Royal College of Psychiatrists Annual Meeting. Manchester, UK. September 11 th 2013.

Transcription

1 Dr Ben Sessa MBBS BSc MRCPsych Substance Misuse Services, Addaction, North Somerset, UK Honorary Senior Research Fellow, Cardiff University Medical School Royal College of Psychiatrists Annual Meeting. Manchester, UK. September 11 th

2 What are Psychedelic Drugs? Classical psychedelics(5-ht2a receptor partial agonists) LSD, Psilocybin, DMT, Mescaline Entactogens (Serotonin receptor agonists) MDMA, MDA, MMDA etc Dissociative anaesthetics (NMDA-antagonists) Ketamine, PCP THC (Cannabinoid receptor agonist) Ibogaine (Nicotinic receptor antagonist) Salvia Divinorum (Kappa-Opioid receptor agonist)

3 What are Psychedelic Drugs? Tryptamines serotonin DMT psilocybin LSD ibogaine Phenethylamines mescaline MDMA

4 Cross-cultural and archaic use of hallucinogens: 4

5 Psychedelic Research Applications and Potentials Neuroscience Creativity Meditation/Spir ituality Psychotherapy Addictions End-of-life issues PTSD

6 The discovery of LSD Dr Albert Hofmann Swiss Chemist First synthesised LSD in 1938 Discovered psychedelic properties in 1943 Campaigned for medical uses for psychedelics until his death aged 102 years 6

7 Early Medical 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 7

8 Pioneers of the British Psychedelic Movement: 8

9 Ronald Sandison: British Psychiatrist and Psychoanalyst Ronald David Laing: Advice for those wishing to become a psychoanalyst: 1. Read the works of Freud 2. Undergo persaldous Huxley and Humphrey Osmond: Two very British intellectuals 3. onal analysis 4. Take LSD To make this trivial world sublime Take a half a gramme of phanerothyme To sink in hell or soar angelic You ll need a pinch of psychedelic 9

10 How do classical psychedelics work clinically? Disinhibition Loosening of the ego Access to the unconscious Repressed memories Can be worked through in real time o Non-directive, supporting emerging experience o Alternating inner focus & talking to therapists o Encouraged to fully experience and express whatever arises rather than avoiding or suppressing Creation of positive set and setting Preparation for sessions Use of breath, music and therapeutic touch Follow-up and integration 10

11 Dr. Stanislav Grof LSD is to the study of the mind what the telescope is to astronomy and the microscope is to biology.

12 "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," Meta-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): ) 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)

13 Risks when using classical psychedelics clinically Physiological risks Psychosis and Suicide Dependency risks Low Low Low Hallucinogen Persisting Perception Disorder (HPPD) Rare

14 BUT. Despite the safe and efficacious results of classical psychedelics used in the clinical setting in the context of the subsequent 1960s explosion of recreational drug use LSD is banned in 1966 and virtually all research stops. 14

15 3,4 Methylenedioxymethamphetamine (MDMA) Short acting (two to five hours) Minimal perceptual distortions Almost always pleasurable Empathogenic Safe in therapeutic applications Easier than LSD to control clinically Allows user to access repressed traumatic memories without being overwhelmed by the usual negative affect

16 Use of MDMA in the 1970s and 80s Used by 1960s psychedelic therapists when LSD was banned Couples Therapy Became scheduled in 1985 Particularly good for PTSD Greer, G. (1985) Using MDMA in psychotherapy. Advances: Journal of the Institute for the Advancement of Health, 2 (2), 57-59

17 The clinical burden of PTSD The lifetime prevalence between 6% and 10% Up to 15% in combat countries Very disabling Polypharmacy common High rates of self-harm and suicide Poor engagement on psychological inputs 50% treatment resistance 17

18 Could MDMA be the perfect agent for psychotherapy? Receptors or site in the brain: Increased Serotonin: 5-HT 1A 5-HT 1B Psychological effects: depression anxiety fear (at the amygdala) aggression and defensiveness self-confidence Why this helps with psychotherapy: Less anxiety and aggression improves relationship with therapist Allows patient to focus on trauma without being overwhelmed by negative affect 5-HT 2A Alterations in perception of meaning Facilitates new ways of thinking of old experiences Increased Dopamine and Norepineprine level of alertness arousal conscious registration of external stimuli (at LC) Improved behavioural readiness Improved recall of state-dependent memories of stressful events Provides Optimum Arousal Zone Increased alpha-2 activity calmness and relaxation Provides improved mental state for exploring negative cognitions Provides Optimum Arousal Zone At the hypothalamus Release of oxytocin Improved attachment with therapist Improved empathy and closeness Sessa, B. (2012) 1 Could MDMA be useful in the treatment of PTSD? Progress in Neurology and Psychiatry. Volume 15, Issue 6, pages 4 7, November/December 2011

19 Contemporary MDMA-Assisted psychotherapy for PTSD study Mithoefer et al (2013) Durability of Improvement in PTSD Symptoms and absence of harmful effects or drug dependency after MDM-assisted Psychotherapy: A Prospective Long-Term Follow-up Study. J. of Psychopharmacol, :28-39.

