The underlying question: What is real to the brain?
In the first part of this series, we reviewed the neurobiological foundations of the visions produced by entheogens, with ayahuasca as the protagonist, as it is the substance with which most available studies have been conducted. The more psychological side of the matter remained: what happens, in terms of mental processes, when someone “sees” with their eyes closed? To approach this, research relies on what are known in psychology as paradigms: experimental designs intended to isolate a specific process. Just as optical illusions are used to study the visual system or word lists to study memory, here volunteers are asked to perform visual tasks under the influence of a hallucinogen to observe what happens.
The neuroimaging study: Photographing the inner vision
Between the publication of the first and second parts of this series, a study appeared in a top-tier neuroscience journal that applied one of these paradigms using functional magnetic resonance imaging (fMRI). It is a pivotal piece of work: fMRI allows us to “photograph” which areas light up while a task is being performed, bridging the gap between purely biological studies—administering the substance and seeing what happens—and purely psychological ones.
Nine people with extensive experience in ayahuasca use participated. Each went through two scans: one under baseline conditions, without having taken anything, and another about forty minutes after drinking the infusion, in addition to several effect questionnaires distributed throughout the session. The task was organized into three-step blocks: first, they passively viewed images of people, animals, or trees; then, they closed their eyes and attempted to mentally recreate that same image; finally, they observed a control image made with the same pixels, but scrambled.
The central finding is striking. The brain areas that were activated when looking at the images under normal conditions were practically the same as those that lit up when imagining them under the effects of ayahuasca. Conversely, before taking anything, imagining those images barely mobilized those areas, just as the pixelated images did not. In other words: to the brain, looking at an image while sober is very similar to imagining it while under the influence. This could be part of the explanation for why many people who drink ayahuasca grant the experience the same status of reality as everyday life: if the neural mechanisms that sustain them are the same, the boundary blurs.
The study also provided two relevant details. The first is the intense activation of occipital areas—the back of the brain, responsible for visual processing—and especially the region known as BA17, which the authors link to the peripheral visual field. It was the only activation that correlated with psychiatric-type scores, suggesting that paranoia or other symptoms that sometimes emerge during the experience could stem from this activation, rather than from the specific content of what the person is thinking. The second detail: when analyzing the functional connectivity between different areas, that same occipital focus appeared to drive the global effect, followed by parahippocampal and frontal regions.
Why sometimes just opening your eyes is enough
If we accept the authors’ interpretation, this peculiar cerebral choreography would fit with a practical idea that the ayahuasca community knows well: that to stop a spiral of discomfort, it is often enough to simply open your eyes. Doing so would interrupt the dominance of that occipital activity and return control to other circuits. Resources like the soplo (blowing smoke) or the facilitator’s chants would fit into the same line, as they redirect the person’s attention rather than “reasoning” with them.
It is best to take this with a grain of salt: it is a reasonable hypothesis, not a closed conclusion. Even so, it has a certain internal coherence. Paranoid experiences usually organize themselves around what is happening “around” us—feeling watched, sensing that people are talking behind our backs—so it would not be surprising if regions linked to peripheral vision are involved. From this, a useful intuition for support arises: it is likely counterproductive to overwhelm a person with words and arguments during a difficult moment, whereas modulating the environment is usually more effective.
A difference from the study discussed in the first part—where these visual areas were not activated—helps to understand this. There, the volunteers simply rested without any instructions; here, they were asked to look or imagine actively. It is possible that the entire process is triggered when the person brings to mind internal images loaded with biographical meaning, and that the remembered content then acquires the same weight as the real one. That BA17 participates in this is not new: it was already known, through mental imagery studies, that the “mind’s eye” relies on these regions. The interesting part is the underlying implication: to the brain, what the inner eye sees under an entheogen is as real as what it sees without one. And that brings us back, inevitably, to an old question: what exactly is reality?
Psychological mechanisms: An experiment with MDA
The third pillar was missing: the strictly psychological mechanisms. And here, the experimental literature—not psychodynamic theories, but laboratory data—is almost a desert. In practice, there is a single reference study, published in an open-access journal, that is worth summarizing.
Its authors start from the premise that hallucinations, in a clinical sense, are usually explained by a combination of three non-exclusive phenomena: a loss of perceptual or sensory capacity; an anomalous increase in neuronal activity (as occurs in certain migraines with aura or some epilepsies); or alterations in the cognitive processing of information. To test each hypothesis, they chose a model drug, MDA, and at the peak of its effects, subjected the volunteers to three different perceptual tests.
The choice of substance has its logic and its limitations. MDA is not as visionary as classic hallucinogens—ayahuasca, psilocybin, LSD—but it is psychologically more manageable, which allows participants to complete the tasks. With a more visionary compound, one would gain intensity in the phenomenon being studied, but risk the effect being too overwhelming to do anything. It is one of those uncomfortable balances in this type of research.
The design was double-blind and placebo-controlled: twelve people with prior experience with MDA. Half reported closed-eye visions under the substance, but not with the placebo (with the curious exception of one participant who claimed to see “beings” with the placebo, something that happens in blind trials). The three tests measured, respectively, the degree of distortion of an optical illusion, the ability to detect the contour of a camouflaged figure, and the recognition of a figure blurred by gradients.
The result was modest and honest: the intensity of closed-eye visions was associated with poorer performance in two of the three tests—contrast integration and object recognition. But no clear relationship appeared between the global subjective effects and that poorer performance. The most that can be concluded is that perhaps people with poorer perceptual organization are more prone to having visions with hallucinogens, which is far from explaining the mechanism. Research, this case reminds us, is frustrating: it rarely gives clean answers and almost always ends by calling for “more studies.” Its value lies not in what it proves, but in being pioneering and in guiding how to design future work better—for example, with more visionary substances or with paradigms like masking and signal detection theory.
A final note: the participants scored high on a scale of mystical experiences, something that has also been observed in recent research with psilocybin. The next installment of the series will address that territory.
Critical reading
These findings are suggestive, but they should be read with caution. The samples are tiny—nine and twelve people—composed of experienced users, and a good part of the interpretations (the role of BA17 in paranoia, the utility of opening one’s eyes) are hypotheses that the authors themselves present as such. Neuroimaging shows correlations, not causes, and “the same areas are activated” does not equate to “it is the same process.” Nor should the functional attribution of a region be confused: different studies describe the BA17 area (primary visual cortex, V1) in ways that do not always coincide with the idea of “peripheral vision” used here.
On a practical level, none of this replaces human support or common sense. This article does not offer doses, preparations, or consumption guidelines: it describes science, it does not recommend practices. The substances mentioned are potent psychoactives with a risk profile that depends on context, psychological state, pharmacological interactions (harmine and other beta-carbolines are MAO inhibitors, which entails real dangers), and personal or family history of psychiatric disorders. That a bad moment can sometimes be redirected by opening your eyes does not mean that every crisis is harmless. In the face of intense distress, the prudent course is to seek safe environments, knowledgeable company, and, if necessary, professional care.
