Learn what psychoneuroimmunology is from Attila Szabo

Dr Attila Szabo is a research fellow at the Norwegian Centre for Mental Disorders Research (NORMENT), University of Oslo, Norway. He holds two Master’s degrees in Biochemistry (MSc) and Philosophy (MA). He received his first PhD degree in medicine, focusing on cellular and molecular immunology, and a second PhD in modern philosophy focusing on phenomenology and the philosophy of consciousness. 

His research interest involves psychoneuroimmunology, immunopsychiatry, biological psychiatry and the molecular biology of inflammation. Attila is also interested in the philosophical questions of mind-body interaction, psychosomatic phenomenon and the phenomenology of altered states of consciousness.

Our founder, Floris Wolswijk, spoke with Dr Szabo to learn about his research and upcoming talk at the Nordic Psychedelic Science Conference.

What will you be speaking about at the Nordic Psychedelic Science Conference? 

I’ll be speaking about psychedelics’ physiological effects, focusing on immune and inflammatory regulation. I’m an immunologist and biochemist. I’ve done immunology research for 20 years, investigating the molecular basis of inflammation and researching the link between psychedelics and innate immune responses for a decade or so. At the conference, I will share some of my findings and my general fascination with the topic.

What got you interested in looking at psychedelics, immunology, and other regulatory functions?

At the beginning of my PhD, I researched a specific branch of immunology called innate immunity and was exploring inflammation and inflammatory regulation in the body. I quickly became fascinated with the biology of serotonin. 

Serotonin is like a Swiss army knife. It has a lot of different functions throughout the body, perhaps the most well-known being roles in cognition and mood regulation. However, it also has many essential roles in maintaining homeostasis. For instance, it helps you regulate body temperature, appetite, as well as immune functions. 

Back in 2010, while working on my immunology PhD, I found tons of papers regarding serotonin receptors, specifically the serotonin (5-HT) 2A receptor, and their role in inflammation and its regulation in the human body.

This receptor happens to be one of the major receptors that modulates psychedelics’ hallucinogenic or psychotropic effects. I found this very exciting and interesting and realised it was something that I wanted to explore further. 

I launched my first project on the psychedelic tryptamines DMT and 5-MeO-DMT under the mentorship of Dr Ede Frecska. I was investigating the effect of these tryptamines on the regulation of inflammation in human immune cells in vivo. I became increasingly interested in exploring the immunomodulatory effects of psychedelic tryptamines. That’s how I ended up where I am today with my projects. My research has evolved along the way, and I’m now exploring these effects from a more systems-level perspective.

Is your research focused on the role of psychedelics in the brain and how they subsequently affect the body? Or are you looking beyond the brain and exploring these effects on serotonin receptors elsewhere in the body? 

In the beginning, I was more interested in the systemic immune effects of serotonin receptor activation; specifically, the regulatory mechanisms elicited by the 5-HT2A receptor and another one known as the sigma-1 receptor. The sigma-1 receptor doesn’t fall into the class of serotonin receptors, but both the 5-HT2A and sigma-1 seem to be important in mediating the effects of psychedelic tryptamines on the immune system. 

I was more interested in the peripheral effects of these receptors as we know that both of these receptors are expressed in immune cells and immune tissues all over the body, and they are involved in mediating essential immune and inflammatory functions. These functions also constitute an important part of the current medical paradigm in which bi-directional communication occurs between the brain and the immune system. This part of the biomedical paradigms is called “psychoneuroimmunology”, and it is also my current field of research and part of my academic specialisation.

Psychoneuroimmunology is a thematic overlap between psychology, psychiatry, immunology and experimental neuroscience. In this field, we explore how certain immune-related signalling processes can influence mental states and how, in turn, the central nervous system can alter immune functions. 

We put everything together and what you get is like an interdisciplinary soup where you’re looking at psycho-neuro-immune modulation, peripheral immune regulation, and neural signalling, with serotonergic psychedelics at the heart of it all. To me, it’s like one big jigsaw puzzle, and I enjoy playing around with it. 

Over the past 12 years, what have you found about how psychedelics influence the body?

Unfortunately, the physiological effects of psychedelics are still very under-researched. When it comes to psychedelic research in general, 99% of the research looks at these substances’ cognitive and psychological effects. The massive potential of psychedelics to treat mental disorders and their role in specific assisted psychotherapies can’t be understated. 

Still, the physiological effects of these substances remain more or less unexplored, and that’s where my research comes in, as I have been exploring these effects with particular regard to immune functions.

So far, I’ve done chiefly so-called preclinical research, including human in vitro and animal in vivo studies. Furthermore, Malin Uthaug, who is also speaking at the conference, and I were involved in an observational study with 11 participants published in Psychopharmacology in 2020. From the preclinical human in vitro, animal in vivo and the observational study, we found that 5-MeO-DMT elicited a consistent pattern of effects relating to immune functions, specifically a potent anti-inflammatory modulation. 

These findings point toward the potential role of 5-MeO-DMT in treating inflammatory, autoimmune, and some neuropsychiatric disorders. As we know, these disorders all share one commonality: they have a (neuro)inflammatory component.

