From Newsgroup: alt.history.what-if

A growing number of medics think they could be.


Steve Shorney is a serious man, quiet and thoughtful. But the first time
he took psilocybin he could not stop laughing. rCLIrCOve never felt so much joy,rCY the 64-year-old says, recounting his participation in a clinical
trial of the active ingredient in magic mushrooms. rCLIt was the most extraordinary experience. I spent a lot of that session laughing in astonishment. All those big questions that one tends to ask about the
meaning of life, the universe and everything rCo those questions were
answered in the most colourful, psychedelic way you could imagine.rCY

ShorneyrCOs second trip, two weeks later, was less happy. rCLIt was pretty dark,rCY he says. rCLI spent a lot of the time crying. I had to deal with
the sort of things that one spends a lifetime avoiding or suppressing.
The drug invites you to go in there and deal with it. That is not easy
to do. It was pretty scary.rCY

Shorney, a father of two who lives with his wife, Jane, in Surrey, has struggled with depression and anxiety for most of his life. The former broadcast journalist had tried counselling and antidepressants, to no
avail. rCLThe world was a flat, grey place,rCY he says. rCLThere wasnrCOt a lot
of joy.rCY

And then three years ago he applied to take part in a trial of
psilocybin at Imperial College London. He was accepted and arrived at a
room in Hammersmith Hospital. rCLThey really did their best to set it up nicely. It was a typical hospital room that had been disguised. There
was a lovely reclining bed with big fluffy pillows and they lined the
walls with forest scenes.rCY

After a cup of tea, he took five little pills, closed his eyes and,
flanked by two therapists throughout the six-hour trip, drifted into
another world. rCLThe immediate impact was rCo wow. There really are no
words to describe it. It just blows the lid off the reality that you know.rCY

Psychedelics were never intended as a party drug. Albert Hofmann, a
Swiss chemist, developed LSD in 1938 as a circulation booster and, five
years later, inadvertently discovered its psychoactive properties when
he accidentally ingested some of the substance he was working on.
Hofmann was always puzzled by its adoption as a recreational drug rCo his accidental first trip, and subsequent self-experiments, revealed a
terrifying aspect to LSD. rCLA demon had invaded me, had taken possession
of my body, mind and soul,rCY he wrote in his book LSD: My Problem Child.
But when he awoke the next morning he felt reborn. rCLEverything glistened
and sparkled in a fresh light. The world was as if newly created. All my senses vibrated in a condition of highest sensitivity, which persisted
for the entire day.rCY

Hofmann, who went on to identify and then synthesise psilocybin as the
active ingredient in magic mushrooms, believed his creation had huge therapeutic potential for psychological conditions. Combined with psychotherapy, he wrote, these drugs could help patients rCLperceive their problems in their true significancerCY.

Yet fate rCo at least for the next few decades rCo would take the drugs in quite a different direction. rCLSince my self-experiment had revealed LSD
in its terrifying, demonic aspect, the last thing I could have expected
was that this substance could ever find application as anything
approaching a pleasure drug,rCY he wrote.

Psychedelics rCo acid, mushrooms and mescaline rCo became a symbol of 1960s hippy culture. The beat poet Allen Ginsberg described psilocybin as a rCLpsychic godsendrCY, the Beatles sang Lucy in the Sky with Diamonds and tripping became synonymous with the summer of love, opposition to the
Vietnam War, turning on, tuning in and dropping out.

Richard NixonrCOs rCLwar on drugsrCY followed and by the early 1970s psychedelics were banned on both sides of the Atlantic. Drugs were
driven underground, but they didnrCOt go away. Generation after generation sought new mind-bending experiences.

The 1980s and 1990s rave scene adopted Ecstasy rCo it had originally been developed to control bleeding rCo as its drug of choice. In 1992 the
Scottish acid house group the Shamen immortalised it in the hit
Ebeneezer Goode (rCLEs are good, Es are good, herCOs Ebeneezer GooderCY). Ketamine, an anaesthetic used on American soldiers in Vietnam, then
became a popular alternative, musically chronicled by the Chemical
Brothers in their 1997 track Lost in the K-Hole and by the rock band PlaceborCOs 2001 song Special K.

