outline where do you want to die?2017/... · • time for final dialogues cancer vital signs:...

The NYU Psilocybin Cancer Project

Stephen Ross, MDAssociate Professor, Department of PsychiatryNew York University School of MedicineSenior Director, Division of Alcoholism and Drug AbuseDepartment of PsychiatryBellevue HospitalNew York, New York

Outline• Where do Americans die?

– Where do they want to die?– What is a “bad” death vs a “good” death

• Cancer-related psychological (ie, anxiety, depression) distress– Prevalence– Relationship to adverse outcomes– Current treatments

• Cancer-related existential/spiritual distress– Phenomenology– Relationship to adverse outcomes– Current treatments

Outline• Prior research of psychedelic treatment for cancer-

related psychological and existential distress

• Recently completed controlled trials of psilocybin-assisted psychotherapy for cancer-related psychological and existential distress– University of California, Los Angeles (UCLA)– Johns Hopkins University (JHU)– New York University (NYU)

• Study design and results of NYU psilocybin-assisted psychotherapy randomized controlled trial for cancer-related psychological and existential distress

• The Future

Where do you want to die?

ICU = Intensive Care Unit.

• Hospital/ICU

• Nursing Home

• Hospital-based hospice

• Home-based hospice

Where do you want to die?

• Approximately 50% die in a hospital

• Approximately 70% die in a hospital, nursing home, or long-term care facility

• Only 25% die at home (Centers for Disease Control and Prevention, 2005)

• 70% say they would prefer to die at home (Time/CNN poll, 2000)

• > 80% with chronic diseases want to avoid hospitalization and ICU care when dying (Dartmouth Atlas of Health Care, 2005)

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

Existential Needs in Advanced/Terminal Cancer

Puchalski CM. Ann Oncol. 2012;23 Suppl 3:49-55.

• As high as 90% of patients cite spiritual/existential themes, but only 10% to 20% of oncologists assess this domain

• Meaning• Purpose• Hope• Seeking forgiveness• Increased importance of relationships with family and

friends• Wanting a closer connection with God or one’s faith• Thoughts of death and dying

In search of a good death

Steinhauser KE, et al. Ann Intern Med. 2000;132(10):825-832.

• Pain and symptom management• Clear decision making• Life review • Contributing to others• Affirmation of the whole person• Importance of spirituality and meaning• Resolution of conflicts• Completion• Spending time with family and friends• Preparation for death• Time for final dialogues

Cancer Vital Signs: United States

National Cancer Institute. 2013.

• 1.6 million new cancer diagnoses/year

• 600,000 cancer-related deaths/year

• 10.5 million with current or past cancer diagnosis

• Approximately 40% will be diagnosed with cancer in their lifetimes

Psychiatric Disorders in Cancer

Mitchell AJ, et al. Lancet Oncol. 2011;12(2):160-174. Miovic M, et al. Cancer. 2007;110(8):1665-1676.

Most common psychiatric diagnoses in patients with cancer

• Major depression and other depressive disorders

• Anxiety spectrum disorders

• Adjustment disorders

• Cancer-related clinically significant anxiety and/or depressive symptoms: 30% to 40% of hospitalized patients

• As many as 50% of patients with advanced or terminalcancer meet criteria for a psychiatric disorder: Adjustment disorders, depressive disorders, or anxiety disorders

Clinically significant anxiety or depression in cancer is associated with:

ER = emergency room.Brown KW, et al. Psychosom Med. 2003;65(4):636-643. Arrieta O, et al. Ann Surg Oncol. 2013;20(6):1941-1948. Jaiswal R, et al. Int Rev Psychiatry. 2014;26(1):87-101.

