Pubdate: Sun, 08 May 2016
Source: Age, The (Australia)
Copyright: 2016 The Age Company Ltd
Author: Konrad Marshall


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