Now, though, psychedelics and other related drugs, such as MDMA and
ketamine, are being reclaimed by the medical profession in a bid to
tackle the mental health epidemic.

One in six British adults live with some form of a common mental health problem, such as anxiety or depression. This quiet crisis has a huge
impact on individuals, on families and on businesses. Mental health
problems cost the UK economy -u118 billion a year, mainly in lost
productivity and work absence, according to a recent study by the London School of Economics and Political Science and the Mental Health
Foundation. That is equivalent to 5 per cent of UK GDP.

Doctors, of course, already have drugs they can prescribe. And prescribe
them they do, in ever-increasing numbers. Antidepressants rCo mostly
selective serotonin reuptake inhibitors (SSRIs) rCo were doled out to 8.3 million people in England alone last year, up more than 5 per cent from
7.9 million in the previous year. But roughly a third of people who take
these drugs see no benefit and many end up trying two, or three, or even
more different medications before they are classed as having rCLtreatment-resistant depressionrCY.

This, a growing number of psychiatrists believe, is where psychedelics
can play a role. Earlier this month the UK start-up Compass Pathways
published the results of the biggest randomised control trial conducted
into psilocybin. The study of 233 people, led by KingrCOs College London
and published in The New England Journal of Medicine rCo the worldrCOs most influential medical journal rCo suggested that Albert Hofmann may have
been right all those years ago. The researchers found that, three weeks
after taking a single capsule containing 25mg of a synthetic crystalline
form of the drug, nearly a third of patients were in remission from depression. These participants had each suffered with their illness for
years, having experienced an average of seven previous depressive
episodes. They had all tried two to four different antidepressants in
the past, without success.

As with any drug, there are side-effects. As Hofmann found, a bad trip
can be terrifying. The Compass researchers had to sedate one patient who
had a frightening episode. Nadav Liam Modlin of KingrCOs College London, a psychological therapist who worked on the trial, says these experiences
are often an intrinsic part of the treatment. rCLEffective psychotherapy
and healing requires encountering or going towards challenging
experiences. We work with participants to develop trust, not only in the therapist, but also in themselves to navigate and actually make use of challenging experiences.rCY

Patients with a history of psychosis have been excluded from the trials
for fear it may make their symptoms worse. Some patients became
suicidal, although this may be part of their underlying condition rather
than a result of the drug itself. These drugs are generally thought not
to be addictive, though overuse can lead to a build-up of tolerance.

Next month Compass is to start two bigger trials, involving a total of
946 people, in an attempt to establish definitively just how effective
the drug is, as well as to quantify the risk of side-effects. By 2025,
the company hopes, it will have enough evidence to apply for medical
licences from drug regulators around the world.

Companies are waking up to the fact that, if they can crack the problem,
there are huge profits to be made. Some 100 million people globally are thought to suffer from treatment-resistant depression. And so, bit by
bit, psychedelics are being reclaimed from the hippies and the ravers.
They are going mainstream.

And it is not just psilocybin that holds potential, and not just
depression that could be treated. Trials are underway of MDMA to treat
former soldiers with PTSD; trial results of a new formulation of
ketamine for depression are expected in the next month;
dimethyltryptamine is being trialled for alcoholism and depression;
psilocybin is being explored for anorexia and fibromyalgia; and
ibogaine, a powerful psychedelic that can induce a 48-hour trip, is
being studied as a way to overcome opioid addiction.

rCLThere is a lot going on,rCY says Professor Robin Carhart-Harris, one of
the pioneers of the psychedelic renaissance. He led the first trials of psilocybin in London rCo including the one in which Shorney participated.
If clinical trials go as expected, within two years he believes the
first licence will be granted. rCLThat will really be the watershed moment
for psychedelic medicine,rCY he says.

