5 Questions for ayahuasca researcher Fernanda Palhano Xavier de Fontes

Palhano-Fontes on the potential therapeutic effects of ayahuasca, and why her research team is beginning to study DMT

More than a decade ago, Fernanda Palhano Xavier de Fontes was finishing dual undergraduate degrees from Federal University of Rio Grande do Norte in Natal, Brazil, and École National Supérieure d’Electrotechnique, d’Electronique, d’Informatique in Toulouse, France. Her classmates were planning to start masters programs in electrical engineering, or taking jobs in the petroleum industry, but none of it felt quite right to her. Then she attended a neuroscience talk about using fMRI imaging to record the brains of people tripping on ayahuasca. At the time, Palhano-Fontes had never heard of ayahuasca, and as an engineering student, hadn’t considered a career in neuroscience. But the talk made a big impression on her and soon after, she started a neuroscience masters program.

Now, Palhano-Fontes is a researcher at Federal University of Rio Grande do Norte studying the neuroscience of psychedelics. The Microdose spoke with her about the potential therapeutic effects of ayahuasca, and why her research team is beginning to study DMT.

What did your first ayahuasca experiments look like?

We had two experiments. In one, we gave ayahuasca to healthy volunteers who were part of the Santo Daime church. Here in Brazil, we have some churches — the Barquinha, União do Vegetal, and Santo Daime — that use ayahuasca as a sacrament. So these participants were people with a lot of experience with ayahuasca; some had taken it a hundred times. Ayahuasca is normally taken orally, and the effects start about 30 to 40 minutes later; the peak is at an hour and a half, and its effects subside after four hours. We used fMRI to investigate the neural basis of psychedelic effects; people were scanned before the study, and 40 minutes after ayahuasca intake. Our research group had two publications from this study, one on the visual imagery people experience during ayahuasca experiences, and another where we investigate the default mode network.

During that time, our colleagues at University of São Paolo began investigating the antidepressant effects of ayahuasca. In the church, it’s very common to hear people talking about how they were depressed or anxious, or had drug use issues, and ayahuasca helped them get better. Based on those anecdotes, the São Paolo group had the idea to bring participants to the hospital for an open-label study, where both researchers and patients knew they were getting ayahuasca. The results were impressive. The patients who had treatment-resistant depression showed improvement a day after their dose, and that improvement continued for 21 days after. So I had the idea to run a second phase of that study, but with a randomized, placebo-controlled, double-blind protocol. Half of the participants got ayahuasca, and half got a placebo. It’s hard to have a true placebo in psychedelics — it’s one of the big issues in the psychedelics field, people can sometimes tell if they were given something or not — so unlike the first study we ran with Santo Daime church members, we did this study with people who were naive to psychedelics. That way they had no preconceived notion of what ayahuasca was like.

Do we know why ayahuasca might be effective?

To address this question, in our studies, we recorded a lot of biomarkers. We wanted to know why ayahuasca might have an antidepressant effect. We measured some hormones, inflammatory biomarkers, fMRI data and questionnaires. We found some biochemical changes after ayahuasca doses. For instance, patients had equivalent levels of cortisol, a stress hormone that is altered in depression, as healthy controls. We also saw changes in brain derived neurotrophic factor or BDNF, a molecule implicated in neuroplasticity, which also is lower in people with depression. We found increased levels of BDNF in patients who took ayahuasca. And there were also changes in C-reactive protein, which is a marker of inflammation; in the beginning of the study, before patients took an ayahuasca dose, their C-reactive protein levels were higher than in controls. But two days after dosing, we saw a decrease in the ayahuasca group but not the placebo. The changes in biomarkers was correlated with improvements in depression. 

But subjective changes might also be important in explaining these results. A big question in psychedelics right now is whether subjective effects, like a mystical experience, mediates therapeutic outcomes. Some research groups say, yes, mystical effects are necessary for therapeutic effects. Others are trying to produce psychedelic analogs that don’t have psychedelic effects, which can be used for treatment. 

Making ayahuasca requires boiling two different plants for a long time. How did you get the ayahuasca for your research?

One of our researchers was friends with a leader from the Barquinha ayahuasca church. We talked to him and he prepared it specifically for our study. The ayahuasca is prepared in the church, they have a specific session for preparing called prepado. Ayahuasca is prepared from two plants: leaves of Psychotria viridis or chacruna, and the bark of caapi, so the proportion between these two ingredients can vary a lot. They boil the two plants with water, and the length can vary from 8 hours to 2 days. This is a thing that’s difficult scientifically – we always want a standardized thing, so it’s hard. Each paper you read that involves ayahuasca, the proportions will be different unless the researchers used the same batch. So to overcome that, we always provide the concentrations of DMT, which comes from the chacruna leaves from the vidix, and we also include the beta-carboline alkaloids. In that way, you can compare between studies. 

What are you studying next?

We’re planning some studies with DMT alone. We moved from ayahuasca to DMT in order to try to understand better the antidepressant effects of ayahuasca. Is it something driven by DMT, or by the beta-carbolines, or does it have to be the intersection of the two? To disentangle that, we have two clinical trials planned, studying people with depression and treating them with either vaporized DMT or intramuscular DMT. 

What’s the difference between those two methods of administering DMT, and what do you hope to find by studying their effects?

Vaporized DMT normally takes about 10 minutes to take effect – it’s really intense, and really quick. Intramuscular DMT takes around 40 minutes to an hour. Ayahuasca often lasts four hours, so the quick onset of DMT can reduce treatment times. If you want to offer a treatment, it’s easier to convince people to stay in the lab for 40 minutes rather than 4 hours, and it costs less. 

For instance, a psilocybin therapy session takes 6 or 8 hours, and it’s expensive to pay professionals for all that time. It’s a beautiful idea to have two therapists besides a patient the whole time, in a very comfortable room with soothing music, but practically speaking, it’s so expensive. Who can afford that? Here in Brazil, it’s not the reality — the patients in our studies are often poor people with economic difficulties, and can’t afford treatments like that. So we’re trying to figure out how psychedelics can actually be a part of a public health system, and what doses might provide therapeutic effects without being overwhelming. 

This interview has been edited and condensed for clarity and length.