A NEW UNDERSTANDING: SCIENCE OF PSILOCYBIN

INTRODUCTION:-

Psychedelic substances like LSD and psilocybin — the active ingredient in magic mushrooms — are
powerful, able to transform the way that people who use them perceive the world. Because of that,
after years of prohibition, psychiatric researchers in the US are hoping to take advantage of that power
to transform mental health treatment.

And as the new documentary “A New Understanding: The Science of Psilocybin” shows, the results
we’ve seen so far are powerful. Perhaps most interestingly, the film shows how these substances
transform the people who undergo this therapy.

“Psilocybin does in 30 seconds what antidepressants take three to four weeks to do,” David Nutt, a
professor of neuropsychopharmacology in the division of brain sciences at Imperial College London
explains in the film. Researchers have found that a single dose of psilocybin accompanied by therapy can
have a transformational effect on mental health — like a “surgical intervention” — able to treat even
cases of depression and anxiety that resist standard treatment.

The film follows the researchers and study participants that are at the forefront of this modern era of
psychedelic study. Cancer patients facing distress about end of life talk about how their experience helps
them overcome that distress and accept their condition. Healthy volunteers who took psilocybin for the
first time to help show that it can be used safely in a therapeutic setting describe the way the “trip”
changed their perception.

On a basic level, a part of the brain that seems to coordinate mood and is very active in cases of
depression seems to basically quiet down for a time, allowing connections to form between regions of
the brain that rarely communicate with each other. This mimics an effect seen in the minds of long term
meditators. Something in this experience seems to cause the “trippy” effects of the drug, which
participants in this research undergo while listening to music and sitting with trained observers.

“In terms of whether these agents cause hallucinations, they’re a little bit misclassified, a hallucination is
an experience in some sensory phenomenon based on a stimuli that doesn’t exist in reality, it’s
internally generated,” says Stephen Ross, an associate professor of psychiatry at NYU School of
Medicine, in an interview in the film. “Versus an illusion would be looking at the wall and the wall is
melting, that would be an illusion, and these drugs tend to cause more illusions than frank
hallucinations, they alter how we perceive real stimuli.”
In order to cause these effects, these drugs activate serotonin 2a receptors, explains David Nichols,
president and co-founder of the Heffter Research Institute.

But something about this experience — the brain activation, illusions, and hallucinations — seems to do
something more profound that’s harder to understand. It’s able to reliably cause what researchers call a
“mystical experience.” That experience is strongly linked with lasting effects.

DOCUMENTARY REVIEW:-

The documentary film, A New Understanding: Science Of Psilocybin (2017) features groundbreaking
research at Johns Hopkins University, University of California, Los Angeles, and New York University on
the use of psilocybin in palliative care and spirituality. Primary accounts and interviews with participants
and researchers in the film provide helpful illustrations of the empirical power of psilocybin-assisted
treatment.

This review outlines and expands on the psycho-social implications of the film with the use of details
directly from the publications, interviews, supplemental panel discussion, paid archives, and from a
2016 presentation given by Dr. Jeffrey Guss, the co-principal investigator of the NYU Psilocybin Cancer
Research Project (the main focus of this film), on the study’s primary clinical outcomes. A brief overview
about some of the science of how psychedelics work in the brain is offered.

Psychedelics and Mystical Experience:-

Psilocybin (pro-drug of psilocin) is considered the main active component of psychedelic mushrooms
and has been safely used in experimental settings to reliably induce religious-like or mystical
experiences, and produce long-term relief from anxiety and depression after a single treatment, along
with improvements in attitudes, moods and personality. Mystical experience (ME) refers to a
phenomenon involving the often awe-inspiring dissolution of the boundaries of the self, and an
immense spreading of the margin of the field [of consciousness], so that knowledge ordinarily
transmarginal would become included, bringing a mass of subconscious memories, conceptions,
emotional feelings, and perceptions of relation, etc., into view all at once, often resulting in profound
joy, ecstasy or rapture. ME is considered important, if not central, in the varieties of religious experience
and exists as the core foundation in the perennial philosophy, a philosophy of cross-cultural spirituality.

MEs are measured retrospectively using the Mystical Experience Questionnaire (MEQ) or as altered
states of consciousness (ASC) with more comprehensive questionnaires such as the 5D-ASC. These scales
evaluate how much participants experienced the following psychometric factors: sense of unity/oneness
(dissolution of the boundaries of the self; the core of MEs), visionary restructuralization (visions,
hallucinatory phenomena), timelessness, noetic quality (tacit knowledge), sacredness (sense of
significance and reverence), ineffability, and paradoxicality . The MEQ and 5D-ASC have served to
further understand psychosocial and neuropsychological implications of naturally-occurring as well as
drug-induced MEs, and are central factors in this analysis.

