I DON T KNOW WHY THEY CALL THIS ECSTASY

Transcription

1 I DON T KNOW WHY THEY CALL THIS ECSTASY WHAT S GOING ON IN MDMA-ASSISTED PSYCHOTHERAPY FOR PTSD? Royal College of Psychiatrists Faculty of Medical Psychotherapy Annual Conference Cardiff, April 2018 Michael Mithoefer, MD, FAPA Charleston, SC, USA Research Sponsor: The Multidisciplinary Association for Psychedelic Studies (MAPS)

2 RESURGENCE OF MDMA CLINICAL RESEARCH November 2001 February 2004 April 2004 As of 2016 August 2017 First Phase 2 protocol approved by FDA. MDMA-assisted psychotherapy for PTSD. DEA approval granted. First participant enrolled. Six Phase 2 MDMA/PTSD clinical trials completed. FDA grants Breakthrough Therapy Designation. Agreement on Special Protocol Assessment reached for Phase 3 trials.

3 WHY STUDY MDMA? VA/DoD Clinical Practice Guidelines (2017): We recommend individual, manualized traumafocused psychotherapy over other pharmacologic and non-pharmacologic interventions for the primary treatment of PTSD. Psychotherapy is the definitive treatment, but doesn t always work What about a drug that could catalyze psychotherapy?

4 STUDY DESIGN: PHASE 2 CHRONIC, TREATMENT-RESISTANT PTSD Stage 1 Unblind Assessment Screening Measures Prep Sessions Integrative Sessions Integrative Sessions Assessment Primary Endpoint Integrative Sessions Assessment Two Month Follow up Assessment Long-term Follow-up Experimental Session Experimental Session Stage 2 Experimental Session Open-label crossover for Low/Medium/Placebo Group

5 Crime-related PTSD PHASE 2 CLINICAL TRIALS Long-term Follow-up Randomized, Triple-Blind, Phase 2 Pilot Study Comparing 3 Different Doses of MDMA in Conjunction with Manualized Psychotherapy in 24 Veterans, Firefighters, and Police Officers With Chronic PTSD (MP-8) Scheduled for Publication 01 May 2018

6 STAGE 1: MEAN CAPS-4 SCORES BY GROUP Time*Group Interaction p=0.015 Mithoefer MC et al. J Psychopharm. 2011;25(4):

7 STAGE 2 Open label MDMA-assisted psychotherapy for participants who originally received placebo-assisted sessions Open Label Cross Over Integration non-drug therapy sessions as in Stage 1 7 of 8 placebo group participants elected to participate

8 STAGE 2 CROSSOVER: MEAN CAPS-4 SCORE BY GROUP Mithoefer MC et al. J Psychopharm. 2011;25(4):

9 LONG-TERM FOLLOW-UP: GLOBAL MEAN CAPS Months Post Final MDMA Session (Mean = 45.4 Months, SD = 17.3 Months) Of 16 CAPS completers: 12% (2/16) relapsed 88% sustained benefit Assuming 3 CAPS non-completers relapsed: 26% relapsed (5/19) 74% sustained benefit Mean CAPS Score Baseline Study Exit LTFU Mithoefer MC et al. J Psychopharm. 2013; 27(1):28-39 * Error bars represent SD.

10 STUDY TO BE PUBLISHED 01 MAY 2018 Randomized, Triple-Blind, Phase 2 Pilot Study Comparing 3 Different Doses of MDMA in Conjunction with Manualized Psychotherapy in 24 Veterans, Firefighters, and Police Officers With Chronic PTSD (MP-8) * Error bars represent SD.

11 VETERANS, FIREFIGHTERS & POLICE OFFICERS PRELIMINARY PTSD OUTCOMES (CAPS-4) NCT Global CAPS Severity Mean (+/-SD) Scores Baseline Primary Endpoint *** 30 mg (N=7) 75 mg (N=7) 125 mg (N=12) ***p<0.001 (75 mg and 125 mg vs. 30 mg) ANOVA of Difference Scores (Primary Baseline)

12 DEPRESSION OUTCOMES (BDI-2) 60 Beck Depression Inventory Total Score Mean (+/-SD) *** 30 mg (N=7) 75 mg (N=7) 125 mg (N=12) ***p<0.001 (125 mg vs. 30 mg) ANOVA of Difference Scores (Primary Baseline) NCT Baseline Primary Endpoint

