>> I'M WIN ARIAS
SENIOR SCIENTIST EMERITUS NIH
HUMAN GENOME INSTITUTE WE
WELCOME YOU TO THE 12TH SESSION
IN THE 23RD YEAR OF THE COURSE
AT THE NATIONAL INSTITUTES OF
HEALTH CALLED DEMYSTIFYING
MEDICINE PURPOSE OF COURSE IS
BRIDGING EXCITING DEVELOPMENTS
AND BUY OL AND ENGINEERING WITH
MEDIC
MEDICINE.
INTENT IS ACQUAINTING EVERYONE
WITH DEVELOPMENTS IN A MANNER
THAT ARE NOT INTENSIVE AND ARE
NOT RESEARCH SEMINARS.
BUT, THE GOAL IS TO EXCITE
INDIVIDUALS INTO THE
OPPORTUNITIES PROVIDED AND
PARTICULARLY BASED UPON THESE
EXTRAORDINARY DEVELOPMENTS AND
SOME PROGRAMS HAVE BEEN TO BUILD
BRIDGES BETWEEN MEDICINE AND
PATIENTS AND BIOLOGY AND
ENGINEERING AND WE HAVE ALSO
CONSIDERED BRIDGES INTO SPACE
AND INTO THE MICRO BIOLOGICAL
WORLD AT THE BOTTOM OF THE SEA
AND ORIGIN OF LIFE AND WIDE
VARIETY OF TOPICS AND TODAY'S
TOPIC IS ONE THAT REPRESENTS AN
INCREASING AREA OF INTEREST FOR
THE PUBLIC IN GENERAL.
AND FOR SCIENCE AND MEDICINE IN
PARTICULAR.
SO, AS I HAVE SAID, THE PURPOSE
OF THIS COURSE IS REPRESENTED BY
THE LOGO.
IT IS THE BROOKLYN BRIDGE. ONCE
YOU BUILD A BRIDGE, THINGS ARE
NEVER THE SAME ON EITHER SIDE.
WE ARE LIKE TWO INDIVIDUALS THAT
ARE ON THE CAT WALK THAT ARE
REPRESENTING OUR SPEAKERS WHO
ARE SEEKING TO TEACH US ABOUT
THE BRIDGE THAT IS EXISTING
BETWEEN PSYCHEDELIC SUBSTANCES
AND NEUROSCIENCE AND MEDICINE
AND DISEASE.
BIGGER PURPOSES OF THE COURSE IS
TO CONVERT SILOS OF INFORMATION
THAT ARE INDICATED IN THE LOWER
RIGHT INTO WHAT BRIDGE TO
COMMUNICATE. THE NEXT SLIDE,
PLE
PLEASE.
CME CREDIT PHONE NUMBER TO TEXT
IS 45389 AND PHONE NUMBER IS
443-541-5052. DR. OLSON HAS A
DISCLOSURE STATEMENT THAT
APPEARS AT THE BOTTOM OF THE
SLIDE.
NEXT SLIDE, PLEASE.
SO, PSYCHEDELICS, WHAT IS IN THE
WORD?
IF WE GO BACK IN HISTORY, THERE
ARE MANY LITERARY DESCRIPTIONS
OF MYSTICAL EXPERIENCES AND
RELIGIOUS EXPERIENCES ASSOCIATED
WITH THE INGESTION OF MUSHROOMS
AND OTHER BIOLOGICALLY DERIVED
COMPOUNDS.
THIS WAS THE STATE FOR MANY,
MANY YEARS.
IN FACT, IN TODAY'S WORLD, THE
POPULARITY AND PUBLIC AWARENESS
HAS GREATLY EXCEEDED THE
DEVELOPMENT OF FUNDAMENTAL
UNDERSTANDING AS TO MECHANISMS.
WE CAN ASK WHAT IS THE NEURAL
BASIS OF THE DIFFERENT TYPES OF
PSYCHEDELICS AND OF
HALLUCINA
HALLUCINATIONS.
