When Ekaterina Malievskaia and George Jay Goldsmith's son started university in New York, he developed severe depression. Standard antidepressants and other therapies didn't do any good. As with parents, Malievskaia and Goldsmith started to think hard about what they could do to help improve their son's mental health.
Malievskaia is a doctor working in internal medicine and public health, and Goldsmith is an entrepreneur. They began drilling down into the science to understand treatment-resistant depression, and see if there was anything they could do to help their son and others with a similar condition.
"We found out that research on one compound in particular – psilocybin – had been carried out for nearly 50 years, with positive results in treating depression and anxiety. Psilocybin has been known to psychiatrists and neuroscientists for a very long time for this link to mental health," Malievskaia told IBTimes UK.
Psilocybin is best known as the psychoactive component of magic mushrooms. Taking it recreationally – which is illegal in many countries – can lead to feelings of euphoria, a distorted sense of time and hallucinations. Negative reactions to the drug can include panic attacks and nausea.
Many small studies have linked psilocybin to improvements in mental health, for example reducing anxiety and depression among cancer patients. But larger-scale clinical trials have been lacking. Without these, the journey towards medical use of psilocybin to treat depression has more or less ground to a halt.
"It was interesting science but there was no pathway to patients," Malievskaia said.
Malievskaia used her medical expertise and Goldsmith his experience in multi-stakeholder collaborations to set up Compass Pathways, a healthcare company aimed at speeding up patient access to new, evidence-based mental health treatments.
"We came at this not from a position of favouring the legalisation of psychedelics. We came from a perspective of creating another option for patients who have exhausted all the others."
In terms of the science, psilocybin has been known and used for thousands of years, Malievskaia points out. There is a great deal of ethnographic observational data and small-scale experimental data. What has been lacking is the large-scale trial data of the effects of psilocybin that would be necessary to develop it for therapeutic use.
"We got to the point when the signals were too strong to ignore. The need was too great. So we decided to put our skills together to accelerate patient access to psilocybin."
Compass Pathways isn't arguing for legalisation of psilocybin or magic mushrooms for recreational purposes, Malievskaia emphasised.
"We are substance-agnostic. It just happened to be that psilocybin is a psychedelic."
The company is now working towards running the largest trial of psilocybin for treatment-resistant depression to date, aiming to recruit a total of 400 patients. The next largest trial done so far was on about 50 people.
Discussions with regulators such as the European Medicines Agency have been positive, Malievskaia said, with a protocol for the trial now confirmed. Next up is holding talks with regulators in the individual countries where the research would be carried out. Seven European countries are contenders, where Compass Pathways would work with academic institutions to run the trial.
As for the mechanism by which psilocybin appears to influence mental health, the jury is still out.
"We have a number of hypotheses, but none of them are confirmed. At this point it's really hard to say anything definitive," Malievskaia noted.
"Research shows it might be due to an increased sense of connection in the brain. It could be something about the nature of the experience, and the effect it has on the personal narrative. It could be the ability to have a different vantage option on your life situation."
If the trial does indeed go ahead in Europe, it may have the potential to reopen this avenue of research in the potential therapeutic effects of psychedelics for mental health, which has been largely dormant since its heyday in the 1960s.