The document discusses the effects of ayahuasca, a traditional Amazonian brew, on brain physiology, highlighting its components such as DMT and beta-carbolines that influence mood, cognition, and therapeutic potential for various disorders. Research indicates ayahuasca enhances neuronal plasticity, creativity, and emotional processing while modulating neurotransmitter activity and producing unique introspective experiences. Overall, it showcases ayahuasca's potential benefits in mental health treatment, demonstrating positive effects without inducing tolerance or dependence.

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Dr. Kevin David Zapata Castañeda
How does Ayahuasca affect the brain – By Dr. Zapata
ayahuasca-retreat.com/how-does-ayahuasca-affect-the-brain
Ayahuasca, an ancestral medicinal brew of the native peoples of the Amazon, has been
gaining popularity and use over the past years. Its use in cities, where it was almost
impossible to find about 20 years ago, has become increasingly common. This has led to
more frequent research on its components and has sparked interest within the scientific
community regarding its potential therapeutic uses, considering the numerous reports about
its benefits, primarily in the fields of psychiatry and neurology. In the last decade, research
on Ayahuasca has been on the rise, especially regarding its main components, DMT
(Dimethyltryptamine), and the Beta-carbolines (Harmine, Tetrahydroharmine, and
Harmaline), which has led to a better understanding of the mechanisms of action and its
effects at the cerebral level.
Key takeaways:
The combination of the substances present in the ayahuasca brew allows the
modifications in the connections in the brain and produce the experience.
The main element present in Ayahuasca is DMT, that is a substance like serotonin and
has implications in the regulation of social behavior, appetite, circadian rhythm, sleep,
attention, anxiety, emotional state, learning process and memory.
Other substances present in the Ayahuasca are B-carbolines with anti-inflammatory
and antioxidant effects in the human body.
The neurophysiological effects on the brain caused by ayahuasca show positive effects
on mood, cognition and possible therapeutic effects for depressive, addiction disorders
and Parkinson´s disease.
What are the components of Ayahuasca or Yagé?
The main alkaloid substances present in Ayahuasca come from two different plants: the vine
Banisteriopsis Caapi, which provides the Beta-carbolines: Harmine (HAR),
Tetrahydroharmine (THH), Harmaline (HML), and the leaves of Psychotria viridis (known as
chacruna), which provide N, N-dimethyltryptamine (DMT). (figure 1). Both components are
responsible for producing the psychoactive effects that induce different states of
consciousness that aid in the healing of the mind, emotions, and spirit. Let´s talk about every
one of them.
Must Read Blog: What is Ayahuasca

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DMT and its importance in Ayahuasca
DMT is one of the components present in the brew and has been widely studied because it is
a molecule that has a similar structure to serotonin (5-HT). Figure 2
DMT is also classified as an endogenous trace neurotransmitter (which means, it is part of
the body´s substances that transmit messages between cells and is present in tissues such
as lungs and brain but in very low quantities)

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What is serotonin and why is it important to know about it?
Serotonin or 5-hydroxytryptamine (5-HT) is a neurotransmitter (a substance used by neurons
to communicate with other neurons and with other cells) that is produced in the central
nervous system(brain and spinal cord) and in other organs of the body (intestines, platelets);
it has implications in the regulation of social behavior, appetite, circadian rhythm, sleep,
attention, anxiety, emotional state, learning process, intestinal movements, memory,
modulator of the hemostasis (regulation of blood clotting), control of blood pressure and also
it is a growth factor which may help in wound healing. Its concentration is reduced under
stress.
Therefore, by understanding the functions of serotonin, we can get an idea of the brain
effects of the beverage.
How does serotonin affect the brain?
There are at least 14 different types of serotonin receptors identified in the brain and each
receptor subtype has specific functions with different signaling pathways, some receptors
can have inhibitory or excitatory effects on neurons.
There are some cells called the neurons of the raphe nuclein, which are the main sources of
5 HT in the brain; from there, the neurons form different pathways. (table 1)
Ayahuasca, DMT and serotonin, what about them?
Ayahuasca contains DMT among its components, which is a substance that acts on the
same parts of the brain as serotonin (5HT1a, 5HT2a, 5HT2c neuronal receptors). We must
consider that its other components (Beta-carbolines) can also act as neurotransmitters, as
they can either bind directly to the stimulated brain area (neuronal receptor) or inhibit the
degradation of serotonin (increasing the availability of serotonin for further stimulation) by
inhibiting monoamine oxidase-A (MAO-A), allowing for greater availability of noradrenaline
and serotonin in the brain.

