Fascinating Fails

Have you ever wondered what it might be like to take a trip?

And no, I do not mean a vacation.

I mean a drug-enhanced experience on LSD is what's called a psychedelic, and its mind altering properties were actually discovered completely by accident in an iconic science story involving a bicycle, and some milk.

But the story of LSD has a dark side too, including top secret CIA mind control Tests now in progress indicate that such agents have significant military potential. And now, after decades of controversy and criminalization, researchers are rediscovering the pot of psychedelics to treat mental healt conditions like depression, addiction eating disorders, and more.

Cool!

So let's take a little trip of our ow But if we're going to talk about LSD, we got to talk about fungus first.

I mean, whos surprised, you guys know I love fungus.

Because LSDs story starts with moldy Starting in about the 800s, we start to get records of a mysterious illness that causes a pretty terrifying set of symptoms: burning sensations in their arms and legs, gangrene, convulsions, vomiting, sores, irrational behavior, and even hallucinations.

This mysterious illness killed tens of thousands of people, if not more, and at the time, was oft attributed to the supernatural or even divine punishment.

Absolute bummer, man.

Nowadays, we know that this disease is actually caused by something calle You experience these symptoms if you' eaten food contaminated with ergot fu It's this parasitic fungal growth that latches onto cereal grains like wheat, oats, barley and rye.

If this contaminated grain is made into bread and somebody eats that bread, that person is at risk of ergotism.

Looking back in history with our modern hindsight, we now understand that this fungus is was causing those mysterious symptoms But we can also now see that there were some people who knew what this was, and who were using it on purpose.

Like the ancient Greeks, who we think might have used this fun during religious festivals as an ingredient in a mind-expanding cocktail called the Eleusinian kykeon And as early as 1000 B.C., midwives were actually using ergot to accelerate birth and to stop women from hemorrhaging afterwards.

Absolutely wild, right?

And this is what brings us to our fai and to Basel, Switzerland, where we h fascinating fail of our own.

Oh, I knew I shouldve brought waterproof pants!

But wait, I'm getting ahead of myself Rewind.

It's the 1930s.

Partially inspired by ergots use in midwifery for so lo scientists at Sandoz Pharmaceutical Labs are trying to make medically useful compounds out of ergot.

And one of those scientists is Doctor He ends up being able to isolate one of ergots chemical building blocks, a molecule called lysergic acid.

Then he did something no one had ever done before.

He mixed and matched different molecu onto the one he isolated, to see if he could make compounds that were medically useful for use in childbirth, for example, or to treat migraines.

Going one by one, a team at Sandoz test each of Hofmann's compounds in mice.

when they get to the molecule labeled LSD-25... disappointment.

It doesn't seem to have the particular properties they're looking for, so it gets tossed in the rejection pi But for some weird reason, Hofmann just can't get LSD-25 out of his head In his book, he describes it as a peculiar present that LSD-25 might have more going on than first met the eye.

So five years later, he comes back to and synthesizes it again.

And halfway through his workday, he starts to feel pretty weird, and he says he has to go home and lie on the floor.

Now, I think we've all experienced a state of overwhelm so great that we just have to go home and lie on the floor.

But Hofmann's is a little different.

In his own words when recounting the he was seized with a peculiar sense of vertigo and restlessness.

He feels an overpowering state of bli characterized by an overactive imagination.

And he experiences an uninterrupted s of fantastic pictures, extraordinary shapes with an intense, kaleidoscopic play of colors.

What's happened here is that Hofmann has accidentally gotten some of his lab juice in his mouth.

This is every scientist's worst night It goes against all lab protocols.

But because this experience was so un and intriguing, he wants to try it again, but this time on purpose.

But because that first time was an accident, he doesn't know how much to take.

So he thinks he'll start with the smallest possible dose and work his way up until he experiences symptoms.

So he starts with 250 micrograms.

That's a quarter of a thousandth of a gram, about the size of your average grain of sugar.

Because he took such a small dose.

Hofmann's not expecting to experience any major symptoms, but a mere 40 minutes later, he starts to feel really weird again and decides he needs to go home.

Hofmann even asks his twenty-somethin assistant, Susie Ramstein, to accompany him on the journey he takes on this exact bicycle.

Are you having the Hofmann experience I think so?

It is feeling pretty wavy up here.

Oh.

Oh!

So this screen is recreating what he might have been seeing while he's on his way home and starting to trip.

But I think we can do a little better than that.

Because its Bicycle Day!

We actually got to go to Basel for this years celebration of Hofman now-famous bike ride, where folks get and replicate the 8-kilometer journey that Hofmann and Susie took from the Sandoz labs to his home.

And this is where things kinda fell a We're having fun.

We're having fun, we're having fun.

We're having fun.

