Developing Psychedelics into Prescription Medicines:

MDMA-Assisted Psychotherapy for Posttraumatic Stress

DisorderBy Rick Doblin, PhD, Executive Director

Multidisciplinary Association for Psychedelic Studies

Entheogenesis Australias December 4, 2010

Replacing Fears... With Facts

•“Probably the worst example they could find of a drug lab they had raided and taken a photo of.” -Dr. David E. Nichols, Ph.D.

•“I love the way the way they always throw the battery acid and drain cleaner into the story, as if prescription drugs were not manufactured using the exact same reagents, which are simply dilute sulfuric acid and sodium hydroxide!” -Dr. Nicholas Vito Cozzi, Ph.D.

Brain SPECT Scan-MTV/Oprah

Holes in the Brain from MDMA?

(Ecstasy. Create Fear.)

Leshner Testimony to Senate Leshner Testimony to Senate Subcommittee on Government Subcommittee on Government

Affairs 7/30/01Affairs 7/30/01

Bottle from experiement of MDMA

Harvard MDMA Cancer - ask John

Documentary Clip

Outline •Why MDMA?

•Why PTSD?

•Questions for Phase II trials

•US Pilot study & follow-up: Design & Results

• International series of Phase II studies

•US MDMA/PTSD war veterans study

•Australian MDMA/PTSD study?

Why MDMA?•Reduces fear response to perceived

emotional threat (reduced activity in amygdala; Gamma, A., et al., 2002)

• Increases trust and empathy (oxytocin, prolactin, similar to post-orgasmic state; Passie et al., 2005)

•Gentle but profound; easier to integrate

•Therapists/psychiatrists more willing to self-experiment than classic psychedelics

Why MDMA?

•Highly demonized: 3500+ papers in Medline about risks/mechanisms of action

•Estimated cost $300 million worth of studies in the public domain

•MAPS spent $150,000 to read and summarize all published scientific peer-reviewed literature on MDMA

Why PTSD? •Current treatment approaches fail to provide relief in a substantial number of patients

• Internationally accepted outcome measure (CAPS)

•Therapeutic change captured by outcome measure (not the case with psychedelic therapy for end-of-life anxiety & depression)

•Highly sympathetic patient population (Veterans, survivors of sexual assault, abuse, accidents, and trauma)

Why PTSD? PTSD

A fear-based disorderMDMA

Treatment for fear

$300 million of existing research

Millions of users, rare side effects known

Top priority combination of psychedelic drug and clinical

condition

=

Phase II Methodological

Issues •Development of our therapeutic model

•Training of therapists

•Cause of PTSD related to treatment method?

•Successful double-blind design

•Variance and magnitude of treatment effect

•Cultural differences

Development of our Therapeutic

Model

Can be viewed at www.maps.org

Training Therapists •5 day training program mostly watching

videos and reviewing treatment manual and adherence criteria

•Psychological effects of MDMA administration in normal volunteers training to conduct MDMA-assisted psychotherapy research

•Review video tapes of first two therapy sessions by raters scoring adherence criteria with feedback from Mithoefers

Cause of PTSD Related to

Treatment Method?•Sexual assault vs. war-related

trauma?

Successful Double-Blinding

•Inactive placebo

•Active placebo

•Dose response

Treatment Effect (Variance & Magnitude)

•Data from US versus Swiss

•get Swiss data from Ilsa

Cultural Differences

US MDMA/PTSD Pilot Study Design•Treatment resistant/pharmacotherapy

& psychotherapy

•Average duration PTSD = 19 years

• Inactive placebo versus 125mg + 62.5mg

•Combination: drug & non-drug psychotherapy

•2-3 MDMA sessions with 2 month & long-term follow-up

Treatment Process

• In addition, therapists have up to a 30-minute phone session with participant for 7 days following each experimental session.

• Outcome Assesment = 2 months after last experimental session

• Follow-up Assessment = 12 months after last experimental session

ScreeninScreening/g/

BaselineBaseline

90-Minute Non-Drug 90-Minute Non-Drug Intro Therapy SessionsIntro Therapy Sessions

11 22 33

MDMA or Placebo

11

22

33

90- Min Non-Drug Integrative

Therapy Sessions

Exp Exp SessionSession

11

22

33Exp Exp

SessionSessionExp Exp

SessionSession

11

22

33

MDMA or Placebo

MDMA or Placebo

Non-Drug IntegrativeTherapy Sessions

Non-Drug IntegrativeTherapy Sessions

OOuuttccoommee

FFoollllooww

UUpp

get from ilsa orMM this yellow colum should be 25%

US Long-Term Follow-Up

Swiss MDMA/PTSD• Improvements not observed in active

placebo group 25mg + 12.5mg BUT did produce some blinding

• MDMA group benefited, but not as much as in US MDMA/PTSD study

• No Serious Adverse Events (no evidence of harm)

• Long-term follow-up to be completed Jan 2011; paper submitted to journal by April 2011

•graph of Swiss data

Swiss •Physiological correlates of PTSD

study conducted by Dr Franz X. Vollenweider, M.D. @ University of Zurich in all 12 participants

•EEG

•Startle reflex

•Heart rate variability (HRV)

•Results will be published as a separate paper

Israel

•5 patients

• No Serious Adverse Events (no evidence of harm)

•No efficacy

Current & Upcoming

Studies

•Canada

•Israel

•Jordan

•US MDMA/PTSD War Veterans

Canada•Can we replicate US results in a

similar cultural context with similarly trained therapists?

•N = 12

•125mg + 62.5mg versus 25mg + 12.5mg

•3 sessions

•Waiting on import permit

Israel

•Different cultural context

•2 sessions instead of 3

•N = 10

•125 + 62.5 versus 25 + 12.5

•Traditional psychiatrists paired with psychologists experienced with PTSD or MDMA

Jordan •Different cultural context

•How do we teach our method?

•N = 12 Iraqi refugees in Jordan

•3 Sessions

•125 + 62.5 experimental dose

•Using a 40mg +20mg low dose- another attempt to work on double-blind

•Arabic caps on next slide

Arabic CAPS

US: MDMA/PTSD Study in

War Veterans•To see if cause of PTSD requires

different method

•Investigate double-blind: 3 dose groups: Low (30 mg + 15mg), medium (75 mg + 37.5) and full dose (125 mg + 62.5)

•Higher risk populations (controlled hypertension and Hepatitis C)

•Potential design for Phase III studies

Timeline •2-3 years to FDA End of Phase II Mtg

•3-5 years for all Phase 3 studies

•1-2 years for FDA review

Zulfi

Text

July 21, 2010

Australian MDMA/PTSD

•25k matching grants for Australia MDMA/PTSD

•+ Protocol devel and approval assistance

•+ therapist training

•+ clinical research oversight

•email from someone who contacted rick from Aus- Vets in Aus who wanted to come participate in US study