Ayahuasca, Dimethyltriptamine, and Neuroplasticity

Elio Geusa

Elio Geusa

february 27, 2023

A basic scientific primer on ayahuasca’s neurological functions and revelatory effects

What you will be learning

In this article, you will learn a great deal about how your brain works, how ayahuasca works, and how the two work together, particularly in regards to mental and emotional well-being. The ideas presented in this article, while they are for informational purposes only, are backed up by dozens of peer reviewed scientific studies; this article alone references almost 40, all of which are listed at the end of the article.

As with so many of the ancient traditions of human knowledge and practice recorded through history, modern science is slowly explaining in its own terms how and why compounds such as ayahuasca provide the benefits that so many users report after taking them. Indeed, ayahuasca and other psychedelic compounds have in recent years moved from relative obscurity and fringe science to more commonly accepted areas of scientific inquiry in the context of post-traumatic stress disorder, depression, and other areas of clinical psychology and psychiatry. This is due in part to recent advances and availability in laboratory testing equipment which facilitate highly data-driven experiments involving psychedelic compounds, and partly due to the enormous amount of historical evidence by way of anecdotes, narratives, testimonies, and previous scientific experiments which point overwhelmingly to the need for further scientific investigation of psychedelics as therapeutic substances. With this combination of increased technological capability and overwhelming evidence, the subject is now practically impossible to ignore any longer.

If you are planning a trip to Peru to participate in an ayahuasca ceremony, or if you are new to psychedelics, or are simply familiarizing yourself with how ayahuasca works, this article is a thorough and user-friendly reference for you to learn about what it is, how it works, and why it is important to understand the biochemical processes involved in using a plant medicine such as ayahuasca. The references contained in this article also provide you with reading and research opportunities for you to investigate further outside the scope of this article.


How Ayhuasca Works – Ayahuasca’s psychoactive chemical compounds

As you may or may not know, ayahuasca is a mixture of two or more naturally occurring plant species native to Central and South America. The principle component is plant matter from the bushy shrub Psychotria viridis, which contains approximately .3% dimethyltryptamine, or DMT, combined with plant matter of the climbing vine Banisteriopsis caapi, which contains the monoamine oxidase inhibitors harmine, harmaline, and tetrahydroharmine. Monoamine oxidase inhibitors are often known by their acronym, MAOIs.

DMT is quickly oxidized – destroyed – by monoamine oxidases in the liver when ingested orally. This normally means that eating or drinking something that contains DMT is not effective for experiencing DMT’s effects. However, when combined with compounds such as those found in Banisteriopsis caapi, the DMT is not destroyed in the liver because the oxidases in the liver are blocked the monoamine oxidase inhibitors, thus their name.

Instead, the DMT stays intact in the system and acts as a serotonergic agonist – that is, it interacts with the all-important neurotransmitter serotonin. Serotonin, chemically known as 5-hydroxytriptamine, or 5-HT, is one of the most important neurotransmitters and most important chemicals found in the human body, involved in everything from learning and memory to mood, digestion and much more. After being made available to these receptors due to the inhibitory action of the MAOIs, the DMT contained in a typical ayahuasca dose can result in an intense experience lasting on average from four to eight hours.

DMT is known to interact with the 5-HT1A and 5-HT2A serotonin receptors. These receptors, which you can think of as stations or gateways where different chemicals arrive, park, and unload different information that create different effects and responses in the body, are associated with a variety of interesting things that are worth thinkingabout.

Looking first at 5-HT1A, a few of the more interesting correlations of this receptor are reduced anxiety¹ and depression², increased dopamine and acetylcholine release³, decreased aggression, an increase in social participation and social comfort levels, a decrease in impulsive actions, assistance in moderating drug craving behaviors, and increased REM sleep, among many other associations found in scientific literature.

The 5-HT2A receptor, on the other hand, is associated with fear, excitement, release of critical hormones and associated with mood, socialization, and bonding, learning and memory¹⁰, and much more. The 5-HT2A receptor in particular is identified as a critical site for signaling transcendental, hallucinogenic, and out-of-body type experiences associated with traditional plant medicines such as ayahuasca¹¹.

