Electric
Want to know what pacifiers have to do with drugs? What toxin causes your brain to swell and how drinking too much water increases the risk? What drug of abuse is currently under review by the FDA as medicine? Listen to find out!
This is the Pick Your Poison podcast. I’m your host Dr. JP and I’m here to share my passion for poisons in this interactive show. Will our patients survive this podcast? It’s up to you and the choices you make. Our episode today is called Electric.
Want to know what pacifiers have to do with drugs? What toxin causes your brain to swell and how drinking too much water increases the risk? What drug of abuse is currently under review by the FDA as medicine? Listen to find out!
It’s 2:00 a.m. in the emergency department. You're looking at a box of stale pastries debating whether or not you should have a second donut. Resisting its strong gravitational pull, instead, you click on the next chart. The patient is a 23-year-old woman with a seizure. Per the triage note, no prior history of seizures.
She’s asleep on the stretcher. You wake her up, she's lethargic but able to answer a few questions. She confirms no prior history of seizures, no medicines and no supplements. That's as far as you get before she falls asleep again.
Her vital signs are: temperature 100.7 (38.1 C), heart rate 110 beats per minute, blood pressure 150/70, oxygen saturation 100% on room air with a respiratory rate of 18. The nurse gets the patient undressed as you examine her. Her pants are soaked with urine, her skin is sweaty. She has large pupils. Her heart and lungs are normal. So is her neurological exam, other than her mental status. Essentially, we have a patient with new-onset seizures with mildly increased heart rate and blood pressure and a borderline temperature.
As I've said before new-onset seizures is an extremely common chief complaint in the ER.
Question number one. Which of the following test or tests should we order?
A. a fingerstick blood glucose
B. an EKG
C. a CT scan of the head
D. electrolytes
Answer: A & B are necessary. If you said, D, you aren’t wrong. We need the fingerstick to make sure this isn’t hypoglycemia or low blood sugar. The EKG isn’t out of concern for a heart attack but rather to evaluate for an arrhythmia which can present as a seizure mimic. I’ve seen this in real life, a patient who looked exactly like they were having a seizure, until a glance at the monitor showed ventricular fibrillation. We do almost always order lab work, though in young healthy people, we don’t anticipate abnormalities. Patients and families always want CAT scans of the head believing it will show a cause of the seizure, in reality it’s extremely low yield in healthy patients. An MRI might provide more information, but these aren’t done emergently in the ER.
As you reach your computer to enter the orders, the nurse calls you back into the room. The patient is having another seizure. A seizure is a burst of uncontrolled electrical activity in the brain. At this point, treatment is indicated. I’d use a benzodiazepine like lorazepam brand name Ativan to prevent another seizure.
The patient’s friend arrives, looking anxious and jittery. You ask him what happened. He says just prior to arrival the patient reported feeling unwell, asked for water, then collapsed to the grass. He describes generalized tonic-clonic seizure activity with contractions of all 4 limbs. You ask where they were and what they were doing. The friend hesitates, fidgeting. You tell him you need the right history to ensure she gets the right care. Eventually, he says they were at an electronic dance music festival. In this scenario, every ER doctor and toxicologist’s thoughts immediately turn to drugs and alcohol. Of course anything is possible, but common things being common, complications of substance use are at the top of the list. The friend says our patient drank alcohol and ingested another substance.
Question 2. What is the likely cause of seizures in this patient? Pick Your Poison.
A. Alcohol
B. MDMA, also called molly or extasy
C. LSD
D. Psilocybin or magic mushrooms
Answer is B. MDMA, popular at festivals and in nightclubs. It was popular in pill form called ecstasy, in the 1990s and 2000s. More recently it's in a powdered form, often called molly. I’m always shocked how many people think it’s completely harmless. No it’s not the world’s most dangerous drug, it’s certainly not fentanyl, but patients certainly end up in the ER after MDMA use and deaths do occur. In fact a paper on this topic from the 1990s has one of my favorite titles, “The Agony of Ecstasy.” The prevailing opinion is that somehow molly is safer than ecstasy, which makes no sense since they're exactly the same drug.
First, let me touch on what are sometimes called club drugs and then come back to MDMA specifically. One of the biggest risks with taking things at a festival or in a nightclub is, like the risk with supplements, you have no idea what it really is. There are tons of studies analyzing drugs from these venues, both confiscated drugs and on voluntary donations. They all show the same outcome. People have absolutely no idea what they’re getting. As much as 50% of molly isn’t even MDMA. Substitutions can be anything from sugar and caffeine to methamphetamine, ketamine and cocaine. If you do get what you paid for, the concentration is extremely variable. Bottom line, patients may or may not be forthcoming about what they took. But even if they are, they don't necessarily know what they've been exposed to.
