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HOT TOPICS: Alcoholism  Addiction  AA  Cocaine  Heroin

Inside the Addiction Drug Pipeline

Over the next decade, new treatments are likely to include "cocktails" of two or three old drugs and possibly a treatment vaccine. Why is the drug pipeline for this major public health problem stuck at a trickle? 

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Scripps Research Institute photo

By Raphael Rosen

07/26/13

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Recovery from substance abuse can sometimes seem like an endless talkfest: therapy sessions, support groups, 12-step meetings and the like.

Scientific advances, however, have put forward a medical model of addiction as a disease rooted less in the mind than in the brain. A new consensus is emerging that medical treatments will be the go-to for getting and staying sober, as is the case with depression in the age of Prozac. Sharing and caring in one meeting or another will remain significant supports, but combinations of psychoactive drugs or even treatment vaccines will do the heavy lifting to reclaim your “hijacked” brain from addiction.

The addiction drug pipeline has never looked so good; it has gone from a drip-drop to a trickle. But substance abusers can look forward to some new treatments over the next decade. None are likely to be a breakthrough on the order of Prozac. Like Vivitrol (naltrexone injections) for alcohol and opiate abuse, they will work well for some people but offer only modest benefits to most.

Addiction is the most neglected disease in drug development, even though it is one of the nation’s leading public health problems. Why the neglect? First, basic research into the brain mechanisms of addiction—neurotransmitters, pathways, etc.—is still full of unknowns. Second, Big Pharma, which alone has deep pockets to bring new drugs to market, has given addiction the cold shoulder, partly because many addicts are poor, uninsured, hard to reach and not especially health conscious. Nor is this highly regulated industry crazy about associating its brand with people who use illegal drugs. But at bottom the neglect stems from the pervasive social stigma of addiction, according to many top researchers.

The drug industry makes one exception: nicotine addiction. As proven by the $750 million annual sales of varenicline (Chantix), the only drug on the market to help smokers quit, drug companies are spending big bucks to back R&D for a global market made up of hundreds of millions of people. Cigarettes are, of course, legal. Dozens of experimental compounds are in clinical trials. 

For all the buzz about addiction as a brain disease, treatment vaccines hold the most promise of a breakthrough—and they do not even target the brain. Like preventative vaccines that protect you against, say, the flu, treatment vaccines prime your body's immune system to produce antibodies that recognize the invading pathogens, destroy it, and then “remember” it in the event of future exposures. But treatment vaccines, as the name suggests, help control a disease that you already have. When applied to addiction, vaccines aim to produce an immune response not to an infectious pathogen but to the substance of abuse. Treatment vaccines prevent you from getting high by preventing the molecule of cocaine, say, or heroin from reaching your brain, where it has its effects.

Vaccine research for substance abuse is appealing partly because vaccines are tried and true; they are pretty simple to make; and they do not muck around with brain processes. But there are plenty of challenges. Most drug molecules are too small for the immune system to recognize. So scientists attach other, harmless molecules to the vaccine agent (the drug molecule) in order to add bulk in order to spark an antibody response. For instance, Thomas Kostens, MD, psychiatry and neuroscience professor at Baylor College of Medicine in Houston—and a leading addiction treatment researcher—fused bits of deactivated cholera bacteria to cocaine molecules to get the attention of the immune system. Its antibodies are big fat proteins; once they glom onto the cocaine-cholera combo, the resulting conglomeration cannot pass through the blood-brain barrier. Blunting the effect of the coke would, in theory, support your effort to quit using. In 2009, Kosten’s vaccine provided the first evidence that this approach could work in people. 

Vaccine research for addiction is appealing because vaccines are tried and true, simple to make—and they do not muck around with the brain.

There are many experimental vaccines currently in test tubes and early studies of animals. Very few will make it to clinical trials in humans. So far, the most promising, like Kosten’s, have gone bust in human tests.

At the center of the addiction vaccine enterprise is the prestigious Scripps Research Institute, a private nonprofit in La Jolla, Calif. Its Committee on Neurobiology of Addictive Disorders (CNAD) has six of the nation’s top addiction scientists studying the intersection of the brain, emotion, stress and addiction; the same six are also members of Scripps' Pearson Center for Alcoholism and Addiction Research, which “translates” CNAD's lab discoveries into experimental treatments.

In the early 1980s, when a vaccine for addiction struck most researchers as absurd, "the stars of two research programs at Scripps aligned," says George Koob, MD, the scientist who chairs CNAD. At the time, Koob’s lab was doing basic research, and Kim Janda, MD, was hunting for a chemical that might put a dent in cocaine addiction. When the two teams began collaborating, the synergy was “momentous.”

Since then, Janda has tried to develop vaccines against nicotine, alcohol, marijuana, heroin, cocaine and methamphetamine. His failures have blazed trails. Most recently, his experimental coke vaccine, created by cobbling together a cold virus particle and the cocaine molecule, got as far as Phase III clinical trials before failing. Yet the trial showed some success: Addicts who had the strongest immune response did not get high when they used and had a longer period of abstinence. But one-fourth of the subjects produced no antibodies to the vaccine.

Scripps presses on, producing a new vaccine candidate almost seasonally. In May, Koob’s lab announced that a heroin vaccine showed efficacy in rat studies. Each substance presents its own particular challenge to a vaccine approach. Heroin quickly breaks down in the body into two other chemicals: 6-acetylmorphine and morphine. An effective smack vaccine would have to target both at once, and the new Scripps candidate fits the bill.

Scripps is also making progress with a vaccine against methamphetamine. Meth’s particular challenge is that its active molecule’s structure is so generic that meth-primed antibodies can mistake many other molecules for it. Scripps' Michael Taffe, PhD, and his team are testing MH6, one of six potential meth vaccines developed in Janda’s lab. In a soon-to-be-published rat study, MH6 decreased the critters’ symptoms of meth addiction.

Scripps doesn't have a monopoly on addiction vaccine research. Baylor’s Kosten and S. Michael Owens, PhD, the head of the Center for Alcohol and Drug Abuse at the University of Arkansas for Medical Sciences, are leaders in the field. Kosten has spearheaded research into the neuroscience of addiction and trauma for decades and has studied a wide range of treatments and would-be treatments, including a cocaine vaccine, immunotherapy for hallucinogens, buprenorphine (Suboxone) for opioid dependence and disulfiram (Antabuse) for cocaine abuse.

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