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Neural communication to further understanding!
We will see a typical example of neuronal communication through serotonin, not forgetting
that this same function can be carried out by DMT.
In the following diagram, we can see two neurons communicating. The first one contains
serotonin molecules inside it (acting as messengers) and is called the presynaptic neuron,
while the second is called the postsynaptic neuron. Serotonin is released into the space
between the two neurons, which is called the synaptic cleft, and from there, it binds to the
5HT receptors on the surface of the postsynaptic neuron, producing stimulation.

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In the image, we can also observe that in the first neuron, there are structures responsible
for trapping the serotonin that remains free in the space and carrying the excess back to the
presynaptic neuron to deliver it to monoamine oxidase (MAO) for its elimination. Figure 3.”
What about the other compounds in Ayahuasca? Let's find out what
Monoamine Oxidases are!
Monoamine oxidases (MAO) are a group of enzymes in the body that are responsible for
controlling the availability of the neurotransmitters serotonin, dopamine, and noradrenaline,
therefore, they also have effects on DMT when it is ingested orally.
There are many types of MAO inhibitors, and some are still used as antidepressants, as it
has been evidenced that their imbalance (too much or too little MAO activity) is thought to be
responsible for several neurological disorders. For example, unusually high or low levels of
MAOs in the body have been associated with depression, schizophrenia, substance abuse,
attention deficit disorder and migraines.
However, Ayahuasca contains Beta-carbolines among its components, which are the
alkaloids responsible for temporarily blocking the action of MAO, and it is this inhibition that
allows DMT to reach the brain, leading to the elevation of serotonin, noradrenaline, and
dopamine levels, and therefore of the DMT.

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Ayahuasca and MAO inhibitors.
Multiple studies have demonstrated the presence of MAO inhibitors in Ayahuasca, namely
the so-called Beta-carbolines: Harmine, Tetrahydroharmine, and Harmaline, which are found
in higher concentrations in the beverage. It is thanks to these substances that DMT can enter
the brain, exerting its effect on serotonin receptors.
Research on Ayahuasca has indicated that the combination of harmine and
tetrahydroharmine may be sufficient to produce the inhibition of the MAO enzyme, with this
inhibition being temporary.
How does the Ayahuasca brew affect the brain?
The effects of ayahuasca on the brain are complex and multifaceted. Research on this topic
is still ongoing, and the exact mechanisms by which ayahuasca affects the brain are not yet
fully understood.
The effect of the brew starts around half an hour after its intake and subsiding within four to
six hours, producing exacerbations of sounds and a transient introspective state
characterized by dream-like visions with closed eyes (that are different to hallucinations
because in that, most people are fully aware of the visual effects), recollection of personal
memories, and intense emotions.
This kind of connection may produce changes in the way people perceive reality, for some
studies have associated the intake of Ayahuasca with modulation of neuronal plasticity (the
capacity of the brain to create new connections with other neurons), one of the mains effects
in the brain.