And that moment is badly needed. Conventional antidepressants,
Carhart-Harris says, are not meeting our needs. rCLItrCOs not a good enough curative action. Some people are helped, but the way theyrCOre helped is a
bit superficial.rCY He cites his former mentor, Professor David Nutt rCo the former government drugs adviser who said that there was rCLnot much differencerCY between taking Ecstasy and horse riding rCo who describes
SSRIs as rCLincubating against stressrCY. Carhart-Harris says this
incubation can make people more resilient. rCLBut the cost of that is
people say theyrCOre not really living. They have to live two years to experience one rCo life is muted somehow, emotion is muted.rCY

Psychedelics work in a completely different way. Instead of taking the
edge off pain, they force people to confront it head on. rCLIt begins with
an opening and a loosening of the mind,rCY Carhart-Harris says. rCLThe
action is one of insight rCo revelation, self-understanding, perspective change.rCY

rCLMental illness is acquired rCo you are certainly not born with it,rCY he continues. While some people may have an innate rCLvulnerabilityrCY or rCLsensitivityrCY, it is the rCLvicissitudes of liferCY that trigger the descent
into mental illness, he says. And those illnesses are each characterised
by rCLentrenched ways of thinkingrCY. Whether it is addiction, anxiety, depression or an eating disorder, mental illness is marked by
ruminations rCo a circular, repeated pattern of thinking. In other words, people get stuck in a rut. rCLTo shift someone out of that rCo thatrCOs the target.rCY

So how do psychedelics work? How do they knock people out of their rut?
For millennia we have struggled to understand and describe the brain,
and even now scientists have barely scratched the surface. But they have
come up with several frameworks that may explain the action of psychedelics.

Neuroscientists say these drugs act on receptors in the brain that
co-ordinate the processing of sensory information as it streams in via
the eyes, the nose, the ears and the skin. The firing of these receptors influences how that information is filed and processed, and this
triggers an emotional response.

The consultant psychiatrist Dr James Rucker of KingrCOs College London,
one of the researchers on the Compass psilocybin trial, says: rCLIf you
put people in an imaging scanner and you look at the way different bits
of the brain talk to each other, then you find that the brain becomes
more chaotic under the influence of psilocybin. That may seem like a bad thing, but it isnrCOt rCo it happens every night when you dream and itrCOs when new connections are formed. Bits of the brain that donrCOt normally
talk to each other start talking to each other.rCY This, he says, creates
a rCLwindow of opportunityrCY in which psychological therapy becomes much
more effective.

Hofmann described the result of this neural plasticity as a rCLdreamlike staterCY involving rCLan uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of coloursrCY.

Many users refer to this as a spiritual or mystical experience. Shorney
says of his own trip: rCLI spent most of the time in an extraordinary
other dimension. But I was also aware of being there in that room. I was
fully conscious of that.rCY

Some people describe these drugs as hallucinogens because of the visions
they trigger, but Carhart-Harris says this is not quite accurate.
rCLPeople donrCOt classically hallucinate under these substances,rCY he says. rCLGenerally speaking rCo but not always rCo visions do tend to be a prominent aspect of the experience. They tend to have their eyes closed and have
these dreamlike experiences. But itrCOs not like they open their eyes and
see green goblins.rCY

Some scientists have tried to create psychedelics that operate without
this trip, these visions. But Carhart-Harris is sceptical. rCLIrCOd stick my neck out and say that is the mechanism,rCY he says. The trip rCo the psychedelic experience rCo is essential, as is psychological support and supervision during the process. rCLI think itrCOs a misunderstanding of how psychedelic therapy works to think you can divorce the drug from the
therapy and get away with it. ItrCOs wishful thinking.rCY

Another way to frame the process is via classical Freudian
psychoanalytic theory. In these terms, someone undergoing a psychedelic
trip is able to bypass the rCLegorCY rCo the part of the subconscious brain that is concerned with rationality. The ego builds up defence mechanisms
rCo repressions and neuroses. And in some people these defences can become unhealthy. Psychedelics strip them away.

Carhart-Harris stresses that ketamine and MDMA do not quite work this
way. These drugs are rCLpsychedelic-likerCY, he says, but not true psychedelics because they do not involve the same dreamlike visionary
state. Ketamine, for example, can involve a rCLdissociativerCY experience,
in which users feel disconnected from their body, but scientists
disagree on whether this is an essential part of the drugrCOs
antidepressant mechanism.

There is a simpler way to explain the process rCo and this is thought to
apply to both psychedelics and rCLpsychedelic-likerCY drugs rCo and that is brain healing. rCLChronic stress degenerates neurons,rCY Carhart-Harris
says. rCLWhether itrCOs depression, schizophrenia, bipolar disorder, significant adversity or trauma, they show cortical thinning.rCY
Psychedelics rCo and other drugs such as ketamine rCo rCLreplenish the synaptic connections that have atrophied under stressrCY. People under
severe strain are rCLjust trying to hang on in thererCY, Carhart-Harris
says. When the brain goes into defence mode, in other words, connections harden, neuronal branches are stripped away and thought processes get
stuck in a rut. rCLWhat the psychedelic gives you is something more than
just getting by,rCY he says. rCLItrCOs like you can come back and start exploring again. You can come out of your shell.rCY

Kirk Rutter, 52, took psilocybin at Hammersmith Hospital in 2016, as
part of an early trial led by Carhart-Harris. His mother, June, had died
five years previously and he was enveloped in grief. A recent
relationship had broken down and, to make matters worse, his housing
situation was terrible, with neighbours who made him feel unsafe in his
own home.

rCLI had tried antidepressants and done a year of talk therapy,rCY says Rutter, an IT technician from east London. rCLBut the main issue for me
was being stuck in this really terrible grief.rCY Despite his deep
depression, he was very nervous about taking psychedelics. rCLPeople were saying, rCyYou donrCOt want to take psychedelics, it will screw up your brain.rCO I had terrible anxiety and I thought it probably wouldnrCOt work.rCY

The first thing he noticed after taking the tablet was the music. rCLIt
just sounded amazing,rCY he says. Greg Haines, the Grateful Dead, opera, classical, ambient music rCo it all sounded incredible. rCLI wonder if I was hearing music with different parts of the brain that wouldnrCOt normally process it. I donrCOt know. But the music sounded novel in a way that you donrCOt normally experience.rCY

This is an illustration of how psychedelics change the structure of
nerve cells, causing them to sprout more branches and spines. The blue
cell is a normal one, while the other has been treated with LSD
This is an illustration of how psychedelics change the structure of
nerve cells, causing them to sprout more branches and spines. The blue
cell is a normal one, while the other has been treated with LSD

A few years previously someone on a holiday had suggested to Rutter that
he should think about rCLletting gorCY of his grief. rCLI was, like, rCyHow dare
you? How dare you?rCO rCY he says. But under the influence of the drug he started processing his bereavement in a different way. rCLI went through
the grief in a soft way,rCY he says. rCLIt gave me a bit of a realisation about how I was rCyinrCO the grief and needed to change my proximity to it.rCY

Rutter replayed memories of sitting next to his mother in her hospital
bed. rCLI wasnrCOt hallucinating but the memories were much more available, much more real than just recalling it. I donrCOt really know how to
explain it, but it was a very loving, nonverbal exchange of presence.rCY

And now? rCLI feel good. IrCOm all right. I feel better. Those ruminations I had, those constant negative thoughts, are gone. I had periods over the pandemic when I recognised my thinking was a bit blocked and I realised
I was going in that direction again. But I could think, rCyI recognise this,rCO so IrCOve stayed positive. And I could let go of the grief rCo not entirely, but I realised letting go was not the same as letting go of
the person, and those little realisations were a big turning point.rCY

Over the past decade pioneering scientists rCo Carhart-Harris, Nutt and
many others rCo have shown that psychedelics may have a role to play in
the mental health crisis. The process of rehabilitating these drugs has
begun. But if psychedelics are ever to achieve their full potential, if
they are ever to be used routinely on the NHS, or by other health
services around the world, it will depend on investors to bring them to market. It will depend on Christian Angermayer.

