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Taking Psychedelics Seriously
Ira Byock, MD, FAAHPM
1,2
Background: Psychiatric research in the 1950s and 1960s showed potential for psychedelic medications to markedly
alleviate depression and suffering associated with terminal illness. More recent published studies have demonstrated
the safety and efficacy of psilocybin, MDMA, and ketamine when administered in a medically supervised and
monitored approach. A single or brief series of sessions often results in substantial and sustained improvement among
people with treatment-resistant depression and anxiety, including those with serious medical conditions.
Need and Clinical Considerations: Palliative care clinicians occasionally encounter patients with emotional,
existential, or spiritual suffering, which persists despite optimal existing treatments. Such suffering may rob
people of a sense that life is worth living. Data from Oregon show that most terminally people who obtain
prescriptions to intentionally end their lives are motivated by non-physical suffering. This paper overviews the
history of this class of drugs and their therapeutic potential. Clinical cautions, adverse reactions, and important
steps related to safe administration of psychedelics are presented, emphasizing careful patient screening,
preparation, setting and supervision.
Conclusion: Even with an expanding evidence base confirming safety and benefits, political, regulatory, and
industry issues impose challenges to the legitimate use of psychedelics. The federal expanded access program and
right-to-try laws in multiple states provide precendents for giving terminally ill patients access to medications that
have not yet earned FDA approval. Given the prevalence of persistent suffering and growing acceptance of
physician-hastened death as a medical response, it is time to revisit the legitimate therapeutic use of psychedelics.
Keywords: depression; existential suffering; MDMA; palliative care patients; pharmaco-assisted therapy; post-
traumatic stress disorder; psilocybin; psychedelic drugs; therapeutic use
Recently published studies in peer-reviewed jour-
nals
1–4
and high-profile articles in the New Yorker,
5
New
York Times,
6
and Wall Street Journal,
7
have rekindled pro-
fessional and public interest in the therapeutic use of psy-
chedelic drugs. It is easy to understand the enthusiasm. The
magazine and newspaper articles include accounts of patients
with profound depression, demoralization associated with
terminal illness, and anxiety related to post-traumatic stress
disorder (PTSD), who experienced remarkable improvements,
including some who had previously considered suicide.
Nevertheless, psychiatric and palliative care clinicians who
care for profoundly depressed, anxious, and seriously ill pa-
tients have every reason to be skeptical. As people become
more mentally or physically ill and established treatments
remain insufficiently effective, patients’ susceptibility in-
creases. Physicians play an important role in protecting
vulnerable patients from spurious, nonevidence-based mir-
acle cures, as well as from scientifically grounded, but
overly zealous burdensome treatments that are certain to do
more harm than good.
An abundance of caution should be accorded psychedelics,
which carry real risks and are formally designated Schedule I
drugs, signifying that they are dangerous, without therapeutic
value, and illegal. Older clinicians remember news stories of
deaths of individuals high on hallucinogens who thought they
could fly, those with bad trips and flashbacks, and studies that
purported to show chromosome damage associated with use
of lysergic acid diethylamide (LSD).
However, given the extent of persistent emotional and
existential suffering that palliative care clinicians encounter
in the patients we serve, these medications deserve serious
consideration by our field.
1
Institute for Human Caring, Providence St. Joseph Health, Torrance, California.
2
Department of Medicine and Community & Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
Accepted December 15, 2017.
ªIra Byock 2018; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative
Commons Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use,
distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
JOURNAL OF PALLIATIVE MEDICINE
Volume XX, Number XX, 2018
Mary Ann Liebert, Inc.
DOI: 10.1089/jpm.2017.0684
1
Background
Psychedelic properties of specific plants (mushrooms and
cactuses) have been used for centuries by indigenous cultures
to induce expanded states of consciousness and spiritual
experiences.
8–10
During the 1950s and early 1960s, research
sponsored by the National Institute of Mental Health dem-
onstrated potential for drugs of this class to markedly alle-
viate depression and existential suffering among people with
cancer.
11–13
Subsequently, nonmedical use of these drugs and
associated political and cultural upheavals resulted in the
Schedule I classification, abruptly banning psychedelics from
further clinical research and medical use. Although many of
the mid-twentieth century clinical trials involved people with
terminal conditions, few references to these published studies
can be found in the literature of palliative medicine, a young
specialty that developed after this period. Over the past 20
years, a few small clinical studies were conducted abroad,
mostly in Europe and the United Kingdom. In the United
States, over the past decade, with support from the Multi-
disciplinary Association for Psychedelic Studies and private
funders, a few tenacious researchers earned governmental
permission to carry out carefully designed trials of pharmaco-
assisted therapy with psilocybin and 3,4-Methylenediox-
ymethamphetamine (MDMA), more commonly known by its
street names, Ecstasy and Molly.
