‘What Happens Next?’: Should We Decriminalise Psychedelics?

Dr Susan Carland:
Welcome to another episode of What Happens Next?. I'm Dr Susan Carland. This time we are looking at the therapeutic potential of using psychedelics to treat mental health conditions such as depression and PTSD. What would happen if we were to legalise psychedelics and what opportunities will we miss out on if we don't?

Paul Liknaitzky:
In Australia, we're just coming through the birth canal now in the space of psychedelic mental health treatment.

Meaghan O'Donnell:
Part of the reason that psychedelic research is hard to do is because it's illegal. It's an illegal drug.

Arthur Christopoulos:
Our society is going to be a mess in 50 years if we keep going down the path that we're going down, especially if we are relying on existing medications the way we have been using them today.

Dr Susan Carland:
But first let's take a historical and anthropological look and see why governments have been so reluctant when it comes to drug decriminalisation.

Dan Lubman:
So my name's Dan Lubman, I'm a professor of addiction studies at Monash University, and the director of the Monash Addiction Research Centre here. I'm also executive clinical director of Turning Point, a national addiction treatment, research and education centre based in Melbourne.

We have a policy that we inherited from the US which is largely prohibitive, and really goes back to the time essentially around Richard Nixon where very strongly he said that he's going to have a War on Drugs and start to get tough on crime –

Richard Nixon:
America's public enemy number one in the United States is drug abuse. In order to fight and defeat this enemy, it is necessary to wage a new, all-out offensive. I have asked the Congress –

Dan Lubman:
And since 1971, the US has spent $1 trillion on its War on Drugs campaign.

Richard Nixon:
This will be a worldwide offensive, dealing with the problems of sources of supply, as well as Americans who may be stationed abroad, wherever the –

Andrea Whittaker:
Decriminalisation or criminalisation is a matter of, if you like, the social and legal fashions of the time.

Dr Susan Carland:
Andrea Whittaker focuses on the social and cultural context of legal and illegal drug use through anthropological and ethnographic studies.

Andrea Whittaker:
Well, as a medical anthropologist, I look at the way in which we have different cultures around things to do with health and illness, and within medical anthropology, we talk about drugs as objects of power, okay? So if you look at it that way then what it means is that each culture has different drugs that it uses in different ways. And so cross-culturally, our drug use differs. So really, I guess what I'm saying is that at the end of the day, drug use is relative and it's a very human activity. There's no culture on earth that doesn't use drugs. A really important concept in anthropology of drug use is the idea of setting and set. And so setting is the sort of environment in which drug use takes place, and set is the sort of mindset, if you like, with which you approach that drug use. But we can learn from other cultures in terms of their moderation of drug use through the use of ritual and through the use of guides.

Dr Susan Carland:
What does drug decriminalisation actually mean?

Andrea Whittaker:
Well, it actually means that you're just changing the social legitimacy of a drug. Not so long ago, cocaine was used as a pick-me-up for bored housewives or for getting sleepy children out of bed.

Dr Susan Carland:
Oh my God.

Andrea Whittaker:
So – and the same with things like morphine as well, and, of course, Coca-Cola used to have coca in it, which is the base from which cocaine comes from. So our attitude towards those drugs have changed enormously over time. Likewise there's things which are now considered fine, which in the past were considered quite scandalous as drugs. So we've changed over time and so it really is just a matter of the social legitimacy of those drugs. Paul Liknaitzky: Some of those factors, I think, are generational. Views on drugs are shifting.

Dr Susan Carland:
Paul Liknaitsky is a joint research fellow within the Turner Institute and the Department of Psychiatry at Monash University, and head of the Clinical Psychedelic Research Lab.

Paul Liknaitzky:
Psychedelic medicine was the next big thing in psychiatry through the ’50s and ’60s. I think there are probably a number of factors that have led to this situation we see now, which is a very important moment in the history of psychedelic psychiatry. The conversation's becoming more mature and nuanced. The old Nixonian and Reagan story of all drugs being bad except for alcohol is just changing now. We've got research now that really shows that among the substances people consume, alcohol is the most damaging of them all. Also a number of brave souls commenced research in the space, or recommenced research in the space. There was a little island of research in the early ’90s and then the beginnings of what we think of now as the ‘psychedelic renaissance’ kicked off around 2000, very slowly at first, and it's been growing exponentially over the last few years. And the weight of evidence, the compelling nature of the results, I think, is something that just can't be ignored. So I think there are a number of scientific clinical and sociopolitical factors that have contributed to the situation we're in now, where psychedelics are really the next big thing in psychiatry again.