• Medication non-adherence• Increased ER visits and hospital stays• Adverse medical outcomes• Lower quality of life• Decreased social function• Increased disability• Increased hopelessness• Increased hastened desire for death• Increased rates of suicide• Decreased survival rates from cancer

Limited Efficacy of Treatments for Cancer-Related Anxiety and Depression

AD = antidepressant; MDD = major depressive disorder. Grassi L, et al. Int Rev Psychiatry. 2014;26(1):44-62. NCCN 2014. Iovieno N, et al. Int Clin Psychopharmacol. 2011;26(2):69-74. Laoutidis ZG, et al. BMC Psychiatry. 2013;13:140. Ostuzzi G, et al. Cochrane Database SystRev. 2015;(6):CD011006.

• Pharmacotherapies and psychosocial treatments: Mixed to limited efficacy

• ADs with limited to no efficacy (compared to placebo) in treating cancer-related depression– 3 meta-analyses: ADs not clearly > than placebo

• Meta-analysis of ADs in MDD with comorbid medical disorders – ADs > placebo for some medical disorders (ie,

HIV/AIDS, post-stroke)• But, ADs = placebo in cancer with placebo

response rate of 40%

Spectrum of Responses to Cancer

• Spectrum of responsivity to diagnosis of advanced/terminal cancer

• Some cope through denial

• Some adapt instinctively through a search for meaning

• Others experience “Existential Distress”

Spiritual Distress/Demoralization

Kissane DW. Aust Fam Physician. 2000;29(11):1022-1025. Anandarajah G, et al. Am Fam Physician. 2001;63(1):81-89.

• Mental turmoil experienced by individuals facing impending death accompanied by:– Disconnected from sources of love– Remorse/guilt – Powerlessness – Futility/Pessimism – Sense of meaninglessness of life – Hopeless – Helpless – Loss of dignity – Isolation/loss of connection (self, family, community,

religion/spiritual practice)– Loss of organization (ie, executive function, intention)– Hastened desire for death

Clinically relevant existential/spiritualdistress in cancer is associated with:

Puchalski CM. Ann Oncol. 2012;23 Suppl 3:49-55.

• Increased pain perception

• Decreased quality of life

• Increased depressive and anxiety symptoms

• Increased health care visits

• Increased desire for hastened death

• Increased suicidal ideation and behaviors

Advanced Cancer, Hastened Desire for Death, Suicidality

HDD = hastened desire for death.Jaiswal R, et al. Int Rev Psychiatry. 2014;26(1):87-101.

• Cancer is associated with a twofold increase risk of suicide

• Outcome still relatively rare in less 1% of patients

• More subtle manifestations of suicidality (ie, HDD) more common particularly with advanced cancer

• Palliative care patients: HDD 9% to 22%

Rodin G, et al. Soc Sci Med. 2009;68(3):562-569.

Improved existential/spiritual well-being associated with

Breitbart W, et al. JAMA. 2000;284(22):2907-2911. Nelson CJ, et al. Psychosomatics. 2002;43(3):213-220. McClain CS, et al. Lancet. 2003;361(9369):1603-1607. Puchalski CM. Ann Oncol. 2012;23 Suppl 3:49-55.

• Improved quality of life• Decreased depression• Decreased hopelessness• Decreased HDD/suicidality

• Need to develop therapies for existential distress increasingly recognized within psycho-oncology and palliative care by– Institute of Medicine– World Health Organization– The Joint Commission– National Comprehensive Cancer Network– National Quality Forum

Treatments for Cancer-Related Existential/Spiritual Distress

• Some evidence-based existentially oriented psychosocial treatments

• No pharmacologic treatments that address existential/spiritual distress or death distress in cancer

First LSD studieson humans

1947

Hoffman synthesizes psilocybin

1958

Used by indigenous

peoples> 1000 years

1950-1965> 1000 studies

on addiction, end of life anxiety,

cognition, behavior

1970 Controlled

Substances act:LSD, Psilocybin,

Mescaline Schedule I

22 year research halt

1943 Hoffman discovers

psychoactive Properties of LSD

Street use associated withcounterculture

movement, Vietnam war

protests1960s

NYU Psychedelic Research Group

2006

Rick Strassman(UNM)

DMT studies1992

1994-present Johns Hopkins, UCLA,

Arizona, NYU, UNM, Alabama research psilocybin, LSD, and MDMA for anxiety, depression,

addiction

First uses of LSD

clinically to treat

psychiatric illnesses

1953

History of Research on Psychedelics

Kast Research

LSD = lysergic acid diethylamide.Kast EC, et al. Anesth Analg. 1964;43:285-291.

