Unveiling the mysteries of psychedelics

October 2023

SB: Hi Deborah, thank you so much for your time and congratulations again for winning the ECNP Poster Award at the 36^th ECNP Congress 2023!
DR: Thank you, happy of being here!

So, tell me a bit about yourself. What is your background and how did you get to work on this topic?
I am originally from Mexico, where I got my Medical Degree and I did my medical practice. I have always been interested in Neuroscience and in how the brain works but never really worked in the field until I started my Master in Genomic Medicine in London. Here I had the chance to learn about the experiences of some study participants that received a dose of psychedelics to treat psychiatric disorders and this got me really interested in the topic. I thought that psychedelic-based interventions hold so much potential to help people that are struggling with mental disorders, and I wanted to understand what are the biological mechanisms underlying their effects. I did some online research about the topic but I could find very little information on the molecular aspects of psychedelic research. I decided to reach out to James Rucker, that is leading the clinical trials on psychedelics at King’s College. I really wanted to work on the molecular effects of psychedelics to understand what happened in the brain but no one was working on molecular projects at the time, so we reached out to Deepak Srivastava and we wrote a PhD a research project with him, that finally got funded. Now I am on my third year of PhD at King’s College.

Understanding the biological mechanisms underlying the effects of psychedelics is indeed a very relevant question and your work shows a promising step towards it! Would you like to tell me something about it?
Sure. In this project we looked at the molecular effects of some psychedelics on neurons derived from human induced pluripotent stem cells (or iNeurons). The main strength of iNeurons is that they derive from human cells, representing a much closer model to the human brain than are neurons coming from animal models, which can be quite different from the human ones, e.g. in terms of receptor function. We used DOI and Psilocin, a 5HT2A receptor partial agonist, and we characterized the effects of these compounds on the expression of immediate early genes involved in synaptic function and neural plasticity. We found that iNeurons expressed functional 5HT2A receptors (responsible for mediating the psychedelic effects) and that both DOI and Psilocin induced the expression of genes involved in synaptic function and plasticity both two and twenty-four hours after treatment. This is really interesting, because it shows that we could use these in-vitro models to understand more about the effects of psychedelics on the human brain.

What were the main challenges of this project for you?
It was certainly a challenging project, under many aspects. First, it was my first time working in a biological lab, so it was a big challenge to learn my way around the lab. Second, lab work, especially when involving cell cultures, requires a lot of planning and a lot of attention, as cells are really delicate. It was quite a challenging journey and my learning curve was very steep in these two years!

Is there anything in particular that surprised you while working on this project?
Yes, many things! The first time that I saw an actual neuron under the microscope I was so amazed, and I thought “this is really incredible!”. It was so fascinating to see how one day my cells had these blob-like shapes and two days later they were fully formed neurons. Also, seeing the results of my qPCR for the first time and understanding how it worked was really impressing and rewarding.

Do you see any clinical translation of these findings into clinical practice?
I think that it is a bit too early to say. However, I think that these models could be very useful to get insights into the mechanisms underlying psychedelic treatment but also into the pathophysiology of several psychiatric disorders. Hopefully in the future it will help guiding treatment choices.

Do you have any next steps regarding this project and your career?
I am planning on making more experiments to better characterize my iNeurons. I am planning on doing some RNA sequencing to see what happens in these cells but also at network connectivity between these cells using electrophysiology. Hopefully, my work will be the first step in a larger project involving the use of cells of patients to gain a complete overview of what these compounds do, also at the individual level.

I am a medical doctor, so I would like to move more towards working in the clinic, but also keep doing research at some level. In particular, I would like to bridge communication between preclinical research and the clinical field, which is something that I feel is often missing. While doing this, I would also like to reinforce my connections with my home country, Mexico.

Well, that sounds exciting. Best of luck with your PhD and your career and thank you so much for your time!
Thank you, you too!