DO THEY HAVE A THERAPEUTIC
POTENTIAL AND IS THAT POTENTIAL
REALISTIC REALITY FOR
PSYCHEDELICS?
HOW DOES ONE STUDY THIS WHETHER
IT BE HALLUCINATIONS OR
PSYCHEDELIC AFFECTS IN NON-HUMAN
SPECIES?
I GUESS THE BIG QUESTION IS CAN
NEUROPLASTIC EFFECTS OF
PSYCHEDELICS IT THAT WE WILL
HEAR ABOUT TODAY OPEN WINDOWS
FOR THERAPEUTICS AND BASIC
NEUROBIOLOGY AND PERHAPS A
BETTER UNDERSTANDING OF
EVOLUTION AND AGING AND
NEURODEGENERATION.
ARE WE CONFRONTING A BRAVE NEW
WORLD?
WELL, THERE IS A DANG THAT IS
LURKING IN THIS PROCESS.
AND THAT IS DUE TO SOCIAL MEDIA
AND BOOKS AND LOTS OF PUBLICLY
AVAILABLE MAGAZINES AND SO
FORTH.
THEY HAVE MADE PUBLIC AWARENESS
OF PSYCHEDELICS FAR IN ADVANCE
OF THE RAPIDLY CATCHING UP
UNDERSTANDING OF BASIC
MECHANISMS.
THIS PUBLIC AWARENESS AND USE
HAS GREATLY PROCEEDED SCIENTIFIC
STUDY.
SO, TODAY, WE ARE VERY FORTUNATE
TO HAVE TWO LEADERS IN THE
SCIENTIFIC ASPECT OF
PSYCHEDELICS.
THEY WILL DISCUSS THESE
QUESTIONS AND THE STATUS OF
THEIR RESEARCH AND INTERESTS.
NEXT SLIDE, PLEASE.
SO, THE FIRST SPEAKER IS FRED
BARRETT WHO IS A COGNITIVE
NEUROSCIENTIST WHO HAD
UNDERGRADUATE DEGREE AT TEMPLE
UNIVERSITY IN MUSIC THAT WILL
APPEAR IN SOME DISCUSSIONS.
AND RECEIVED HIS PHD AT THE
UNIVERSITY OF CALIFORNIA, DAVIS
AND DID FURTHER TRAINING AT
JOHNS HOPKINS AND BEHAVIORAL
PHARMACOLOGY AND FRED IS
ASSOCIATE PROFESSOR OF
PSYCHIATRY AND BEHAVIORAL
SCIENCES AT JOHNS HOPKINS CENTER
FOR PSYCHEDELIC CONSCIOUSNESS
AND RESEARCH AND RESEARCH
CONCERNING NEURAL BASIS OF
EMOTION AND ALTERED CONNESS THAT
IS RELATIVE TO MUSIC AND
FORMCOLOGICAL INFORMATION AND
COMPUTERIZED TESTING AND BRAIN
IMAGING AND FOR YEARS
COLLABORATED WITH ROLAND
GRIFFITH FOUNDER FOR PSYCHEDELIC
CONSCIOUSNESS AT HOPKINS.
SECOND SPEAKER, NEXT SLIDE,
PLEASE. IS DAVID OLSON WHO
GRADUATED FROM UNION COLLEGE AND
RECEIVED HIS PHD IN NEUROBIOLOGY
AND CHEMISTRY AT STANFORD
UNIVERSITY AND DID A POST
DOCTORAL FELLOWSHIP AT BROAD
INSTITUTE AT MIT IN CAMBRIDGE
AND IS ASSOCIATE PROFESSOR OF
CHEMISTRY, BIOCHEMISTRY AND
MOLECULAR MEDICINE AND DIRECTOR
OF INSTITUTE FOR PSYCHEDELICS
AND NEUROTHERAPEUTICS AT
UNIVERSITY OF CALIFORNIA, DAVIS.
DAVID'S RESEARCH IS VERY
REDUCTIONIST.
