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By targeting the stress-response system in the brain, an LSU pharmacologist has discovered a way to decrease drug craving and relapse into drug use.

鈥淢eth is bad up here in northwest Louisiana,鈥� said Nicholas Goeders, Head of the Department of Pharmacology, Toxicology & Neuroscience 星空无限传媒 Health Shreveport, who has been studying addiction and the neurobiological effects of drugs for more than 35 years. 鈥淎t least 80% of the people who come into our psychiatric emergency rooms are there because of methamphetamine. It鈥檚 a huge problem. Meth is affordable, available, and everywhere.鈥�

鈥� While almost all research on addiction to stimulants (such as meth, cocaine, nicotine, caffeine, and alcohol) remains focused on dopamine and the body鈥檚 internal pleasure-and-reward system, Goeders took a different approach. 鈥�

Goeders is working on new therapies for addiction, including to meth and cocaine. 鈥淣ew鈥� isn鈥檛 quite right, however. Mostly because there are no 鈥渙ld鈥� or existing pharmacological therapies for meth and cocaine addiction on the market today (unlike for opioid addiction), but also because Goeders鈥� eureka moment happened decades ago. While almost all research on addiction to stimulants (such as meth, cocaine, nicotine, caffeine, and alcohol) remains focused on dopamine and the body鈥檚 internal pleasure-and-reward system, Goeders took a different approach. Instead of reward, he began looking at stress and the body鈥檚 stress response system, which is mediated by the hypothalamic-pituitary-adrenal (HPA) axis. Stimulants as well as stress can cause a lot of activity along the HPA axis, which then leads to the production of cortisol, a stress hormone. What if he could decrease HPA axis activity and block the hormone? Goeders got to work in his lab.

鈥淲hile still a graduate student, I went to a neuroscience meeting in Los Angeles and the guru of drug addiction at the time came to look at my poster and said, 鈥楪oeders, this is never going to work鈥攜ou should give up,鈥欌�� Goeders remembered. 鈥淭hat鈥檚 all I needed to hear鈥攁 challenge. I came back to the lab and within a year I had my first research publication, and it was in the journal Science.鈥�

鈥� Almost 80% of the subjects who received the recommended dose of Goeders鈥� experimental medication twice-daily and came in for clinic visits twice-weekly had no trace of cocaine in their urine at the end of the study. In the placebo group, the number was just over 20%. 鈥�

Goeders developed a theory. By combining two already FDA-approved drugs with different effects on the HPA axis, metyrapone (an adrenal suppressant) and oxazepam (an anti-anxiety medication), but giving them at such a low dose that each wouldn鈥檛 have an effect on its own (thus reducing potential side effects and the risk of developing an addiction to the medication itself), could he perhaps get a synergistic effect that was bigger than the sum of its parts? Preliminary studies were encouraging, and finally, a six-week pilot study at the LSU Health Shreveport Psychopharmacology Research Clinic with 45 cocaine-addicted volunteers from the surrounding area provided real, albeit limited, data in 2008. Almost 80% of the subjects who received the recommended dose of Goeders鈥� experimental medication twice-daily and came in for clinic visits twice-weekly had no trace of cocaine in their urine at the end of the study. In the placebo group, the number was just over 20%.

Meanwhile, Goeders鈥� innovation had attracted additional investment. He became a co-founder, together with a Ross Barrett鈥攁n LSU School of Law alumnus鈥攐f a specialty pharmaceutical company named , formed around Goeders鈥� research.

鈥淣ick鈥檚 invention has several potential applications. Using the same core technology, we can fight many types of addiction.鈥�

Bob Linke, executive chairman of Embera NeuroTherapeutics

Today, Embera continues to hold an exclusive license for the technology from LSU. Bob Linke is the company鈥檚 executive chairman and previous CEO, operating in the Boston area.

鈥淣ick鈥檚 invention, one among many, has several potential applications,鈥� Linke said. 鈥淯sing the same core technology, we can fight many types of addiction. It鈥檚 all about addressing the human stress response system鈥檚 role in driving craving and relapse.鈥�

Embera is currently in the final stages of two separate Phase 2 human studies to evaluate the effectiveness of Goeders鈥� medication in helping people quit smoking and stop using cocaine. Results from both studies should be available later this year. If results in cocaine use are promising, the Embera team plans to advance the treatment in additional clinical trials towards regulatory approval for cocaine use, as well as study the treatment for methamphetamine use disorder.

