Psilocybin-Assisted Therapy Has the Power to Ease Existential Distress For the Dying
In the tech-driven world that we know today, our loss of human connection seems greater every year. As a result, the broader American culture is depleted or even void of many things that humans once relied on to maintain their well-being. Among these losses is our ability to adequately view death and dying as processes that should be respected and honored, and provide those facing death with the peace and dignity they deserve. In America, death is kept in the dark – so many of us struggle with death anxiety, lack basic death literacy, and even carry deep regrets about how a loved one’s death was handled.
This cultural departure – from viewing death as a sacred, personal journey to a scary taboo that serves to provide an endless fuel source for the medical-industrial complex – can be traced back to the mid-twentieth century when dying began to move out of the family home and into the hospital. Through this process, we have been collectively robbed of the tools to authentically traverse the liminal space that is dying, death, and grief – but an important change may be on the horizon.
Across the globe, an increasing number of people experience life-threatening illness at all stages of life – and so the need to expand our understanding of how to best care for the dying is also increasing. At the very moment when our need to bring death back into the broader cultural conversation has reached a crest, a new chapter in the exploration of psilocybin is unfolding. Each year that goes by sees an increase in public awareness of, and approval for, this potential miracle drug. Through his conversations with premier psilocybin researcher Roland Griffiths of Johns Hopkins University, journalist Richard Shiffman (2016) reports that “psychedelics are not just tools for exploring the far reaches of the human mind…they show remarkable potential for treating conditions ranging from drug and alcohol dependence to depression and post-traumatic stress disorder” (para. 5).
For now, those nearing or experiencing end-of-life (EOL) in the United States currently have a tragically limited number of options with which to address the debilitating death anxiety and depression that can come during this ultimate transition. As new and exciting research emerges, leaders in the EOL care community have come to understand that psilocybin-assisted therapy, due to its startling ability to dramatically reduce death-related anxiety and depression in patients after a single dose, has the potential to become the standard of care for those facing end-of-life.
Psilocybin As Sacred Medicine
The concept of psilocybin as a therapeutic tool is not new. In fact, its spiritual and medicinal use predates recorded history. Used in ceremony and healing rituals since at least 3000 BC, this ancient medicine was considered sacred by pre-Columbian Mesoamerican cultures – the Aztec people gave it the name teonanacatl, meaning ‘flesh of the gods.’ In a review titled “Hallucinogenic drugs in pre-Columbian Mesoamerican cultures,” researcher F.J. Carod-Artal (2014) states, “archaeological evidence points to mushroom use in Mexico, Guatemala, Honduras, and El Salvador, where the ‘mushroom stones’ carved to represent hallucinogenic mushrooms have been found” (para. 17). The use of entheogenic mushrooms in indigenous American sacred practices were recorded in the 16th century by religious and colonial invaders. A Franciscan missionary, fray Bernardino de Sahagún, reported in one of his numerous books documenting the Aztec people, that teonanacatl was “used as medicine for fever and gout” (Carod-Artal, 2015, para. 18). There is also evidence to suggest that psilocybin mushrooms have been at the center of many spiritual and medicinal ritualistic practices across the world for thousands of years.
The deeply intertwined natural and ancient history of psilocybin-containing mushrooms is just the beginning of this intriguing story, however. The drug’s initial introduction to the world of western medicine is perhaps the most important piece of the puzzle in understanding how this unlikely breakthrough therapeutic has reached the crossroads at which it currently stands. It began in 1955, when Gordon and Valentina Wasson traveled to the city of Huautla de Jimenez, in the state of Oaxaca in southern Mexico, to participate in a traditional sacred mushroom ceremony with the Mazatec people. This would lead them to publish detailed accounts of their experiences with psychedelic mushrooms – reporting intense visions, the fracturing of their own identity, and communications with ‘God’ – in a 1957 issue of Life Magazine, under the title, “Seeking the Magic Mushroom” (Wasson, 1957).
