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A REVIEW OF RESEARCH INTO THE USE OF PSILOCYBIN- ASSISTED PSYCHOTHERAPY TO TREAT END-OF-LIFE ANXIETY AND DEPRESSION NIGEL STRAUSS & MICHAEL KUGEL RANZCP FACULTY OF PSYCHIATRY OF OLD AGE CONFERENCE, MELBOURNE 3/11/16

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A REVIEW OF RESEARCH INTO THE USE OF PSILOCYBIN-ASSISTED PSYCHOTHERAPY TO TREAT END-OF-LIFE ANXIETY AND DEPRESSIONNIGEL STRAUSS & MICHAEL KUGELRANZCP FACULTY OF PSYCHIATRY OF OLD AGE CONFERENCE, MELBOURNE 3 /11 /16

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FRANCIS CRICK: “A person's mental activities are entirely due to the behavior of nerve cells, glial cells, and the atoms, ions, and molecules that make them up and influence them.”

OLIVER SACKS: “To speak of a biological basis and biological precursors of religious

emotion says nothing of the value, the meaning, the function, of such emotions,

or the narratives and beliefs we may construct on their basis”.

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END OF LIFE ANXIETY & DEPRESSION

- Innovative treatment methods are helping to prolong survival time in cancer sufferers but addressing the psychological and spiritual needs of patients with end stage cancers has often received far less attention and are very limited.

- The final months for people dying of cancer are often burdened with extreme levels of suffering both physical (pain) and mental (anxiety, depression and psychological isolation)

- The inevitable and impending death often provokes feelings of defeat, helplessness and despair

CAN WE ENHANCE THE QUALITY OF LIFE DURING THE PATIENTS’ FINAL MONTHS?

MAYBE with psilocybin-assisted psychotherapy!

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END OF LIFE ANXIETY & DEPRESSION: EXISTENTIAL DISTRESS

- 32% of terminal patients in large survey study have death anxiety1

- “Greater attention to death anxiety is…recommended by contemporary approaches to palliative care”2

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Meaning-Centered Therapy and Demoralization Syndrome

WILLIAM BREITBART: “Targeted therapies to be effective must aim to explore and restore meaning and hope within the context of advancing psychotherapy”

DAVID KISSANE: “Hopelessness, loss of meaning, and existential

distress are…the core features of the diagnostic category of

demoralization”

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PSILOCYBIN

1. Serotonin receptor agonist

2. Derived from about 200 species of (psilocybin )mushrooms (mainly genus psilocybe) and used traditionally by central American Indians in particular, for religious and spiritual purposes

3. A naturally occurring psychedelic (mind manifesting) drug

SerotoninPsilocybin

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PSYCHEDELIC DRUGS - Psychedelics tend to affect the mind in ways that result in the experience being qualitatively different from those of ordinary consciousness: transpersonal or mystical states or radical changes in consciousness

- The psychedelic experience is often compared to non-ordinary forms of consciousness such as religious ecstasy or spiritual states

- Ego free states

- Hallucinations common

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PHENOMENOLGICAL DIMENSIONS OF MYSTICAL EXPERIENCE

1. Unity

2. Sacredness or reverence

3. Noetic quality

4. Deeply felt positive mood

5. Transcendence of time & space

6. Ineffability & paradoxicality

(Pahnke-Richards Mystical Experience Questionnaire)

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PSILOCYBIN ASSISTED PSYCHOTHERAPY

- Psychotherapy with a psychoactive substance is used to describe psychotherapeutic methods that apply psychoactive substances as tools to assist and intensify a therapeutic process

Examples: Psilocybin & MDMA (empathogen)

- No standardized technique of psychedelic psychotherapy but researchers suggest that the drugs themselves are not the healing agents but are facilitators, and results are determined by the structure of the therapy and the quality of the therapist

- Thus therapists need extensive training

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SET AND SETTING - "Set” (mental state) refers to the personality, intention, mood, and preparation of the individual ingesting a drug

- "Setting" is the environment in which the drug is taken, including physical, interpersonal, and cultural aspects

- Stress, fear, or a disagreeable environment, may result in an unpleasant experience (bad trip). Conversely, a relaxed, curious person in a warm, comfortable supportive and safe place, is more likely to have a pleasant and manageable experience

- Apart from the drug ingestion, a psychedelic therapy session and recreational psychedelic usage, have very little in common

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PSILOCYBIN ASSISTED PSYCHOTHERAPY(UCLA, John Hopkins, and NYU)

Griffiths, Bossis and their colleagues hope psilocybin could address a treatment gap. To test that possibility, they've designed their studies in cancer patients to be double-blind, placebo controlled and methodologically rigorous. Volunteers in the trials each participated in two blinded sessions, receiving an active placebo in one and psilocybin in the other.

