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Fixing the Fix

Some surprising new weapons are in development to aid those battling addiction...

Some surprising new weapons are in development to aid those battling addiction.

By many standards, Mark held the world in his palm. He had gone to Harvard Business School, was good-looking, with plenty of charm. By the time he was 42, he was a hedge fund manager making $15 million annually and had a wife and two children. But along with his rapid wealth and success came stress and self-doubt. To manage it, Mark began hooking up with women he met online and visiting strip clubs where he paid women for sex. He also slipped into a daily cocaine habit. After a while, the cocaine was the only thing that made him feel in control—the glue that held him together.

Until everything else fell apart. When his wife discovered a text conversation with an escort describing the cocaine used in their last encounter, she left with the kids to their vacation home. Mark, his addictions now unchecked, went on a two-day binge of sex clubs, cocaine, and martinis. When he woke up at a hotel without his wallet and keys, he realized he needed help. He checked into a 56-day treatment program at Caron Renaissance Ocean Drive, a clinical treatment center in Boca Raton, Fla., where he finally began the process of addressing his addictions.

Paul Hokemeyer, PhD, a senior clinical advisor at Ocean Drive, says that Mark’s story (his name and personal details have been changed to protect confidentiality) is typical of the patients he sees. “They have reached a point where they have an enormous amount of financial success, but the quality of their lives is in tatters,” he says. Addiction—whether to alcohol, prescription pills, or cocaine—often goes hand in hand with accomplishment. “The brain has registered that substance as the thing that enables them to succeed in the world,” Hokemeyer says.

Increasingly, scientists are uncovering the biological underpinnings of addiction. Some people are more susceptible to addiction, either because of a genetic predisposition or because of life experiences such as neglect or abuse in childhood. But addiction itself changes the brain. If someone looked inside Mark’s brain, they would see that cocaine had taken over its reward pathways, interfered with decision-making, and robbed him of his ability to make better choices.

Even people who are motivated to quit find that kicking an addiction can take months to years. But scientists are developing innovative treatments that could someday help people like Mark unravel the deep habits that keep them reaching for their next fix. One day, for instance, he could get a cocaine vaccine as part of his treatment, essentially inoculating him from its powerful high.

Vaccines are currently in development for cocaine, nicotine, heroin, and methamphetamine. “It would protect the brain from the large rush of the drug,” says Michael Owens, PhD, a pharmacologist at the University of Arkansas for Medical Sciences, of the meth vaccine he is working on.

Some of these vaccines work much like an infectious disease vaccine: An addicted patient gets a few injections of a molecule similar to the drug, attached to a foreign protein designed to rouse the immune system. The body responds by producing antibodies against the foreign substance. The next time a person takes a hit, these antibodies find and attach to the drug in the bloodstream. The antibody-bound drug molecules have a harder time crossing from the blood into the brain, keeping them from having a strong effect.

The trick is to stimulate the immune system potently. A cocaine vaccine developed by Thomas Kosten, MD, at Baylor College of Medicine is the farthest along in clinical trials. It has shown promise in keeping more people in treatment, but was only able to stimulate enough antibodies to be therapeutic in about half of the subjects. Scientists are also looking at a different kind of vaccine; rather than stimulate the body to produce antibodies, they manufacture molecules called monoclonal antibodies that attach to a specific part of the drug, which are directly infused into an addicted person. Researchers at the Scripps Research Institute in La Jolla, Calif., are developing a monoclonal antibody vaccine for cocaine, and Owens is developing one for methamphetamine. The treatment is expensive to produce, but could be more effective than a traditional vaccine. Owens says an infusion might last three or four weeks.

Like many treatments in development, a drug vaccine is not meant to be a cure for addiction. “It’s not a standalone medication. [The patient] must really be involved in some sort of behavior modification program or cognitive behavioral therapy to deal with the issues that keep them going back to the drug,” Owens says. But it could provide a crucial edge to people who are trying to change.

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The 13th Step?