The initial Phase 1 safety study on Goeders鈥� medication was conducted 星空无限传媒鈥檚 Pennington Biomedical Research Center in Baton Rouge, and completed in 2016. Based on the resulting data, Embera, in collaboration with Goeders, was able to secure a $11 million grant from the National Institute on Drug Abuse, which falls under the National Institutes of Health. That money allowed the company to start Phase 2 testing in subjects addicted to cocaine in 2020.

鈥淐linical studies on addiction can be particularly challenging because the drop-out rate tends to be high and you want high confidence in your results,鈥� said Bruce McCarthy, chief medical officer at Embera.

鈥淲e鈥檙e now approaching the most significant milestone in our company鈥檚 history, which is human efficacy data on our product,鈥� Linke added. 鈥淭he potential impact of FDA approval would be tremendous, given there is nothing on the market to treat cocaine addiction; nothing to treat methamphetamine addiction. Further, I would be remiss not to mention Embera鈥檚 loyal Louisiana investors, since we wouldn鈥檛 be where we are today without their continued support.鈥�

鈥淎ddiction is a really terrible disorder,鈥� McCarthy continued. 鈥淚t鈥檚 terrible for the patients, it鈥檚 terrible for their families, and it鈥檚 terrible for communities. It鈥檚 a huge burden on society, so if we can move toward FDA approval for this medication, it will be very exciting.鈥�

Goeders is quick to point out that stress can be both good and bad. Uncontrollable stress tends to have a negative effect on a person while also making drugs more addictive. Controllable stress, meanwhile, is something most people seek out, such as getting a new job, getting married, having a baby, or鈥攊n more extreme cases鈥攋umping out of an airplane with a parachute.

鈥淧eople who feel like they don鈥檛 have control over what鈥檚 going on in their lives are more likely to use drugs and more likely to become addicted,鈥� Goeders said. 鈥淎nd yet, many of the most wonderful things to happen in our lives are just as stressful, but lead to pleasure. This is highly important to remember.鈥�

The main reason Goeders didn鈥檛 want to focus on blocking dopamine as a way to treat addiction is because he believes people always will choose to feel good, if given the option.

鈥淚f you give people a drug that blocks dopamine, everything that makes them happy is going to be blocked, too,鈥� Goeders said. 鈥淧eople will say, 鈥楾his makes me feel bad, so I鈥檓 not going to take it,鈥� and that鈥檚 understandable. Our approach, therefore, is different. By short-circuiting the stress response in the brain that is activated by triggers connected to drug use, people will be less likely to experience the kind of craving that leads to relapse.鈥�

鈥淚 can鈥檛 tell you my last phone number, but I can tell you the number of the bar where my father would go. My mother would have me call that number to talk to the bartender to ask my father to come home. That was more than 60 years ago and I still remember.鈥�

Nicholas Goeders

Now in his 60s, Goeders admits that understanding addiction has been the dominant theme throughout his life.

鈥淚鈥檝e always studied addiction, whether I knew it or not,鈥� Goeders said. 鈥淚 was adopted as a baby and it turned out that my new parents were alcoholics. I didn鈥檛 think anything about it; I didn鈥檛 realize I was living in a dysfunctional 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 set him off. He really struggled. He wanted to stop drinking and would go into rehab over and over again, but there wasn鈥檛 anything for him. He kept drinking. I can鈥檛 tell you my last phone number, but I can tell you the number of the bar where my father would go. My mother would have me call that number to talk to the bartender to ask my father to come home. That was more than 60 years ago and I still remember. And when he did come home, there was a lot of turmoil, a lot of fighting. It had a huge impact on me.鈥�

鈥淭his is why I do the work I do,鈥� Goeders continued. 鈥淚 want to help someone, and also the family that鈥檚 around them. If I can stop one kid from being neglected or abused, that means something to me. If one person can be helped, then it鈥檚 all been worth it.鈥�

Nicholas Goeders received the Excellence in Innovation award from the LSU Health Shreveport Office of Research in 2021. He is the Executive Director for the Louisiana Addiction Research Center (LARC) 星空无限传媒 Health Shreveport.