Project Overview

Psychedelic Research Implications for Palliative Care & End-of-Life Existential Distress

Anthony P. Bossis, Ph.D. New York University School of Medicine

Psilocybin Psilocybin

❖ Naturally occurring compound in many species of mushrooms

❖ Called “Flesh of the Gods” by the ancient Aztecs

❖ Long history of ceremonial use by indigenous cultures for religious insight and healing

❖ Psilocybin possesses a chemical structure similar to the neurotransmitter serotonin

❖ Rapidly metabolized to psilocin, an agonist at serotonin 5-HT-2A (primary receptor) and 5-HT-2C receptors

❖ Psychedelics do not lead to addiction / dependence (O’Brien, 2001); no evidence of association between lifetime use and increase in mental disorders (Krebs & Johansen 2013). Lifetime use of psychedelics was associated with a reduced likelihood of suicidal thinking, planning and attempts (Hendricks et al. 2015; Johansen & Krebs 2015) Psilocybin in the Mayan Culture

(1000 B.C. - 600 A.D.)

The Eleusinian Mysteries Ancient Greece ❖1600 BC – 392 CE. Annual festival celebrated the myth of Demeter and Persephone.

❖Participants included Plato and Cicero

❖Sacred Way from Athens.

❖κυκεών - believed to be entheogen ergot -grew on wild grass (Paspalum distichum) Entheogens in Ancient Greece

Eleusinian Mysteries (1500 B.C. - 392 A.D.) Seeking The Magic Mushroom by R. Gordon Wasson Brief History of Psychedelics 1938 - Present

Albert Hoffman Good Friday Study Recent & Ongoing Research: synthesizes Marsh Chapel Psilocybin, LSD, MDMA: LSD-25 Cancer anxiety, alcoholism, tobacco - Alan Watts / Joyous cessation, PTSD, meditators, Cosmology depression, religious leaders

First LSD psychiatric Strassman treatment: DMT Studies H. Osmond LSD w Alcoholics Sandoz Swiss Archives 1953 Produces of Neurology UCLA psilocybin on LSD Psilocybin Cancer 1960 Controlled 1947 Substances Act Anxiety Published June 1, 1967 1970 2011 1938 1962 1990-1995 1953 1943 1960 2006 Hoffman Aldous Huxley uses Harvard 1953-1977 Johns Hopkins ingests LSD mescaline Psilocybin Project 2016 •1000 clinical & research reports Psilocybin Mystical Leary, Alpert, NYU – JHU 1954 • 40,000 subjects Experience Published Metzner Psilocybin Cancer Doors of Perception • End of life distress and alcoholism 1957 Distress Published Gordon Wasson • Spring Grove Research: • Used in psychoanalysis

1964 Eric Kast LSD EOL study “To the extent that all mystical or peak- experiences are the same in their essence and have always been the same, all religions are the same in their essence and have always been the same.

This something common, this something which is left over after we peel away all the localisms, all the accidents of particular languages or particular philosophies, we may call the ‘core- religious experience’ or the ‘transcendent experience’” Psychedelic

ψυχή δηλείν

(psyche meaning soul or mind and delos meaning “make visible, manifest, or reveal”)

Entheogen

ἔνθεος and γενέσθαι

(“becoming divine within” or “becoming god within”) Characteristics of Mystical States of Consciousness (MEQ) (W. Pahnke, 1963; Pahnke & Richards, 1966) Unity

A strong sense of the interconnectedness of all people and things – All is One. Sense of oneness achieved through self transcendence. The Noetic Quality

Named by William James - a feeling of profound insight or intuitive knowledge with a tremendous force of certainty - of encountering ultimate reality. Sacredness

Intuitive response of awe, humility, holiness, reverence and wonder in the presence of inspiring reality. Deeply Felt Positive Mood

Joy, blessedness, peace and love to an overwhelming degree of intensity, often accompanied by tears.

Ineffability and Paradoxicality

Experience is felt to be beyond words, non-verbal, and impossible to describe.

A sense of reconciliation of opposites Transcendence of Time/Space

A sense of timelessness- transcending past, present, and future, and beyond ordinary three-dimension space in a realm of eternity or infinity.

