Psychedelic science has faced a great difficulty since the 1950s: the changes in consciousness that each substance causes vary greatly both in the biochemical aspect and in the personal experience of each psychonaut. Correlating subjective effects with specific brain receptors and neurotransmitters requires an unknown map, but one that is beginning to be drawn.
When the final letter is concluded, this is the expectation, it would, in principle, be possible to go the opposite way: starting from the symptoms and experiences narrated by the patient to indicate the drug or drug combination most appropriate for his psychic pain.
The feat fell to Galen Ballentine, from the State University of New York (Suny), Samuel Friedman, from the Broad Institute (MIT and Harvard), and Danilo Bzdok, from McGill University (Canada). His outline of open territory for travel appeared last Wednesday in the journal Science Advances.
The title of the article says quite a bit: “Travel and Neurotransmitters: Discovering Principle Patterns Amid 6,850 Hallucinogenic Experiences.” In a commentary in the same issue, psychiatrists Daniel Barron and Richard Friedman compare the work to a Rosetta stone (a tablet that allowed the deciphering of Egyptian hieroglyphics) to “translate symptoms into molecules” and “match the right drug to the right patient”.
The so-called psychedelic renaissance launched research into substances such as MDMA, psilocybin and DMT from ayahuasca. The goal in view is to treat mental disorders such as depression, post-traumatic stress and chemical dependency.
In the wake of science came pioneering biomedicine companies. They are engaged in a fierce race for psychedelic patents and a billion-dollar market of patients who don’t get better with available drugs.
The 6,850 subjective reports came from the Erowid portal, which since 1995 has collected testimonies of experiences with psychoactive compounds. The descriptions of the trips were submitted to computerized analysis of the words most used by the psychonauts in each report, for example three times “voices”, two “universe” and one “love”.
14,000 words were considered, then listed by the highest number of occurrences and repetition between reports. Constellations categorized as inner (nausea, fatigue, sleep, belly) and outer (sight, hearing, film) and related to the particular type of drug used emerged.
The next step was to correlate the characteristics of these reports with what is known about the affinity of each of the 27 psychedelic substances to 40 neuronal receptors and the respective neurotransmitters involved. Then, map the areas in the brain where these receptors are found in greater density.
One of the implications of the study is to relativize the traditional separation between “classic” psychedelics (mescaline, psilocybin, LSD, DMT) from the rest (MDMA, ketamine, ibogaine, etc.), based on their known affinity for the serotonin 5HT2A receptor.
Until now, it was pointed out that this would be the mechanism par excellence of the therapeutic potential. In all cases considered, however, there are large numbers of receptors involved, in combinations that vary from drug to drug, but with subtle variations and some overlapping dose.
In the words of Danilo Bzdok, the pattern apprehension algorithm jointly decomposed the semantic context space and the receptor affinity space: “This was the key ingredient that allowed us to extract the archetypes of receptor-experience combinations” and “map in the brain which distinct aspects of the psychedelic experience are linked to which neurotransmitter receptor combos.”
“This, in turn, paves the way for future strategies to design targeted drugs, explore new pharmacological agents that target uniquely or specifically distinct aspects of what are now mixed experiences with visual hallucinations, auditory cues, ego dissolution, emotional reactions etc.”
In their commentary, Barron and Friedman point out that Bzdok and co-authors only used information already available in databases, without performing a single experiment. All they needed was computational resources and a lot of statistics.
“The study is valuable, but it does not explain that it follows the path pioneered by the research group of Enzo Tagliazucchi, from the University of Buenos Aires”, says Sidarta Ribeiro, a neuroscientist at the Instituto do Cérebro at the Federal University of Rio Grande do Norte (ICe- UFRN).
Ribeiro refers to the article “The Varieties of the Psychedelic Experience: A Preliminary Study of the Association between Reported Subjective Effects and Binding Affinity Profiles of Substituted Phenethylamines and Tryptamines”, published by Tagliazucchi in 2018. In fact, the work was cited by Bzdok and was already making use of the Erowid collection.
“In our 2018 work we showed that it is possible to infer how certain groups of receptors are associated with certain subjective effects, in particular through discourse analysis. Furthermore, we suggested that it might be possible to use this approach to ‘reverse engineering’ and designing compounds with certain desired effects for psychedelic psychotherapy,” Tagliazucchi told this blog.
I asked the Argentine researcher why the idea launched four years ago has only now been put into practice in a comprehensive way: “There are still few people investigating psychedelic drugs from the perspective of language”, he commented. “Furthermore, when we published the work in 2018, we encountered a lot of resistance from reviewers and editors because the pharmacological data are not optimal.”
Tagliazucchi says that he followed in the same direction, but never managed to incorporate all the information to carry out the mapping of speech in the brain areas. He thinks that it would also be possible to include a non-semantic analysis of the reports, like the research he conducted with Sidarta Ribeiro and Natália Mota with graphs, a method that only takes into account chaining and repetition of words, not their meaning.
The neuroscientist reports that there is already a company exploring this strategy, Mindstate Design Labs. “I personally believe that these studies may have application in the medium term.”
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To learn more about the history and new developments of science in this area, including in Brazil, look for my book “Psiconautas – Travels with Brazilian Psychedelic Science”
Chad-98Weaver, a distinguished author at NewsBulletin247, excels in the craft of article writing. With a keen eye for detail and a penchant for storytelling, Chad delivers informative and engaging content that resonates with readers across various subjects. His contributions are a testament to his dedication and expertise in the field of journalism.
