The Dose Makes the Poison: A Q&A with Robert Hoffman, MD

by AMNH on


Robert Hoffman, MD (Pick Your Poison Adult Course, 2013)
Robert Hoffman, MD

After a conversation with New York University medical toxicologist Robert Hoffman, MD, you may well come to see your daily routine—coffee in the morning, a glass of wine in the evening—in a different light.

Dr. Hoffman spoke recently with us about how toxicologists define the word “drug”; basic neurochemistry behind prescription and recreational drugs; and the top tool in medical toxicology today (not necessarily the one you’ll see on TV).

How do you define the word “drug”?

This is a beautiful toxicology question. The father of toxicology, Paracelsus, said that everything is a poison—and the dose makes the poison. We need oxygen, but too much oxygen can kill you. We need water to live, but too much water can kill you.

And a drug can be pharmaceutical, that is, made and packaged for use, or it can be illicit, illegal, with no accepted legitimate medical use—or something in-between.

Apothecary Bottles (Sherbrooke Village Museum)
What is a drug? Apothecary bottles line the shelves of a drug store at Sherbrooke Village Museum (a restored 1860s lumbering and shipbuilding community) in Nova Scotia, Canada.
By France3470/ via Wikimedia Commons

What are some examples?

Acetaminophen (found in over-the-counter pain-relievers) isn’t really considered a drug of “abuse,” but overdose can be toxic. 

The gray zone, where there are things that have legitimate medical benefits, like a lot of things we use to fight pain—oxycodone, hydrocodone—can be drugs of abuse, as well.

What neurochemistry do you need to know to understand how drugs work in the body?

 Basically, there are major molecules that affect mood and behavior, some of which are normally present in the body, and sometimes the drugs we take mimic or manipulate levels of those molecules to affect behavior.

What are some molecules affected, or manipulated, by drugs?

Let’s start with some easy ones. The happy neurotransmitter is serotonin, what makes you feel good. Antidepressants like paroxetine get there by modulating serotonin.

LSD and psilocybin, two of the best hallucinogens known to man, also work through modulating serotonin. And Ecstasy (or Molly) works by modulating serotonin, too.

Ecstasy pills
Ecstasy pills Wikimedia Commons

Epinephrine, adrenaline, it’s there for fight-or-flight. When you get scared, you feel your heart beat, get sweaty—you can run away from the wild creature that wants to eat you. Cocaine works so well by increasing your epinephrine. People who take too much cocaine get really sweaty and have a really high blood pressure.

Getting really excited is great—that’s why people go on roller coasters. But getting too excited can kill you.

I may ask the class: How many of you use a mind-altering substance on a daily basis? The vast majority may not raise their hands, but caffeine is without a doubt a drug. It has definite psychoactive effects, no doubt you can get addicted to it.

Cup of Coffee Wikimedia Commons

If you include nicotine, caffeine, or alcohol as mind-altering drugs, the vast majority of adults in American society use one or more of these daily.

As a medical toxicologist, what do you do all day?

Medical toxicology is a relatively new specialty in medicine—we’re one of the youngest disciplines in medicine. And we are a group of interesting individuals—only a few hundred in the country—whose expertise is in taking care of people who are acutely and chronically poisoned…We are the medical detectives of the modern age.

What tools do you use as a sleuth?

We may use tests like gas chromatography or mass spectrometry to figure out how much of something is in something else. But our best tool is still to take a patient’s full history and to do a good physical exam. We also look at symptoms and context, of course. In the right context, if a person is unconscious, barely breathing; has low blood pressure and pulse, has tiny pupils—that’s someone who likely took too much opioid. I don’t need tests to observe that.

The Museum greatly acknowledges The Mortimer D. Sackler Foundation, Inc. for its support to establish The Sackler Brain Bench, part of the Museum’s Sackler Educational Laboratory for Comparative Genomics and Human Origins, in The Spitzer Hall of Human Origins.

Learn more about drugs and poisons of all types in a new exhibition, The Power of Poison, opening Saturday, November 16.