The ‘renaissance’ of psychedelic therapy in mental health

In his 1790 book, The Marriage of Heaven and Hell, poet William Blake wrote, “If the doors of perception were cleansed everything would appear to man as it is, infinite.”

Writer and philosopher Aldous Huxley went on to use the title The Doors of Perception for his 1954 autobiographical book, which explored the Englishman’s encounters with psychedelics.

American rockers The Doors, no strangers to altered perception themselves, took their name from the phrase in the mid-60s.

And according to the co-founder of psychedelics start-up Enosis Therapeutics, Dr Prash Puspanathan, the message still rings true about 230 years after Blake coined it.

“We all have these perceptual filters through which we see the world, and it’s always clouded,” he says.

“Anything that cracks open those perceptual filters makes us more permeable to the world around us, and allows us to see it through a completely different light and lens.”

That could be a paradigm shift from despair to opportunity. Or from knowing something logically, to finally feeling that freeing truth in your bones.

Or at least, that’s the idea.

But looking at the burgeoning global and domestic psychedelic sectors, the compounds don’t just open up the doors of perception. They also open up potential pathways to riches.

According to the believers, psychedelics such as mushrooms and MDMA (perhaps better known by the street name, ecstasy) offer a radical new way to treat treatment-resistant depression, anxiety and post-traumatic stress disorder (PTSD).

More than 600 trials have been completed and another 300 are under way around the world, according to law firm King and Wood Mallesons. Many are trying to figure out whether and how psilocybin, found in magic mushrooms, and MDMA, found in ecstasy, can be safely administered to deliver health benefits.

Others are also looking into ketamine, LSD and ayahuasca, a hallucinogenic tropical vine found in the Amazon, which can be taken as a drink for spiritual purposes.

The idea is that psychedelics can alter activity within the brain’s networks, delivering a profound change in perception and reducing excessive rumination.

Access to psychedelics is limited in Australia. Classed as a Schedule 9 substance, they are technically poisonous. However, psychiatrists can apply to the Therapeutic Goods Administration (TGA) to prescribe MDMA or psilocybin under the Special Access Scheme. The TGA has approved 12 applications for MDMA and five for psilocybin.

The drugs can also be used in clinical trials, but in December 2021, the TGA rejected calls to reschedule them as Schedule 8, or controlled substances.

Although it described the preliminary findings from clinical trials as “promising”, it warned that psilocybin still posed a “high danger for both acute and long-term effects if abused or misused”.

Despite the knockback, the sector is convinced that approval is coming within a few years.

Biotech and cannabis companies Little Green Pharma (the parent company of psychedelics company Reset Mind Sciences), Creso, Incannex and Emyria are developing psychedelics strategies, and have a combined market cap of $380 million.

The Australian government is also getting behind this, announcing in January last year that it would invest nearly $15 million into research into the use of MDMA, psilocybin and ketamine to tackle major depressive disorder, PTSD, and eating and addiction disorders.

“What is clear is that the Australian government and other governments around the world are investing significantly in this area,” says King & Wood Mallesons partner Suzy Madar.

“I suspect that there won’t only be one winner; there’s going to be different compounds, different treatment methods, different formulations. It’s not just a race to one finish line in this space.”

Madar specialises in intellectual property, an area she believes will be critical for companies that have invested significant amounts into exploring psychedelics.

“The particular compounds that we’re talking about here in most cases can’t be patented, so it’s the research around these molecules that is new and that is much more likely to be able to be protected in an intellectual property sense.”

She says drug exploration and development often occur in phases of exponential increases, and she likens the current psychedelics race to the huge advances in antidepressant research in the early 2000s.

“That was a very significant period in which the treatment options radically increased in number and the intellectual property protection went along with it,” she says.

“[Psychedelics] is obviously a very valuable industry and a space of very significant investment.

“It’s getting that intellectual property piece right and ensuring that any innovations are protected at a very early stage which will enable R&D companies and innovators to make sure that they can recoup on their very significant investments.”

Psychedelaissance

Shaun Duffy, CEO of Reset Mind Sciences, says a lack of development in the antidepressant space has sparked the “renaissance” of psychedelics.

“There hasn’t really been a breakthrough in mental health treatment since antidepressants first came onto the market,” says Duffy.

“And I think a lot of people who take them are frustrated that all they’re doing is just masking symptoms. So, I think there’s a real openness from people to consider a new treatment that might actually provide a more lasting benefit than just being on a pill a day.”

Reset Mind Sciences uses in-house cultivated mushrooms to develop synthetic psilocybin, and is working with the University of Western Australia on a clinical trial testing the use of the drug for depression. The trial has been submitted for ethics approval and the goal is to launch it next year.

Hancock Prospecting has invested $15 million in Little Green Pharma, which owns Reset Mind Sciences.

Duffy’s not the only one to use the word “renaissance” to describe Australia’s small but hopeful sector.

“It’s a commonly used term now,” says Josh Ismin, founder of the Daniel Petrie-backed psychedelics company, Psylo.

“It’s pretty amazing. Growing up in the ’90s at the height of the drug war, talking about this stuff was just completely a non-starter, and so to be in a world now, where I’m on a daily basis listening to podcasts, reading books by prominent academics who are talking about psychedelic research is just – it’s mind-boggling to me,” he says.

“The underlying issue that we’re looking to solve here is the challenge of a lack of solutions, with respect to treating a variety of indications, but most notably mental illness.”

Psylo aims to develop new psychedelics without the hallucinogenic effects, with a focus on MDMA-assisted therapy.

Debates

But surely the hallucinations are ... kind of the whole idea?

