The saying goes that no one is a prophet in their land. And a lot of times it's true. It's something you know very well Jordi Riba, a Catalan pharmacologist who has just been included in the North American magazine Rolling Stone In the list of the 25 most people influential In the prospective Of the science. Riba (Barcelona, 1968) enjoys recognition abroad. “I give an average of 10/12 conferences a year across Europe and the US,” he says. But here his investigations, so far, have not had as much impact. Maybe it's because of the substances he studies, which are somewhat exotic. This scientist is dedicated to the pharmacology of the central nervous system and to neurosciences in general. He has studied psychoactive substances that cause changes in perception and cognition, such as Ayahuasca, a kind of concoction that the indigenous peoples of the Amazon have been consuming since time immemorial. Thanks to his research, Riba, head of the Neuropsychopharmacology group at the Hospital de Sant Pau Research Institute, has unveiled part of the potential What is hiding this beverage, and he wanted to share it with La Vanguardia.
How does one feel when they choose one of the 25 most influential people in the future of science.
Well, totally surprised and dumbfounded. It makes me happy to think that there are people who recognize the work we are doing. I have been working for 20 years in an unorthodox area, which has been growing a lot in recent years, especially abroad. Precisely, one of the things that I am glad to have been included in this list is that, perhaps, the area in which I work is better known here. I have to say that in the world of science there are millions of times better people than me [laughs]. I take it as recognition without creating delusional thoughts about my abilities.
Quite a responsibility, isn't it?
No, you have to shield yourself a little bit of that. When I arrived here 20 years ago [at the Hospital de la Santa Creu i Sant Pau] and proposed to start studying psychoactive substances, the person who was the head of pharmacology at the time, Dr. Manel Barbanoj, found it interesting, he was a person with a very open mind. But the reactions I perceived around me were one of quite skepticism.
His studies are somewhat exotic...
Yes, it's a very exotic area. If you are pursuing something that is not part of a project that is already funded, that runs on its own, it means that the effort you will have to make will be a hundred times greater. I followed my path, despite skepticism, doubts, possible criticisms and various obstacles, because I understood that what I wanted to investigate was interesting enough to give my attention. But it's still a commitment to myself, I don't feel a special responsibility to have been included in that list.
How did Ayahuasca cross your path?
I have always been interested in brain biochemistry. I learned about works by anthropologists who had gone to study ayahuasca in South America. I read some of the stories and established contact with one of them. Later, in the mid-90s and by chance in life, I met some of the people who began to organize ayahuasca drinks in Catalonia, especially around Barcelona, who were approaching a series of practices, rituals, that came from Brazil and that involved drinking a drink that had psychoactive properties.
In the 90s there were already groups here that organized takeovers...
There was another group in the Balearic Islands, another in Madrid... I was struck by the motivations of those people to take that substance. I expected to encounter a more playful use of psychoactive substances, but I ran into quite the opposite.
What was found?
These people met every fortnight. They explained to me, through their subjective experience with ayahuasca, that they entered a state of introspection in which they experienced a whole series of sensations. Above all, about the recovery of emotional memories. That was very important to them. I saw that these memories, which sometimes appeared in the form of visions similar to dreams, helped them to revisit some aspects of their biography, and all this without ever losing the awareness that this was produced by what they had taken.
Curious.
They said that it helped them overcome some conflicting situations, traumas, that they had experienced throughout their lives. Twenty years later, ayahuasca has become extremely popular. Now, some of the people who approach this ritual are people who suffer from post-traumatic stress, such as former U.S. combatants in Afghanistan or Iraq, for whom nothing has worked so far. They continue to have intrusive memories and a whole series of disabling symptoms. This is the most recent move.
He told me about the mid-90s and about today. But in between, what kind of people consumed this drink?
People who had serious problems with addiction to cocaine and heroin and who were able to stop this type of use after a period in which they would take perhaps six to ten times ayahuasca. After that, they decided to completely abandon that self-destructive path they were taking.
It sounds surprising.
When I hear these stories I think that what I do seems like it can help someone. If I try to understand the mechanism of action behind all this, I can warn the scientific community that perhaps attention should be paid to this question. When I started out, little attention was paid to these substances, something that made them attractive to me as it was an incognito land. If you have an investigative spirit, this is what you like to do.
Is the interest greater now?
