Green Fairy

Want to know what medical myths are associated with absinthe? What famous figure carried a hollowed-out cane filled with alcohol? And what plant was used in an expression by Shakespeare to indicate the bitter truth?

This is the Pick Your Poison Podcast. I'm Dr JP. ER doctor. Toxicologist, and

unapologetic lover of all things poison. Wanna know what medical myths are associated with absinthe? What famous figure carried a hollowed-out cane filled with alcohol? And what plant was used in an expression by Shakespeare to indicate the bitter truth?

Stay right here to find out.

This is an interactive story.

Survival isn't guaranteed.

Will our patient live or die?

It's up to you and the choices you make.

So grab your stethoscope.

Today's episode starts in front of an unmarked door.

You check your phone confirming it's the address your friend sent.

This has to be it.

You push the door open.

You're immediately wrapped in low, drifting music and quiet conversation. The lighting is dim, catching Velvet and Dark Wood. It feels like stepping out of time into Belle Époque Paris.

At the far end of the bar, you spot your friend. She smiles, stands, and pulls you into a quick hug. You take the stool beside her.

It's an absinthe bar.

The bartender begins the elaborate ritual of making the drink. He puts a small glass down in front of each of you and then, with a soft clink, puts a silver slotted spoon on top of the glass. On the spoon he places a sugar cube and pours several ounces of clear green absinthe into the glass beneath. He then lights the cube on fire and slowly drips cold water over the entire mixture until it turns a cloudy opalescent green.

You take a sip. It's strong, bitter at first, and has a lingering medicinal taste.

Your friend says she's been wanting to come for months. "I know the owner; we dated briefly, but remain friends. He promised he'd come say hi."

You feel your shoulders relaxing as some of the tension from the long day fades in the calm atmosphere.

Then a door behind the bar slams open. The sound cuts through the quiet. A tall man strides through. Your friend smiles and starts to say hi. Clearly, It's the owner though he isn't doing much for the ambiance. He shouts at the bartender for a drink.

The smile disappears from your friend's face. The owner has a knife in his hand and is staring directly at her. He's swearing at the top of his lungs and carrying on a conversation with someone who clearly isn't there.

Then he shouts, "It was you," and rushes toward her with the knife.

For a brief second you wonder what kind of relationship they'd had, before your instincts kick in. You kick over the barstool next to you, directly in his path. He trips and falls, fortunately not on the knife. It skitters across the floor.

You grab your friend's arm to get out as fast as possible. The man is lying on the ground, looking confused as to how he got there. He's muttering to himself about being followed and recorded. Something about Hollywood controlling his actions with neural implants.

You hesitate for a second.

"Does he have mental illness?" you ask.

"Well he was a little unusual," she says "but not that I know of."

Did he ever try to hurt you?

"No" she says, " He was never violent."

Question #1. This is most likely

1. Personality disorder

2. Panic attack

3. Psychosis.

4. PTSD

Answer: this is probably C. psychosis. He seems to be talking to someone that's not there and is obviously very paranoid. Neither of those is a hallmark of personality disorders or panic attacks. Occasionally people with PTSD can have psychosis, but it's rare, and this doesn't look like a flashback.

Around you the bar is emptying as people rush to leave.

Call 9-1-1, you say to your friend. Though it's unclear if this is a matter for the police or an ambulance.

The bartender says the owner's behavior had been increasingly erratic and violent for the past few months. He said he'd been considering a new job but had never anticipated his boss would try to kill someone.

You and your friend wait outside. Both police and medics arrive. After a lot of shouting from inside and crashing noises, the medics roll out with the owner handcuffed to a stretcher, accompanied by the police. He's spitting at them and fighting against the handcuffs.

This is fiction so of course you're the doctor.

On arrival to the emergency department the patient remains extremely agitated. You call for security assistance and six large men show up. Just transferring him from the EMS stretcher to the hospital one is going to be difficult. He is spitting and trying to bite anyone who gets close.

Question #2. What is the first step?

