Pubdate: Sun, 08 May 2016
Source: Age, The (Australia)
Copyright: 2016 The Age Company Ltd
Contact: http://www.theage.com.au/
Details: http://www.mapinc.org/media/5
Author: Konrad Marshall
SAFE TRIP
What if LSD could treat PTSD, or magic mushrooms could help you quit
smoking? Overseas research is advanced, but trials of psychedelic
drugs can't get approval in Australia. Are we missing out on cures?
Konrad Marshall reports.
When Martin Williams' research plan was first rejected by an ethics
committee in 2012, he understood why.
The medicinal chemistry researcher could see some valid sticking
points. For one, the psychiatrist attached to his detailed protocol
didn't quite have the requisite clinical trials experience.
Fair enough, Williams thought. Still, there were also less defensible
reasons for the experiment being turned down. Troubling reasons.
Williams was surprised, for instance, when the independent review
board "overstepped their remit" by citing a lack of obvious funding
for the proposal. And he was left shocked when they refused to enter
into any dialogue around where the money would come from. Instead of
judiciously questioning and assessing the merit of the
trial engaging in to and fro over the details they seemed to just
take his $5000 application fee, cut contact and move on.
That's disappointing, Williams thought. "But we were able to learn a
few things, make some changes," he said. "For next time."
Next time was only a few months ago, in December last year. By then
Williams, 51, had brought together a more bona fide team of potential
researchers and also made particular note of the proposed funding
model for the research, which would test a promising but bold new
method of therapy for people suffering from acute posttraumatic
stress disorder.
He was confident and happy to submit what seemed like a "watertight"
plan to the ethics committee of a large university in Melbourne, yet
the rejection letter this time was far more blunt. It wasn't a
letter, either, so much as an unofficial pre-emptive email from the
deputy vice chancellor of research.
"It basically said 'forget it, this university is not interested',"
Williams said. "I didn't bother remonstrating too loudly. I expect
the same might happen with any Australian university."
It is an expectation based solely on the drug Williams is proposing
to use in his trial, namely MDMA or methylendioxymethamphetamine -
which is often a component in the party drug ecstasy but has also
been used recently around the world - along with an array of other
psychoactive substances or "psychedelic drugs" - to great therapeutic effect.
You see, Williams, a Yarra Glen winemaker, pilot and autodidact, is
something of an outlier in Australian medical research. He is neither
an established or esteemed name, but nor is he without experience.
He has an honours degree in chemistry and biochemistry from the
University of Sydney along with a PhD in medicinal chemistry and
pharmaceutical science from Monash University at Parkville.
He was until recently a postdoctoral research associate there,
publishing papers with titles such as Backbone and side chain 1H, 15N
and 13C assignments for the oxidised and reduced forms of the
oxidoreductase protein DsbA from Staphylococcus aureus.
Yet his most notable role is as president of PRISM or Psychedelic
Research In Science and Medicine, a small not-for-profit lobbying
group that would see global gold standard research replicated in
Australia, using everything from "acid" (LSD) and "magic mushrooms"
(psilocybin) to cure anything from end-of-life anxiety to nicotine addiction.
The idea is far less far-fetched than it sounds.
Over the past decade, such research has been ramping up all over the
world at significant institutions from Switzerland to Canada and Tel
Aviv to London. In the United States, schools including Johns Hopkins
Medicine, NYU and UCLA have begun using psychedelics in randomised
controlled trials to treat alcohol dependence, depression and anxiety.
Others are exploring the potential benefits of mescaline (an alkaloid
derived from the Peyote cactus and used in religious ceremonies by
Native Americans for millennia) and dimethyltryptamine (found in the
shamanic Peruvian brew known as Ayahuasca).
But perhaps the most revelatory and well-chronicled therapeutic new
frontier is the use of MDMA to treat PTSD. In 2000, it was used to
treat female victims of sexual assault in Madrid. In 2001, the target
group were South Carolina survivors of childhood abuse.
Later studies have involved police and emergency responders all of
whom were well-served by the drug, which is not used as a
prescription medication but rather administered in a clinical setting
and followed by hours of intense psychotherapy.
The pure synthetic compound reduces activity in the amygdala (where
fear is processed) and increases activity in the frontal lobe (where
people put ideas in context), meaning patients are able to look
closely at traumatic events without being paralysed by fear.
The subjects are screened and carefully prepared, and they are guided
by a therapist with whom they are better able to bond, again, thanks
to the drug.