Doors are opening in other countries, such as England and the United States. Highly prestigious universities and research centers are studying analogous substances. In my case I study ayahuasca, the active ingredient that produces visions is called dimethyltryptamine (DMT), but there are other studies that have been done with psilocybin, and also with MDMA, the active ingredient in ecstasy. We are seeing that there are a whole series of substances, which had a very bad reputation, that if used in an appropriate context - for a specific purpose and with a well-chosen population of patients - can have beneficial effects.
And where do you place the tipping point, the turn of the trend?
In the discovery, about ten years ago, of an anesthetic called ketamine that, at sub-anesthetic doses, produces very intense changes in perception. A group of psychiatrists in the United States found that, administered at certain doses, it was a powerful antidepressant that acted very quickly. And now there is a boom in research into this type of antidepressant, which act rapidly through mechanisms that are very different from those used in traditional drugs.
I understand.
With traditional antidepressants, three to four weeks take three to four weeks until you start to see any improvement in symptoms. With ayahuasca, in a study we did in Brazil, we saw improvements in symptoms a few hours after administering a single dose, and the effect is maintained for three weeks.
Surprising.
These results have been achieved consistently with ketamine, and this has opened the minds of many people. Something that was stigmatized as a drug that was consumed in 'raves', we see that it works in some patients. The thing about depression is that there is a very significant percentage of patients for whom no medication works. We are talking about patients for whom electroconvulsive therapy, electroshocks, has not worked.
And how does it work at the brain level?
This is a rather complex preparation. It is an infusion, a tea, obtained mainly from a liana, called ayahuasca and which gives its name to the drink, which grows in the upper Amazon (Bolivia, Venezuela, the westernmost part of Brazil, Peru and Ecuador). This liana contains a series of active ingredients that we have now seen that have very interesting effects on the central nervous system and that are not responsible for vision. The procedure consists of crushing the liana and making an infusion with the leaves of another plant. In these leaves there is a compound, DMT, which is very structurally similar to psilocybin, which is another psycholedical compound.
I'm following him.
Psilocybin can be taken orally, is not broken down and is absorbed. But DMT, if taken alone, even in amounts of grams, is completely degraded and does not reach the blood, so it has no effect. The curious thing about the case is that the active ingredients in liana block the degradation of DMT. And you wonder how it is that the inhabitants of this area of the planet, which is one of the places with the most plant biodiversity imaginable, decided to combine this liana with the leaves of another plant.
Exciting.
The liana is very robust, it is like a trunk. Breaking it, mashing it and making the infusion is a huge job, it's not done by chance. No one knows how they came to the conclusion that this combination worked. What has arrived in Europe and the US is this combination, but there are other groups that add other plants that contain other psychoactive substances and that their consumption could pose a greater risk to health.
Caution must be taken.
Many people who want to experiment with ayahuasca travel to the Peruvian Amazon, go to the first person who tells them he is a shaman and drink what they are offered without knowing what they are taking. There may be, for example, scopolamine (popularly known as burundanga), which is a substance that can endanger your life.
Let's get back to your investigations...
We have done neuroimaging studies, and what we have seen is that under the effects of ayahuasca what happens is an activation of the areas of the brain that are involved in the processing of emotions, memory and areas that are on the border between cognitive and emotional aspects. There is also a certain activation of the visual areas, although it is not something very striking, so we are not sure that this phenomenon is responsible for the visions.
I understand.
The final result is that the person is recovering, as if abruptly, visions that tend to contain significant emotional burdens. There are people who, for example, relive a relationship with someone who was important in their life. The experience is quite intense and can be overwhelming. If you watch a session from outside, you see the person with their eyes closed sitting in a chair. But suddenly, after a while, she may start to cry.
How long can the effect last?
Typically, after taking a dose the effects start after about 45 minutes, it takes quite a while. From there, there is a gradual onset, with a maximum effect reaching about an hour and a half or two hours. Then it starts to diminish and after four or six hours after taking the effects have completely disappeared. It also depends on the amount that has been ingested.
In general, is there a responsible consumption of ayahuasca?
It's a little dizzy to see how it's being trivialized. You see people who organize ayahuasca sessions everywhere, how it appears in the 'New York Times' as an experience that is in fashion... I understand that there are people who go to these sessions thinking that they will have a pleasant, playful and playful time. People, after the experience, say 'wow, wow, wow! '.
Leave a mark...
