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PROFESSOR DAVID NUTT - PSYCHEDELIC ASSISTED PSYCHOTHERAPY – NEW NEUROSCIENTIFIC APPROACHES TO ADDICTION AND DEPRESSION

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The world is entering a new phase of psychiatric treatments. After the psychotherapy and medical treatment phases in the last century, we are at the start of the phase where we use drugs to assist and empower psychotherapeutic processes. The origins of this exciting new development are the massive growth of neuropsychopharmacology, particularly in relation to the use of psychedelics (e.g. LSD, Psilocybin) and entactogens (e.g. MDMA). New research on the impact of these drugs on brain functions show clear impacts on brain processes that contribute to maladaptive behavioural processes. Parallel research has demostrated e cacy for psilocybin and MDMA in disorders such as resistant depression and PTSD. In this ground-breaking talk, Professor Nutt will cover these remarkable new developments and show how they may be used more broadly in psychiatry/psychotherapy in the future.

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PROFESSOR DAVID NUTT - PSYCHEDELIC ASSISTED PSYCHOTHERAPY – NEW NEUROSCIENTIFIC APPROACHES TO ADDICTION AND DEPRESSION

  1. 1. David Nutt FMedSci Imperial College London d.nutt@imperial.ac.uk profdavidnutt@twitter.com Psychedelic assisted psychotherapy - New neuroscientific approaches to addiction and depression
  2. 2. Psychedelics are an enduring feature of human existence
  3. 3. Maybe also fueled Christianity?
  4. 4. LSD – the big breakthrough LSD  synthetic and more potent psychedelic  wide medical and research use Albert Hoffman – the discoverer of LSD and psilocybin - at 100
  5. 5. If the doors of perception were cleansed every Thing would appear to man as it is, infinite. For man has closed himself up, till he sees all Things thro’ narrow chinks of his cavern. William Blake, 1793 Aldous Huxley and mescaline Peyote cactus “The brain is an instrument for focusing the mind”
  6. 6. DepressionAddiction The brain reconstructs the image to what it expects But always with limitations “Man sees thro’ the chinks of his cavern” William Blake 1793 Neuroscience proves Huxley and Blake right
  7. 7. Early Psychiatric Uses for LSD 1. Psychotomimetic 2. Self-experimentation by mental health professionals 3. Psychedelic Psychotherapy • High dose single drug session • Mystical / Peak experience • Favoured in the US 4. Psycholytic Psychotherapy • Low doses • Frequent, regular sessions • Favoured in the UK 7Ben Sessa
  8. 8. “To sink in hell or soar angelic You’ll need a pinch of psychedelic” Ronald David Laing: UK Humphrey Osmond: UK CanadaUSA Advice for those wishing to become a psychoanalyst: 1.Read the works of Freud 2.Undergo personal analysis 3.Take LSD Psychiatry protagonists
  9. 9. Clinical Interest in LSD in the 1950s and 1960s • Hundreds of psychiatrists worldwide • 140 NIH grants • 1000 clinical papers • 40,000 patients • 40 books • 6 International conferences Results were overwhelmingly positive, describing safe and effective treatments. (Masters and Houston, 1971)
  10. 10. Pooled analyses in the 1960s • 44 psychiatrists, 5000 subjects and 25,000 drug sessions: Rate of psychosis: 0.2% Rate of suicide of 0.04% (Cohen S. (1960) LSD: side effects and complications. Journal of Nervous and Mental Disorders 130: 30-40) • 700 psychedelic drug sessions: One case of prolonged psychosis (Chandler Al. & Hartman Ma. (1960) LSD-25 as a Facilitating Agent in Psychotherapy. AMA Arch Gen Psychiatry; 2(3):286-299) • 350 patients over four years of outpatient treatments: One attempted suicide (Ling TM, Buckman J (1963) The Treatment of Anxiety with Lysergic Acid and Methylphenidate. Practitioner 191: 201-4) • Review of 20 years of psychedelic therapy in the UK, 4000 patients and 50,000 psychedelic drug-assisted sessions. Two completed suicides Thirty-seven patients with a prolonged psychosis (Malleson, N. (1971) ‘Acute Adverse Reactions to LSD in clinical and experimental use in the UK.’ Br J Psychiatry. 18(543): 229-30) "Treatment with LSD is not without acute adverse reactions, but given adequate psychiatric supervision and proper conditions for its administration, the incidence of such reactions is not great,"
  11. 11. Psychedelics for alcoholism? Some years after his atropine-induced sobriety conversion Bill Wilson, founder of AA, came to believe that LSD could help “cynical alcoholics” (those who did not believe in a higher power”) achieve spiritual awakening
  12. 12. Wilson’s psychedelic experience “Suddenly the room lit up with a great white light. I was caught up in an ecstasy which there are no words to describe. It seemed to me in my mind's eye, that I was on a mountain and that a wind not of air but of spirit was blowing. And then it burst upon me that I was a free man.”