More and more Doctors who treat addiction see it as a chronic disease. “People who suffer from addiction require long-term, perhaps indefinite, follow-up treatment that often requires the use of medications,” says Jason Jerry, MD, an addiction psychiatrist at the Cleveland Clinic’s Alcohol and Drug Recovery Center. Most people never seek treatment at all; according to the National Institute on Drug Abuse, an estimated 22.7 million Americans had a drug or alcohol use problem in 2013, and only 2.5 million underwent treatment at a specialty facility. Those who do get treatment often wait until addiction has caused damage—an arrest, a lost job, an overdose, a broken family.

While studies find that many substance abusers eventually overcome their problem without treatment, others have a much harder time changing their behavior. “People usually have to make multiple quit attempts,” says Mark Willenbring, MD, founder and CEO of Alltyr addiction treatment clinic in St. Paul, Minn. His clinic emphasizes ongoing long-term care, similar to what patients with diabetes, heart disease, or arthritis would receive.

Those who treat addictions are increasingly recognizing that medications can help people make the changes they need to make. A handful of drugs are currently available for opioid, alcohol, and tobacco dependency, but not specifically for dependency on cocaine, methamphetamines, or marijuana. Methadone and buprenorphine (Subutex, Suboxone) help people overcome opioid addictions by mimicking the drug to reduce withdrawal symptoms and cravings, but without the high. Naltrexone (Revia, Vivitrol), which blocks the effects of opiates, is used to treat opiate addictions as well as alcohol dependence as a daily pill or monthly injection. Studies on its effectiveness as a treatment for alcoholism have been equivocal, though, and suggest it works best in those with the strongest alcohol cravings and in people of specific genetic backgrounds. Acamprosate (Campral) can also help reduce alcohol cravings, and disulfiram (Antabuse) has been used to treat severe alcoholism since the 1920s, but because it makes people feel ill when they have alcohol, some fail to keep taking it.

Medications like these have been controversial in the addiction treatment community because of the persistent belief that addicts must exercise their own free will to overcome the habit. But Marina Picciotto, PhD, a neuroscientist at Yale University, says that science shows just how challenging that is. “The ability to change behavior is much, much harder for an addict,” she says. “You have to understand your free will as an expanding or contracting balloon.” Addiction actually diminishes the ability to make better choices.

Various addictive substances affect the brain differently, but they all hijack a set of brain regions called the reward circuit, which releases the chemical signal dopamine—the “high” one gets from a drug like cocaine. “Once you’ve experienced cocaine many times, the system adapts,” Picciotto says. You develop tolerance to the drug’s effects, and the dopamine system stops functioning properly—it loses the ability to respond to normal pleasures.

Current medications for addiction work by targeting the reward circuit, either by blocking the effects of the drug or controlling cravings for it. Ibudilast, a medication developed in Japan as an anti-inflammatory, could actually repair the reward system in a different way. Researchers at the University of California, Los Angeles are testing the drug for methamphetamine addiction. Keith Heinzerling, MD, the addiction physician at UCLA who is leading the meth study, says that animal research finds that the massive release of dopamine that methamphetamine stimulates is damaging to brain cells and causes an inflammation response in the brain. Ibudilast is thought to calm that inflammation by reducing the activity of microglia, immune cells found only in the brain. “It’s essentially an anti-inflammatory medication for the brain’s immune system,” Dr. Heinzerling says. A team from Columbia University is also leading a phase 2 study of ibudilast in heroin users. The drug, which is also being tested as a multiple sclerosis treatment, was given fast-track status by the Food and Drug Administration, which helps speed a medication through clinical testing if it shows promise for treating serious conditions.

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Rerouting Habits

The reward circuit explains why drugs are addictive, but it does not explain why some people cannot stop, even if they want to. Drug-taking transforms from a chosen act into a habit, and eventually a compulsion. The behavior becomes entrenched and less accessible to conscious decisions. By imaging the brains of drug-addicted people, scientists have found differences in a part of the brain called the prefrontal cortex, a kind of executive decision-maker in the brain. Edythe London, PhD, director of the Laboratory of Molecular Neuroimaging at UCLA, says that addiction impairs the ability of this decision-maker to do its job. Addicts have problems with the interplay between responding to environmental cues and conscious control of their actions—an exaggerated response to reward—in the prefrontal cortex, she says.

