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, who’s surprised,
you guys know I love fungus. Because LSD’s 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 should’ve
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 ergot’s 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 it’s 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 didn’t 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 public’s opinion
to turn against the use of LSD. They're damaged for life. The brains They go into institutions,
they’re 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. You’re 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. Okay, bye.