Dr Susan Carland:
For the people that don't know, what's MDMA and what's psilocybin?

Paul Liknaitzky:
Sure. So MDMA is what is considered ecstasy or molly on the streets. And unfortunately, given the illegal drug markets, often what is thought to be MDMA does not contain much MDMA. So pure MDMA is quite different in a number of respects than what a lot of people think of as ecstasy. It's not ecstasy per se, but it's what's referred to as an empathogen. It's a drug that includes both stimulant properties. So it stimulates people, it's got amphetamine qualities in it, and it also makes people feel more empathic and connected and open and warm, a little bit like oxytocin might.

So MDMA, combined with a form of specialised psychotherapy, has been used in the treatment of PTSD – post-traumatic stress disorder – and that research program in terms of the psychedelic field is the furthest along than any other. There's an organisation in the US called MAPS, the Multidisciplinary Association for Psychedelic Studies, and they have been leading the charge in that space, and just recently published the first of two, what are called ‘phase three’ studies, which are the final kinds of studies you need to do before you can register a new medicine.

Psilocybin is the active ingredient in magic mushrooms. So we use synthesised and pure psilocybin in the trials and that is what's referred to as a classical psychedelic, so different than MDMA, which is often considered a psychedelic in the broad use of the term, but it's not a classical psychedelic. It's got some psychedelic qualities and some other kinds of qualities, but psilocybin is very much a classical psychedelic, a bit like its cousin LSD, which was the most prominent psychedelic in the first wave in the ’50s and ’60s.

And so psilocybin has very different effects than MDMA, some overlapping effects too. It produces some substantial alterations to conscious awareness, everything from perception to emotion, to the way you think and what you do, can be dramatically altered. Importantly, it produces a fundamental altered state of consciousness, which is a fascinating and remarkable phenomenon. And in terms of clinical efficacy, it has a number of effects that are thought to be very useful in the treatment of disorders of rigidity or perseveration, like addictions and depression and other disorders.

And these include pretty dramatic alterations in perspectives on your life or your relationships or yourself. And these perspectives, importantly, are deeply felt. They're not abstracted or just cognitive. They're really embodied and emotional and really felt, and for various interesting reasons, those new perspectives, which include realignment with your priorities in life, seem to drive change. They drive change in attitudes, in affect, in behaviour.

And the changes that we see in these early trials go quite far out. Some of the trials have followed up patients six months, a year, in some cases, even a few years later, and a majority of participants have a very different experience of life and are doing things very differently after just a short treatment programme. Just one to three dosing sessions and some psychotherapy around it. So there's some very interesting questions around how this works, of course, given the half life of these drugs is in the order of hours.

Dr Susan Carland:
What happens if we, as a species, don't try to investigate the world of psychedelic psychotherapy? If we just continue down the same path that we are with the medicine and treatment that we're using?

Paul Liknaitzky:
Certainly it would be a massive missed opportunity to not engage with and support and further develop both psychedelic assisted therapies and the fundamental sciences on psychedelics. Given the limited funding to-date – recently funding has kicked into the field dramatically over the last 18 months – but prior to that there was very limited funding and the trials were small and slow. And so I can say we're still at an early phase of research in this field, but the results to-date have been nothing short of remarkable.

Dr Susan Carland:
Arthur Christopoulos is Dean of Monash University's Faculty of Pharmacy and Pharmaceutical Sciences. He's leading the team working on new research into the use of illicit drugs such as MDMA and psilocybin to treat mental illness. He explains how little new science there has been in this area, and why it's worth trialling whether these drugs could be effective as faster-acting, shorter-term treatments for mental health conditions, including PTSD, depression and anxiety.

Arthur, welcome. Imagine we continue along the same path we are in Australia, with our approach to the medications we use for mental illness. Say nothing changes. What does our society look like in 50 years?

Arthur Christopoulos:
Our society is going to be a mess in 50 years if we keep going down the path that we're going down, especially if we are relying on existing medications the way we have been using them to date. There are different paths we can go down in terms of why. One situation is – one scenario, I should say – is the science itself behind these medicines is more than 50 years old. Most of them were discovered by accident, and if you look at the latest productivity commission and findings, for example, it was pretty damning in what it said around the medicines. They're overused, they're overprescribed. The only thing you're essentially guaranteed are adverse effects. It's hard to come off, and their effectiveness is 30 to 40 per cent irrespective of the kind of neuropsychiatric disorder you're trying to treat.

Dr Susan Carland:
So why are we not innovating? When it comes to – mental health is such an issue in our society. I think 4 million Australians suffer from some sort of mental illness out of a population of 26 million. That's a significant percentage. Why is this not a matter of urgency?