Some research suggests that it is for its potential to reliably induce MEs that psychedelic-assisted
psychotherapy leaves a profound and lasting impression on the participant, often taking place as the
single most, or among one of the five most meaningful experiences of their lives. High scores in
measures indicative of “full mystical experience” are strongly correlated to positive therapeutic
outcomes.

Suffering and Spirituality:-

Cancer diagnoses are commonly accompanied by depression, anxiety, existential (or psycho-spiritual)
distress, and demoralization syndrome, especially in the terminally-ill. An end-of-life diagnosis is often
characterized by the loss of sense of meaning, loss of hope, a sense of being a burden to others, loss of
dignity, loss of will to live and desire for hastened death .

Depression, anxiety, and social isolation may contribute to the development and progression of disease,
such as to the onset and mortality of cancer . In response, interventions focused on cultivating meaning
and improving spiritual well-being and quality of life have been helpful in protecting against and treating
these conditions.

Spirituality as a term has recently been medicalized for these purposes, referring to “the way individuals
seek and express meaning and purpose and the way they experience their connectedness to the
moment, to self, to others, to nature, and to the significant or sacred,” according to the Report of the
Consensus Conference on spirituality in palliative care. In line with these premises, the primary
psychosocial platform used in NYU’s psilocybin-assisted psychotherapy study was meaning and the
rediscovery of meaning .
Subjects:-

Subjects are here paired to their studies for context: Matt was a volunteer for the NYU Psilocybin Cancer
Research Project which examined the safety and efficacy of psilocybin-assisted psychotherapy on
psychosocial distress with advanced and/or recurring cancer. Annie was a volunteer for the UCLA
Psilocybin study which examined the safety and efficacy of psilocybin-assisted psychotherapy as a
treatment for psychological distress associated with the existential crisis of terminal disease. Sandy was
a volunteer in a Johns Hopkins University psilocybin study which investigated the effect of mystical-type
experiences occasioned by psilocybin on the attribution of personal meaning and spiritual significance.

Sessions:-

All studies in the film began with 1-3 preparatory psychotherapy sessions to allow each patient to tell
their stories, build a therapeutic alliance, undergo a meaning-making intervention and life review
exercise, and prepare them for the dosing session. Two clinicians trained to devote reverent, focused
attention to their actions and intentions then accompanied the patients throughout each 6-8 hour
psilocybin experience. Dosing sessions occurred in a welcoming, comfortably furnished room, and
patients were invited to lie down, put on eye shades, listen to carefully pre-selected instrumental music,
and direct their attention inward and allow themselves to experience negative emotions instead of
moving away from them. Follow-up integrative psychotherapy sessions helped patients contextualize
and understand the experience, and prepare them for re-adjustment following the end of the
therapeutic relationship.

In print:-

Results from these studies, and others like them, reveal a remarkable and sustained relief from anxiety,
depression, and existential distress, as measured by STAI, BDI, and HADS scales, respectively.
Concomitantly, improvements were observed in mood; psychological and spiritual wellbeing;
personality; attitude towards self, life, disease progression, and death; pain perception; life-satisfaction;
quality of life; with altruistic/positive social effects; and moderate to extreme positive behavioral
changes. No psilocybin-attributed serious adverse events occurred, and there were no medical nor
psychiatric side-effects .

A Short Review of Psychedelic Science:-

Positive therapeutic outcomes are most strongly associated with: depth of mystical experience, intensity
of Visionary Restructuralization , experience of epiphany, lasting memory of the experience, and sense
of love: “a loving kindness towards self, a love for people in their lives and people earlier in their life, and
then this broader sense of universal or cosmic or God love” .

These experiences contain visionary restructuralizations (VR), wherein episodic memories are
experienced at a similar level to external stimuli, in fact interrupting it, perhaps emerging from the
medial temporal lobe and flooding the visual cortex . The result is a lifelike surfacing of varying levels
and combinations of psychodynamic and autobiographical content. In his session, Matt had a vision of
whirling dervishes spinning to the Turkish tune that was playing, “and the faster they spun, the closer
they felt to God–or the pinnacle of love.” Vividness of visionary restructuralization is strongly correlated
to experience of meaning and significance and to measures of subjective well-being at follow-up.
Psilocybin’s propensity to facilitate episodic recall in this way may help patients explain and understand
where their fears are coming from and how to better deal with pain. This is akin to the acceptance and
mindfulness strategies applied in acceptance and commitment therapy, in which patients are
encouraged to open up and explore their unpleasant emotions and their causes.

