Regulator under fire as experts question rollout of MDMA and psilocybin medicines

Health and government insiders believed there was not enough evidence to support the clinical use of psychedelic drugs just weeks before the approval to use them to treat mental health.

Psilocybin mushrooms. Picture: Getty Images

Health and government insiders believed there was not enough evidence to support clinical use of psychedelic drugs just weeks before Australia became the first country in the world to approve their use to treat mental health.

Amid calls for a fresh review into the regulator’s call on psychedelics, in-depth interviews by Monash University with politicians, frontline researchers, senior members of mental health peak bodies, a consumer organisation and the union for mental health workers reveal universal concerns that the evidence was “not there yet” for the widespread clinical use of psychadelics.

Insiders were concerned there had only been a very small number of clinical trials of psychedelics, with short durations and small sample sizes.

The interviews were conducted between September 2022 and January this year, just a month before the Therapeutic Goods Administration made the shock decision to down-schedule psilocybin for clinical use in treatment-resistant depression and MDMA for the treatment of post-traumatic stress disorder.

Interviewed in the months leading up to the decision, key experts – who described themselves as “cautiously optimistic” about using psychedelics to treat mental health conditions in the future – expressed reservations.

“All organisational representatives expressed concern regarding the quality of existing evidence, noting that insufficient evidence limits trust and, subsequently, prevents organisations from supporting the clinical use of psychedelics,” says the paper, published in Public Health Research & Practice, a peer-reviewed journal of the Sax Institute. “Many representatives felt that the evidence ‘is not there yet’ as it lacks maturity (due to a small number of publications) and/or has several methodological flaws, such as poor blinding practices, small sample sizes, short durations, lack of comparison to existing treatments, and narrow populations not reflective of the general population.”

Paper co-author Chris Langmead, deputy director of the Neuromedicines Discovery Centre at Monash, said the fact evidence was still emerging was “not to say there’s not evidence”.

“We still do need to do more clinical trials, bigger clinical trials, we need to do clinical trials that essentially monitor patients for longer to ensure that these medicines are safe and efficacious. The medicines have been able to be prescribed since July 1.

“Australia has put itself in a position now where the eyes of the world are on us in terms of how we do this. I think it’s really important that nationally, we invest in research in this space.”

The paper’s publication has sparked fresh scrutiny of the controversial TGA decision in February, with a key scientific adviser commissioned by the regulator to co-author an independent report into the risks and benefits of psychedelics, psychiatrist and public health physician Steve Kisely, now revealing “the certainty of evidence was rated as low or very low” when the TGA was weighing up its decision.

The TGA, which rejected an earlier application from charity and lobby group Mind Medicine Australia, decided to down-schedule the psychedelics despite the conclusions of the Kisely paper, in an anonymous “delegate only” decision made without reference to its own committee of experts, after being deluged with submissions.

In a recent paper entitled “The down-scheduling of MDMA and psilocybin: Too fast and too soon”, Professor Kisely detailed serious problems with the evidence that appeared to influence the TGA’s decision.

“In the view of this author of the independent report to the TGA, the decision to down-schedule is ahead of the available scientific evidence especially as unresolved issues remain surrounding relapse, long-term safety and the challenges of conducting randomised controlled trials in this area,” Professor Kisely said in his paper. “The TGA’s decision to down-schedule in the absence of advice from its own independent group of experts, or new scientific findings, seems premature especially given that Australian trials are under way that might better establish efficacy.”

Prominent psychiatrist Ian Hickie said the Monash paper was “entirely consistent with most of the people who are active in the field”. “They’re concerned about the lack of substantive evidence to justify the TGA decision in the first place. But now that we’re going down that road: what are the mechanisms for collating real-world evidence of the benefits and potential side-effects of this treatment?”

But Mind Medicine Australia’s Peter Hunt blamed the concerns on vested interests from researchers who stood to lose access to funding.

“Our rescheduling submissions was full of data which showed safety and efficacy,” Mr Hunt said. “There were over 13,000 submissions lodged which were 98 per cent in favour of rescheduling with about 40 per cent coming from researchers.”

The TGA has acknowledged concerns “that there are not appropriate controls in place to protect patient safety” but stressed the drugs could be prescribed only by certain trained psychiatrists with permissions from a human ethics committee. “To help prevent this and keep patients safe, we have put strict rules in place,” the TGA said.

There are only three clinics in Australia able to prescribe now or in the near future. A single course of psilocybin will cost on average $25,000.

Several frontline researchers in psychedelics are now calling for the TGA’s decision to be reviewed, and are insisting there be independent data collection from people who are administered psilocybin and MDMA.

“To me, the real concern is safety,” said Gill Bedi, senior research fellow at Orygen and the University of Melbourne. “The main concerns we have is with regards to psychiatric negative reactions and the potential onset of psychiatric difficulties that didn’t exist beforehand.

“I think there actually does need to be a review of the TGA process itself.”

The chair of the Royal Australian College of General Practitioners’ Specific Interests Psychological Medicine group Cathy Andronis echoed that call.

“I would totally support that view,” Dr Andronis said. “The gold standard with new medicine is to do independent controlled trials with quite rigorous protocols, with informed consent. It’s about understanding the risks and benefits.”

Sally Meikle, a frontline researcher in psychedelic-assisted pharmacotherapy at the University of Melbourne, said the TGA had not consulted with the research community.

“There just isn’t the evidence base to support a wider rollout at this stage,” she said. “There’s been a few clinical trials across the world but the numbers are still really quite small. We were really shocked that it went through.”

Swinburne University cognitive neuroscientist Susan Rossell agreed. “We are incredibly passionate about doing the research but we want to do it in very controlled and safe and regulated ways,” Professor Rossell said. “We’re all on the same page about this which is why The TGA decision is quite frankly ridiculous.

“It does really put into light the degree of lobbying that occurred, and the lack of transparency.”