• 1964 Pain Study – Compared opioid pharmacotherapy

(hydromorphone, meperidine) to LSD in 50 patientswith severe pain

Results: – LSD group with improved analgesia compared to

hydromorphone and meperidine both acutely and lasting for several days to weeks

– Also noticed• Decreased depressed mood• Improved sleep• Decreased fear of death

Kast Research (cont’d)

Kast E. Psychiatr Q. 1967;41(4):646-657.

• N = 128 patients with metastatic cancer• Open-label treatment

• LSD 100 mcg with little to no preparation!

• Results– Reduction in acute pain 2 to 3 hours after LSD

administration– Pain reduction lasted for 2 to 3 weeks– Decreased anxiety and depression– Improved sleep– Decreased fear of death

Kast Research (cont’d)

Kast E. Chic Med Sch Q. 1966;26(2):80-87.

• 1966: N = 80 patients with terminal cancer with weeks to months left to live

• Open-label treatment• LSD 100 mcg IM with little to no preparation!

• Results– Reduced pain– Improved mood– Improved sleep – Decrease death anxiety– Improved communication with treatment team– “Happy Oceanic Feelings” lasting 12 days 24

LSD-Assisted Psychotherapy with Terminal Cancer Patients

Grof S, et al. Int Pharmacopsychiatry. 1973;8(3):129-144.

• 60 terminal cancer patients studied open-label pre-and post-treatment at the Maryland Psychiatric Research Center, Spring Grove, Maryland

• 1967–1973• Federally funded• N = 60

– 44 received LSD (200–500 mcg)– 19 received dipropyltryptamine (60–105 mg IM)– Systematic ratings on 31 patients treated with LSD

• Age: 35–81 years (Mean = 54 years)• Gender: 23 females; 8 males• No control group

LSD-Assisted Psychotherapy with Terminal Cancer Patients (cont’d)


• Inclusion criteria: Anxiety/depression associated with terminal cancer, pain, life expectancy 3 months

• Exclusion criteria: Major psychiatric illness, brain damage, epilepsy, severe cardiovascular illness

• Measures:– Anxiety, depression, pain, fear of death, isolation,

mystical states of consciousness• Analysis: Pre- and post-test within group analyses

Therapy Procedures


• Preparatory psychoeducational/psychotherapeutic stage– 6 to 12 hours (average 10)– Male/Female dyad teams– Rapport building– Review of current situation including unresolved conflicts– Problems of confronting and accepting diagnosis– Prognosis and Death– Significant intra-psychic conflicts– Inclusion of family members– Review of the psychedelic session: including potential adverse

events• Drug session with guides: inclusion of music and lying in supine

position with eyeshades• Post-session psychotherapy focusing on:

– Working through, integrating, and consolidating the psychedelic experience

Results


NMean Global Index

Mean Global Index

Mean Difference

T-Score P

Pre Post

Depression 31 -3.05 +0.43 3.48 10.05 0.001

Anxiety 31 -2.94 +0.33 3.27 9.13 0.001

Pain 31 -2.21 +1.06 3.26 7.32 0.001

Fear of Death

24 -2.22 +1.05 3.27 6.97 0.001

Isolation 31 -0.40 +1.92 2.32 6.95 0.001

Management 31 -0.50 +1.26 1.76 4.68 0.001

Global Improvements


Dramatically

Improved (Global Index Increase ≥ 4)

9 29%

Moderately

Improved (Global Index increase between 2 & 4)

13 42%

Unimproved (Global Index increase between 0 & 2)

7 23%

Worse (Global Index decrease between 0 & 1)

2 6%

Grob Psilocybin Cancer Article

Grob CS, et al. Arch Gen Psychiatry. 2011;68(1):71-78.

