February 2022

Psyched in: psychedelics in the spotlight as trials begin

Once the focus of highly promising research in psychiatry in the 1950s and ’60s before being outlawed, psychedelic drugs are being returned to the light by a new generation of researchers.

The so-called ‘psychedelic renaissance’ is seeing the ‘classic’ psychedelics – mescaline, LSD, DMT and psilocybin (found in ‘magic mushrooms’) – again being explored for their potential, in combination with psychotherapy, to alleviate a range of mental health disorders from post-traumatic stress disorder (PTSD) and depression, to end-of-life distress and addiction. They are also providing, through cutting-edge brain-imaging technology, new insights into human consciousness.

Long history of human use

Humans have used consciousness-expanding substances for healing and sacramental purposes for thousands of years. It wasn’t, however, until Albert Hoffman first synthesised LSD in 1938 and R Gordon Wasson ‘discovered’ Mexico’s mind-altering mushrooms 17 years later that Western scientists began to try to understand these extraordinary molecules and to theorise what they might be useful for. Initially they were regarded as ‘psychotomimetics’ – drugs capable of producing effects similar to psychotic states – but this misconception soon gave way to the idea that they might be able to bring about profound psychological healing when combined with therapy.

Within just a few years, this initial wave of research, comprising more than a thousand studies, would be shut down by a global moral panic around the recreational and countercultural use of hallucinogenic drugs.

In the decades since then they have been largely off-limits to researchers.

Now dozens of clinical trials are under way around the world as psychedelics emerge from the underground and enter the mainstream. It’s estimated that the market for these drugs will reach US$10.75 billion by 2025, with corporations such as the Australian Securities Exchange-listed drug development company Emyria Limited also getting in on the act.

Australia, once lagging behind the rest of the world in psychedelic science, is not only catching up with but even surpassing the efforts of other countries.

Australia, once lagging behind the rest of the world in psychedelic science, is not only catching up with but even surpassing the efforts of other countries. In March 2021, Australia’s government became one of the first in the world to announce funding for psychedelic-assisted clinical trials through its $15 million Innovative Therapies for Mental Illness Grant Opportunity, administered by the National Health and Medical Research Council (NHMRC) under the Medical Research Future Fund (MRFF).

Meanwhile, trials are already under way looking at psilocybin for end-of-life anxiety (St Vincent’s Hospital in Melbourne), generalised anxiety disorder (Monash University), methamphetamine addiction (St Vincent’s Hospital in Sydney) and treatment-resistant depression (Swinburne University). Although they aren’t technically psychedelics, MDMA (the empathy-promoting active ingredient in ecstasy) and ketamine (traditionally used as an anaesthetic) are also the focus of trials on PTSD (Monash University and Edith Cowan University) and adult depression (various sites), respectively.

Researchers at Melbourne’s newly established non-profit psychedelic research centre the Psychae Institute are exploring yet another compound featured in the psychedelic renaissance: the South American psychoactive brew ayahuasca, one of the active ingredients of which is the potent hallucinogen DMT.

In 2021 Psychae Institute’s Co-Directors Professor Jerome Sarris and Associate Professor Daniel Perkins contributed to a research paper on the effects of ayahuasca use on depression and anxiety symptoms. Using an international cross-sectional study, the authors found that 78 per cent of the 11,912 ayahuasca drinkers surveyed reported that their depression was either “very much” improved (46 per cent) or “completely resolved” (32 per cent). Of the participants with anxiety, 70 per cent reported that their symptoms were “very much” improved (54 per cent) or “completely resolved” (16 per cent).

The paper’s authors noted that, while most participants reported significant benefits from their ayahuasca use, worsened symptoms were reported by a small percentage of drinkers.

Prof. Jerome Sarris

People need to be aware of the dangers. We need more medical options to treat psychiatric disorders; it’s just the case that from our perspective we want to do it in a safe medical framework.

Professor Jerome Sarris

Jerome says there are “potential risks” when it comes to hallucinogens, especially if used outside of clinical environments. As people seek out ‘underground’ psychedelic therapy in ever greater numbers, Jerome says they “need to be aware of the dangers”.

“We need more medical options to treat psychiatric disorders; it’s just the case that from our perspective we want to do it in a safe medical framework,” he says. (A standard protocol of trials involving psychedelics, established during the first wave of research, is the screening out of people with conditions such as bipolar disorder or who have a family history of psychosis.)

Jerome and Daniel have submitted an application for an MRFF grant to enable Psychae Institute to conduct an ayahuasca-focused clinical trial in partnership with Penington Institute (publisher of The Bulletin). Jerome says the trial will have three arms. “It’s treatment-resistant major depressive disorder,” he says, “but also alcohol use disorder, as well as dual diagnosis. And the data we do have on alcohol and drug use [treatment] with ayahuasca shows very stunning results in terms of people reporting dramatic reductions in their alcohol and drug use. So we’re very excited to put this through in a clinical trial to assess that.”

A boost for psychotherapy?

