Download MDMA - Multidisciplinary Association for Psychedelic Studies

FDA as Honest Broker
• FDA’s institutional mission is to develop
medicines to reduce suffering.
• FDA is not in favor of psychedelics or
marijuana, just in favor of research.
• FDA responded fairly rapidly to
submissions and did not cause most delays.
FDA Organizational Changes
• The Division at FDA that blocked most
psychedelic research throughout the 1970s
and 1980s had the review of Schedule 1
Drugs taken away in 1989.
• New policies, ratified by an FDA Drug
Abuse Advisory Committee in 1992 and
reaffirmed by FDA management in 1999,
permit well-designed human research with
psychedelics and marijuana.
FDA’s Track Record
• Since 1990, FDA has
approved human
studies with:
• DMT
• MDMA
• Ibogaine
• Psilocybin
• Mescaline
• Marijuana
Missing In Action
Psychedelic Research
Around the World- Therapy Studies
• Ketamine in the treatment of heroin
addiction, Dr. Evgeny Krupitsky, St.
Petersburg, Russia.
• Single v. Multiple (3) Doses of KetamineAssisted Psychotherapy (KPT), Double-blind
• Five year study, now in the second year.
Dr. Krupitsky’s
Previous Ketamine Research
• This study follows a 3-year study comparing one
high-dose KPT session (2 mg/kg i.m.) to one lowdose, placebo control session (0.2 mg/kg i.m.).
• The rate of abstinence in the high dose group was
significantly higher than that of the low dose group,
starting from the first month and then within all
twenty-four months of follow-up.
• Paper in review by J. of Substance Abuse Treatment
Patient Account: Mr. P.F.
• Dose is 2.0 mg/kg i.m.
• “I am one of the stars. Then the whole dome
collapsed and turns into one dot. A gold
splash appears against the blue background.
It turns into a flower. The flower opens and
there, in the flower, I see my son, and
somebody’s voice is saying: “That is most
important.”
Dr. Krupitsky’s
Ketamine Therapy-1st Stage
• Preliminary non-drug psychotherapy in
order to build Therapeutic Alliance. Review
the subject’s personal motives for treatment,
goals for new life without drugs, theory
about the causes of addiction and
its’consequences and so on.
• Discuss the effects of Ketamine.
Dr. Krupitsky’s
Ketamine Therapy - 2nd Stage
• Session is directed toward the resolution of
personality problems and formation of a
stable orientation to a future without drugs.
• Carefully direct the subject’s experiences by
verbal influences and guiding the musical
background toward the symbolic resolution
of personality conflicts as well as a final
cathartic peak experience.
Dr. Krupitsky’s
Ketamine Therapy -3rd Stage
• Non-drug integrative therapy sessions.
• Discuss and interpret the personal
significance of the symbolic content of their
experience with the psychotherapist.
• Generate new insights that enable subjects
to integrate new, often unexpected,
meanings, values and attitudes.
Dr. Krupitsky’s
Ketamine Research
• 60 Subjects receive 3 KPT sessions
• 60 subjects receive 1 KPT session ( the first
session for everyone is a KPT session) and 2
Placebo sessions.
• Sessions take place after completion of in-patient
detox, Sessions 4 weeks apart. When subjects
return for second session, randomized to either 3
or 1 KPT sessions.
Dr. Krupitsky’s
Ketamine Research
• 52 patients randomized so far into either single or
multiple KPT sessions group.
• 5 additional patients dropped out after the first
ketamine session, and didn’t show up for the
second session one month later.
Dr. Krupitsky’s
Ketamine Research
• Measures
• Abstinence, followed for two years through Urine
Tests, Reports of Significant Others
• Complete Battery of Psychological Measures such as
MMPI, Zung Depression Scale,
• Hallucinogen Rating Scale
• Locus of Control Scale
• Questionnaire of Terminal Life Values, Purposes-inLife Test, and Spirituality Scale
Jose Carlos Bouso
MDMA/PTSD Protocol
• MDMA in the treatment of women survivors
of sexual assault suffering from chronic
posttraumatic stress disorder (PTSD).
• Double-blind, Placebo-controlled, DoseResponse Pilot Study. Funded by MAPS.
• The only study in the world currently
investigating the therapeutic use of MDMA.
Personal Account: Marcela
• 1984: “Adam [MDMA] has helped me look
at all this suffering, see my life, as a whole
and understand it better. It has given me the
courage to face the fears instead of ignoring
them, to know that the most important thing
is to struggle to trust myself.”
• Fall 2000: Licensed therapist, MA degree,
therapist on MDMA/PTSD study in Madrid.
Jose Carlos Bouso
MDMA/PTSD Protocol
• PURPOSES OF THE STUDY
To determine the most effective therapeutic dose
of MDMA as an adjunct to psychotherapy with
women suffering from PTSD as a result of having
survived sexual assault.
