Rick Doblin, Ph.D. Founder and Executive Director,Multidisciplinary Association for Psychedelic Studies (MAPS)

Scientific Freedom for Psychedelic and Marijuana Research

World Congress for Scientific FreedomEuropean ParliamentBrussels, BelgiumApril 13, 2018

A Brief History of MDMA 1912-2018

1912

MDMA first synthesized and patented by the pharmaceutical company Merck as “Methylsafrylamin.”

It was an unimportant precursor in a new synthesis for clotting agents.

First pre-clinical pharmacological tests with MDMA by Merck, nothing interesting found. 1927

1953-1954

The United States Army used animal models to investigate the toxicity and behavioral effects of MDMA and seven other related compounds, but the results remained classified until 1973.

Merck conducts further animal studies, nothing interesting found.

1959

An American chemist, Alexander “Sasha” Shulgin resynthesized MDMA and experimented with the drug himself.

Mid-1970s

Alexander “Sasha” Shulgin

MDMA used in psychotherapy with good results. Estimated 500,000 doses of MDMA used in therapeutic growth settings from mid-1970s until 1984. Reported to increase communication, and found to be especially useful for couples therapy.

Leo Zeff

Late-1970s

By the early 1980s, "ecstasy" (MDMA + other psychoactive substances) became a popular drug often at dance clubs and raves in the US and Europe.

1980-1984

The Drug Enforcement Administration (DEA) moves to classified MDMA as a Schedule 1 controlled substance. Advocates file for Administrative Law Judge (ALJ) hearing within 30 day public comment period.

1984

The Drug Enforcement Administration (DEA) classified MDMA as a Schedule 1 controlled substance using emergency scheduling authority, later declared invalid.

1985

1986

The Multidisciplinary Association for Psychedelic Studies (MAPS) is founded April 8, 1986.1986

FDA rejects five different Phase 1 or Phase 2 protocols for MDMA clinical trials.

1986-1992

FDA approves first Phase 1 dose response safety study for MDMA in humans.

Dr. Charles Grob

1992

Sponsored by MAPS, the first randomized, placebo-controlled, double-blind study investigating MDMA-assisted therapy, conducted in women with treatment-resistant PTSD, commenced in 2000 in Spain but ended due to political pressures after only 6 women were treated.

2000

Seven IRBs reject or refuse to review MAPS’ first FDA-approved MDMA/PTSD protocol.

2000-2004

Out of desperation, MAPS called Copernicus Group IRB based on their name.

Copernicus Group IRB approves the first MAPS-sponsored MDMA/PTSD protocol.

2004

Pilot MDMA/PTSD study is published.Mithoefer et al. (2010). J. Psychopharmacology

Long term follow up paper is published.Mithoefer et al. (2012). J. Psychopharmacology

2010 2012

Expansion of neuroscience research with psychedelics and MDMA.

“The world’s populations need more compassion and empathy for one another. The study of MDMA provides one small but potentially important step toward reaching that goal.”

Boris D. Heifets & Robert C. MalenkaStanford University School of Medicine

Cell, Vol. 166, Issue 2 July 14, 2016

Photo by Nirvan Mullick, PrescriptionX – The Rick Doblin Story

MAPS completes international series of six Phase 2 pilot studies of MDMA-assisted psychotherapy for PTSD.

Nov 29, 2016 Successful End of Phase 2 Meeting with FDA.

2016

MAPS Sponsored Phase 2 Clinical Trials for MDMA-Assisted Psychotherapy for Chronic,

Treatment-Resistant PTSD

Study Location Intent to Treat Sample

MP1 Charleston, SC 23MP2 Switzerland 14

MP4 Vancouver, Canada 6

MP8 Charleston, SC 26MP9 Israel 10

MP12 Boulder, CO 28Total 107

N=31N=90

Unpublished Data

N=100 (N=77 had 3 sessions)

FDA and MAPS reach agreement regarding the Phase 3 protocol designs through the Special Protocol Assessment process.

