I DON'T KNOW WHY THEY CALL THIS "ECSTASY"

 
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I DON'T KNOW WHY THEY CALL THIS "ECSTASY"
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)
I DON'T KNOW WHY THEY CALL THIS "ECSTASY"
RESURGENCE OF MDMA CLINICAL RESEARCH

November 2001             February 2004           April 2004            As of 2016               August
                                                                                                  2017

 First Phase 2 protocol                                                                         FDA grants
                                                                          Six Phase 2      Breakthrough Therapy
    approved by FDA.                              First participant
                          DEA approval granted.                       MDMA/PTSD clinical   Designation. Agreement
     MDMA-assisted                                    enrolled.
                                                                       trials completed.    on Special Protocol
psychotherapy for PTSD.
                                                                                            Assessment reached
                                                                                             for Phase 3 trials.
I DON'T KNOW WHY THEY CALL THIS "ECSTASY"
WHY STUDY MDMA?

VA/DoD Clinical Practice Guidelines (2017):
 “We recommend individual, manualized trauma-
 focused 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?
I DON'T KNOW WHY THEY CALL THIS "ECSTASY"
STUDY DESIGN:
          PHASE 2 – CHRONIC , TREATMENT-RESISTANT PTSD
                                                               Unblind
                               Stage 1

Assessment                                                     Assessment                Assessment   Assessment
 Screening                                                       Primary                  Two Month    Long-term
            Prep                Integrative         Integrative Endpoint      Integrative Follow up
 Measures Sessions                                                                                     Follow-up
                                 Sessions            Sessions                  Sessions

                     Experimental         Experimental               Experimental
                       Session              Session                    Session

                                         Stage 2
             Open-label crossover for Low/Medium/Placebo Group
I DON'T KNOW WHY THEY CALL THIS "ECSTASY"
Crime-related PTSD

PHASE 2 CLINIC AL TRIALS

                            Long-term Follow-up

                             Randomized, Triple-Blind,
                                 Phase 2 Pilot Study
                           Comparing 3 Different Doses of
                                                               Scheduled for
                            MDMA in Conjunction with
                                                               Publication
                            Manualized Psychotherapy in
                                                               01 May 2018
                            24 Veterans, Firefighters, and
                            Police Officers With Chronic
                                   PTSD (MP-8)
I DON'T KNOW WHY THEY CALL THIS "ECSTASY"
STAGE 1: MEAN CAPS-4 SCORES BY GROUP

                                                           Time*Group Interaction
                                                                 p=0.015

Mithoefer MC et al. J Psychopharm. 2011;25(4):439-452
I DON'T KNOW WHY THEY CALL THIS "ECSTASY"
• Open label MDMA-assisted psychotherapy
      STAGE 2             for participants who originally received
                          placebo-assisted sessions

                        • Integration non-drug therapy sessions as in
Open Label Cross Over     Stage 1

                        • 7 of 8 placebo group participants elected to
                          participate
I DON'T KNOW WHY THEY CALL THIS "ECSTASY"
STAGE 2 CROSSOVER: MEAN CAPS-4 SCORE BY GROUP

Mithoefer MC et al. J Psychopharm. 2011;25(4):439-452
I DON'T KNOW WHY THEY CALL THIS "ECSTASY"
LONG-TERM FOLLOW-UP:
               GLOB AL MEAN C APS-4                                        17 – 74 Months Post Final MDMA Session
                                                                               (Mean = 45.4 Months, SD = 17.3 Months)

  Of 16 CAPS completers:
                                                                         100
         12% (2/16) relapsed

                                                       Mean CAPS Score
                                                                          80
         88% sustained benefit
                                                                          60

  Assuming 3 CAPS non-completers relapsed:                                40

         26% relapsed (5/19)
                                                                          20
         74% sustained benefit
                                                                           0
                                                                                Baseline        Study Exit            LTFU

Mithoefer MC et al. J Psychopharm. 2013; 27(1):28-39                                                            * Error bars represent SD.
I DON'T KNOW WHY THEY CALL THIS "ECSTASY"
Randomized, Triple-Blind,
                             Phase 2 Pilot Study
                        Comparing 3 Different Doses
STUDY TO BE PUBLISHED
     01 MAY 2018         of MDMA in Conjunction
                              with Manualized
                            Psychotherapy in 24
                         Veterans, Firefighters, and
                        Police Officers With Chronic
                               PTSD (MP-8)

