The Healing Potential of MDMA

The Healing Potential of MDMA Dr. Ingrid Pacey Principal Investigator MDMA / PTSD Research in Canada Multidisciplinary Association for Psychedelic Studies

May, 2014

Why MDMA for PTSD? Obstacles to treating

PTSD

MDMA Diminishes the

Obstacles:

Fear

Decrease fear and defensiveness

Hyper vigilance

Increase trust and empathy

Defensiveness / numbing

Provide Affirming experiences

Lack of trust

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

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Amygdala and Prefrontal Cortex 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

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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: 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

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A Window of Tolerance

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

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“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

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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 PASAT No change pre and post MDMA or placebo •Changes in Vital signs during sessions similar between

MDMA and Placebo Group

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Common Side Effects More common with MDMA: Decreased concentration Jaw Clenching

Dizziness Dry mouth

More common with inactive placebo: Anxiety Drowsiness Insomnia

Feeling cold Impaired Balance Anxiety 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.

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Toxicity in Recreational Users 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

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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 90 min Prep Sessions

90- Min Integrative Sessions

1

1

Screening/ Baseline

1

2

2 3

12 mn

Exp Session MDMA or Placebo

3

2 Exp Sessio n

3

O u t c o m e

1 2 Exp Session

3

MDMA

O u t c o m e

F o l l o w U p

Stage 2 phone session for 7 days following each experimental session

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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

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Private Practice Setting

ER Doctor Psychiatrist, IFS, Holotropic Breathwork Assistant Clinical Professor Medical University of South Carolina

Psychiatric Nurse Holotropic Breathwork Hakomi 14

PTSD Severity-Mean CAPS Score by Group after MDMA or Placebo

Baseline Session 3

Post Session 2 Placebo/Active

Post

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

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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.” 16

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, YazarKlosinski, 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.

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