Effects of Psilocybin in Advanced-Stage Cancer Patients with Anxiety (UCLA)

SUD = substance use disorder.

• Inclusion Criteria– Anxiety associated with terminal cancer– Primary outcome variable: Anxiety– Secondary outcome variables: Depression, pain,

spiritual measures, quality of life

• Exclusion Criteria – Medically unstable; end organ damage– Lifetime history or family history of schizophrenia,

bipolar disorder, other psychotic illness– Active SUD

Treatment Stages• Preparatory psychotherapy

– Minimum of 6 hours– Rapport building– Review of life history– Informed consent– Risks and benefits clearly defined

• Drug administration sessions – 8 hours– Lie supine on a couch– Pre-selected standardized music– Eye-shades on: Instructed to “focus internally”– Male-female co-therapist teams sit with patient providing

presence and re-assurance• Default: no active guidance or interpretation

– Lorazepam and olanzapine available for acute anxiety and/or psychosis

Treatment Stages (cont’d)

• Post-integrative Psychotherapy– Minimum of 8 hours

– Goal of integrating the experience into the patient’s current life

– Psychedelic-assisted psychotherapy

– Embedding of experience in psychotherapy

– Models: Supportive, psychodynamic, palliative, cognitive-behavioral, motivational, family systems

Results

SAE = serious adverse event.

• Age: 36–58 years• 12 participants: 11 women; 1 man

• Feasibility established

• Safety– No major cardiovascular or medical sequelae– No adverse psychological events– No severe anxiety reactions or “bad trips”– No need for pharmacologic intervention– No hospitalizations– No substance misuse or addiction– No SAEs

• Results: Significant and trend reductions in anxiety and depressive symptoms

Altered States of Consciousness (ASC)

Figure 2: 5-Dimension Altered States of Consciousness Profile (5D-ASC)

State-Trait Anxiety Inventory (STAI)

Beck Depression Inventory (BDI) Profile of Mood States (POMS)

Gasser P, et al. J Psychopharmacol. 2015;29(1):57-68.

Results

• N = 12• Cross-over at 2 months• Active: LSD 200 mcg• Control: LSD 20 mcg• No SAEs

• Experimental group with significant short-term (2 months) reductions in anxiety on the STAI

• 12-month follow-up: Sustained reductions in anxiety, increased quality of life, and no adverse psychological or medical sequelae

LSD Therapy in Life-Threatening Illnesses

Ross S, et al. J Psychopharmacol. 2016;30(12):1165-1180.

Griffiths RR, et al. J Psychopharmacol. 2016;30(12):1181-1197.

Study Design


• N = 29; ages 18–76 years• 9-month duration• Double-blind, placebo-controlled • Randomization• Cross-over design at 7 weeks• One dose each of psilocybin and niacin• Psilocybin 0.3 mg/kg• Comfortable living room-like setting• Dyad Therapy Team• Preparation before dosing sessions• Follow-up evaluation and integration

2–4 weeks

1 D

ay

Prep PT3 Sessions (6 hrs total)

Pre-treatment

7 weeks

Psilocybin (0.3 mg/kg)

Niacin (250 mg)

1 D

ay

1 D

ay

Post-Integrative PT (3 Sessions; 6 hrs total)+ Safety Prep for Dose B

Pre-crossover

D1

26 Weeks

Ongoing Support & Integration

with Study Therapist

Post-crossover


Niacin (250 mg)

1 D

ay

Post-Integrative PT 3 Sessions (6 hrs total)