The experience has virtually nothing in common with a warehouse dance
party - except of course in the chemical sense.
"The therapy itself achieves the positive outcomes - the MDMAis only
an adjunct," Williams said. "There's no magic effect that cures the
patient - it just enables them to get to the root cause of their
condition and work through that."
A group in the United States known as the Multidisciplinary
Association for Psychedelic Studies (MAPS) has already guided its
MDMA research through phase two trials. With good safety and efficacy
data, they are preparing a submission to the Federal Drug
Administration, and have begun fund-raising for phase three trials -
the final step before potential widespread US approval in 2021.
Their process began 30 years ago, in 1986, when a man named Rick
Doblin founded MAPS. Since then, he said, more than 1000 people have
taken MDMAin clinical research, and more than 5000 papers on
psychedelics and various therapies have been published on
MedLine the US National Library of Medicine.
MAPS has also offered $25,000 in matching funds for any study launched locally.
"It's a little bit hard for me to understand what the resistance is
in Australia. It should be easier for PRISM a simple regulatory
challenge," Doblin said. "But how much of a follower does Australia
want to be, and how much of a leader?"
Williams in fact designed his protocol with the help of MAPS, to
mirror their widely published research, which has already been
subject to countless international review boards: "We're not
groundbreaking in any way other than we're trying to do it in Australia."
He intends to trial the drug here on veterans of war, many of whom
have tried cognitive behavioural therapy and anti-depressants and yet
been "treatment resistant". The test group could just as easily be
victims of rape, assault, or even family violence.
But the target group is not the issue so much as the culturally-laden
term "psychedelics" (which actually has a straightforward and good
faith meaning, namely "manifesting the mind").
One Melbourne psychiatrist with decades of experience counselling
victims of trauma said he was stunned by the "establishment
resistance" to such a promising treatment option.
"There is an immediate reaction of fear," he said, on condition of
anonymity. "The public perception needs to be altered, but it has to
be done slowly and gradually. I think we have to tread warily."
That psychiatrist, who is also a lecturer at a large university, has
tried establishing his own small-scale study using MDMA, but the idea
was quickly rebuffed by an academic ethics committee as "too dangerous".
"The reaction is almost medieval in some ways," he said. "We're
reasonable people with good reputations and a considerate, highly
controlled proposal. It's not a slaphappy operation. We should be
welcomed in, but we're not and it's unfortunate."
Professor Suresh Sundram, head of the psychiatric neuroscience
research program at Monash University and a scientist with no grudge
against or interest in such work - identified four major factors
contributing to the dearth of local study in this area.
First, he said, there is fear on the part of researchers, around the
response they might expect from ethics committees who would likely
("and rightfully") view such studies with extreme caution.
Second is the impact such research might have on a scientist's
reputation. "They may not be received with the same respect," Dr
Sundram said. "They might be seen as marginal and extreme."
(Doblin says he is baffled by this: "Treating patients who are
suffering with a life-threatening illness? You think that would be
good for your reputation.")
Third, funding bodies could perceive the work to be "too radical",
meaning any trial would require the safety net of a large
philanthropic contribution. (Perhaps $500,000 would be enough to
launch a small study; a larger trial might cost $5 million.) And
finally, the experts already studying depression or PTSD may not be
as enamoured with psychedelics as they are current alternatives.
(Researchers, Dr Sundram noted, often become "one-eyed about their drug".)
Professor Patrick McGorry, executive director of Orygen, the National
Centre of Excellence in Youth Mental Health, can attest to that
notion, and said he had not even heard of the psychedelic research
being done around the world.
The "big thing" in research right now, he said, was ketamine (also
often abused as a party drug), as well as work being done with
cannabidiol to treat anxiety in young people. (Shrooms and Lucy in
the Sky with Diamonds are just not on his radar.)
"Don't get me wrong - my immediate reaction is curiosity," he said.
"We do need to explore new treatments that examine the interaction of
biology and psychology. But like most researchers, we need a
benefactor to give us some blue sky funding."
One final consideration is that the value of working with
psychedelics may be far greater for developing our fundamental
understanding of brain function than in treating psychological
disorders. At Imperial College in London, healthy volunteers were
recently given LSD after which researchers used fMRI and
magnetoencephalography to see what activity took place in the brain,
and came away amazed at what they saw. David Nutt, a former drugs
adviser for the British government and a senior researcher on the
study, told media that the work had profoundly deepened our
understanding of consciousness: "This is to neuroscience what the
Higgs boson was to particle physics."