A sense of past and future collapse into the present moment—an infinite realm with no time/space boundaries . Healing is the personal experience of the transcendence of suffering

E.Cassell, C.Hammersclag, E. Kubler-Ross, C. Saunders, B. Seigel, G. Stephens

Egnew, T. (2005). “The most beautiful and profound emotion we can experience is the sensation of the mystical.

It is the fundamental emotion that stands at the cradle of true art and true science”

Albert Einstein Research on Entheogens and Mystical Experience

1962: Marsh Chapel Experiment (“The Good Friday Experiment”)

Walter Pahnke, Harvard Medical and Divinity School

• Psilocybin subjects “experienced phenomena which were indistinguishable from, if not identical with” the categories of naturally occurring mystical experience”

• Majority of subjects who received psilocybin scored highly on most or all mystical experience measures

• Conclusion: ‘the results of our experiment would indicate that psilocybin is important tools for the study of mystical state of consciousness”.

2006 -Johns Hopkins University School of Medicine 2006

• 61% of psilocybin group vs 11% placebo complete mystical experience

• 14 month follow-up: 67% top 5 most significant spiritually experience; 58% most meaningful Long-Term Follow-Up of Good Friday Experiment (Doblin, 1991)

Category Experimentals Controls Six month Long-term Six months Long-term 1. Unity A. Internal 60 (77) 5 (5) B-External 39 (51) 1 (6)

2. Transcendence of Time and Space 78 (73) 7 (9)

3. Deeply Felt Positive Mood 54 (56) 23 (21)

4. Sacredness 58 (68) 25 (29)

5. Objectivity and Reality 71 (82) 18 (24)

6. Paradoxicality 34 (48) 3 (4)

7. Alleged Ineffability 77 (71) 15 (3)

8. Transiency 76 (75) 9 (9)

Average for the Categories 60.8 (66.8) 11.8 (12.2)

9. Persisting Positive changes in Altitude and Behavior 48 (50) 15 (15)

10. Persisting Negative Changes in Attitude and Behavior 6 (6) 2 (4) Psilocybin Participant Verbatim Comments / 14 Month Follow-Up Study Griffiths, R., Richards, W. et al., (2008. Journal of Psychopharmacology.)

The sense that all is One, that I experienced the essence of the Universe and the knowing that God asks nothing of us except to receive love. The part thatI [experienced] continues to astick reality out thatfor me was was clear, knowing beautiful, and bright seeing and experiencing with every sense and fiber of my being that andall things joyful... are In connected. short, this experience opened me up (gave To cease to be, as Ime understand a tangible it, vision) was not of whatfrightening. I think Itis wasattainable safe every day. and much greater than I have words for or understanding of. Whatever is larger than the state of being is what was holding me. The profound grief I experienced as if all of the pain and sadness of the world were passing through me cell by cell tearing apart my being. Religious and Mystical Experiences

Half of Americans (49%) say they have had “a religious or mystical experience – that is, a moment of religious or spiritual awakening.”

Similarities Between Naturally Occurring and Entheogenic God Encounters (Johns Hopkins University)

• 70% participants reported the experience to be more real than everyday normal consciousness

• 75% described communication with something described as sacred, 75% benevolent, 75% eternal

• 75% rated the experience as among the the most personally meaningful and spiritually significant of their life

• More than two-thirds identified as atheist before the experience no longer identified as atheist afterwards “I assert that the cosmic religious sense is the strongest and noblest driving force behind scientific research”

Albert Einstein Where and How Do Americans Die?

Despite Gallup polls finding that 9 out of 10 terminally ill patients with less than six months to live would choose to die at home, a majority of Americans today die in institutions, surrounded by medical equipment and medical staff.1,2,3

Research reveals that in general, Americans are dying not “good deaths”, but “bad deaths” marked by needless suffering and disregard for patients’ and families’ wishes or values. 4

1Foreman (1996). 70% would pick hospice, poll finds. Boston Globe. October. 2National Hospice Organization. (1996). New findings address escalating end-of-life debate (press release). October. 3Seidlitz et al. (1995). Attitudes of older people toward suicide and assisted suicide: an analysis of Gallup poll findings. J American Geriatric Society. 43:993-998 4 Breitbart, W., Gibson., C., & Chochinov, H. (2005). Palliative care. In: Textbook of Psychosomatic Medicine.

Institute of Medicine (1997) Approaching Death: Improving Care at the End of Life

Depression in the last year of life has increased 26 percent

A. Singer, . et al. Annals of Internal Medicine. (2015).

Demoralization Syndrome Depression and hopelessness strong predictors for desire for a “a state in whichhastened hopelessness, death inmeaninglessness, end-of-life patients. and existential distress are the core phenomena” Breitbart et al., 2000. Kissane et al., 2001 A Call for Addressing Existential and Psycho-Spiritual and for Effective Therapies Identified by:

World Health Organization (WHO)

Institute of Medicine (IOM)

National Comprehensive Cancer Network (NCCN)

Joint Commission (JC)

National Consensus Project (NCP)

National Quality Forum (NQF)] Key Components of Palliative Care

❖ Affirms life and regards dying as a normal process

❖ Neither hastens nor postpones death

❖ Integrates the psychological and spiritual aspects of patient care

❖ Encouraging life review to help recognize purpose, value, and meaning Spirituality at the End of Life

Qualitative thematic analysis of empirical literature on end-of-life spirituality

Meaning and purpose in life Attitude toward death

Self-transcendence Appreciation of life

Transcendence with a higher being Reflection upon fundamental values

Feelings of communion and Developmental nature of spirituality mutuality Conscious aspect Beliefs and faith

Vachon,Hope B., Fillion, L., & Achille, M. (2009). A Conceptual analysis of spirituality at the end-of-life. Journal of Palliative Medicine. 53-57 “Meaning can be found in life literally up to the last moment, up to the last breath, in the face of death”

Viktor Frankl Role of Meaning and Spirituality In Coping

• Palliative care literature has emphasized the need for greater focus on spiritual and existential therapeutic interventions in end-of-life care.

• Spirituality and existential approaches form the basis for emerging novel therapeutic modalities to meet this growing need.

• Spiritual well-being and meaning have demonstrated to be buffers against hopelessness, depression, and desire for hastened death in patients with advanced cancer and at the end of life.

Nelson. C, Rosenfeld, B., Breitbart, W. Galieta M. (2002). Spirituality, religion, and depression in the terminally ill. Psychosomatics. 43:213-20.

Breitbart W., Rosenfeld B., Pessin H., Kaim M., Funesti E., Galietta M. (2000). Depression, hopelessness, and desire for death in terminally ill patients with cancer. Journal of the American Medical Association. 284:2907-11.

McClain C., Rosenfeld B., Breitbart W. (2003). Effect of spiritual well-being on end-of-life despair in terminally ill cancer patients. Lancet. 361:1603-07.

Breitbart, W., Gibson., C., & Chochinov, H. (2005). Palliative care. In: Textbook of Psychosomatic Medicine.

Breitbart, W., Gibson, C., Poppito, S., Berg, A. (2004). Psychotherapeutic interventions at the end-of-life: A focus on meaning and spirituality. Canadian Journal of Psychiatry 49:6. 366-372 Depression, Hopelessness, and Desire for Hastened Death in Terminal Cancer Patients

Depression and hopelessness provide independent contributions to desire for hastened death

High rates of clinical depression linked with desire for hastened death

Depressed patients were 4 times more likely to have high desire for hastened death compared with nondepressed patients (47% vs. 12%) Among patients neither depressed nor hopeless, none had high desire for hastened death vs. two thirds of patients with both depression and hopelessness had high desire for hastened death

Breitbart, Rosenfeld et. Al Depression, hopelessness, and desire for hastened death in terminal cancer patients. Journal of the American Medical Association. 2000 v. 284, 22, 2907-2911 “Man is not destroyed by suffering; he is destroyed by

suffering without meaning”

Viktor Frankl Man’s Search For Meaning Transcendence in Existential Suffering at the End-of-Life

Transcendence is probably the most powerful way in which one is restored to wholeness… Everyone has a transcendent dimension, a life of the spirit. This is most directly expressed in religion and the mystic traditions...

When experienced, transcendence locates the person in a far larger landscape. Such an experience need not involve religion in any formal sense; however, in its transpersonal dimension, it is deeply spiritual. The quality of being greater and more lasting than an individual life gives this aspect of the person its timeless dimension.