  13. 13. And he was right re alcoholism!
  14. 14. 6 LSD trials in alcoholism Effect size > = all current therapies Since the banning – one clinical trial + only two neuroscience studies - all in last two years
  15. 15. Psychedelics, used responsibly and with proper caution, would be for psychiatry, what the microscope is for biology and medicine, or the telescope is for astronomy Stan Grof - but how do they work? A necessary research tool?
  16. 16. Why were psychedelics banned? Because the CIA were worried about American youth refusing to fight in Vietnam – and cultural change (flower power) Scare stories e.g. trying to fly
  17. 17. The lies the media told!
  18. 18. LSD scares in the film media The usual cocktail of sex drugs and youth  moral outrage in the old
  19. 19. LSD and all other psychedelics banned in face of opposition from senators Bobby Kennedy: Why if [clinical LSD projects] were worthwhile six months ago, why aren’t they worthwhile now? . . . We keep going around and around. . . . If I could get a flat answer about that I would be happy. Is there a misunderstanding about my question? I think perhaps we have lost sight of the fact that LSD can be very, very helpful in our society if used properly.” quoted in Lee & Shlain, 1985, p. 93) Has there ever been a worst example of research censorship? Well not since …….
  20. 20. The banning of the telescope! 1616 The papal Congregation of the Index banned all books advocating the Copernican system of explaining planetary motion Not revoked until 1758 Galileo Galilei 1564-1642 Giordano Bruno 1548-1600 Nicolaus Copernicus 1473-1543
  21. 21. How the UN Conventions on drugs destroyed research
  22. 22. Read more about it Nature reviews Neuroscience 2013 March 2015
  23. 23. Fighting back – psychedelics for addiction Modern replication study Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study J Psychopharmacol March 2015 29: 289-299, first published on January 13, 2015 Bogenschutz MP1, Forcehimes AA2, Pommy JA2, Wilcox CE2, Barbosa PC3, Strassman RJ2.
  24. 24. Psilocybin for alcoholism
  25. 25. Psilocybin and smoking cessation
  26. 26. Psilocybin and smoking cessation - Results
  27. 27. Krupitsky et al. Ketamine Psychotherapy for Heroin Dependence Single Versus Repeated Sessions of Ketamine-Assisted Psychotherapy for People with Heroin Dependence† Evgeny M. Krupitsky, M.D., Ph.D.*; Andrei M. Burakov, M.D., Ph.D.**; Igor V. Dunaevsky, M.D., Ph.D.***; Tatyana N. Romanova, M.S.****; Tatyana Y. Slavina, M.D., Ph.D.***** & Alexander Y. Grinenko M.D., Ph.D.****** Abstract— A prior study found that one ketamine-assisted psychotherapy session was significa nt ly more effective than active placebo in promoting abstinence (Krupitsky et al. 2002). In this study of the efficacy of single versus repeated sessions of ketamine-assisted psychotherapy in promoting abstinence in people with heroin dependence, 59 detoxified inpatients with heroin dependence received a ketamine- assisted psychotherapy (KPT) session prior to their discharge from an addiction treatment hospital, and were then randomized into two treatment groups. Participants in the firs t group received two addiction counseling sessions followed by two KPT sessions, with sessions scheduled on a monthly interval (multiple KPT group). Participants in the second group received two addiction counseling sessions on a monthly interval, but no additional ketamine therapy sessions (single KPT group). At one-year follow-up, survival analysis demonstrated a significa nt ly higher rate of abstinence in the multiple KPT group. Thirteen out of 26 subjects (50%) in the multiple KPT group remained abstinent, compared to 6 out of 27 subjects (22.2%) in the single KPT group (p < 0.05). No differences between groups were Journal of Psychoactive Drugs 13 Volume 39 (1), March 2007 Abstract— A prior study found that one ketamine-assisted psychotherapy session was significa nt ly more effective than active placebo in promoting abstinence (Krupitsky et al. 2002). In this study of the efficacy of single versus repeated sessions of ketamine-assisted psychotherapy in promoting abstinence in people with heroin dependence, 59 detoxified inpatients with heroin dependence received a ketamine- assisted psychotherapy (KPT) session prior to their discharge from an addiction treatment hospital, and were then randomized into two treatment groups. Participants in the firs t group received two addiction counseling sessions followed by two KPT sessions, with sessions scheduled on a monthly interval (multiple KPT group). Participants in the second group received two addiction counseling sessions on a monthly interval, but no additional ketamine therapy sessions (single KPT group). At one-year follow-up, survival analysis demonstrated a significa nt ly higher rate of abstinence in the multiple KPT group. Thirteen out of 26 subjects (50%) in the multiple KPT group remained abstinent, compared to 6 out of 27 subjects (22.2%) in the single KPT group (p < 0.05). No differences between groups were found in depression, anxiety, craving for heroin, or their understanding of the meaning of their lives. It was concluded that three sessions of ketamine-assisted psychotherapy are more effective than a single session for the treatment of heroin addiction. Keywords—hallucinogens, heroin addiction, ketamine, psychedelics, psychotherapy, treatment †This study was supported by the Multidisciplinary Association for Psychedelic Studies (MAPS), Sarasota, Florida, USA and by the Heffter Research Institute, Santa Fe, New Mexico, USA. The authors are also very thankful to Rick Doblin, Lisa Jerome, Valerie Mojeiko, and Dr. George Greer for assistance in editing the manuscript, and to Tatyana Volskaya, M.A., for data management. *Chief of the Research Laboratory, St. Petersburg Regional Center of Addictions and Psychopharmacology, St. Petersburg State Pavlov Medical University, St. Petersburg, Russia. **Psychiatrist, St. Petersburg Regional Center of Addictions and Psychopharmacology, St. Petersburg State Pavlov Medical University, St. Petersburg, Russia. ***Anesthesiologist, St. Petersburg Regional Center of Addictions and Psychopharmacology, St. Petersburg State Pavlov Medical University, St. Petersburg, Russia. ****Clinical Psychologist, St. Petersburg Regional Center of Addictions and Psychopharmacology, St. Petersburg State Pavlov Medical University, St. Petersburg, Russia. *****Psychiatrist and Medical Director, St. Petersburg Regional Center ofAddictions and Psychopharmacology, St. Petersburg State Pavlov Medical University, St. Petersburg, Russia. ******Director, St. Petersburg Regional Center of Addictions and Psychopharmacology, St. Petersburg State Pavlov Medical University, St. Petersburg, Russia. Please address correspondence and reprint requests to Evgeny M. Krupitsky, M.D., Ph.D., St. Petersburg Regional Center of Addictions and Psychopharmacology, Novo-Deviatkino 19/1, Leningrad Region 188661, Russia. Email: kru@ek3506.spb.edu Psychedelic-assisted psychotherapy utilizes the acute psychological effects of psychedelic, or hallucinogenic, drugs to enhance the normal mechanisms of psychotherapy. Many studies carried out in the 1950s and 1960s suggested that psychedelic-assisted psychotherapy might be an effic i ent treatment for alcoholism and addictions (Grinspoon & Bakalar 1979). However, it is difficu l t to generalize across these studies because of differences in methodology. After they were scheduled in 1970, the use of psychedelic drugs in research was strictly limited, significantly curtailing Ketamine for heroin addiction