The reward system itself also becomes damaged over time. In those who abuse stimulants, less dopamine is released as abuse continues, so the addict needs to use more to get close to the first-time experience, when a greater surge of dopamine was released. Meth causes even more destruction. It opens the door for dopamine to exit the vesicles where it is stored in the cell and enter the synapses, where it auto-oxidizes, damaging cells.

Peter Kalivas, PhD, a neuroscientist at Medical University of South Carolina, says that scientists are excited about creating new treatments that target the brain changes that mire many people in their addictions. “The treatment should really be focused on relapse, and the vulnerability to relapse,” he says. In animal studies, scientists have found that brain areas involved in learning and habit formation become more active as an addiction progresses. Kalivas, like London, points to the prefrontal cortex, which Kalivas says normally can modify habit circuitry. Even though you habitually take a certain route to work, for instance, your prefrontal cortex can help decide on a better route if there is a traffic jam. When someone is addicted to a drug, Kalivas says, he may receive “error messages” telling him to alter his behavior—a spouse threatens to leave, or he falls behind at work. But somehow, these messages do not lead to behavior change. “The addict can tell you what’s wrong, they just can’t use that information,” Kalivas says. “Through cortical intervention most of us can make a plan to change the habit or adapt it. But addicts are not able to do that.”

Can we give someone better self-control in a pill? It may seem far-fetched, but many scientists believe something like this is possible. Kalivas’s research has focused on glutamate, a chemical signal in the brain that is important for allowing the prefrontal cortex to change habits. His lab found that drug-addicted animals lack the ability to alter the connections between the prefrontal cortex and a part of the brain’s habit circuitry called the basal ganglia, a changeability called synaptic plasticity. The defect seems to stem from an inability to clear glutamate out of synapses, the junctions between neurons. Normally, the chemical is released in a specific location by neurons in the synapse and then quickly vacuumed back into nearby supporting cells called glia, resulting in a brief chemical signal at a specific synapse. In drug addiction, he explains, the glia lack the ability to vacuum glutamate away.

Kalivas’s lab has been studying molecules that help promote the transport of glutamate back into cells. One of them turns out to be a common antioxidant health food supplement, called N-acetylcysteine (NAC), which is being tested as an addiction treatment in cocaine users and cigarette smokers.

Another way that medications might aid a recovering addict is by targeting serotonin. Though the neurotransmitter is best known for its role in depression, Kathryn Cunningham, PhD, a pharmacologist at the University of Texas Medical Branch at Galveston, is leading a new federally funded center that will investigate molecules targeting the brain’s serotonin system as potential addiction treatments. She says that an imbalance in serotonin seems to have a role in behaviors that cause people to relapse. “We’re trying to understand the biology of what’s driving the relapse,” she says, “and trying to help alleviate some of those issues.”

Medication-Free Treatments

Many Scientists believe that drugs’ effects are so widespread, that they are not the ideal way to treat problems in specific brain areas. Therefore, researchers are starting to explore other methods for stimulating the brain.

A study published in Nature in 2013, led by Antonello Bonci, MD, scientific director at the National Institute on Drug Abuse, used optogenetics to test whether stimulating the prefrontal cortex might give rats more control over an addiction. His team studied rats that had learned to self-administer cocaine. As with humans, some rats kept using the drug even when it meant getting a mild electric shock. The researchers introduced a gene into the brains of the rats that produced light-sensitive proteins called rhodopsins in the prefrontal cortex allowing them to turn brain cells on and off. They found that stimulating the cells wiped out the compulsive behavior. In contrast, switching the cells off in those rats that had stopped taking cocaine after the shocks suddenly caused the animals to take the drug in spite of the negative consequences.

Optogenetics cannot be performed safely in humans. But Dr. Bonci says that another noninvasive approach called repetitive transcranial magnetic stimulation (rTMS) can stimulate specific brain areas in humans. The technique, which uses a magnetic field applied on the scalp to stimulate brain cells, has been used for several years to treat depression, though its effectiveness is still under study. If the technique proves effective, Dr. Bonci posits it could be modified to stimulate other brain areas that might be implicated in addiction.