13 SLEEP QUALITY OUTCOMES (PSQI) 30 Pittsburgh Sleep Quality Index Total Score Mean (+/-SD) * 30 mg (N=5) 75 mg (N=5) 125 mg (N=10) PSQI was added after an amendment, therefore N is smaller. *p<0.05 (75 and 125 mg vs. 30 mg), ANOVA of Difference Scores (Primary Baseline) NCT Baseline Primary Endpoint

14 NCT SPOSTTRAUMATIC GROWTH OUTCOMES (PTGI)

15 SIX COMPLETED PHASE 2 STUDIES MDMA-ASSISTED PSYCHOTHERAPY FOR PTSD Study Sample (N) Dose Comparison Location Code Intent to Treat Active Comparator Published J. Psychopharm Publication pending Charleston, SC MP-1 N= mg 0 mg Switzerland MP-2 N= mg 25 mg Vancouver, BC MP-4 N=6 125 mg 0 mg Charleston, SC MP-8 N=26 75 or 125 mg 30 mg Tel Aviv, Israel MP-9 N=8 125 mg 25 mg Boulder, CO MP-12 N= or 125 mg 40 mg All Studies Intent to Treat N=105 Active ( mg) vs. Comparator (0-40 mg)

16 Six MDMA/PTSD Studies at Long-Term Follow-Up 120 Stage 1 Comparator (0-40 mg, n=31) Stage 1 Stage 2 LTFU PTSD OUTCOME ANALYSIS All subjects had full dose MDMA in Stage 1 or Stage 2 *** p < ANOVA of Difference Scores (End of Stage- Baseline) *** p < ANOVA of Difference Scores (End of Stage- Baseline) *** p < ANOVA of Difference Scores (LTFU - Baseline) Primary Outcome Between group Cohen s d effect size: 0.9 (Large) Mean CAPS-4 Total (+/-SD) Scores *** Stage 1 Active ( mg, n=74) Stage 2 Open Label ( mg, n=27) *** *** 0 Stage 1 Baseline Primary End of Stage 1 Stage 2 Baseline End of Stage Month Follow-up

17 EXPANDED ACCESS Photo by Nirvan Mullick, PrescriptionX The Rick Doblin Story

18 PHASE 3 SITES

19 OUR THERAPEUTIC APPROACH IN MDMA-ASSISTED PSYCHOTHERAPY

20 THERAPEUTIC APPROACH Our adaptation of the foundation laid by Stanislav Grof, MD and many others

21 THERAPEUTIC APPROACH Non-directive, supporting emerging experience Inner healing intelligence Reclining, headphones with music, eyeshades Alternating inner focus & talking to therapists Allows for therapists individual variation Importance of preparation and integration

22 WHY DOES MDMA HELP PEOPLE PROCESS TRAUMA?

23 WINDOW OF TOLERANCE Hyperarousal Increased sensation Emotional reactivity Intrusive imagery Disorganized cognitive processing Arousal Window of Tolerance / Optimal Arousal Zone Hypoarousal Numbing of emotions Disabled cognitive processing Adapted from Ogden P et al. Psychiatr Clin North Am. 2006;29(1): , xi-xii

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25 ELEMENTS OF OTHER THERAPIES THAT ARISE IN MDMA-ASSISTED SESSIONS Safe, supportive setting Imaginal exposure Cognitive restructuring Transference Psychodynamic Somatic Multiplicity of the psyche Transpersonal/Spiritual Corrective attachment Active imagination

26 SO WHAT S GOING ON???? Does MDMA facilitate exposure therapy? Does MDMA facilitate CPT and other CBT? Does MDMA facilitate psychodynamic therapy? Does MDMA facilitate Somatic Therapies Does MDMA facilitate IFS or Psychosynthesis? Does MDMA facilitate Jungian Analysis

27 PSYCHIATRIC DISORDERS ARE INHERENTLY MULTI- FACTORIAL KENNETH KENDLER, MD MAYBE HEALING IS INHERENTLY MULTI- FACTORIAL

28 THE THERAPIST MUST STRIVE TO CREATE A NEW THERAPY FOR EACH PATIENT. IRVIN YALOM, MD OR MAYBE THE THERAPIST MUST STRIVE TO ALLOW AND ENCOURAGE EACH PATIENT TO CREATE A NEW THERAPY FOR THEMSELVES

29 WINDOW OF TOLERENCE Maybe one of the things the drug does is let your mind relax and get out of the way because the mind is so protective about the injury.

