Researchers at Imperial's Centre for Psychedelic Research are using brain imaging to understand addictions and devise new approaches to treating them.
Addiction is like having your brain hijacked. The activities that used to make you feel happy and satisfied leave you cold, and only the object of the addiction triggers the brain's reward mechanisms. Now, researchers at Imperial are looking at new ways of setting the hijacked brain free, using psychedelic substances such as psilocybin.
In particular, they are working on psychedelic therapies for behavioural addictions such as gambling, building on promising results in the treatment of substance addictions, from nicotine and alcohol to harder drugs.
"We want to find out if psilocybin therapy can reverse or restore the dysfunction that we see in gamblers' brains," says Dr Rayyan Zafar, a postdoctoral researcher in the Centre for Psychedelic Research, part of the Department of Brain Sciences at Imperial. "Does a psychedelic therapy reset or re-broaden the reward spectra that have been limited by the addiction?"
The therapeutic use of psychedelics such as LSD and psilocybin, the active ingredient in magic mushrooms, is receiving increasing attention in the medical world. Researchers at Imperial have been active in this area for nearly two decades, carrying out brain imaging research and clinical trials with psychedelics in conditions such as depression, anorexia, obsessive-compulsive disorder and fibromyalgia.
The Centre for Psychedelic Research was founded in 2019 to consolidate this work, and is now led by Professor David Nutt, a leading figure in drug research and policy development, and clinical senior lecturer in psychiatry Dr David Erritzoe.
Picturing addiction to gambling
Dr Zafar studied the neurobiology of gambling addiction in his PhD research at Imperial, using functional magnetic resonance imaging (fMRI) to map responses to gambling stimuli in the brains of volunteers, some with gambling disorder, some without.
"We compared the results when individuals were presented with videos relating to gambling and videos relating to other primary rewards, such as food," he says. "We also included some secondary rewards, such as nature and social cues, which are also meant to be pleasurable for people to look at. The aim was to understand the complexity of the brain's response to these environmental stimuli."
The results of this work, which have yet to be published, were positive. "We found what we were looking for, in that the gamblers brains lit up in core reward processing regions in response to gambling-related videos, which was not seen in the healthy control subjects."
The next step is to carry out a limited trial to see if the mechanisms identified are affected when someone takes psilocybin. This work is being supported with a UKRI Impact Acceleration Account grant, funding that is designed to bridge the gap between a scientific discovery and its application. "We are looking for a proof of principle," Dr Zafar explains. "We want to see if there is an impact on brain function that is related to the clinical end-point, something that tells us an individual's dysfunctional reward circuits have been recalibrated or re-set."
This would be the stepping stone to a deeper investigation of possible therapies. "The hope, if it works out, is that we can launch a proper clinical trial and see if this kind of therapy is safe and effective in clinical populations."
Development of this approach would involve work at the CIPPRes clinic, a partnership between Imperial's Centre for Psychedelic Research and Central and North West NHS Foundation Trust.
Reset and reconnect
Psychedelic therapy is thought to work through the effect the substance has on a patient's perception of the world. "It helps you enter an expanded state of consciousness, typically with a profound sense of oneness," explains Dr Erritzoe. "It stimulates insightfulness and gives you new perspectives on your self."
At the same time, it is very important that the psychedelic is taken in a controlled setting, with support from a trained psychotherapist. "We aim to prepare the patients as well as we can, so that they can lean into the experience."
This is not just a safety net. It is likely that the psychedelic experience and the psychotherapy are working in the same way, and might complement each other.
"The work that you do in relapse prevention groups, or other therapy models, has an element of trying to broaden back out the reward spectrum, and take back the space in the brain and behaviour that has been hijacked by the addiction," Dr Erritzoe says. "Psychedelics tap directly into the psychotherapeutic paradigms that we are applying, so it is a compelling idea to test them together."
Unlike conventional drug treatments for behavioural disorders, patients would probably not need to take repeated doses of a psychedelic in order to sustain the effect. "Expecting this to be a magic bullet is slightly optimistic, but for some patients a single session might have long-lasting effects. It might be what it takes for them to break out of the addiction."
Building a translational research pathway
Adding brain imaging to the therapeutic process has the potential to personalise it even further. "We are interested in finding out if the imaging can predict patient reactions, and the response to treatment later on," says Dr Erritzoe. This work is advancing rapidly thanks to artificial intelligence systems that can make sense of the large amount of complex data produced by imaging and other brain monitoring techniques.
This brain scanning will be taken forward on a brand-new MRI system that is being installed at Invicro, a contract research organisation collaborating with the Imperial team. "This cutting edge, high-power, research-grade system will allow us to look at the brain effects of psychedelics in unprecedented detail," says Dr Matt Wall, Head of MRI Applications at Invicro London.
Instead of inspiring industry to scale-up after we have paved the way, we are thinking of holding our results a bit closer in future. Dr David Erritzoe Centre for Psychedelic Research
Funding such as the UKRI Impact Acceleration Account grant that is supporting Dr Zafar's work plays an important role in de-risking this line of research, taking it to the point where intellectual property can be identified and protected. This translational pathway now needs to go further, and options for grant and partnership funding are being explored.
Until now, the Centre has left commercialisation of this work to others, but now it is considering taking the initiative itself, with the support of experts in Imperial Enterprise. "Instead of inspiring industry to scale-up after we have paved the way, we are thinking of holding our results a bit closer in future," says Dr Erritzoe. "So, if we are testing psilocybin for a new indication, such as gambling, then we will protect the intellectual property involved and then consider industry partnerships or create a spinout company to take it further."
