WSJournal. A Vaccine to Curb Addicts' Highs New research

WSJournal. A Vaccine to Curb Addicts' Highs
New research shows that our immune system can mute the effects of cocaine and other stimulant drugs
http://online.wsj.com/article/SB1000142412788...P_review_0

One vaccine combines molecules of cocaine with a harmless piece of cholera, prompting an immune response to both.

I met Shirelle as she entered treatment for cocaine addiction at the height of the crack epidemic in the 1980s. An ancient-looking African-American woman who was in fact in her late 30s, she met my gaze with a look that I had seen all over the blighted neighborhoods of Detroit: a disturbing combination of twitchy facial movements and inert, vacant eyes. Feeling ashamed and suicidal about how her addiction was destroying her family, she had entered treatment—out of desperation, not with any confidence that it would help her.

Shirelle had already been through rehab, counseling and 12-step meetings, to no avail. She spoke slowly because her lips were badly burned from her crack pipe, but her direct question was easily understood: "Isn't there anything else?" "Not really," I responded.

As an expert in addiction treatment, what depresses me is that a quarter-century later, I would still have to give her the same answer. But another possibility is now on the horizon: a vaccine for addiction to cocaine and other stimulant drugs.

The idea of using the body's immune system to combat the effects of addictive drugs goes back to animal studies conducted in the early 1970s, but the first evidence that a vaccine could help people with cocaine addiction didn't emerge until 2009. In a groundbreaking clinical trial, Thomas Kosten of Baylor College of Medicine and his colleagues tested a vaccine that combines molecules of cocaine with a harmless component of cholera. Sensing what appears to be an emerging infection, the body generates an immune response to the cholera that extends to the cocaine. At the end of the trial, patients whose bodies generated a strong immune response to the vaccine had almost 30% more cocaine-free drug tests than did patients who generated a weak response or who received a placebo.

What would such a vaccine mean to a cocaine addict like Shirelle? Her body would treat the drug like an invading germ and produce antibodies that bind to it and change its size and shape. The cocaine she ingested, which once would have crossed into her brain rapidly and en masse, would get there slowly, if at all. In colloquial terms, cocaine would be no fun for her anymore. The theory, which Dr. Kosten's study went some way to support, is that when cocaine addicts no longer get a euphoric rush from the drug, they will stop using it.

Treating addiction with a vaccine strikes most people, including many of my colleagues in the field, as radical. For other addictions (to nicotine, alcohol and opiates like heroin) the approach has been very different: The pharmacologic breakthroughs have come from medications that alter neurochemistry to reduce cravings or block the rewarding effects of drugs at particular receptors in the brain. Billions of dollars have been spent trying to develop similar medications for cocaine and methamphetamine addiction, but the results have been disappointing. A vaccine to combat addiction to these drugs would work as soon as the drug enters the body, before it has a chance to exert its powerful effects in the brain.

A vaccine would not be a magic bullet; it couldn't stand on its own as a solution to cocaine and methamphetamine addiction. Cognitive-behavioral psychotherapy and 12-step groups have been shown to reduce stimulant drug use in rigorous research studies. Another approach using small, prompt rewards contingent on stopping drug use—rewards like meal vouchers and movie tickets—has been shown to be effective both in health-care settings and in the criminal justice system. But like everyone else in the addiction treatment field, I know that these approaches aren't always helpful and might become more effective if combined with a medical approach.

There are a number of discouraging facts, however. In Dr. Kosten's study, only 38% of patients injected with the vaccine developed a strong immune response. The rest developed a weak response or none at all, for unknown reasons. Even when the vaccine did work, the effects faded over time, requiring re-injection every few weeks. And not everyone will be willing to try the vaccine, for the very reason that it is so promising: It makes drug use less enjoyable without immediately reducing the physical and psychological craving for the drug.

Future vaccines may not have to depend on the uncertainties of each patient's body to generate a strong immune response. S. Michael Owens of the University of Arkansas for Medical Sciences has synthesized antibodies to methamphetamine that can be infused into addicted patients. So rather than waiting to see if a patient's body will produce its own antibodies, as in Dr. Kosten's study, Dr. Owens notes that with this approach "we can give you enough antibody and we can do it fast and at the right dose, just like any other medication."

The problem of immune response fading over time may also be solved one day. Theoretically, future vaccines could use a virus to deliver genetic material that reprograms liver cells to consistently produce antibodies to stimulant drugs. Shankar Vallabhajosula of Weill Cornell Medical Colleague recently used brain scans to demonstrate that such a gene-therapy vaccine blocked cocaine from entering the brain of monkeys as long as four months after injection. A trial in humans is planned.

Perhaps the biggest obstacle to developing a vaccine is funding. Nora Volkow, the director of the U.S. National Institute on Drug Abuse, says she is "very excited by the possibilities of vaccines." But the entire $1 billion annual budget of her grant-giving agency is barely equal to what the pharmaceutical industry spends to bring a single medication to market. The big money for research and development is in the private sector, which has shown little interest in addiction vaccines.

The pharmaceutical industry knows that for an addiction vaccine to be profitable, large numbers of clinicians have to prescribe it. But only some 3,500 physicians in the U.S. specialize full-time in addiction, as compared with a population of about 21 million Americans with diagnosable drug and alcohol problems. A significant portion of physicians don't see addiction as a legitimate medical condition and therefore aren't interested in treating it. Others look at the high failure rate of addiction treatment and instinctively recoil: Physicians hate failure even more than they hate managed-care executives.

Early in my career, depression was often seen as a sign of weak character that doctors were helpless to affect. Then came the Prozac revolution. When doctors and patients saw that depression responds to a medication, they came to view the condition more as an illness than as a character defect.

If vaccine researchers can give doctors an effective medical treatment for stimulant drug addiction, a similar virtuous cycle could begin. The existence of a medication would legitimize cocaine and methamphetamine addiction as medical disorders, which in turn would make doctors more comfortable treating the addiction of patients like Shirelle. Only then would the pharmaceutical industry make the investments that will be required for the rapid development of this potentially lifesaving technology.
—Dr. Humphreys is a professor of psychiatry at Stanford University and a former senior policy adviser in the White House Office of National Drug Control Policy.