                                             * Error bars represent SD.
VETERANS, FIREFIGHTERS & POLICE OFFICERS
                                          PRELIMINARY PTSD OUTCOMES
                                                                   (C APS-4)
                                                  120
                                                                                          30 mg (N=7)
              Global CAPS Severity Mean (+/-SD)
                                                                                          75 mg (N=7)
                                                  100

                                                                                          125 mg (N=12)
                                                   80
                                                                                -11
                           Scores

                                                   60

                                                                                -44
                                                   40
                                                                                         ***
                                                                                -58
                                                   20                                          ***p
DEPRESSION OUTCOMES
                                                                 (BDI-2)
                                                60

                                                                                     30 mg (N=7)
              Beck Depression Inventory Total

                                                50
                                                                                     75 mg (N=7)

                                                40                                   125 mg (N=12)
                      Mean (+/-SD)
                          Score

                                                30

                                                                           -4.5
                                                20

                                                                           -24 ***           ***p
SLEEP QUALITY OUTCOMES
                                                                           (PSQI)

                                                           30

              Pittsburgh Sleep Quality Index Total Score                                      30 mg (N=5)

                                                           25                                 75 mg (N=5)

                                                                                              125 mg (N=10)
                                                           20
                            Mean (+/-SD)

                                                                                          PSQI was added after an amendment,
                                                                                                therefore N is smaller.
                                                           15

                                                           10

                                                                                     *
                                                                                          *p
SPOSTTRAUMATIC GROWTH OUTCOMES
                           (PTGI)

NCT01211405
SIX COMPLETED PHASE 2 STUDIES
                         MDMA-ASSISTED PSYCHOTHERAPY FOR PTSD

                          Study             Sample (N)              Dose Comparison
                    Location         Code    Intent to Treat       Active         Comparator

    Published    Charleston, SC      MP-1        N=23             125 mg            0 mg
J. Psychopharm    Switzerland        MP-2        N=14             125 mg            25 mg
                 Vancouver, BC       MP-4        N=6              125 mg            0 mg
Publication
                 Charleston, SC      MP-8        N=26          75 or 125 mg         30 mg
 pending
                 Tel Aviv, Israel    MP-9        N=8              125 mg            25 mg
                  Boulder, CO       MP-12        N=26          100 or 125 mg        40 mg

                                            Intent to Treat        Active (75-125 mg) vs.
                       All Studies
                                                N=105              Comparator (0-40 mg)
Six MDMA/PTSD Studies at Long-Term Follow-Up

                                                                                                          120                        Stage 1 Comparator (0-40 mg, n=31)

          PTSD OUTCOME ANALYSIS                                                                                                      Stage 1 Active (75-125 mg, n=74)

                                                                       Mean CAPS-4 Total (+/-SD) Scores
                                                                                                                                     Stage 2 Open Label (100-125 mg, n=27)
                                                                                                          100
                                                                                                                            ***
           All subjects had full dose MDMA
                 in Stage 1 or Stage 2                                                                     80
Stage 1
   *** p < 0.001 ANOVA of Difference Scores (End of Stage- Baseline)                                                                                                    ***
Stage 2                                                                                                    60                                               ***
   *** p < 0.001 ANOVA of Difference Scores (End of Stage- Baseline)
LTFU
                                                                                                           40
   *** p < 0.001 ANOVA of Difference Scores (LTFU - Baseline)

            Primary Outcome                                                                                20

Between group Cohen’s d effect size: 0.9 (Large)
                                                                                                            0
                                                                                                                Stage 1    Primary    End of    Stage 2    End of    12+ Month
                                                                                                                Baseline              Stage 1   Baseline   Stage 2   Follow-up
EXPANDED ACCESS

      Photo by Nirvan Mullick, PrescriptionX – The Rick Doblin
      Story
P H ASE 3 SI T E S
OUR THERAPEUTIC APPROACH
IN MDMA-ASSISTED PSYCHOTHERAPY
THERAPEUTIC APPROACH

Our adaptation of the foundation
 laid by Stanislav Grof, MD and
           many others
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
WHY DOES MDMA HELP PEOPLE
     PROCESS TRAUMA?
WINDOW OF TOLERANCE

                                                        Increased sensation
                                                        Emotional reactivity
     Hyperarousal                                       Intrusive imagery
                                                        Disorganized cognitive processing
Arousal

                               Window of Tolerance / Optimal Arousal Zone

                                                        Numbing of emotions
     Hypoarousal
                                                        Disabled cognitive processing