Long-term reductions in pain and fear (anxiety) could be accomplished through a process of primary re-
appraisal, leading to more healthy responses to distressing thoughts and experiences. With the eye-
shades off, for example, Matt re-appraised frightening masks hung up in the room instead as “designed
to scare the fear out of you,” and added that psilocybin could help “take people out of feeling paralyzed
and filled with fear.” After the experience was over, Annie expressed a loss of rumination about death
and about medical procedures. Matt echoed this, stating “I feel I can die now with peace in my heart.”

It is possible that reductions in pain perception could be explained by the lasting relief from anxiety and
stress, which are also known to contribute to the development and exacerbation of disease.

An alternative explanation could involve a modification of the neuro-matrix, in which the self is viewed
as distinct from its surroundings and “the perception of unity of the body with all of the surrounding
qualities felt from the body, including pain.” . The core feature of ME is a sense of unity and oneness,
characterized by a dissolution of the boundaries of the self. It is possible that this temporary disruption
in the neuro-matrix could alter self-perception and therefore the experiences of pain and distress. How
exactly this occurs in the brain is still a matter of debate.

Some nuroscientific observations correlated with psilocybin-induced experiences with potential

therapeutic implications: reductions in thalamic gating, allowing for internal and external stimuli to flow
throughout the brain ; disintegration of the normal anti-phase relationship between active and resting
brain states (the task-positive and default-mode networks) characterized by greater inter-connectivity
and tightly synchronized communication between their respective anatomical regions ; reduced
amygdala activity with increases in orbito-frontal and anterior cingulate (ACC) cortices, having known
implications for mediating the disagreeableness of pain. These findings offer an array of possible
explanations for why psilocybin affects things like pain, anxiety and depression.

Pain:-

Pain has been implicated in disrupting interpersonal relationships, in affecting the ability to engage in
work and maintain healthy economic circumstances, in contributing to depression and anxiety, and in
the propensity for substance abuse. Psilocybin may reduce pain through its potent anti-inflammatory
properties due to its high activity at the serotonin-2A receptor. However, immuno-surveillance can help
prevent disease progression, and the immunomodulatory effects of psilocybin are still poorly
understood.

Social isolation and lack of social support also contributes to disease progression. Even when social
support is available, interpersonal distress often accompanies cancer diagnoses. Hopelessness,
helplessness and pessimism contribute to poor psycho-social adjustment and well-being. Recent
research finds psilocybin effective for reducing social pain and enhancing empathy. Recent pilot studies
also show promise for psilocybin-assisted treatment for tobacco and alcohol dependence.

Transformation:-

In the film, doctors witnessed in their participants a transformation and healing of interpersonal
relationships. After Annie’s diagnosis, she became irritable and started quarreling with her husband,
whom was her primary caretaker. When she returned home, her husband said that “it was like someone
had put on a light bulb inside of Annie’s head. She was literally glowing,” and found that she was no
longer as irritable.

Similarly, Guss describes Matt’s transformation as an “experience of being profoundly loved. Bathed in
light and love and a security that stayed with him throughout the remainder of his life. And he went
from being somebody who could not let himself be taken care of to somebody who could depend on
others and let others love him.” This experience appears to be common and may contribute to trusting
in health care providers, which could affect adherence to medical procedures.

These examples, including Sandy’s re-acquaintance with her husband, display how psilocybin-assisted
psychotherapy can have important implications beyond the individual, into social and interpersonal
domains, and could result in improved social support. Concurrently, psilocybin has been found to
acutely increase levels of oxytocin, which may improve the ability to manage stress , and could
contribute to increased trust in the health-care providers and thereby better adherence to their
recommendations.
A recent study found a moderate lasting increase in personality trait Openness, and that 90 percent of
patients reported increased psychological and physical self-care, after a single psilocybin session, and
that these changes were recognised by family members.

A New Hope:-

The profound effects of this therapy on depression and anxiety, for the individual and those around
them, along with its short-term duration compared to traditional psychotherapy, provides rich research
opportunities that might also lead to dramatically reduced cost of palliative and health care along with
priceless human experiences for the dying. The researchers hope to eventually make psilocybin-assisted
psychotherapy available to those with diagnoses of major depression and other anxiety disorders, and
not just to the terminally ill.