Depression: caution with serotonin, ayahuasca, psilocybin – 02/26/2023 – Psychedelic Turn

Today a column appeared in Folha that could have been posted here, with the title “Learn why psychedelics work better against depression” and the subtitle “Ayahuasca and mushrooms act faster than neurotransmitters by penetrating neurons”. Since I couldn’t talk about everything there, here’s a complement.

For those who haven’t seen or read it: the column takes a long contextualization turn to end talking about what matters most, the research by David Olson, from the University of California at Davis and the company Delix Therapeutics, showing with rodents that psychedelics like DMT can activate serotonin 5HT2A receptors within neurons.

Well, serotonin itself can’t do that. This neurotransmitter, dubbed the “happiness hormone,” unlike psychedelics, does not cross cell membranes, the study indicated.

“Olson and his collaborators suggest that the differences in effect between serotonin and different psychedelics on neuroplasticity would be dependent on the distinct ability of these substances to cross the cell lipid membrane and reach type 2A receptors located inside neurons”, explains Stevens Rehen, neuroscientist from UFRJ.

“At the end of the day, more important than having the key is knowing how to get to the lock”, sums up the Brazilian, who now works at Promega and the Usona Institute in Wisconsin (USA). It was Rehen who brought Olson’s work to my attention.

Neuroplasticity, or the formation of new brain connections, seems to be decisive for understanding why, although acting on the same receptor, serotonin does not produce an immediate effect or trigger the subjective effect of psychedelic “trips”. Not even when its concentration is increased at synapses by SSRI antidepressants (selective serotonin reuptake inhibitors), such as fluoxetine.

It is said in my text that the experiments that prove the rapid antidepressant effect of DMT from ayahuasca and psilocybin from the so-called “magic” mushrooms are preliminary and limited, due to the low number of participants. In the case of psilocybin, increasingly larger studies, one of them with 233 patients.

Some readers felt that the column was irresponsible in supposedly recommending psychedelics, which it did not. Clinical trials with them are still experimental, although well on the way to approval in the US (as MDMA for post-traumatic stress disorder). And these substances remain prohibited, with some exceptions that this blog has reported.

One of them is the religious use of ayahuasca, allowed in countries like Brazil and the USA, where tens, perhaps hundreds of thousands of people drink the tea regularly, usually every fortnight, without major problems. Prejudice persists, however, and there were those who claimed that it causes schizophrenia or that it triggers psychotic episodes.

There is no news that ayahuasca causes schizophrenia. On the contrary, there are observations that the mental health of people who frequent ayahuasca religions is equal to or even slightly better than the average of the population.

Outbreaks, yes, can be triggered by psychedelics. And that’s why priests, shamans and researchers of these substances interview participants before giving them the drink, refusing it when the person has a personal or family history of psychosis.

In clinical studies with psychedelics, such a history is a criterion for immediate exclusion of the volunteer. The same goes for heart problems and uninterrupted consumption of other drugs and some medications.

But of course, conservative-minded people and institutions will highlight the rare cases of serious adverse effects, outbreaks and deaths to refuel social prejudice against the so-called “drug scourge”. For consistency, they should fight the legality of alcohol and tobacco, which cause much worse individual and social harm.

In any case, even if psychedelics are eventually approved as drugs, they will not be the panacea that fluoxetine and other SSRIs promised to be in the 1980s. It is now known that they do not work for many people and can have serious adverse effects.

There is no miracle cure. Much less for the evils of the contemporary mind, tormented by the sharp times of the pandemic, antisocial networks, climate change, fundamentalism and the risk of generalized war.

Future psychedelic-supported therapy (PAP) will not be for everyone. Not everyone will be willing to face a few hours of intense changes in consciousness and perception, which can be wonderful, but also disturbing (only those who have never experienced one of them speak of “recreational use”).

It will have contraindications, such as those mentioned above. And it won’t work for a lot of people, as it does for a third of depressed people treated with SSRIs.

David Olson’s research seeks to unravel basic biochemical mechanisms of action of psychedelics in the nervous system. The plan of his company Delix is ​​to create molecules similar to them that produce the desired neuroplasticity without triggering the subjective psychedelic effect (“trip”), substances that he calls “psychoplastogens” and have already been dubbed here as “parapsychedelics”.

Many psychonauts believe that the therapeutic benefit will not be the same, or not as intense, without the deep dive into one’s own psyche provided by ayahuasca and the like. They are probably right. But there’s no harm in trying to develop drugs that can help those who can’t face their own psychedelics, for whatever reason.

We have to hope for Olson’s success, while maintaining a critical spirit in the face of business interests and distortions. There’s too much unhappiness in the world to get into this antidepressant sommelier thing. Lithium, tricyclics, SSRIs, psychedelics, psychoplastogens – the more tools in the hands of sufferers and healers, the better.
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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: