Fighting the Opioid Epidemic
Overcoming Addiction, Through Science
Love, pleasure, hopefulness, gratitude – the feelings and experiences of day-to-day life shape our brain’s wiring over time. The mosaic of circuits they build shape our personality, our behavior and our sense of ourselves.
Addiction hijacks all this. It redirects brain circuits toward feeding our addiction, until, in the end, addiction robs us of ourselves.
At Scripps Research, we seek to understand the healthy brain and the addicted brain at a molecular level. We pursue those insights to help develop next-generation addiction recovery medications and vaccines.
Relieving Pain Safely, Through Science
Research shows that unlocking the molecular “door” to pain relief in the brain also can lead to addiction and breathing suppression, the dangers of overdose. The challenge, then, is enabling pain relief without activating unwanted side-effects.
At Scripps Research, we’re employing state-of-the-art technologies, innovative chemistry and genomic insights in pursuit of new ways to minimize overdose and addiction risk associated with pain relief. We’re simultaneously working to engineer a new generation of safer, advanced pain medications targeted to your personal genetic code.
Read on to learn about the strides being made in our laboratories. Addiction is everyone’s problem. At Scripps Research, our scientists work daily on solutions.
Your tax-deductible donation can accelerate this important work.
Genomic-Informed Prescribing
Neuroscientist Kirill Martemyanov, PhD, describes a future where doctors will look up your genomic profile before selecting your pain medication, so that they make the optimal choice —one better at relieving your pain and less likely to lead to addiction or breathing suppression.
Inside the body, drugs such as morphine, oxycodone, fentanyl and codeine all work by connecting with docking stations on the surface of nerve cells called opioid receptors. What happens next—effective pain relief, euphoria, suppressed breathing—depends on people’s individual genetic make-up, Martemyanov says.
“Why do different people react differently to different drugs? The basis of this is our genetic diversity,” Martemyanov says.
His lab is working to profile how very small genetic differences may contribute to the different responses to different pain medications. With 38 different opioid pain medications on the market, and such a high risk of abuse, precise prescribing guidance is needed, he says. Even naloxone, which is supposed to be an antidote for overdose, does not affect all individuals uniformly, he and his colleagues found in a recent study.
“There are genetic variants that respond to it as if it were an opioid, and it has the completely opposite effect,” he says. “If you give naloxone to someone who had this variant when they are overdosing, they might actually die.”
Martemyanov’s lab is also developing ways to chemically improve existing pain medications so that they can avoid launching addiction and breathing suppression signaling cascades.
“When you activate something as powerful as the opioid receptor, it’s like launching a nuclear attack,” he says. “We are trying to find what the fail-safe mechanisms and the control points are and exploit them to develop new, safer pain medications.”
Modifying Memories to Prevent Relapse
For those in recovery, small memories can drive cravings to return to drug use: Handling money, tasting greasy pizza, smelling vape smoke. Such emotionally charged memories can trigger cravings no matter how strong-willed people are, explains Scripps Research neuroscientist Courtney Miller, PhD.
“A lot of current users aren’t even aware of what their triggers are until they encounter them. These triggers can maintain their ability to drive craving for a person’s entire life, meaning a lifetime relapse risk,” Miller says.
Miller, working with Scripps Research colleagues Pat Griffin, PhD, and Ted Kamenecka, PhD, is developing an experimental medication that disrupts the molecular stability of drug-linked emotional memory circuits. In early models, the experimental treatment appears to extinguish drug-seeking behaviors, and testing suggests it may do so permanently.
That’s what makes this exciting,” Miller says. “This would be the first compound to directly target the motivational power of craving triggers.”
With funding from the Blueprint Neurotherapeutics Network, a translational research program of the National Institutes of Health, Miller’s memory-modulating compound is moving toward clinical trials as soon as 2020.
The compound appears to work in the context of multiple substances, including methamphetamine, meth-opioid, or meth-nicotine addictions, Miller says.
Biased for Safety
People who experience severe pain from cancer, car accidents, surgeries, burns and other traumas frequently require powerful pain relievers, sometimes for sustained periods. Because tolerance develops over time, their physicians often must increase dosage to maintain pain relief, raising the risk of overdose and addiction.
New pain medications that diminish pain, minimize risk of overdose and other side effects, and also limit abuse potential are sorely needed, says Scripps Research Professor Laura Bohn, PhD.
Bohn had long questioned whether the painkilling activated by opioids could be unlinked from activation of breathing suppression. Her team spent years developing potential drug molecules and working with chemists to tweak the structures. Over time, they succeeded in systematically varying the drugs’ “bias” of blocking pain versus suppressing respiration.
They have been able to keep the painkilling potency while producing no suppression of breathing. They are currently working to alleviate the development of tolerance following repeated dosing, which would reduce the amount of drug needed to maintain pain relief over time.
“Rather than turn on a system or turn off a system, we have actually discovered how to fine-tune a system, to give us some effects, while not inducing others,” Bohn says.
Scripps Research is ranked the most influential scientific institution in the world for its impact on innovation. A nonprofit, bicoastal institution based in San Diego, California and Jupiter, Florida, Scripps Research leads breakthrough studies that address the world’s most pressing health concerns. Unique capabilities at Calibr, the institute’s drug-discovery arm, allow for rigorous laboratory testing and even early clinical trials. At the Scripps Research Translational Institute, scientists incorporate clinical research and genomic medicine to advance individualized therapies. The institute’s educational and training programs, including the Skaggs Graduate School of Chemical and Biological Sciences, mold aspiring researchers into the next generation of leading scientists.
Ultimately, Scripps Research develops precision medicine for patients, helping them live longer, healthier lives.
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