  28. 28. Ketamine one –v- three doses heroin abstinence Krupitsky et al. Ketamine Psychotherapy for Heroin Dependence emotional support for the participant and carried out psycho- therapy during the ketamine session. The psychotherapy was existentially-oriented, focusing on assisting the participant to consider and formulate a purposeful or meaningful life, but also took into account the participant’s individuality, ending or apocalypse, and often ended in an experience of rebirth associated with oceanic, or positively experienced, ego loss and boundlessness. All of these experiences were emotionally intense and compelling. Many people reported great diffic u l ty in expr essing their experiences in words. It FIGURE 1 Kaplan-Meier Survival Analysis P < 0.01 Krupitsky et al 2007
  29. 29. Ketamine for alcoholism • Krupitsky, E. M., Grinenko, A. Y., Berkaliev, T. N., Paley, A. I., Tetrov, U. N., Mushkov, K. A., & Borodikin, Y. S. (1992). The combination of psychedelic and aversive approaches in alcoholism treatment: The affective contra- attribution method. Alcoholism Treatment Quarterly, 9(1), 99-105. doi:10.1300/ J020V09N01_09 MRC-funded UK study in alcoholism underway in UK Celia Morgan and Val Curran with Krupitsky
  30. 30. The Beckley Foundation/Imperial College Psychedelic Research Programme Fighting back
  31. 31. LSD Mescaline Affinity for 5-HT2A Potency in manGlennon et al. 1984. Human dose data from Shulgin 1978 Resurrecting psychedelic research with psilocybin All these drugs stimulate 5HT2A receptors Psilocybin – magic mushrooms Short acting if used iv = 30 min effect
  32. 32. PET image [11C]Cimbi-36 5HT2A receptor agonist Copenhagen 5HT2A receptors most densely expressed cortex Human brain has highest density of any brain The 5-HT2A receptor in human brain revealed by PET
  33. 33. Psilocybin fMRI: ONLY DECREASES in brain activity + regionally specific Posterior Cingulate Thalamus Anterior cingulate Carhart-Harris et al PNAS 2012
  34. 34. Psilocybin uncouples frontoparietal connectivity (default mode network, DMN) Saline – strong correlations in activity in these regions Psilocybin – correlations lost or even negative Seed regionCarhart-Harris et al PNAS 2012
  35. 35. LSD disrupts default mode network Carhart-Harris et al PNAS 2016
  36. 36. The default mode network & depression A) PCC functional connectivity B) Greater PCC to SCC (subgenual cingulate cortex) connectivity in depression PCC - SCC functional connectivity predicts rumination (Berman et al. 2011)
  37. 37. Brain sites of depression – PET imaging “It is a positive and active anguish, a sort of psychical neuralgia wholly unknown to normal life. Cg25 F9 F9Cg24 Treatment Resistant Depression William James, revisited So can we selectively turn the active anguish OFF? Mayberg et al 2005 Neuron Red = overactive region Blue = underactive region
  38. 38. z = -4 z = +4 L Deep Brain Stimulation – stops overactivity Cg25 mF10 oF11 Cg24 hth Cg25 F9 ins F46 mF ins 3 months DBS CBF Change Responders Cg24 vCd sn Cg25 Cg25 Cg24 F9F9 F47 hth Baseline CBF PET All PT vs NC Cg25 mF10 oF11 Cg24 hth bs Cg25 mFF9 ins F9 F46 Cg31 6 months DBS CBF Change Responders Helen Mayberg
  39. 39. Cg24 vmF dmF Hth Cg25 Antidepressants also switch off this region bs Cg31 Hth Cg25 bs Cg31 DBS SSRI antidepressant Helen Mayberg
  40. 40. Psilocybin attenuates activity in the brain region linked to depression Carhart-Harris PNAS 2012 fMRI BOLD image Psilocybin attenuated mPFC activity As do treatments for depression SSRIs Kennedy et al. 01 CBT Goldapple et al. 04 Sleep deprivation Gillin et al. 01 ECT Bonne et al. 96 Placebo Mayberg et al. 02 Deep brain stimulation Mayberg et al. 05 Ketamine Deakin et al. 08
  41. 41. Meditation reduces DMN activity - basis of mindfulness therapy? Coloured bars reflect different sorts of meditation Yale group
  42. 42. Mood and wellbeing • Users often report enduring effects • Formal studies – Roland Griffiths John Hopkins – confirm this • As did our subjects Single high dose of psilocybin: Two-thirds of participants rated their experience as one of their top 5 most meaningful life experiences (Griffiths et al. 2006) Is this an antidepressant effect?
  43. 43. Our MRC psilocybin depression trial Grant awarded 2012 Ethics – took 3 iterations – 1 year Drug supply – 30 months Regulatory approvals – 32 months Cost per dose = £1500!