We believe the friend’s history, of course, but do we believe this is an MDMA exposure? Or do we think she took something else?
Question 3. Which of the following is true?
a. the patient is experiencing symptoms consistent with MDMA toxicity
B. the patient was given another toxin
Answer: A. Seizures due to MDMA use are a well-known complication. This is a pretty classic story, so I don’t think we need to look much further. A good way to confirm our suspicion and that is with her lab tests, so I’m glad we sent those earlier.
Question 4. MDMA toxicity causes what disturbance on labs, causing seizures?
A. Potassium
B. Magnesium
C. Calcium
D. Sodium
Answer: D. MDMA cause hyponatremia, or low sodium. The patient’s sodium comes back at 117 mEq/L. Normal is 135-145, so this is dangerously low. Hyponatremia is caused by an imbalance in sodium and water. Either too little sodium, or too much water. This is why sodium and other electrolytes are measured as a concentration mEq, or mmol per Liter. One way to narrow down the cause is to look at the patient’s volume status. Edematous legs, swelling, can result in hypervolemic hyponatremia due to too much water from say congestive heart failure or liver disease. A dehydrated patient has too little water which is hypovolemic hyponatremia, for example from vomiting or diarrhea. Or patient’s volume status is normal making this euvolemic hyponatremia, classically associated with marathon runners and MDMA.
Low sodium levels cause an altered mental status, seizures, coma and require emergent treatment. If we wait, her brain might swell, become too big to fit in her skull and get squished out, leading to brain herniation and death. Lorazepam is the right choice for treating undifferentiated seizures, but it won’t stop a seizure due to a sodium disturbance.
Most IV fluids contain sodium, or salt. However, she needs a lot more than the amount contained in a bag of normal saline. The treatment is 3% hypertonic saline, fluid with a high sodium concentration. If you screw it up, this treatment can be as dangerous as the low sodium she has now and it’s easy to do more harm than good. If you give too much, the sodium will become high, resulting in altered mental status, seizures, and death. With too rapid correction, there’s a risk of osmotic demyelination (formerly called central pontine myelinolysis). Essentially, the brain can’t readjust quickly enough and becomes dehydrated. Patients develop locked-in syndrome, paralyzed and able to move only their eyes. No one wants this.
Calculating the sodium deficit and how quickly to fix it is very complex and several different formulas exist. I like a simplified protocol, skipping the confusing calculations. You give 100 ml 3% NaCl as a bolus over 10 min and can repeat 3 times until the acute symptoms subside. The goal is to provide an urgent correction by 4 to 6 mEq/L to prevent brain herniation.
Back to our patient. Now you can’t wake her up. She’s tremulous, like she’s about to have another seizure. You give several doses of hypertonic saline. She stops shaking and opens her eyes. A great sign. She’s certainly not back to normal, but hopefully, she no longer has a dangerously low sodium. The nurse draws more blood and sends another specimen to check.
While we’re waiting, let’s talk about how MDMA cause hyponatremia. Interestingly enough, via two pathways. One due to the drug, one due to the patient. MDMA itself causes release of vasopressin, also known as antidiuretic hormone, from the pituitary gland. A diuretic is a water pill, so an antidiuretic like vasopressin causes your body to retain water, diluting sodium down to low levels. The second problem is if the patient drinks too much water, ie free water, while on MDMA. Drinking water to prevent dehydration is often encouraged in clubs and festivals. People may sweat due to dancing and hot weather or a crowded club. Some water is good, too much water exacerbates the low sodium already caused by MDMA’s effects in the brain.
After about an hour, our patient now awake and alert, sitting up talking to her friend. Her repeat sodium level comes back at 121 mEq/L. Still low, but not dangerously so. Water restriction for a short time should be enough to fix it from here. She’s arguing with the friend, saying it must’ve been a bad batch of drugs, as it couldn’t be MDMA which everyone knows is safe. You tell her about MDMA’s side effects, eventually she stops arguing, though it’s not at all clear she believes you.
Obviously MDMA does a lot more than just effect sodium levels. What else does it do? The chemical name gives us some information. It’s methylenedioxymethamphetamine. So, it’s an amphetamine, the reason our patient had a fast heart rate, a high blood pressure and large pupils. However, MDMA has only about 1/10 of the stimulant effect of amphetamine. In high doses, you can see hyperthermia with life-threatening multisystem organ failure, though this is rare with MDMA.
I’m sure you know MDMA is different than classic amphetamines or meth. Why? The methylenedioxy part.
