I DON'T KNOW WHY THEY CALL THIS "ECSTASY"
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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)
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.
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?
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
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)
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
• 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
STAGE 2 CROSSOVER: MEAN CAPS-4 SCORE BY GROUP Mithoefer MC et al. J Psychopharm. 2011;25(4):439-452
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.
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 ***pDEPRESSION 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 *** ***pSLEEP 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
*
*pSPOSTTRAUMATIC GROWTH OUTCOMES
(PTGI)
NCT01211405SIX 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-upEXPANDED ACCESS
Photo by Nirvan Mullick, PrescriptionX – The Rick Doblin
StoryP 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 othersTHERAPEUTIC 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
integrationWHY 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-xiiELEMENTS 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
THEMSELVESWINDOW 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 workAn 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-8TRANSPERSONAL/
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
SessionDeep 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
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