One of the major foci of Dr. Schacht’s work over the last 5-10 years has been understanding the role that genetics play in responses to treatment for AUD and other substance use disorders.  

Many of the medications used to treat AUD (and other psychiatric disorders) target specific neurotransmitters—or their receptors—in the brain. Differences in the genes underlying these neurotransmission systems can cause differences in the concentration of neurotransmitters and the way they bind to their receptors.  

In other words, the genes that affect how our neurotransmitters work can also affect how medications intended to modulate those neurotransmitters work as well—an idea called pharmacogenetics. Pharmacogenetic, or “personalized”, medicine uses genetics to target or select medications for patients most likely to benefit from them.  

Dr. Schacht does primarily very early-stage research on pharmacogenetic treatments for substance use disorders. fMRI is important in these early stages of drug development, which requires a close look at the biology of the organ of interest – which, for substance use disorders, is the brain.

Why does this work matter?

When asked by Dr. Epperson for the significance and importance of his work, Dr. Schact tells her, “AUD and addictive disorders are devastating disorders. These are disorders that rob people of their lives, of the things that are meaningful to them in their lives. And they’re such paradoxical disorders. They are disorders where people have difficulty with choices. They have difficulty choosing what seems to be the obvious healthy thing to do. I’ve always wanted to make it easier to help people make healthy choices.”  

Negative effects of alcohol on the brain 
In pharmacology, alcohol is considered a “dirty drug,” meaning that it has many different effects on the brain. One of its primary effects is on the neurotransmitter GABA, which is the primary inhibitory neurotransmitter in the brain—causing brain activity to “slow down.” Alcohol adds to the effects of GABA on the brain, which is why after two drinks with dinner you’ll start to feel sleepy. Other effects of alcohol on the brain, however, are excitatory. Too much consumption of alcohol can disrupt the balance of inhibitory and excitatory neurotransmitters in the brain and have larger scale impacts. 

Alcohol use: how much is healthy, and how much is too much?

Dr. Epperson asks Dr. Schacht to help listeners understand what a healthy level of alcohol consumption is. He answers, “We understand from some public health research that some level of alcohol consumption is probably healthy—on the order of 1-2 drinks per day has been associated with some level of cardiovascular benefit.”  

However, drinking more than this amount is associated with increasing harms to the brain and other organs. The NIAAA recommends that women should not drink more than 7 drinks per week (1 drink a day), and men should not drink more than 14 drinks per week (2 drinks a day) to prevent toxicity to the brain and other organs, like the liver.  

Young adults are particularly vulnerable to the direct neurotoxicity of alcohol, given their still-developing brains and comparative likelihood to binge drink. Dr. Schacht confirms for Dr. Epperson that drinking 7 drinks in one day is not the same as drinking 1 drink per day 7 days a week – binge exposure is far more likely to do damage. 

Dr. Schacht closes the episode with a final message to parents: “The single most influential risk factor for Alcohol Use Disorder is the age at which you have your first drink. The longer you can delay that age, the less likely that at any other point subsequent in your life will you meet diagnostic criteria for AUD. If you can make it to age 18 before having your first drink, you can reduce your likelihood of developing AUD by more than half.”