The following text was written because we believe it is important to share certain scientific findings regarding the study of Ayahuasca—primarily pharmacological and biochemical aspects that allow us to understand its interaction with the human body. We are providing this text because we believe that many people interested in experiencing Ayahuasca are not only drawn to the ritual, cultural, and spiritual aspects of this ancestral medicine but also have an interest in scientific discoveries concerning it.
The central visionary component of the ayahuasca brew is N,N-dimethyltryptamine (DMT), found mainly in the leaves of the chacruna shrub. At a biochemical level, DMT is a simple but extremely potent indole alkaloid. However, it is important to note that if a human being ingests DMT orally, they will not experience psychoactive effects. This is due to the presence of the Monoamine Oxidase (MAO) enzyme in the digestive tract, which degrades the molecule before it reaches the bloodstream.
This is where the surprising nature of ancestral knowledge occurs and Banisteriopsis caapi comes into play, providing beta-carbolines (harmine, harmaline, and tetrahydroharmine). These compounds act as Reversible Inhibitors of Monoamine Oxidase (RIMA) and have the power to temporarily deactivate the MAO enzyme, allowing DMT to pass through the intestinal barrier, reach the brain, and cross the blood-brain barrier. As Jonathan Ott pointed out, this combination is a perfect example of how Amazonian peoples solved a bioavailability problem millennia before Western pharmacology.
A crucial point, highlighted by authors such as Strassman and corroborated by current neurochemistry, is that DMT is an endogenous compound. It has been detected naturally in human cerebrospinal fluid, blood, and urine. Its presence in the body suggests it is not a foreign substance, but rather a molecule with which the body is already familiar.
Molecularly, DMT bears a striking structural similarity to serotonin (5-hydroxytryptamine or 5-HT). Both possess an indole nucleus. Due to this similarity, DMT acts as an agonist for serotonin receptors, primarily 5-HT2A. When ayahuasca is ingested, the central nervous system undergoes a profound modulation. The interaction of DMT with 5-HT2A receptors in the pyramidal cells of the prefrontal cortex triggers a cascade of neurophysiological events.
Physiologically, an activation of the sympathetic nervous system is observed. This translates into a slight increase in blood pressure, heart rate, and pupil dilation (mydriasis). One of the most notable effects is the "purge" or emesis (vomiting), which Naranjo and other researchers interpret not just as a physical event, but as a process of psychosomatic release. Biochemically, this occurs due to the high density of serotonin receptors in the gastrointestinal tract.
At the psychic level, an alteration of the Default Mode Network (DMN) occurs. By decreasing the activity of this network (associated with the ego and self-referential thinking), the brain enters a state of hyperconnectivity. This allows areas of the brain that do not normally communicate to begin doing so, facilitating the retrieval of emotional memories and the generation of complex visions.
Unlike other psychoactive substances or conventional drugs, ayahuasca and DMT exhibit a notable characteristic: the absence of tolerance. Studies by Riba and Barbanoj demonstrated that repeated administration of ayahuasca doses does not require an increase in quantity to achieve the same effect. The body does not generate immediate pharmacodynamic resistance, which allows for its use in ceremonial contexts lasting several days.
Regarding quantity, doses used in clinical studies usually range between 0.5 mg and 1.0 mg of DMT per kg of body weight. In a traditional context, this is equivalent to a small cup of concentrated brew (approximately 50-100 ml). The human body is extremely efficient at processing these molecules due to their endogenous nature and the reversible character of the vine's inhibitors.
This is a question many people ask. In strictly lethal terms, the toxic dose is extremely high—well beyond what a human being could physically ingest in a ceremony. The real risk is not the toxicity of DMT, but pharmacological interaction.
The primary danger is Serotonin Syndrome, which occurs if ayahuasca is combined with antidepressant medications (especially SSRIs) or substances that drastically increase serotonin levels. In these cases, the excess serotonin can cause hypertensive crises, tremors, and, in extreme cases, systemic collapse. However, under professional supervision and by following dietary and pharmacological restrictions, ayahuasca is considered physiologically safe.
Once the effects of ayahuasca wear off (generally between 4 and 6 hours after ingestion), the body initiates a process of cleansing and restoration. At the cellular level, assimilation is rapid. MAO-A recovers its normal function in a matter of hours. DMT is primarily metabolized into indoleacetic acid, which is excreted through urine. No toxic residues remain in the liver or kidneys.
The most interesting part happens afterward. Recent studies suggest that the interaction of ayahuasca with sigma-1 receptors promotes neurogenesis and synaptic plasticity. After the substance has passed through, neurons show a greater capacity to form new connections.
The serotonin receptor system regulates itself quickly. The "down-regulation" phenomenon (reduction of receptors) that occurs with drugs of abuse does not take place, which explains why there is no "crash" or withdrawal syndrome, but rather a state of clarity known as the afterglow.
Research by Riba, Barbanoj, Ott, and Escobar has validated what Naranjo sensed decades ago: ayahuasca is a consciousness modulator that operates in harmony with human biochemistry itself. By mimicking and enhancing compounds that already reside within us, ayahuasca acts as a master key that opens doors to the psyche without compromising the long-term physiological integrity of the organism. Its assimilation is a testament to biological elegance: a potent molecule that enters, transforms perception, and exits the system without leaving traces of toxicity, leaving in its place fertile ground for psychological integration.
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