In the same year, Roger Heim, a French mycologist, officially identified the sacred mushrooms to be of the genus Psilocybe, nearly all varieties of which contain psychedelic compounds, and was later able to cultivate them. Samples of the mushroom were sent to Swiss chemist Albert Hofmann – the very same scientist who accidentally discovered LSD in 1943 – and he and his research team became the first scientists to isolate and identify the mushrooms’s psychoactive alkaloids psilocybin and psilocin (Hofmann, 2009). Armed with accounts of the mystical and healing powers of psychedelic mushrooms, Hofmann’s employer Sandoz, a pharmaceutical company out of Switzerland, began producing and distributing pure psilocybin for use in research and clinical settings. This would mark the beginning of an unhindered period of rapid growth for researchers interested in psilocybin as a therapeutic for a variety of challenging human conditions, including terminal cancer. According to Griffiths and colleagues (2016), “Several unblinded studies in the 1960s and 70s suggested that such compounds might be effective in treating psychological distress in cancer patients” (para. 2).
However, only a few years later, a sea-change in the social and political climate of the United States would bring most psychedelic research to a screeching halt. The combined effect of a growing moral panic regarding the recreational use of LSD, and all psychedelics by association, and a concerted governmental prohibition effort, resulted in psilocybin being federally classified as a Schedule 1 drug under the Controlled Substance Act of 1970. This caused laws to harden to the point of shuttering many promising psilocybin-related research studies.
It wouldn’t be until more than 20 years later when researchers like Roland Griffiths would take up the mantle of psilocybin research (Shiffman, 2016). When research on psilocybin as a potential therapeutic finally reemerged, quietly in the last decade of the 20th century, researchers attempted to pick up where their predecessors had left off. This included developing studies around the use of this drug for treatment of addiction, mental health conditions and the terminally ill. What they would find would change the landscape of potential treatment options for those suffering from debilitating existential distress at end-of-life.
SSRIs vs Psilocybin-Assisted Therapy
While the early 1990’s saw this revolutionary research getting back underway, it also saw Serotonin Reuptake Inhibitors (SSRIs) become the new standard for treating anxiety and depression in terminally ill populations. However, in the roughly 30 years that SSRIs have been the gold-standard for treating a host of mental health conditions including major depressive disorder, generalized anxiety disorder, bipolar depression, obsessive-compulsive disorder, panic disorder, and post-traumatic stress disorder, evidence has continued to pile up against these widely used drugs.
For healthcare providers who wish to ease the burden of death-related depression and anxiety, SSRIs have proven insufficient, in part because the drug must build up in a patient’s system for weeks, or even months, before any relief can be felt. It is possible that, for those with an aggressive terminal diagnosis, the waiting period required for these medications to become active may make up a significant portion of their remaining time. Add to this an often questionable rate of efficacy, an ever-changing list of both physical and mental side effects, and a relatively high rate of overdose – as a result, antidepressant and anti-anxiety medications like Lexapro, Zoloft, and Paxil are no longer regarded as a desirable care standard for existential distress at EOL by many healthcare providers.
In an article for The Guardian, Dr. Robin Carhart-Harris (2021), of the Imperial College of London’s Centre for Psychedelic Research, commented on what makes psilocybin therapy different from more traditional modalities: “While SSRIs dampen emotional depth by reducing the responsiveness of the brain’s stress circuitry, helping to take the edge off depressive symptoms, psilocybin seems to liberate thought and feeling. It does this by ‘dysregulating’ the most evolutionarily developed aspect of our brain, the neocortex. When this liberation occurs alongside professional psychological support, the most common outcome is a renewed breadth of perspective” (para. 9). In other words, while SSRIs only serve to dampen emotional response – and thereby temporarily reduce depressive symptoms – psilocybin appears to actually go into the brain and make contact with the damaging thought patterns responsible for the debilitating mental health condition. Simply put, SSRIs treat only the symptoms, whereas psilocybin-assisted therapy can treat the cause.
