Psilocybin Study To Investigate the Serotonin System in Autism
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Interest in the use of psilocybin and other psychedelic compounds has increased sharply in recent years, with some studies suggesting they may be able to help people living with treatment-resistant depression or obsessive-compulsive disorder (OCD). Psilocybin activates the brain’s serotonin system, which is thought to be involved in the development of some psychiatric and neurodevelopmental disorders.
Some studies have suggested that the serotonin system, including serotonin transporters and receptors, differs between autistic and non-autistic individuals. To study this relationship further, COMPASS Pathways this year announced an investigator-initiated study using its patented formulation of synthetic psilocybin, COMP360, to investigate how the serotonin system may work differently in autistic and non-autistic adults.
Technology Networks spoke to Tobias Whelan, PhD student at King’s College London and research scientist at COMPASS Pathways, who is conducting the study, to learn more about this first-ever mechanistic study of psilocybin in autistic adults.
Sarah Whelan (SW): What is COMP360 psilocybin? Has this already been used in clinical trials?
Tobias Whelan (TW): Psilocybin is an active ingredient found in certain species of mushrooms (often referred to as “magic mushrooms”) and COMP360 is COMPASS Pathways’ proprietary formulation of synthetic psilocybin. COMPASS is funding this investigator-initiated study that will use COMP360 psilocybin to explore how psilocybin affects specific brain pathways in autistic adults. The study is co-sponsored by King’s IoPPN and South London and Maudsley NHS Foundation Trust, led by Professor Grainne McAlonan, professor of translational neuroscience at King’s Institute of Psychiatry, Psychology and Neuroscience (IoPPN), and conducted by me.
COMPASS presented positive results from their phase IIb study of COMP360 psilocybin therapy in treatment-resistant depression at the American Psychiatric Association annual meeting in May 2022 – the study was the largest psilocybin therapy clinical trial ever conducted. They are also conducting phase II studies of COMP360 in other areas of unmet need, specifically post-traumatic stress disorder and anorexia nervosa.
SW: Can you explain to us what the serotonin system is, and why it is important?
TW: Serotonin is a chemical (termed a “neurotransmitter”) involved in the transmission of information in the brain and throughout the body from one brain cell (or neuron) to the next. It plays numerous roles including in the modulation of mood, cognition, social behavior, sensory processing, learning and memory – as well as in physiological functions such as digestion. These crucial biological processes require a large network of neurons that use serotonin as the messenger to communicate – we call this the serotonin system.
SW: What do scientists already know about how the serotonin system is linked to neurodevelopmental conditions such as autism?
TW: Serotonin plays a crucial and varied role during the development of the nervous system, which suggests a potential role for serotonin in neurodevelopmental conditions such as autism. Research has consistently shown differences in the serotonin system in autism when compared to those without autism. These differences can be observed at the behavioral level (such as in social behavior) or at a much smaller scale, including different levels of serotonin receptors (which bind serotonin to “receive” its message) and serotonin transporters (which move serotonin into neurons), or increased levels of serotonin in the blood of around one-third of autistic individuals.
SW: How do you plan to study the serotonin system in autistic adults using COMP360 psilocybin? Why use COMP360 psilocybin in particular?
TW: The study will look at whether the serotonin system functions differently in the autistic brain compared to the non-autistic brain by directly activating this system using COMP360 psilocybin, which we know acts on the serotonin system. The study will recruit 70 adult participants (40 of whom will be autistic and 30 non-autistic) to join us at the IoPPN at King’s College London for the study.
We’ll use several imaging techniques such as magnetic resonance imaging (MRI) and electroencephalography (EEG) to examine the brain after participants have taken either a placebo or a single, low dose of COMP360 psilocybin. We call studies like these “shiftability” studies as we’re looking for “shifts” in biological markers of autism following the administration of psilocybin.
SW: What is the significance of this study, and what are its long-term goals?
TW: There are no approved pharmacotherapies that target the core features of autism for those that experience challenges and seek support. One of the reasons for this is the heterogeneity of the autistic population, illustrated by a well-known expression in the autistic community: “If you’ve met one person with autism, you’ve met one person with autism.”
Through this study, co-sponsored by King’s IoPPN and South London and Maudsley NHS Foundation Trust, we are aiming to identify subgroups amongst the autistic population with similar biology as it’s unlikely that one particular mechanism underlies all autistic features. Our work has shown that the autistic brain responds differently to drugs compared to non-autistic individuals, so it’s unsurprising that the current support options (that aren’t tailored to autism) are insufficient.
Importantly, we see a lot of variability in the brain response of the autistic participants themselves. By giving a low dose of COMP360 psilocybin and looking at individual responses in the autistic group we can see who experiences a “shift” in their serotonin system after COMP360 psilocybin. Seeing this “shift” would suggest that one’s serotonin system is functioning differently from a non-autistic individual, and that serotonin underpins the challenges they may experience. This implies that a care model which targets this system (such as psilocybin) could be more appropriate for this individual. This way we are putting the individual and their biology first, rather than categorizing using a broad overarching diagnosis. It’s a crucial step towards personalized, tailored care models for individual needs, which is especially important in autism.
SW: What drew you to this area of research?
TW: My 12-year-old brother Rafferty is autistic, and I began learning more about autism following his diagnosis almost a decade ago to support him as well as my parents, who were also relatively naïve to autism. I was in the middle of my undergraduate degree in neuroscience at the time and went on to complete several research projects on the topic, including my master’s thesis. But it’s really my own personal experience with Rafferty that made me aware of the challenges autistic people can face and the lack of appropriate support available.
The development of better support options for autistic people through research like ours, for me, empowers autistic people to choose as more options become available, and any such attempt should be alongside our collective effort to make environments more appropriate and accepting of autistic people - it’s that world that my brother will grow up into.
Tobias Whelan was speaking to Sarah Whelan, Science Writer for Technology Networks.