Psychedelic therapy is back on the research agenda, with local drug developers mixing potentially magic molecules.
It was a chance meeting between serial entrepreneur Joshua Ismin and medicinal chemist Sam Banister at a University of Sydney function that spawned Australia’s first psychedelic biotech company, Psylo.
Ismin had recently sold his successful startup The Video Network (TVN) and after investing in a number of meat alternative biotech companies, he decided to go back to being an operator – and thought psychedelic medicine was going to be the next big thing.
“I started to notice a lot of investors I was working with were interested in psychedelic start-ups, and I realised that if I was going to start a company in this area, I would need to network with researchers and scientists to partner with,” he says.
Luckily for Ismin, his wife runs the Sydney Knowledge Hub, a research commercialisation centre at the University of Sydney (a co-working space and initiative that allows startups to lease university space and labs to further their own goals), which is where he bumped into Banister.
“Sam has a long-standing appreciation for psychedelics: that’s the reason he got into medicinal chemistry in the first place,” Ismin recalls. “It’s the idea that a tiny molecule can change one’s entire perspective and create entirely new modes of consciousness, while also leading to all these beneficial health outcomes.”
For both founders, it was also personal: while Ismin had dabbled in psychedelics in his youth and knew first-hand of their potential, Banister had just lost a friend (his second) to suicide following years of unsuccessful treatment with approved anti-depressant medication. So the pair applied for the Startmate Accelerator programs, eventually ending up at University of NSW, where they have taken up residence as part of a research collaboration with the university to develop new treatments for mental health disorders.
Despite Psylo’s stellar science credentials – out of a team of nine, seven have PhDs, and include three medicinal chemists, two molecular and behavioural pharmacologists, and two computational scientists — it can be tough to cut through in an area with such an ethically loaded history.
As renowned food writer Michael Pollan writes in his book on psychedelics How To Change Your Mind, when LSD was first discovered in the 1940s, it seemed to researchers, scientists and doctors as if the world might be on the cusp of psychological revolution. But in the 1960s, due to the backlash against the counterculture, all further research into psychedelics was banned, and abandoned until recently.
But sometime in the last few years, psychedelics became all the rage. Pop culture is awash with psychedelic references: actress-turned-entrepreneur Gwyneth Patrow included a trip to the dark side in an episode of her Netflix show The Goop Lab, and Pollan, in dedicating a whole book to psychedelics, has bestowed on the drugs a certain gravitas. This re-emergence of psychedelic drugs in modern pop culture is no small feat: mass culture plays a big part in liberalising attitudes towards psychoactive substances and their use.
This increased social liberalism – influenced in part by the softening stance on cannabis for medical use – alongside the development of sophisticated technologies has slowly returned psychedelics to medical research. That’s led companies such as Psylo to begin addressing the limitations of current psychedelic therapeutics by developing three types of “next-generation” psychedelic medicines that are safe, effective, and accessible to those suffering from hard-to-treat mental health conditions.
“We are focusing on three main product families [types of drugs],” says Banister. “A short-acting psilocybin-like drug (the active molecule in magic mushrooms), which would leave the system within two to three hours; drugs that can be used to safely microdose; and non-hallucinogenic psychedelics which deliver the same health benefits as those with hallucinogenic properties, but without the need for supervised administration.”
Psylo is looking to develop drugs that are an alternative to SSRI antidepressants, which evidence suggests are only 20% more effective than a placebo and come with a variety of side effects.
Part of Psylo’s program uses modern medicinal chemistry techniques to modify first-generation psychedelic molecules to create highly optimised versions of those compounds. But what enables Psylo to be so expansive in its vision is the use of virtual docking, a process by which researchers computationally “dock” different types of molecules at a particular protein to see which ones will bind. Ismin and Banister explain it like this: if you picture a padlock as the receptor and molecules as a key, what they’re doing is fitting millions of computationally discovered keys into the lock to see which ones fit.
Those molecules that fit (or bind) well are then moved into a real-world lab experiment, where the team tests them to see if they can be further developed into the types of drugs they’re looking to make.
The Psylo team is interested in 5HT serotonin receptors, which are found in multiple areas of the brain and are most strongly expressed in areas that have previously been involved in psychosis and psychotic symptoms, such as the prefrontal cortex, striatum, ventral tegmental area and the thalamus. Serotonin carries messages between nerve cells in the brain and throughout the body, and plays a key role in all sorts of body functions such as mood, sleep, digestion, nausea, wound healing, bone health, blood clotting and sexual desire.
Although the 5HT system has been a historical research target of interest, drug developers have actively optimised drugs away from the 5HT2a subtype, due to its propensity to induce hallucinatory effects. Psylo is part of a new breed of drug-development companies that are specifically focused on the therapeutic benefits of 5HT2a agonists.
Ismin and Banister believe that short-acting drugs will not only be cheaper to administer (patients must be accompanied by a doctor for safety reasons when they’re on the drug, and those doctors get paid more the longer they’re supervising), but also will entice more people to try them if they know they won’t be “tripping” for hours.
This is the same with the third offering they’re working on, a non-hallucinogenic psychedelic, which they hope “will deliver neuroplasticity without the trip experience”. So far, Psylo have computationally discovered more than 1,000 molecules that are likely to bind to the 5HT2a receptor, which they’ve classified into “structural families”, selected a few from each family, and are now testing in a physical lab setting.
Despite a growing body of evidence suggesting the medicinal effectiveness of psychedelic drugs to treat mental health conditions such as depression, companies like Psylo still have a long road ahead. A key problem with the research to date (although the weight of evidence is tilted towards safety and effectiveness in a clinical context) is that few trials have involved more than 100 participants.
While optimistic about their chances, Psylo is still in the pre-clinical synthesising and screening phase, creating and assessing molecules that could become therapy candidates. The company is initiating animal studies, and Ismin says they expect to have their first clinical candidate identified by the end of 2023. In terms of commercialisation, Ismin believes the shorter-acting psilocybin has the most obvious potential, as it’s been the “most validated in clinical trials”. That said, “if by the end of 2023 it is proven that micro dosing is clinically efficacious, we may go with that first”, he adds.
“The FDA [US drug approval body] has several times designated psilocybin as a breakthrough therapy, and MDMA will be legally available as a prescription drug in the next 12 to 18 months in the US,” Ismin says. “Psilocybin will not be far behind that.”
In fact, MDMA and psilocybin can already be used in clinical trials in Australia, and accessed via what’s known as the Special Access Scheme pathway B; the TGA has approved SAS-B applications for psilocybin and MDMA to be used for treatment-resistant depression and PTSD, but access to the actual substance is controlled by the states, which have so far refused their permission.
Still, the appetite is clearly there: in January this year, the Australian government allocated almost $15 million to seven clinical trials testing the use of potential breakthrough combination therapies to treat debilitating mental illnesses. The largest trial is a University of Melbourne examination of MDMA-assisted psychotherapy for treatment-resistant social anxiety in young adults with autism spectrum disorder. Today, there are more than 70 clinical trials into psilocybin and MDMA underway in the US and Europe, six in Australia and four registered in New Zealand. In the meantime, Psylo’s team of chemists will continue to fit millions of molecules at their 3D computerised 5HT2a receptor. The hope is that some of them will bind in such a way as to erase all doubts about psychedelics – and highlight their ability to help the millions suffering from debilitating mental illnesses worldwide.
Caroline Zielinski is a freelance journalist based in Melbourne. She writes on health, science, social affairs and all issues related to women