60 Scientific American, February 2022nism by which the fda approval process can be made faster and
more transparent. The SPA allows a sponsor—in this case, MAPS—
to reach an agreement with the fda on the study design, including
a specific number of subjects, dosing, analysis plan and outcome
measures. Because face time with the fda is a rare and valuable
commodity, it was quite a boon to receive a coveted SPA in 2017—
and even better to be awarded Breakthrough Therapy Status the
same year. The breakthrough designation grants expanded access
to agency support and guidance and allows fast-tracking through
the approval process if a drug is being developed to treat a serious
or life-threatening condition.
Even once all the appropriate regulatory and compliance is-
sues have been tackled, there is still the matter of manufacturing
the compound. For clinical trials, this step must be performed in
a “good manufacturing practices” (GMP)-certified laboratory.
GMP ensures that production is consistent and conducted in a
clean environment and meets fda-prescribed quality standards.
Although the process was seemingly straightforward, it took sev-eral tries to identify a GMP-certified lab able to reliably generate
a pure compound. MDMA is also a painfully static molecule and
tends to stick to everything it should not, meaning that it took
practice for the GMP facility to successfully encapsulate the drug.CROWDFUNDING A CLINICAL TRIAL
Bringing any new drug to market is difficult, but for psychedelics
the process has been downright daunting. The first study of
MDMA for PTSD, also funded by MAPS, obtained fda approval in
2001, but recruitment of research participants for phase 3 did not
begin until November 2018. Even an SPA and Breakthrough Ther-
apy Status mean nothing without research funding. It costs an av-
erage of $985 million to bring a new drug to market. Because fed-
eral agencies typically do not support clinical research on Sched-
ule I compounds, most funding for MDMA research to date has
come through philanthropy and even some crowdfunding. (An
aside: if someone had suggested to me 10 years ago that anyone,
anywhere, would ever be conducting a phase 3 drug trial funded
by crowdsourcing, I would have laughed them out of the room.)
The financial situation may soon improve, however. Just a few
years ago, when psychedelics again started being tested in hu-
man trials, pharmaceutical companies were not exactly banging
down the door to join the club. But in the past year enthusiasm
has been dialed up, and psychedelic start-up companies now
abound. With any luck, this funding and interest will help MAPS
propel the first application for approval of MDMA for clinical use
through the fda within the next two years.
Although more than half a dozen phase 2 studies have dem-
onstrated the effectiveness and safety of MDMA for PTSD, early
trials often fail to accurately predict the outcome of the larger,
multi site phase 3 trials that follow. In the case of MDMA, we have
been lucky. At 15 study sites across three countries, working with
more than 70 different therapists and with study participants
with childhood trauma, depression and a treatment-resistant sub-
type of PTSD, we have obtained incredibly promising results.
Phase 3 study participants receiving MDMA-assisted therapy
showed a greater reduction in PTSD symptoms and functional im-
pairment than participants receiving placebo plus therapy. In ad-
dition, their symptoms of depression plummeted. By the end of the
study more than 67 percent of the participants in the MDMA group
no longer met criteria for PTSD. An additional 21 percent had a
clinically meaningful response—in other words, a lessening of anx-
iety, depression, vigilant mental states, and emotional flatness.
And although there had been concern that administering any
new medication to people with suicidal ideation could worsen
their problems, MDMA-assisted therapy did not increase mea-
sures of suicidal thinking or behavior. MDMA also did not dem-
onstrate any measurable misuse potential (which
should compel us to reconsider the reasoning behind
the war on drugs and scare tactics of the 1990s).
Yet despite these encouraging findings, it would be ir-
responsible to expect similarly impressive outcomes for
MDMA in less clinically controlled situations and more
heterogeneous populations. The success of psychedelic
medications depends on tight control of variables such
as the experience of the therapist team, the environment
or setting in which the therapeutic is administered, and
the amount of time participants spend integrating what
they learn during the psychedelic session. Our work has
no bearing, though, on recreational use of MDMA, which typical-
ly occurs in settings dramatically different from those of fastidi-
ously planned clinical experiments and relies on street drugs that
are often cut with all kinds of adulterants.
We are currently collecting long-term follow-up data from the
phase 3 study. One important question is how long the therapeu-
tic effects of MDMA and other psychedelics might last. Clearly,
these compounds differ from drugs such as SSRIs (selective sero-
tonin reuptake inhibitors), which must be administered daily, usu-
ally for years and sometimes indefinitely. We do not yet know
whether our participants will have to return every couple of years
for additional MDMA-assisted therapy. Although early clinical
studies suggest that the therapeutic effects of psychedelics can be
quite long-lasting, we also do not yet know whether there are sub-
sets of our clinical population for whom the effects are particular-
ly durable and others for whom additional dosing sessions or in-
tegration work will be needed.
MDMA is an experiential medicine, so its therapeutic effects
are influenced by the setting in which it is administered. This is
a key distinction from other medications. I would not expect a
blood thinner to have certain effects if I took it in my parents’ liv-
ing room versus in my neighbor’s kitchen. I would not expect it
to work differently depending on my mood.
Psychedelics are undeniably different. They are dependent on
frame of mind and environment. For this reason, it is essential to
educate participants on the potential effects of the compound be-
fore consumption. The treatment setting must be thoughtfully con-
structed to provide the right amount of support and protection. It
is even more critical that participants be guided through the expe-MDMA typically lets a person
engage in active and open
discussion about traumatic
experiences without becoming
emotionally overwhelmed.