1. Let him refuse care and leave.

2. Intubation

3. Sedation

Why are we doing this? He is clearly a danger to other people, he just tried to stab your friend, and therefore lost the right to refuse care. We need to do a medical evaluation to see if this is a medical issue and if not he needs psychiatric care. Security manages to slide him across and unfortunately you have to apply four-point physical restraints, tying his arms and legs to the bed.

The physical restraints are a temporizing measure. I would definitely give him some medicine for sedation so he doesn't hurt himself fighting against them. There are a lot of options. We could discuss this at length. Most of the options are benzodiazepines or antipsychotics, with risks and benefits to both. In this case I probably would order an antipsychotic given that he appears just that psychotic.

The nurse gives him an intramuscular injection in the arm with the help of two security guards to hold him down. Twenty minutes later he's much calmer and the nurses can safely put in an IV and check his vital signs. His temperature is 98.6 or 37°C, Heart rate 120 beats per minute, Blood pressure 120/80, Respiratory rate 18, with oxygen saturation 100% on room air.

Your physical exam is very limited but he is able to tell you the year and the month. He tells you he's 31 years old. He can't cooperate with the full neurological exam but there's nothing obviously wrong. his heart and lungs are clear, his abdomen is soft and non-tender, and he is for sure moving all of his extremities with superhuman strength.

In the meantime your friend has tracked down his family through friends of friends and the patient's mother arrives at the bedside. She says he has no prior past medical history. As far as she knows he doesn't take any medicines and has definitely never had any prior psychiatric history.

So what is happening to our patient? This could be a case of new-onset psychosis. Psychosis is when a person loses contact with reality. Essentially they can't tell real from imaginary. Classically they can have auditory hallucinations. In medicine we call this "responding to internal stimuli," meaning they are talking to someone who wasn't there.

This could also be delirium from a medical cause. Say he had some sort of untreated infection like meningitis; he could become delirious. How do you differentiate the two? Question #3.

1. Timeline

2. Violent behavior

3. Age.

4. History of insomnia

The answer is the timeline would be most useful here. Patients can be violent in psychosis or delirium. Insomnia is not particularly relevant. Age doesn't distinguish between the two, though we do know that psychiatric illness like schizophrenia often begin in the twenties. Delirium happens over a few days because it's due, again, to an acute medical problem. Psychosis happens more gradually, typically over months or years. He clearly wasn't psychotic when he was dating your friend but the bartender noted a decline in his behavior over the past few months. I'd be suspicious this is psychosis but The real answer: we need a medical work-up to exclude causes of delirium and psychosis caused by medical problems.

Essentially our job in the emergency department is to rule out medical causes. If we can't, patients are admitted to the hospital for more workup. If we don't find anything concerning then we talk to psychiatry about the possibility of new-onset psychosis. It can be tough in the emergency department because we don't have a lot of time for this workup and we also know that psychiatric causes are very common in otherwise healthy 20- and 30-year-olds.

What should we do? Well we start with the basics: labs to check for electrolyte disturbances and evidence of infection. I'd certainly get a chest X-ray and a urine specimen to look for pneumonia or a urinary tract infection. Some people might want a CT scan of the head. It's not unreasonable although I'll tell you it's pretty low yield in these cases.

An hour later everything comes back stone-cold normal: Labs, including his white blood cell count as well as his electrolytes and his sodium. The CT scan of his head is normal as is his chest X-ray and urine.

The nurse tells you the patient is agitated again and wants to know if you will order another dose of sedatives. What's now? In cases like these you have to consider a spinal tap to make sure it isn't something like meningitis or encephalitis. It's always a tough question because on the one hand you do want to do a thorough workup but on the other hand, doing a spinal tap on a psychotic person is nearly impossible and is definitely not without risks so you have to do a serious analysis to weigh the risks and benefits.

Before a spinal tap in this patient, I'd consider toxicologic causes, there are a lot of things that can cause psychosis. What about a urine drug screen? Did I hear you say? You can send one but the results will have to be interpreted with a healthy dose of caution. Why? Because of the tremendous possibility of false positives and false negatives. First, if something is positive in the urine, we have to decide if it's really the cause of the psychosis. What if it's just an incidental finding? Something he randomly took an attempt to self-medicate. Second, we've discussed that urine drug screens only screen for a handful of substances so if the urine drug screen is negative, it by no means rules out toxicologic causes.

