NIDA’s Volkow Defends New Medications for Addiction

On Big Data, Big Vaccines, and a Big New Agency.

In her Director’s Report to the 2011 meeting of the College on Problems of Drug Dependence in San Diego last week, Dr. Nora Volkow, director of the National Institute on Drug Abuse, sought to refute allegations that NIDA lately has been too focused on pharmacological approaches to treating addiction—“magic bullets” in the form of pills or vaccines. Dr. Volkow presented figures showing, as the CPDD Community Website reported, that “NIDA funding allocation for new medication development has remained stable at about 12% for some time, despite concerns expressed by some researchers that funding in other areas is being sacrificed to support the medication development portfolio.” Basic and clinical neuroscience research accounts for 45% of expenditures, she said.

In other news, Volkow expressed her avid interest in the possibilities presented by so-called “big dataset science”—the act of pooling together huge amounts of data in order to generate greater statistical power. She traced a set of disciplines—genetics, epigenetics, proteomics, brain imaging, clinical data, and systems biology—and said that the NIH’s Working Group on Data and Informatics  was seeking systematic ways of integrating and analyzing large biomedical datasets in these crucial areas.

As for treatment, the current emphasis is on stimulants. Volkow said that work continues on finding reliable antagonist drugs to combat the dopamine disruptions promoted by active drug abuse. She suggested that work on buspirone, the D3 receptor antagonist and partial serotonin 5HT agonist used to treat generalized anxiety disorder, has shown that it may reduce cocaine self-administration in rhesus monkeys. This would be of considerable clinical interest, since addiction medicine presently has no effective drug treatments to offer for stimulants like cocaine and methamphetamine. A large clinical study now underway is showing that buspirone blocked D3 receptors in monkey brains in a way that reduced their interest in cocaine.

And she referred to the failed promise of NicVax, the short-lived vaccine for cigarette addiction. The treatment “failed to meet the primary endpoint in Phase II trials.” In other words, it flunked out. Only 30% of addicted smokers developed sufficient antibodies from NicVax to do them any good. But she cited new research on an alternative approach to vaccines, including a new cocaine vaccine (dAd5GNE) shown to be effective in reducing cocaine addiction-related behaviors in rats through the long-term blockade of dopamine transporters.

In a related approach to producing a reliable anti-cocaine antibody, researchers in the Department of Genetic Medicine at Weill Cornell Medical College went to work on “an adeno-associated virus (AAV) gene transfer vector as the delivery vehicle to persistently express an anti-cocaine monoclonal antibody in vivo, which would sequester cocaine in the blood, preventing access to cognate receptors in the brain.” An AAV is a small virus that is infectious but not pathogenic in humans. You might have it right now, but wouldn’t know it, since AAV doesn’t cause disease. So, the researchers used an AAV to build a transporter mechanism for their monoclonal antibody, GNC92H2. In mice, the result was “persistent serum levels of high-affinity, cocaine-specific antibodies that sequestered intravenously administered cocaine in the blood.”

And finally, while the name is still up in the air, a new national institute combining the study of alcohol and the study of all other addictive drugs will follow after final recommendations submitted to NIH Director by year’s end. Volkow briefly laid out the timeline of the merger for the assembled scientists. Call it the Institute for Substance Use Disorders, or the Institute for Addiction Disorders, or the National Institute of Substance Abuse, but whatever the eventual name, it will be fully operational by late 2013, or at least that’s the plan—and Nora Volkow, the current director of the NIDA, which will merge with, or rather absorb, the National Institute on Alcohol Abuse and Alcoholism (NIAAA), won’t be its director (See "NIH Turf Wars"). Whether that’s good or bad is the subject of much debate, but the project marches on, and seems sensible in the end.

Random Notes from the College on Problems of Drug Dependence

Opening day addresses at the annual meeting.

(These are notes on research in progress, not findings written in stone).

--NIDA director Nora Volkow talked up buspirone (Buspar) as a treatment for cocaine addiction, and referred to favorable results on buspirone for cocaine self-administration in monkeys in a large clinical trial. Also, different vaccine strategies are in the works, including different pharmacological approaches to blocking specific dopamine transporter molecules.

--Edward Sellers of DL Global Partners, a drug research consulting firm, emphasized the importance of enzyme variations in smoking. Variants of the CYP2A6 enzyme of metabolization allow us to identify “slow metabolizers” who respond well to placebo or nicotine patch therapy, and other smokers who don’t.

--Sherry McKee of the Yale University School of Medicine reminded everyone that cigarette smokers—even very light smoking “chippers”— are far more likely to have concurrent drinking problems than non-smokers. Smoking helps drinkers drink more and longer. To demonstrate such “potentiated reinforcement,” she showed a delightful video of her child eating cookies, then craving a glass of milk, then succumbing to another round of cookie consumption…

--Jack Henningfield of Pinney Associates, and former NIDA research chief, said that the reason the National Institute on Alcohol Abuse and Alcoholism (NIAAA) became an agency focused on “one molecule” is because Senator Harold Hughes, recovering alcoholic from Iowa, and Bill W., co-founder of Alcoholics Anonymous, wanted it that way.

--David Penetar of Harvard Medical School and McLean Hospital added more evidence of the link between alcohol and cigarettes, noting that “90 per cent of smokers drink,” and that smokers are three times as likely to be alcoholics than non-smokers. He pointed to research documenting a disturbing “increased desire to drink” when wearing a nicotine patch. With a patch, subjects reported feeling the effects of alcohol sooner and longer.

Photo Credit: http://www.thejournalshop.com/

Bath Salts and the College on Problems of Drug Dependence

CPDD holds annual meeting.

I’ll be out of the office for a few days, attending the annual meeting of the College on Problems of Drug Dependence (CPDD), the oldest group in the United States dedicated to addressing problems of drug addiction. The organization functions as an independent body, and is affiliated with other scientific and professional societies involved in the study of drug dependence and abuse. The meeting dovetails with the 2012 NIDA International Forum. A broad selection of the nation’s top drug and addiction researchers will be there, along with Nora Volkow, Director of the National Institute of Drug Abuse (NIDA), and Drug Czar Gil Kerlikowske, director of the Office of National Drug Control Policy.

 I’m pleased to be the recipient of the organization’s 2012 CPDD/NIDA Media Award, which is given each year for “contributions through the media that have enhanced the public understanding of scientific issues concerning drug use disorders.” That’s pretty nice of them, and you can find an interview I did for their CPDD blog HERE.

While in attendance, your faithful correspondent will be attending what looks to be a massively interesting panel discussion called “A Stimulating Soak in “Bath Salts”: Investigating Cathinone Derivative Drugs.” Look for a blog post on that one.

I’m also planning to attend a symposium on “Exercise as a Treatment for Drug Dependence in Humans,” and plan to report back on that topic as well.