TThe 44-year-old German billionaire, via his company Apeiron Investment
Group, has a stake in nearly 300 patents for psychedelics, with another
125 pending. He helped found Compass Pathways rCo the UK company leading
the latest psilocybin trials rCo and in 2018 created Atai Life Sciences,
into which he has plunged much of his personal wealth. Between them, the
two companies have eight compounds in clinical trials, from MDMA and
ibogaine to dimethyltryptamine.

Angermayer, casual in a black Ralph Lauren hoodie and dark blue jeans
despite the swish corporate setting of his London office, says everyone
told him that he was crazy when he first began investing in
psychedelics. rCLPharma is just a very boring distribution machine,rCY he says. rCLTheyrCOre never willing to take any risks. We took the risk early
and they all want to partner with us now. But actually itrCOs a very risk-protected play, because we have the anecdotal experience out of the Sixties, and we maybe also have the solution for the biggest problem of
all time rCo mental health.rCY

AngermayerrCOs mantra is that these drugs should stay illegal. rCLWe want to get all these psychedelics approved as medications,rCY he says. rCLWe took
the decision early on not to go down the cannabis route and try to lobby
for legalisation, but to go down the medical route of clinical trials
and applying to the FDA [Food and Drug Administration]. For most of
these treatments we want it to be not just a prescription medication,
but a treatment you can only take while you are with your therapist.rCY

This approach has earned him criticism. rCLThere are people who say, rCyYourCOre a hypocrite, why donrCOt you advocate for making these substances broadly available? You are taking God-given molecules and putting
patents on it. You are evil.rCO rCY

Angermayer, though, insists these were never meant to be recreational
drugs. rCLThe Sixties were an anomaly. If you look back at 10,000 years of
the history of psychedelics among religious cults, it was always highly regulated.rCY The shamans in the Amazon and the Greek Eleusinian Mysteries cult, he says, insisted on strict rules when followers were taking psychedelics.

rCLThey always said certain things,rCY he says. rCLFirst of all, this is not an escape drug. You do it maybe just once in your life, maybe once or
twice a year, but not more often. And you have to take the learnings of
your trip and integrate them into your life. There was always an intense preparation rCo you had to fast, you had to go to the temple. And this job
was done by priests and shamans. Now itrCOs done by psychotherapists and psychologists.rCY

Angermayer is an unlikely champion of these drugs. He is teetotal rCo
growing up, he never touched a drop of alcohol or experimented with
drugs. rCLI was a hypochondriac. I thought if I drank beer it was going to ruin my brain cells.rCY

A childhood prodigy, Angermayer started a tutoring business at the age
of 14. By the time he left school at 18 he had earned 100,000
deutschmarks, the equivalent of about -u45,000. At just 19, as an undergraduate at the University of Bayreuth, he founded the company
Ribopharma with two of his biotech lecturers. The start-up focused on
the emerging field of gene silencing rCo a technology that is now being
used on everything from cholesterol to hereditary disease rCo and in 2003
it merged with the US pharmaceuticals company Alnylam in a $43 million
deal. rCLThat was the foundation of my own investments,rCY Angermayer says.

It was after meeting a neuroscientist at a dinner party who told him
about the research of David Nutt that Angermayer became interested in psychedelics. Then, in 2014, he was on holiday with friends in the
Caribbean. rCLThey were, like, rCyHey, werCOre doing mushrooms tomorrow, and we know you donrCOt want to, but just so you know what werCOre doing.rCO And I said, rCyYou know what, IrCOm going to do it.rCO rCY

Angermayer smiles at the memory. rCLIt was hands down the most important
thing in my whole life. It was amazing. I thought, rCyHoly shit, if itrCOs [giving] this amount of positivity to me as a happy, healthy person, I
can totally see what it could do for others.rCO And then my business mind kicked in.rCY

Initially he was warned off investing in the sector. rCLEvery single
person said, rCyEnjoy it, but donrCOt talk about it rCo itrCOs going to ruin your career.rCO rCY He persisted and eventually met Ekaterina Malievskaia
and George Goldsmith, the married couple with whom he founded Compass.

