The Hallucinogenic Fungi That May Treat Alzheimer’s

This SciShow video was supported by Ground News, a website and app that lets you compare how major events are being covered so you can see more signs of more stories. You can go to ground.news.com or click the link in the description to get 30% off the Vantage-level subscription. Imagine you're just having, like, a nice sandwich for lunch, and everything seems fine at first. But then, a few hours later, you're overwhelmed with convulsions, muscle spasms, and frightening hallucinations. Doesn't sound like the kind of party I'd like to go to, but during the Middle Ages, this was a shockingly common occurrence brought on by rye flour that was contaminated with a fungi called ergot. And that's because these particular fungi are packed with poisonous and psychoactive compounds. But here's the kicker. Ergot has also been used throughout the centuries for its medicinal qualities. From inducing labor in the 16th century to modern therapies for Alzheimer's, these fungi have a long, complicated history. To stop animals from munching on them, ergot fungi produce a nasty selection of nitrogen-based compounds called alkaloids. And they prepare like a proper smorgasbord, too. Researchers have managed to isolate over 70 different alkaloids from ergot. And oh boy, do these compounds put an unlucky consumer through the ringer. Some affect the circulatory system, while others target the neurological system. And in the latter case, they are metaphorically fond of interfering with the jobs that neurotransmitters like serotonin and dopamine are supposed to do—transmitting signals between nerve cells and helping to keep your body running the way that it should. One ergot alkaloid that you may have heard of is lysergic acid, better known as the LS part of LSD. And LSD is rather notorious for its hallucinogenic qualities. But these same compounds that wreak havoc on a human body and mind can also be harnessed for good. Midwives were some of the first to recognize the benefits of ergot, and started using it to induce labor as early as the 1500s. And they didn't do this out of the blue, of course. This was after they had observed the fact that pregnant pigs would go into premature labor after being fed ergot-contaminated rye. Unfortunately, giving patients ergot carried a risk of the child being stillborn. So by the 1820s, these fungi were recommended for use only as a way to stop hemorrhaging after birth. And lucky for everyone involved in the birthing process, in the 1930s, researchers successfully purified the ergot alkaloid responsible for putting a stop to that hemorrhaging. It's called ergometrine, and it is a vasoconstrictor, which means it narrows blood vessels and slows the flow of blood. So not only is it particularly useful for preventing something as dangerous as a hemorrhage, it can also be used to reduce the symptoms of stuff like migraines. And yes, ergometrine, as well as other similar ergot-based alkaloids, are still being used to treat both of those conditions today. But that is far from everything these fungi have done for medicine. Several ergot-based therapies have been developed over the past century, including treatments for Parkinson's. With Parkinson's, the neurons that make dopamine have started to break down. A body needs dopamine to transmit instructions. If it doesn't have enough, it'll have a hard time coordinating its movements. That's why one of the hallmark symptoms of Parkinson's is tremors. But researchers have figured out how to take ergot's natural defense system, which evolved to disrupt the dopamine system in a healthy body, and harness it for good. Like, maybe this has happened to you, where you walk into a store wearing clothes that look a bit too much like the company uniform. And then you wind up helping an adorable grandma pick out a new stand mixer because she thought you worked there, and you're like, I guess I work here now. It's kind of like that. In a patient with Parkinson's, the ergot alkaloids basically swoop in and pick up dopamine slack by bonding with the right receptors and sending the appropriate signals. Motor functions can return to normal, and the tremors can stop. But there is one important negative side effect. When these medications are taken long term, patients can develop a risk of fibrosis, which is an increase in connective tissue around organs. This is extra bad when it hits the heart, because then your heart has to work harder to do its job. So these days, other drugs are often recommended as a treatment before a patient turns to one of these ergot-based therapies. And some countries have even banned the therapies altogether, at least for treating the symptoms of Parkinson's. But research has not stopped there. Ergot-based therapies have also been investigated as a treatment for other chronic diseases, like diabetes and Alzheimer's. For example, the semisynthetic alkaloid marketed in the US under the brand name Cycloset was initially used to treat Parkinson's, but the FDA approved it back in 2009 to treat type 2 diabetes as well. Type 2 diabetes occurs when a person's body becomes resistant to insulin, which means they have a harder time regulating their blood glucose levels. But Cycloset binds to the dopamine receptors in a specific part of the brain called the hypothalamus, triggering the release of hormones like cortisol and growth hormone. These hormones can then work together to reset the body's internal rhythm and maintain the right levels of sugar and fats. And research has shown that, in combination with a change in diet and exercise, taking this drug really can help regulate the blood sugar levels of people with type 2 diabetes. But Cycloset may have yet another use. According to research published in 2023, scientists are investigating whether it can be used to treat Alzheimer's. Just like Parkinson's, Alzheimer's is a neurodegenerative disease, which means we're dealing with the death of neurons. But a key symptom of Alzheimer's, in particular, is the buildup of amyloid beta-peptides in the brain. And those peptides are targeted by another protein called Toll-like Receptor 4, or TLR4 for short. Normally, TLR4 helps out your immune system. When you need to fight off an infection, it sends out a signal for your body to make some inflammatory compounds that'll make the fight easier. So when TLR4 binds to those amyloid beta-peptides, it holds up a proverbial megaphone and yells, hey, immune system, do the chemicals! Just like it's supposed to. But a buildup of amyloid beta-peptides means extra TLR4 activity, and therefore extra inflammation in your brain. And too much inflammation for too long can cause serious problems, like killing your neurons. So if scientists can find a way to keep TLR4 from producing too many inflammatory compounds, we might have found a way to help slow the progression of Alzheimer's. And here's where cycloset comes in. It can bind to TLR4 and take away that megaphone. But this research is still in very preliminary stages, so we don't know if that chemical trick will translate into an effective treatment for Alzheimer's, at least not yet. If it does, researchers believe it could become a single drug therapy, instead of the cocktail of drugs patients typically have to take. And if it doesn't, it's certainly not the end for ergot. With all those alkaloids, who knows what medical applications we'll uncover next. I'll just wait here, as science does its work, eating every non-hallucinogenic sandwich I can get. Thanks to Ground News for supporting this SciShow video. When it comes to topics like medicines to improve your brain health, news outlets can ignore certain stories based on their narrative. But it's important to get different viewpoints and stay well-informed of our blind spots to make sure we're consuming and sharing the most accurate information. That's where Ground News comes in. Ground News is a startup founded in 2018 by former NASA engineer Harleen Kaur. Their app and website compile news from around the world into one place, offering curious people like you a comprehensive view of current events. For example, they compiled over 45 sources reporting that, quote, ancient DNA reveals the reason for high multiple sclerosis and Alzheimer's rates in Europe. 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