20 Is MDMA dangerous for humans? Early animal studies unsound Selection bias and confounding factors if investigating human ecstasy users Toxicity argument irrelevant to clinical propositions Highly politicized debate: Flawed studies, government restrictions The Risk-Benefit argument 20

21 Psychedelics as tools for treating addictions 21

22 Psychedelics as tools for addictions "The only cure for Dipsomania is Religiomania William James, The Varieties of Religious Experience, 1902 Peak Experience Sobriety It is a generally acknowledged fact in spiritual development that ego reduction makes the influx of God s grace possible. If, therefore, under LSD we can have a temporary reduction, so that we can better see what we are and where we are going well, that might be of some help. The goal might become clearer. So I consider LSD to be of some value to some people, and practically no damage to anyone. - Bill Wilson, Founder of Alcoholics Anonymous

23 Psychedelics as tools for addictions Personality Change Organic Psychosis (DTs) Peak Experience Sobriety Psychedelic Experience

24 Psychedelics as tools for addictions LSD for alcoholism Meta-Analysis Krebs, T.S and Johansen, P.O. (2012) Lysergic acid diethylamide (LSD) for alcoholism: a meta-analysis of randomized controlled trials. Journal of Psychopharmacology, 9 March 2012 Review of psychedelic treatments for addictions Bogenschutz, M. P. & Pommy, J. A. (2012) Re-Examining the Therapeutic Potential of Classical Hallucinogens in the Treatment of Addictions. Drug Testing and Analysis Drug Testing and Analysis 4 (7-8) Double-Blind RCT for Ketamine-Assisted Psychotherapy for alcohol and Opiate addictions Krupitsky, E.M. & Grinenko, A.Y. (1997). Ketamine psychedelic therapy (KPT): a review of the results of ten years of research. Journal of Psychoactive Drugs 29 (2):

25 Contemporary Psychedelic Research: Completed Studies DMT human dose-response study Strassman,R.J. (1996) Human psychopharmacology of N,N-dimethyltryptamine. Behav. Brain Res.73, ) Ketamine to treat Alcohol Dependence Krupitsky, E.M. & Grinenko, A.Y. (1997). Ketamine psychedelic therapy (KPT): a review of the results of ten years of research. Journal of Psychoactive Drugs 29 (2): Psilocybin to treat Obsessive Compulsive Disorder Moreno FA, Wiegand CB, Taitano EK & Delgado PL. Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder.. J Clin Psychiatry. 2006;67: ) Psilocybin and the Spiritual Experience Griffiths, R.R., Richards, W.A., McCann, U., & Jesse, R. (2006). Psilocybin can occasion mystical experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology, 187, MDMA to treat PTSD Mithoefer et al (2013) Durability of Improvement in PTSD Symptoms and absence of harmful effects or drug dependency after MDMA-assisted Psychotherapy: A Prospective Long-Term Follow-up Study. J Psychopharmacol, :28-39 Psilocybin to treat Anxiety in end-stage cancer Grob, C., Chopra, A.L. Danforth, M.C. Hagerty, C.R. McKay, A.L. Halberstadt, and G.R. Greer (2010) Pilot Study of Psilocybin Treatment for Anxiety in Advanced-stage Cancer Patients [with G.S.].Arch Gen Psychiatry, 68(1):71-78 LSD to treat Anxiety in end-stage cancer Gasser, P. 25

26 Further Studies Underway MDMA Therapy for PTSD in War Veterans, USA MDMA Therapy for PTSD for Boulder, USA MDMA Therapy for PTSD Israel MDMA Therapy for PTSD Canada Psilocybin-Assisted Psychotherapy for nicotine addiction, NYU, USA Psilocybin-Assisted Psychotherapy for alcohol addiction, Psilocybin-Assisted Psychotherapy for end-stage cancer, Johns Hopkins, USA Psilocybin-Assisted Psychotherapy for end-stage cancer, Johns Hopkins, USA Ibogaine Therapy as a treatment for addictions, San Diego, USA Ayahuasca Therapy as a treatment for addictions, Canada

27 Contemporary Psychedelic Research in the UK Bristol Psilocybin Project 2009 Imperial Psilocybin Project 2012 Imperial MDMA fmri Project 2012 Imperial Depression Psilocybin 2014 Cardiff MDMA for PTSD 2014 Oxford Ketamine Project 2012 Imperial LSD Creativity Project

28 The Cardiff MDMA project Ben Sessa, Mat Hoskins and Jon Bisson Cardiff University Hospital Medical School CUBRIC, MAPS and Imperial University, London Double-blind, placebo controlled crossover fmri study of combat veterans with chronic treatment-resistant PTSD. Twenty-four subjects will receive two fmri scans; one with 125mg of MDMA and a second, two weeks later, with an inactive placebo. Measure the neurobiological correlates of MDMA vs. Placebo using four behavioural paradigms, which relate directly to the symptoms of PTSD. Recall of autobiographical memories Social judgements paradigm Exposure to fearful faces Traumatic script cue paradigm. Participants recruited from the University Hospital of Wales Veterans Service, screened according to safety and diagnostic suitability criteria and randomly allocated into one of two groups.

29 Contemporary Renaissance of Psychedelic Research: 29

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32 The Forefather of Psychedelic Therapy in Britain? 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.