D2

NYU Psilocybin Cancer Study: Study Design

Assessment Schedule Baseline1-day pre-

Dose 1Dose 1

1-day post-

Dose 1

2-wks post-

Dose 1

6-wks post-

Dose 1

7-wks post-Dose 1

1-day pre-Dose 2

Dose 21-day post-

Dose 2

6-wks post-

Dose 2

26-wks post-

Dose 2

Primary Outcomes

Adverse Events ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓BP/HR ✓ ✓ ✓

Depression/Anxiety ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓

Secondary Outcomes

Existential Distress ✓ ✓ ✓Quality of Life ✓ ✓ ✓

Spirituality ✓ ✓ ✓Persisting Effects of

Psilocybin ✓ ✓Mystical Experience ✓ ✓ ✓

Bas

elin

e

2‒4 weeks

Prep PT3 Sessions (6 hrs total)

7 weeks

6-wks post-D1

2-wks post-D1


Niacin (250 mg)

Post-Integrative PT (3 Sessions; 6 hrs total)+ Safety Prep for Dose B

6-wks post-D2

Post-Integrative PT 3 Sessions (6 hrs total)

Ongoing Support & Integrationwith Study Therapist

26-wks post-D2

26 Weeks


Niacin (250 mg)

1 D

ay

1 D

ay

1-da

y pr

e-D

2

1-da

y po

st-D

2

1 D

ay

1 D

ay1-

day

pre-

D1

1-da

y po

st-D

1

7-wks post-D1

D1

D1

BP = blood pressure; HR = heart rate.

NYU Psilocybin Cancer Study (methods)

• Inclusion Criteria– Cancer with an estimated life expectancy of at least

1 year

– Anxiety disorders• Generalized anxiety disorder• Anxiety disorder due to a general medical

condition (ie, cancer)• Acute stress disorder• Adjustment disorder with anxiety

Exclusion Criteria• Medical Illness

– Severe cardiovascular illness– Abnormal hepatic and renal function– Diabetes– Medications

• Anti-epileptics; insulin; oral hypoglycemic drugs, cardiovascular medications

• Psychotropics: ADs, mood stabilizers, antipsychotics

• Psychiatric– Lifetime history or family history of schizophrenia,

schizoaffective disorder, bipolar disorder, delusional disorder, other psychotic illness

– Active SUD– Structured Clinical Interview for DSM Disorders (SCID) I &

II done on screening

Integrative Psychotherapy

• Goal of combining information from preparatory sessions + dosing sessions to effect symptom improvement– Psilocybin-assisted psychotherapy

• Change can occur on multiple levels– Cognitive– Behavioral– Psychodynamic– Spiritual– Existential– Experiential

NYU Approval Process• Bellevue Psychiatry Research Committee• FDA issuance of an IND• NYU Oncology Protocol Review & Monitoring Committee

(PRMC)• NYU Institutional Review Board (IRB)• NYU-HHC Clinical and Translational Science Institute (CTSI) • NYU College of Dentistry Bluestone Center for Clinical

Research (BCCR) • NY State DOH Bureau of Narcotic Enforcement (BNE)• DEA through issuance of a schedule I license for psilocybin

use in a clinical trial

• NYU: 3rd medical center to receive governmental approval for psilocybin research in advanced cancer application; 4th psilocybin license for clinical use granted in the United States in the last 40 years

31 Randomized

15 Completed Dose A

2 removed due to secondary illnesses

14 Completed Dose B

14 Completed 6-Wk Post Dose A Assessments

10 Completed 6-Month Follow-Up Assessments

1 Withdrew due to disease progression

1 withdrew due to disease progression

1 withdrew due to disease progression1 withdrew due to resumption of SSRI medication

2 passed away

1 lost to follow-up 11 Completed 6-Wk Post Dose

B Assessments

15 randomly assigned to Niacin 1st group 16 randomly assigned to Psilocybin 1st group

14 Completed Dose A

14 Completed 6-Wk Post Dose A Assessments

12 Completed Dose B

12 Completed 6-Wk PostDose B Assessments

12 Completed 6-Month Follow-Up Assessments

42 Enrolled

108 Pre-Screened

9 ineligible for randomization1 passed away1 withdrew consent

Characteristics CategoriesPsilocybina 1st Niacinb 1st Total

n = 14 n = 15 n = 29

SexFemale 7 50% 11 73% 18 62%

Male 7 50% 4 27% 11 38%Age; mean (SD) Range 22–75 52 (15.03) 60.27 (9.45) 56.28 (12.93)

