BATON ROUGE – Aiming for a system of stress response in the brain, LSU pharmacologist has found a way to reduce drug cravings and drug reuse. The need for new solutions to addiction has reached an all-time high. More than 2,000 Louisians died from drug overdoses last year – 10 times more than two decades ago. This is in line with national trends. While synthetic opioids, such as fentanyl, are causing an epidemic of overdose, cocaine and methamphetamine (meth) are not lagging behind. In fact, methamphetamine is the biggest killer in nearly half the country, especially in states west of the Mississippi River, according to the latest Centers for Disease Control and Prevention.
“Matt is harmful here in northwestern Louisiana,” said Nicholas Geders, head of the Department of Pharmacology, Toxicology and Neurology at LSU Health Shreveport, which has been studying the addiction and neurobiological effects of drugs for more than 35 years. “At least 80 percent of the people who come to our psychiatric wards are there because of methamphetamine. This is a big problem. Methane oil is available, available everywhere. ”
While almost all research dependent on stimulants such as metametine, cocaine, nicotine, caffeine and alcohol is still focused on dopamine and the body’s internal pleasure and reward system, Geders has taken a different approach.
Instead of rewarding, he began to look at stress and the body’s response system to stress, which is mediated by the hypothalamic-pituitary-adrenal axis, or HPA. Stimulants as well as stress can cause greater activity along the HPA axis, which then leads to the production of cortisol, a stress hormone. What if it can reduce HPA axis activity and block the hormone?
Nearly 80 percent of subjects who received the recommended dose of Geders experimental drugs twice a day and visited the clinic twice a week had no traces of cocaine in their urine at the end of the study. In the placebo group, the figure was just over 20 percent.
Geders developed the theory. Combining two already FDA-approved drugs with different effects on the HPA axis, metirapone, which is an adrenal suppressant, and oxazepam, which is an anti-anxiety drug, but giving them in such a low dose that each will not have or can does it get a synergistic effect greater than the sum of its parts? Previous research has been encouraging, and finally a six-week pilot study at the LSU Health Shreveport psychopharmacological clinic involving 45 volunteers addicted to cocaine from the surrounding area yielded real, albeit limited, data in 2008. Nearly 80% of subjects who received the recommended dose of the experimental Heathers medication twice daily and visited the clinic twice a week had no trace of cocaine in their urine at the end of the study. In the placebo group, the figure was just over 20 percent.
“It was great,” Geders said. “Especially since neither the doctors nor the subjects had any idea whether they were taking medication or a placebo – the study was double-blind, and I had no idea what was going on until it was over.”
Meanwhile, Geders ’innovation has attracted additional investment. He co-founded with Ross Barrett, a graduate of LSU Law School, a special pharmaceutical company, Embera NeuroTherapeutics, based on Geders’ research.
Today, Embera continues to have an exclusive technology license from LSU. Bob Linke is the company’s executive chairman and former CEO working in the Boston area.
“Nick’s invention, one of many, has several potential uses,” Linke said. “Using the same basic technology, we can fight many types of addictions. The whole point is to address the role of the human stress response system in stimulating traction and relapse. ”
Embera is currently in the final stages of two separate Phase 2 studies in humans to evaluate the effectiveness of Geders ’drugs in helping people quit smoking and quit cocaine use. The results of both studies should be available later this year. If the results of cocaine use are encouraging, the Embera team plans to advance treatment in additional clinical trials to get permission for cocaine use, and to study the treatment of a methamphetamine-related disorder.
The initial phase 1 study of the safety of Geders ’drugs was conducted at the Pennington Center for Biomedical Research in Batan Rouge and completed in 2016. Based on the findings, Embera in collaboration with Goeders was able to receive a $ 11 million grant from the National Institute on Drug Abuse, which falls under the National Institutes of Health. This money allowed the company to start in 2020 phase 2 testing in cocaine addicts.
“Clinical addiction studies can be particularly challenging because dropout rates tend to be high and you want to be highly confident in your results,” said Bruce McCarthy, Embera’s chief physician.
“We are now approaching the most significant milestone in the history of our company, which is data on the effectiveness of our product for humans,” – added Linke. “The potential impact of FDA approval would be huge, given that there is nothing on the market to treat cocaine addiction; nothing cures methamphetamine dependence. Also, I would be wrong not to mention the loyal Embera investors from Louisiana, as we would not be where we are today without their continued support. ”
“Drug addiction is a really terrible disorder,” McCarthy continued. “It’s scary for patients, it’s scary for their families, and it’s scary for society. It’s a huge burden on society, so if we can move on to this FDA approval, it will be very interesting. “
Three of Geders ’seven patents relate to Embera-licensed technology, including a specific combination of methyrapone and oxazepam to treat addiction. While Geders knew early on that this combination was effective, he didn’t fully know why, and continues to conduct research in his lab to understand the exact mechanisms. In recent years, his focus has shifted from the HPA axis of the brain to the prefrontal cortex, where neuroactive steroids such as cortisol can also be synthesized.
Heathers quickly shows that stress can be both good and bad. Uncontrolled stress tends to negatively affect a person and also causes more addiction to drugs. Meanwhile, most people are looking for controlled stress, such as getting a new job, getting married, having a baby, or – in more extreme cases – jumping off a plane with a parachute.
“People who feel out of control about what’s going on in their lives are more likely to use drugs and more likely to become addicted,” Geders said. “And yet, many of the most wonderful things that happen in our lives are just as stressful but lead to fun. It’s very important to remember. “
The main reason why Geders didn’t want to focus on dopamine blockade as a treatment for addiction is that he believes people always choose to feel good when the opportunity arises.
“If you give people a dopamine-blocking drug, everything that makes them happy will also be blocked,” Geders said. “People will say,‘ It makes me feel bad, so I won’t take it, ’and that’s understandable. So our approach is different. As a result of the short circuit of the stress response in the brain, which is activated by triggers associated with drug use, people will feel less cravings, which leads to relapse.
Now in his 60s, Geders recognizes that understanding addiction has been a dominant theme throughout his life.
“I’ve always studied addiction, whether I knew it or not,” Geders said. “I was adopted as a child, and it turned out that my new parents were alcoholics. I didn’t think anything about it; I didn’t realize I was living in a good family. But I learned a lot about addiction and how it affects people, especially my father, who was a very friendly and very kind person until something pushed him. He really struggled. He wanted to quit drinking and went to rehab again and again, but he had nothing. He continued to drink. I can’t tell you my last phone number, but I can tell you the bar number where my dad would go. My mother would like me to call this number to talk to the bartender and ask my father to come home. That was over 60 years ago and I still remember. And when he did come home, there was a lot of fuss, a lot of fighting. It had a huge impact on me. “
“That’s why I do the work I do,” Geders said. “I want to help someone as well as the family around them. If I can prevent one child from being neglected or abused, it means something to me. If one person can be helped, then everything is worth it. “
Nicholas Geders received the Outstanding Innovation Award from the LSU Shreveport Health Research Office in 2021. He is the executive director of the Louisiana Addiction Research Center, or LARC, at LSU Health Shreveport.
Working in Louisiana: LSU Health Shreveport Discovery offers a new approach to addiction https://www.lsu.edu/working-for-louisiana/news/2022/01-solving-addiction.php