update on psychedelics & end of life distress Dr James Hawkins

When I wrote the original version of this short chapter, two of the areas that I focused on were the growing body of research showing that psychedelic-assisted therapy can dramatically ease severe existential distress associated with terminal illness.  A second, less well studied area I discussed was the observation that psychedelic experience reduces death anxiety in the general population.  I described relevant research studies that had been published up to 2020.  Now writing this update in March 2023, a whole series of further papers have emerged. 

For easing severe existential distress associated with terminal illness, there are developments on a number of fronts.  One is exploring whether MDMA-assisted therapy could also have a part to play here alongside the more established use of psilocybin-assisted therapy (Barone, 2022).  Another is the potential value of using psilocybin more broadly for catastrophic diagnoses other than just cancer (Ross, 2022), for earlier in the whole process – for example when a diagnosis of developing dementia has just been made (McManus, 2022) and for later in the whole process – for example as therapy for prolonged grief disorder in survivors (Gonzalez, 2022).  

The most recent 2023 literature review in this area (White, 2023) concludes: “Psychedelics have a unique mechanism of action that might be well suited for treating anxiety and depression associated with cancer. This offers new promise for patients who are not being sufficiently treated with current antianxiety or antidepressant medications.”  There is also the more practical paper “Top ten tips palliative care clinicians should know … “ (Rosa, 2022).

And as for the benefits and importance of psychedelic-associated reductions in death anxiety in the general population, it has been argued that “death anxiety appears to be a basic fear at the core of a range of mental disorders, including hypochondriasis, panic disorder, and anxiety and depressive disorders” (Iverach, 2014 & Menzies, 2019).  It’s intriguing then to note that a more recent paper (Moreton, 2023) found in a retrospective survey that “Reductions in death anxiety significantly mediated the effects of (psychedelic-induced) mystical experience on satisfaction with life, positive affect, and negative affect.”

Clearly psychedelics have the potential both to relieve difficult to treat forms of suffering and to enhance wellbeing in the general population.  It’s very interesting to see that in both situations, psychedelic-associated reductions in death anxiety seem to play a major part.   

psychedelics and end of life distress

I’m writing here about “Psychedelics and fear of death”.  It’s an important subject in all kinds of ways.  With the limited space I have, I will comment briefly on four overlapping areas.  One is the growing body of research showing that psychedelic-assisted therapy can dramatically ease severe existential distress associated with terminal illness.  A second, less well studied area, is the observation that psychedelic experience reduces death anxiety in the general population.  Thirdly, it’s interesting to note the similarities between some descriptions of psychedelic states and reports of near-death experiences.  And lastly, I will discuss how psychedelics might produce these effects.

So first, what about the developing research on psychedelics and terminal illness distress?  Stephen Ross’s paper “Therapeutic use of classic psychedelics to treat cancer-related psychiatric distress” is an excellent systematic review of clinical trials in this area, published from 1960-2018.  He found six open label trials that came out between 1964 and 1980, involving 341 patients, that suggested that psychedelic-assisted therapy (mostly with LSD) can improve cancer-related depression, anxiety, and fear of death.  Between 2011 and 2016 there were four randomized controlled trials published, involving 104 patients mostly treated with psilocybin.  This stronger scientific evidence demonstrated that “psychedelic-assisted treatment can produce rapid, robust, and sustained improvements in cancer-related psychological and existential distress”.  Understandably and rightly these very encouraging findings are triggering a flurry of further research. 

Two other recent papers have also reviewed the use of psychedelics for end of life distress – Reiche et al’s “Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review” and Varley’s “Psychedelic-assisted therapy for anxiety and depression in the face of death: A critical review with an anthropological lens”.  And to get a fuller, more personal sense of how psychedelics can affect cancer-related distress, see the series of short video interviews with research trial participants viewable online at the Heffter Research Institute’s website.  I would strongly recommend watching a few of these short 5 minute or so stories.  They colour in an understanding of the potentially tremendous value of psychedelics in this area in a way that simple numbers never can.

A major next step in making psychedelics better understood and more available for severe end-of-life distress is the forthcoming multicentre trial with Charles Grob from Harbor-UCLA and Anthony Bossis from NYU due to start early in 2021.  Grob has commented “What makes this study different from preceding studies is that it has broadened the patient population, it will take place in palliative care settings, and it will train practitioners … We will be training different palliative care practitioners including doctors, nurses, chaplains, social workers and psychologists.  What also makes this research different is that in the pioneering investigations with psychedelics in the 1960’s and in the modern era, we looked at individuals with advanced cancer.  In this study, we are opening it up to people with many additional medical illnesses that might be fatal and who are already enrolled in palliative programs.  I think the study will start in early spring 2021 … It will be a double-blind placebo-controlled study and we have budgeted for 60 subjects, but we have been advised to estimate about 80 subjects.  We are not advocating that people use psychedelics in the dying process. The study subjects must have an estimated life expectancy of six months and a palliative care diagnosis for an illness that could lead to a potentially fatal outcome. The study will take place at four to five different sites around the U.S. using the same methodology, the same entry criteria, and the same outcome measures.”

Psychedelics clearly have a potentially significant part to play in helping with severe end of life distress.  What about the less studied observation that psychedelic experience reduces death anxiety in the general population?  The Death transcendence scale has been the main assessment measure used with research in this area.  Small, exploratory studies have shown significant changes in scores on this scale still evident a year after even a single high-dose psychedelic experience – see “Long lasting effects of LSD in normal subjects” and “Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors”.  And again I think watching a couple of short videos of cancer-sufferers’ experience quickly illustrates why similar ‘inner journeys’ might well impact fear of death for anyone (not just people suffering from cancer).  I have a personal sense of this.  I lead a very happy, fulfilling life, but on a couple of occasions coming back down after deep psychedelic ‘pilgrimages’, I have felt a real sense of pain and sadness to be once more ‘confined’ into a small, efficient and very small ego structure.