Well, it's raining.

And also, I can't feel my fingers because it's so cold.

And also, we've lost the group and we don't know where we're going, so we're feeling good.

But honestly, this was kind of authen because things weren't going so great for Hofmann at this point, e because he's experiencing symptoms from what he thought was such a tiny He's pretty freaked out, and he think he may have poisoned himself.

He's generally feeling anxious and paranoid, and his visions and altered perception are becoming kind of nightmarish, not pleasant like they were before.

But fear not, we did eventually make We found them!

And so did Hofmann, all the way to his house where he felt an undeniable urge to lie down and drink a lot of milk.

Like more than two liters of it.

at the time, it was thought that milk could act as a general poison antidot We've since learned that that's absolutely not true, by the way.

This is going to do nothing for you in a poisoning situation.

Also, this is oat milk.

Anyway, Hofmann woke up the next day no hangover and a renewed zest for li He knew immediately that he had uncov something that could have huge implications for science and medicine And he dove into researching it furth starting with getting everyone else in his lab to try it, too.

But how does LSD do what it does?

For that, we've got to talk about the brain and leave freezing Basel behind for a warm cup of tea.

Hello!

Tea is served!

-Thank you so much!

-I didnt have any scones and cream, So the brain is a chemical organ.

The communication between nerve cells the brain is conducted by chemicals we call neurotransmitters.

One of the most important neurotransmitters is called serotonin In your day to day life, serotonin affects all kinds of things all over your body.

When it binds to its matching recepto on a neuron, it helps regulate your m can influence how you behave, and imp things like appetite, sex drive, sleep, memory, and so much more.

But these receptors in your brain don only bind to serotonin, they can also bind to other molecules And it turns out that LSD binds to your brain's serotonin receptors even more tightly than serotonin itse and the receptor that LSD targets is peculiarly highly expressed in the most recently evolved parts of the human brain.

The parts where we do the things that really only humans ca which is this high level conceptual thinking, planning, anticipating, understanding.

Its effect is all through that one particular receptor subtype.

And LSD and related psychedelics when they bind to that receptor, they massively activate the neurons that those receptors are And those neurons are the neurons which communicate across the brain.

And so they dramatically increase connectivity across the brain.

It helps explain phenomena like synes you know, where people can see sounds, for instance, you know, because that hyper connectivity can put together the visual cortex and the auditory cortex.

After Hofmann's accidental discovery, Sandoz sent samples of LSD all over the world for testing and resear so people could explore its potential And it quickly became clear that this substance could be used to treat mental health conditions like depression, anxiety, and alcohol There was a massive amount of researc largely funded by the US government.

40,000 patients were studied.

A thousand papers were published.

This was the revolution in psychiatry and that was fine for ten years.

And then gradually LSD began to creep out into other uses.

It began to transform art.

It began to transform music.

And then it began to transform politi Now this is going to sound totally fa But while the scientific community saw the therapeutic promise of LSD, the government saw it a little differently.

In the 1950s, the CIA actually bought the entire wo supply of LSD as part of a top secret project called MK-ULTRA.

They were exploring mind control.

I'm being so serious right now- and thought LSD could be used as a truth serum and brainwashing agent.

They conducted experiments by dosing unconsenting subjects in prisons and hospitals who had no i what was happening to them.

The decision was made to do testing on unwitting victims.

It was decided they should be on the fringes of soci because they were most vulnerable.

Spoiler alert: This was wildly unsuccessful.

LSD does not do these things.

And when MK-ULTRA was declassified de later, it was a pretty big scandal.

In the 1960s, LSD and other psychedel like magic mushrooms became associated with the counterculture sc that emerged: movements like the anti-Vietnam War protests and the fight for civil rights, and even just more transgressive musi Plus, a few of the most famous figure who were studying LSD at the time, conducted some highly publicized stud that crossed more than a few ethical boundaries.

This, plus the overall unregulated us of the drug in research and recreatio plus the political environment at the time, led the media and theref the mainstream publics opinion to turn against the use of LSD.

They're damaged for life.

The brains They go into institutions, theyre through for the rest of their In 1970, LSD was declared a Schedule substance in the United States.

Schedule 1 classification means that the drug has a high potential for abu and the drug has no currently accepte medical uses.

And that's still true today, making the kind of research that David and his colleagues do pret What are some of the things you guys are looking into with these drugs tod when we started using psychedelics, our ambition was very simple.

It was to understand what the psyched state was in the brain.

Having done that, we realized that we could potentially use those brain changes to treat disorders like depression.

So we did a head to head comparison.

Psychedelic versus six weeks of taking an antidepressant And we showed remarkable outcome in treatment-resistant depres And it did it in a very different way We believe it's because psychedelics target different parts of the brain to other treatments.