Not so, says Ismin. And this is the first of two debates splitting the sector.

“You have some folks who say that the intensity of hallucinations that people experience are directly correlated with the therapeutic benefit that they get from taking a psychedelic,” he says.

“Then there are other folks who say, ‘Well, we’re able to see ... the downstream effects of taking a psychedelic, and we can replicate those with compounds that do not induce a psychedelic effect’.”

Psylo is in the animal experimentation phase, working to discover if the compounds it has developed show promise as antidepressants, with a goal of human clinical trials next year.

Trials are already well under way over at virtual reality psychedelic start-up Enosis Therapeutics. The company is headed by Puspanathan, a medical doctor and former neuropsychiatry fellow at The Alfred Hospital in Melbourne, and Agnieszka Sekula, a biomedical engineer and scientist.

Puspanathan has been talking about psychedelic therapy for the best part of a decade – “way before it got fashionable”.

His business is built more around the value of the hallucinations, coupled with human-led therapy and virtual reality journeys designed to embed the radical learning that happens during a trip.

Enosis is working with Ovid Clinic in Berlin, a psychotherapy clinic, on a pilot offering psychedelic-augmented therapy, after conducting a study with Swinburne University and the Psychedelic Society of Belgium into using VR stimulation to anchor psychedelic-induced insights.

But he is clear on one big and uncomfortable truth – tripping out isn’t always easy. And in some ways, it shouldn’t be.

“People worry, ‘Well, what if I have a bad trip?’ That’s the point – it’s meant to be challenging, it’s meant to take you to your deepest, darkest places, it’s meant to confront you, when you face your biggest fears,” he says.

“It’s meant to teach you that you can work your way out of that little dungeon and emerge into the sunshine. It’s really hard work, and the idea that it should be this really smooth process that you just dive in, and you come out and there are fairies, and sparkles and dolphins – it doesn’t add up.”

He says the media, pop culture and advocacy groups are all guilty of pushing this narrative.

Puspanathan says he is glad the TGA made the call not to reschedule the drugs yet.

“You can suggest that the TGA has overstepped the mark by refusing to reschedule psychedelics because as a substance, psychedelics have such a low-risk profile,” he says.

“[But] psychedelics don’t exist in isolation, they exist as a process in psychedelic therapy.”

This is the second, more bitterly fought debate.

Puspanathan believes Australia doesn’t yet have the infrastructure and will not for another two or three years.

“The only way we get there is by more research, by clinical trials and clinical trials in which therapists can be safely trained. And that’s how we start to create that culture of academic excellence and quality assurance, within how you execute on psychedelic therapy.”

One group on the other side of the divide is the registered – if controversial – charity, Mind Medicine Australia.

Founded by opera singer Tania de Jong and her husband investment banker Peter Hunt, Mind Medicine Australia is the peak advocacy body pushing for psychedelics to be classed as a Schedule 8 substance.

If the TGA fails to reschedule the substances, Australians with enough cash will simply fly to countries such as the Netherlands, where psychedelic therapy is more readily available, says Hunt.

Those without the means will lose out, or turn to underground dealers. And, he adds: “It’s completely inappropriate for people who’ve got mental illness to try and make up their own minds about which therapist in the underground is safe.

“It needs to have that sort of licensing regulation around it, to make sure that the person who looks after the person with illness really does have that person’s interests at heart, and is properly qualified. And you’ve got no assurance of that when you go into the underground.”

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In September 2022, Four Corners aired allegations that Mind Medicine Australia had harassed a former employee and directed staff to underground psychedelic therapists.

The charity defended itself against the claims, and in August applied to the Federal Court to expose the identities behind two Twitter accounts critical of the group.

Mind Medicine Australia also offers a $9000 psychedelic therapy course. Those who complete it need to have some form of mental health credentials, such as in psychiatry, psychology and counselling.

But unlike therapists trained in clinical settings to administer psychedelics, the Mind Medicine Australia course uses holotropic breathing to simulate an altered state of consciousness.

“If you breathe in a certain way, you actually do go into an altered state, and you’re no longer in the present,” Hunt says.

“They use that as a way of enabling the students to understand what somebody on psilocybin is going to go through.”

The chief executive of listed drug developer Emyria, Dr Michael Winlo, uses the word “factions” to describe the structure of Australia’s psychedelic community.

Emyria has been working on medicinal cannabis for four years, before turning to psychedelics, and in particular MDMA. The Andrew Forrest-backed company has partnered with the University of Western Australia to examine the neurological effects of MDMA.

Forrest’s investment company Tattarang invested $5 million in Emyria in November 2021.

Winlo says Emyria is looking at how psychedelics can be altered to improve some features and remove others; for example, shorten the time of the trip from six to 10 hours to two to three hours.

Winlo believes rescheduling the substances will pave the way for more real-world studies, and notes that tightly controlled clinical trials can limit the generalisability of the outcomes to broader populations.

“We need an opportunity to demonstrate safety in the broader patient.”

Emyria is also working with Mind Medicines Australia to deliver a psychedelic-assisted therapy care program for sufferers of PTSD.

Winlo says the great challenge lies in developing scale: “How do we do this for not just 10 patients, how do we do this for 10,000 patients?”

Without TGA approval, that friction is going to persist.

“We feel really stuck in the crossfire too, because we’re trying to work with both sides,” he says.

“It’s certainly made us cautious about wading in and picking allegiances ... The turf wars on who should lead the research, and who’s legitimate here.

“The suspicion of commercial interests moving in is really heightened in this space too – it’s a really challenging environment. But we need all parties to be involved.”