Dr. Ingrid Pacey
Principal Investigator
MDMA / PTSD Research in Canada
Multidisciplinary Association for Psychedelic Studies
May, 2014


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):319-327; Greer & Tolbert, J Psychoactive Drugs, 1998; 30(4):371-379
2

PTSD
Mediated by emotional memory- increased amygdala activity
MDMA
Reduces fear & suppresses activity in amygdala
Rauch SL et al. Biol Psychiatry . 2006;60(4):376-382, Gamma et al. 2000
3


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):400-410; Dumont, et al. Soc Neurosci, 2009, 4(4): 359-366; Hysek, et al. Psychopharmacology (Berl), 2012, 222(2): 293-302; Bedi et al., Biol Psychiatry, 2010, 68(12): 1134-1140; Guastella, et al. Biol Psychiatry, 2010, 67: 692-694; Parrott, et al. Neuropsychobiology, 2009, 60(3-4): 148-158; Cami, et al. Ann N Y
Acad Sci, 2000, 914:225-237; Harris, et al. Psycopharmacol (Berl) 2002, 162(4): 396-405; Farre, et al. Psycopharmacol (Berl) 2004, 173(3-4): 364-375
4

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):263-279, xi-xii
5

“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
6

• 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
7

More common with MDMA:

Decreased concentration

Jaw Clenching

Dizziness

Dry mouth

Feeling cold

Impaired Balance

Anxiety
More common with inactive placebo :

Anxiety

Drowsiness

Insomnia
Jerome L. (+/-)-3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) Investigator’s Brochure. December
2007. www.maps.org/research/mdma/protocol/ib_mdma_new08.pdf. Accessed Aug. 16, 2012.
8


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
9

•
Enhances psychotherapy, not taken as ongoing medication
•
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).
10

Screening/
Baseline
90 min Prep
Sessions
1
2
3
90- Min
Integrative
Sessions
1
2
Exp
Session
MDMA or
Placebo
3
Exp
Sessio n
1
2
3 t c
O u o m e
Exp
Session
MDMA
1
2
3 t c
O u o m e
Stage 2
 phone session for 7 days following each experimental session
12 mn l l
F o o w
U p
11


.

Clinician Administered PTSD Scale (CAPS)

Beck Depression Inventory (BDI-II)

Global Assessment of Functioning (GAF)

Posttraumatic Growth Inventory (PTGI)

Pittsburgh Sleep Quality Index (PSQI)

NEO Personality Inventory (NEO)

VAS for pain and tinnitus

Monitoring for Safety
• Side effects , adverse events
• Concomitant medication
• Suicidality
• Vital Signs
12

13

ER Doctor Psychiatrist,
IFS, Holotropic Breathwork
Assistant Clinical Professor
Medical University of South Carolina
Psychiatric Nurse
Holotropic Breathwork
Hakomi 14

Baseline Post Session 2 Placebo/Active Post
Session 3
Mithoefer MC et al. J Psychopharm. 2011;25(4):439-452
15

“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.”
16

www.maps.org
www.mdmaptsd.org
www.facebook.com/mapsmdma www.youtube.com/mapsmdma http://www.bluelight.ru/MAPS-Forums
17

Mithoefer, MC, Wagner, MT, Mithoefer, AT, Jerome, L, Doblin, R. The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study.
J
Psychopharmacol, 2011. 25 (4): p. 439-52.
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 {+/-}3,4methylenedioxymethamphetamine-assisted psychotherapy: A Prospective
Long-term Follow-up Study. J Psychopharmacol, Epub online 2012, Nov 20.
18