Adapted from Ogden P et al. Psychiatr Clin North Am. 2006;29(1):263-279, xi-xii
ELEMENTS OF OTHER THERAPIES
   THAT ARISE IN MDMA-ASSISTED SESSIONS

Safe, supportive setting   Somatic

Imaginal exposure          Multiplicity of the psyche

Cognitive restructuring    Transpersonal/Spiritual

Transference               Corrective attachment

Psychodynamic              Active imagination
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
“PSYCHIATRIC DISORDERS
ARE INHERENTLY MULTI-
FACTORIAL”

    KENNETH KENDLER, MD

                            MAYBE HEALING

                          IS INHERENTLY MULTI-
                                FACTORIAL
“THE THERAPIST MUST STRIVE
TO CREATE A NEW THERAPY
FOR EACH PATIENT.”

     I RV I N YA L O M , M D

                               OR MAYBE THE THERAPIST MUST
                                  STRIVE TO ALLOW AND
                               ENCOURAGE EACH PATIENT TO
                                CREATE A NEW THERAPY FOR
                                       THEMSELVES
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.”
IMAGINAL EXPOSURE

“I don’t know why they call
       this Ecstasy!”
TRANSFERENCE

“Will you brush my hair!”
RESISTANCE
                                              “If the resistance is itself
                                              unconscious, as so often
 “It feels almost like the inner healer or    happens owing to its
 the MDMA is like a maid doing spring         connection with the repressed
cleaning. It’s as if you thought you were     material, we make it
cleaning before but when you got to the
   things you didn’t really want to deal      conscious.”
with you’d just stick them in the attic. If
   you’re going to clean the house you                             Freud
     can’t skip the stuff in the attic.”
THIS VETERAN STOPPED
       OPIATES

“Iraq changed my brain,
MDMA changed it back.”
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.”
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.”
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.”
BOTTOM UP PROCESSING
       (SOMATIC)
                                               • Bring awareness to the body

                                               • Encourage movement
      “Allowing the body to have
experiences that deeply and viscerally         • Optional mindful use of touch with
 contradict the helplessness, rage or
                                                permission and careful agreements
  collapse that result from trauma.”
                   The Body Keeps the Score     • Nurturing touch
                         Bessel van der Kolk
                                                • Focused release work
An Iraq veteran during an MDMA session

                                             Therapist:
MDMA AP P E AR S TO P ROMOT E
  SE CUR E AT TAC H ME NT                     “What are you noticing about the MDMA?”

                                             Participant:

“Traumatized human beings recover             “It’s allowing me to ... really view this part of
                                             my life that we’re talking about in a new way
  in the context of relationships…           than I have before, in a more complete way
   Recovery from trauma involves             and to understand it a bit better.”
reconnecting with our fellow human
              beings.”                       Therapist:
                 The Body Keeps the Score      “Are you feeling connected to us?”
                       Bessel van der Kolk
                                             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”
“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.”

Firefighter and MAPS Study Participant, MP-8
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”
SAFE T Y OF T H E SE T / SE TT ING

     I MAG I NAL E X P OSU R E

MU LT I P L ICI TY OF T H E P SY C H E

     AC T I V E I MAG I NAT I ON

  Video of Marine Veteran
   During MDMA-assisted
              Session
Deep appreciation for the MAPS team, members, donors, investigators &
                                     All the study participants!

Clinical Research Team
Amy Emerson, Director of Clinical Research                    Clinical Investigators
Berra Yazar-Klosinski, PhD, Clinical Research Scientist       Michael Mithoefer, MD, Lead Clinical Investigator, Medical Monitor
Rebecca Matthews, Clinical Trial Leader                       Annie Mithoefer, BSN, Co-Investigator, Charleston
Charlotte Harrison, Senior Clinical Research Associate        Marcela Ot’alora, MA, LPC, Primary Investigator, Boulder
Alia Lilienstein, MD, Clinical Research Associate-Physician   Bruce Poulter, Co-Investigator, Boulder
Allison Feduccia, PhD, Clinical Data Scientist                Moshe Kotler, MD, Primary Investigator, Israel
Colin Hennigan, Clinical Data Manager                         Peter Oehen, MD, Primary Investigator, Switzerland
Allison Wilens, Clinical Study Associate
Ilsa Jerome, PhD, Research & Information Specialist           Ingrid Pacey, MD, Primary Investigator, Canada

                        maps.org                       mmithoefer@mac.com
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