A New Frontier In Mental Health
For those new to psychedelic research, the physical experience of being treated with a large dose of psilocybin might appear as a bit of a mystery. As Emily Whinkin (2023), of the Advanced Integrative Medical Science (AIMS) Institute in Seattle, WA, explains, “the immediate effect of psilocybin (within 20–40 min of administration) range from a near-indetectable change in perception, to profound visions, mystical experiences, and insights [but] the range of documented experiences depends on the dose” (Whinkin, et. al, pg. 52). While the psychological mechanisms at work in psilocybin-assisted therapy are not yet fully understood, new research is emerging that points to specific parts of the brain being impacted by this type of treatment, particularly a system called the Default Mode Network (DMN), or the part of the brain that’s responsible for our rigid thought patterns and assumptions about self and the world.
According to Kristina M. Conner, MD (2023), Chief of Palliative Medicine at Exeter Health Resources, “As the brain develops over a person’s lifespan, the DMN develops rigid pathways of communication between brain regions, forming the ‘neurological basis for self’ which involves thinking about the future and remembering the past. An overactive DMN can lead to rumination and excessively negative self-reflection, and has been associated with depression, chronic pain, and drug cravings” (para. 8). Charles Nemeroff, co-director of the Center for Psychedelic Research & Therapy at the University of Texas at Austin, told the Washington Post that patients with psychiatric disorders find that the “[DMN] is stuck in a circuit that [it] can’t get out of, and psychedelics break that cycle,” (Morris & Soong, 2023, para. 13). Adding that, when psilocybin enters the human brain, it allows areas that don’t normally communicate with each other to begin to make contact.
In 2016, Dr. Carhart-Harris and colleagues conducted a study examining the impact of psilocybin, with psychological support, on patients with treatment-resistant depression which showed some surprising results: a dramatic reduction in depression symptoms for up to three months after treatment (Carhart-Harris, et. al, 2016). In an attempt to explain the previous study’s incredible level of efficacy on this stubborn mental health condition, Carhart-Harris carried out a follow up study using an fMRI to peer into the brains of participants as they were receiving the therapy. The findings were exciting, revealing in particular that psilocybin reduced blood flow to the DMN, functioning a bit like a reset button – turning it off, disorganizing it, and then reconsolidating to render it much more flexible to new thought patterns (Carhart-Harris, et. al, 2017).
Is Psilocybin-Assisted Therapy Safe?
With excitement growing around psilocybin-assisted therapy for patients suffering from EOL distress, there have also been questions raised regarding the safety of this therapeutic for members of vulnerable populations, such as geriatric patients or the terminally ill. The concerns around this issue are two pronged, with some worrying about potential side effects and others more focused on the substance’s potential for abuse. Negative side-effects from psilocybin are extremely rare – from mild effects such as temporary dehydration and sleep disturbances, to more severe reactions, such as the possibility of triggering psychosis. While the possibility of the drug to trigger underlying mental health conditions does exist, it is extremely remote, and there are no documented cases of psilocybin inducing such conditions.
On the other hand, the use of SSRIs have repeatedly proven to increase the risk of psychosis and other poor mental health outcomes in patients. According to Scientific American, “Prior studies found increased suicidal ideation with…[SSRI] use [and] in 2004 the FDA gave these drugs a black box warning – a label reserved for the most serious hazards” (Kwon, 2016, para. 8). Compare this with psilocybin-assisted therapy occurring in controlled research or clinical settings, where there have been no reports of sustained psychosis (Pollan, 2018), and we see a significant reduction in risk of serious side-effects from the current standard of care.
Furthermore, there is no evidence to suggest any risk of psilocybin overdose. Compare this to the overdose rates for SSRIs, the current standard of care for EOL existential distress, which are in the thousands per year in the US. In fact, 2021 saw an all time high of 5,859 overdose deaths from antidepressants (NIDA, 2023). Regarding the possibility of abuse, The Federal Food and Drug Administration (FDA) has voiced concern in a recently issued draft guidance aimed at researchers working with psilocybin. The FDA noted that recorded mood and cognitive changes, as well as its status as a federally controlled substance (the obsolete remnants of a government-manufactured moral panic around psychedelic use) require special attention in research of this kind.