July 28, 2017

FDA Phase 3 Study Design:MDMA-Assisted Psychotherapy for PTSD

2-Month Follow-up

Screen & Enroll

80 or 120 mg 80 or 120 mg80 mg

Inactive Placebo

Inactive Placebo

Inactive Placebo

3 Prep Sessions 9 Integrative Psychotherapy Sessions

3 Prep Sessions 9 Integrative Psychotherapy Sessions

2017

FDA grants Breakthrough Therapy Designation for MDMA-assisted psychotherapy for PTSD. Large scale studies planned to begin enrollment in Spring 2018.

August 15, 2017

DEA meeting to discuss increase in Schedule 1 licenses needed for Phase 3 and Expanded Access programs.

December 19, 2017

First Breakthrough Planning Meeting with the FDA Department of Psychiatry Products. Discussed submitted questions regarding program requirements for approval.

December 20, 2017

First meeting with European Medicines Agency (EMA) to begin negotiations for approval in Europe.

Scientific Advice Briefing Document for Phase 3 MDMA/PTSD clinical trials in Europe submitted to EMA.

March 1, 2018 April 4, 2018

To be continued…

FDA Phase 3 Site Locations

• San Francisco, CA | research institution • Farmington, CT | research institution• New York, NY | research institution• Madison, WI | research institution• Vancouver, Canada | research institution• Israel | research institution• San Francisco, CA | private practice• Los Angeles, CA | private practice• Boulder, CO | private practice• Fort Collins, CO | private practice• New Orleans, LA | private practice• New York, NY | private practice• Charleston, SC | private practice• Boston, MA | private practice• Montreal, Canada | private practice

Potential European Phase 3 Site Locations

• Prague, Czech Republic

• Utrecht, Netherlands

• Amsterdam, Netherlands

• Berlin, Germany

• Hanover, Germany

• Bristol, England

• Cardiff, England

• Others?

Potential Post Approval Risk Mitigation Strategies

• Only prescribed by certified therapists trained by the sponsor.

• Only administered in certified clinics.

• Defined safety screening for specified patient populations.

Data Exclusivity

Drug Price Competition and Patent Term Restoration Act of 1984 (Hatch/Waxman Amendments)

September 24, 1984

Expanded Access, Compassionate Use

“Under FDA’s statute, a sponsor or a physician may submit an expanded access request for widespread access to an investigational product if certain criteria are met”

Off-Label Prescription Use Post-Approval

Potential Indications:

• Anxiety

• Depression

• Social Anxiety

• Eating Disorders

• Substance Use Disorder

• Schizophrenia

• Dissociative Identity Disorder

US Controlled Substance Act (1970)

“Sec. 101. The Congress makes the following findings and declarations: (1) Many of the drugs included within this title have a useful and legitimate medical purpose and are necessary to maintain the health and general welfare of the American people.”

“Sec. 201 (b). The recommendations [about scheduling] of the Secretary [of HHS] to the Attorney General shall be binding on the Attorney General as to such scientific and medical matters.”

US Improving Regulatory Transparency for New Medical Therapies Act (2015)

The purpose of this law is to expedite scheduling of newly approved drugs that are currently in Schedule I or not controlled.

Requires DEA to initiate a scheduling action for new FDA-approved drugs within 90 days.

Safety and Efficacy of Marijuana for Treatment of Posttraumatic Stress Disorder (PTSD) in 76 US Veterans

Funded by a $2.15 million grant to MAPS from the Colorado Department of

Public Health and Environment

“To facilitate research involving marijuana and its chemical constituents, DEA is adopting a new policy that is designed to increase the number of entities registered under the Controlled Substances Act (CSA) to grow (manufacture) marijuana to supply legitimate researchers in the United States.”

Return to Law and Order & Drug War Escalation

Attorney General Jeff SessionsPresident Donald Trump

Ending the NIDA Monopoly on DEA Licensed Marijuana

With MAPS’ support, Professor Lyle Craker applied for a DEA license in 2001 and 2017

Scientific Freedom: