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Psychedelics and end of life distress

I've been asked to write a short book section on "Psychedelics and dying" and that has nudged me into looking at this territory here on the blog.  It's a fascinating subject in all kinds of ways.  With the limited space I have, I'd like to 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'd like to talk about 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 distressis 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 & 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".  The latter paper interestingly comments "The recent trials have higher methodological quality and demonstrate the profound impact of psychedelics for this particular patient presentation.  However, a number of gaps, including understanding the meaning of death and dying in Western society; the nature of the psychedelic experience and how this lends itself to assisting those who are facing death; and how suffering and psychological distress are defined and understood in current psychiatric and medical frameworks.  This article provides a critical evaluation of the recent publications and suggests how anthropology may contribute knowledge to this emerging field."  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.

So it really looks as though psychedelics 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 in research in this area.  Small, exploratory reseach 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 subjectsand "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". 

These findings 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.  So Timmerman & 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 "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)." 

So I've now said 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, and thirdly I've noted similarities between some descriptions of psychedelic states and reports of near death experiences.  The fourth & last point I want 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."  He 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 explores the way people can transcend their self-focus & fear of death by asking about their links with five areas - mystical, religious, creative, nature & biosocial.    

More to follow ...

 

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