HE IS CONCERNED WITH REGULATION
OF NEURAL PLASTICITY AND
LEARNING AND MEMORY AND AS
PRODUCED BY SMALL MOLECULES SOME
OF WHICH ARE ANALOGUES AND
DERIVATIVES OF PSYCHEDELIC
COMPOUNDS EXISTING IN NATURE AND
LAB USES A VARIETY OF TECHNIQUES
FROM CHEMICAL BUY OJ TO
SYNTHETIC CHEMISTRY AND
MOLECULAR NEURAL BUY OL AND
BEHAVIORAL NEURAL FARM COLAND WE
WELCOME BOTH OF YOU AND
APPRECIATE YOUR VERY MUCH
SPENDING THIS TIME WITH US AND
PERHAPS, FRED, IF YOU WOULD,
PLEASE BEGIN.
>>THANK YOU VERY MUCH, DR.
ARIAS FOR YOUR GENTLE AND
WONDERFUL INTRODUCTION.
TODAY WE WILL TALK ABOUT
DEMYSTIFYING MUSHROOMS. IT IS
AN HONOR TO BE HERE TO SHARE A
SMALL SLICE OF THE FIELDS AND
GROWING FIELD WITH YOU ALL.
I SHOULD DISCLOSE I'M A
SCIENTIFIC ADVISOR FOR MIND LABS
AND CONSULTED WITH
PHARMACEUTICALS AND LIFE
SCIENCES AND NOTHING IN MY
PRESENTATION WILL INVOLVE
ANYTHING THAT I HAVE CONSULTED
WITH THEM FOR.
I WOULD LIKE TO START WITH A
QUESTION. WHAT ARE PSYCHEDELIC
DRUGS?
LOOKING IN DICTIONARY YOU WILL
FIND A DEFINITION INCLUDING
PHRASES AND IDEA SUCH AS SENSORY
PERCEPTION AND SENSORY
DISTORTION AND HALLUCINATIONS --
AND THOSE THAT EXPERIENCE THESE
DRUGS IT IS NOT NECESSARILY THE
CASE IN ANY OF THESE THINGS THAT
DOESN'T REALLY KIND OF DO
JUSTICE TO WORD PSYCHEDELIC
ITSELF AS IT IS ORIGINALLY
INTENDED AND PSYCHEDELIC IS
COINED BY HUMPHREY OS-MONDAY A
BRITISH SCIENTIST EX PATRIOT IN
CANADA AND FIRST INDIVIDUAL TO
ADMINISTER PSYCHEDELIC AND HE
TOOK THEM AND OTHER COMPOUNDS
BECAUSE HE WANTED TO UNDERSTAND
HOW COMPOUNDS WORKED AND WHAT
THEY DID AND THOUGHT BY DOING SO
HE MIGHT BETTER UNDERSTAND HOW
THESE COMPOUNDS COULD BE
THERAPEUTIC IF AT ALL. HE WENT
ON TO ADMINISTER LSD TO
THOUSANDS OF PATIENTS IN HIS
CLINIC AT THE TIME FOR WHAT WAS
CALLED ALCOHOLISM AND CLAIMED
THAT OVER 40% OF HIS PATIENTS
ACROSS THE YEARS REMAINED
ABSTINENT FOR AT LEAST A YEAR
AFTER TREATMENT WITH LSD THAT IS
A REMARKABLE OUTCOME FOR THAT
TIME AND WOULD STILL BE A
REMARKABLE OUTCOME TODAY AND
GAVE LSD TO -- RATHER MESCALIN
TO ALBUS HUXLEY WHO IS FAMOUS
AUTHOR PENNING DOORS TO
PERCEPTION THAT IS CLASSIC TEXT
IN MIND OF PHILOSOPHY IN MIND AS
IT RELATES TO PSYCHEDELICS.
