Tag Archives: National Institute of Health

10/13/14

Russian Roulette with Heroin?

Some of the most intriguing research into addiction treatment being done today is with vaccines. The idea is rather simple. Drugs of abuse pass through the blood-brain barrier because they are too small, too simple to be targeted by the immune system. So researchers have designed vaccines that take key fragments of the drug molecules and attach them to larger, more immune-provoking carriers (such as a cholera toxin or a tetanus toxin). The antibodies produced by this work-around will attack the drug and prevent it from passing through the blood-brain barrier and reaching the reward pathway in the brain. In other words, you can ingest the drug BUT WON’T GET HIGH!

Vaccines are being developed for drugs of abuse like alcohol, marijuana, heroin, methamphetamine, nicotine, and cocaine. A previous blog post, “Raising the Stakes in the War on Cocaine Addiction,” looked at the attempts to develop a cocaine vaccine by Thomas Kosten. His research has developed to the stage of clinical trials with humans, but a concern was discovered. Some of the human participants used ten times as much cocaine while attempting to override the blocking action of the cocaine vaccine. That trick could kill an individual who tried it with heroin.

Heroin has been a moving target for vaccine research because it quickly degrades into 6-acetylmorphine (6AM) and morphine. Kim Janda and his team of researchers associated with The Scripps Research Institute have developed a “dynamic vaccine” that creates antibodies against heroin and its psychoactive metabolites. You can read the academic journal article on their work found in the Proceedings of the National Academy of Sciences here or a summary of their research on The Scripps Research Institute website here or here.

There are positives and negatives to Janda’s dynamic heroin vaccine. First, while it will attach to heroin and its metabolites, it won’t work with oxycodone (OxyContin) or hydrocodone (Vicodin, Zohydro); or any other opioid. This is a trade-off because of the above-mentioned rapid degradation of heroin into its psychoactive metabolites. Second, this means the dynamic vaccine also won’t work with methadone or buprenorphine (Suboxone, Subutex), which are both opioids. So it can be used in conjunction with opioid maintenance therapy.

Although Janda’s research suggested that his vaccine helped limit heroin seeking behavior and halted the progression of compulsive heroin taking with rats, there are easy work-arounds for human beings. A human addict could ingest oxycodone or hydrocodone while taking the heroin vaccine to get high. They could even take a benzodiazepine along with their methadone or Suboxone for a nice, heroin-like buzz while taking the Janda vaccine. These limitations were acknowledged by Janda’s research team: “Although the dynamic heroin vaccine is not targeted to treat the ‘addicted’ brain, it represents a robust tool in the continuous blockade of all heroin activity.” In the concluding paragraph of the journal article, the research team said:

The prospect of heroin vaccine use in the treatment of addiction presents a high-payoff, low-risk opportunity. Drug vaccination requires minimal medical monitoring and compliance to maintain opiate resistance, allowing for greater potential worldwide accessibility. Furthermore … drug vaccines represent a low risk for long-term side effects. . . . Although it may not be a “magic bullet” against all aspects of drug addiction, the dynamic nature of our heroin vaccine represents a promising and innovative adjunct therapy in the treatment of heroin addiction.

But Janda’s research is stalled because it ran out of funding. In an interview with The Fix, he said: “We are not anywhere near human trials because nobody wants to pay for them.” Earlier funding was obtained by the Scripps Research Institute, the Pearson Center for Alcoholism and Addiction Research and the National Institute of Health (NIH). Janda and others have approached the NIH for additional funding, but so far have been unsuccessful.

Pharmaceutical companies aren’t interested either. Janda commented: “I have talked to many different companies and not one has shown any interest whatsoever. They don’t feel there is value for their company.” He doesn’t understand this from the standpoint of the greater good of society, but will attempt the route of applying for more research grants from the government. “I think we’ll probably just have to keep going it alone.”

I have mixed feelings about this vaccine, not because of the research, but because of what I know about how some addicts think. The research from the cocaine vaccine clinical trails discussed above noted how some addicts tried to test the vaccine with ten times as much cocaine as they usually ingested to get high. If heroin addicts test Janda’s heroin vaccine in a similar way, they will be risking their lives. It will be like playing Russian roulette with heroin.