I have been evaluating people who have consumed it for some time and they explain to me that they believe that after the lived experiences they acquire knowledge that is useful for their lives, but that sometimes they are in the session about to drink the infusion and think 'what am I doing here knowing what is coming! '. Everyone emphasizes that it is not a recreational drug, quite the contrary. If you are looking to escape your problems, taking ayahuasca is the last thing you should do, because it puts them in front of your eyes and you often reexperience them in a painful way.
In other words, nothing playful about drugs.
It has a number of drawbacks that make it unpleasant. In its usual form, it tastes horrible, it also smells bad, it produces a burning sensation in the stomach and practically immediate nausea at the time of taking it. In addition, it is quite common for the person, after taking it, to vomit. There is very little playful about it. If you add to this that experiences can be shocking and painful from an emotional point of view... This is a safety barrier for me.
In what sense?
I do studies with patients who have addiction problems, and the people who work with them tell me: 'Are you telling me that you want to experiment with someone who has addiction problems by giving them something that contains a powerful psychotropic that could have the potential for abuse? ' I assure you that no one will drink ayahuasca for pleasure, 100% guaranteed.
It's good news...
One thing we've recently found is that the compounds in liana, which were thought to only help keep DMT from degrading, have some pretty interesting biological effects. In the adult brain of mammals, there are a number of stem cell niches that produce new neurons. This phenomenon has not been given much attention because the production rate is frankly low. Now, we have seen that two of the compounds that are present in the liana, beta-carbolines, have very powerful neurogenic effects.
Do they help generate neurons?
They stimulate the proliferation of the number of these stem cells and their migration to integrate into pre-existing brain circuits where they are transformed into functional neurons. These three processes are stimulated by these two compounds in the liana. These are the conclusions of an article that we have just published and that has left everyone quite surprised, me the first.
It sounds hopeful.
When I explain that there are people who, through the consumption of ayahuasca, have made a change of life, who were immersed in depression or addiction and have been able to redirect it, and I describe the subjective experience they relate, I find many faces of skepticism. But when you are biologically testing these compounds and you see that they are acting in the same way as antidepressants that work clinically, then you have data that are more easily transmitted and that can be better received and accepted by the community dedicated to the study of neuroscience.
Ayahuasca seems to have a lot of potential.
It is very clear that it produces an effect at the biological level. We have also seen, doing functional magnetic resonance studies (that is, looking at brain structure and brain function), that 24 hours after the consumption of ayahuasca there is a decrease in activity in an area of the brain, the medial area of the parietal lobe, which is directly associated with what would be the intimate perception of your own self. In pathological situations, where there may be depressive symptoms, this area is in a state of hyperactivity, and this hyperactivity is directly related to obsessive and negative thoughts.
I understand.
If we compare ourselves to other great apes (gorillas, chimpanzees, bonobos) one of the things that sets us apart from them is a large expansion of this medial area of the parietal lobe. There is increasing evidence that this part of the brain is possibly associated with self-awareness processes. A specific state in this area seems to be correlated with negative thoughts. We have seen that once the acute effects of ayahuasca have disappeared, there is a deactivation of this area.
Interesting.
On a psychological level, we have observed that after the acute effects of ayahuasca, there is a decrease in the constant harmful critical evaluation of oneself made by certain people. This is a deficit that my colleagues in the psychiatry department see in many patients regardless of their diagnosis.
I see that this substance has many applications.
Talking to colleagues who treat people with addiction problems, they tell me that for the treatment of, for example, cocaine addiction there is currently nothing. It's not that there's nothing that works, it's that they have nothing to give them. Everything is symptomatic: if the patient is anxious because they give them benzodiazepines, if they have psychotic symptoms because they give them antipsychotics, they also give them drugs that balance sudden changes in mood... We did a study with people who were diagnosed exclusively with cocaine addiction and we saw changes in their brain structure.
What type?
The connection and volume of the areas of the brain that are constantly seeking gratification had been reinforced and, at the same time, we observed that the areas of the brain that help you assess a situation and warn you of possible dangers were deactivated. No wonder, seeing what we detected, that these people find it extremely difficult to give up their addiction, because there are structural changes, their entire brain has been reconnected.
Astonishing.
These are very problematic situations. But when I see, in parallel, that there are people who, thanks to ayahuasca, explain to me, have managed to give up their addictions, because despite the stigma that it is a substance used by indigenous people, the stigma that it is psychoactive, psychedelic, hippie, etc., I feel an obligation to investigate it, because if I don't, I am failing in my obligation as a researcher. The path I started was rather lonely from 1996 to 2005, but then studies with psilosibin began to appear in the United States, no more or less than at the best medical school in the country, Johns Hopkins.
