Would Ben Franklin have taken Ozempic?

If one were to pick a “Drug of the Year” for 2023, the undisputed winner would be semaglutide (Ozempic), the blockbuster medicine that has cordoned a moment in the medical, and cultural, zeitgeist. It is not without appropriate accomplishments. Let us stand in awe for a moment for a medicine that is able to curb one of our most basic, vital instincts: eating.

Semaglutide is part of a class of new medicines, GLP-1 agonists. Studies published so far on weight loss have been impressive, with a New England Journal of Medicine study demonstrating 15% loss of body weight versus 2.4% in placebo. Now its uses are being tested on other perhaps more destructive cravings, namely alcohol, tobacco, and drug use. With half a million lives lost to tobacco each year, and over 100,000 to drug overdoses, positive results are desperately needed.

The struggle with temperance vexed Philadelphia’s most prominent Founding Father, Benjamin Franklin. In his autobiography he sets out a clear goal to, “Eat not to dullness; drink not to elevation.” He goes on to analyze the subject from a point of rationality, “As I knew what was right and wrong, I did not see why I might always do the one and avoid the other.”

What accounts for this cleavage between our knowledge of what’s good for us and evident self-sabotage is now known to have a clear neurobiological underpinning. Frank Leone and Sarah Evers-Casey, tobacco addiction specialists at the University of Pennsylvania, have outlined the issue clearly in their new book Why People Smoke.

They divide the parts of the brain that control behavior into three parts, known as the triune brain. The one to develop first, aptly named our First Brain, controls basic instincts and behaviors that need to be automatic — such as escaping an aggressive animal.

The Third Brain is our neocortex, where our conscious thoughts and abstractions manifest. It is here we consider the importance of art, of math, of language and love. It is here we also analyze the past, consider the present, and attempt to transcend the future.

The Third Brain is where we think control of our actions lie, but there is heavy influence from our subconscious Second Brain, the invisible hand that has infuriated everybody with an obsessive behavior.

It is this Second Brain that compels us to eat that dessert, the whole time our conscious Third Brain is telling us we don’t need it. Even worse, we are likely not even enjoying that piece of cake.

The part of the Second Brain neuroscientists have honed in on is the mesolimbic system. It is here addictions are reinforced, with the neurotransmitter dopamine not only giving us feelings of satisfaction and reward, but at the same time creating neurological pathways that make that behavior harder to resist in the future.

GLP-1 agonists like semaglutide slow our stomach down to create satiety, but they also seem to work centrally in the brain to quiet the mesolimbic system’s dopamine pathways. This is presumably why some patients on semaglutide for weight loss also report they have given up alcohol as well, often without trying. Researchers with the NIH are now studying in-depth its effects on alcohol abuse and cigarette smoking.

“One happy accident of GLP-1 agonists is to clearly demonstrate that addictive behaviors are not moral failings, but a very complex interaction of neurotransmitters and neurological pathways that we do not fully understand, and certainly cannot fully control with conscious thought,” said Leone.

There is risk, too. As humans, blessed with consciousness, we are ever striving to explore, to understand, to create, and to transcend. But with a drug like semaglutide, the ability to curb appetites could be extrapolated to a state of anhedonia, or manipulated to value a reward that is not in our best interests.

It is fair to assume that, like any technology, it will be how we use it. With his quote “Wine is constant proof that God loves us and wants to see us happy,” one wonders if Ben Franklin would have been a user of semaglutide. I would like to think if he was, perhaps only a small dose.

Michael J. Stephen M.D. is a Penn Medicine pulmonary physician and author of “Breath Taking, A Biography of the Lungs.”