Opinion – Psychedelic Turn: UFRJ and Unesp sequence DNA from ayahuasca plants

An ayahuasca session can trigger consequences that are predictable to a certain extent, such as the conversion of an atheist into a believer, or unexpected, such as the project to analyze the DNA of the plants used in psychedelic tea. Francisco Prosdocimi met both of them.

A researcher specializing in genomics, the science dedicated to transcribing the biochemical alphabet of chromosomes to identify genes and their possible functions, until May 2016 he considered himself a skeptical rationalist and secularist. He was in Cuzco (Peru) and decided to take ayahuasca, for the first time, with a local shaman.

“I left that ceremony believing in God, in entities, in angels, in spirits and in reincarnation”, says the biologist from the Institute of Medical Biochemistry Leopoldo de Meis, from UFRJ, now 43 years old. “I had a very strong connection with the spiritual world, which until then had denied and delegitimized all life.”

Mystical experiences happen, although not with all those initiated into entheogenic substances. Prosdocimi says that, in the months after the Peruvian experience, he received a spiritual call to work with ayahuasca in his specialty, genome spelling (he had already participated in the sequencing of the gene collection of a species of parrot, for example).

The project bore its first fruit last October, with the publication of DNA sequences of structures from the chacrona bush (Psychotria viridis), one of the essential ingredients of ayahuasca. The other is the vine-mariri, or jagube (banisteriopsis caapi).

The sequenced structures, in this case, were two cellular organelles: the mitochondria (the cell’s power plant) and the chloroplast (where photosynthesis takes place) of the chacrone. They have their own genomes, much smaller and easier to spell than the many chromosomes found in cell nuclei.

The complete genomes of the plants are almost ready, awaiting only a decision on a BRL 300,000 grant submitted to FAPESP (São Paulo State Research Support Foundation). The request was made by Alessandro Varani, from the Faculty of Agrarian and Veterinary Sciences at Unesp in Jaboticabal, Prosdocimi’s partner in the undertaking.

With this budget, the duo hopes to repeat some sequencing to fill gaps in the “good drafts” they already have in hand, according to Varani. With sequences finalized and analyses completed, they must submit, by the end of the year, one or two articles for publication in scientific journals.

The plan is to follow the “platinum” standard of current genomics, as required in first-rate journals: definitive sequencing and mapping of each chromosome, one by one, without shuffling the sentences (genes) that, in a book, would be located in chapters specific (chromosomes).

Having done this, Prosdocimi hopes to find clues at least for the proteins responsible for the biochemical pathways for the production of dimethyltryptamine (DMT) in chacrone and for the mariri alkaloids, such as harmine and harmaline. It is considered that DMT is responsible for the psychic effect (alteration of consciousness), which also depends on the alkaloids of the vine.

These mariri compounds, known as betacarbolines, inhibit the digestive enzymes capable of degrading DMT, which would prevent it from reaching the brain. To this day, it is a mystery how the technology for combining the properties of the two plants to prepare ayahuasca, used in rituals by various indigenous peoples in Brazil, Peru, Colombia and Ecuador, emerged in the Amazon.

Dráulio de Araújo’s group at the Federal University of Rio Grande do Norte (UFRN) investigates the antidepressant effect of ayahuasca tea (or daime) and DMT. Prosdocimi, Varani and Araújo are studying a partnership to sequence another DMT-producing plant, the jurema-preta (Mimosa tenuiflora).

Prosdocimi is not looking for drugs or pharmacological therapies, although he does not criticize those dedicated to developing ayahuasca pills. “My intention with the project is to praise the sacred plants and thank them for the healing they have brought me,” she says.

“Ayahuasca should be used in a religious context with the guidance of a shaman or shaman. With songs, dances and prayers, the healing experience is much deeper and more effective. This is an ancient tradition of the Amazonian Indians. healing power of the ceremony performed with a spiritual leader on sacred indigenous soil.”

His idea with the project is to start a kind of synthesis of science and spirituality. “I believe that knowledge, basic science, is important, and that this could better clarify how the cure for ayahuasca takes place from a scientific point of view.”

For the UFRJ researcher, ayahuasca provides what he calls a nootropic effect, an increase in cognition and senses –hearing, touch, smell and vision, in addition to proprioception, self, ability to relate ideas and concepts, creativity, etc. This increase in cognitive abilities would make it possible to see regularities that actually exist, in his way of understanding, and not hallucinations, but that escape ordinary cognition.

