The Healing Potential of MDMA

Dr. Ingrid PaceyPrincipal Investigator

MDMA / PTSD Research in CanadaMultidisciplinary Association for Psychedelic Studies

May, 2014

Why MDMA for PTSD?

Obstacles to treating PTSDFear

Hyper vigilance

Defensiveness / numbing

Lack of trust

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

MDMA Diminishes the Obstacles:

Decrease fear and defensiveness

Increase trust and empathy

Provide Affirming experiences

More realistic perspective about present circumstances/safety

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Amygdala and Prefrontal Cortex

PTSDMediated by emotional memory- increased amygdala activity

Decreased activity in prefrontal cortex- Thought Center

MDMAReduces fear & suppresses activity in amygdala

Increased blood flow and Activity in prefrontal cortex

Rauch SL et al. Biol Psychiatry. 2006;60(4):376-382, Gamma et al. 20003

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:OxytocinVasopressinCortisolProlactinDehydroepiandrosterone (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

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A Window of Tolerance

•Increased sensation•Emotional reactivity•Intrusive imagery•Disorganized cognitive processing

•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

Hyperarousal Zone

Hypoarousal Zone

Window of Tolerance / Optimal Arousal Zone

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“Before, I knewthe path wasthrough a battlefield,but I could not getthrough it.During MDMA therapy,I knew I couldwalk through it andI wasn’t afraid.MDMA gave methe abilitynot to fear.”Donna, a patient inthe US pilot study

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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 PASATNo change pre and post MDMA or placebo

•Changes in Vital signs during sessions similar between MDMA and Placebo Group

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More common with MDMA:

Decreased concentration

Jaw Clenching

Dizziness

Dry mouth

Feeling cold

Impaired Balance

Anxiety

Common Side Effects

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

Toxicity in Recreational Users

Rare cases of Serious acute toxicity in recreational usersNeurotoxicity in animals at high, repeated IV doses, not relevant to doses used in human studiesPET scans- no change in estimated serotonin transporter binding sites 4 weeks after a clinically relevant dose of MDMAModerate abuse potential

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; Mithoefer MC et al. J Psychopharm. 2011;25(4):439-452; Mithoefer MC et al. J Psychopharm. 2012; In press. 9

Benefits of MDMA

•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).

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Study Design

phone session for 7 days following each experimental session

Screening/Baseline

90 min Prep Sessions

1

2

3

MDMA orPlacebo

1

2

3

90- MinIntegrativeSessions

ExpSession

1

2

3ExpSession

ExpSession

1

2

3

MDMA

Outcome

12 mn

Follow

Up

Outcome

Stage 2

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Objectives and Measures

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

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Therapeutic Approach

Characterized as non-directive and supportive of the emerging experience

Treatment Manual is available at www.maps.org 13

Private Practice Setting

ER Doctor Psychiatrist,IFS, Holotropic BreathworkAssistant Clinical ProfessorMedical University of South Carolina

Psychiatric NurseHolotropic BreathworkHakomi

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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):439-45215

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“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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Visit us online at:www.maps.org

www.mdmaptsd.org

www.facebook.com/mapsmdma

www.youtube.com/mapsmdma

http://www.bluelight.ru/MAPS-Forums

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Publications of this Work

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 {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy: A Prospective Long-term Follow-up Study. J Psychopharmacol, Epub online 2012, Nov 20. 18