The recently published research strengthens findings of
earlier studies, showing significant efficacy and few adverse
effects when these medications are administered as adjuncts
to psychotherapy to carefully screened patients, under med-
ical supervision.
1–3
Three drugs, psilocybin, ketamine, and
MDMA, have attracted most of the recent attention. Psilocybin,
a naturally occurring drug found in psilocybe mushrooms, has
strong and durable benefits for some patients with treatment-
resistant depression, and for those with demoralization, anxiety,
and depression associated with terminal illness. Ketamine, a
Federal Drug Administration (FDA)-approved anesthetic
with analgesic and psychedelic properties, has been used off-
label in patients with treatment-resistant depression. In case
studies and small clinical series, ketamine has shown notably
positive effects.
14–16
MDMA, a drug synthesized in 1912 as a
potential anticoagulant, was later found to have strong psy-
choactive properties. In the 1970s and early 1980s, psychiatrists
who administered MDMA in the context of psychotherapy
observed sometimes dramatic improvements in patients suf-
fering from severe, treatment-resistant PTSD.
17,18
In deciding how to think about these drugs, the distinction
between skepticism and cynicism bears examining. Skepti-
cism is warranted, but cynical nonscientific bias can result in
therapeutic nihilism. The history of medicine is studded with
occasional leaps in progress—consider small pox vaccination,
penicillin, and computed tomography scans—that, shortly be-
fore they occurred, might have seemed too good to be true.
When I graduated from medical school, the idea that duodenal
ulcers were caused by bacteria would have been risible; stem
cell transplants and gene-editing therapies were the stuff of
science fiction. Surprising medical advances humbly remind
us to suspend cynicism and that honest inquiry is warranted.
The Need Is Great
While not only for people who are dying, specialty palliative
care teams serve the sickest patients in our health systems and
communities. It is, therefore, not surprising that we occasion-
ally encounter incurably ill people whose suffering persists
despite all available evidence-based treatments.
In treating pain and other physical distress, established
treatment protocols guide escalations of doses and combinations
of analgesics and co-analgesic medications. When a patient is
dying and physical pain, dyspnea, seizures, or agitated delirium
persists and causes intolerable suffering, as a last resort, com-
fort can reliably be achieved with proportionate sedation.
19
However, not all suffering is based solely in physical
distress. Palliative care clinicians and teams also encounter
patients whose misery is rooted in emotional, social, exis-
tential, or spiritual distress. Cancer, heart failure, liver failure,
and amyotrophic lateral sclerosis (ALS) or motor neuron
disease are among the diseases that can result in a progression
of personal losses: Of feeling in control. Of taking care of
one’s self. Of contributing to others.Of enjoyment. Of meaning
and purpose. Ultimately, some ill people say they have lost any
reason to go on living.
People who are incurably ill and living with progressive
disease-related disabilities can experience anxiety, depression,
and demoralization.
20,21
Psychotherapy alone and drug treat-
ments for such syndromes are often insufficient. Medications for
depression may take weeks to become effective or prove inef-
fective. Antidepressants and anxiolytics carry side effects that
can include mental slowing and confusion. These adverse ef-
fects are particularly common and hazardous in patients with
advanced physical illness, who are also at risk of polypharmacy,
multidrug interactions, and concomitant disequilibrium and
falls. When nonphysical suffering persists despite prudent ap-
proaches, published, evidence-based guidelines are limited.
Severe psychological and existential suffering can rob
people of feeling that life is worth living. A sense of unending
helplessness and hopelessness compels some to consider
ending their lives. Suicide rates have risen 24% over the past
two decades and are highest among middle-aged and elderly
adults, particularly men who may suffer most from feelings
of dependency.
22,23
Public health data from Oregon show that
since implementation of the Death with Dignity Act, the large
majority of patients who received prescriptions for lethal
drugs were motivated by nonphysical suffering. Current or
fear of future pain contributed in just 26.4% of cases, while
loss of autonomy (91.4%), decreased ability to enjoy life
(89.7%), and loss of dignity (77.0%) most often brought these
people to contemplate hastening their deaths.
24
Exercising Abundance of Caution: Screening,
Supervision, Set and Setting
Prescribed to carefully screened patients, in recommended
doses, in the context of professional counseling and supervi-
sion, psilocybin and MDMA have proven to be notably safe.
They have no tissue toxicity, do not interfere with liver func-
tion, have scant drug–drug interactions, and carry no long-term
physical effects.
These drugs are not intoxicants in the usual sense. They do
not dull the senses or induce sleepiness. On the contrary,
sensory perception is intensified and attention is aroused.
Although abuse syndromes have been reported, few people
become habituated to these drugs.
Adverse physiological effects are few and of short duration,
but can be substantial. During the onset of psychedelic
2 BYOCK
experiences nausea and vomiting are not unusual. In this first
hour or more, visual and spatial orientation are commonly
disrupted, which can give rise to anxiety. Sympathetic ner-
vous system arousal may occur both because of fear, and from
direct effects of the drugs. Particularly during the initial phase
of sessions, psychedelics dissolve barriers between physical
senses resulting in synesthesia; touches, smells, and tastes can
take on sounds, shapes and colors. Similarly, emotions and
thoughts may evoke visual images and sounds. These phe-
nomena explain why the term hallucinogen is often used
synonymously with psychedelics to refer to this class of drugs.
Clinicians and researchers familiar with this class of phar-
maceuticals emphasize the importance of screening, supervi-
sion, and ‘‘set and setting.’’
Screening
Not every suffering patient is a candidate for therapy in-
volving psychedelic drugs. As a general guideline, people
who have cognitive and emotional conditions associated with
disorganized or diminished ego strength are not good can-
didates for pharmaco-assisted therapy with psychedelics.
MDMA may represent a partial exception to this exclusion,
because it has fewer cognitive and sensory effects and more
salutary emotional and interpersonal properties. Contra-
indications include people with borderline personality dis-
orders or schizophrenic tendencies.
Supervision
Supervision is necessary for ensuring safety of psychedelic
experiences. Short-term psychological effects are profound.
If used in unsupervised fashion by unselected and unprepared
people, these drugs can be highly dangerous and, in extreme
cases, cause death. The sensory effects described above in-
terfere with hand-eye coordination and fine motor function,
making operating a vehicle or machinery or even walking in
public potentially dangerous. These effects are sufficient to
emphasize that professionals who are skilled in managing ad-
verse effects must be present. Most research into pharmaco-
assisted therapy with psychedelics has by protocol required
subjects to remain in a single comfortable room throughout the
sessions. In addition to safety, the supervising therapists are
able to guide patients through their experiences to optimize
the drug’s beneficial potential.
Set and setting
Anthropologists studying traditional use of psychedelics
by shamans and indigenous people recognized the influence
of expectations and motivation on subjective experience.
Since the earliest psychological research into pharmaco-
assisted therapy with psychedelics, clinicians have empha-
sized the importance of ‘‘set and setting.’’
The dissolution of assumptions and diminution of barriers
caused by these drugs extend to psychological and interper-
sonal realms of experience. An enhanced sense of connection
to others not only underpins some of the therapeutic effects,
but also results in vulnerability to emotional contagion. When
taken without adequate preparation and when surroundings
are anxiety-provoking—either physically uncomfortable or
emotionally intimidating—the psychedelic experience pre-
dictably results in fear, a prolonged sense of dread, or full
panic. Conversely, in controlled settings with elements of soft
light, art, and appropriate music, or nature, and gentle, com-
passionate people, such adverse reactions are rare.
With adequate counseling and preparation, and when psy-
chedelic experiences unfold in calm, aesthetically pleasing en-
vironments, they prove beneficial in a high proportion of
cases.
17
In these situations, the healing motivations of both
therapists and patients may contribute to therapeutic outcomes.
Therapeutic Effects
Clinical case studies and research trials describe common
patterns of subjective experiences that are associated with
therapeutic benefits for people with severe anxiety and de-
pression. As the initial phase of psychedelic experience
wanes and people regain familiar barriers between visual,
auditory, tactile, olfactory senses, people typically report
heightened cognitive clarity and expanded emotional recep-
tivity. Previously unrecognized or unquestioned assumptions
related to one’s place in the world and relationships to nature,
one’s physical and social environments become available to
being considered anew.
While psychedelic experiences vary significantly from one
individual to another, research subjects and people interviewed
for journalistic articles commonly express attributes, which
include heightened clarity and confidence about their personal
values and priorities, and a renewed or enhanced recognition of
intrinsic meaning and value of life. People often voice a sense
of exhilaration, insight, and strengthened connection to others,
as well as a richer sense of relationship with nature or God.
25
People who take psychedelics with an intention of spiritual
introspection often report that the drugs opened windows into
deeper realms of existential experience.
5,9
In safe and sup-
portive environments, these effects typically induce a state of
wonder, conceptual frame shift, expanded capacity for love,
and an intensified sense of connection. Patients living with
medical conditions that had robbed them of hope or reason to
live may experience a transformative shift in perspective and
experience of inherent meaning, value, and worth.
Not all psychedelics drugs are alike and subcategories have
been described.
10
Drugs, such as psilocybin and LSD, classified
as entheogens,
26
are associated with introspection and new in-
sights, shifts of perspective, and reframing of experience and
relationship to others and the world. MDMA is characterized as
an empathogen, referring to prominent emotional effects of
interpersonal warmth, empathy, and openness.
27
These prop-
erties may underlie the benefits of MDMA in the context of
therapy for those suffering from severe PTSD.
For most of these drugs, a single six to eight-hour session
or short series of sessions suffices for therapeutic benefit.
Alleviation of anxiety and depression may persist for weeks
to months and, for some, proves permanent. Exceptions to
this treatment pattern include protocols of daily low-dose
ketamine for depression
15
and recent nonmedical reports of
daily or every third day micro-dosing of LSD.
28,29
Political and Regulatory Considerations
Psychedelic drugs were closely associated with the cultural
wars of the 1960s and 1970s when strong political under-
currents contributed to this class of drugs being classified
Schedule I. Similarly, MDMA became well known as Ec-
stasy or Molly, a popular, illicit rave and party drug.
7
In the
TAKING PSYCHEDELICS SERIOUSLY 3
mid-1980s, despite evidence of MDMA’s striking efficacy
and relative safety when used therapeutically, the FDA de-
clared MDMA a Schedule I agent. Court rulings challenged
that classification; however, in 1998 the FDA reaffirmed and
made the Schedule I classification permanent.
30
The process of renewing clinical research of psychedelics
has been long and painstaking. Future efforts to reclassify
selected psychedelics, such as psilocybin, as Schedule II
drugs, enabling both research and clinical administration will
likely meet predictable political resistance. There are com-
pelling reasons, however, to address the expected concerns of
opponents and proceed with efforts to reclassify these drugs.
Treatment-resistant depression and anxiety associated
with PTSD causes untold suffering and contributes to thou-
sands of deaths each year. A few population health studies
suggest that rising suicide rates may in part be due to suicide
becoming less shameful and more socially acceptable, low-
ering barriers for people who feel hopeless.
31,32
A person
with severe depression, who has a coexisting serious, life-
threatening physical condition, may feel that his or her
quality of life is not worth living and may forgo arduous, but
potentially life-saving treatments. Additionally, nearly one
sixth of Americans live in states where physician-hastened
death is legal and those with terminal illness may choose this
option in absence of alternative sources of relief.
There may be higher ground on which political conser-
vatives and progressives—as well as those on opposing sides
of the issue of legalizing physician-hastened death—might
build consensus. Given the life-threatening nature of persis-
tent, treatment-resistant depression and PTSD, including
among veterans of America’s wars, and the rising incidence
of suicide, the reclassification of psilocybin and MDMA can
be legitimately cast as a right-to-try issue. Right-to-try leg-
islation has been used to provide terminally ill patients access
to potentially life-extending medications that have been tes-
ted in Phase I trials but are of uncertain benefit.
33,34
Similarly,
the FDA’s expanded access or compassionate use provisions
may make use of drugs that have not been approved available
to patients who are otherwise facing death.
35,36
By dimin-
ishing a desire to die among people with severe depression,
anxiety, PTSD, and those with terminal cancers, genetic and
neurodegenerative diseases, psychedelics may have greater
life-saving effects than other drugs that have earned right-to-
try and expanded access status.
37
Business Considerations
Business models for medical uses of these drugs are not
clearly defined. Alleviating persistent depression or PTSD with
one or two doses of an inexpensive, un-patentable compound
may threaten existing markets for antidepressant and anxiolytic
medications. Therefore, it is possible that the pharmaceutical
industry may oppose legalization and supervised use of these
medications. If so, industry lobbying could complicate regula-
tory processes needed to research legitimate uses of these drugs.
The way forward may include folding the cost of these
medications into professional fees for pharmaco-assisted
therapy.
38
This alternative business model would align well
with the therapeutic rationale for requiring psychedelic ses-
sions to be supervised by trained counselors, who are able to
control set and setting and capable of preventing and man-
aging any adverse reactions.
Final Thoughts
Faced with novel therapies with reported clinical benefits
that seem too good to be true, skepticism is warranted to
protect vulnerable patients from harm. Cynicism, however,
may prove more dangerous still. Unscientific bias and nihil-
istic assumptions can keep effective treatments from people
who desperately need them.
Despite the controversial history of psychedelic medica-
tions, palliative specialists who care for patients with serious
medical conditions and common, difficult-to-treat nonphys-
ical suffering have a duty to explore these hopeful, potentially
life-preserving treatments. Against the backdrop of physician-
hastened death becoming legal in five states, expanded research
of clinical psychedelics must proceed.
In reexamining the use of psychedelics in pharmaco-assisted
therapy, we must not allow preconceptions, politics, or puri-
tanism to prevent suffering people, who are now considered
helpless and hopeless, from receiving promising, at times
life-saving, treatments.
Author Disclosure Statement
No competing financial interests exist.
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Address correspondence to:
Ira Byock, MD, FAAHPM
Institute for Human Caring
Providence St. Joseph Health
5315 Torrance Boulevard
Suite B-1
Torrance, CA 90503
E-mail: ira.byock@gmail.com
TAKING PSYCHEDELICS SERIOUSLY 5
