the human brain is vast .
researchers who’ve studied how
perceptions of meaning change when people
take the psychedelic drug known as LSD have
traced that sense of meaningfulness to
particular neurochemicals and receptors in the
brain. The findings are reported in Current
Biology on January 26.
The findings add to our fundamental
understanding of the human experience. They
also point to potentially new targets for drugs
to treat psychiatric illnesses or phobias, which
come with abnormalities in the attribution of
personal relevance to particular sensory
experiences or cues, the researchers say.
“Our results increase our understanding of
how personal relevance attribution is enabled
in the human brain,” says Katrin Preller of the Zürich
University Hospital for Psychiatry. “[We now
know] which receptors, neurotransmitters, and
brain regions are involved when we perceive
our environment as meaningful and relevant.”
Earlier studies showed that LSD alters the
attribution of meaning and personal relevance
to the environment, Preller explains. LSD also
changes the way people perceive themselves,
as the distinction between the self and the
world outside the self blurs. But it wasn’t clear
exactly what parts of the human brain and which
neurochemicals were responsible.
Preller and colleagues first confirmed the
usual effects of LSD on study participants’
state of consciousness, mood, and anxiety in
the lab. They found that those psychedelic
effects of LSD were erased when participants
took a second drug called ketanserin that
blocked the ability of LSD to act on serotonin
receptors known as 5-HT2ARs. That finding
came as something of a surprise because LSD
is also known to stimulate dopamine
receptors, Preller says.
To explore LSD’s influence on the way people
attribute meaning to things in their world, the
researchers asked participants taking a
placebo, LSD, or LSD plus ketanserin to rank
the meaning attached to a series of songs.
Some of those songs were ones that
participants told the researchers were
particularly meaningful to them. Others were
either neutral or without meaning.
The researchers found that musical pieces that
were previously meaningless to participants
took on special meaning when those
individuals were under the influence of LSD.
That effect was diminished when participants
were given the second drug to counteract
LSD’s effects on the human brain’s serotonin
receptors. Brain imaging studies also linked
those changing attributions of meaning to
particular brain areas.
“By combining functional brain imaging and
detailed behavioral assessments using a
specific experimental paradigm to investigate
personal relevance or meaning of music
pieces, we were able to elucidate the
neurobiological correlates of personal
relevance processing in the brain,” Preller
says. “We found that personal meaning
attribution and its modulation by LSD is
mediated by the 5-HT2A receptors and
cortical midline structures that are also
crucially involved in enabling the experience of
a sense of self.”
Preller says they now plan to explore whether
they observe the same effects in response to
visual or tactile stimuli. They also hope to
explore the relevance of their findings to
dysfunctional attributions of meaning in
people with psychiatric disorders.
“Excessive stimulation of 5-HT2A receptors
seems to underlay the experience of loosening
of self/ego boundaries, disrupted self-
referential processing and thus the related
impairment of making meaning and attributing
personal relevance to percepts and
experiences seen in various psychiatric
disorders,” she says. “Therefore, it is important
to consider this receptor subtype as potential
target for the treatment of psychiatric illnesses
characterized by alterations in personal
A separate study in Cell on the structure of
LSD and its receptor, and what this teaches us
about the drug’s potency, was also published
on January 26.
This study was financially supported by grants
from the Heffter Research Institute, the Swiss
Neuromatrix Foundation, the Usona Institute,
and the Swiss National Science Foundation.