Hallucinogenic drugs could soon work like a ‘surgical intervention’ for mental illness

desert silhouette
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Dinah Bazer was diagnosed with ovarian cancer in the spring of

The Brooklyn resident, an ice-skating teacher and former bank IT
programmer in her 60s, was devastated. Luckily, doctors were able
to successfully treat her disease with chemotherapy, but the
dread of a re-occurrence just wouldn’t go away. It was like
waiting for the other shoe to drop.

“I was totally consumed with fear and anxiety,” she said on a
recent call with a group of reporters.

So in 2011, Bazer enrolled in a trial at New York University
where a group of researchers were looking to test a substance
that they hoped would have a seemingly “mystical” ability to lift
depression and anxiety connected to fear about life’s end.

The drug they were testing wasn’t one dreamed up in a lab. It’s
the essential component of psychoactive magic mushrooms,

In a living room-like setting at the Bluestone Center at the NYU
College of Dentistry, accompanied by trained therapists, Bazer
took a pill. At first she couldn’t know whether it was going to
be the drug or a placebo, but once the effects started to come
on, it would have been clear. Sure enough, within about 40
minutes, she started to “trip.”

“I visualized my fear as physical mass in my body,” a black
concentration, she said. She became angry, volcanic.

She screamed. “Get the f–k out!”

And then, this woman who said she had been an atheist her entire
adult life — and still is — had a strange sensation.

“I was bathed in God’s love and that continued for hours,” she
says. “I really had no other way to describe this incredibly
powerful experience.”

The feeling faded, but so did her fear, depression, and anxiety.
They have not returned.



Spring for psychedelics

Bazer was a participant in one of two controlled clinical trials
of the effects of psilocybin on patients dealing with depression
and distress related to facing the end of life. Aside from a few
smaller pilot studies, these two trials — one by researchers from
Johns Hopkins University (JHU)
and the other, which Bazer
participated in, at NYU
— were the first major ones of their
kind. The results from both studies were published in the Journal
of Psychopharmacology on December 1, along with 11
accompanying commentaries
by prominent experts in the field
of psychiatry.

The results from both trials were encouraging enough that the
scientists involved hope they’ll be able to get FDA consent to
move forward to a large-scale Phase 3 study, the third and final
of three sets of human trials that are needed before the FDA
considers approving a new drug.

“This is a potential pathway to clinical approval,” says
Roland Griffiths
, a professor of psychiatry and behavioral
sciences at JHU School of Medicine, who led the JHU study and is
one of the pioneers in the modern era of psychedelic research.
“But that [approval] requires the next step of going to the FDA
and getting permission to move forward.”

The recent announcement that
the FDA decided to allow trials using MDMA
(the chemical name
for drugs commonly known Molly or ecstasy) to treat PTSD to move
to Phase 3 gives him hope too, especially since he says that MDMA
might have even more “baggage” than psilocybin when it comes to
getting approval.



In a certain sense, this is a renewal of research into the power
of psychedelic substances, according to Griffiths and Stephen
Ross, an associate professor at NYU’s School of Medicine, who led
the NYU study. In the 1950s and 60s, psychiatrists were
enthralled by the power of LSD, psilocybin, and other
hallucinogens, substances which seemed able to re-organize the
way that patients viewed the world, and, they say, appeared to
also help them overcome struggles with alcoholism and other
addictions. But the drug prohibition era put an end to that
research for decades.

Scientists have only recently begun to experiment again with
these substances. Griffiths tells Business Insider that he
started looking into experiments with healthy volunteers around
2000, at a time that such a suggestion shocked review boards, who
thought it would be far too dangerous. But slowly, he was able to
convince them. He began to recruit volunteers who hadn’t tried
LSD or magic mushrooms (this was one of the hardest parts, he
says, since they wanted people naive to psychedelics, but most of
the people they found that weren’t scared of the idea had already
done some experimentation).

A single dose

After studying a number of healthy people, certain things about
psylocybin’s effects became clear. In a therapeutic setting, the
researchers didn’t find any serious long-lasting adverse effects
of the drug. That doesn’t mean that they found it to be
totally risk-free, however. Griffiths is also the senior
researcher on another
published December 1 in the Journal of
Psychopharmacology that surveyed people who took hallucinogens
outside a clinical setting about their worst experiences. Some
people said they had gone through difficult or dangerous
experiences, some of which caused them to seek psychological
treatment later (that’s a small percentage of psychedelic use
cases, and many still said their experiences were important and
meaningful, but it’s worth being aware of).

But in a clinical setting, a high percentage of volunteers
reported that the experience was one of the most meaningful
they’d ever had in their life, calling it spiritual, something
that inspired reverence and increased their overall life

Most compelling was the fact that this substance appeared capable
of reliably and consistently inducing what are known as “mystical

These profound effects were so powerful that eventually,
Griffiths and other researchers decided to try psilocybin on
people struggling to cope with anxiety about the end of life
because they’d been diagnosed with a life-threatening illness or
disease like cancer. As he told Business Insider, we don’t
have a good way to treat the existential anxiety and depression
which is prominent in cancer patients and doesn’t respond well to
traditional treatment.

Psilocybe Pelliculosa Mushrooms

Pelliculosa mushrooms


Yet a single dose of psilocybin did seem helpful, in a
profound way.

The researchers gave patients a dose that was about 20mg of
psilocybin for a 70kg or 154 pound person. Griffiths’ previous
work has shown that people who have “bad trips” frequently take
more, a median of 30mg (approximately 4g of dried mushrooms). It
takes about 20 to 40 minutes for people to start feeling the
effects. Patients listened to music during their experience.
Griffiths says their playlist includes a mixture of classical
music, including Henryk Górecki, Bach, and Beethoven; Indian
chant, including Russil Paul’s Om Namah Shivaya; new age work;
and world music. They’re studying the “best” music for the
experience. And the effects of psilocybin fade after about 4
hours, one of the reasons researchers like to work with that
instead of LSD, which can last up to 12 hours.