• To gather preliminary evidence about the
therapeutic effectiveness of MDMA as an adjunct
to psychotherapy in women suffering from PTSD
as a result of having survived sexual assault.
Jose Carlos Bouso
MDMA/PTSD Protocol-Rationale
• Within a psychotherapeutic context, MDMA
can help to create an environment where the
subject can re-experience her trauma
without the terror she has associated with it.
• This successful reliving of the traumatic
event is thought to give the patient a greater
sense of subjective control over the memory
– thereby reducing the symptoms of PTSD.
Jose Carlos Bouso
MDMA/PTSD Protocol-Rationale
• This ease of accessing and expressing deep
feelings breaks the affective hold of the
disorder, permitting an acceleration of the
process of establishing a therapeutic
alliance, the variable most predictive of
therapeutic changes.
Jose Carlos Bouso
MDMA/PTSD Protocol
• 29 Subjects, 5 have been treated to date.
•
•
•
•
•
4 Subjects in 50 mgs group (3 MDMA, 1 placebo)
7 Subjects in 75 mgs group (5 MDMA, 2 placebo)
7 Subjects in 100 mgs group (5 MDMA, 2 placebo)
7 Subjects in 125 mgs group (5 MDMA, 2 placebo)
4 Subjects in 150 mgs group (3 MDMA, 1 placebo)
MDMA Research in Spain:
Basic Safety Studies
• Dr. Magi Farre, Dr.Jordi Cami and Team
Institut Municipal d'Investigacio Medica
(IMIM), Barcelona, Spain. Spanish
Government funded.
• Phase 1 Studies, Pharmacokinetics,
• Effects of MDMA and Alcohol and immune
system functioning.
US Psilocybin/OCD Study
• Dr. Francisco Moreno, U. of Arizona
• Pilot study of psilocybin in patients with
Obssesive/Compulsive Disorder.
• First FDA-approved investigation of
psilocybin in patients in 30 years!
• Heffter and MAPS funded.
Research Objectives
• Evaluate the safety and therapeutic
potential of serotonin (5-HT)-2A/2C
receptor agonist treatment of OCD.
• Note: Primarily pharmacologic, not
psychotherapeutic mechanism of action is
proposed. However, MAPS has brought
experts to U. of A. to train the researchers in
how to work with psychedelic experiences.
Basic Design Elements
• Double-blind pilot study, 10 patients.
• Outpatients, will not be hospitalized prior to
or after the psilocybin experience.
• Dose-escalation study, 4 dose levels,
0.025, 0.1, 0.2 and 0.3 mgs/kg,
• Up to 4 Sessions, each 2 weeks apart.
Local Connection
• Psilocybin
manufactured for
MAPS by Organix,
Inc. in Woburn, MA.
• $12,250 for one gram,
the world’s most
expensive psilocybin!
Dr. Mash’s Ibogaine Research
• Deborah Mash, Ph.D. University of Miami,
treating patients with ibogaine to reduce
withdrawal from opiates and cocaine, and to
promote abstinence. About 150 treated.
• NIDA rejected grant application so Dr.
Mash established a clinic in St. Kitts.
Treatments funded by patients, mostly a
safety study with limited follow-up.
www.healingvisions.com
Personal Account- Roberto
• Roberto: “All of a sudden, out of the water,
this big angel came out. It was like Mother
Earth, like my creator, something higher
than me letting me know everything was
going to be all right."
Personal Account- Roberto
• "I can’t say more... I don’t know how to
explain it. I got in touch with the kid who
got lost between the drug world and the
insanity of my life. And now I’m more at
peace. I still have to fight my addiction, but
now I feel like I got a foundation."
Dr. Mabit’s Ayahuasca Research
• Dr. Jacques
Mabit, Takiwasi,
Peru
• Uses ayahuasca
and other plants
to treat drug
addicts within a
shamanistic
context.
The Spirit of Ayahuasca
by Pablo Amaringo
•
•
Dr. Vollenweider’s Research Team
University of Zurich
• Franz Vollenweider, U.
of Zurich, 14 people
• Psilocybin doseresponse studies
• MDMA Neurotoxicity,
Blocking studies
• Heffter and Swiss
Government funded
•
University of Zurich- MDMA
• Prospective MDMA Neurotoxicity Study
• MDMA-naive subjects and controls. Doses
of 1.5 -1.7 mgs/kg. Pilot study completed.
• PET scan, same ligand as used by George
Ricaurte to measure serotonin uptake sites.
• PET Scan before and two weeks after
MDMA. No significant serotonin changes.
• Paper being written, report sent to FDA.
University of Zurich- Psilocybin
• Preparing for a psilocybin therapy study.
• Patient population still being discussed but
probably people with eating disorders.
Future Directions
• “ We have moved beyond the model
psychosis framework. We have left that
behind.”