Arthur Christopoulos:
Basically because big pharma have burnt themselves out over the last say, 10 years, and the pendulum has pretty much swung away from neuropsychiatry. There've been a lot of clinical trials that failed and so they pretty much walked away.

Dr Susan Carland:
So let me interrupt you there. When you say they've done a lot of clinical trials that have failed, as in, they've tried new things, it hasn't worked, and they've decided there's nothing to be done here?

Arthur Christopoulos:
There's not enough return on their investment to be done because of the approach they've been using. I think the issue is, as I said, most of the drugs that we have to-date were discovered from the ’50s through... Prozac was discovered in 1972. People forget that. It made it into the market in the mid- to late-’80s and blew up in the ’90s, and of course everyone's been calling it a wonder drug. Most of the drugs that have come since have been variants of the Prozac approach to SSRI, so they’re called selective serotonin reuptake inhibitors, but the science is quite old.

This goes all the way back to the beginning of neuropsychiatric drug discovery. Most of these medicines were discovered for something else, right? Then we found that they had psychiatric effects and for a number of people they helped, but we essentially – this is just my personal take on it – the way I look at it is we essentially reverse-engineered what the medicine does by accident, or it’s been discovered by accident, to say that this therefore is underlying what causes the disease. And I think that mismatch is what really has not driven the type of innovation we need to be driving. And so people have been looking under the same spotlight for so long. Of course, nothing has come that's been any better and they've pretty much walked away for now until someone comes up with something different.

Dr Susan Carland:
So what do you want to see happen?

Arthur Christopoulos:
I want to see us take some obvious examples of where there are other psychoactive substances, where there's plenty of evidence that they're doing something already, and then work out how they're working and also progress them forward into trials.

Dr Susan Carland:
So like what? What's working?

Arthur Christopoulos:
Well, we have some... There's been a renaissance, I would say, since the mid-2000s in the space of the psychedelics.

Dr Susan Carland:
Okay. I can hear alarm bells going off around the country with you saying that. Why do you want everyone to be high, Arthur?

Arthur Christopoulos:
I don't. I don't. So, first of all, we're not talking about cannabis, but I know what you're referring to. No, I think if I take a step back and get rid of the baggage in the language, and think about the type of, what I refer to as neuromedicine, you'd like going forward. What you want is not to be medicated, right? What you want is a medicine that contrasts to all pretty much all existing psychiatric medicines. You want something that has an actually fast onset, the effect comes on quickly, right?

Dr Susan Carland:
Yes. Which I'm guessing current medications –

Arthur Christopoulos:
Do not. That's right. Okay. Especially when you look at antidepressants, you've got to be taking for weeks before you start to see any sort of effect kicking in. You want something that is fast onset, you want something that you only take for a little bit, and then you want to facilitate non-medicinal psychotherapy to help the patient in remission and go on, continue.

And the commonality of existing agents that we have seen that have that effect are things like classic psychedelics, which are hallucinogenic drugs, like psilocybins and the LSDs, MDMA, which is actually, I consider, not a psychedelic drug. It's actually an amphetamine derivative, but it has a similar effect. And even things like ketamine, which is an anaesthetic, right? What you find in all of these instances is they are fast onset, they change your consciousness to the state where you are then receptive to processing your thoughts and having post-medicinal psychotherapy. And because you would only ever use them in a clinical setting like that, you only have a couple of sessions, especially with things like the psychedelic drugs and the MDMAs.

And that's kind of at the moment, the impetus towards trying to see if medicinal therapy to assist non-medicinal psychotherapy is the new type of treatment modality we should be moving towards for treating mental illness, especially treatment-resistant mental illnesses.

Dr Susan Carland:
So when you said that we'd only need to take it for a short period of time, I wondered if it meant because it was in some way curing something or reconfiguring the brain. But it actually sounds like what you're saying is it just opens a space in the mind where – for people who may be really struggling with significant depression, for example. When you're in that place, you cannot consider that there would be any benefit in therapy, that nothing will change, that nothing will help.

Arthur Christopoulos:
That's right.

Dr Susan Carland:
So it simply opens a curtain in the mind to allow something else to work.

Arthur Christopoulos:
Absolutely. As we study this further, we may learn more about when and where the place for these sorts of medicines would be going forward more than once, twice, three times. But the current thinking and the innovation, the approach, is exactly that.