  44. 44. 0 1 2 3 0 5 10 15 20 25 30 Baseline 1 week 2 weeks 3 weeks 5 weeks 3 months 6 months Effectsize(Cohen'sd) QIDSScore DepressionSeverity (QIDS) P1 P2 P3 P4 P5 P6 P7 P8 P9 P10 P11 P12 P13 P14 P15 P16 P18 P19 P20 MEAN Cohen's d Psilocybin for resistant depression Carhart-Harris et al Psychopharmacology 2017
  45. 45. Fearful Amygdala – Faces - SSRIs Depression > “Healthy” SSRIs reduce activity
  46. 46. Antidepressants and amygdala - meta-analysis a et al. (2015), Molecular psychiatry Reduced activity to negative emotional faces
  47. 47. Fearful Happy Neutral Baseline and 1-day after therapy (“after-glow”) Passively viewing Blocks of 15 seconds Amygdala in psilocybin assisted therapy Roseman et al submitted
  48. 48. Fearful Happy Neutral Fearful>Neutral y=-5 y=-2 y=-3 y=1 3.5Z=2.3 Amygdala activation increased after psilocybin-assisted therapy 1-day after therapy > Baseline Roseman et al submitted
  49. 49. More amygdala activation  better clinical outcome Fearful > Neutral Remitters (n=11) > Non-remitters (n=8) y=-1 x=20 Remission (No depression) BDI <= 9 1 week 3.5Z=2.3 Roseman et al submitted
  50. 50. Anti-depressant Psychedelic- assisted therapy Amygdala Fearful Decrease Increase Amygdala Happy Mixed Increase Strategy of therapy Relieve negative emotions Confront and work through emotions Result = opposite to antidepressants
  51. 51. Carhart-Harris and Nutt – Journal of Psychopharmacology 2017 – free download 5-HT receptors in depression - our current model
  52. 52. Psilocybin changes attitude They can change patients’ outlook Normalised post-treatment P < 0.01 P < 0.01 Pessimism bias pre-treatment P < 0.01 “My outlook has changed significantly. I'm more aware now that it's pointless to get wrapped up in endless negativity. I feel as if I've seen a much clearer picture.” [Patient from depression trial, male, aged 52, >20yrs depression] Watts et al Journal of Humanistic Psychology 2017, Vol. 57(5) 520
  53. 53. It was like when you defrag the hard drive on your computer, I experienced blocks going into place, things being rearranged in my mind, I visualized as it was all put into order, a beautiful experience with these gold blocks going into black drawers that would illuminate, and I thought my brain is bring defragged, how brilliant is that! (P11) My mind works differently [now]. I ruminate much less, and my thoughts feel ordered, contextualized. Rumination was like thoughts out of context, out of time; now my thoughts feel like they make sense, with context and logical flow. (P11) “ “ Another quote Watts et al Journal of Humanistic Psychology 2017, Vol. 57(5) 520
  54. 54. Self worth/self love: ‘I had an experience of tenderness towards myself, a feeling of true compassion I’d never felt before (P16) New perspectives: ‘She was so eloquent, she kept calling me ‘my darling’: “Life is to be lived my darling” She talked to me in such a loving way, all these things to say about my life’ (P12) Activities: ‘I started writing music again’ (P1) (jobs, driving, acting, building, flying, volunteering, travel) Inner therapist: ‘Its like ingesting your own psychotherapist’ (P19) “ “ Connected to self Watts et al Journal of Humanistic Psychology 2017, Vol. 57(5) 520
  55. 55. Connection to the world Connection to work 7 Connection to nature 11 Connection to spiritual principle 9 Before I enjoyed nature, now I feel part of it. Before I was looking at it as a thing, like TV or a painting. You’re part of it, there’s no separation or distinction, you are it. (P1) Watts et al Journal of Humanistic Psychology 2017, Vol. 57(5) 520
  56. 56. Talking therapy: disconnection: I’m sick to the back teeth of telling people again and again the backstory. All the talking therapies, each time you go for an 8 or 6 week course of that stuff, you spend the first few weeks going over the stuff, they ask all the questions again then its session 4, and then, you think who’s learning something here, ‘cos I’m not. You are! (P13) They all seemed to be trying to fit a person into a preconceived set of patterns: ‘try to do this’, ‘make this your goal, and we’ll measure it’. But just having these goals set for you is more pressure and when you don’t meet those goals, you feel even worse because you’re letting them down, and you already feel let down yourself! (P1) TOO DIRECTIVE TOO SHORT “ “ I got up the courage to tell him, I’d never told anyone. And [the psychiatrist] just looked at his shoes.’ (P16) DON’T ADDRESS TRAUMA: “
  57. 57. “Those who cannot change their minds cannot change anything” George Bernard Shaw (1856-1950) Can our research help change peoples’ mind about psychedelics?  a new Enlightenment perhaps.....