Where do you think psychedelics can affect the immune system? Is there one psychedelic that may be better than others in eliciting such effects?

I would say we can only speculate here. Unfortunately, we can’t be sure of these effects due to the lack of data and experimental evidence. However, based on our and others’ publications, psychedelic DMT analogues, such as psilocybin and 5-MeO-DMT, seem to be exceptional candidates for immune modulation. 

For instance, their potential in modulating anti-stress responses (such as hypoxic stress to the brain or other tissues resulting from traumatic brain injury, stroke or a heart attack) can be essential in formulating future clinical therapeutic modalities. 

Regarding these pathophysiological insults, the other receptor that I’ve mentioned, the sigma-1 receptor, seems to be more important. However, the sigma-1 receptor is most likely acting alongside the 5-HT2A receptor and are both involved in mediating the effects of serotonergic tryptamines, so we have two receptors or two major domains of physiological activity and regulation. The known physiological effects of psychedelic tryptamines make them the most promising receptor pathway candidates, but I might be slightly biased given that this is my area of interest.

Within the field of psychedelics, there is an ongoing discussion regarding the necessity of the “trip.” What you’re describing now sounds like processes outside of someone’s conscious control and maybe are necessary for someone to have the trip. Do you see space for psychedelics without a trip that might still influence the sigma-1 receptor, which might not be that important for the acute psychedelic experience? 

Absolutely. With my background in biomedical sciences, I’m looking for the biological and biochemical mechanisms that underlie these therapeutic effects observed in clinical studies. I believe that both components, the biological effects and the phenomenology of the experience, are important for the overall therapeutic effects of psychedelic-assisted psychotherapy. 

While I can’t comment on the subjective-psychological aspects as it’s not my field of research, I believe that we can’t say one aspect is more important than the other. However, ultimately, I think “extra-trip” psychedelic effects have a role to play in the bigger picture as we go forward.

You’ve been working with psychedelics for quite a while. For any young researchers out there, what would you recommend they do to get involved in this research? Is there a certain path that you took that they might be able to follow?

Following your passion is perhaps what’s most important. 

From a biomedical perspective, you can take an undergraduate degree in biology, chemistry or whatever feels fitting to your best interests. Then go for a Master’s or PhD in a more focused field such as neuroscience, cognitive neuroscience or systems biology. Again, passion is the most important thing.

On a side note, I just talked about the physiological effects of psychedelics last week at the University of Oslo. It’s making me very happy to see the great number of people attending and participating in these discussions and activities. It is clearly the best time to get involved in psychedelic research. 

We’re at the beginning of a biomedical renaissance of psychedelics, and this is the best time to just go for it if you have the passion and interest in this type of research. And do it now because the next five to ten years will probably be the Golden Age of biomedical psychedelic research.

How much of this work do you see taking place in the context of universities, or conversely, what will the role of corporate development be in bringing these medicines forward?

Academia is important. Amongst the extensive network of psychedelic researchers across various fields that I have been fortunate enough to develop, I see more and more people engaging with academia which is a good thing and a positive trend. 

There is another trend in the corporate side of things that is also pretty cool. More and more spin-off companies are sprouting from university labs which are helping to push things forward.

I’ve never been a profit-oriented person. With academic research, you’re exploring new territories. You’re in the frontline of a given field, trying to help bring that line forward by figuring out how things work.

On the other hand, many companies in the space now seem to be more interested in generating profits promoting a capitalistic tendency, something that I’m not necessarily a fan of. I am not involved in any companies or corporate-based research. 

Don’t get me wrong. I don’t think it’s a bad thing that companies are establishing their portfolio based on psychedelics because, at the end of the day, they are disseminating information regarding the importance of psychedelics and helping to change the global mindset on these substances, and this is something that we need to do. 

In a decade or so, I hope that we’re in a world where psychedelics are being used as effective treatments for many different disorders, from neuropsychiatric to autoimmune. I would not like to see some people profiting from these medicines and keeping them inaccessible while the great majority who need them continue to suffer. I hope this will be a fruitful psychedelic renaissance and not a capitalistic nightmare.

When people come to your talk at the Nordic Psychedelic Science Conference, what is one key takeaway you want people to go home with?

My main message is that there is a biomedical aspect to psychedelic studies, and how this relates to their therapeutic applications has been under-researched. 

I would like to spark people’s interest to get more involved in the biomedical aspects of psychedelic research as it is incredibly important. 

One thing we do know about psychedelics is that they are very effective in treating certain psychiatric disorders. Still, people tend to forget that we need to understand the underlying physiological mechanisms through which these substances exert their effects. 

In the long run, understanding these mechanisms is particularly important to design “new generation” psychedelics that are even more effective than the ones currently available. Understanding the underlying biological principles will be paramount to developing these molecules and helping patients get the treatment they need.

To learn more about Attila Szabo’s talk and see him in person, go to the Nordic Psychedelic Science Conference website.

Nordic Psychedelic Science Conference is dedicated to developing the field of psychedelic research within the Nordic countries. Participants will get the chance to be updated on the latest research, discover what opportunities might exist in the future and get to meet the experts within the field. The conference is especially relevant for academics, healthcare professionals and students.