For better or worse, Australia is suddenly at the cutting edge of the so-called psychedelic renaissance.
In February the TGA announced that MDMA (3,4-methylenedioxymethamphetamine, the main active constituent of ecstasy) and psilocybin (found in “magic mushrooms”) will be rescheduled, allowing them to be prescribed by psychiatrists as of July 2023.
This announcement was unexpected because only three months ago the TGA’s interim decision indicated that the rescheduling application would be denied.
This decision has propelled Australia into the forefront of the global movement to medicalise psychedelic substances, as the first country to formally recognise these substances as medicines.
What are the implications of this decision? How will it be implemented? And why are some people in the field – including us – concerned? The TGA’s decision, and further information provided since the announcement has left key questions unanswered.
What does the science say?
The findings to date about MDMA and psilocybin are certainly promising. A number of trials show that – in carefully screened patients, combined with psychotherapy and in a controlled environment – MDMA reduces symptoms of post-traumatic stress disorder (PTSD) and psilocybin reduces treatment resistant depression (and here).
We are clinicians and researchers in mental health and understand the desperate need for innovation in treatments to meet increasing needs. We are conducting trials of several new treatment approaches, including MDMA-assisted psychotherapy. Yet, given small samples in existing studies and a range of other limitations (and here), our view is that the current evidence is not yet sufficient to ensure safety if these methods are used outside of clinical trials.
What is changing?
MDMA and psilocybin are currently listed in Australia under Schedule 9 of the Standard for the Uniform Scheduling of Medicines and Poisons, indicating a prohibited substance that can only be used for research. Under the changes, both substances will receive bifurcated scheduling, with one listing under Schedule 8 for medicinal use under limited circumstances, and one under Schedule 9 for all other uses.
Under the Schedule 8 listing, both medications can be prescribed by a psychiatrist who has received approval via the Authorised Prescribers Scheme. The medications can only be used for PTSD for MDMA or treatment-resistant depression (TRD) for psilocybin. To obtain approval, the psychiatrist’s proposed treatment protocol – including safety measures – will be reviewed by a human research ethics committee and then by a senior officer of the TGA. Once approved by both, authorised prescribers will be required to report regularly on the number of patients treated and adverse effects experienced.
The Schedule 9 listing of MDMA and psilocybin as a prohibited substance will continue unchanged for all other purposes – including for use in clinical trials for indications other than PTSD or TRD.
How will this work in practice?
One surprising aspect of the TGA’s decision is the extent to which important details remain unclear. A critical question is whether these substances will be used in conjunction with psychotherapy. If so, what type of psychotherapy should be employed, and who is best equipped to deliver this?
This is important because all of the recent clinical trials published – on which this decision is reportedly based – use these substances not as stand-alone medications, but combined with intensive psychotherapy. Indeed, the rationale for use of MDMA and psilocybin as medications rests on the idea that they catalyse normal psychotherapeutic processes (hence “psychedelic-assisted psychotherapy”). This idea – that MDMA and psilocybin act to create space for psychological change – is a marked departure from the mechanisms thought to underpin the effects of other psychiatric medications.
There also remains ongoing debate (and here) as to the best psychotherapeutic approaches to be used in psychedelic-assisted psychotherapy. Some of the psychotherapy platforms used in existing trials draw heavily from methods developed in the “first wave” of psychedelic research, over 50 years ago. This means that they do not reflect current best-practice psychotherapy approaches. Some include components that are well outside of normal psychiatric boundaries, such as “nurturing touch”, potentially increasing patient vulnerability and risk.
All of this suggests that further research is needed to inform implementation.
Why is this change worrying?
Since the TGA’s announcement, some – including us – have expressed concerns. There are several aspects of this decision that give us pause.
A key issue is the lack of clarity around why the TGA changed course in the three months between the interim and final decisions. One phase II study was published supporting the potential short-term efficacy of psilocybin for TRD during this time. This does not seem a substantial enough change in the evidence to justify the new direction, raising the possibility that this decision was more influenced by lobbying and public pressure than evidence.
We are also concerned about the potential for widespread dissemination of these interventions before there is clear evidence of their efficacy and safety. While initial findings are promising, samples are small and highly selective. For instance, in the only phase III study to date, less than 7% of people volunteering for the study passed screening.
Broader implementation in more complex patients than those able to pass stringent clinical trial criteria will almost certainly alter the risk:benefit ratio. Given that up to 50% of people with depression do not respond sufficiently to existing treatments, large numbers of people may be eligible for psilocybin-assisted psychotherapy in particular.
In the month since the TGA’s announcement, Mind Medicine Australia, the advocacy organisation that applied for the rescheduling, has already contracted with a Canadian company to manufacture GMP MDMA and psilocybin for the Australian market and is setting up a network of pharmacies to dispense the medications. The group is also ramping up their training for psychedelic-assisted psychotherapy providers and providing a portal for patients to register interest in receiving psychedelic-assisted psychotherapy. This rapid action on behalf of Mind Medicine suggests that broad dissemination of these interventions under the new regulations is a real possibility.
What is the way forward?
Given the intense hype surrounding psychedelic medicine and increasing rates of mental ill-health in the community, we expect that GPs are already fielding multiple requests for referral to psychedelic practitioners.
GPs can play a key role in informing patients of the limits of existing evidence, in fostering realistic expectations, and in assessing for factors that may increase the risks of psychedelic treatments. For example, complex mental ill-health (i.e., comorbidities beyond TRD or PTSD – the norm in many clinical populations) may confer increased risk of negative outcomes. Patients with histories of psychotic illness, and those with close family histories of psychosis, are particularly likely to be at risk of adverse responses to psychedelic medications (for this reason these patients are excluded from clinical trials of psychedelic interventions).
Ideally, patients considering psychedelic treatments should have access to expert clinical care and existing evidence-based treatments for their mental illness as a first step. GPs referring patients for psychedelic treatments will also need to consider aftercare – there are currently no accepted guidelines for ongoing care following psychedelic-assisted psychotherapy. To some extent this will depend on the specific psychedelic treatment protocol being employed (i.e., the number of psychotherapy sessions offered following MDMA or psilocybin-assisted sessions).
For better or worse, Australia is suddenly at the cutting edge of the so-called psychedelic renaissance. The many remaining questions about implementation reflect the fact that the evidence base and international policy approaches remain very much a work in progress. We hope that further research will better guide implementation in the future, to enable the potential of psychedelic-assisted psychotherapy interventions to be realised while also safeguarding vulnerable patients.
Associate Professor Gillinder Bedi is the head of substance use research at Orygen.
Professor Patrick McGorry AM is executive director of Orygen and professor of youth mental health at the University of Melbourne.