You can ask his mom about drugs of abuse though clearly she's not going to be the best source. You text your friend back thanking her for her help and asking her to see if she can get any more history from the other friends in their circle.

His mom says he doesn't smoke, drinks some but not too much, and doesn't use any drugs. Your friend texts back, "He drinks like crazy. I mean he owns a bar that's why I only went on a few dates with him. He also used a lot of cannabis. The first couple dates were fun, after that it was clear he had serious substance use issues."

What about drugs? She says, "I never saw him do anything else but let me ask around."

Let's talk for a minute about drugs that cause psychosis. What we see a lot of in the U.S. these days is methamphetamine. It can cause severe psychosis where patients can become suicidal and homicidal. Other sympathomimetics can cause it: cocaine, etc. Cannabis is popular worldwide, long-term cannabis use carries a risk of psychosis.

A classic cause of agitated violent behavior in the emergency department is PCP. I'm sure you've seen a picture of someone strapped in restraints to a stretcher, high with superhuman strength, agitated and psychotic and flips the stretcher over. I saw something online a few months ago saying that this was a myth. Clearly that person had never worked in an emergency department.

Anyway. Could this be meth, cocaine or PCP? It's certainly possible but he doesn't have a classic sympathomimetic toxidrome. He does have a rapid heart rate but he doesn't have high blood pressure or sweaty skin.

He is obviously hallucinating as we said. What about hallucinogens? Definitely LSD or any others could be a culprit.

We mentioned alcohol since he owns a bar and alcohol withdrawal can certainly cause hallucinations. Think of the classic pink elephant. Could this be withdrawal? It's a potentially life-threatening diagnosis and knowing his history we have to consider it. Patients do hallucinate but we don't usually see this kind of wild agitation. He is tachycardic with a rapid heart rate, which goes along with it but his blood pressure was normal. On exam we didn't see a serious tremor or any tongue fasciculations. I think withdraw is less likely at this point but if he's admitted to the hospital, they'll have to monitor him closely in case he develops it.

What about plain old alcohol intoxication? Is he just drunk? One of the things that argues against many of the toxins we mentioned is that he continues to be agitated. Meth is long-lasting. It can last for 24 to even 36 hours but with things like alcohol, hallucinogens, and cocaine he might not be better in a few hours but he should be improving and not still wildly agitated. Confirming this, his serum alcohol comes back at zero. His urine drug screen comes back positive for cannabis but negative for everything else. Could this be psychosis from chronic cannabis use? It's something to consider. There's no test for that. If we rule out other medical causes, we could discuss the possibility further with psychiatry.

Wait a minute, did I hear you say, we were at an absinthe bar? Could this be absinthe toxicity? Time to pick your poison. It's question number 4. This most likely due to

Absinthe.

A true,

B false.

Before we answer this question, let's talk about what absinthe is and what it's famous for and the historical figures it's associated with. Absinthe, as I said earlier, is a licorice-flavored drink. It's made from wormwood. Dried wormwood in ethanol, along with anise and fennel. What's wormwood? It's a plant, Latin name Artemisia absinthium. It gets its name, as with so many things, from Greek. It's named after the goddess of childbirth, Artemis, because it was often used for gynecological complaints.

The active ingredient in the wormwood is a compound called thujone. Thujone is a GABA receptor antagonist, reducing the effect in the brain. Meaning it works the opposite of ethanol or alcohol, which increases GABA, increasing sedation.

Absinthe was created in Switzerland in the late 1700s by a physician. As I'm sure you know, it became extremely popular in Paris in the late 1800s and early 1900s. In Paris happy hour became known as the green hour, with absinthe itself being called the green fairy. It was associated with the Belle Époque and there's a whole mythology surrounding it due in large part because of the famous people who drank it and some of the medical issues they displayed. Ernest Hemingway drank it. Oscar Wilde, said, "What difference is there between a glass of absinthe and a sunset?". Toulouse-Lautrec famously carried a hollowed-out cane containing absinthe inside.