It is a very prestigious center.
There is another psychiatrist doing the same thing at the University of California at Los Angeles (UCLA). The FDA, the North American drug agency, has also given MDMA a priority therapy designation for treating post-traumatic stress, a huge problem in the United States, and there is another group at Imperial College London carrying out this type of study. The United States was also where the first research was done with ketamine for therapeutic use. When sacred institutions like these start doing this type of research, you get more people to pay attention to you when you talk about it.
I previously commented that some compounds in the liana have the property of generating neurons. Could it have its practical application in diseases such as Alzheimer's?
We are very far away. We are very cautious. The rate at which niches within the adult brain of mammals produce new neurons is low. You can stimulate it, but there has always been a question as to what extent and if this stimulation could counteract the neural loss associated with a neurodegenerative disease. We don't have the answer for this yet. The next step we want to do is test it in animal models, we want to see if cognitive deficits could be prevented or reversed.
If all these investigations you have done do not one day end up with a therapeutic translation, how will you feel?
I started studying all of this because I was very intrigued by its mechanism of action. I am not a clinician, I am very interested to know how the brain works and how it was possible that very simple substances a priori could alter in such a profound way the capacity in which we perceive and think our emotions, as well as the perception of our self and of our role in the world. That was my main interest. I was the number one skeptic that these investigations would one day have therapeutic applications. It wasn't my goal. But others have seen that I could have it, and they almost had to convince me. In this case, I think that the risk-benefit ratio would be fully justified.
What's the use of knowing how a substance acts in the brain if it doesn't have a therapeutic translation afterwards?
Newton's laws date back to the 17th century and were not applied to reach the Moon until 1969. Possibly Newton never thought about it, he did it for the sake of understanding how gravitation worked.
You research for the pleasure of knowing...
Yes, basically I do it for the sake of knowing. You spend very long periods of time in emotional misery, but the day you get results, that day you feel satisfied.
It's hard for a neophyte like me to understand that something isn't being researched for a practical purpose.
Then you look for her. This is the big mistake that is being made with regard to the approach being given to science. When you ask for resources for a project, they ask you about the translational capacity it will have in the form of a benefit to society. It's a vision that you can apply to engineering, but none of the great medical findings have come through a pre-established objective. It is often said, wrongly, that something has been discovered by chance.
Serendipity.
Fleming was with his bacterial cultures and one day, by chance, he was contaminated with a fungus. He could have picked up that plate and said 'it has been contaminated, what a bad thing, I clean it and continue with the experiment'. But instead he stopped and saw how around where the fungus had grown there were no bacteria. And he wondered: 'Is this fungus preventing bacteria from growing? ' But if you had locked Fleming away for 10 years of his life telling him 'you must discover the antibiotic' he wouldn't have found anything.
I understand.
Currently, the powers that be don't understand this, and they want you to find the application now. But that's when you ask yourself: 'Where are the most powerful pharmaceutical companies from? Well, from Germany and Switzerland. And when did they start producing drugs? At the beginning of the 20th century'. I started studying organic chemistry, and all the names of the reactions had, and have, German names. Why? Because they were experimenting with chemistry that was useless throughout the 19th century. They spent a hundred years discovering that this with the other reacted in such a way and that such a thing could be obtained, and then, in the 20th century, they were a pharmaceutical powerhouse. But they were chopping stone for a century.
Something we don't do here.
In Spain we want to skip all this, and they want the application now. You're killing the possibility of discovering things. What are we seeing now? , that many targeted investigations have led to nothing. And many pharmaceutical companies are leaving the central nervous system industry because millions have been spent on targeted research and haven't found anything.
It's not the way to go.
Surely, the guy who thought 'I'll give ketamine to depressed people' had to fight a stigma. 'If that's what the geeks take in the 'raves'. You want to give people a drug, 'they would tell him. But now this man appears in 'Nature' as a great reference. If I had listened to some disgusted faces I saw around me when I got here, I wouldn't have done anything. But you do it because there is something that encourages you to follow that path.
If I had to define in a few sentences what ayahuasca is, how would I do it?
A well of therapeutic potential that we should investigate further. I would also say that I wish I had more resources to research because after 20 years of starting his study he is still giving me surprises. It's an opportunity to possibly develop drugs that can help people who right now have nothing to solve their problem.
Source: La Vanguardia
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