In a 2006 interview with Johns Hopkins Medicine, Roland Griffiths weighed in on the issue: “No mind-affecting drug is absolutely safe. But the risks of the hallucinogens can be managed in appropriate research settings. Unlike drugs of abuse such as alcohol and cocaine, the classic hallucinogens are not known to be physically toxic and they are virtually non-addictive, so those are not concerns” (Johns Hopkins, 2006, para. 9). It is important to note that, in spite of its lingering designation as a Schedule 1 controlled substance, the FDA has given psilocybin the distinction of “breakthrough therapy” not once but twice in recent years, due to the unprecedented results seen in clinical studies involving those with major depressive disorder.
A 2013 analysis of over 130k survey respondents, through the Department of Neuroscience at Norwegian University of Science and Technology, “found no relation between lifetime use of [psilocybin] and any undesirable…mental health outcomes, including serious psychological distress…symptoms of panic disorder, major depressive episode, mania, social phobia, generalized anxiety disorder, agoraphobia, posttraumatic stress disorder, or non-affective psychosis” (Krebs & Johansen, 2013, para.19). While these results show a low correlation between psilocybin use and poor mental health outcomes – and instead show a clear reduction in conditions such as depression anxiety in those who used the drug over extended time periods, researchers and clinicians are still extremely careful about who they treat with psilocybin therapy. As Fred Barrett, Johns Hopkins Center for Psychedelic and Consciousness Research director, told the Washington Post, “researchers who study psilocybin generally screen out people who have family or personal history of psychosis, schizophrenia, mania and bipolar disorder” and as a result of this abundance of caution, “they don’t tend to see any prolonged negative effects from the drug” (Morris & Soong, 2023, para 26).
A New Way To Approach End-of-Life
What does all of this mean for those experiencing death-related anxiety and depression? An unprecedented level of efficacy for treating end-of-life distress with a very low risk of side effects. This can improve the quality of life for those approaching death by reducing the life-limiting symptoms of these mental health conditions. It is clear that the low risk of side effects, coupled with rapid and dramatic symptom reduction, makes this drug extremely suitable for sensitive populations such as the elderly or the terminally ill. As a result of this emerging information, a shift in public opinion is occurring in Western society around the use of psilocybin as a potential therapy for those experiencing end-of-life distress. According to New York Times reporter Dana G. Smith, Ph.D, social and political shifts are helping this process along. Wildly popular books such as Micheal Pollan’s “How To Change Your Mind,” and its accompanying Netflix series, as well as decriminalization and legalization efforts in various US states, have opened up the public conversation about the promise of psychedelics for a wide range of ailments – pointing out that, “psychedelics have surged in popularity in recent years: 1.4 million Americans tried hallucinogens for the first time in 2020” (Smith, 2023, para 6).
This rapid social destigmatization of psilocybin use can be seen in a variety of phenomena. For example, in a Canadian population survey investigating the social acceptability of psilocybin-assisted therapy for those experiencing EOL distress, Université Laval researchers Plourde and colleagues (2024) found the results to be overwhelmingly in favor of allowing the dying to access psilocybin, concluding that, “In terms of acceptability, 79.3% of Canadians considered psilocybin-assisted therapy a reasonable medical choice for a patient suffering from existential distress at the end of life” (para. 12). The results of this study shows that legalization of psilocybin for medical purposes transcends political and social barriers. Mendoza (2022), a Tulane University Medical Center doctor of psychology specializing in bereavement, attributes the accelerating loss of stigma around psilocybin-assisted therapy for those in EOL partially to an increase in death awareness and education over the past 10 to 15 years.
Indeed, the recently coined ‘Death Positive Movement’ has made significant strides towards re-humanizing death and dying in our modern society – primarily through efforts to get people talking about their own, and their loved one’s, inevitable death. This new kind of death-aware conversation, combined with an abundance of promising new research into ‘alternative’ therapeutic options, has shifted the way that end-of-life care providers, the broader medical community, and the public, view the future of competent and compassionate care for the dying. As psychedelics research pioneer Roland Griffiths told journalist Richard Shiffman, “psychedelics may never be available on the drugstore shelf…but the scientists do envision a promising future for these substances in controlled clinical use” (2016, para. 7).