Race

White/ Caucasian 13 93% 13 87% 26 90%Black/ African

American0 0% 0 0% 0 0%

Hispanic/ Latino 0 0% 0 0% 0 0%

Asian 0 0% 0 0% 0 0%American Indian/ Native American

0 0% 0 0% 0 0%

Other 1 7% 2 13% 3 10%

Religious/ Spiritual Beliefs

Atheist/ Agnostic 4 29% 10 67% 14 48%

Jewish 4 29% 1 7% 5 17%Catholic 2 14% 0 0% 2 7%

Other Christian 3 21% 1 7% 4 14%Other Faith/ Tradition 1 7% 3 20% 4 14%

Site of Cancer

Breast 4 29% 5 33% 9 31%Reproductive 3 21% 5 33% 8 28%

Digestive Cancers 3 21% 2 13% 5 17%Lymphoma/ Leukemia

2 14% 2 13% 4 14%

Other Types 2 14% 1 7% 3 10%

Characteristic CategoriesPsilocybina 1st Niacinb 1st Total

n = 14 n = 15 n = 29

Stage of Cancer

Stage IV 3 21% 7 47% 10 34%

Stage III 4 29% 4 27% 8 28%

Stage II 1 7% 4 27% 5 17%

Stage I 5 36% 0 0% 5 17%

Other 1 7% 0 0% 1 3%

SCID (DSM-IV) Diagnosis

Adjustment Disorder w/ anxiety &

depressed mood, chronic

2 14% 6 40% 8 28%

Adjustment Disorder w/anxiety, chronic

10 71% 8 53% 18 62%

Generalized Anxiety Disorder

2 14% 1 7% 3 10%

Hallucinogen UseNo 7 50% 6 40% 13 45%

Yes 7 50% 9 60% 16 55%

Psilocybin-Related Adverse Events

AEs• Medical

– Mild elevations in blood pressure: 76%

– Headache/migraine: 28%

– Nausea: 14%• Psychiatric

– Transient anxiety: 17%– Transient psychotic-like

symptoms: 7%

SAEs• Medical – None• Psychiatric – None

– No need for pharmacologic interventions

– No psychosis– No psychiatric

hospitalizations– No hallucinogen

persisting perception disorder

Cardiovascular Safety Assessments Psychological Safety Data: Psilocybin Human Research

• In the last 15 years of research on psilocybin in the United States and Europe, over 2000 doses of psilocybin administered to research participants (Studerus E, et al. J Psychopharmacol. 2011;25(11):1434-1452.)

• No medical or psychiatric SAEs– No participants required pharmacologic intervention– No participants required psychiatric hospitalization– No evidence of onset of addiction to hallucinogens or psychosis

• Key safety precautions:– Paying attention to set and setting– Exclusion of personal and family history major mental illness

especially psychosis– Careful, extensive preparation prior to sessions focusing on

rapport and trust building– Integration of the experience subsequently

STAI-State STAI-Trait

* P < 0.05** P ≤ 0.01

*** P ≤ 0.001

***

**

*******

** *

***

Psilocybin-first group

Niacin-first group

** *

HADS Anxiety

*

****

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

• Improvement evident at 1 day post Dose 1

• Sustained for 6.5 months

Results: Anxiety

HADS = Hospital Anxiety and Depression Scale.

HADS Depression BDI

* P < 0.05** P ≤ 0.01

*** P ≤ 0.001

***

***

**

**

*

* *

*

*

Psilocybin-first group

Niacin-first group

Psilocybin treatment produced similar immediate, substantial, and enduring improvements on several measures of depression:

• Improvement evident at 1 day post Dose 1

• Sustained for 6.5 months

Results: Depression

Carhart-Harris RL, et al. Lancet Psychiatry. 2016;3(7):619-627.

