What a trip: The new frontiers of MDMA and psilocybin in mental health 

Australia has become the first country to legalise MDMA and psilocybin in restricted therapeutic settings. An Irish psychiatrist says easing restrictions surrounding these psychedelic drugs here would speed up clinical research

Psilocybin is a naturally occurring psychoactive ingredient found in magic mushrooms and the subject of ongoing clinical trials. Pic: iStock

While adults are experts at honing in on a task and filtering out background noise, babies and young children are masters of absorbing absolutely everything — whether it is a toothbrush, a sock, or an empty crisp packet.

Alison Gopnik, a US developmental psychologist, coined the phrase “lantern consciousness” to describe this awe-struck, diffuse state of awareness. According to Gopnik, our baby “lanterns” narrow into more focused, adult “spotlights” with time and the loss of novelty in everyday experiences.

According to Prof Susan Rossell, a cognitive neuropsychologist at Swinburne University of Technology in Melbourne, this lantern consciousness is not so different from the expansive state induced by a psychedelic drug.

When you give someone the active component of magic mushrooms, it is almost like they revert to that little kid state again, says Rossell, who is currently running the largest phase II clinical trial of psilocybin in Australia. 

“All of their senses are [heightened] as if they were just experiencing the world for the first time.” 

Rossell believes this increase in what scientists call “cognitive flexibility”, coupled with psychotherapy, can help with depression and other mental disorders characterised by rigid negative thought patterns. This is a view echoed by Dr John R Kelly, a psychiatrist and clinical senior lecturer at Trinity College Dublin and Tallaght University Hospital.

Kelly was the principal investigator at the Irish site of a recent international phase II trial of psilocybin for treatment-resistant depression (TRD), sponsored by British mental health company Compass Pathways. The trial results, published in the New England Journal of Medicine last year, showed that more than a third of the 233 participants experienced significant symptom reduction for at least three weeks after receiving a 25mg dose of psilocybin.

Since then, Kelly and his team have received research grants from the Health Research Board (HRB) to study the effects of psychedelics on the immune system and to test the feasibility of psychedelic-assisted therapy as a treatment for cocaine addiction. In addition, Kelly and his colleagues will soon be heading the Irish segment of an international Compass Pathways-sponsored phase II trial of psilocybin for anorexia nervosa at Tallaght University Hospital. This is a “progressive step forward,” says Kelly, who has ambitions for Ireland to be at the forefront of the revolution in psychedelic medicine.

Australia is leading the way in this widely anticipated revolution — it has just become the first country to legalise psychedelic drugs MDMA, commonly known as ecstasy, and psilocybin for use in restricted therapeutic settings.

Due to a change made by Australia’s drug regulator, the Therapeutic Goods Administration (TGA), legally reclassifying MDMA and psilocybin from schedule 9 (“prohibited substance”) to schedule 8 (“controlled drug”), psychiatrists are now authorised to prescribe MDMA for post-traumatic stress disorder (PTSD) and psilocybin for TRD. The cost of a single psilocybin treatment is steep, ranging from A$15,000 to A$25,000 (€8,990 to €14,984).

Rossell argues that the current state of research leaves scientists and clinicians uncertain about the long-term safety profiles of psychedelic drugs and the specific patients for whom they will be effective or contraindicated. Rossell’s unpublished results from the Australian psilocybin trial suggest that psilocybin is not without risks: While around 40% of patients with TRD experience transformative recoveries, another 40% show limited to no response, and approximately 20% worsen due to “bad trips”.

According to Dr Eiko Fried, an associate professor of clinical psychology at Leiden University, another challenge lies in not properly evaluating the success of blinding efforts (Did participants remain unaware of what they were receiving — psychedelic or placebo?) and underreporting adverse events in randomised controlled trials. Without these safeguards, he questions whether we are accurately measuring the true efficacy of these drugs.

“Folks with severe mental illness are among the most vulnerable populations. Are these the people to experiment on without sufficient evidence?” Fried asks.

Kelly believes that an excess of “regulatory red tape” can impede scientific progress. “Some [regulatory] easing would be a good thing,” he says. 

“It would help move the clinical trials along by reducing some of the barriers for researchers like me and others.”

Currently, psychedelic drugs like psilocybin and MDMA are classified alongside crack cocaine and heroin as Schedule 1 substances under the Misuse of Drugs Act, indicating a substantial potential for abuse and negligible therapeutic value. Placing psychedelics in the same category as illegal street drugs may perpetuate the widely held misconception that they are addictive. “We know that all addictive substances interact with the dopaminergic system, but psychedelics are not dopaminergic. Instead, they affect [serotonin activity]. If you take too many psychedelics, it just makes you vomit, so there’s no way you can get addicted to them,” Rossell says.

“It’s important to emphasise that psychedelic therapy is not going to be useful for everyone, but there are definitely therapeutic benefits for subgroups and it’s very important that we continue to explore and scientifically investigate these compounds,” says Kelly, who is cautiously optimistic that patients might have access to psychedelic-assisted therapies within the next two years. Based on the unpublished results of a survey involving 151 psychiatrists, he says that attitudes among Irish clinicians are changing.

“Psychiatrists want additional treatment strategies,” says Kelly. “There’s a great deal of support for the therapeutic application of psychedelics and far less stigma.”