location, serotonin is liable to make very different things happen—
sometimes exciting a neuron to fire, other times inhibiting it. Think of it
as a kind of word, the meaning or import of which can change radically
depending on the context or even its placement in a sentence.
The group of tryptamines we call “the classical psychedelics” have a
strong affinity with one particular type of serotonin receptor, called the 5-
HT2A. These receptors are found in large numbers in the human cortex,
the outermost, and evolutionarily most recent, layer of the brain.
Basically, the psychedelics resemble serotonin closely enough that they
can attach themselves to this receptor site in such a way as to activate it to
do various things.
Curiously, LSD has an even stronger affinity with the 5-HT2A receptor
—is “stickier”—than serotonin itself, making this an instance where the
simulacrum is more convincing, chemically, than the original. This has
led some scientists to speculate that the human body must produce some
other, more bespoke chemical for the express purpose of activating the 5-
HT2A receptor—perhaps an endogenous psychedelic that is released under
certain circumstances, perhaps when dreaming. One candidate for that
chemical is the psychedelic molecule DMT, which has been found in trace
amounts in the pineal gland of rats.
The science of serotonin and LSD has been closely intertwined since
the 1950s; in fact, it was the discovery that LSD affected consciousness at
such infinitesimal doses that helped to advance the new field of
neurochemistry in the 1950s, leading to the development of the SSRI
antidepressants. But it wasn’t until 1998 that Franz Vollenweider, a Swiss
researcher who is one of the pioneers of psychedelic neuroscience,
demonstrated that psychedelics like LSD and psilocybin work on the
human brain by binding with the 5-HT2A receptors. He did this by giving
subjects a drug called ketanserin that blocks the receptor; when he then
administered psilocybin, nothing happened.
Yet Vollenweider’s discovery, important as it was, is but a small step
on the long (and winding) road from psychedelic chemistry to
psychedelic consciousness. The 5-HT2A receptor might be the lock on the
door to the mind that those three molecules unlock, but how did that
chemical opening lead, ultimately, to what I felt and experienced? To the
dissolution of my ego, for example, and the collapse of any distinction