction drug research has largely fallen to the federal government, especially the National Institutes of Health (NIH). “That's why the NIH is so important,” says Donald Vereen, MD, the director of the University of Michigan Substance Abuse Research Center. Vereen served at the NIH during the Clinton and Bush II administrations; he was also deputy drug czar. The NIH, Vereen says, often partners with pharmaceutical companies to move promising compounds through trials and to market. Indeed, buprenorphine (Suboxone) owes its success to this collaboration. (The drugmaker gets all the profits, however.) The National Institute on Drug Abuse (NIDA) also has a medication development division—a sign, Vereen says, of private industry’s neglect of the field.
“Nobody wants to work on developing drugs for addicts," he says, echoing the sentiments of other top researchers. Why? Because of social stigma and the criminalization of substance use. In the end, these are bigger deterrents to progress than the limits of neuroscience and the cost/benefit analyses of Big Pharma.
“The lack of treatment for addicts is ultimately a civil rights issue," Vereen says. That is not a problem that gets solved by scientists in labs.
Raphael Rosen is a Brooklyn-based science communications professional, social media strategist and independent museum consultant. He has written for the Wall Street Journal, The Fix, the World Science Festival, Discover magazine, Sky & Telescope and NASA.
- hijacked brain
- addiction drug pipeline
- Thomas Kostens
- Baylor College of Medicine
- Scripps Research Institute
- Committee on Neurobiology of Addictive Disorders
- Pearson Center for Alcoholism and Addiction Research
- George Koob
- Kim Janda
- Michael Taffe
- Michael Owens
- Center for Alcohol and Drug Abuse
- University of Arkansas for Medical Sciences
- Center for Studies of Addiction
- Kyle Kampman
- Addiction Treatment and Medication Development Division
- Cocaine Medication Development Center
- Affordable Care Act
- Donald Vereen
- University of Michigan Substance Abuse Research Center
- National Institutes of Health
- National Institute on Drug Abuse
- Raphael Rosen