Addictive substances hijack normal brain pathways, but Tom Kosten, M.D., and Therese Kosten, Ph.D., hope a cocaine vaccine they developed is the key that frees millions from their addictions.

The husband-and-wife team recently relocated from Connecticut to Houston to join BCM’s Menninger Department of Psychiatry & Behavioral Sciences. It was the latest leg in a journey that began as teenagers when the two were paired for figure skating competitions.

They partnered up again several years later at Yale University. He was there doing his residency after completing medical school at Cornell University. She was there completing her Ph.D. in psychology and neuroscience. This time, the partnership took on a new level of permanency. In addition to their marriage vows, the two have been committed to substance abuse treatment for more than 30 years .

What if a syringe helped conquer drug addiction instead of causing it? That’s the goal of Baylor College of Medicine’s newest research duo, Tom Kosten, M.D., and Therese Kosten, Ph.D., who have developed a promising cocaine vaccine and have plans for similar vaccines for methamphetamine and nicotine addiction.

“We are both interested in developing medications to treat addictions,” said Thomas Kosten. “One attraction for me is the immense social implications of the area.”

According to the Substance Abuse and Mental Health Services Administration, 22.2 million people in the United States were classified with substance dependence or abuse in 2005. It is a costly habit. The National Institute on Drug Abuse estimates that addiction costs the nation $484 billion a year, almost three times as much as cancer. Substance abuse strikes every facet of society and its consequences can be grave.

“When intoxicated—and often for another week or more after stopping—some abusers have a tendency to behave sociopathically, and even kill people,” said Thomas Kosten. “Through brain imaging studies, we have learned that many abusers can be insensitive to feelings and emotions in others. The abuser’s brain just doesn’t register that another person is in pain or that the abuser may be causing that emotional—and in extreme cases, that physical pain. This obviously is severe pathology, the hijacking of normal brain pathways that are required for you to function socially.” Since coming to BCM, the Kostens have worked on developing and testing a cocaine vaccine. Traditional vaccines work by creating immunity to a specific disease, such as tetanus or chicken pox. Essentially that is what the Kostens think their cocaine vaccine will do—create “immunity” to the drug.

Cocaine and many other drugs consist of particles so tiny that the human body cannot “fight” it by making antibodies, which are proteins used by the immune system to identify and neutralize foreign and potentially harmful particles, usually bacteria or viruses.

“The only way you can get people’s bodies to make antibodies is to trick the immune system,” said Thomas Kosten. That is how he has engineered the cocaine vaccine to work.

He used inactivated cholera toxin proteins and attached cocaine to the outside. Inactivating the cholera proteins prevents them from causing disease, but the immune system can see them when they are injected. It makes antibodies to cholera and cocaine at the same time. That means the person is vaccinated against both cholera and cocaine in the same injection.

During early studies in humans, researchers vaccinated subjects repeatedly over a period of three months. During this time, the subjects made large amounts of cocaine-specific antibodies. While the antibody levels drop within a year, they remain significantly high during the first few months. In that early period, if a vaccinated subject used cocaine, the antibodies prevented it from entering the brain and giving the person the cocaine “rush” that is attractive to addicts.

“Blood vessels are distributed all over the brain, but the cocaine does not get into the brain because when it is bound to the antibodies, which are fairly large proteins, it cannot get through the blood-brain barrier (a natural formation that prevents foreign substances from going into the brain),” said Thomas Kosten. “It’s just like a big sponge for cocaine in the bloodstream.”

The idea is to “soak up” enough cocaine that addicts cannot get their “high.” If this goes on long enough, the researchers hope the addicts will quit the drug. A common tenet in psychology is if there is no reward, the behavior will ultimately stop.

Cocaine and other drugs of abuse are addicting because they affect the normal pathways used by important chemicals in the brain. For example, cocaine uses the dopamine reward pathway in the brain.

“Drugs of abuse activate pathways to a 20-fold extent greater than the usual pleasures of life; good food, sex, music, etc. When you are doing that repeatedly, the whole system down-regulates, meaning that it simply doesn’t respond to the usual rewards in life anymore, because they are below the threshold.”

Another detrimental effect of cocaine use is that it can cause brain cells to die. As large amounts of dopamine are released by stimulants like cocaine, it accumulates. Dopamine is usually broken down into an inactive state very quickly by enzymes. When it builds up to a point where the enzymes cannot break it down fast enough, different enzymes start working on it and convert it into a substance that is toxic to the brain.

Many abusers of cocaine and other stimulants develop Parkinson’s disease-like symptoms. Parkinson’s is defined as having damage to 80 percent of the neurons in the part of the brain that controls motor function and aspects of cognition, emotions and learning.

“In brain imaging studies of 20- to 25-year-old cocaine or stimulant abusers, their brains have deteriorated enough to look like that of a 60-year-old Parkinson’s patient,” said Thomas Kosten. “It does not take much of an imagination to realize that their prognosis is not good.”

The use of cocaine and other stimulants in general is a big problem in this country. There are approximately 4 million cocaine users and between 1.5 and 2 million methamphetamine users in the United States, said Thomas Kosten. The hope in the development of a vaccine is to get many of them to stop and to prevent substantial brain damage. Preliminary results from the first clinical trials in humans suggest that the vaccine holds tremendous promise. The Kostens hoped to achieve a 50 percent reduction in drug use. They found that twice as many people who were vaccinated were able to achieve at least a 50 percent reduction in cocaine use compared to those who received a placebo. Some who were vaccinated even stopped using drugs completely.

Since coming to BCM, aside from developing and testing a cocaine vaccine, the Kostens and their colleagues have developed a methamphetamine vaccine with which they hope to run a clinical trial in humans in the next few years. There are also plans in the works to start a study on a nicotine vaccine in collaboration with The University of Texas M. D. Anderson Cancer Center.

In addition to developing treatments, Therese Kosten has always been interested in determining what causes addiction. “Not everyone who uses goes from casual use to addiction,” she said. “Some are more vulnerable to developing addictions than others whether a result of environmental or genetic factors; though I am convinced you have to have both.” She found that early life stress, in particular, plays an important role in addiction. In one study, rat pups were separated from their mother and siblings for one hour a day. The pups that experienced this early life stress later learned to self-administer cocaine more readily than those who were not. They also maintained the addictive behavior at a higher rate.

Whether it is because of environmental or genetic factors, or both, many people in this country develop addiction and struggle with its detrimental effects every day, as does society as a whole. The Kostens, even more determined now than when they were spinning on the ice together, hope to create effective solutions to this ever growing problem of drug addiction and abuse.