Absinthe's most famous association is with Vincent van Gogh. Did absinthism cause him to cut off his ear? The whole story is incredibly interesting. Many of the details were reported by Gauguin. In 1888 Van Gogh had left Paris and removed himself to Arles, France, a more rural area, and convinced Gauguin to come there to start an artist colony.

Van Gogh's work from this period is amazing and it's where he created many of his famous works, like the sunflowers. His behavior, though, became increasingly erratic. A few days before Christmas, Van Gogh drank a glass of absinthe and then flung it at Gauguin. The next day he apologized but then later in the day rushed towards Gauguin with a razor in hand. Van Gogh turned off at the last minute before injuring him and went home.

According to Gauguin's subsequent reports he regrets not chasing after Van Gogh to take away the razor because that night is when Van Gogh cut off his ear. Afterwards he ran to a nearby brothel and gave the ear to the madam, telling her to keep it in a safe place. She alerted the authorities and shortly thereafter Van Gogh was admitted to a psychiatric facility for further care. Writing poignantly to Gauguin in a letter, he said "Aren't we all mad?"

What was the cause of Van Gogh's mental problems? The cause of Van Gogh's mental illness is debated to this day. His physician diagnosed him with epilepsy, a word that was widely applied and doesn't mean the same as we would use it today. It's noted that he was never reported to have had a generalized tonic-clonic seizure but rather partial seizures or fainting episodes. Epilepsy can cause psychosis but many others have suggested bipolar disease or medical causes like porphyria. Some suggested exposure to substances he used in painting, like turpentine and camphor, causes psychosis.

Interestingly, His physician treated him with bromide salts, which we've talked about before in episode Bad Advice. Bromide was used in psychiatry as a sedative in those days. Reporting to his brother, he said, "The unbearable hallucinations have ceased, and are now reduced to simple nightmares, in consequence of taking bromide of potassium, I think."

Unfortunately his symptoms became more severe and in July of 1890 Vincent Van Gogh shot himself in the chest and died at the age of 37. It's very much unclear but I think everyone agrees that whatever underlying disease he had was exacerbated by the copious amounts of alcohol that he drank. At the time many people believed the absinthe itself was to blame.

Absinthism is a historical description characterized by hallucinations, seizures, sleeplessness, tremors, and even paralysis. Obviously given the name, it was attributed at the time to excessive consumption of absinthe. Doctors wanted to determine whether it was absinthe itself or just alcohol causing many of these issues. A French physician gave a dog oil of wormwood, noting that the dog had seizures. These findings were repeated in other animals.

There were sensational news reports attributed to absinthe use. A Swiss man, found lying on top of the dead body of his daughter in his yard, did not recall killing his pregnant wife and two daughters the day before. The police investigation showed he had drunk two glasses of absinthe and the murders became known as the "absinthe murder," even though he had also had wine, crème de menthe, and brandy.

Because of these issues, Absinthe was first banned in the Republic of Congo in 1898, followed by Belgium in 1905. Concern that absinthe was responsible for the mass desertion of French troops in World War I led to its ban in 1915. I guess it was easier for the French government to believe Desertion was caused by alcohol rather than death, destruction, and trench warfare.

A not insignificant contributory factor to the ban was the French wine industry. The French wine industry was suffering a dramatic setback from phylloxera infestation. This caused wine prices to increase, making absinthe a cheaper alternative and increasing its popularity. The wine industry contributed to concerns about the dangers of absinthism.

What do you think now about absence as the cause of our patient's psychosis? Well you might be aware that there was a reversal of the absinthe bans and it is now available in the US and Western Europe. Why is that? Because the symptoms attributed to absinthism have not been subsequently proven to be caused by wormwood. They were most likely due to a combination of mental illness, other medical problems, and alcohol. modern research does not support absinthe as the cause of the mental illness in the famous artists in the 1900s or in modern times. Why not? Because the concentrations are too low to cause toxicity even with chronic exposure. You're going to have significant alcohol poisoning way before you're able to get Thujone poisoning. The laws were reversed when it was shown that there was no evidence to support absinthe causing significant toxicity.

