122 | SCIENTIFIC AMERICAN | SPECIAL EDITION | WINTER 2022Roger Cremers/Bloomberg/Getty ImagesOPINIONA Psychedelic Renaissance
Psilocybin and MDMA represent a first wave
of therapies for psychiatric disorders
that help patients by changing the way
they view reality
By Danielle Schlosser and Thomas R. Insel
T
hrough a May 2021 article he
wrote in the Independent, we
learned about Steve Shorney, who
lived with depression for most of his life
despite years of psychotherapy, medica-
tion, yoga and many other attempts at
holistic treatments. With his decision to
enroll in a psilocybin clinical trial at
Imperial College London, his life “radical-
ly changed.” Psilocybin was different from
every other treatment or experience he
had had. As he recalled in the Indepen-
dent article, “I had seen an alternative
reality, another way of being, and knew
beyond anything I’d known before that
day that life is extraordinary. And in that
moment I felt happier, more alive, and
more Me than I imagined was possible.”
The use of psychedelics, especially psi-
locybin and MDMA (also known as Ecsta-
sy or Molly), is undergoing a renaissance.
More than five decades ago psychedelics
were an active area of research, with more
than 40,000 patients receiving LSD or psi-
locybin for alcoholism, anxiety or depres-
sion. While we do not have rigorous clini-
cal trials from that time, the use of these
drugs garnered both scientific and public
interest, with Hollywood celebrities such
as Cary Grant promoting their use. But
the War on Drugs, beginning during the
Nixon years, led to a long, dark periodwhere these drugs were lost to science,
although they were still used in recre-
ational and religious settings.
New studies have reignited the hope
that psychedelics could be powerful medi-
cines for mental disorders. In a New Eng-
land Journal of Medicine report, two dos-
es of the chemical from the psilocybin
mushroom appeared as effective as six
weeks of escitalopram (Lexapro), a stan-
dard antidepressant, for people with long-
standing moderate-to-severe major de -
pressive disorder (MDD). On many of the
secondary measures of depression, such
as remission of symptoms, psilocybin ap -
peared better than the standard treat-
ment, with 57 percent of subjects showing
remission on psilocybin versus 28 percent
in remission with escitalopram, although
the au thors caution that more research
will be needed to confirm these results. In
a study reported in Nature Medicine,
MDMA was found to be more effective
than placebo for people with severe post-
traumatic stress disorder (PTSD). After
three sessions with MDMA, 67 percent no
longer met criteria for their diagnosis,
and 33 percent showed complete remis-
sion, relative to 32 and 5 percent, respec-
tively, after receiving a placebo.
Patients with disorders such as MDD
and PTSD can certainly use more innova-tive, effective and safe treatments. Fewer
than half of people with these disorders
respond to medications or psychothera-
py, and about a third of MDD patients
have so-called treatment-refractory de -
pression that fails to respond at all. Dis-
covering new approaches to treat mental
health conditions is critical. If psychedel-
ics prove to be effective and safe for these
disorders, they could be transformative
in two interesting ways.
First, these medications appear to be
effective after acute administration. Most
psychiatric drugs, such as escitalopram for
MDD, need to be taken for weeks, months
or years to be effective. Presumably, they
control symptoms but do not alter the dis-
order. When effective, psychedelics appear
to confer long-term effects, sometimesPSILOCYBIN MUSHROOMS