The profession of medicine appears to ignore the human spirit. When I see patients in nursing homes who have become only bodies, I wonder whether it is not their transcendent dimension that they have lost.

Eric Casell, New England Journal of Medicine 1982 Mar 18:306 (11) Seeking Meaning at the End-of-Life

“You can find a degree of wholeness as a person, whether you get better or not, whether you are suffering or not, and I certainly have seen people finding a wholeness as they die.”

Cicely Saunders If you become whole again, you’re healed” E. Kubler-Ross The dying face “increasing pain, increasing anxiety, increasing morphine, with the ultimate disintegration of personality and a loss of the opportunity to die with dignity” (Island, 1963) “Death must become a more human experience. To preserve the dignity of death and prevent the living from abandoning or distancing themselves from the dying is one of the great dilemmas of modern medicine.

[Hallucinogens]…may one day provide a technique for altering the experience of dying."

Cohen S. Harper's, September. 1965: pp. 69-78. Psychedelic Research and End-of-Life Distress

1964 – 1977

2011-2016

Grob, C., Danforth, A. Chopra, G, Hagerty, M, McCay, C., Halberstadt, A., Greer, G. (2010) Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Archives of General Psychiatry. Griffiths R.R., Johnson, M.W., Carducci, M.A., Umbricht, A., Richards W.A., Richards B.D.,..Klinedinst, M.A. (2016) Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. Journal of Psychopharmacology. Ross, S., Bossis, A., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B.,…Schmidt, B.L. (2016) Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology. Gasser, P., Holstein, D,, Michel, Y., Doblin, R., Yazar-Klosinski, B., Passie, T., & Brenneisen, R. (2014). Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. Journal of Nervous and Mental Disease. Mystical Experience / Psychedelic Research and End-of-Life Distress

To date, over 450 cancer and end-of-life patients have received and shown significant clinical benefit (enhanced spiritual and existential well-being)

Kast, E.C. and Collins, V.J. (1966). LSD and the dying patient. Chicago Medical School Quarterly. Pahnke W, Kurland A, Goodman L, Richards W. (1969). LSD-assisted psychotherapy with terminal cancer patients. Psychedelic Drugs. Grof, S., Goodman, L., Richards, W. Kurland, A. (1973). LSD-assisted psychotherapy in patients with terminal cancer. Int. Pharmacopsychiat. Richards, W.A., Rhead, J.C., DiLeo, F.B., Yensen, R. & Kurland, A.A. (1977). The Peak experience variable in DPT-assisted psychotherapy with cancer patients. Journal of Psychedelic Drugs. Grob, C., Danforth, A. Chopra, G, Hagerty, M, McCay, C., Halberstadt, A., Greer, G. (2010) Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Archives of General Psychiatry. Griffiths R.R., Johnson, M.W., Carducci, M.A., Umbricht, A., Richards W.A., Richards B.D.,..Klinedinst, M.A. (2016) Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. Journal of Psychopharmacology. Ross, S., Bossis, A., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B.,…Schmidt, B.L. (2016) Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology. Gasser, P., Holstein, D,, Michel, Y., Doblin, R., Yazar-Klosinski, B., Passie, T., & Brenneisen, R. (2014). Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. Journal of Nervous and Mental Disease. NYU Psilocybin / Cancer Anxiety Research Project

• U.S Government FDA and DEA Approved Clinical Trial. (Other sites Johns Hopkins and UCLA)

• Investigated effectiveness of one psilocybin session (0.3 mg/kg) upon persons with existential and psycho-spiritual distress associated with cancer or at the end of life

• Placebo controlled, double-blind, randomized protocol with 7 week cross=over

• Evaluated the benefits that psilocybin may provide in helping cultivate meaning, enhance well-being, and foster a greater acceptance of dying with less anxiety “This changed my life” “I felt this constant state of becoming – I felt gratitude like I never felt before in my life. I felt totally welcome” “Right now I have no fear of recurrence of cancer – it does not enter my mind” “Less afraid of death, death is part of life”

“Everything“Death is love” doesn’t matter” “I cant even imagine it” (fear of cancer). “Something else I experienced was the feeling that one is eternal. And that all of existence happens in every moment” NYU Psilocybin / Cancer Anxiety Project Outcome Measures Mood, Psychological Well-Being, Psychiatric Inventory Consciousness, Spirituality, Mystical States, Meaning in Life Death Anxiety, Death Acceptance, Hopelessness