There is also an “addiction” to the ritual of getting high (tying off, cooking the heroin, etc) for some addicts that the vaccine will not touch. I’ve known heroin addicts under the influence of this kind of obsession who compulsively “shoot up” water attempting to satisfy this urge. As Janda himself said, while it will blockade all heroin activity, it is not targeted to treat the “addicted brain.”

 

05/26/14

Raising the Stakes in the War on Cocaine Addiction

War on Drugs

image courtesy of iStock

A 28 year old Viennese neurologist named Sigmund Freud read about the benefits of cocaine on Bavarian soldiers. He decided to use it to treat his own problems with depression and chronic fatigue and acquired some from Merck. On April 30th 1884, Freud used cocaine for the first time. He thought it was “a magic drug.”

Cocaine turned his bad mood into cheerfulness; it even helped his indigestion.  He wrote to Martha, his fiancée: “In short, it is only now that I feel I am a doctor, since I have helped one patient and hope to help more.” Freud encouraged Martha to try cocaine, “to make her strong and give her cheeks a red color.” He warned her that when he came for a visit, she should expect “a big wild man who has cocaine in his body.”

He gave cocaine to his sisters and also to medical colleagues—both for themselves and for their patients. By July of 1884 he had written and published his first essay praising the therapeutic uses for cocaine. His hope was that he would become a pioneer in the medical uses of cocaine. But there would not be a happy ending to the story of Freud and cocaine.

These days the ongoing saga of medicine and cocaine is the quest to find a vaccine to cure those who become addicted to it.

I’ve been following the attempts to develop a vaccine for cocaine and other illicit drugs since 2009, when the National Institute of Health (NIH) reported on the work of Thomas Kosten with TA-CD. Nora Volkow, the Director of the National Institute on Drug Abuse (NIDA), said: “The results of this study represent a promising step toward an effective medical treatment for cocaine addiction.”

But some of the participants in Phase 1 of the clinical trials reported using TEN TIMES as much cocaine when trying to override the blocking action of the cocaine vaccine. The Washington Post, reported on the Kosten’s research in January of 2010, saying: “Some of the addicts reported to researchers that they had gone broke buying cocaine from multiple dealers, hoping to find a variety that would get them high.”

A 2011 article in the New York Times highlighted the work of Kim Janda who was working on a cocaine vaccine. His laboratory, the Scripps Research Institute, has also worked on vaccines for nicotine and heroin. In June of 2011 Janda published positive results with what he called an “anti-heroin vaccine.”

New York Magazine reported in September of 2013 that Ronald Crystal, the head of genetic medicine at Weill Cornell, had success with the third version of Janda’s original cocaine vaccine. He hopes to begin human trials by the middle of 2014. A side bar indicated that vaccines were in development for alcohol, nicotine, marijuana, heroin, methamphetamine and rohypnol (the date rape drug).

But as Clint Rainy commented in his New York Magazine article, the problem with addiction is it’s not just a physical problem, it’s also psychological. “Even if you can cancel the effects of drugs, can you make us not want to take them?” Crystal thinks that shouldn’t be a problem for his compound, as it was with TA-CD, because they tweaked their compound (dAd5GNE) to have a “more robust” immune response. Crystal’s response seems to miss an important limitation to a purely physiological attempt to cure addictive “disease.” The vaccine can only inhibit the physiological response to the drug; not the psychological one.

While Kosten’s work with TA-CD has begun clinical trials with humans, the work of Janda with heroin and Crystal with cocaine has yet to be tried on humans. But it’s coming soon. One person who responded to the New York Magazine article about Crystal’s cocaine vaccine said: “This would be a dream come true for me and save my life.” He believed that with the vaccine, he wouldn’t get high. After a few months, he imagined he wouldn’t be thinking about it anymore, but would “just keep getting vaccinated to be safe.”

But it seems that developing a cocaine vaccine as an attempt to end cocaine addiction merely raises the stakes for some addicted individuals by requiring larger amounts of the drug to overcome the vaccine. A vaccine doesn’t address the psychic desire for the drug. If a vaccine is successfully developed for heroin and other opioids, their current potential for deadly use could also increase tenfold.