As I said earlier, Thujone inhibits GABA. This means it causes overstimulation in the brain and can, in high concentrations, cause seizures. But as I also said before this is in direct contrast to the action of alcohol, making me wonder if you drink Thujone in alcohol if there are any effects at all or if the higher concentration of alcohol cancels it out. Does absinthe cause seizures? It doesn't because the concentrations are too low and Anybody who drinks massive quantities will develop severe complications of alcohol toxicity long before they drink enough to develop wormwood or thujone toxicity.

But Thujone itself can be toxic in large concentrations. Let me tell you about a few interesting case reports. In 1997 a 31-year-old man was found confused and disoriented he had a seizure. This patient drank 10 mL of oil of wormwood, assuming it was absinthe. This is a highly concentrated amount of thujone. His main issue after this was rhabdomyolysis, i.e. muscle breakdown. In another case in Switzerland a man was admitted with mania after ingesting 1 L of an infusion of Artemisia vulgaris.

So yes high concentrations of Thujone can cause an altered mental status, seizures, and rhabdo but not the extensive medical and psychiatric issues reported in the past and attributed to absinthe.

The issue of concentration is always an interesting one. Initially in the late 90s and 2000s, when some of the absinthe bans were lifted in the U.S. and Europe, there were limitations on thujone concentrations. This was due to a mistaken belief that absinthe in the past contained extremely high quantities of thujone. Initial estimates suggested that absinthe in the 1800s had 260 mg/L of thujone but modern testing of samples from that time showed it was much lower, around 25 mg/L.

There was another interesting speculation that copper toxicity might be responsible for absinthism, given that absinthe is not naturally green and coloring agents were often added. This was also disproven with analysis of bottles from the 1800s. Showing copper levels lower than amounts permissible in drinking water.

Wormwood, the plant prior to the 1900s, has been used extensively as a medicine since ancient Egyptian times. In the Middle Ages it was used to get rid of tapeworms thus the name wormwood, I suppose.

Question #5. A compound derived from Artemisia plants was found to treat which of the following diseases, and in fact its discoverers were awarded the Nobel Prize in Medicine in 2015. Is it

1. Cholera.

2. Syphilis

3. Tuberculosis

4. Malaria.

A different compound found in Artemisia species called artemisinin is used in medicines to treat malaria. Interestingly, In the 1840s absinthe was given to French troops in Algeria to prevent malaria this wouldn't have worked because it may not have contained artemisinin and even if it did it would not have been long-lasting enough in the body.

So back to our patient and to finally answer question number 4. False. Absinthe is definitely not the cause of his psychosis. After an extensive workup including a spinal tap, no medical cause is identified. After an extensive evaluation psychiatry concludes that he has bipolar disease with psychosis likely exacerbated by chronic alcohol and cannabis exposure. He started on anti-psychotics with marked improvement in his mental status. He's advised to stop drinking alcohol and cannabis and you're aware that he has a long and difficult road ahead of him.

There are many references to Wormwood throughout history. It's mentioned several times in Shakespeare. In Romeo and Juliet the nurse says that she weaned Juliet by applying the bitter taste of wormwood to her breast. In Hamlet a character expresses distaste for remarriage and Hamlet responds, "That's wormwood," meaning it's the bitter truth, referring to his mother's remarriage.

The last question in today's podcast: What city is named for Wormwood in its native language?

1. Chernobyl

2. Damascus

3. Istanbul

4. Tbilisi.

Follow the Twitter and Instagram feeds both @pickpoison1 for the answer. Remember, never try anything on this podcast at home or anywhere else.

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While I'm a real doctor this podcast is fictional, meant for entertainment and educational purposes, not medical advice. If you have a medical problem, please see your primary care practitioner. Until next time, take care and stay safe.