1430 17 DECEMBER 2021 • VOL 374 ISSUE 6574 science.org SCIENCE
2021 BREAKTHROUGH OF THE YEAR^ | RUNNERS-UP
IMAGES: TOP TO BOTTOM MULTIDISCIPLINARY ASSOCIATION FOR PSYCHEDELIC STUDIES; KTSDESIGN/SCIENCE SOURCEA psychedelic PTSD remedy
The mind-altering power of psychedelic drugs has raised hopes
that they can ease psychiatric disease, but few large, rigorous
trials have shown they’re effective. This year brought a big win for
the field: A multicenter, randomized, controlled trial found that
3,4-methylenedioxymethamphetamine (MDMA), popularly called
ecstasy, significantly reduced symptoms in patients with post-
traumatic stress disorder (PTSD).
The study, published in Nature Medicine in May, tested an in-
tensive combination of talk therapy and MDMA, which can create
a sense of well-being and empathy that may help people process
traumatic experiences. The trial’s 76 participants had three 8-hour
guided therapy sessions with either the drug or a placebo, plus a set
of shorter “preparatory” and “integration” sessions with therapists
before and after treatment. After 2 months, 67% of those who got
MDMA no longer met the diagnostic criteria for PTSD, versus 32% in
the placebo group.
The results prompted enthusiasm, but also caution. Such trials
face a “Gordian knot of blinding and placebo effects,” neurologist
Matthew Burke and psychiatrist Daniel Blumberger of the University
of Toronto warned in Nature Medicine in October. That’s because
MDMA’s psychoactive effects are obvious to participants and could
influence their expectations—and even the odds they will improve.
(Follow-ups with participants after the study suggested as many as
90% correctly guessed which group they were in.) And simply accept-
ing that such expectations are part of the treatment “would require a
complete overhaul of how we measure efficacy in psychiatry,” Burke
and Blumberger write.
Still, psychedelic research is booming as academic labs and
companies explore the potential of MDMA and other psychedelics to
treat conditions like depression, anxiety, and addiction. In November,
the London-based mental health care company COMPASS Pathways
announced positive results from a 233-participant randomized trial
of psilocybin, the substance in so-called magic mushrooms, in people
with treatment-resistant depression. The company is now planning a
larger trial. And if an ongoing follow-up study can confirm the initial
MDMA results, its sponsor—the nonprofit Multidisciplinary Associa-
tion for Psychedelic Studies—plans to seek approval from the U.S.
Food and Drug Administration as early as 2023. —Kelly ServickArtificial antibodies tame
infectious diseases
Labmade antibodies called monoclonals have revolutionized the
treatment of some cancers and autoimmune diseases, but they’ve had
limited success against infectious diseases. That changed this year, as
monoclonal antibodies (mAbs) made inroads against SARS-CoV-2 and
other life-threatening pathogens, including respiratory syncytial virus
(RSV), HIV, and malaria parasites.
To make mAbs, scientists isolate the most powerful antibodies from
lab animals and humans and reproduce them in massive quantities.
As medicines, they are mostly used to tamp down immune responses
or mark tumor cells for destruction. The only mAbs approved for
infectious diseases in the United States are limited to rare maladies:
Ebola, inhalational anthrax, recurrent Clostridium difficile, RSV in
high-risk infants, and HIV in people for whom all drugs have failed.
India has approved a mAb for rabies.
With advances in cloning, animal models, and x-ray crystallo-
graphy, researchers can now make and screen more mAbs than ever
before, simplifying their search. SARS-CoV-2 mAbs showed promising
results in clinical trials in 2020, and by late this year, the U.S. Food
and Drug Administration had granted emergency use authorization
to three to treat COVID-19 and, in some cases, prevent infection.
Monoclonals are also being developed against influenza, Zika, and
cytomegalovirus. High hopes surround two candidates designed to
prevent RSV in all infants. And in one HIV prevention study that
failed overall, the candidate worked well against some strains.
High costs and the need to infuse mAbs in a clinic have put them
out of reach for many. But as prices plummet, injections replace
infusions, and more potent mAbs come to market, they may become
standard weapons in the infectious disease arsenal. —Jon CohenMDMA treatment for post-traumatic stress disorder includes trained supervision.Antibodies (red
and blue) attack
SARS-CoV-2 (purple)
in an artist’s concept.