Shots to End Cocaine Addiction, Prevent Overdose May Soon Start Human Trials

Shots to End Cocaine Addiction, Prevent Overdose May Soon Start Human TrialsVaccination is a medical technique originally designed to reduce one's risk for developing a dangerous infectious disease by introducing a weakened or dead form of that disease into the body. This purposeful introduction forces the immune system to make specialized proteins called antibodies, which act as a rapid response team and protect the body during any future exposure to the source of infection. Current evidence indicates that doctors can use vaccinations to help block the chemical effects of cocaine. Researchers are also investigating vaccination as a technique to halt the immediate, potentially deadly effects of a cocaine overdose.

A Weapon for the Body

When you encounter a new type of infectious microorganism, your immune system initially has no way to "recognize" that organism as a source of danger. Because of this lack of recognition, the microorganism can reproduce itself without any great difficulty and produce its harmful effects on the body. However, over a period of days or weeks, your immune system will begin to understand the threat it's facing and start to produce antibodies for the source of infection. Essentially, these proteins place a chemical/biological "tag" on the invading microorganism and give the immune system's frontline cells a way to identify the microorganism and respond to it rapidly.

The human body will make antibodies on its own. However, without medical intervention, this happens only after the body is exposed to live, fully active forms of an infectious organism. In the case of dangerous or potentially deadly infections, many people will develop serious health complications or die before their immune systems can begin forming antibodies.

Vaccinations come in two forms--active and passive. During active vaccination, doctors introduce a source of infection into the body and wait for the immune system to produce antibodies. During passive vaccination, doctors introduce previously created antibodies that come from another human or from a laboratory. Both techniques provide the body with a way to protect itself before a dangerous infection occurs. However, because it involves the direct introduction of preexisting antibodies, passive vaccination can produce much quicker and stronger results than active vaccination

Vaccination to Prevent Cocaine Addiction

In 2012, researchers from Cornell University's Weill Cornell Medical College reported their efforts to produce an active vaccine that prevents cocaine addiction by stopping the drug from reaching the brain. During their work, they injected monkeys with a protein complex that contained harmless materials derived from various viruses; this complex was specifically designed to closely resemble the structure and chemical appearance of a cocaine molecule. Because of the viral nature of the protein complex, it's visible to the human immune system, and in response to its presence, the immune system forms antibodies. When the researchers introduced cocaine into the systems of vaccinated monkeys, antibodies previously formed in response to the cocaine-like protein complex "recognized" molecules of the drug and tagged them as foreign invaders. In turn, this tagging process changed the shape of the cocaine molecules and made them too big to pass through the blood-brain barrier, a network of blood vessels that restricts the passage of certain substances and organisms from the main circulatory system into the brain.

"Our very dramatic data shows that we can protect mice against the effects of cocaine, and we think this approach could be very promising in fighting addiction in humans," says the study's lead investigator, Dr. Ronald G. Crystal, chairman and professor of genetic medicine at Weill Cornell Medical College.

Vaccination to Treat Cocaine Overdose

A cocaine overdose occurs when blood levels of the drug rise too high and start to override normal activity inside certain portions of the body's nervous system. People in the midst of such an overdose can easily die from critical alterations of their normal heart or lung function. According to a study published in 2012 in the journal Molecular Pharmaceutics, a multi-institution research team has designed a passive vaccine that can disrupt an overdose by denying cocaine access to the central nervous system (brain and spinal cord). During their research, the authors of the study injected mice with preformed cocaine antibodies derived from the active vaccination process described above. These preformed antibodies can attach themselves to cocaine molecules at a rate that's roughly 10 times faster than the rate found in active vaccination. As a result, they blocked cocaine's effects successfully enough to reverse overdose symptoms in the test subjects.

"This would be the first specific antidote for cocaine toxicity," said Kim Janda, PhD, senior author of the report. The researchers are now trying to find ways to produce their antidote economically and in large quantities. "If we can do that, then there would be no reason not to push it into clinical trials," Janda said.

He notes that such a treatment could be useful not only in reducing the immediate effects of an overdose, but also in preventing near-term relapses. "A lot of people that overdose end up going back to the drug rather quickly," Janda said, "but this antibody would stay in their circulation for a few weeks at least, and during that time the drug wouldn't have an effect on them." Likewise, this antibody could be administered to patients in addiction recovery or detox programs as a prophylactic treatment to supplement other medications, such as antidepressants, and counseling. An acute relapse during this recovery period would be immediately nullified by the antibody dose that is already in circulation.

Posted on March 21st, 2013

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