• State-Trait Anxiety Inventory (STAI) •Forgiveness Questionnaire (FORGIVE)

• Brief Profile of Mood States (POMS-SR) •Mysticism Scale

• Beck Depression Inventory (BDI) •Altered States of Consciousness Scale (5D-ASC)

• Brief Psychiatric Rating Scale (BPRS) •Hallucinogen Rating Scale (HRS)

• Positive and Negative Affect Schedule Expanded Form •Mystical Experience Questionnaire (PRMEQ)

• Hospital Anxiety and Depression Scale (HADS) •Kast Questionnaire

• Brief Symptom Inventory (BSI) •Purpose in Life Scale (PIL)

• Spiritual Transcendence Scale (STS) •Death Transcendence Scale (DTS)

• WHO Quality of Life, Spiritual, Religious and Personal Beliefs •Death Anxiety Scale (DAS) (WHO-SPRB) •Modified Beck Hopelessness Scale

• Demoralization Scale (DEM) •Hopelessness Assessment and Illness Scale (HAI) Clinical Phases of Psilocybin Research

Preparatory Period

• Three-four week psycho-educational and therapeutic period while establishing trust and rapport;

• Trust / rapport minimizes fear, anxiety, and other adverse reactions.

• Address past and current psycho-social and interpersonal history

• Address meaningful aspects of patient’s life

• Discuss emotional and physical concerns related to cancer or end-of-life.

• Describe and detail the organization of the sessions and potential perceptual, affective, cognitive experiences of psilocybin

Medication Session

Integration Sessions

Effects of Psilocybin on Anxiety and Psychosocial Distress in Cancer Patients New York University School of Medicine

⚫ Exclusion Criteria ⚫ Medical Illness • Severe cardiovascular illness • Abnormal hepatic and renal function • Diabetes • Medications o Anti-epileptics; insulin; oral hypoglycemics, anti-HTN (clonidine; aldomet); cardiovascular medications o Psychotropics: anti-depressants, mood stabilizers, anti-psychotics

⚫ Psychiatric ▪ Lifetime history or family history of schizophrenia, schizoaffective disorder, bipolar disorder, delusional disorder, other psychotic illness ▪ Active substance use disorder (SUD) ▪ SCID I & II done on screening Demographics & Clinical Characteristics

– The experimental and control groups were compared by t tests for the 3 main outcome variables by demographic or clinical characteristic dichotomous factors:

• Gender • Prior use of hallucinogens • Spiritual/religious faith vs none • Early vs later stage cancer

– None of these differences were statistically significant, nor did any approach significance. Psilocybina 1st Niacinb 1st Total Characteristics Categories

n=14 n = 15 n = 29 Female 7 50% 11 73% 18 62% Sex Male 7 50% 4 27% 11 38% Age; mean (SD) Range 22-75 52 (15.03) 60.27 (9.45) 56.28 (12.93) White/ Caucasian 13 93% 13 87% 26 90% Black/ African 0 0% 0 0% 0 0% American Hispanic/ Latino 0 0% 0 0% 0 0% Race Asian 0 0% 0 0% 0 0% American Indian/ 0 0% 0 0% 0 0% Native American Other 1 7% 2 13% 3 10% Atheist/ Agnostic 4 29% 10 67% 14 48% Jewish 4 29% 1 7% 5 17% Religious/ Spiritual Catholic 2 14% 0 0% 2 7% Beliefs Other Christian 3 21% 1 7% 4 14% Other Faith/ Tradition 1 7% 3 20% 4 14% Breast 4 29% 5 33% 9 31% Reproductive 3 21% 5 33% 8 28% Site of Cancer Digestive Cancers 3 21% 2 13% 5 17% Lymphoma/ Leukemia 2 14% 2 13% 4 14% Other Types 2 14% 1 7% 3 10% 48 Psilocybina 1st Niacinb 1st Total Characteristic Categories n=14 n = 15 n = 29 Stage IV 3 21% 7 47% 10 34% Stage III 4 29% 4 27% 8 28% Stage of Stage II 1 7% 4 27% 5 17% Cancer Stage I 5 36% 0 0% 5 17% Other 1 7% 0 0% 1 3% Adjustment Disorder w/ anxiety & 2 14% 6 40% 8 28% depressed mood, SCID (DSM-IV) chronic Diagnosis Adjustment Disorder 10 71% 8 53% 18 62% w/anxiety, chronic Generalized 2 14% 1 7% 3 10% Anxiety Disorder Hallucinogen No 7 50% 6 40% 13 45% Use Yes 7 50% 9 60% 16 55% 49 Anxiety and Depression Outcome Hospital Anxiety and Depression Scale-Total Score (Pre-Crossover)

