Ecstatic Chemistry

How do psychedelics work in the brain? Psychedelics do things to and in and for the brain in ways that remain a mystery...

DMT is, most simply, almost everywhere you chose to look. It is in this flower here, in that tree there, and in yonder animal."

Alexander Shulgin

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Psychedelics do things to and in and for the brain in ways that remain a mystery, since scientists have only begun to scratch the surface of the chemistry of hallucinogens. These alkaloids – generally either a phenethylamine or tryptamine -- are the chemicals that affect our mind, emotions, perceptions and consciousness.

Chemicals phenethylamine tryptamines

It is hard if not impossible to define the chemicals phenethylamine or tryptamines for nonchemists. A phenethylamine is a naturally occurring compound, endogenous to the human brain, containing a phenethylamine structure. A tryptamines is a naturally occurring compound, also endogenous to the human brain, containing a tyrptamine structure (see picture). Both these chemical groups can also be modified by chemical constituents at the appropriate positions in the molecule. Just about all psychedelics are either psychoactive phenethylamines or tryptamines.

Not surprisingly, these psychedelics phenethylamines and tryptamines tend to look a lot like the biologically active compounds in the brain – particularly the neurotransmitter fluids serotonin, dopamine and norepinephrine. The essential chemical feature of these compounds is that they activate a key brain target, which then allows the brain to shift from ordinary waking consciousness into the psychedelic realm. Most psychedelic chemists now believe that the switch for psychedelics molecules is at a site known as the serotonin 5-HT2A receptor. We believe that psychedelics are 5-HT2A agonists, meaning they act upon that receptor site. As psychedelic research David Nichols explains it

David Nichols explains it:
  • “Just as turning on the power switch of a television enables the TV to display
    images, but is not responsible for what is seen, psychedelic molecules, by
    activating this brain receptor, turn on some other set of amplifiers and processors that allow nonordinary feeling and states of consciousness to occur.”


Chemically most of the major psychedelics are so similar to serotonin, dopamine or norepinephrine that these psychedelics fit right into the brain’s same receptor site. Psychedelics are psychedelic because they are like our own natural neurotransmitter fluids. Structurally mescaline looks like the neurotransmitter norepinephrine; psilocybin and psilocin are close chemical cousins of serotonin. The powerful hallucinogen DMT (N,N-dimethyltryptamine) is actually naturally found in our brains, where it serves some as yet undiscovered purpose. MDMA or ecstasy as well as most of today’s research compounds or designer drugs are just modified mescaline or some other psychoactive phenethylamine or tryptamines.

In the human body serotonin is synthesized from the amino acid tryptophan.
Phenethylamines as noted earlier are structurally similar to serotonin, and tryptophan forms the chemical root to the psychedelic tryptamines. So in a certain way, psychedelics are most natural to the human body, similar to the chemicals that modified how to we see, interpret and perceive the world.
For more information, the reader would be encouraged to read the dual volumes

  • PIKHAL: Phenethylamines I have known and loved (1991)
    Alexander & Ann Shulgin
  • TIKHAL: Tryptamines I have known and loved (1997)
    Alexander & Ann Shulgin