Interestingly, in addition to its activity as a serotonin agonist, the constituent ingredients of ayahuasca have been shown to have other health-inducing properties. B. caapi, for example, contains the antioxidants epicatechin and procyanidine¹², while DMT itself has been shown to play an immunological role in cells involved in inflammation and infection¹³.

For the balance of this article, we will highlight some of the more significant and fascinating effects that ayahuasca has on the human condition, both in the acute phase of consumption of ayahuasca, and in the longer term after the acute effects of ayahuasca have come and gone.


Ayahuasca, Emotional Intelligence and Awareness

One common effect of ayahuasca is enhanced emotional arousal and awareness. This is true for many people while they are experiencing the effect of ayahuasca active in their systems, as well as it is true for many people residually as a long-term effect of their ayahuasca experience – they report a lasting and improved connectivity to their emotions, an increase in empathy, and a decrease in hostility and aggression. This makes a great deal of sense given that administration of oral ayahuasca results in significant activation of the frontal lobe and increased blood flow to the anterior insula, anterior singulate, and amygdala regions of the brain.

graphic of human brainLooking at these regions of the brain briefly one at a time: the anterior insula is understood as critical in the creation of feelings¹⁴. It plays a major role in empathy¹⁵, and is a critical nexus that ties together our experiences with their effect on us and our resultant behaviors¹⁶.

The anterior singulate, located behind the forehead, is a richly complex and unique area of the brain the bridges the emotional limbic system with the cognitive prefrontal cortex¹⁷, involved in empathy responses, social interactions¹⁸, and decision-making¹⁹.

Finally, the amygdala is famously known to be the place where we assign emotional meaning to our experiences – and although the amygdala is most well known for its involvement in fear and anxiety, it also plays an important role in the interpretation of pleasant experiences²⁰.


Ayahuasca: Creating the Pathways of Perception

To truly appreciate some of the more profound ways in which a psychoactive such as ayahuasca can influence and change the nature of a person’s experience as a living and conscious being, it is important to understand how our central nervous system works to interpret sensory data and assign meaning to our experiences.

Neurons – the cells that make up our central nervous system – use a highly complex and sophisticated system of communication to transmit information from one neuron to another, and from neurons to other cells such as muscle and organ cells. Keeping this as simple as possible, neurons have long arms that reach out and connect to each other to pass information. The neuron that sends has a very long arm called an axon, and the neuron that receives has a long arm called a dendrite. Information is passed from a sending neuron’s axon, which fires electrochemical information to the receiving neuron’s dendrite, which is a network of receptors that accept the information from the sender. Amazingly, this all happens at approximately the speed of light.

picture of neural dendrite connectionsEach dendrite – that’s the receiving arm that gets the information – has hundreds or thousands of tiny spiky structures on them called dendritic spines. These spines receive information and propagate it – multiply and spread it – to the main body of the cell. The more spines present on a dendrite, the better the received signal is propagated to the receiving cell. In other words, the more dendritic spines, the clearer the signal and thus the more powerful the thought, or emotion, or feeling, or inspiration the person experiences.

The place where this exchange of information occurs is called the synapse. It is a meeting place where a cell receives information.

Without synapses, information cannot travel between cells. In practice a lack of synapses would mean no thought, no physical motion, no memory, feelings, or any of the experiences that we consider fundamental to life. And a lack of synapses is medically associated with everything from Alzheimer’s to depression²¹. On the contrary, an increase in synapses is associated with increased memory and learning²².

Synapses all working together to carry information signals around the brain and throughout the body are known as neural networks – deeply complex, interwoven networks of nervous system cells through which information is sent and received, which form the basis for memory and learning.

graphical depiction of neural networksImportantly, neural networks are dynamic – they shift, rewiring themselves and growing continually as a result of new experiences. As they reorganize and expand, neural networks accommodate more memories and open themselves to learning more knowledge, skills, and behavior patterns. The more often a channel of information inside a neural network is used, the stronger the channel becomes, and thus the belief, action, or feeling associated with that channel is reinforced and becomes more available in the future, while the less often a channel is used, the weaker it becomes until it potentially breaks, and thus the associated belief, action or feeling becomes weaker until it potentially disappears.