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Psilocybin treatment produced immediate, substantial, and sustained improvements in several measures of anxiety:

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• Improvement evident at 1 day post Dose 1 Niacin-first group • Sustained for 6.5 months Psilocybin-first group Depression Outcome Hospital Anxiety and Depression Scale-Depression (Pre Crossover) 10 d=1.32 d=1.23 *** d=1.12 d=0.98 n 8 ***

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HADS Depression BDI

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H D 10 2 0 0 2-wks 26-wks 2-wks 26-wks post-D1 post-D2 post-D1 post-D2 Toward a Theory of Death Transcendence

“In the most sense, death is transcended through identification with phenomena more enduring than oneself”

Hood, R., & Morris, R. Toward a Theory of Death Transcendence. Journal for the Scientific Study of Religion. 1983,22 (4) 353-365. Death Transcendence Scale VandeCreek L (1999) The Death Transcendence Scale (Hood & Morris, 1983). In: Hill PC and Hood RW (Eds) Measures of Religiosity. Birmingham, AL: Religious Education Press, pp.442–445.

Statements• My death endorsing does not an experienceend my personal in which: existence. •I felt• everythingDeath is a transition in the world to somethingto be part ofeven the greater same whole. than this life. •I realized• I believe the oneness in life after of myself death. with all things. •In •whichDeath all isthings never seemed just an toending, be unified but is into part a ofsingle a process. whole. •In •whichThere I became is a force aware or power of the that unity controls of all things. and gives meaning to •In whichboth I feltlife myselfand death. to be absorbed as one with all things. Death Transcendence Scale Experience of death being transcended through identification with phenomena more enduring than oneself Hood, R., & Morris, R. 1983

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52% rated the psilocybin experience as the top 5 most spiritually significant experiences, including single most of their life.

87% reported improvement in general well-being and life satisfaction

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A 20 post-Dose 1 post-Dose 2 F 0 2-weeks 26-weeks post-Dose 1 post-Dose 2 Response/Remission Rates by Treatment Group

BDI Response Rates BDI Remission Rates HADS-A Response Rates 100 100 100

** **

s s

s ** **

t t

80 t 80 80

n n

a a

a *

i i

c c

c 60 60 60

i i

i **

P P

P 40 40 40

f f

o o

% % 20 % 20 20

0 0 0 -1 -1 -2 -1 -1 -2 -1 -1 -2 n n n n n n n n n io io io io io io io io io s s s s s s ss ss ss es es es es es es e e e s s s s s s s s s st st st st st st st st st o o o o o o o o o p p p p p p p p p d s s d s s d s s 1 k k 1 k k 1 k k w w w w w w 7 6 7 6 7 6 2 2 2 HADS-D Response Rates HADS-D Remission Rates HADS-T Response Rates

100 100 100

s s s

t t

80 ** t 80 ** 80 **

n n

n **

a a a

p p p

i i i

c c

60 c 60 60

i i i

t t t

r r r

a a a

P P

40 P 40 40

f f f

o o o

% % 20 % 20 20

0 0 0 -1 -1 -2 -1 -1 -2 -1 -1 -2 n n n n n n n n n o o o o o o o o o si si si si si si si si si es es es es es es es es es 80 s s s s s s s s s st st st st st st st st st o o o o o o o o o ) p p p p p p p p p l d s s d s s d s s

a 1 k k 1 k k 1 k k 80 t 60 w w w w w w

o 7 6 7 6 7 6 Niacin 1st group 2 2 2

T * p<0.05

(

)

l 40 Psilocybin 1st group ** p≤0.01

a I

t 60

C A

T 20

( F

40 T

I 0

C 2-weeks 26-weeks

A 20 post-Dose 1 post-Dose 2 F 0 2-weeks 26-weeks post-Dose 1 post-Dose 2 Cardiovascular Measures by Treatment Group Systolic Blood Pressure Diastolic Blood Pressure Heart Rate

