4 June 2022 | New Scientist | 47trip-free psychedelics would, he says, remove
the risk of bad trips, known as “bottom-margin
cases”, which happen most often in people
with pre-existing psychiatric conditions, such
as schizophrenia and bipolar disorder, and
can significantly worsen mental health. And
they would also remove the requirement
for lengthy and expensive therapy, making
it accessible for as many people as possible,
he says. “I worry that this is going to become
a treatment only for the people who can
afford to pay out of pocket,” says Olson.
To create these “non-hallucinogenic
psychoplastogens”, Olson’s team
systematically masks different parts of the
chemical structure of psychedelics to
understand which bits give rise to which
effects. “You can just keep the features that are
beneficial and remove the features that are
not,” he says. One hallmark of depression,
post-traumatic stress disorder and substance
addiction is the wasting away of brain cells in
the prefrontal cortex, the region associated
with complex behaviours and higher-level
thinking. Evidence suggests that psychedelics
regrow and realign these brain cells, so Olson
hung on to these functions while removing
the parts that give the visceral experience.
Moments of meaning
Psychoplastogens have produced promising
results in mice, regrowing neurons and
making their brains more malleable, while also
reducing behaviours associated with addiction
or depression. “It’s very comparable to what
you see with hallucinogenic compounds, and
that gave us a hint that it might be possible to
do this,” says Olson, who is planning human
trials later this year with Delix Therapeutics,
a company he co-founded. In theory,
psychoplastogens could be picked up at the
pharmacy like any other prescribed pill.
But some are sceptical that trip-free
psychedelics will work in humans. David
Yaden, a neuroscientist at Johns Hopkins
University in Maryland, agrees that low-level
brain cell changes play an important role
in how psychedelics work, but stresses that
psychoplastogens are still hypothetical. “It’s
hard to infer on the basis of rodent research
what will happen in human clinical trials,”
he says. “My strong suspicion is that the acute
subjective effects will be necessary for full and
enduring therapeutic impacts.”
Yaden is referring to the intense personal
experiences people have when they take
psychedelics and the meaning that comes >