The TGA’s approval of MDMA and psilocybin is a story of hope for these much maligned substances and patients with treatment-resistant PTSD and depression.

The news that the Therapeutic Goods Administration (TGA) is going to make MDMA (3,4-methylenedioxymethamphetamine) and psilocybin available for prescription as Schedule 8 drugs in Australia in 2023 has already caused more than a few looks askance, locally and around the world. Even among the OGs of advocacy in Australia, this was unexpected.

How could that be? In most public discussions of such drugs in Australia, both are erroneously identified as illicit drugs of ‘high lethality’, portrayed ubiquitously in the tabloid press as the demonic products of choice of a feckless generation of consumers, who have an over-fondness for smashed avocados.

For those whose reading extends to the science, a different story is emerging. It’s a story of substantial hope for the repurposing of these much maligned substances, and the potential benefits their therapeutic use could bring to patients.

The argument that such drugs can be nothing other than harmful was never true.

Overseas, both MDMA and psilocybin have been undergoing a rehabilitation as therapeutic agents. This ‘re-medicalisation’ is supported by some emerging and heavy-duty science and scientists. Both drugs are being increasingly advanced for medical conditions resistant to normal treatment — refractory post-traumatic stress disorder (PTSD), in the case of MDMA, and refractory depression, with psilocybin.

In fact, when MDMA was originally banned in 1985, it was already being used as a medicine by psychiatrists. The attempt to have it prohibited by the United States Drug Enforcement Administration, ostensibly because of its seepage into the recreational community and unpublished allegations about neurotoxicity, was originally thrown out. It required an overrule by presidential decree, by one of America’s original drug warrior presidents, Ronald Reagan, to derail its progress as a useful medicine.

Then US president Ronald Reagan addressing a press conference in 1985. Photo: Mirrorpix/Alamy Stock Photo

MDMA and connection as therapy 

MDMA is a peculiar creature, even for experts whose life’s work is the study of drugs. At first glance, it looks like it should be an amphetamine with hallucinogenic properties, but under the bonnet, it is much more than that. Discussion of its workings at a neurotransmitter level is beyond scope here, but by way of action, it helps to form a connection between therapist and patient. It is sometimes called an ‘entactogen’, promoting affiliation and social behaviours, as well as reducing anxiety and leading to what is often a very deep state of personal reflection.

For a generation of festival-goers, MDMA has been used informally as a way forming a connection, under lights and music with fellow revellers. That very unique action is what seems to make it useful in therapy. It allows patients to revisit the very deepest of fears, underpinning the events behind their PTSD, and engage in meaningful therapy with their psychiatrist. The MDMA ‘facilitates’ the therapeutic engagement, and unlike many of the drugs we use in medicine, only a short course seems to be required for that benefit to occur in a group of patients for whom nothing else has worked.

So far, the results have been so promising that both the US’s equivalent of the TGA, the Food and Drug Administration, and the Innovative Licensing and Access Pathway in the UK, have fast tracked trials as a breakthrough therapy.

Psilocybe bohemica mushrooms. Photo: Afanasiev Andrii/

Mushroom medicine reboots the mind 

Psilocybin is a slightly different kettle of fish. It is the prodrug — an inactive compound that must be metabolised in the body to activate — of a potent hallucinogen naturally found in a variety of mushrooms, many which grow in Australia. These mushrooms had sacred and perhaps therapeutic uses in prehistory, but were banned from use in the US in 1968, and subsequently by the 1971 UN Convention on Psychotropic Substances.

But in the last few years, hard-hitting academic centres including Johns Hopkins University in the US  and Imperial College London have been looking at its therapeutic potential for the treatment of conditions such as refractory depression and grief associated with terminal conditions. Again, it seems that treatment with only a few doses allows a ‘reset’ of dysfunctional ways the injured mind has fallen into thinking, and out of which it cannot find its way.

Through observation of clinical outcomes in patients, coupled with the very latest in functional imaging of the human brain over the course of treatment, this research has successfully showed the regaining of normal responses and concrete changes in brain function. This is massively exciting for those delving into the complexities of the human mind — not only is psilocybin providing a therapy, but it is also unlocking the secrets of who we are and how we ‘work’.

From marginalisation to medicine 

The ‘re-medicalisation’ of drugs historically considered illicit is happening around the world, perhaps most explicitly with cannabis in the last decade. In the case of MDMA and psilocybin, a number of factors might have been behind this.

Firstly, the success of traditional treatments for refractory PTSD and depression have been average at best — as the name suggests, they are ‘refractory’ to treatment. These conditions are not just any other illness, they are quietly and desperately lethal, every bit as much as many other medical conditions that receive much more attention and funding.

Particular groups that are affected by PTSD — people who have returned from service in the Australian Defence Force, and first responders to the growing number of natural disasters in Australia, for example — are groups that people ‘want’ to help. The current management of these conditions is outrageously expensive, running to billions of dollars over the lifetime of patients. So in a perfect storm, readily available life rafts in the form of novel therapies such as MDMA and psilocybin were always going to be seized upon.

Associate Professor David Caldicott. Photo: Tracey Nearmy/ANU

There have been concerns expressed about the safety of these substances. Fingers are pointed at deaths at music festivals and elsewhere as evidence of the foolishness of this treatment approach. But even our 16th century Father of Toxicology, Paracelsus (famed for his “the dose makes the poison” refrain), recognised that the circumstances of the ingestion of drugs and poisons determined outcomes.

The majority of harm caused by illicit MDMA occurs as consequence of misidentification, excessive dosing, contamination of product, mixing or interactions with other drugs, or the environment in which the product is taken. Radically different from these scenarios, the TGA’s change to classification of MDMA and psilocybin allows for a tightly selected group of patients to be administered a fixed dose of pure product under close medical supervision. As newly classified Schedule 8 ‘controlled drugs’, their therapeutic use will require all of the documentation, secure storage and chain of control of other drugs we are used to handling.

This is not the time for advocates to crow about this battle victory in a wider war.

As to the long-term effects? Well, in simple terms, probably millions of young people have used ‘ecstasy’ since it was banned in 1985. We have yet to see the generational impact of any significant widespread neuropathology, or harms to the brain. It seems unlikely then that several doses of MDMA administered under close medical supervision would result in significant harm.

What’s next on the list of substances likely to be brought back from marginalisation, into medicine? Ketamine is already being used in a repurposed fashion, from an anaesthetic drug to the treatment of depressive illness. LSD is under investigation for the treatment of generalised anxiety disorder. Ibogaine and ayahuasca are lining up for their time in the sun.

The argument that such drugs can be nothing other than harmful was never true, and those that promoted it were either being dishonest, or knew so little about them as to be disqualified from participating in policy debates. This view represented an absolutism in belief that bordered on the theological, and there was always going to be a reckoning.

But this is not the time for advocates to crow about this battle victory in a wider war. These developments are part of a shift in a worldview and debate about drugs and drug use; one that has been conspicuously absent and avoided in both family dinner table discussions and federal debate. That such decisions are generating open frank discussion on the topic of drugs policy in Australia, and the very overdue need for reform, is a matter for celebration in its own right.  

Top image: Ali Bakhtiari/Unsplash

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