  58. 58. Acknowledgements Mendel Kaelen, Leor Roseman, Mark Bolstridge, Chris Timmermann, Tim Williams, David Erritzoe, Ben Sessa, Suresh Muthukumuraswamy, Richard Wise, Luke Williams, Kevin Murphy, Robert Leech, Eduardo Schenberg, Neiloufar Family, Matt Wall, Val Curran, Karl Friston, Rosalyn Moran, David Nichols, Robin Tyacke, James Stone, Laurence Reed, Nadar Abbasi, Enzo Tagliazucchi, Dante Chialvo, Roland Griffiths, Katherine MacLean, Matt Johnson, Charlie Grob, Bill Richards, Jeff Guss, George Goldsmith, Ekaterina Malievskaia, Celia Morgan, Mitul Mehta, Alexander Lebedev, Pete Hellyer, Csaba Orban, John McGonigle, Remi Flechais, Michael Bloomfield, Steve Pilling, Matt Brookes, Tim Nest, Paul Expert, Giovanni Petri, James Rucker, Camilla Day, Shlomi Raz, Catherine Scrace, Kabir Nigam, John Evans, Peter Hobden, Wouter Droog, Yvonne Lewis, Mark Tanner, Ineke de Meer; Alison Diaper, Ann Rich, Sue Wilson, volunteers, patients and more… Robin Carhart-Harris Amanda Feilding
  59. 59. Brain sites of depression – PET imaging “It is a positive and active anguish, a sort of psychical neuralgia wholly unknown to normal life. Cg25 F9 F9Cg24 Treatment Resistant Depression William James, revisited So can we selectively turn the active anguish OFF? Mayberg et al 2005 Neuron Red = overactive region Blue = underactive region
  60. 60. z = -4 z = +4 L Deep Brain Stimulation – stops overactivity Cg25 mF10 oF11 Cg24 hth Cg25 F9 ins F46 mF ins 3 months DBS CBF Change Responders Cg24 vCd sn Cg25 Cg25 Cg24 F9F9 F47 hth Baseline CBF PET All PT vs NC Cg25 mF10 oF11 Cg24 hth bs Cg25 mFF9 ins F9 F46 Cg31 6 months DBS CBF Change Responders Helen Mayberg
  61. 61. Cg24 vmF dmF Hth Cg25 Antidepressants also switch off this region bs Cg31 Hth Cg25 bs Cg31 DBS SSRI antidepressant Helen Mayberg
  62. 62. Bhagwager et al 2006 Am J Psychiatry Recovered depressed patients have increased 5HT2A receptors Maybe an attempt to make up for deficiency of 5HT? So would psilocybin replace what’s missing ?
  63. 63. Figure 3a. 5-HT2A binding in frontolimbic regions correlates with trait neuroticism in 84 healthy subjects38 . Figure 3b. Cortical 5-HT2A binding correlates with dysfunctional attitudes (pessimism) in medicated free depressed patients39 . Figure 3c. Regions where 5-HT2A binding correlates positively with pessimism in med-free depressed patients39 . More 5HT2A receptors  pessimism Meyer et al Maybe an attempt to make up for deficiency of 5HT (serotonin) Could psilocybin rectify this?
  64. 64. “The future may teach us how to exercise a direct influence, by means of particular chemical substances, upon …the neural apparatus. It may be that there are other still undreamt of possibilities of therapy.” From An Outline of Psychoanalysis Sigmund Freud London 1938. 64 But we were not the first! Was Freud the forefather of psychedelic therapy?
  65. 65. If the doors of perception were cleansed every Thing would appear to man as it is, infinite. For man has closed himself up, till he sees all Things thro’ narrow chinks of his cavern. iam Blake, 1793 Aldous Huxley and mescaline Peyote cactus “The brain is an instrument for focusing the mind”
  66. 66. DepressionAddiction The brain reconstructs the image to what it expects But always with limitations “Man sees thro’ the chinks of his cavern” William Blake 1793 Neuroscience proves Huxley and Blake right
  67. 67. By switching of the “control centres” psilocybin increases brain connectivity Petri et al J. R. Soc. Interface 11: 20140873. http://dx.doi.org/10.1098/rsif.2014.0873 Normal Psilocybin

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