Psychedelics – how modern neuroscience research is leading to new treatments for brain disorders

Psychedelic therapies have the potential to vastly improve the treatment of mental health disorders such as depression. The Imperial Centre for Psychedelic Research is paving the way in exploring these innovate treatments using psilocybin – the active ingredient in magic mushrooms. Here, Professor David Nutt from the Department of Brain Sciences discusses. 

When most people think of psychedelics, the first thing that comes to mind is LSD-inspired Flower Power during the 1967 Summer of Love in the USA, with its associated revolution in art and music. This explosion of use was seen to be fuelling the protests against the war in Vietnam and so rapidly led to LSD and related psychedelics such as psilocybin (the active ingredient in magic mushroom) being banned, first in the USA and then later globally. This ban still exists today and has effectively censored research for over 50 years. The ban is very unfortunate as prior to this there were hundreds of studies that showed psychedelics were effective treatments for a range of mental illnesses as well as some other brain disorders. Millions of patients may therefore been denied access to potentially life-saving treatments.

This situation is beginning to change with several universities setting up psychedelic research groups including the Centre for Psychedelic Research at Imperial, which was the first and is now five years old. The impetus to these new research centres is twofold. First, today we have much more powerful neuroimaging methods to examine the impact of psychedelics on the brain and second, these neuroimaging studies have revealed possible mechanisms underpinning the therapeutic activity of psychedelic drugs, so encouraging more clinical research. This research has revealed remarkable efficacy in a number of patients who have not responded to prior conventional treatments and may be the start of a whole new phase of novel therapies for mental illnesses.

Powerful mental health benefits

We now know that the most commonly known psychedelic drugs (LSD, psilocybin, DMT from ayahuasca, mescaline from peyote) all act to stimulate one of the many serotonin receptor subtypes in the brain – the 5-HT2A receptor. This receptor is especially concentrated in the most high-level recently evolved brain regions that are responsible for the most complex and sophisticated aspects of human consciousness. Imaging research from Imperial using both fMRI and EEG have shown that serotonin-acting psychedelics enhance connectivity in these brain regions and this explains their psychedelic effects. What is perhaps even more remarkable is that this transient disruption of brain function can lead to long-term changes in attitude to past traumas and provide powerful mental health benefits.

When we started our neuroimaging work with psychedelics over ten years ago, we hadn’t expected to be developing new psychiatric treatments, but the brain changes we found pointed to the possibility of lifting depression. We managed to get funding from the Medical Research Council to conduct a small trial in patients who had failed to respond adequately to both antidepressants and psychotherapeutic treatments. We found that just a single psilocybin trip produced a powerful improvement in mood in the majority. Perhaps even more remarkable was that this effect was long-lasting and some of those first patients are still not depressed ten years later. Since then, a number of other academic groups have replicated our findings and several companies have been set up to take psilocybin or other psychedelics to market for depression and other mental health disorders.

Breaking negative thinking patterns

We ourselves have decided to use our expertise in translational medicine to focus on two things. First, the brain mechanisms underlying the antidepressant efficacy, and second, whether psilocybin could treat other disorders such as anorexia nervosa, obsessive compulsive disorder (OCD), addiction, and even chronic pain syndromes. You might think the latter ambition odd since these disorders have very different symptoms from depression. But they all have one thing in common – the patient can’t break out of repetitive thinking patterns we call rumination. In depression it’s about worthlessness and guilt, in OCD it’s cleanliness, in anorexia nervosa it’s body image, and in addiction it’s the drug. While pain is slightly different, it seems that pain feedback loops get locked into the brain even when the original painful injury has long gone. Psychedelics can help to break these thought loops and so free patients minds to think about other more pleasant and useful thoughts and activities.

To find out more about how these drugs actually affect the brain we conducted the first ever head-to-head study of a psychedelic with a standard antidepressant called escitalopram (SSRI), and imaging the patients’ brains before and after treatment. We found fundamental differences in that escitalopram worked in the emotional brain centre – the limbic system – to dampen down its stress sensitivity. On the other hand, psilocybin worked in the cortex to make it more flexible, specifically helping patients change their thinking patterns. We are now using  imaging in the other disorders too so will be able to see if this increased brain flexibility is found after psilocybin treatment in those too. Ultimately, we hope that our research with psychedelics could provide the evidence needed to unlock their full potential, providing valuable new treatments for patients.

About the author

David Nutt FMedSci is the Edmond J. Safra prof of neuropsychopharmacology in the Division of Psychiatry at Imperial College London and director of the Centre for Psychedelic Research. His new book on Psychedelics has just been published by Hodder.