Angermayer still takes magic mushrooms twice a year, travelling to the Netherlands or South America, where it remains legal. rCLWhen the ego is
gone the interesting thing is that there is something else there,rCY he
says. rCLSome call it a soul, the inner voice, your subconsciousness. But
that is when you start really learning about yourself, facing yourself.rCY

How will any of this work in the cash-strapped, resource-poor NHS, where
it is difficult enough to get a GP appointment, let alone an entire
dayrCOs treatment in a cosy candle-lit room accompanied by two therapists? Carhart-Harris admits this will be a challenge. rCLWhat an upgrade from
five minutes in the doctorsrCO consulting room and out with a prescription
for escitalopram [a type of antidepressant]. But it will be expensive.
We donrCOt know how much, but some estimates put it at $20,000 per patient.rCY

Ekaterina Malievskaia, the co-founder of Compass, insists the company is already in discussions with the prescribing watchdog Nice, as well as
the South London and Maudsley NHS Trust, to ensure psilocybin is
affordable for the NHS.

However, Dr Ravi Das, a neuroscientist at University College London,
says he doubts whether these treatments will ever be adopted by the NHS
in their current form. rCLYou generally wouldnrCOt get that level of
intensity for an intervention unless it was major surgery,rCY he says.

Angermayer points out that there may be an answer to the costs issue.
One of his companies, Perception Neuroscience, is trialling a new
formulation of ketamine called arketamine, which scientists believe will
have neuroplastic healing effects rCo at least in the short term rCo but without the dissociative psychedelic-like experience of ketamine itself. rCLWhat you really want is the rapid acting, antidepressant effects of ketamine, but without the dizziness,rCY Angermayer says. rCLThat is the holy grail because you could have it for home use, and that really brings the
cost down.rCY

Trial results are due within a month. If successful, and the results
show there is no dissociation, a self-injector trial for home use will
follow.

And what about Steve Shorney? Has he been cured? rCLThe depression is
still there,rCY he says. rCLThis is not a magic bullet. But IrCOve learnt to deal with it. I think for me the most value in the experience was it
showed me another reality. If things get bleak and IrCOm feeling down, it
has become a point of reference for me. IrCOve seen how much better things
can be.rCY


Ben Spencer



The drugs and their potential uses

Psilocybin
Found in more than 200 species of mushroom. First isolated by the Swiss chemist Albert Hofmann in 1958.
Effects: psychedelic visions
Potential uses: depression, anxiety, addiction, PTSD, cluster headaches,
OCD, AlzheimerrCOs, anorexia, fibromyalgia

MDMA
First synthesised by Anton K||llisch in 1912, it was initially developed
to control bleeding but then found a different use as the party drug
Ecstasy. It is not a classical psychedelic rCo it does not trigger a
visionary or dreamlike state rCo but it causes feelings of
depersonalisation and elation.
Effects: euphoria, depersonalisation
Potential uses: PTSD, narcolepsy, ADHD

Ketamine
First created in the 1960s, it is a common anaesthetic and still used in
our hospitals today. Not a true psychedelic, it can still induce a
strong dissociative effect rCo a feeling of floating, or an out-of-body experience. The drugs giant Janssen started marketing esketamine rCo a formulation of the drug rCo as a nasal spray in 2019, but it is not funded
on the NHS. A new formulation rCo arketamine rCo which is thought not to
have the dissociative impact, is being developed as an at-home injection. Effects: dissociation
Potential uses: depression, anxiety, bipolar disorder, addiction,
chronic pain, arthritis, fibromyalgia

--- Synchronet 3.21d-Linux NewsLink 1.2