This dynamic adaptation of neural networks is called plasticity – the ability of neurons to rewire themselves, shift, adapt, grow, and die back to create new connections through which electrochemical signals can travel.


DMT and the Expansion of Consciousness

With all of that basic neuroscience as a context, it is now possible for us to explore the profound effect that a compound such as ayahuasca can have on the human condition.

Consider, for example, that a substance such as DMT, the active component of ayahuasca, has the ability to significantly stimulate the growth of growth of neurons and create an increase in synapses²³.

What does this mean? It means that ayahuasca is potentially a means of facilitating an increased ability of our neural networks to make new and meaningful connections, potentially leading to an increase in learning ability, increased communication between different parts of the body, and much much more. Let’s reiterate and explore this critically important point.

DMT triggers the increased growth of neurons – brain cells. Neurons are the primary component of the nervous system and are responsible for everything from learning and memory to self-awareness, feelings, moods, emotions, and physical movement. DMT further creates an increased number of synapses – gateways where information can flow between different brain cells. Quite literally, this implies an increased ability to create connections between different thoughts and experiences, make realizations and draw conclusions about things that were previously not possible because the neural connections did not previously exist. Amazing!

lights connected togetherNot only does this insight have profound implications for anyone who sets the intention to experience a deeper understanding of themselves, their world, their relationships, or anything else significant in their lives, but it also has profound implications for neurodegenerative diseases such as Alzheimer’s, as well as other conditions such as depression and addiction²⁴ which are associated with increased neuronal atrophy – the disuse, wasting, or failure of brain cells, particularly those in the prefrontal cortex of the brain²⁵.

Even in the absence of acute conditions such as Alzheimer’s or addiction, an increase in neurons and synapses is a desirable outcome of any treatment. Thus the use of DMT as a neurostimulative supplement supporting ongoing brain health and mental activity is of great interest now and going forward. It may well find its own place amongst other so-called nootropics that support brain function, as well as other behaviors and practices such as problem solving and other mental stimulation which are known to stimulate brain activity and protect against mental decline²⁶.

These insights even reach as far as remedying experiential traumas. Compounds which create a fast-acting environment of increased neuroplasticity, facilitating the ability to ‘reprogram’ the brain’s understanding of and meaning assigned to previous events, are known as psychoplastogens. It has been shown, for example, that psychoplastogens are effective at reducing stressors²⁷ associated with the onset²⁸ of post-traumatic stress disorder²⁹. Ayahuasca is also being looked at for other related diseases and ailments, including Parkinson’s disease³⁰, which is also a neurodegenerative disease.

Amazingly, DMT has also been shown to have an anti-inflammatory effect, reducing the production of certain molecules that causes inflammation and increasing production of molecules that reduce inflammation³¹ including reducing the stress caused by reduced oxygen in cells³².

One important feature of neuroplasticity is the fact that neurons become far less plastic with age. The neural networks of a child are many times more flexible and adaptable than those of a grown adult, and this makes sense to any adult who has begun to feel their years – over time certain things become more and more ‘hardwired’ in to the adult brain, whether it is because of repetitive use or a lack of experiences that create new connections and force the existing network to change.

You can think of something like ayahuasca, then, as a tool to restore some of this previous elasticity to the central nervous system’s network – both for the short-term of the active psychedelic experience, and to a lesser extent for the long-term after the acute experience is over. Ayahuasca can provide a means to experience a state of consciousness that is quite unique when understood in the context of neuroscience: a state of consciousness where the years of meaningful experience that come with adulthood, exist within neural networks which are temporarily highly plastic like those of a child.