In several meetings before and after the trials, volunteers met with a therapist who helped them establish expectations and discuss the feelings and emotions stirred up by the psychedelic session. Therapists were also present to guide and help volunteers, if necessary, during the drug sessions. Integrative sessions after the psychedelic session also crucial.

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CRITERIA FOR VOLUNTEERS

1. Diagnosis of terminal cancer with associated anxiety

2.No personal or family history of psychosis or severe psychiatric disorder, epilepsy, diabetes, abnormal liver function, or severe cardiovascular disease

3. Cease all psychotropic medication

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PSILOCYBIN RESEARCH Contemporary: 2016

Who: Carhart-Harris et. al., - Imperial College London6

Sample Size: 12 patients with chronic, treatment-resistant depression

Design: Placebo-controlled, double-blind

Results: 67% of patients achieved complete remission after 1 week

42% remained in complete remission 3-months later

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PSILOCYBIN RESEARCH Contemporary: 2006

Who: Griffiths et. al., - John Hopkins University3

Sample Size: 36 healthy volunteers with no psychedelic experience

Design: 2 sessions, one with psilocybin and one with placebo, double-blind

Results: Most reported mystical experiences that 2 months later continued to have significant personal meaning

Participants also reported positive changes in attitude and behaviour

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PSILOCYBIN RESEARCH Contemporary: 2008

Who: Griffiths et. al., - John Hopkins University4

Sample Size: 36 healthy volunteers with no psychedelic experience

Design: Follow-up survey

Results: At 14-month follow, 58% said it was one of the most meaningful experiences of their lives

66% said it had increased their well being or life satisfaction

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PSILOCYBIN RESEARCH Contemporary: 2011

Who: Grob et. al., - Harbor-UCLA Medical Center5

Sample Size: 12 patients with terminal illnesses

Design: Placebo-controlled, double-blind

Results: All patients showed significant reductions in anxiety sustained at 3-month follow up

67% had significantly decreased depressive symptomology at 6-month follow up

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CURRENT STATE OF RESEARCH

Ongoing Phase 2 studies:

1) Johns Hopkins University – 51 volunteers

2) New York University – 29 volunteers

- In a medically controlled setting with expert screening and preparation, psilocybin can relieve the symptoms of anxiety and depression often found in cancer sufferers.

- At UCLA, John Hopkins Uni, and NY Uni, there have been 3 completed Phase 2 studies with a total of 92 participants – all demonstrating statistically significant improvements with enduring effects for months after a single psilocybin treatment session

- At NYU & John Hopkins, after 500 administrations of psilocybin the researchers reported no serious side-effects

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CHALLENGES 1. Overcoming the stigmatization of psychedelic drugs to facilitate research (clearly differentiating the recreational and therapeutic usage of psychedelics)

2. Sample sizes small

3. Neuroscience: Default mode network inhibition(?)

4. Double blinding psychedelics

5. Research costs (psychedelic drugs off patent and good methodological research expensive)

6. Training of therapists: ethics and psychotherapy

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References 1 Lodhi, M., Cheema, U., Stifter, J., Wilkie, D., et. al., (2014), Death anxiety in hospitalized end-of-life

patients as captured from a structured electronic health record: differences by patient and nurse characteristics, Research in Gerontological Nursing, 7, (5), pp.224-234

2 Tong, E., Deckert, A., Gani, N., Nissim, R., et. al., (2016), The meaning of self-reported death anxiety in advanced cancer, Palliative Medicine, 30, (8), pp.772-779

3Griffiths, R., Richards, W., McCann, U., Jesse, R., (2006), Psilocybin can occasion mystical experiences having substantial and sustained personal meaning and spiritual significance, Journal of Psychopharmacology, 187, pp.268-283

4Griffiths, R., Richards, W., Johnson, M,. McCann, U., Jesse, R., (2008), Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14-months later, Journal of Psychopharmacology, 22, (6), pp.621-632

5Grob, C., Danforth, A., Chopra, G., Hagerty, M., et. al., (2011), Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer, Archives of General Psychiatry, 68, (1), pp.71-78

6Carhart-Harris, R., Bolstridge, M., Rucker, J., Day, C., et. al., (2016), Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study, The Lancet Psychiatry, 3, (7), pp.619-627