In 2006 we began our scientific studies with psychedelics, starting with ayahuasca, an Amerindian invention with intense psychedelic effects. Our early studies used functional Magnetic Resonance Imaging (fMRI) to explore the neural basis of the Ayahuasca's effects. We observed that ayahuasca selectively increases the activity of extensive neural networks involved with vision, memory, and introspection, including the Default Mode Network (DMN). We also observed increased entropy of connectivity between different areas of the brain during the effects of ayahuasca, consistent with the notion that a greater spectrum of experiences is accessible under the influence of psychedelics when compared to the ordinary state of consciousness.

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In 2008 we began our studies about the antidepressant effects of ayahuasca. We conducted the first open-label trial in 17 patients with treatment-resistant depression (TRD) who attended a single ayahuasca session in a University Hospital. A significant decrease in the severity of depression was observed already 24 hours after the ayahuasca session, and the symptoms remained reduced for 21 days. In a follow-up study, we conducted a randomized placebo-controlled trial at the University Hospital Onofre Lopes (the Federal University of Rio Grande do Norte - UFRN). In this study, 29 patients with TRD were assigned to receive either an intervention with ayahuasca or a placebo. We observed significant antidepressant effects one day after the ayahuasca session, which persisted for at least 7 days when compared to the placebo. We found response rates of 50% on one day, 77% on day 2, and 64% on day 7 after ayahuasca administration. This study was the first RCT in the world to test a psychedelic substance to treat TRD.

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The evidence is promising, and equally important is to understand the nature of these effects. Our studies suggest that the therapeutic response results from the combination of modulation of important neuroimmune, neuroendocrine, and neuroplasticity pathways for homeostatic regulation, as well as the phenomenology of acute effects. On the one hand, we observed that the antidepressant effects of ayahuasca were correlated with certain aspects of the experience, such as changes in visual and auditory perception during the experience. Furthermore, we observed that antidepressant effects were correlated with stress markers such as cortisol, BDNF involved in neuroplasticity, and inflammatory markers such as c-reactive protein.

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In recent years, we have changed our focus from ayahuasca to isolated DMT. In part, this change occurs due to the greater practical and economic viability of short-acting psychedelics, such as vaporized DMT. This new study program, which we call "DMT from A to Z", uses multiple approaches ranging from DMT and derivatives chemistry, such as its extraction or synthesis, purification, and characterization, to understand DMT biological functions, and the development and testing of viable and safe DMT-based products and protocols aiming at health and wellness.

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We have conducted preliminary safety and tolerability of DMT in a phase I clinical trial and have just completed a fase II clinical trial in patients with depression.