It is not by chance that the plant samples used in the sequencing were obtained through a collaboration with the União do Vegetal (UDV), a religion that uses psychedelic tea –called hoasca by its practitioners– as a sacrament. The UDV maintains a scientific department and has supported several researches with the drink and who takes it since the 1990s, at least.

The vegetables were collected in Serra da Cantareira, at the Menino Galante nucleus of the UDV in Mairiporã, SP (by coincidence, the place where this blogger drank tea for the second time, as narrated in the book “Psiconautas”). An international protocol was followed that requires immediate freezing of the samples at -80ºC, to preserve the DNA and thus improve the quality of the sequencing data.

The samples were sent for processing at the University of Arizona, which has extensive experience with plant genomes and with which Varani has collaborated for years. He clarifies that all the material is destroyed after sequencing, as determined by Brazilian legislation on genetic heritage.

The analysis of the chacrona genome is taking longer because it is much larger than expected, says the researcher from Unesp. The project predicted 2 billion bases (“letters”), but they are actually 4.48 billion – one and a half times the size of the human genome, which took a decade to be transcribed and published in 2003 (sequencing techniques, today , are much faster than three decades ago).

A hypothesis to explain the astonishing data predicts that the chacrona, a relative of the coffee tree, is a hybrid of two close plant species that kept the genome duplicated, which made it incompatible with the parent species. An allotetraploid, as they say in the jargon of the field.

In addition to eventually indicating the metabolic pathways that produce DMT in the chacrone, the sequencing could shed light on another enigma in the case of the mariri. There are varieties of the vine, called morphotypes, such as the caupuri and the tucunacá, but Varani thinks that the analysis of the respective genomes, as they are doing, could indicate that they are different species.

“It will be a study data-drivenwe will do what the data themselves guide us”, says Prosdocimi. “I don’t want to promise anything because we know that many promises of the genome do not come true.”

The researcher does not say he is concerned about the possibility that other laboratories or companies will use genomic information from chacrona and vine to develop drugs and obtain patents, to the detriment of indigenous peoples who bequeathed such knowledge to biomedicine. In his evaluation, when any technology is created, there is the possibility that it will be misused, but this should not stop something that comes to clarify, enlighten, understand.

Prosdocimi declares himself in favor of sharing eventual gains from this traditional knowledge with native peoples, as provided for in the Nagoya Protocol. “The only thing is that the State needs to intervene, to clarify how this sharing would be. It seems to me that ayahuasca is a diffuse traditional knowledge, which appeared several times independently.”

In addition to Prosdocimi and Varani, they work on the Simone Santos project, from UEPB; José Beethoven Barbosa, from UFRR; Vitor Miranda and Saura Santos, from UNESP; and Danilo Oliveira, from UFRJ. They all went to Menino Galante in September 2021 to collect and work on the genomes of the organelles.

“We go little by little, with great humility and respect, working with responsibility and dedication to praise the teacher plants and learn more about their molecular secrets”, says Prosdocimi.

—

NOTICE TO NAVIGATORS – Psychedelics are still experimental therapies and certainly do not constitute a panacea for all psychic disorders, nor should they be the subject of self-medication. Speak with your therapist or doctor before venturing into the area.

To learn more about the history and new developments of science in this area, including in Brazil, look for my book “Psiconautas – Viagens com a Ciência Psychedelica Brasileira”.

On the tendency to legalize the therapeutic and adult use of psychedelics in the US, see the article “Cogumelos Livres” in the December 2022 issue of Piauí magazine.

Be sure to also see the articles in the series “A Ressurreição da Jurema” in Folha:

https://www1.folha.uol.com.br/ilustrissima/2022/07/reporter-conta-experiencia-de-inalar-dmt-psicodelico-em-teste-contra-depressao.shtml

https://www1.folha.uol.com.br/ilustrissima/2022/07/da-caatinga-ao-laboratorio-cientistas-investigam-efeito-antidepressão-de-psicodelico.shtml

https://www1.folha.uol.com.br/ilustrissima/2022/07/cultos-com-alucinogeno-da-jurema-florescem-no-nordeste.shtml