As researchers look deeper into the neurobiology of addiction, they are finding connections between the brain circuits involved in substance abuse, compulsive gambling or sex, and eating disorders. “We’re beginning to think about addictive disorders as a more general phenomenon than abuse of one drug,” says Edythe London. “We’re thinking toward a unified concept of addictive disorders.” All of which should help address the problems that keep people from exercising the healthy choices they desperately want to make.

Clinical Trials

For more information about clinical trials for the methamphetamine vaccine, contact Intervexion Therapeutics, 501.554.2377; ibudilast for methamphe–tamine addiction, contact Keith Heinzerling at the University of California, Los Angeles, 323.461.3106, kheinzerling@mednet.ucla.edu; the cocaine vaccine, contact Coreen Domingo at Baylor College of Medicine, 713.794.7497, cdomingo@bcm.edu; ibudilast for heroin and opioid addiction, contact Sandra D. Comer at the New York State Psychiatric Institute, 646.774.6146, comersa@nyspi.columbia.edu.

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Respected Recovery

These six centers provide the best possible treatments in distinguished and discreet settings.


St. Paul, Minn.

This outpatient medical center was founded in 2012 to provide “addiction treatment for the 21st century” based on a chronic-disease model of care. It avoids ideology or a set recovery program and instead offers patients individualized treatment from a range of science-based therapeutic options, including cognitive therapy and medications. Though not a residential center, it can provide more intensive outpatient care if needed and works with out-of-town clients to arrange regular visits or housing nearby. 651.348.7611, alltyr.com

AToN Center

Encinitas, Calif.

This intimate rehab center serves 12 clients at a time on its four-acre estate in the San Diego hills. It focuses on cognitive behavioral therapy, and clients can choose whether to follow a 12-step-based approach. Drug and alcohol detox and treatment for co-occurring mental health disorders are offered on site. AToN (the acronym stands for “aid to navi-gation”) takes a holistic approach to treatment, offering massage, yoga, and meditation, as well as recreational amenities. 888.535.1516, atoncenter.com

Caron Renaissance Ocean Drive

Boca Raton, Fla.

Caron Treatment Centers, a nonprofit addiction treatment ­organization, launched this facility to address the needs of clients of “influence and affluence.” Rather than simply pampering its guests, the luxurious environment supports intense recovery work. Residents stay in private, manor-like homes near the center, with meals cooked by an executive chef. The treatment program emphasizes family counseling, and patients work with an individual therapist, physician, and psychiatrist. 800.221.1170, caronoceandrive.org

CMC: Berkshires

New Marlborough, Mass.

Part of the Center for Motivation and Change in New York City, a group practice of addiction clinicians and researchers, CMC: Berkshires is a treatment center on a wooded estate with room for 13 patients. CMC eschews the Alcoholics Anonymous model of strict abstinence, and instead focuses on motivational interviewing and cognitive therapy. It also supports the use of medications when needed. 413.229.3333, motivationandchange.com/cmc-berkshires

Hazelden Betty Ford Foundation

Center City, Minn., and Rancho mirage, calif.

These two icons of rehabilitation recently merged, making them the largest nonprofit treatment provider in the United States. The centers offer fewer amenities than some other private rehab centers, but they are well respected for their 12-step recovery model. In addition to its campus in City Center, Minn., Hazelden has clinics in Oregon, Florida, Illinois, and New York. The Betty Ford Center is located on 20 acres near Palm Springs, Calif. Hazelden Center: 800.257.7810, hazelden.org; Betty Ford Center: 888.748.9032, bettyfordcenter.org

Sierra Tucson

Tucson, Ariz.

This desert retreat on 160 acres has been treating addiction for more than 30 years. In addition to offering counseling programs, it is licensed as a hospital and has dedicated staff who treat eating disorders, chronic pain, and post-traumatic stress disorder, as well as substance use disorders. The facility’s therapy types range

from standard cognitive approaches to adventure therapy on an outdoor challenge course. 855.373.7752,  sierratucson.crchealth.com

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