These findings on death transcendence are deeply intriguing and to add still further interest, subjective experiences during psychedelic trips can feel very similar to experiences reported in near-death situations.  Timmerman and colleagues recently gave the psychedelic DMT to a group of subjects who “then completed a validated and widely used measure of NDE’s (near-death experiences)” – see the paper “DMT models the near-death experience”.  The researchers went on to report “we found significant relationships between the NDE scores and DMT-induced ego-dissolution and mystical-type experiences … Furthermore, we found a significant overlap in nearly all of the NDE phenomenological features when comparing DMT-induced NDEs with a matched group of ‘actual’ NDE experiencers. These results reveal a striking similarity between these states that warrants further investigation.”   

In a much larger study using the Erowid experience vaults, Martial et al – in their paper “Neurochemical models of near-death experiences: A large-scale study based on the semantic similarity of written reports” – reported “Near-death experiences (NDEs) are comparable among individuals of different cultures, suggesting an underlying neurobiological mechanism.  Anecdotal accounts of the similarity between NDEs and certain drug-induced altered states of consciousness prompted us to perform a large-scale comparative analysis of these experiences.  After assessing the semantic similarity between ≈15,000 reports linked to the use of 165 psychoactive substances and 625 NDE narratives, we determined that the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine consistently resulted in reports most similar to those associated with NDEs.  Ketamine was followed by Salvia divinorum (a plant containing a potent and selective κ receptor agonist) and a series of serotonergic psychedelics, including the endogenous serotonin 2A receptor agonist N,N-Dimethyltryptamine (DMT).” 

I’ve now written a little about psychedelic-assisted psychotherapy’s potential for easing severe end of life distress, and a bit too about psychedelic experience’s ability to reduce death anxiety in the general population.  Thirdly I’ve noted similarities between some descriptions of psychedelic states and reports of near-death experiences.  The fourth and last area I would like to look at is how psychedelics might produce these effects.  One can try to answer this question at multiple levels – see, for example, Robin Carhart-Harris’s recent paper “How do psychedelics work?” with its comment about “various scales of action, from the molecular (serotonin 2A receptor agonism) through to the anatomical and functional (heightened plasticity) and up to the dynamic (increased brain entropy), systems level (network disintegration and desegregation) and experiential.”  Robin proposes that “psychedelics initiate a cascade of neurobiological changes that manifest at multiple scales and ultimately culminate in the relaxation of high-level beliefs. The purpose of psychedelic therapy is to harness the opportunity afforded by this belief-relaxation to achieve a healthy revision of pathological beliefs.” 

The Death transcendence scale (Gjolaj, 2011) explores the way people can transcend their self-focus and fear of death by asking about their links with five areas – mystical, religious, creative, nature and biosocial.  Psychedelic experience is profoundly about connection – see the fine 2018 paper “Psychedelics and connectedness” (Carhart-Harris, 2018) – and this experience can deeply strengthen links with these five areas.  It seems to me that our sense of being separate, individual, to an extent isolated, selves is a development in evolution that has successfully promoted survival.  However, it comes with several costs, and fear of death seems to be one of those costs.  Psychedelic experience can allow us to feel deeply that this ‘separate self’ view is just one way of experiencing the world … and that it isn’t the most aware or profound way of being.  This realisation changes our response to the dissolution of our separate ego.  May this use of psychedelics continue to develop and flourish.  There is so much potential here for relieving deep & extensive suffering. 

Carhart-Harris, R. L. (2019). “How do psychedelics work?” Current Opinion in Psychiatry 32(1): 16-21.

Carhart-Harris, R. L., et al. (2018). “Psychedelics and connectedness.” Psychopharmacology (Berl) 235(2): 547-550.

Erowid Experience Vaults – website at http://www.erowid.org

Gjolaj, N. and D. A. MacDonald (2011). “Confirmatory factor analysis of a revised Death Transcendence Scale.” Archive for the Psychology of Religion 33(1): 79-91.

Griffiths, R. R., et al. (2018). “Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors.” J Psychopharmacol 32(1): 49-69.

Heffter Research Institute – website at www.heffter.org

Harrison, A. (2020).  “Pioneering psychedelic researcher once again paves the way with historic psilocybin study for end of life patients.”  Lucid News, August 3.

Martial, C., et al. (2019). “Neurochemical models of near-death experiences: A large-scale study based on the semantic similarity of written reports.” Consciousness and Cognition 69: 52-69.

Ross, S. (2018). “Therapeutic use of classic psychedelics to treat cancer-related psychiatric distress.” International Review of Psychiatry 30(4): 317-330.

Reiche, S., et al. (2018). “Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review.” Prog Neuropsychopharmacol Biol Psychiatry 81: 1-10.

Schmid, Y. and M. E. Liechti (2018). “Long-lasting subjective effects of LSD in normal subjects.” Psychopharmacology 235(2): 535-545.

Timmermann, C., et al. (2018). “DMT models the near-death experience.” Frontiers in Pharmacology 9(1424).

Varley, J. (2019). “Psychedelic-assisted therapy for anxiety and depression in the face of death: A critical review with an anthropological lens.” Journal of Psychedelic Studies 3(1): 14-18.

Vandecreek, L. and C. Nye (1993). “Testing the Death Transcendence Scale.” Journal for the Scientific Study of Religion 32(3): 279-283.