Imagine that cocaine addiction could be eradicated, poof, with a simple vaccine. At Weill Cornell Medical College, Dr.Ronald G. Crystal, who for years has been working on just such a vaccine, now thinks his team has actually figured out a very clever trick to make that dream a reality.
“The vaccine eats up the cocaine in the blood like a little Pac-Man before it can reach the brain,” is his pop description of the biology weapon he has fashioned and is about to begin using in human tests after highly successful results with lab animals.
Clearly, any anti-cocaine vaccine that could hold up under further tough testing would permanently alter the landscape of illegal drug abuse in America and might open the door to vaccines for other drugs. According to The National Institute on Drug Abuse, more than 1.9 million Americans used cocaine in 2009, with more than a million of those classified as cocaine abusers. If Crystal’s new cocaine vaccine is proven effective, the impact of reducing that number by even five percent would be impressive.
But that is a very big doing and requires a number of “big if” hurdle-climbs.
Scientifically, cocaine is a tiny molecule, a crystalline tropane alkaloid, obtained from the leaves of the South American coca plant. When imbibed, the molecules cross over into the brain and bind to the dopamine transporter, effectively blocking the ferrying of dopamine out of the synapses. Dopamine is the “pleasure” neurotransmitter in the brain. Trapped in the synapses, the result is a massive flooding of the pleasure centers. In short, you get high.
Crystal’s anti-cocaine vaccine combines bits of the common cold virus with (and here is the trick) a particle that mimics the structure of cocaine. When the vaccine is injected, the body “sees” the cold virus and mounts an immune response against both the virus and the cocaine mimic that is hooked to it. Essentially, the immune system is fooled into generating antibodies that will then be activated once real cocaine is imbibed.
“Once immune cells are educated to regard cocaine as the enemy, they produce antibodies against cocaine the moment the drug enters the body,” Crystal says.
In Crystal’s animal studies, when the mimic antibodies were extracted and put into test tubes containing cocaine, the antibodies attached themselves to the cocaine molecules and literally gobbled up the cocaine. This caused the cocaine molecules to increase in size to the point where they could not cross over the blood-brain barrier.
In the second stage of Crystal’s research, only 20% of the cocaine was able to cross over the blood-brain barrier and hook onto the dopamine transporters of the vaccinated primates. Moreover, at 20% there were almost no intoxicating effects on the animal subjects. Such a massive drop is the reason why Crystal and his team believe the anti-cocaine vaccine will work in human beings.
“This is a direct demonstration in a large animal…that we can reduce the amount of cocaine that reaches the brain sufficiently so that it is below the threshold by which you get the high,” Crystal told The Fix.
Crystal’s supposition about cocaine’s specific effect on the brain builds on some previous human research. Dr. Nora Volkow, the Director of the National Institute on Drug Abuse, used a brain imaging technology called positron emission tomography (PET) to study the brains of long-term cocaine users. Like Crystal, she noted that the intensity of a cocaine-induced high was connected directly to cocaine’s ability to block the dopamine transporter system.
Using intravenous injections of cocaine at typical doses, Volkow found that cocaine blocked between 60% and 77% of the dopamine transporter binding sites in the coke-users’ brains. She also discovered that the threshold at which the volunteers said they were experiencing a drug-induced high occurs when at least 47% of the binding sites are blocked by the cocaine.
Knowing this, any vaccine that would diminish cocaine’s access into the brain and potentially thereby seriously alter addictive behavior would be major progress in human immunology, with wider positive implications for drug treatment.
AND THEN THERE ARE THE OBSTACLES
One big one is the addicts themselves and the reality that drug abusers will do anything to chase their high. Hence a vaccine, even one that works perfectly, might not attract many addicts – and those that do try it, might bolt fairly quickly.
Can patients with a notable history of drug abuse be reliable?
Drug addiction treatment amounts to $180 billion in healthcare costs every year in the U.S. Cocaine and crack kill more Americans every year than car accidents. Despite the increased focus on recovery in the past decade, the relapse rate within the first year for cocaine addicts is 55%, 85% for crack addicts.
The track record to date of other research efforts with cocaine is meaningful here.
In 2010, an earlier study by Dr. Thomas Kosten of the Baylor College of Medicine, collapsed largely due to addict behavior.
Kosten, currently the co-director of the Dan Duncan Institute for Clinical and Translational Research at the Baylor College of Medicine, noted in an exchange with The Fix that, “Our cocaine-abusing patients had a tendency to try to override any blockade that we set up using these antibodies.”
One of the problems with Kosten’s study derived from his choice to work with heroin addicts being treated with methadone — an indication that their hunger for cocaine had been full-blown. Even with Kosten’s vaccine in their systems, many of the addicts in his tests compulsively chased the high.
The Baylor trials had 115 addicted participants. Surprisingly, only 38% produced enough antibodies to dull the effects of cocaine. Among the high-antibodies group, only 53% stayed free of cocaine 50% of the time.
“Immunization did not achieve complete abstinence from cocaine use,” Kosten admitted at the time of the study.
Did the methadone affect the performance of the vaccine? By choosing such a patient population, was Dr. Kosten’s study even feasible?
Disturbing to researchers is what happened to the “successful” study participants. Cocaine levels in the bodies of many participants were found to be elevated. Many had as much as ten times the amount of cocaine in their bloodstream than expected. Although nobody overdosed and died, such an outcome was a real possibility.
The extremely high abuse levels revealed an obvious attempt by test subjects to get high no matter what the cost. Some participants even complained of financial troubles caused by their compulsion. In an attempt to beat the vaccine, cheating addicts spent as much money as they could muster on cocaine. Rather than foster recovery, the vaccine seemed to trigger extreme addictive behavior.
Will Kosten’s troubles repeat in Crystal’s new human trials even without using methadone patients as a test base?
Kosten told The Fix that he would advise Crystal to take a different approach in his human trials: use “patients who have already attained several weeks of abstinence rather than using patients who need to become abstinent.” Crystal has refused to comment on any specifics in regards to his upcoming human trials beyond what is stated in his press release.