160 90 80

u u

150 s 85 *** 75 s

s *

s ** e e **

*** r * e

r * t

P ** P

*** *** *** a

140 80 70 d

d ** R

*** o

130 75 65

s s

120 a 70 60 y

i Niacin Administration S D Psilocybin Administration 110 65 55 e e e n in in in in in in in in n in in in in in in in in n in in in in in in in in li m m m m m m m m li m m m m m m m m li m m m m m m m m se d d d d d d d d se d d d d d d d d se d d d d d d d d a -a -a -a -a -a -a -a -a a -a -a -a -a -a -a -a -a a -a -a -a -a -a -a -a -a B st st st st st st st st B st st st st st st st st B st st st st st st st st o o o o o o o o o o o o o o o o o o o o o o o o p p p p p p p p p p p p p p p p p p p p p p p p in in in in in in in in in in in in in in in in in in in in in in in in m m m m m m m m m m m m m m m m m m m m m m m m 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 6 9 2 8 4 0 6 3 6 9 2 8 4 0 6 3 6 9 2 8 4 0 6 1 1 2 3 3 1 1 2 3 3 1 1 2 3 3 * p<0.05 ** p≤0.01 *** p≤0.001 Summary of Findings

• Safety established: • Mystical Experience induced by psilocybin: • No medical or psychiatric SAEs • Mystical Experience mediated • AE: Mild elevation BP improved clinical outcomes • HA 28%; Nausea 14% • Spiritually significant and meaningful • Feasibility established: experiences: • Rapid acting anxiety and anti-depressant • Decreased existential distress: effects: • Demoralization • large magnitude of improvement • Hopelessness • Approximately 60-80% of participants • Improved quality of life, spiritual well being, continued with clinically significant mood, behavior; death transcendence (self- reductions in depression or anxiety rated positive attitudes about death) • Sustained anxiolytic and anti-depressant effects: • Overwhelmingly positive response from • at least 7 weeks but likely up to 8 public/media months • press release >1.5 billion views

Ross S., Bossis A., Guss J., et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology. Dec. 30, 2016 (12):1165-1180. Depression, Anxiety, QoL, Death Acceptance Johns Hopkins University, Journal of Psychopharmacology 2016

GRID-HAMD (Depression) Beck Depression Inventory HADS Depression 25 20 12

Low Dose 1st Low Dose 1st High Dose 1st High Dose 1st High Dose 1st 10 Low Dose 1st 20 15 8

r r

+ r

o o

10 o 6

c c

+ * c +

S S 10 * * 4 5 5 2

0 0 0 Baseline Post 1 Post 2 6 Months Baseline Post 1 Post 2 6 Months Baseline Post 1 Post 2 6 Months Timepoint Timepoint Timepoint

HAM-A (Anxiety) STAI Trait Anxiety POMS Total Mood Disturbance 30 50 70

Low Dose 1st Low Dose 1st High Dose 1st High Dose 1st 25 High Dose 1st 60 Low Dose 1st 45 50

e e

e 40

r r r

o o

o 15 40

c c

c +

S S S + 30 + 10 * * * 20 35

5 10

0 30 0 Baseline Post 1 Post 2 6 Months Baseline Post 1 Post 2 6 Months Baseline Post 1 Post 2 6 Months Timepoint Timepoint Timepoint

Brief Symptom Inventory McGill Quality of Life (Total) LAP-R Death Acceptance

50 9 40 High Dose 1st High Dose 1st High Dose 1st Low Dose 1st Low Dose 1st Low Dose 1st 40 8 35 *

30 + 7

e e

r r

r +

o o

* o c c 30

+ c

S S

* S 20 6

25 10 5

0 4 20 Baseline Post 1 Post 2 6 Months Baseline Post 1 Post 2 6 Months Baseline Post 1 Post 2 6 Months Timepoint Timepoint Timepoint

this experience, all of it, is my new becoming. I have been emptied and filled with something new. dying is going to be OK…because we go back into this

death will be OK

There is no fear, all washed away

Never felt such gratitude, never felt such surrender. Lessons on Love from Near Death Experiences

“And of all lessons of the near death experience, none is greater than the importance, indeed the primacy, of love. And what the near death experience teaches about love is that everything is love, and is made of love, and comes from love”

K. Ring, 2006. P.187 Near death experience (NDE) researcher on observations from decades of research “Birth and death is a lot of work”

Patrick Mettes Our true nature is the nature of no birth and no death.