In other words, ayahuasca creates a state of being where the brain can create new synaptic connections and rewire existing connections in ways that are not normally possible. Normally a highly neuroplastic brain – that of a child – does not enjoy the long history of life experiences that an adult does, and a highly experienced brain – that of an adult – does not enjoy the high degree of neuroplasticity that it once did as a child. Ayahuasca provides the willing adult mind with the best of both worlds, so to speak – an experienced adult brain, full of memory and learning, that is also highly plasticized, capable of creating, expanding, and rewiring its richly detailed adult neural networks in ways that the brain is normally able to do only when it is younger. This, one can conclude is the reason that ayahuasca is often called ‘revelatory’.

Finally, let’s talk briefly about brainwaves. As you may know, the brain’s natural frequency can vary from just a few cycles per second to several dozen per second. Various brainwave frequencies are associated with various states of being, physical activities, and feelings or emotional states of being. Beta waves, for example, between approximately 15 and 30 cycles per second, are associated with normal waking life, simple and repetitive tasks, and normal problem solving activity, while delta waves are associated with deep sleep and theta waves are associated with creativity and imagination.

person meditation, triggering theta brain wavesAyahuasca has been shown to increase the brain’s output of gamma waves³³, which are associated with high-level mental activity³⁴, including deep thought, moral considerations and reasoning, and spiritual and meditative states. Gamma waves have recently been tied to increased compassion³⁵, happiness, love³⁶, and learning intelligence³⁷. You might know the feeling of gamma wave activity by the feeling of being ‘in the zone’ – focused and not easily distracted from anything outside of what you are doing. Those are the gamma waves of the brain. Meditation, for example, is one of the more well-known endeavors that promotes increased gamma wave activity in the brain³⁸.

In Conclusion

If some of the more technical information above was confusing or difficult to follow, that’s OK. You don’t need to worry about understanding every little detail of brain chemistry or how such a complicated thing as the human nervous system responds to plant medicine. The important thing to understand and take with you is this: ayahuasca can facilitate the opportunity for your brain to quite literally grow in its capacity to

• receive sensory information from the world
• make meaningful connections between past, present and future experiences
• rewire neural pathways to emphasize and deemphasize beliefs and behaviors

These abilities are not simply conjectures or claims by unqualified observers. They are grounded in hard science and have been demonstrated with peer-reviewed academic studies from all over the world now dating back several decades.

As you learn about and plan for your ayahuasca retreat, remember that your experience will perhaps be powerful, mystical, and even inexplicable, but you can rest assured that it is an experience that is understood by scientists as well as by the professional practitioners of AYA Healing Retreats, who bring years of experience to your ayahuasca ceremonies and guide you through the process with the best of care and concern for your healing potential. Book your retreat with the confidence of being in good hands during your time with us in Peru.


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¹² Wang YH, Samoylenko V, Tekwani BL, Khan IA, Miller LS, Chaurasiya ND, Rahman MM, Tripathi LM, Khan SI, Joshi VC, Wigger FT, Muhammad I. Composition, standardization and chemical profiling of Banisteriopsis caapi, a plant for the treatment of neurodegenerative disorders relevant to Parkinson’s disease. J Ethnopharmacol. 2010 Apr 21;128(3):662-71. doi: 10.1016/j.jep.2010.02.013. Epub 2010 Feb 26. PMID: 20219660; PMCID: PMC2878139.


¹³ Szabo A, Kovacs A, Frecska E, Rajnavolgyi E (2014) Psychedelic N,N-Dimethyltryptamine and 5-Methoxy-N,N-Dimethyltryptamine Modulate Innate and Adaptive Inflammatory Responses through the Sigma-1 Receptor of Human Monocyte-Derived Dendritic Cells. PLoS ONE 9(8): e106533.


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¹⁹ Claudio, Lavin, Melis, Camilo, Ezequiel, Mikulan, Carlos, Gelormini, DAVID, HUEPE, Agustin, Ibanez. The anterior cingulate cortex: an integrative hub for human socially-driven interactions. Frontiers in Neuroscience. 2013-7. DOI=10.3389/fnins.2013.00064.


