Psilocybin-assisted therapy for depression. Peak experience, Amygdala changes

Transcription

1 Psilocybin-assisted therapy for depression Peak experience, Amygdala changes

2 Psilocybin-assisted therapy n = 20 Treatment resistant major depression Two doses of psilocybin (10mg & 25mg) separated by 1 week

3 Therapy room

4 Clinical outcome p < baseline v all time-points. Black bars = means +SEM. Red dots = effect sizes

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6 Pharmaco-mechanism of clinical outcomes 5-HT 2A Receptor agonist Long term changes Placebo Psilocybin

7 Psycho-mechanism of clinical outcomes 5-HT 2A Receptor agonist Long term changes Placebo Psilocybin Acute experience

8 Beginning of psychedelic therapy 50 s Osmond Hoffer Hubbard

9 Psychedelic-induced peak/mystical experience Experience of unity or loss of sense of self Transcendence of time and space Deeply felt positive mood Sense of awe-someness Meaningfulness of psychological or philosophical insight Ineffability and paradoxicality. Pahnke Richards

10 Peak experience is part of our human potential Maslow 1959

11 Peak experience is part of our human potential Peak experience leads to self-actualization Maslow 1959

12 Maslow

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14 2006 Griffiths Richards

15 2011 MacLean

16 2011 MacLean

17 2014 Garcia-Romeu Johnson

18 2015 Bogenschutz

19 2016

20 Psilocybin-assisted therapy

21 Responders vs non-responders at 5 weeks Response 50% reduction in depression Responders (n=9) Non-responders (n=10)

22 Responders vs non-responders at 5 weeks Response 50% reduction in depression Responders (n=9) Non-responders (n=10)

23 Correlation of retrospective ASC and QIDS 5 weeks ASC Pearson's r p (2-tail) I felt particularly profound I had particularly inventive ideas I experienced a profound inner peace Worries and fears of everyday life felt irrelevant I felt one with my surroundings I experienced past, present, and future as a unity Oppositions and contradictions seemed to resolve Many things appeared incredibly funny to me I felt connected to a higher power I experienced boundless joy [..] [..] I was scared without knowing why I felt paralyzed I experienced everything as frighteningly distorted I felt as if I was half-asleep I felt tortured I had the feeling that something terrible was going to happen I had the feeling of unbearable emptiness I felt threatened Time passed slowly in a painful way

24 Caveat: other possible mediators

25 Emotional openness to music during therapy predicts outcome Reduction in Depression (QIDS) 5 Weeks r = 0.51 p = n = 19 Acute openness to music in the therapy session Kaelen 2017

26 Other possible mediators Emotional Breakthrough Catharsis Reliving trauma Clear view on the self Childhood experience Therapeutic alliance Quality of integration..

27 Experience Efficacy

28 Schmiege

29 Amygdala emotional processing

30 Amygdala Faces SSRIs Fearful SSRIs reduce amygdala reactivity to negative emotions Ma et al. (2015), Molecular psychiatry

31 Amygdala Psilocybin assisted therapy Baseline vs. 1-day after therapy Fearful Happy Neutral

32 Amygdala activation after psilocybin-assisted therapy Fearful Happy Neutral Fearful>Neutral Z= day after therapy > Baseline

33 Amygdala increase relate to clinical outcome Non-depressed (n=11) > depressed (n=8) Fearful > Neutral Z=

34 Psilocybin-assisted therapy vs. antidepressants Anti-depressant Psilocybin-assisted therapy Amygdala Fearful Amygdala Happy Decrease Mixed Increase Increase

35 Psilocybin-assisted therapy vs. antidepressants Anti-depressant Psilocybin-assisted therapy Amygdala Fearful Amygdala Happy Decrease Mixed Relieve negative emotions Increase Increase Confront and work through them Strategy of therapy

36 Long term psychological changes Ros Watts 6 month interviews 1) Avoidance Acceptance 2) Disconnection Reconnection 3) Previous treatments reinforced avoidance Watts(2017), Journal of Humanistic Psychology

37 Quotes from a patient "I also see my Dad abusing me again something that has flashed into my head now and again ever since it happened but, once again, rather than pushing the image to one side and avoiding the situation, I look him in the eyes and move through the discomfort and fear (in and through, in and through) [ ] With my demons fully revealed and presented to me, having looked my deepest fears directly in the eye, I enter a state where I feel completely elated, at peace, absolutely euphoric, the most relaxed and content I have ever been.

38 Psychedelic Therapy Psychiatry

39 Thanks Dr Robin Carhart-Harris Ros Watts Dr David Erritzoe Mendel Kaelen Chris Timmermann Prof David Nutt Dr Rob Leech Amanda Feilding

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41 Sherwood Preparation

42 Bill Richards Integration

43 Correlation between experience and depression scores (ΔQIDS) 5 weeks

44 Whole brain analysis Fearful Happy Neutral Fearful>Neutral

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46 Acute psilocybin and amygdala activation Kraehenmann et al. (2015), Biological psychiatry

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49 Amygdala mask After therapy > baseline y=-5 y=-2 y=-3 y=1 Fearful Happy Neutral Fearful>Neutral Volume (mm 3 ) Max (z) MNI_152 (x,y,z) ,-4,-24 26,-2,-26 26,-4,-26 32,0,-22 Z=

50 Acute LSD and facial emotion recognition Dolder et al. (2016), Neuropsychopharmacology

51 Correlation between experience and ΔQIDS 5 weeks

52 Altered State of Consciousness Questionnaire

53 Correlation between experience and ΔQIDS 5 weeks PQ Pearson r p I felt an inner warmth I felt amazing I felt a profound inner peace I felt loved up I felt really sharp I felt energised and enthusiastic about things My thoughts wandered freely I felt like I was floating The experience had a spiritual or mystical quality Sounds influenced things I saw I experienced a disintegration of my 'self' or 'ego' I saw geometric patterns I experienced a sense of merging with my surroundings My imagintaion was extremely vivid Edges appeared warped The experience had a supernatural quality My perception of time was distorted I saw scenes from my past How intense were the drug effects when at their peak? My sense of size and space was distorted I saw movement in things that weren't really moving Things looked strange The experience had a dream like quality I felt unusual bodily sensations My thinking was muddled I felt entirely normal I feared losing control of my mind I felt suspicious and paranoid I felt afraid

54 Beginning of psychedelic therapy 60 s, onwards Pahnke Grof Richards

55 Default mode network (DMN)

56 DMN =Default Mode Network Decreased DMN integrity Acute psychedelic induced Ego-dissolution Carhart-Harris et al., 2012; PNAS - Psilocybin Carhart-Harris et al., 2016; PNAS - LSD Palhano-Fontes et al., 2015; PLoS One - Ayahuasca

57 Increased DMN integrity 1-day after therapy Changes in connectivity (z)

58 Acute Post-psilocybin

59 Speculation Acute Peak experience Post-psilocybin self-actualization Maslow 1959

60 Around Within Within