The Healing Potential of MDMA

Transcription

1 The Healing Potential of MDMA Amy Emerson Director of Clinical Research Multidisciplinary Association for Psychedelic Studies TRI March, 2014

2 PTSD Traumatic event Event passes, fearful memories remain Symptoms do not resolve after 1 month 10% of general population 14% of military personnel returning from war Accompanied by Depression, Suicidal Thoughts, Addiction Chronic, treatment-resistant in about 1/3 of population

3 Fagelson M, VMAC Study 12007; Vol ; American Journal of AudiologyJ PTSD and Tinnitus Each occur in 10% of the population Co-presents with depression, anxiety and suicidal ideation Increased Startle Response Decreased loudness tolerance Exacerbated by sounds, anxiety, stress and trauma recall Shared Neural Mechanisms, changes in hippocampus and amygdala

4 Why MDMA for PTSD? Obstacles to treating PTSD Fear Hyper vigilance Defensiveness / numbing Lack of trust MDMA Diminishes the Obstacles: Decrease fear and defensiveness Increase trust and empathy Provide Affirming experiences More realistic perspective about present circumstances/safety Integration Present and connected during the experience Greer & Tolbert, J Psychoactive Drugs, 1986; 18(4): ; Greer & Tolbert, J Psychoactive Drugs, 1998; 30(4):

5 Amygdala and Prefrontal Cortex PTSD Mediated by emotional memory- increased amygdala activity MDMA Reduces fear & suppresses activity in amygdala Decreased activity in prefrontal cortex- Thought Center Increased blood flow and Activity in prefrontal cortex Rauch SL et al. Biol Psychiatry. 2006;60(4): , Gamma et al. 2000

6 Neurotransmitters and Hormones Monoamine release and reuptake inhibition Serotonin (5-HT) Norepinephrine (NE) Dopamine (DA) Greatest effects are on serotonin release Elevates plasma concentrations of a number of hormones: Oxytocin Vasopressin Cortisol Prolactin Dehydroepiandrosterone (DHEA) Adrenocorticotropic hormone (ACTH) Wolff, et al. J. Psychopharm, 2006, 20(3): ; Dumont, et al. Soc Neurosci, 2009, 4(4): ; Hysek, et al. Psychopharmacology (Berl), 2012, 222(2): ; Bedi et al., Biol Psychiatry, 2010, 68(12): ; Guastella, et al. Biol Psychiatry, 2010, 67: ; Parrott, et al. Neuropsychobiology, 2009, 60(3-4): ; Cami, et al. Ann N Y Acad Sci, 2000, 914: ; Harris, et al. Psycopharmacol (Berl) 2002, 162(4): ; Farre, et al. Psycopharmacol (Berl) 2004, 173(3-4):

7 A Window of Tolerance Hyperarousal Zone Increased sensation Emotional reactivity Intrusive imagery Disorganized cognitive processing Window of Tolerance / Optimal Arousal Zone Hypoarousal Zone Relative absence of sensation Numbing of emotions Disabled cognitive processing Reduced physical movement Ogden P et al. Psychiatr Clin North Am. 2006;29(1): , xi-xii

8 Before, I knew the path was through a battlefield, but I could not get through it. During MDMA therapy, I knew I could walk through it and I wasn t afraid. MDMA gave me the ability not to fear. Donna, a patient in the US pilot study

9 Positive Safety Profile Phase 1 & Phase 2 clinical trials > 800 people No unexpected unexpected drug-related serious adverse events in medical research settings using pure MDMA Adverse Events are generally mild to moderate and self limited Neurocognitive function RBANS and PASAT No change pre and post MDMA or placebo Changes in Vital signs during sessions similar between MDMA and Placebo Group

10 Common Side Effects More common with MDMA: Decreased concentration Jaw Clenching Dizziness More common with inactive placebo: Anxiety Drowsiness Insomnia Dry mouth Feeling cold Impaired Balance Anxiety Jerome L. (+/-)-3,4-methylenedioxymethamphetamine (MDMA, Ecstasy ) Investigator s Brochure. December Accessed Aug. 16, 2012.

11 Toxicity in Recreational Users Rare cases of Serious acute toxicity in recreational users Neurotoxicity in animals at high, repeated IV doses, not relevant to doses used in human studies PET scans- no change in estimated serotonin transporter binding sites 4 weeks after a clinically relevant dose of MDMA Moderate abuse potential Jerome L. (+/-)-3,4-methylenedioxymethamphetamine (MDMA, Ecstasy ) Investigator s Brochure. December Accessed Aug. 16, 2012; Mithoefer MC et al. J Psychopharm. 2011;25(4): ; Mithoefer MC et al. J Psychopharm. 2012; In press.