Melbourne-based Doctor Nigel Strauss has been a psychiatrist for more than 40 years and has long been fascinated by altered states of consciousness. In addition to his interest in psychedelic-assisted psychotherapy, Nigel says he is also an “avid meditator” and a keen student of Eastern philosophy. In his capacity as a trauma therapist, he has worked with survivors of the Port Arthur massacre and the Black Saturday bushfires.

Nigel says he “personally sponsored” the open-label trial at Monash University’s clinical psychedelic lab BrainPark which is examining the safety and efficacy of MDMA-assisted psychotherapy with 25 participants with PTSD. As well as being an investigator in Australia’s first modern psychedelic trial, looking at end-of-life anxiety and depression with psilocybin at St Vincent’s hospital in Melbourne, he is also involved in a trial investigating the utility of MDMA on psychopathy (a neuropsychiatric disorder marked by a lack empathy).

“Unfortunately,” he says of the trials he is assisting with, “the only one going at the moment is at St Vincent’s in Melbourne” because of disruptions caused by the COVID-19 pandemic. His hope is that the trial he is working on at Swinburne, examining the effects of psilocybin on participants with treatment-resistant depression, will start up early this year.

Nigel says there is “a natural conservative resistance among psychiatrists” to psychedelic-assisted psychotherapy, which is in part why in 2020 he established a group called Australia New Zealand Psychiatrists for Psychedelic-Assisted Psychotherapy (ANZPPAP). What critics of psychedelic-assisted psychotherapy often fail to understand, Nigel says, is that psychiatrists like him don’t view psychedelics as a panacea. Unlike other mental health treatments such as electroconvulsive therapy (ECT) and SSRI anti-depressants, Nigel explains, with psychedelic-assisted psychotherapy it is the patient, rather than a machine or a pill, who has to do the work. “Psychotherapy is the key, not the drug” is how he puts it.

Dr Nigel Strauss

Psychotherapy is the key, not the drug.

Doctor Nigel Strauss

This is why, while supporting the eventual wider uptake of psychedelic-assisted psychotherapy, he advocates a slow and steady approach. Having received training by the American non-profit Multidisciplinary Association for Psychedelic Studies (MAPS), he has spent a lot of time thinking about clinical guidelines for how psychedelic therapists should be trained in Australia. At present, Nigel says he doesn’t feel there are enough adequately trained or experienced psychotherapists for psychedelic therapy to be rolled out across the community, especially ahead of the completion of phase three clinical trials.

The rescheduling debate

Others are less circumspect. In September 2020, the non-profit Mind Medicine Australia (MMA) petitioned the Therapeutic Goods Administration (TGA) to down-schedule MDMA and psilocybin from Schedule 9 (prohibited) to Schedule 8 (controlled) drugs. Theoretically, such a rescheduling would make it easier for people with mental health disorders to access psychedelic-assisted psychotherapy.

Following a review of therapeutic value, risks and benefits by an independent expert panel, the TGA announced in December 2021 that it had made a final decision not to reschedule MDMA and psilocybin. Although the panel noted the “promising” findings of clinical trials, it argued that both the Royal Australian and New Zealand College of Psychiatrists and the Australian Medical Association supported its position that further high-quality research using larger-scale studies was necessary to determine the safety and efficacy of using psilocybin and MDMA in the treatment of mental illness.

Eli Kotler

One person who disagrees with the TGA’s decision is Doctor Eli Kotler, a Melbourne-based consultant psychiatrist. As well as having been appointed the principal investigator for Emyria’s upcoming clinical trial on MDMA-assisted psychotherapy for treatment-resistant PTSD, Eli is taking legal action in the Moorabbin Magistrates’ Court in a bid to be allowed to treat one of his patients with MDMA. It’s the first case of its kind in Australia.

“The significance of this case for one person, as well as those who live in their world, can’t be overstated,” Eli says. “This person continues to suffer with emotional turmoil and suffering which impacts her thoughts and behavioural patterns in destructive ways. She has had years and years of treatments but continues to suffer because her emotional world remains too anxiety-provoking and overwhelming.”

Eli says he questions the TGA’s decision on the basis of its own guidelines. “The TGA had to make the arguments that the medicines have no accepted therapeutic value and that they are highly dangerous. In reality, there is evidence of therapeutic value and there is good evidence that when used according to accepted protocols there are minimal risks.”

While he waits for the case to return to court early this year, Eli says, “MDMA-assisted therapy brings us face to face with our fears, our emotional worlds, our traumas, and facilitates an integration of those parts of ourselves which live in the shadows of our psyches. Studies clearly show increases in both functional and structural plasticity, correlating with the experiences of integration which people describe.”

When I ask him if he sees psychedelics traveling the same path as medical cannabis and becoming a legally accessible health treatment in conjunction with therapy in the coming years, he is unequivocal: “It’s clear that it’s a matter of ‘when’ rather than ‘if’. Like all treatments which have not obtained sufficient evidence to be used as a first-line treatment, the current important question is ‘when’ will these medicines become available for compassionate use. Unfortunately, this important question seems to get lost, yet in my opinion is the most pressing concern currently.”

 

– Ben Brooker