²⁰ Mathias, Weymar, Lars, Schwabe. Amygdala and Emotion: The Bright Side of It. Frontiers in Neuroscience. 2016-10. DOI=10.3389/fnins.2016.00224


²¹ Wurtman RJ. Synapse formation in the brain can be enhanced by co-administering three specific nutrients. Eur J Pharmacol. 2017 Dec 15;817:20-21. doi: 10.1016/j.ejphar.2017.09.038. Epub 2017 Oct 12. PMID: 29031899.


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²⁵ Ly, Calvin, et al. Transient Stimulation with Psychoplastogens Is Sufficient to Initiate Neuronal Growth. ACS Pharmacology & Translational Science 2021 4 (2), 452-460. DOI: 10.1021/acsptsci.0c00065


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²⁷ Parker Kelley, Dennis. Evaluation of Hippocampal Allostatic Load-Associated Factors in Animal Models of Post-Traumatic Stress Disorder: Relevance to Human PTSD. 10.31390/gradschool_dissertations.5761


²⁸ Grieco, Steven F., et al. Psychedelics and Neural Plasticity: Therapeutic Implications. Journal of Neuroscience 9 November 2022, 42 (45) 8439-8449; DOI: 10.1523/JNEUROSCI.1121-22.2022


²⁹ Parker Kelley, D. et al. Pharmahuasca Reduces ROS Production and inammatory Gene Expression in the Brain in a Model of PTSD: Exploration by RNA Sequencing. June 15th, 2021. DOI: Preprint.


³⁰ Wang YH, Samoylenko V, Tekwani BL, Khan IA, Miller LS, Chaurasiya ND, Rahman MM, Tripathi LM, Khan SI, Joshi VC, Wigger FT, Muhammad I. Composition, standardization and chemical profiling of Banisteriopsis caapi, a plant for the treatment of neurodegenerative disorders relevant to Parkinson’s disease. J Ethnopharmacol. 2010 Apr 21;128(3):662-71. doi: 10.1016/j.jep.2010.02.013. Epub 2010 Feb 26. PMID: 20219660; PMCID: PMC2878139.


³¹ Szabo A, Kovacs A, Frecska E, Rajnavolgyi E (2014) Psychedelic N,N-Dimethyltryptamine and 5-Methoxy-N,N-Dimethyltryptamine Modulate Innate and Adaptive Inflammatory Responses through the Sigma-1 Receptor of Human Monocyte-Derived Dendritic Cells. PLoS ONE 9(8): e106533.


³² Szabo A, Kovacs A, Riba J, Djurovic S, Rajnavolgyi E, Frecska E. The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells. Front Neurosci. 2016 Sep 14;10:423. doi: 10.3389/fnins.2016.00423. PMID: 27683542; PMCID: PMC5021697.


³³ Schenberg EE, Alexandre JFM, Filev R, Cravo AM, Sato JR, Muthukumaraswamy SD, et al. (2015) Acute Biphasic Effects of Ayahuasca. PLoS ONE 10(9): e0137202.


³⁴ Panagariya A. Living longer living happier: My journey from clinical neurology to complexities of brain. Ann Indian Acad Neurol. 2011 Oct;14(4):232-8. doi: 10.4103/0972-2327.91931. PMID: 22346008; PMCID: PMC3271458.


³⁵ Lutz, Antoine, et al. Long-term meditators self-induce high-amplitude gamma synchrony during mental practice. 101 (46) 16369-16373. November 8, 2004.


³⁶ Rubik B. Neurofeedback-enhanced gamma brainwaves from the prefrontal cortical region of meditators and non-meditators and associated subjective experiences. J Altern Complement Med. 2011 Feb;17(2):109-15. doi: 10.1089/acm.2009.0191. Epub 2011 Feb 8. PMID: 21303197.


³⁷ Bauer, Elizabeth P., Paz, Rony, Paré, Denis. Gamma Oscillations Coordinate Amygdalo-Rhinal Interactions during Learning. Journal of Neuroscience 29 August 2007, 27 (35) 9369-9379; DOI: 10.1523/JNEUROSCI.2153-07.2007


³⁸ Cahn, B. Rael, Delorme, Arnaud, Polich, John. Occipital gamma activation during Vipassana meditation. 16 December 2009. DOI 10.1007/s10339-009-0352-1.


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