If you take a step back, if you look at something like an SSRI, which people take for depression and they're on it for a long time and in fact, I know a lot of people on SSRIs. I know very few that have been able to come off them, for instance. Now that works in a different part of the brain. It works in a similar transmitter system. It's a chemical called serotonin, which is really important, but it works in another part of the brain where it's almost like – There's a psychopharmacologist, a very famous one in this field, called David Nutt, and he's got a really good analogy. With an SSRI, it's like putting a plaster cast around the part of the brain called the limbic system that helps whatever. So basically you put the plaster cast around this part of the brain and you try and wait for the stress to heal.

Psychedelics work in a different part of the brain, our cortex, alright? And there, they actually open up exactly what you said, those thought processes, they almost fracture the cortex and re-allow new connections to be made in your thought processes, which then allow you to process the memories of trauma and such. It's a totally different part of the brain and a totally different mechanism. And there is emerging evidence that these things may also engender this thing called neuroplasticity, which may allow new connections to be formed.

Dr Susan Carland:
So where has this been done successfully elsewhere that's made you think this could be an option?

Arthur Christopoulos:
I think there are a number of groups around the world doing this for me. One of the big breakthroughs was work from Johns Hopkins, a guy called Roland Griffiths who's very well known in this space. He was one of the first people to really – it was around the mid-2000s – use psilocybin first in people that were healthy people, but also later there's been a lot of work that was done in end-of-life anxiety situations, where just one session with these sorts of things changed people's perspective on their anxiety.

I also have a very good friend called Dave Nichols. Now, Dave is probably the world's best psychedelic chemist. He's been doing this since the 1960s and he's been a great friend and mentor. And he also was the first person to switch me on, so to speak, to the fact that these new trials had begun, with end of life patients. So that study, Roland's work, was a real turning point. And since then there have been other groups like Rick Doblin, who formed MAPS, which is the Multidisciplinary Association for Psychedelic Scientists, I think. And a lot of people really... And they're funding a lot of work. So I think that the mid-2000s was the turning point. But a lot of that is still being funded essentially by philanthropists that want to make a difference. What I think the –

Dr Susan Carland:
Not the big pharmaceutical companies?

Arthur Christopoulos:
No, no. I think big pharma are just sitting here waiting this out. They're waiting to see how this is going to pan out because the analogy that a lot of people make, and I think it's probably the wrong analogy, is this is like medicinal cannabis. We've seen what's happened with medicinal cannabis and it's been a huge boom and a huge industry, but psychedelic drug research is going to be a different type of treatment model.

But a lot of companies, smaller companies, are already springing up looking to whether to fund this or to see where this goes. But it's a different treatment paradigm and pharma know this. They know there's something to this, but they're just going to wait to see how it pans out. And one of the reasons, I think one of the big reasons, is generating the type of clinical trial data that will get these things registered. That's the next challenge and that's going to be tricky.

Dr Susan Carland:
But why would big pharma not want to do this? Claim the patent...

Arthur Christopoulos:
Well, there are two reasons. One is you're not going to be able to patent something like a psilocybin or an MDA that's old, but if you find new chemical matter, of course, you can do that.

The second one is I believe they would need to patent or regulate or register not just the drug, but the associated psychotherapy that goes with the medicine. And that's a different model to how most other drugs on the market. You patent the drug as a drug itself.

Dr Susan Carland:
Yeah. This is the endpoint.

Arthur Christopoulos:
This is the endpoint, yeah. And I think, I believe part of the regulation issue is one, doing the trials to the rigour. That's going to get them registered, but it's going to have to include the therapy associated with that.

And then there's the economic argument. People are going to say, “Well, what's the cost benefit? When you combine the drug with the therapy, two or three sessions, is it worth our while? It may cost X amount of dollars. Will it be reimbursed? Will it get Medicare and all of that?”  Those things are to be sorted out.

So there's a regulatory and economic argument. I think the economic ones are going to pan out, because if you – the cost to society of the burden of mental illness is going to far outweigh that.

Dr Susan Carland:
Yes. What would you say to the people out there that are hearing what you're saying, and all they can think is, “This is a disaster. These drugs are prohibited for a reason, this is not a good idea.”?

Arthur Christopoulos:
“Prohibited for a reason” is an interesting and loaded term, because I think the reason that these substances is prohibited has got nothing to do, really, with what their pharmacology suggests, alright? Psychedelics in particular, there is almost no evidence whatsoever that they can be addictive in any way. They do not cause withdrawal effects, they do not cause self-seeking reinforcing behaviour. That's been very, very well established.

Dr Susan Carland:
What negative side effects do psychedelics have then?