They target the cortex, the very high level parts of the brain where you do your thinking about your Whereas the antidepressants work in a very different way, a deeper par of the brain in the emotional centers dampening them down.

But they don't actually target the cause of the stress.

Whereas psychedelics target the thinking that causes the stress.

So disorders like depression, like addiction, obsessive compulsive disor like anorexia, disorders where people get locked into thought processes that they often know are wrong, but they can't stop the thoughts.

LSD, by disrupting those thought loops, can allow people to escape from them.

And you can see that if you image the brain after psychede the brain is more flexible.

It changes its state more readily.

It's kind of almost weird that you can actually image a psychological experience like cognitive flexibility.

Studies like the one David is talking are sometimes part of a clinical tria testing the use of these substances for therapeutic treatment settings.

I wanted to know more about how these actually work.

So I said goodbye to David and his adorable pack of labradors.

Good boy, Freddy.

Youre a gorgeous boy, aren't you? And I actually went to visit the clin where some of these treatments happen There's usually four basic parts to a psychedelic trial, starting with determining if applicants are a good fit for it.

And for trials like the ones run by D and his colleagues, there are pretty strict selection rules in place.

They make sure that participants don't have any physical issues like epilepsy, heart disease, or traumatic brain injury, or any psychological vulnerabilities like a history of psychosis, schizoph or bipolar disorder, All of which put someone at much high risk of having a negative reaction to these drugs.

Now, outside of a psychedelic interac with any of those preexisting conditi the substances themselves tend to be pretty nontoxic, like it would be very, very, very difficult, nigh impossible to take a lethal dose of one of these drugs.

But that doesn't mean that they're harmless.

These drugs don't interact with everyone's minds in the same way and there's always the chance that so could come out on the other side of a psychedelic experience with a negative mental health outcome That's why the setting and the superv and the support are so important.

And why research into these drugs and how they work in the brain is so essential.

But I'll let Sara say more about this Yes.

So I am Sara Reed.

I am the lead psychedelic research therapist at Imperial College London.

To give a sense of what the dosing sessions are like, participants are joined by two guides who support them in having what's called an inner-directed experience.

And part of that inner-directed experience includes, of course, participants ingesting the medicine, as well as participants using eye shades and headphones to help them be more immersive in their experience and really focus on whatever is emerg from their subconscious and unconscious mind.

And then after dosing sessions, there's always an integration period.

As a psychedelic therapist, I want to say that it's arguably the most important stage of them all, because it's not just a matter of having these glorious psychedelic experiences that produce change.

It's really about taking the insights gained from those experiences and putting th into a practice in real time, and really making meaning of, what's happened in their dosing days.

You know, I learned for the first tim when making this video that the word psychedelic has only been around since the 1950s.

And yes, LSD was created in a lab.

But many of these other psychedelic substances are natural and have been for centuries by indigenous cultures as part of spiritual practices.

So I wanted to get your take on how we in the Western world are maybe medicalizing and institutionalizing these substances.

For me, science at its essence is spiritual, that science and nature truly mirror each other.

One way that I'll share that I try to honor the traditional uses of this medicine Is acknowledging that I don't know everything that there is to know about this medicine, that there is a lot of mystery around the medicine and to really make space for what I don't know.

And I guess because this field is so and it's so emerging, it's actively being shaped right now.

What are some of the things that you that it needs to do as, as it moves into the future.

So one of the limitations that I have experienced and witnessed in the psychedelic therapy field is a lack of diversity.

it's important so that you can experi a participant pool that actually is reflective of the patients that you're gonna serve in the real w So if you have an overrepresentation or an underrepresentation of a partic group of folks, we actually don't kno how psychedelic therapy may or may not be a fit for a variety of different demographics.

And personally, I've experienced a lack of diversity with what it means to not be culturally sensitive in psychedelic therapy.

And how this can show up is therapists or guides saying racist or homophobic or transphobic things to participants unknowingly that can create unintentional harm and, at worst, even potential trauma.

On one hand, it is an honor to witness participant who have been in therapy for decades and nothing has worked, or to have met participants who have been suicidal and have enrolled in a trial and say that this trial has saved my life.

At the same time, we are still figuring out what are the models of care that are going to be best practices because not all therapy modalities actually complement psychedelic-assisted work.

And so, yeah, it's not all good.

-It's not all bad.

It's nuanced.

-Exactly!

This is one of my all-time favorite science failures, because it's such a good example of revisiting something that you and maybe everyone else thought was a complete and total fail Listening to your gut, following your curiosity, and letting your mind be expanded as a result.

Anyway, I hope you enjoyed this trip throughout time and thanks for watchi Come on, boys.

Come on.

Come on.

Good boy.

Come on Sonny, he's such a good boy.