12 Why MDMA for PTSD? Enhances psychotherapy, not needed chronically Desirable effects on brain activity, neurochemistry and hormones Positive Risk/Benefit Ratio Attenuates the fear response and decreases defensiveness without blocking access to memories while encouraging a deep and genuine experience of emotion (Metzner et al. 1988).

13 Study Design Screenin g/baselin e 90 min Prep Sessions Exp Sessio n MDMA or Placebo 90- Min Integrative Sessions Exp Sessio n O u t c o m e Exp Sessio n MDMA O u t c o m e 12 mn F o l l o w U p Stage 2 phone session for 7 days following each experimental session

14 Objectives and Measures Clinician Administered PTSD Scale (CAPS) Beck Depression Inventory (BDI-II) Global Assessment of Functioning (GAF) Posttraumatic Growth Inventory (PTGI) Pittsburg Sleep Quality Index (PSQI) NEO Personality Inventory (NEO) VAS for pain and tinnitus. Safety Side effects, adverse events Concomitant medication Suicidality Vital Signs

15 Therapeutic Approach Characterized as Non-directive and supportive of the emerging experience Adapted from the work of Stanislav & Christina Grof, George Greer & Requa Tolbert, Ralph Metzner, Leo Zeff and many others Treatment Manual is available at MAPS.ORG

16 Private Practice Setting ER Doctor Psychiatrist, IFS, Holotropic Breathwork Assistant Clinical Professor Medical University of South Carolina Psychiatric Nurse Holotropic Breathwork Hakomi

17 PTSD Severity-Mean CAPS Score by Group after MDMA or Placebo Baseline Post Session 2 Placebo/Active Post Session 3 Mithoefer MC et al. J Psychopharm. 2011;25(4):

18 CAPS Score MP8: PTSD Severity-Preliminary First 12 participants: 10 vets, 2 firefighters 120 Average CAPS Scores by Condition mg: mg: mg: mg 75 mg 30 mg Baseline (N=12) Outcome Assessment Post 2 Blinded Sessions (N=12)

19 BDI-II Score Beck Depression Inventory (BDI-II) Preliminary first 12 participants 70 Average Depression Scores by Condition mg 75 mg 30 mg Baseline (N=12) Outcome Assessment Post 2 Blinded Sessions (N=12)

20 PTGI Score Posttraumatic Growth Inventory (PTGI) Preliminary first 12 participants: 10 vets, 2 Average Posttraumatic firefighters Growth Scores by Condition mg 75 mg 30 mg 0 Baseline (N=12) Outcome Assessment Post 2 Blinded Sessions (N=12)

21 Reports of Tinnitus in MDMA/PTSD Symptom Profile Baseline Trials PTSD Severity Post-treatment Self-reported outcome 0803 Left ear 1 yr Prior to PTSD 25 Unknown 0804 Unknown 1 yr Prior to PTSD 6 Unknown 0808 Bilateral 5 yr Prior to PTSD 55 Unknown 0809 Unknown 33 yr Prior to PTSD 0811 Unknown Coincident with PTSD 0812 Bilateral Coincident with PTSD 34 No change 108 Some improvement 24 No change 0813 Unknown Not noted 78 Went away during session and 48 hrs after, then intermittent 0815 Bilateral 7 yr Prior to PTSD 7 Reduction in occurrence 0816 Intermittent 3 yr After PTSD 15 In treatment

22 After the MDMA took effect, my soul sparked back to life. I felt connected to a vibrant life force, and I awakened to a childlike curiosity and inner power. I learned that I shape my reality and control my destiny with how I perceive and how I act. Now I feel that my true strength is facing my weaknesses and fears, and moving on from there. I am not perfect, but I have learned a lot about myself. If something gets the fear going, I can see it as something I can learn from.

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24 Publications of this Work Mithoefer, MC, Wagner, MT, Mithoefer, AT, Jerome, L, Doblin, R. The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamineassisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. J Psychopharmacol, (4): p Mithoefer, MC, Wagner, MT, Mithoefer, AT, Jerome, L, Martin, SF, Yazar-Klosinski, BB, Michel, Y, Brewerton, T, Doblin, R. Durability of Improvement in Posttraumatic Stress Disorder Symptoms and Absence of Harmful Effects or Drug Dependency after {+/-}3,4- methylenedioxymethamphetamine-assisted psychotherapy: A Prospective Long-term Follow-up Study. J Psychopharmacol, Epub online 2012, Nov 20.