In the big picture, psilocybin-assisted therapy is still in the relatively early stages of clinical research – however, it has already shown an incredible amount of promise for addressing treatment-resistant mental health conditions relating to a terminal diagnosis. Perhaps the most notable study to emerge from the modern wave of psilocybin research is Roland Griffiths groundbreaking 2016 study, published in The Journal of Psychopharmacology, with the telling title: “Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer” (Griffiths, et. al, 2016). This randomized double-blind trial assessed 51 patients, with life-threatening or terminal cancer and significant existential distress, before and after taking a dose of lab-synthesized psilocybin. The study included pre and post therapy sessions focusing specifically on the patient’s depression and anxiety regarding the concept of their own death. The size of the dose varied and, unsurprisingly, the researchers found that the higher the dose, the more positive an impact it had on an individual’s perception of their own mortality.
More than three quarters of participants reported a significant reduction in their illness/death-related depression and anxiety, with the effects continuing at the same rate 6 months after treatment. Participants also experienced a very low rate of side-effects, with a temporary moderate rise in blood pressure and transient mild nausea at the time of the event, occurring in a small percentage of the population (Griffiths, et. al, 2016). This study demonstrates the staggering impact that a single large dose of psilocybin, in conjunction with targeted therapy methods, can have on a person’s fear of death while approaching the end of their lives. As Griffiths told Scientific American, “More than three-quarters [of participants] reported significant relief from depression and anxiety – improvements that remained during a follow-up survey conducted six months after taking the compound” (Shiffman, 2016, para. 6).
In another 2016 study, Associate Director of the NYU Langone Center for Psychedelic Medicine, Stephen Ross, looked at 29 individuals with cancer-related depression and anxiety who were given a single large dose of psilocybin coupled with psychotherapy. The results astonished Ross’s team, demonstrating that “psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and antidepressant effects (approximately 60–80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death” (Ross, et. al, 2016). The results of these two studies in a nutshell? A single-dose psilocybin has a high likelihood of producing dramatic and sustained improvements in depression and anxiety relating to death, particularly in those struggling with a terminal diagnosis. When it comes to the potential for psilocybin-assisted therapy to change the way we care for the dying, the groundbreaking nature of the Johns Hopkins and NYU studies served to throw the door wide open on a new frontier of exciting treatment possibilities. As Ross told Scientific American, “It is simply unprecedented in psychiatry that a single dose of medicine produces these kinds of dramatic and enduring results” (Shiffman, 2016, para. 7).
The Future of Psilocybin Therapy in Palliative Care
Plans for putting psilocybin-assisted therapy into practice are already well underway. Dr. Kristina Conner (2023) offers a snapshot of how this new modality might play out in a palliative care setting, beginning by stressing the importance of patients’ receiving psychotherapy before and after a psilocybin treatment and going on to explain, “a typical approach may involve the following: Screening for…severe mental illness…, multiple pre-treatment counseling sessions, a single dose of psychedelic medication administered in a comfortable, safe session, with trained therapists present throughout the several hours long experience, [and] multiple post-treatment counseling sessions” (para. 12). As several other US states prepare to follow Oregon and Colorado in their successful effort to legalize psilocybin-assisted therapy for a variety of health challenges, and federal funding is beginning to flow into psilocybin research for the first time in 50+ years, many experts in the field are diligently preparing for a near future where this therapeutic method will be the new standard of care for the dying.
For those entering the field of palliative or hospice care, as well as those training to enter into EOL doulaship, such promising new treatment modalities bring a fresh wave of excitement and enthusiasm. Those who choose to provide end-of-life care serve a sacred and essential role in our society – acting as protectors and guides for those passing from this place into the next. Psilocybin-assisted therapy promises to be a powerful new tool for facilitating a dying experience filled with peace, dignity, and perspective in this modern world – as well as a renewed hope for reclaiming our collective cultural understanding of this universal human experience.