Since being diagnosed with depression in 1995, Leonie Schneider has been prescribed antidepressants for over 24 years.
“To be honest, at some level the medication was necessary,” she said. “But in the long term, it numbed me to the highs as well. I felt as though I was living life through a letterbox. There was no real range or movement to life, just a narrow space I existed within.”
Eventually, doctors concluded Schneider had what is known as “treatment-resistant depression”. When an opportunity arose in 2019 to take part in a trial for those with severe depression at Imperial College London using psilocybin — the psychedelic compound found in magic mushrooms — she seized it.
“Before the trial, I was constantly searching outside myself for solutions — the next doctor, the next drug,” she said. “I always believed the next one would fix me, but nothing ever truly did.
“During my Imperial College trial, I had a profound moment. At one point, I removed my eye mask and headphones and said, ‘I’m surprisingly unbroken’. That insight gave me back a sense of agency,” she said.
“Instead of believing someone else needed to fix me, I realised this was my journey, my healing, and my responsibility.”
Schneider said she has not been on an antidepressant since.
For the first time, an NHS hospital is working with a private partner to take part in a similar trial, and researchers hope psilocybin compounds — which act on serotonin receptors in the brain — could eventually become part of mainstream care.
Clerkenwell Health, a specialist in mental health trials, has launched an NHS-embedded commercial research site in Doncaster, South Yorkshire, dedicated to mental health conditions.
Developed alongside Rotherham Doncaster and South Humber NHS Foundation Trust (RDaSH), the aim is to give NHS patients earlier access to investigational treatments and build a prototype for how these mental health trials could be delivered inside the health service.
Mehul Vaghani, head of corporate development at Clerkenwell Health, said the trials marked the first time these psychedelics had been administered in the North East under legal conditions.
Participants are administered a short-acting psychedelic through a strip in their mouth and are then constantly monitored in the hospital’s beds by their own therapists and mental health nurses from the Trust.
The hope underpinning the trial is that if these drugs are approved and become medicines, NHS staff from the hospital will already have experience of caring for the patients who are eligible to take them.
“There are many different causal pathways or hypotheses on how psychedelics improve mental health,” Vaghani said. “A big one is neuroplasticity . . . after we stop being children our brains become quite static and the idea is these compounds give your brain essentially the ability to move and grow.”
With treatment-resistant mental health conditions, he continued, “it can be very difficult for a brain, once it’s set, to challenge and change thought processes. What psychedelics may allow, in theory, is for a person to reframe and restructure the way they think about certain things.”
Vaghani, using an analogy of a mountain covered in snow, added: “You ski down the path and you create a line where you follow down, and that’s built into the snow then.
“What the psychedelics might be able to do is put a new coat of snow down so you can create some new paths to ski down.”
Ibreez Ajaz, a research physician working on the trial, said the participants had been “cautiously optimistic” so far and “of course not having a ‘hospital-like’ feel in the setting” had helped.
Sarah Moll, research and innovation manager at RDaSH, noted that these drugs were stored under controlled conditions, inside a safe bolted into the floor. Late last year, officials from the Home Office came to inspect the premises.
Compass Pathways, a British pharmaceutical, is also developing a medical-grade form of psilocybin for treatment-resistant depression and is currently seeking approval from the US Food and Drug Administration (FDA).
If approved, experts hope the UK medicines regulator, the Medicines and Healthcare products Regulatory Agency, could follow suit, allowing its use within the NHS.
Professor David Nutt, a former government adviser on drug policy who led the Imperial study, believes these compounds should be approved for use in treating patients with severe depression across the NHS.
“It is now proven that psilocybin is a powerful, often single-dose therapy for people with treatment-resistant depression,” he said. “That is actually a major breakthrough.”
He added the reason he went into this field was that it worked in a very different way to other treatments.
“It has a fundamentally different mechanism of action and a different target in terms of brain circuits,” he said.
“It changes the way people think about their disorders and about themselves. They are no longer captured by repetitive, ruminative thoughts.”
However, for some professionals the potential side effects of psychedelic-assisted psychotherapy have not received enough attention.
Joanna Moncrieff, a professor of critical and social psychiatry at University College London, said that while she did not entirely object to the practice “we have no data whatsoever on their long-term safety”.
She added that the evidence from clinical trials should be interpreted cautiously because participants can usually tell whether they have received a psychedelic rather than a placebo. “It’s impossible to blind these trials,” she said. As a result, she argued, “a large part of the benefits we’re seeing are amplified placebo effects or expectancy effects”.
Professor Oliver Howes, consultant psychiatrist and spokesperson for the Royal College of Psychiatrists, pointed out that new treatments are rarely developed for people with mental illness “whose needs are often overlooked”.
But he warned that there “remains a need for more studies” to see how psilocybin performed in routine practice, including alongside psychotherapy.
“If future research and evidence show that psilocybin is safe and effective then we would consider supporting it being approved for use in medical settings in the UK, but this still needs large, well-designed trials to be completed,” Howes said.
He added: “We strongly advise against people self-medicating or using ‘backstreet’ clinics as there are risks in doing so.” This piece has been updated to clarify that this is the first time an NHS hospital has worked with a private partner on a psilocybin trial.
Source: Financial Times
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