Afterwards, patients talked and wrote about what they’d gone

Even six months after the experience, 80% of the 51 participants
in the JHU study showed significant decreases in depression and
anxiety, as measured by what’s considered a gold standard
psychiatric evaluation. The NYU team says that between 60% and
80% of their 29 participants had similarly reduced anxiety and
depression 6.5 months after a single psychedelic trip.

These findings correspond
with the results
that have appeared from these and other
pilot studies on psilocybin so far. These studies on treating

depression and anxiety related to cancer
have been
promising enough that researchers have begun small
studies on using psilocybin
to treat more common forms of
depression. And so far, those results have been encouraging.

Traditional medicine for these conditions is taken over time,
with side effects, and often isn’t much better than a placebo. In
this case, one dose seemed able to make a huge difference.

Griffiths says that one way psychedelic researchers have
characterized this is like the inverse of PTSD. With PTSD, one
terrible experience can change the way the brain causes a person
to perceive the world, with long-lasting effects. This is like
the opposite of that, a single meaningful experience that people
highly value and has transformational enduring effects.

“I don’t think we have any models in psychiatry like that, it’s
more like a surgical intervention,” Griffiths said on the press

Still, it is early in the research process. Hundreds of people
have now safely received doses of psilocybin, but the drug is
still considered a Schedule 1 drug by the Drug Enforcement
Agency, meaning it legally has no currently accepted medical use.
Any researcher will tell you that before they can truly say
psilocybin is a safe and effective drug, it needs to get through
the strenuous FDA approval process.

And with psilocybin and other psychedelics, there’s still a
massive unanswered question, one that we may be far away from
understanding: How do they work?

human brain connectome
Human Connectome Project, Science, March

Mystical experiences in the brain

We know that people who take psilocybin and other hallucinogens
(in these studies, participants consume synthetic psilocybin, not
the mushroom form) report that they have mystical or spiritual
experiences, things they consider significant. But we don’t know
what causes those experiences.

As Griffiths explained to me, we still don’t know what in the
brain is responsible for consciousness itself. We don’t really
have a good way to scientifically characterize the things that
transform consciousness.

“We’re at very primitive levels of understanding deeper
experiences of this type,” he says.

We have theories. One interesting one has to do with a network in
the brain known as the default mode network, something we
associate with self-referential thought, thinking about
ourselves. In depressed people, activity in this brain network
goes way up, perhaps due to some sort of self-obsession or
rumination associated with depression.

But at certain times, activity in this network drops. Meditation
seems to be associated with a strong drop in brain activity in
this network, which seems to correspond with the idea of ego
dissolution that is the goal of some meditative practices,
according to Griffiths, who says he actually became interested in
studying psilocybin because of his long-standing meditation
practice, which made him think about consciousness and the
meanings of spiritual experiences (though he says he was
initially a skeptic about hallucinogens). Psilocybin seems to
cause a drop in default mode network activity that’s very similar
to that induced in certain meditators.

shrooms brain networks

of the brain connections in the brain of a person on psilocybin
(right) and the brain of a person not given the drug.
Other researchers have found that psilocybin’s activity enables
new connections across the brain.

of the Royal Society Interface

But the induced mystical experience is so profound that Griffiths
thinks that decrease in activity can’t be all that’s going on.

“I’m very suspicious of simplistic stories,” he says. Even people
who don’t really find the experience “mystical” still seem to
have the re-organization experience in the brain that changes
their perception of the world, something that seems beyond
explanation so far. Even harder to understand are the long term
changes caused by the drug.

Looking forward

The patients in the studies published December 1 were all dealing
with cancer-related end of life anxiety, and for now, it should
be stressed that those are the only people who we have some idea
of how psilocybin affects in a clinical sense.

elderly aging old man walking

The two studies had relatively similar designs, though there were
some differences. There was more of an organized psychotherapy
component to the NYU study and the people that observed the
participants were trained therapists. In the JHU study, which
involved more participants, some of the observers were
psychologists, others had no formal training.

In both studies, participants had two interventions, one with a
full dose of psilocybin and another with a sort of placebo. NYU
used niacin, a form of vitamin B, as a placebo. JHU gave
participants psilocybin both times, but once was a very low
non-psychoactive dose, 1mg/70kg instead of 20mg. Griffiths says
that since participants knew they were going to be getting
psilocybin both times, they had some ability to measure the
significant difference between the times patients expected to
feel better because they’d “taken psilocybin” and the times
they’d actually had the full psychedelic experience.

And, while these are the largest studies of their type so far,
they’re still pretty small.

Researchers say they’ll need to see similar results in a larger
number of hundreds of patients dealing with end of life anxiety,
most likely from cancer at first. Griffiths and Ross both said
that they expect other studies will then look at other patients
dealing with potentially terminal illnesses and existential
anxiety, though there is definitely a chance that if psilocybin
proves effective in these cases, it could work for other cases of
depression and other sorts of anxiety. They’re beginning to
design trials for that research now.

“This is just a long and continuing process,” says Griffiths.
“When I initiated this research, most of my colleagues were
skeptical … people thought I had gone a little nuts … now I
get calls all the time from students who are familiar with what
I’m doing and say, ‘I want do that.'”

“I would think in time, whether it’s 10 years or 20 years, we’re
going to have learned how to optimize the use of these compounds
and we’re going to have really good models for using them
therapeutically,” he says. “Some of this past baggage will fall

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