HADS Total: Pre-crossover HADS Anxiety: Pre-crossover HADS Depression: Pre-crossover

BDI: Pre-crossover STAI-State: Pre-crossover STAI-Trait: Pre-crossover

d=1.39***

d=1.46***

d=1.69*** d=1.36

***

d=0.80*

d=1.03**

d=1.18**

d=1.07**

d=1.23***

d=1.12**

d=0.98**

d=1.32***

d=1.10**

d=0.99**

d=0.82*

d=1.27*** d=1.18

**d=1.20**

d=1.45***

d=1.07**

d=1.49***

d=1.31***

d=1.29***

d=0.95**

* P < 0.05** P ≤ 0.01

*** P ≤ 0.001

Psilocybin-first groupNiacin-first group

*


Demographics and 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

Limited Efficacy of Treatments for Cancer-Related Anxiety and Depression

Iovieno N, et al. Int Clin Psychopharmacol. 2011;26(2):69-74. Laoutidis ZG, et al. BMC Psychiatry. 2013;13:140. Ostuzzi G, et al. Cochrane Database Syst Rev. 2015;(6):CD011006. Iovieno N, et al. Int Clin Psychopharmacol. 2011;26(2):69-74.

• ADs with limited to no efficacy (compared to placebo) in treating cancer-related depression– 3 meta-analyses: ADs not clearly > than placebo

• Meta-analysis of ADs in MDD with comorbid medical disorders – ADs > placebo for some medical disorders (ie,

HIV/AIDS, post-stroke)– But, ADs = placebo in cancer with placebo response

rate of 40%

Response/Remission Rates by Treatment Group

BDI Response Rates BDI Remission Rates HADS-A Response Rates

HADS-T Response RatesHADS-D Response Rates HADS-D Remission Rates

Psilocybin 1st group

Niacin 1st group * P < 0.05** P ≤ 0.01

** **

*

** **

**

** ** ** **



Niacin 1st group

* P < 0.05** P ≤ 0.01

*** P ≤ 0.001

Demoralization

** * *

Hopelessness

** ** **

Psilocybin led to immediate and sustained decreased cancer-related demoralization and hopelessness:

**

***

Meaning/Peace

***

*****

Faith

*

****

Spiritual Well-Being

*

and improved spiritual well-being:


Niacin 1st group

* P < 0.05** P ≤ 0.01

*** P ≤ 0.001

Results: Demoralization, Hopelessness, Spirituality

Death Anxiety Scale


Niacin 1st group

Psilocybin did not impact death anxiety:

Death Transcendence Scale

*

* P < 0.05

But did increase a measure of death transcendence:


Niacin 1st group

*

Environment **

*

Physical Health

**** ***

**

Psychological

**

Social Relationships

*

Psilocybin treatment increased several domains of quality of life:

Results: Death Anxiety/Transcendence, Quality of Life

PEQ (% of max score)

Niacin 1st 2 wkspost dose-1

Psilo 1st 2 wks post dose-1

Niacin 1st 26 wk post dose-2

Psilo 1st 26 wkpost dose-2

n = 14 n = 14 n = 12 n = 11

Positive attitudes life 20.65 (3.51) 60.66 (3.51)*** 61.49 (3.69)*** 63.43 (3.80)***

Negative attitudes life 29.69 (0.66) 26.15 (0.71) 26.15 (0.71) 22 (0.74)

Positive attitudes self 20.13 (2.97) 53 (3.08)*** 52.2 (3.12)*** 52.63 (3.25)***

Negative attitudes self 35.09 (0.68) 20.91 (0.71) 36.9 (0.72) 24 (0.75)

Positive mood changes

16.67 (2.43)*** 53.84 (2.52)*** 48.09 (2.55)*** 54.44 (2.66)***

Negative mood changes 3.98 (0.60) 0.84 (0.62) 2.87 (0.65) 1.36 (0.67)