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If we divided the substances presents in Ayahuasca, we can find that:
DMT, harmaline and tetrahydroharmine have shown antioxidant effects at cellular level, that
is, they trap substances that damage cells.
Harmine and Harmaline increases the concentration of Dopamine, which could have benefits
in the management of Parkinson´s disease.
Harmine has been shown in some studies to have anti-inflammatory effects in the body by
inhibiting internal cellular responses to stimuli such as stress, ultraviolet radiation, bacteria
and viruses.
DMT promotes the generation of new neurons (a process called neurogenesis) by activating
specific areas of the hippocampus (a zone in the brain) where exists a large number of
neural stem cells, therefore, improving learning and spatial memory skills.
DMT has a protective effect on cells against oxidizing agents (those that cause aging in the
cells) and effects on myelination process (which is responsible for providing protection to a
part of the neurons called axons)
The combinations of the substances present in ayahuasca infusion has antidepressant
activity; a therapeutic effect usually linked to hippocampal neurogenesis.
At a psychological level, an increase in creativity and creative thinking has been evidenced.
There has also been described a series of subjective experiences involving ethical lessons,
leading the individual to establish deep connections with inner self and with the so-called
‘source', which brings benefits in terms of consciousness, affection, life satisfaction, self-
acceptance, and compassion.
Other benefits at the behavioral level involve enhancing introspection, leading to reduced
stress levels, improved judgment processing, enhanced internal reactivity, which induces
changes in the perception of events, emotions, and cognitive processes, ultimately resulting
in improved management of anxiety, panic, depression, hopelessness, and addictions.
As an interesting fact, from a pharmacological standpoint, Ayahuasca does not produce
tolerance (a decrease in effects when used repeatedly) nor physiological dependence, as the
studies conducted have not evidenced associated psychiatric disorders (withdrawal,
tolerance, abuse behavior, and social alterations).
The default mode network and the Ayahuasca.
In the brain there is a zone that is called the default mode network. It has multiple functions,
which include recognition of the self (autobiographical memories and events, own emotions),
thoughts about others (empathizing with the emotions, making judgments about what is fair

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or not, social interactions), memories about the past, thoughts about the future and
consolidation of memories. This part of the brain is important since multiples studies have
shown effects of the Ayahuasca in this region.
One of these studies shows that ayahuasca produces a significant activation of the frontal
and paralimbic brain regions, increasing blood perfusion in the right hemisphere and
activation of the left amydgala and parahippocampal gyrus, which leads to interact with
neural systems that are central to introspection and emotional processing.
Another study from Sampedro et al. found post-acute reductions in glutamate and glutamine
that lead to neurophysiological modifications in brain regions of the default mode network
after ingestion of Ayahuasca, which was correlated with increase in “non-judging” subscale
scores, in mindfulness capacities and a rapid and sustained antidepressant effects in
treatment-resistant patients, providing an explanation for the described experiential effect of
post-ayahuasca “after-glow”.
Neurophysiological studies show a suppression of the inhibitory alpha rhythm in the occipital
and parietal cortex, including the posterior cingulate cortex, a key node of the default mode
network with a prominent role in self-reflection and consciousness.
Recently, ayahuasca was found to induce post-acute increases in “decentering” ability, that
is, the capacity to observe one’s thoughts and emotions in a detached manner, and to
reduce automatic negative judgmental attitudes and inner reactivity. It thus enhanced a
series of “mindfulness” capacities traditionally cultivated by meditation schools and that are
known to be impaired in many forms of psychopathology.
Conclusion
After conducting a study on the brain mechanisms of action of the compounds involved in
Ayahuasca and their function as neurotransmitter that temporary increases in connectivity
between brain regions and alterations in the activity of brain networks, there is no doubt
about the multiple functions and therapeutic potential of this beverage. To date, benefits have
been reported in mindfulness, changes in functional and psychological balance, and
modulating effects of neuronal plasticity, which translate into improved mood, enhanced
cognitive processes, increased introspection, better stress and anxiety management,
enhanced impulse control, and improved creativity, not to mention the effects on brain
functions such as neurogenesis, myelination, and antioxidant effects at the neuronal level,
reaffirming its therapeutic potential to facilitate emotional processing that improves
psychological well-being.
References

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review of medicine, 60, 355-366.
2. Lam, D. D., Garfield, A. S., Marston, O. J., Shaw, J., & Heisler, L. K. (2010). Brain
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3. Ruffell, S., Netzband, N., Bird, C., Young, A. H., & Juruena, M. F. (2020). The
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administration of harmine elicits antidepressant-like effects and increases BDNF levels in rat
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12. Baroffio Irazabal, F. (2023). Caracterización in vitro de los componentes principales de
Ayahuasca y su combinación como agentes antioxidantes y neuroprotectores.
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Additional information:
There is a great YouTube Video / Podcast out with Dennis McKenna and Tim Ferris where
they go in depth about this topic as well:
Watch Video At: https://youtu.be/ShBqAcBLqaI