Question 5. This part of the molecule has a similar structure to:
A. Mescaline (Peyote)
B. Psilocybin (Magic mushroom)
C. LSD
D. Cannabis
Answer: A. Mescaline. Mescaline is a hallucinogen and increases serotonin levels. So does MDMA. This doesn’t happen with other amphetamines. In fact, it’s similar to the effect of hallucinogens like LSD and psilocybin. MDMA causes euphoria, feelings of an expanded consciousness and peacefulness, enhanced sensory perception and heightened sexuality. It’s classified as an entactogen, from the Greek meaning touching within. Less desired MDMA effects include restlessness, confusion, and difficulty with concentration and memory. It also causes bruxism or tooth-grinding, this is why you see pacifiers at festivals.
We don’t know much about the long-term effects of MDMA on the brain. More on why this matters in a few minutes.
First, I want to talk about why MDMA has recently been the topic of controversy and headline news. A drug company called Lycos Therapeutics has filed and application with the FDA to manufacture MDMA specifically for the treatment of PTSD. Hearing about the controversy, I assumed it was a dry, academic debate about data or statistics. In fact, the controversy is about crime and cover-ups.
First, a word about psychedelic assisted psychotherapy. There is some evidence use of hallucinogens may help patients during therapy. There are a few small, but really interesting studies suggesting psilocybin, the ingredient in magic mushrooms, helps relieve anxiety and depression in hospice patients, for example.
Ann Shulgin wife of Alexander Shulgin, the famous chemist and psychonaut credited with popularizing MDMA, called it “penicillin for the soul”. Despite the beliefs of utility from what some have termed a “cult” of psychotherapists, almost no data is published. It was kept quiet out of fear the FDA would schedule MDMA, which did happen in 1985. This is a troubling beginning, in my opinion. Medicine, especially use of a mind-altering drug during therapy, shouldn’t be done in secret. More recently, some patients with PTSD, including veterans, have reported MDMA helps.
Fast forward to today. Lykos reports 86% of patients in their study showed improvement in PTSD symptoms and 71% no longer met criteria for PTSD at all, versus the placebo with 69% improving and 48% no longer meeting criteria. Sounds great right? So what’s the issue?
The is can we believe this data or has Lykos Therapeutics lied and manipulated it. First, the study isn’t blinded, because participants can tell if they get MDMA or placebo. The FDA was aware of this, most agree there’s no way to do a blinded study. Second, Lykos is accused of recruiting both therapists and patients with biases toward use of psychedelics. Meaning, both the patients and therapists are more likely to report good experiences rather than bad.
It wasn’t just bad experiences that occurred during the study. Crimes were also committed. A warning about the next two minutes. Content may be disturbing to some listeners. I'm going to touch briefly on sexual assault. If you are a parent who prefers your children not listen, or an adult who feels triggered or wants to avoid, please skip ahead 1 minute.
A study patient, paired with a husband-and-wife therapist team was sexually assaulted. The footage has been released and is extremely disturbing. The woman, with a history of PTSD from sexual assault, is assaulted by the male therapist. She’s clearly distraught and saying no. The reason for the male-female pair? It’s thought to be safer after two therapists in the 1980s were convicted of sexual assault during MDMA assisted sessions.
Obviously, any violation of the therapeutic relationship is horrific. It’s even worse when victims have an altered mental status and may not even be able to say no. These women were in therapy because of PTSD due to sexual assault. Horrifying.
If you skipped ahead, we are back to our normal content here. Basically, this trial is full of medical and ethical concerns. It doesn’t answer the question of MDMA treatment for PTSD. Many researchers are concerned the poor quality of this trial will derail future studies into the use of psychedelics.
This news is really hot off the press, earlier this month an FDA advisory panel of independent experts, asked to review the data, recommended the FDA not approve the application. The FDA doesn’t have to follow the committee’s advice, but typically does. The decision is expected in August.
This brings us back to the question of the long-term effects of MDMA on the brain. Animal data shows a reduced number of serotoninergic neurons in the brain after MDMA use. Less serotonin is associated with depression and memory problems. PET scans in humans who've stopped using MDMA show decreased brain activity in regions related to emotions and memory.
Why does this matter? Because if using MDMA changes our brains, and especially if it causes depression in patients already suffering with mental illness, this big risk would have to be balanced with a big reward to justify it’s use in psychotherapy.
I don’t know what the future holds for MDMA specifically and psychedelics in general, but I’m interested and waiting to see. This is a fictional case, as are all our cases, to protect the innocent. But it is based on real poisonings.
Last question and today’s Pop Culture Consult. Which of the following artists doesn’t refer to MDMA in lyrics?
A. Kanye
B. Jay Z
C. Madonna
D. Taylor Swift
Post your answers on our Twitter and Instagram feeds both @pickpoison1. Follow and you’ll see the answer when I post it. 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. Thank you. Until next time, take care and stay safe.