Ten stories above New York’s Central Park, one of the nation’s largest collections of brains sits preserved in the lab of Yasmin Hurd.

A neuroscientist and the Director of the Addiction Institute at Mount Sinai, Hurd studies the brains of deceased drug addicts, the majority of whom succumbed to heroin. What she sees in these brains is jumbled genetic expression. Epigenetic tags that control the genes’ on/off positions are in disarray: certain genes that should be switched on, expressed, are turned off, and some genes that are off should be on.

Hurd’s colleague, Eric Nestler, has found a similar epigenetic landscape in animals addicted to cocaine or opioids. It is also similar to the epigenetic jumbling found in cancer cells.

When considered together, Hurd says, “Targeting epigenetic tags has huge potential for treating addicted individuals. It may be possible to use epigenetic medicines actively being developed for cancer to treat addiction.” Hurd’s studies have already demonstrated that certain approved cancer drugs successfully reduced heroin consumption and drug-seeking behavior in addicted rats. “Now we’re developing human trials to see if this approach is effective in humans,” she says.

Repurposing cancer drugs is one of several strategies to treat addiction being explored by scientists at the Icahn School of Medicine at Mount Sinai and elsewhere. Their research has revealed that addiction is far more complex than previously recognized. There are numerous paths to the illness, which can include epigenetics gone awry, dysregulation of neurotransmitters, and genetic predisposition. “There have been enormous advances in the past few decades in understanding addiction. Mount Sinai can claim ownership of an impressive amount of that research,” says Nestler, Director of The Friedman Brain Institute, Dean for Academic and Scientific Affairs, and the Nash Family Professor of Neuroscience at the Icahn School of Medicine.

With more than 2 million Americans in the grip of an opioid addiction, that research has taken on new urgency. Treatments today focus predominantly on replacement therapy: administering methadone or buprenorphine to opioid abusers or nicotine patches to smokers. But these drugs don’t rectify the neurobiological changes that characterize addiction, so they fail to solve the underlying problem. This failure has spurred scientists like Hurd and Nestler to explore the fundamental mechanisms that drive addiction.

One mechanism is being explored by Venetia Zachariou, Associate Professor of Neuroscience and Pharmacological Sciences at the Icahn School of Medicine. She recently identified a protein, RGSz1, that regulates the opioid receptor in a brain region associated with pain relief. In mice that lack the gene that codes for RGSz1, Zachariou’s research showed that opioids lost their addictive power, while at the same time, the mice achieved pain relief with much lower doses of the drugs. Normally, opioids become less effective with repeated administration. But this process of analgesic tolerance was significantly delayed in the mice. “Blocking the protein RGSz1 may provide a new avenue to optimize the effects of pain-relieving drugs such as morphine, fentanyl, and oxycodone, with no risk of addiction,” Zachariou says. Her team is now working to develop a molecule that can act in a similar way to enhance the pain-alleviating effects of opioids without promoting addiction.

Paul Kenny, the Director of the Drug Discovery Institute and Chair of the Department of Neuroscience at the Icahn School of Medicine, is exploring a different mechanism of addiction: identifying brain circuits that regulate the avoidance of addictive drugs. While scientists know a reasonable amount about the brain circuits that cause pleasure-seeking, they know much less about the circuits that signal avoidance of noxious chemicals.

In the course of his research, Kenny has found that a hormone called GLP-1 (glucagon-like peptide-1) can decrease the pleasurable effects of nicotine and promote its avoidance, essentially serving as a satiety signal for nicotine.

“If we can engage brain satiety systems—by enhancing the activity of neurons that secrete GLP-1, developing drugs that mimic its actions in the brain, or through other approaches—then we may have an entirely new way to treat drug addiction,” Kenny says. Several human clinical trials are now exploring whether compounds that enhance GLP-1 signaling can reduce tobacco smoking. Kenny is also exploring the brain satiety circuits through which GLP-1 acts. “This is an elegant way of deciphering how the brain responds to drugs and how alterations in such responses may lead to addiction. You can leverage that information to test innovative ideas about how addiction arises and create new therapeutics to battle addiction,” Kenny says.

These insights have the potential to radically transform drug addiction therapy. “Most of the treatments for opiate addiction we’ve had to date are other potent opioids,” Hurd says. “We have to work towards developing medicines that are not addictive in order to give people back their lives.”

To learn more about how scientists are translating research into life-changing treatments, visit the New Heights in Medicine.