Only when we touch our true nature can we transcend the fear of non-being, the fear of annihilation

Thich Nhat Hanh I maintain that the human mystery is incredibly demeaned by scientific reductionism, with its claim that materialism can account for all of the spiritual world in terms of patterns of neuronal activity.

We have to recognize that we are spiritual beings with souls existing in a spiritual world as well as material beings with bodies and brains existing in a material world.

Sir John Eccles, Nobel Neurophysiologist Evolution of the Brain: Creation of the Self (1989) p 241 “Science without religion is lame, religion without science is blind”

Albert Einstein Implications of Psilocybin-Mystical Experience For Palliative Care and End of Life Distress

❖ A shift in awareness with the potential to transform assumptions and beliefs regarding the nature of being, self, the body, and death.

❖ The experience of cancer may be transformed and no longer be an anxiety-provoking experience as a person experiences connection to the transpersonal realm, others, nature, or the sacred.

❖ Improved psychological, spiritual, and existential well-being

❖ Increased capacity for appreciation of time living. Increased sense of meaning and purpose

❖ Increased acceptance and peace with death as a natural cycle of existence.

❖ Enhanced relationships and capacity for expressions of love, intimacy, forgiveness

Grob, C.S., Bossis, A.P., & Griffiths, R.R. (2013). Use of the classic hallucinogen psilocybin for treatment of existential distress associated with cancer. In: B.I. Carr & J.L.Steel (Eds), Psychological Aspects of Cancer. New York: Springe Implications

• Improving how we die. Experiences of peace, acceptance, and dignity are possible even within the immanent separation from this life. Future studies.

• Provides method to reliably trigger and scientifically study the phenomenology of mystical experience states of consciousness

• Improve understanding of the neuroscience / neurobiology of mystical and peak states of consciousness.

• Pro-social and ethical implications

• Treatment of addiction , PTSD, depression, and other therapeutic applications

• Implications for inter-religious, inter-spiritual, and inter-faith dialogue.

• Implications for religious and consciousness studies – are we wired for meaning?

• And if so, why? Implications For Consciousness Research

❖ Can states of consciousness facilitated by psilocybin and related compounds be utilized for investigating the nature of consciousness?

❖ What is consciousness? Where is consciousness?

❖ Is consciousness generated solely by complex brain function?

❖ Or does consciousness exist ‘outside’ biology, i.e. non-local consciousness?

❖ Has it always existed?

❖ Is it the fabric of the ‘ground of being’, the universe?

❖ What happens to consciousness upon physical death?

❖ What if anything is enduring? The biggest joy was on the way home. In my cockpit window, every two minutes: The Earth, the Moon, the Sun, and the whole panorama of the heavens. And that was a powerful, overwhelming experience.

And suddenly I realized that the molecules of my body, and the molecules of the spacecraft, the molecules in the body of my partners, were prototyped, manufactured in some ancient generation of stars. And that was an overwhelming sense of oneness, of connectedness…it wasn't 'Them and Us', it was 'That's me!', that's all of it, it's one thing.

And it was accompanied by an ecstasy, a sense of 'Oh my God, wow, yes', an insight, an epiphany.

Edgar Mitchell, Astronaut Apollo 14. February 1971 “Alienation from nature and the loss of the experience of being part of the living creation is the greatest tragedy of our materialistic era. Therefore I attribute absolute highest importance to consciousness change. I regard psychedelics as catalyzers for this. They are tools which are guiding our perception toward other deeper areas of our human existence, so that we again become aware of our spiritual essence.

Psychedelic experiences in a safe setting can help our consciousness open up to this sensation of connection and of being one with nature. It is my great concern to separate psychedelics from the ongoing debates about drugs, and to highlight the tremendous potential inherent to these substances for self-awareness, as an adjunct in therapy, and for fundamental research into the human mind”.

Dr. Albert Hofmann, April 2007