Arthur Christopoulos:
Well, obviously in an uncontrolled environment, if you've got a consciousness alteration, you can have an accident. You can hurt yourself, right? Secondly, there are concerns that in predisposed individuals, they may induce a psychotic-like state. That's been well looked at, but interestingly not conclusively proven. But what we're talking about, going to the first part of your question, is these things won't be a disaster, because the way they would be used is only under clinical supervision. Only once, twice, three times. Then no drug in between.

I'll give you an analogy. Fentanyl, right? Fentanyl is heroin, but 10 times more potent. It's literally 10-times-more-potent heroin. You know what the problems that fentanyl causes and that's way more dangerous out there, but the way we use it in this country – and I know, because a couple of years ago I lost a kidney and I had to have an operation and they gave me fentanyl and it was great – but they only gave it to me in the operating theatre. As soon as you get out of the operating theatre, you don't get fentanyl anymore, right? So if you have it in a clinically controlled environment, there's no harm there.

Dr Susan Carland:
What would you do to protect against that risk, as you said, that in some people LSD may cause a psychotic episode? How would you mitigate against that?

Arthur Christopoulos:
All patients going into any trial –and even if the trials are successful, it becomes a therapy – they're pre-screened as you do with anything else. If there is actually any incident of a personality disorder or predisposition toward psychosis, you will not be allowed to take this substance. Similarly, the most common side effects of these, both the psychedelic drugs and the MDMAs for instance, are alterations in your blood pressure. Your heart rate, your temperature a little bit. And so people, for instance, that would have difficulty with the uncontrolled blood pressure would also be not taken into a clinical trial. It's no different to, if you got uncontrollable hypertension, they're not going to give you Sudafed, which is going to raise your blood pressure. So it's about the clinician screening the patient before they allow them into the therapy. That's key.

Dr Susan Carland:
I started our chat by asking you what our future looks like if we don't change things. Imagine now that you go back to your office and you get an email from the federal government and the TGA. They've sent out a joint email to you and said, “Great news. We've decided that this really is an area we want to invest in. We'd like to really ramp out clinical trials.” What do we look like in 50 years then?

Arthur Christopoulos:
Well, that will be... Well, to get that right, given that the government are the ones that email me, the TGA are the ones that emailed me, we have the opportunity to basically set up an end-to-end clinical chain centre. Sorry, I'll take a step back. An end-to-end consortium or centre where we have discovery development, formulation and clinical trials in this country. It's going to be a game-changer. I think most of the work to-date has been largely funded by philanthropy around the world, largely focused on clinical trials, around psilocybin and MDMA. It makes sense. You need a starting point. But imagine if you can turn this into a full neuropsychiatric drug discovery industry, but including the therapy models as well as the drugs.

I look at them as antibiotics for the mind. You only take them for a little bit to get off other drugs and that's what the future would look like to me. We would have a whole new trained workforce where these people know the psychotherapy aspects of the counselling. We would be looking at mental illness in a different way, because you don't want to be taking meds, but if you had to take meds, this is the way to go.

And the rest is really value-adding to all the other things that the governments have already put in place. All the things, as I said, about patient access gateways, collaborative centres, more trained counsellors. All of that. The missing piece has been the medicinal bit.

Dr Susan Carland:
Do you think a big part of what it comes down to is that MDMA and psychedelics just have bad PR?

Arthur Christopoulos:
Yep.

Dr Susan Carland:
If it were anything else...

Arthur Christopoulos:
Yep, yep. Bottom line, yes. As I said, if you take away the baggage and if you take away the terminology and you look at these things – I mean, let's take the psychedelics. As I said, these substances on their own, they're so safe. In fact, I'm not aware of any deaths associated with an overdose of a psychedelic drug, unless they're an accident. Someone took a big dose and they jumped off a building for instance, and I'm not trying to be... That's true. In a clinical environment, there's never been any issue associated with that.

The psychosis link has been studied, but has not been definitively proven and in fact, the therapeutic index of psilocybin, that means how much do you have to take relative to how much works to cark it, for want of a better term, is a thousand. Whereas, you know, Panadol is 10, right? And then secondly, if you look at MDMA, MDMA is an amphetamine derivative. We're already giving amphetamine derivatives for ADHD, for narcolepsy. It's not that different to Ritalin, and it's not that different to Adderall and yet they're being used. So why aren't we looking at it in those terms?

Dr Susan Carland:
Arthur, this has been so interesting. Thank you so much.

Arthur Christopoulos:
Oh, my pleasure.

Dr Susan Carland:
In our next episode, we speak to experts working in the field about some of the early trials using psychedelics, such as MDMA and psilocybin. Hope you'll join us next time on “What Happens Next?”.