Dr. Franz Vollenweider
August 9, 2001
Dr. Tancer’s MDMA Research
• Dr. Manny Tancer, Dr. Bob Schuster, Wayne
State, Michigan.
• They are conducting a series of MDMA
mechanism of action and safety studies
looking at temperature, receptor sites, coadministration with SSRIs
• NIDA Funded for 5 years.
Dr. Roy Mathew’s
Mescaline Research
• Dr. Roy Mathew, Duke University Medical
School, Durham, North Carolina.
• Using PET to study time perception under
the influence of mescaline (has used THC)
• First FDA-approved study in the US with
mescaline in over 35 years.
Dr. Mithoefer’s
MDMA/PTSD Protocol
• Double-Blind, Placebo-controlled, Pilot
study.
• 20 subjects receive 13-14 hours of non-drug
psychotherapy for preparation and
integration.
• All 20 receive two 6-8 hour therapy sessions,
3-5 weeks apart. 12 receive a dose of 125
Dr. Mithoefer/MAPS MDMA/PTSD
• FDA approves protocol on November 2,
2001. We’re still working on IRB approval.
• This is the first FDA-approved MDMA
therapy protocol since 1985, when MDMA
was criminalized.
MAPS and MDMA Research
• As part of FDA application, MAPS funded
a comprehensive review of virtually the
entire published literature on MDMA, at a
cost of $80,000 over two years. This is
posted on the MAPS website.
• Congress recently passed an Anti-Ecstasy
bill that gives NIDA $1.5 million for an
MDMA literature review.
Dr. Mithoefer’s
MDMA/PTSD Protocol
• Measures
• Standard PTSD outcome instruments
• Neurocognitive evaluations
• Physiological, blood
• Subjects must have failed on one course of
SSRIs (since Zoloft and Paxil are the only
FDA- approved medicines for PTSD).
MAPS and MDMA Research
• MAPS has elaborated a 5-year, $5 million
Clinical Plan designed to develop MDMA
into an FDA-approved prescription
medicine.
• In press, J. of Psychoactive Drugs
Next Protocol
• After MDMA/ PTSD protocol is underway,
MAPS will submit to FDA a protocol to
administer MDMA to hospice patients to
treat anxiety and depression associated with
terminal illness.
• History of LSD research in cancer patients
was quite promising. This Timeless Moment
by Laura Huxley.
NIDA Imagery:
Ideology, not Science
Basis of NIDA Image
•
•
•
•
PET study 14 MDMA users, 15 Controls
Average exposure to MDMA - 228 times
Average dose each time - 386 mgs.
Serotonin uptake sites are reduced in
MDMA users v. controls
• McCann U, Szabo Z, Scheffel U, Dannals R, Ricaurte G.
Positron emission tomographic evidence of toxic effect of
MDMA ("Ecstasy") on brain serotonin neurons in human
beings. Lancet. 1998 Oct 31;352(9138):1433-7.
Scatter Plot of
MDMA and Control Subjects
Is NIDA’s Image
True to the Data?
• A fair comparison : PET scans of the
MDMA and control subjects closest to
mean values.
• Is NIDA’s slide of subjects at or near the
extremes, or at the mean?
• If not the means, the comparison captures
individual variability unrelated to MDMA
Leshner Testimony to Senate Subcommittee
on Government Affairs 7/30/01
Dr. Chang’s SPECT Study
Part 1/ Retrospective
• 21 MDMA users compared to 21 controls
• Mean use of MDMA 211 times, median 75
• Estimated mean total dosage 13.1 grams
• Chang, L. et al., Psychiatry Research:
Neuroimaging, Section 98, pp. 15-28, 2000.
Dr. Chang’s Data
MDMA Users v. Controls
• No significant difference in global or
regional rCBF between 21 MDMA users and
21 controls at baseline.
• “Low dose recreational MDMA uses does
not cause detectable persistent rCBF changes
in humans.”
• Low dose = median 211 exposures, average
lifetime consumption of 13.1 grams!
Dr. Chang’s Study
Part 2 Prospective
• 10 of the 21 MDMA users with baseline
scans in Part 1 were given MDMA 2X in
Dr. Charlie Grob’s Phase 1 study, then given
another SPECT scan.
• 8 scanned 2-3 weeks after dosing
• 2 scanned 2-3 months after dosing
Dr. Chang’s Data
Prospective MDMA Study
• 8 subjects, 2-3 weeks after 2 doses of
MDMA, lower rCBF in several regions.
• 2 subjects, 2-3 months after 2 doses of
MDMA, elevated rCBF in several regions.
• Short term drop, return to baseline, no longterm change in CBF seen in SPECT scans.
MDMA SPECT Scan Shown
on MTV and Oprah
Holes in the Brain
Graphically Manipulated Image
Future Potential
• "Psychedelics,
used responsibly
and with proper
caution, would be
for psychiatry what
the microscope is
for biology and
medicine or the
telescope is for
astronomy."
• Dr. Stan Grof