Dr Alex Wodak, president of the Australian Drug Law Reform
Foundation, is one person you might expect to throw his full weight
behind the therapeutic use of illicit drugs - but you would be wrong.
His interest rests more in work like that above, from Imperial
College, in finding out more about how the drugs work before coming
up with how they might be used.
"The more we know about the mechanisms," he said, "the more likely we
are to get dividends."
Dr Wodak just returned to Australia following a week at the United
Nations in New York, attending a general assembly on the World Drug
Problem. He noted that research will be hard to establish given the
seemingly unending "War on Drugs". Little has changed since 1971 when
Richard Nixon famously coined that term, and then branded Timothy
Leary "the most dangerous man in America". (Leary, once a
psychologist at Harvard University, was evangelical about the
potential of LSD.)
America, Dr Wodak said, frames the way drugs are regarded around the
world, and no administration has shifted from the prohibitionist path
set by Nixon 45 years ago.
Not coincidentally, most research into illicit substances is related
to the amount of damage they can do, rather than the benefits they might offer.
The same is true locally, where there are actually no formal legal
prohibitions against academic and clinical research using
psychoactive substances. Research with "scheduled compounds" can take
place with the permission of the local health ministers.
Dr Stephen Bright, a clinical psychologist specialising in alcohol
and other drugs and lecturer at Curtin University (and member of
PRISM), points out that such research has already been done in
Melbourne. The catch is that the research (so far) supports the
"dominant pathogenic narrative of drugs", which limits discussion to
the harm they can cause. The only recent local research using a
psychedelic, he points out, was a 2010 study at Swinburne University
entitled The effects of MDMA and methamphetamine on car driving
simulator performance, cognitive skills and mood states, designed to
measure how impaired people become when using such drugs. "But
there's very little potential for psychedelic drugs to be abused in a
clinical setting," he said. "They're low toxicity, and they're
non-dependence forming. They're not taking it and going to a rave."
Fiona Patten, the Sex Party MP, has been lobbying for drug law reform
for some time, mostly on health and civil libertarian grounds, and
believes an attitudinal shift is overdue. "The beauty of many of
these substances - which is not great for anyone wanting to make
money from them - is they don't need continued use.
"It's not like getting on Prozac for the rest of your life - the
drugs are only used a few times for psychotherapy, and they can't be
patented, which may be why 'Big Pharma' is not interested."
In some ways the problem is financial but the solution could be as
well. The legal and ethical impediments to cannabis research, for
instance, fell away rapidly after a BRW rich lister donated $33
million to the University of Sydney specifically to look at medical
uses for pot.
Williams can only sit back and hope a similar white knight emerges.
He will keep nudging the change along, too. Within six months he will
be ready to submit his protocol to yet another ethics committee. The
ideal way things would play out?
An eminent scientist says, " yes, absolutely, I would love to do this
research with you".
A wealthy private benefactor says, " here's $500,000".
An ethics committee says, " looks good to us". The state health
minister says, " sure, you can import that compound from Germany".
Then PRISM would locate their subjects and get testing.
For Williams, that would sate his twin appetites for knowledge and
the desire to do something socially useful more so than standing at
a laboratory bench grinding away at the mysteries of biological science.
He believes an injustice has been perpetrated and a lot of good
denied to humanity in holding back this research for so long.
"I just feel that it's time to pick up the ground swell and turn it
into a wave of social change.
"At a time when society seems to be getting more and more restrictive
and scared, we need to take a stance," he says.
In the meantime he will pursue his hobby, building a Glasair IISTD
propeller plane in a little hangar at Lilydale Airfield.
That's the thing about Williams - he loves projects, and challenges.
In his former life as a winemaker and vineyard consultant, he used to
fly planes to meetings among the vines at Coonawarra and Tocumwal,
and has been making his own light aircraft for two years now.
He imagines it will be ready to fly within 12 months, perhaps at the
same time - hopefully, maybe - that his research dream takes off. He
can picture it now. The twin-propeller beauty will wait its turn
between parachute planes and cruising craft, between Piper Warriors
and Cherokees, then barrel down a thin airstrip on the rural-urban
fringe of the city.
After reaching top speed it will soar up into the blue under his
careful control.
And he will look down from on high, floating above the clouds, seeing
beyond the horizon.
It will be quite the trip.
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MAP posted-by: Jay Bergstrom