“It does not seem to be an exaggeration to say that psychedelics, used responsibly and with proper caution, would be for psychiatry what the microscope is for biology and medicine or the telescope is for astronomy. These tools make it possible to study important processes that under normal circumstances are not available for direct observation.”
From Molecules to Consciousness
by Jennifer Them & Isolde de Jong
I was running a bit late and hurried into the room where Dr. Enzo Tagliazucchi gave a lecture about his research for the Amsterdam Psychedelic Research Association (APRA). To my surprise and pleasure the room was quite full of people. I sat down next to familiar faces and awaited excitedly the lecture. Seeing more and more people becoming interested in psychedelic science, a topic that is really dear to my heart, is always really gratifying for me.
I already knew that Dr. Enzo Tagliazucchi is one of the leading scientists in computational neuroscience and psychedelic research with passion for understanding how the brain can support different states of consciousness. With my background in Cognitive Science which includes neuroscience, machine learning and philosophy I was eager to see what his current research was about. The construct of consciousness has always been a fascinating and also controversial topic in philosophy, science and for me. With science evolving, more and more possibilities of investigating and understanding consciousness arise.
There are multiple ways to investigate different stages of consciousness including REM sleep, anesthesia and psychedelic substances. The REM-sleep cycle (rapid eye movements) returns approximately every 90 minutes and is characterized with fast and restless eye movements. This sleep phase is especially associated with dreams. Unfortunately, due to the fixed time slot there is only little room to study the REM sleep parametrically. Studying the brain under the influence of anesthesia, which strongly resembles the brain when it is dreaming, is easily done in a lab, but way too simple in terms of their phenomenology. The third and most promising way of studying consciousness is with the help of psychedelic substances like LSD, mescaline and psilocybin which provide reversible interventions that alter the state of consciousness. The problem of these substances is that they are not only illegal but also a very sensitive topic to talk about. But Enzo has quite a unique way of addressing this sensitive topic – great humor included.
Suppose someone consumes a typical dose of lysergic acid diethylamide (LSD). The molecules are absorbed by the body and cross the blood-brain barrier, finally interacting with proteins located at the cell membrane (receptors). Depending on the receptor and the type of interaction with the LSD molecule, different intracellular second messengers are recruited, which in turn modify the biophysical properties of the cell and influence its activity. The next two known facts are that the contents of the subject’s consciousness are deeply modified, and that such modifications are related to changes in brain activity, as measured with tools such as fMRI, EEG and MEG. But what happens in between?
Currently, we have knowledge about the two ends of the process, but how can we connect both ends? Enzo moved between theory and experiment to propose a way to link scales based on the following hypotheses:
- That it is possible to map the state of the brain (at different scales) into a space with a distance function or metric (i.e. there is a notion of the proximity between two states)
- That it is possible to map the contents of consciousness into a similar space
- That it is possible to investigate how the distance functions from both spaces relate to each other, e.g. does “being close” in one space imply “being close“ in the other?
Mapping consciousness into a lower dimensional space – that really aroused my curiosity. But what they used as lower dimensional space impressed me even more. Enzo and his team gathered over 20.000 trip reports from Erowid with detailed subjective effects from various psychoactive substances to perform a corpus analysis. Afterwards a latent semantic analysis (LSA) was used to investigate semantic similarity between different trip reports from the same substances and between different substances. And there was it – the lower dimensional space that you can map your subjective experience into – language.
For further analyses they used 18 different psychedelic substances to compute structural similarity between molecular structures and previously obtained binding affinity profiles. Their results did not only surprise themselves but also the reviewers as they had to replicate their experiment again. They found that the semantic similarity correlates with the molecular and binding affinity profile similarities. That means you can relate the language used to describe their psychedelic trip to molecular structure of the substances they ingested and even to the binding affinity of that substance.
Despite the complexity of the topic, the crowd seemed to appreciate Enzo’s innovative approach of using machine learning to move directly from substances receptor binding affinities to subjective reports. At the end of the lecture, an engaging discussion with the audience ensued, during which Enzo answered specific questions on his work and gave his perspective on the future of the field. I left with the feeling that there was something for everyone to learn in this lecture, from scientists and researchers to non-specialists simply curious about the science of psychedelics.
To listen to the interesting and humorous lecture he gave for APRA, head to our youtube channel: