The following excerpts are from an essay entitled "Phytochemistry and Neuropharmacology of Ayahuasca" by J.C. Callaway, PhD. The essay can be found in this collection, which is recommended for anyone interested in the science of ayahuasca as well as modern Western perspectives on ancient sacred plant medicine. All rights belong to the author.
Dr. Callaway writes:
Certain psychoactive plants have been called "plant teachers," because of the information they apparently impart to the user. Most of these plants are now known to contain secific chemical entities that, if administered in their pure form at sufficient dosagesbring about analogous modifications in perception and awareness in most human beings. As these effects are increasingly identified with certain chemicals, it is just as appropriate to speak of them as "molecular teachers," for these molecules are the most fundamental forms of matter that can precipitate these effects...
The neurotransmitter serotonin, chemically known as 5-hydroxytryptamine, or 5-HT, is produced throughout the brain and gastrointestinal tract and seems to be responsible for higher functions of behaviour, such as planning and other time-related events. It is produced in the body from L-tryptophan, an essential dietary amino acid. In addition to serving as a nerotransmitter, serotonin is also the metabolic precursor of melatonin, which the human body makes during the night and when eyes are closed, as in some forms of meditation. Deficiencies in tryptophan and serotonin have been linked to mental mental disorders such as violent alcoholism, anxiety, depresson, and suicide. Decreased serotonergic activity can stem from too little tryptophan entering the brain, too little serotonin produced from available tryptophan, aggressive uptake of serotonin from the synaptic cleft, or excessive activity of the enzymes that metabolize serotonin. Increased serotonergic activity, however, can be induced by pharmacological means, and this is the primary goal of modern antidepressant medications.
Serotonin's major function is basically one of inhibition within the complex neurochemical pathways of the central nervous system (CNS), as if to screen out spurious bits of data to allow one to better focus on the task at hand. Modifying the action of the serotonergic functions within a living organism typically results in observable changes in behaviour. Many psychotropic substances, whether purified synthetic powders or crude natural products, affect at least some aspect of serotonergic activity.
Most serotonin is eventually metabolized to 5-hydroxyindoleacetic acid (5-HIAA) by monoamine oxidase (MAO), an enzyme in the body that also deactivates other neurotransmitters by a specific oxidation reaction. While the other neurotransmitters may use additional metabolic pathways, serotonin is fairly dependent on the activity of MAO for its deactivation. Thus, when MAO is inhibited, levels of serotonin in the brain begin to increase as its production continues unabated. This action alone can have noticeable psychoactive effects as the brain becomes hyperactivated by its own neurotransmitter...
The purpose of this brief discourse on neurochemistry is to bridge the relationship between the neurochemistry of ayahuasca and the human CNS. There are some striking parallels to consider and a basic familiarity with serotonergic activity is pivotal in understanding the neuropharmalogic actions of this unique beverage...[which is] without a doubt, one of the most sophisticated and complex drug delivery systems in existence. The salient feature of this brew is the presence of harmala alkaloids, typically derived from the woody liana Banisteriopsis caapi, which serve as inhibitors of the enzyme MAO...it is suggested herein that both MAO inhibition and serotonin uptake inhibition work together through ayahuasca to safely increase levels of seratonin by simultaneously both its metabolism and neuronal reuptake, respectively.
Thus, it can be said that a beverage made entirely from B. caapi is psychoactive, subsequent to its neuroactivity, although this activity is primarily due to hyperserotonergic actions. Such preparations are used and do have utility, particularly as a purgative and perhaps in removing intestinal parasites. The nausea and vomiting that often occur after drinking ayahuasca are probably due to increasing levels of serotonin in the brain, which results in excessive stimulation of the vagus nerve as previously mentioned. For religious purposes and the induction of visions, however, DMT is typically added to the brew through the leaves of Psychotria viridis. This particular combination of plants is nothing short of a blessing from nature [there is roughly a 1 in 6 billion chance of finding this combination of plants in the Amazon].
The serotonin syndrome is a toxic state that results from increased serotonergic activity. It typically results from the combination of MAO inhibitors and some other serotonergic drug, particularly one of the specific serotonin reuptake inhibitors (SSRIs) that are currently so popular in the treatment of depression, obsessive-compulsive disorders, and some forms of substance abuse. This syndrome can even occur by combining tryptophan with a SSRI...the combination of MAO inhibitors with SSRIs is potentially lethal.
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