Altruistic/positive social effects

19.36 (2.66) 49.58 (2.76)** 53.56 (2.86)*** 52.49 (2.98)***

Anti-social/negative social effects

3.49 (0.66) 0.84 (0.69) 3.27 (0.69) 0.71 (0.72)

Positive Behavior changesb

21.4 (0.32) 64.6 (0.33)*** 65.8 (0.34)*** 68.8 (0.36)***

Negative Behavior changes

4.2 (0.12) 3 (0.12) 2 (0.13) 0 (0)

Increased Spirituality 17.46 (7.05) 52.65 (7.31)*** 50.03 (7.37)*** 57.42 (7.67)***

Decreased Spirituality 0.68 (0.54) 1.47 (0.56) 1.99 (0.58) 1.21 (0.61)

Persisting Effects Attributed to Psilocybin Administration

PEQ (% of max score)

Niacin 1st 2 wkspost dose-1

Psilo 1st 2 wks post dose-1

Niacin 1st 26 wk post dose-2

Psilo 1st 26 wk post dose-2

Psiloattribution

26 wk post dose-2a

n = 14 n = 14 n = 12 n = 11 n = 23

Top 5 most meaningful,

including single most (%)

7 54 75 64 70

Top 5 most spiritually

significant, including single

most (%)

0 46 42 64 52

Increased well-being or life

satisfaction moderately or very

much (%)

21 85 91 82 87

Persisting Effects Attributed to Psilocybin Administration

Psilocybin vs Niacin Treatment

Anxiety/Depression

MEQ totalMediation Model:

ab = Indirect effect of psilocybin on anxiety/depression mediated by mystical experiencec’= Direct effect of psilocybin on anxiety/depression not mediated by mystical experience

Indirect Pathway (ab)

Direct Pathway (c’)

a b

c

MEQ Factor Scores by Treatment Group

7 hours post-Dose 1 7 hours post-Dose 2 26 weeks post-Dose 2

********

*******

********

**** ********

****

*** P ≤ 0.001**** P ≤ 0.0001

Scores on the MEQ Mediated the Impact of Psilocybin Treatment on Anxiety/Depression Measures

MEQ = Mystical Experience Questionnaire.

Could Psilocybin Have Anti-suicidal Properties?

• ?Acute anti-suicidal effects• ?Sustained anti-suicidal effects• Population based cross-sectional data• Ketamine data• Potential decreased HDD/suicidality

– Decreased depression– Decreased hopelessness– Decreased demoralization– Increased intrinsic spirituality

Hendricks PS, et al. J Psychopharmacol. 2015;29(3):280-288. Rodin G, et al. Soc Sci Med. 2009;68(3):562-569.

Summary of Findings• Safety established

– Transient anxiety and psychotic-like symptoms in a small minority

– No SAEs• Feasibility established• Rapid acting anxiolytic and

antidepressant– Large magnitude of

improvement• Sustained anxiolytic and

antidepressant effects– At least 7 weeks, but likely up to

8 months– Approximately 60% to 80% of

participants continued with clinically significant reductions in depression or anxiety at 6.5 month follow-up

• Mystical Experiences induced by psilocybin– Mystical Experience

mediated improved clinical outcomes

• Highly spiritually significant and meaningful experiences

• Decreased existential distress:– Demoralization– Hopelessness

• Improved quality of life, attitudes towards death, spiritual well-being, altruism, mood, behavior

Impact and Next Steps• NYU and JHU articles co-

published 12/1/16 in Journal of Psychopharmacology

• Accompanied by a dozen supporting articles by key opinion leaders internationally – 2 former presidents of APA– Palliative care– Psycho-oncology– Molecular

psychopharmacology– Addiction– Regulatory

• Overwhelmingly positive response from public/media– Press release > 1.7 billion

views internationally

• Phase III planning• Funded by the Usona

Research Institute• Active discussions with

FDA• Multicenter trials• Re-scheduling

outline where do you want to die?2017/... · • time for final dialogues cancer vital signs:...

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