Showing posts with label ondansetron. Show all posts
Showing posts with label ondansetron. Show all posts

Friday, February 17, 2012

Interview with Dr. Bankole Johnson of the University of Virginia


Tailoring addiction medicine to fit the disease.

(The “Five-Question Interview” series.)

25 years ago, when Dr. Bankole Johnson first began giving lectures about addiction and neurotransmitters in the brain, he had a hard time getting a hearing. That’s because 25 years ago, everybody knew what addiction was: a lack of “moral willpower.” Or, at best, some sort of psychological “impulse control” disorder.  

As a neuropharmacologist by training, and currently professor and chairman of the University of Virginia’s Department of Psychiatry and Neurobehavioral Sciences, Dr. Johnson thought otherwise, and went on make a name for himself by discovering that topiramate, a seizure drug that boosts levels of the neurotransmitter GABA, could be used in the treatment of alcoholism. “I just wasn’t a hospital-type doctor,” he once said. “I was for more intersted in research than clinical practice.” Johnson’s work was featured in the 2007 HBO series, "Addiction."

Born in Nigeria, Dr. Johnson attended the University of Oxford and received his medical degree in Glasgow, Scotland in 1982. At the time, medical understanding of addiction was poor to nonexistent. “Everything we knew—really knew—probably could be written on the back of a postage stamp,” he recalled.

Since then, Dr. Johnson has published numerous articles on psychopharmacology and addiction, and has served on several National Institutes of Health committees and panels. (See my earlier POST on Johnson’s study of drugs for addiction in the American Journal of Psychiatry.)


1. You’re a native of Nigeria. How did you first become interested in medicine?

Bankole Johnson: My father was a doctor and encouraged me. Back then, I had little interest in medicine and was more interested in the arts and perhaps going to law School, for which I had been promised a scholarship.

2. Addiction is called a “disease of the brain,” in Alan Leshner’s famous phrase, but it is still a hugely controversial subject. Are innate biological differences the cause of addiction?

Johnson: Addiction is a brain disease. The roots of the disease lie in brain abnormalities, and these are exacerbated when a vulnerable person uses alcohol excessively or takes illicit drugs.

3. How did you discover that topiramate helped some alcoholics drink less?

Johnson: It was an idea that developed from a hypothesis I came up with based on brain neurochemistry. The central idea was to alter the signals of dopamine, a critical path for the expression of rewarding behavior, through two different and opposite systems—glutamate and GABA.

4. That work led to Topamax for alcoholism, and your more recent work with ondansetron, another GABA antagonist. But what role do environmental and sociocultural factors play in the development of addiction?

Johnson: The environment interacts with genes and brain chemistry to govern behavior. But in the end, it is the changes in the brain that ultimately direct alcohol and drug taking behavior.  The environment therefore provides the context and tuning of the neurochemical signals in the brain.

5. Some people find the notion of addiction as a progressive and incurable condition a hard pill to swallow, so to speak. Why has effective medical treatment for addiction been so slow to develop, and why hasn’t talk therapy been more effective?

Johnson: Talk therapy has some effectiveness, but alone it is not a comprehensive or robust treatment. Progress in the last two decades has been quite rapid. With growing and clear acceptance of the neurobiological underpinnings of addiction, the next decade should herald even more exciting discoveries.  For example, our work on pharmacogenetics promises to provide effective medications—such as ondansetron—that we can deliver to an individual likely to be a high responder, based on his or her genetic make up.

Photo Credit: Luca DiCecco

Friday, January 21, 2011

Personalizing Addiction Medicine


Gene variants make anti-craving drugs a hit-or-miss affair.

Rather than taking on another broad hunt for the genes controlling the expression of alcoholism, noted addiction researcher Dr. Bankole Johnson and co-workers at the Department of Psychiatry and Neurobehavioral Sciences at the University of Virginia took a different tack. The researchers focused, instead, on investigating whether genetic variations among alcoholics might affect their responses to a specific anti-craving medication.

This post was chosen as an Editor's Selection for ResearchBlogging.orgThe result, according to Kenneth Warren, acting director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), is a study that represents “an important milestone in the search for personalized treatments for alcohol dependence.”

For any addiction, once it has been active for a sustained period, the first-line treatment of the future is likely to be biological. New addiction treatments will come—and in many cases already do come—in the form of drugs to treat drug addiction. Every day, addicts are quitting drugs and alcohol by availing themselves of drug treatments that did not exist fifteen years ago. As more of the biological substrate is teased out, the search for effective approaches narrows along avenues that are more fruitful. This is the most promising, and, without doubt, the most controversial development in the history of addiction treatment.

The researchers were interested in variations in the gene controlling the expression of a serotonin transporter protein. Dr. Johnson’s earlier work had centered on teasing out the influence the serotonin 5-HTT transporter exerts on the development of alcoholism. Previous research had focused attention on the so-called LL and TT variants of this transporter gene. After performing genetic analyses to determine which test subjects were carrying which versions of the gene in question, Dr. Johnson and his colleagues conducted a controlled trial of ondansetron on a randomized group of 283 alcoholics.
The findings were published in the American Journal of Psychiatry.

Ondansetron is an anti-emetic medication that has shown promise in treating addictions, particularly alcoholism. Ondansetron (trade name Zofran), helps block the nausea of chemotherapy by altering serotonin activity in the GI tract. (Vomiting is a serotonin-mediated reflex.) The scientists found that “individuals with the LL geno-type who received ondansetron had a lower mean number of drinks per day (-1.62) and a higher percentage of days abstinent (11.27%) than those who received placebo.”  This put the ondansetron drinkers under five drinks a day. All of the placebo drinkers continued to exceed the five drinks per day mark.

But the strongest difference was found in the group of alcoholics who possessed both the LL and TT genetic variants. The LL/TT alcoholics taking ondansetron “had a lower number of drinks per drinking day (-2.63) and a higher percentage of days abstinent (16.99%) than all other geno-type and treatment groups combined.” 

The goal here is straightforward. In an email exchange, Dr. Johnson told me: “I agree that it would be great if we could use a pharmacogenetic approach to study other anti-craving drugs. The idea of providing the right drug to the right person is definitely important for optimizing therapeutic effects and minimizing side-effects.” Here is a video of Dr. Johnson discussing the research, courtesy of the University of Virginia:

It won’t be easy. Such genetic testing is still in its infancy, and complications abound. For example, in an earlier study in the Journal of the American Medical Association, Dr. Johnson found that diagnosed patients who received ondansetron over an 11-week period increased their days of abstinence compared to alcoholics on placebo. However, in that study, “The researchers found no differences between ondansetron patients with late-onset alcoholism and those who received placebo.” This suggests that, along with genetic variations, ondansetron’s effectiveness with alcoholics may also depend on the type of alcoholism under consideration: early onset or late onset.

We have a long way to go, but individualized pharmaceutical assistance in the early stages of addiction recovery remains the Holy Grail for many addiction researchers. And hopes are running high.

Johnson, B., Ait-Daoud, N., Seneviratne, C., Roache, J., Javors, M., Wang, X., Liu, L., Penberthy, J., DiClemente, C., & Li, M. (2011). Pharmacogenetic Approach at the Serotonin Transporter Gene as a Method of Reducing the Severity of Alcohol Drinking American Journal of Psychiatry DOI: 10.1176/appi.ajp.2010.10050755

Graphics credit: Sergey Ivanov at http://pn.psychiatryonline.org/content/
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