Unless you are a chemist, it is quite possible that you haven’t hear of the word “tryptamine” until now. Tryptamines play a big part of what you know as “psychedelics”.  We are still learning more and more about tryptamines everyday. Even discovering new tryptamines as we continue to learn more. That being said… arguably the three most popular psychedelic substances in the United States are all tryptamines:

  • LSD
  • DMT
  • Psilocybin


What are Tryptamines?

So the question remains, what makes these substances tryptamines?  What exactly is a tryptamine?  Two books that have become popular and important resource for psychedelics were written by Alexander and Ann Shulgin.  The Shuglins were chemists that sought out to document psychedelic substances that they enjoyed. These books are entitled PIHKAL and TIHKAL.  TIHKAL stands for “Tryptamines I Have Known And Love” and there is a definition for tryptamines in this book that we can find particularly beneficial. 


Definition from the Book TIHKAL The Continual

trypt-amine \ ‘trip-ta-,m?n\ n. [tryptophan fe. tryptic, fr. trypsin, fr. Gk. tryein, to wear down (from its occurrence in pancreatic juice as a proteolytic enzyme) + namine fr. NL ammonia] 1: A naturally occurring compound found in both the animal and plant kingdoms. It is an endogenous component of the human brain. 2: Any of the of compounds containing the tryptamine skeleton, and modified by chemical constituents at appropriate positions in the molecule.

Tryptamine structure


This tryptamine skeleton is particularly important. It is the chemical backbone of the most popular psychedelic structures: LSD, DMT, Psilocybin.  This is particularly important because of the structures ability to bind to 5HT2A receptors.  This is what releases the distinctive tryptamine serotonin rush and offers the particular feel too. 5HT2A receptors are also associated with thought and sensory processing. Tryptamine psychedelics have ranged from being termed psychotomimetic, hallucinogen, psychedelic, entheogen, and even psychoplastogen compounds based on the range of effects possible between subject and observer positions as well as biological and phenomenological effects.

So what the hell is a tryptamine?

Well basically… a tryptamine is a compound that has a specific chemical structure (the tryptamine skeleton) that allows it to bind to 5HT2A receptors.  This not only causes a surge of serotonin but also affects the way we think and the way our senses perceive the world around us. 


Neuroscience of Classic Tryptamines

Tryptamine psychedelics are known to disrupt the default mode network (DMN), a prominent and interconnected neural network in the human brain that becomes particularly active when the mind is at rest or not engaged in a specific task.  The DMN basically just means the way the brain normally works when you aren’t focused on anything in particular. This is how the brain works when you daydream.

Disrupting the DMN allows for different areas of the brain, that don’t normally communicate with one another, to communicate with each other. This allows for greater interconnectedness of the brain and has been used to explain changes to thought processes and sensory perceptions for people who have consumed these psychedelics.  In sum, tryptamines allow for us to perceive the world differently and change the way we think by changing the way different areas of the brain communicate with each other.

These phenomena have led to theories such as the ‘entropic brain’ or ‘relaxed beliefs under psychedelics’ (REBUS) models of psychedelic mechanisms in which the brain experiences a chaotic state that allows for a relaxation of prior belief models. Essentially, the entropic brain and rebus concepts propose that psychedelics induce a state of heightened cognitive flexibility, allowing the mind to explore unconventional connections and generate complex symbolic imagery. This unique mode of cognitive functioning may underlie the profound alterations in perception, self-awareness, and mystical experiences reported by individuals under the influence of psychedelics.

On a molecular level, serotonergic psychedelics have been shown to promote neurogenesis or structural and functional plasticity as well as adaptive change.  These effects occur in specific brain regions, such as areas of the pre-frontal cortex that have been associated with treatment-resistant psychiatric illnesses.  In other words, these types of psychedelic have shown promise for rebuilding and restructuring  the brain itself.

In sum, it seems tryptamine psychedelics profoundly disturb the brain’s default state and can disrupt pathologic patterns of neurotransmission while opening a window of neuroplasticity.  These effects promote formation of new neural pathways and can offer rapid improvements in symptoms of several psychiatric illnesses as well as offering a window with enhanced potential for subsequent behavioral changes.


Do Classic Tryptamines Have a Lethal Dose?

Psilocybin, LSD, and DMT act as partial agonists at the 5HT2A receptor, meaning they do not fully activate the canonical serotonin signaling pathway. Partial agonism in conjunction with an inability to increase intrasynaptic 5HT may explain the low risk of life-threatening serotonin toxicities in overdose or in combination with other substances. Psychedelic tryptamine overdoses are rarely (if ever) lethal and offer relatively safe physical safety profiles. For example, lethal doses of psilocybin or LSD are more than 100x the normal dose.

In other words. There is indeed a dose of tryptamines that could kill you. However, it would be impossible to take a dose of that size. Tryptamines are generally safe and can be taken with no worry of overdose. The most dangerous risk of taking too many tryptamines is psychological distress.  Potent and profound mental shifts as well as mild-moderate physiological effects can lead to traumatizing experiences, behavioral toxicity, or distressing post-use effects.

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