30 IMAGINAL EXPOSURE I don t know why they call this Ecstasy!

31 TRANSFERENCE Will you brush my hair!

32 RESISTANCE It feels almost like the inner healer or the MDMA is like a maid doing spring cleaning. It s as if you thought you were cleaning before but when you got to the things you didn t really want to deal with you d just stick them in the attic. If you re going to clean the house you can t skip the stuff in the attic. If the resistance is itself unconscious, as so often happens owing to its connection with the repressed material, we make it conscious. Freud

33 THIS VETERAN STOPPED OPIATES Iraq changed my brain, MDMA changed it back.

34 THE PROCESS CONTINUES UNFOLDING OVER TIME I have respect for my emotions now What s most comforting is knowing now that I can handle difficult feelings without being overwhelmed.

35 THE PROCESS CONTINUES UNFOLDING OVER TIME As interesting as the sessions are, I know from experience now that it's even more interesting what happens after the sessions when you're making connections.

36 IMAGES I m a huge pile of fertilizer composting and turning into beautiful rich soil. It s a perfect time to have rain. I m a converter, I m the earth, I am. Leaves, rain, even acid rain hit me, and I have a powerful ecosystem, all can be absorbed. What we re doing here is turning compost.

37 BOTTOM UP PROCESSING (SOMATIC) Allowing the body to have experiences that deeply and viscerally contradict the helplessness, rage or collapse that result from trauma. The Body Keeps the Score Bessel van der Kolk Bring awareness to the body Encourage movement Optional mindful use of touch with permission and careful agreements Nurturing touch Focused release work

38 An Iraq veteran during an MDMA session MDMA APPEARS TO PROMOTE SECURE ATTACHMENT Traumatized human beings recover in the context of relationships Recovery from trauma involves reconnecting with our fellow human beings. The Body Keeps the Score Bessel van der Kolk Therapist: What are you noticing about the MDMA? Participant: It s allowing me to... really view this part of my life that we re talking about in a new way than I have before, in a more complete way and to understand it a bit better. Therapist: Are you feeling connected to us? Participant: Yea that s why I m able to say these things. I don t think if I didn t feel connected to you I d be able to talk about these things

39 Firefighter and MAPS Study Participant, MP-8 Before my treatment, PTSD was an island on which I was stranded. I now attend weddings, birthdays, church, and even go to the grocery store without panic, finally feeling connected to my life and my family again.

40 TRANSPERSONAL/ SPIRITUAL I think that s the first time in my life that I actually stopped thoughts and relaxed and when I did that, that s when I started feeling that oneness with everything, merged with the whole room and everything and just was. I ve learned better how to just be

41 SAFETY OF THE SET/SETTING IMAGINAL EXPOSURE MULTIPLICITY OF THE PSYCHE ACTIVE IMAGINATION Video of Marine Veteran During MDMA-assisted Session

42 Deep appreciation for the MAPS team, members, donors, investigators & All the study participants! Clinical Research Team Amy Emerson, Director of Clinical Research Berra Yazar-Klosinski, PhD, Clinical Research Scientist Rebecca Matthews, Clinical Trial Leader Charlotte Harrison, Senior Clinical Research Associate Alia Lilienstein, MD, Clinical Research Associate-Physician Allison Feduccia, PhD, Clinical Data Scientist Colin Hennigan, Clinical Data Manager Allison Wilens, Clinical Study Associate Ilsa Jerome, PhD, Research & Information Specialist Clinical Investigators Michael Mithoefer, MD, Lead Clinical Investigator, Medical Monitor Annie Mithoefer, BSN, Co-Investigator, Charleston Marcela Ot alora, MA, LPC, Primary Investigator, Boulder Bruce Poulter, Co-Investigator, Boulder Moshe Kotler, MD, Primary Investigator, Israel Peter Oehen, MD, Primary Investigator, Switzerland Ingrid Pacey, MD, Primary Investigator, Canada maps.org