February 2022, ScientificAmerican.com 61rience by trained facilitators—often doctors or psychologists with
special training—who know how to gently shift and shape the ex-
perience and to help them process the many facets of trauma that
will arise. Additionally, if, as the animal data suggest, the MDMA-
induced reopening of a critical period could last for several weeks,
every effort should be made to use that time to heal, learn and grow.
Our study participants came from a multitude of backgrounds
and cultures, but all had been diagnosed with severe PTSD and
had been suffering from it for, on average, more than a decade.
Many of them were considered treatment-resistant, having tried
other PTSD therapies and therapeutics to no avail. More than 90
percent of them reported depression that accompanied their trau-
ma, as well as suicidal thoughts.
Participants typically underwent three preparatory sessions
with their therapy team before embarking on their three all-day
experimental sessions. These prep sessions helped us set expec-
tations for treatment and described what the subjects should an-
ticipate if they were among those who received MDMA. Because
this was a double-blind, placebo-controlled trial, these sessions
also gave us a chance to explain what it might feel like to receive
a placebo and how to manage disappointment about it. (Although
it can be nearly impossible to fully mask the effects of a psyche-
delic, some of our participants guessed that they had received
MDMA when in fact they had received placebo, and some guessed
that they had received a placebo when they had received MDMA.)
Preparatory sessions were followed by an experimental session.
Participants reclined on a sofa in a comfortable, dimly lit room and
received a blister pack of study drug and a glass of water to begin
their journey. Later came three integration sessions in which facil-
itators worked with participants to further untangle the trauma
laid bare during the experimental session.
There is still much to learn about the neurobiological mecha-
nisms of action of MDMA therapy, but it typically enables partic-
ipants to engage in active, open discussions about their trauma
without becoming emotionally overwhelmed—a major challenge
to those suffering from PTSD. They frequently discuss their trau-
matic experiences with tremendous self-compassion, which some
of our therapists speculate is the key to their eventual liberation
from their burdens. By the end of the study participants are some-
times noticeably changed in physical appearance. They stand up
straighter, they meet our eyes and they even smile.
WHICH IS IT?
one of the Biggest unanswered questions as we develop psyche-
delic medications is whether the subjective “psychedelic” experi-
ence is necessary for the therapeutic actions or is an irrelevant side
effect that should be engineered away to make the treatment pro-
cess faster and more marketable. Indeed, drug companies intent
on developing “nonpsychedelic” psychedelics (those that have no
psychoactive or hallucinogenic effects) have suddenly come out of
the woodwork. Yet given the myriad data suggesting that the in-
tensity of the mystical experience correlates with therapeutic im-
provement—and subjective reports espousing the beneficial im-
pact of a psychedelic epiphany on years of negative thinking—it
seems prudent to continue to focus on truly psychedelic compounds.
In addition to PTSD, data support the use of MDMA for de-
pression, anxiety, eating disorders, and alcohol and drug use dis-
orders. dea rescheduling could reduce the barrier to clinical as-
sessment of MDMA for these and other indications. Even afterdea and fda approval of MDMA for PTSD has been obtained, how-
ever, a slew of tasks must be completed before the drug can reach
the market. There should be a pipeline for training and creden-
tialing psychedelic facilitators and for generating a system of clin-
ics through which they can practice. Drug developers will need to
develop a risk-evaluation and mitigation strategy and submit it
to the fda for approval—this step is to confirm that clinical use of
MDMA carries no unchecked risks or side effects—and they will
have to design a treatment cost structure to encourage HMOs and
insurance providers to cover the expenses.
I first read about the potential therapeutic effects of psyche-
delics for anxiety and addiction in college, and by the time I en-
tered graduate school I was convinced that understanding these
compounds would lead to better treatments for a variety of men-
tal health disorders. Because we were never able to obtain access
to psychedelics for lab testing, we instead focused on separating
out the various components of their biochemical activity (typi-
cally termed reverse engineering).
Most psychedelics have multiple pharmacological targets, and
it is possible to tease them apart and test them one step at a time
with more easily accessible drugs. For example, if a psychedelic
induces the release of serotonin and oxytocin, we can try modify-
ing behavior with an SSRI or oxytocin. If it acts as an NMDA re-
ceptor antagonist, which blocks the signaling molecule glutamate,
we can use an NMDA receptor antagonist such as ketamine. Many
of us have spent decades investigating the neural mechanisms and
behavioral effects of potential therapeutics in this way based on
our knowledge of the biochemistry of psychedelics. Although the
fields of neuroscience and behavioral pharmacology have come
quite a long way in terms of understanding behaviors such as anx-
iety, fear, substance craving and impulsivity, we have still fallen far
short of generating a panacea for the suffering caused by these
conditions. Perhaps it is time to take a different tack.
More than 50 years ago, after a decade of growing civil unrest
and in response to the spreading recreational use of psychedelics,
the pendulum of acceptance swung sharply. The turmoil and fear
of the 1970s propelled a national agenda of regulation and crimi-
nalization. Half a century later the pendulum has swung again, and
we find ourselves considering anew the medical value of psyche-
delic drugs. In addition to several dozen new studies on the effects
of MDMA, there are now ongoing clinical trials for several other
psychedelics, including psilocybin, LSD, ayahuasca and ibogaine.
As enlightened as this new direction might feel, we must take
care to ensure that the zeal of the converted does not color our de-
cision-making. We need to take the time to thoroughly investigate
these powerful compounds—to understand both their benefits and
their shortcomings. Without scientific rigor, the pendulum could
swing again. “Nothing to excess” and “the dose makes the poison”
are the adages I hear time and again. The road to MDMA approv-
al as the first medical psychedelic may still be long and bumpy, but
if the enthusiasm and drive I encountered in that hotel conference
room nearly five years ago are any indication of things to come,
then I believe we are steadily heading in the right direction.FROM OUR ARCHIVES
Hallucinogens as Medicine. Roland R. Griffiths and Charles S. Grob; December 2010.
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