HUMPHREY OS-MONDAY THOUGHT THAT
COMPOUNDS MANIFESTED SOME SENSE
OF MIND THAT INDIVIDUAL WASN'T
AWARE OF OR DIDN'T HAVE ACCESS
TO COURSE OF NORMAL WAKING
CONSCIOUSNESS AND COINED PSYCHE
AND DELOS AND PSYCHEDELICS
MANIFESTED ASPECTS IN MIND AND
MEDICINE THAT IS MIND
MANIFESTING PROPERTY THAT IS
ESSENTIAL TO THERAPEUTIC
EFFICACY OR POTENTIAL OF
PSYCHEDELIC DRUGS AND TAKEN AT
BROADEST DEFINITION OF SOMETHING
MANIFESTING MIND OF COFFEE I'M
DRINKING THAT IS MIND
MANIFESTING AND IN A SENSE
HUMPHREY OSMOND DIDN'T MEAN THAT
AND THERE IS A WIDE RANGE OF
COMPOUNDS BY SOME AT LEAST ARE
CALL OR CLAIMED TO BE
PSYCHEDELIC INCLUDING NOT ONLY
PSILOCYBINO OR MESCALINE OR
SYNTHETIC DRUGS LIKE WILL. SD
AND MORE EXOTIC COMPOUNDS LIKE
SALVINORIN AND MDMA AND THC IS
CALLED PSYCHEDELIC BY SOME AND
COMPOUNDS SPAN A WIDE AND
DIVERSE RANGE OF FARM COLONL CAL
CLASSES WITH VERY DISPARATE
MOLECULAR TARGETS IN THE BRAIN
AND LIABILITY USE CASES AND
OTHER THINGS POINTING THIS OUT
THAT NOT EVERYTHING IS THE SAME
AND THESE ARE NOT OR ARE VERY
DIFFERENT DRUGS AND WANT TO
BRING YOUR ATTENTION TO THAT AND
TALKING ABOUT PSYCHEDELIC DRUGS
I'M TALKING ABOUT CLASSIC
PSYCHEDELICS THAT I WILL SHARE
IN A FORM OR ANOTHER PROPERTY OF
BEING AGONIST OR PARTIAL AGONIST
OF CERTIFY TONIM A RECEPTOR IN
THE BRAIN MODULAR SYMPTOM IN
BRAIN AND WE WILL FOCUS ON SILO
KRIEB BIN FOR REST OF MY TALK
WITH MENTIONS TO LSD -- PLANT
SOURCES AND OTHERWISE USED FOR
RELIGIOUS AND SPIRITUAL PURPOSES
IF NOT OTHER PURPOSES AND
SPECULATION OF CEREMONIAL USE OF
SIMILAR PSYCHOACTIVE COMPOUNDS
FOR THOUSANDS OF YEARS AND
EVIDENCE IS REALLY CALLED INTO
QUESTION WHAT YOU SEE ON THE
RIGHT IS A PHOTO OF A CAVE
DRAWING FOUND IN ALGERIA THAT
APPEARS TO BE SHAWMAN KOVRED IN
MUSHROOMS AND EVIDENCE IN CAVE
DRAWN MANY THOUSANDS OF YEARS
OLD AND OTHER ARCHAEOLOGICAL
FINDS THAT IS NOTABLE THAT
MUSHROOMS OF [INDISCERNIBLE]
GENERALUS AND MUSHROOMS IN IT
AND RELATED -- THEY ARE FOUND ON
ALL CONTINENTS AND CEREMONIALLY
SOOILO KRIEB BIN CONTAINING
MUSHROOMS HAVE CONTRACTED MORE
CONCRETELY IN 15TH CENTURY BY
INDIGENOUS PEOPLE IPEOPLE IN ME
LSD ITSELF IS FIRST SYNTHESIZED
BY ALBERT HOFFMAN IN 1938 AND
NOT UNTIL 1943 THAT HE
SERENDIPITOUSLY OR ACCIDENTALLY
DISCOVERED EFFECTS OF LSD BY
ACCIDENTALLY DOSING HIMSELF AS
STORY GOES AND NOT LONG AFTER
THAT LABORATORIES THAT ALBERT
HOFFMAN WORKED BEGAN TO MAKE LSD
AND CLINICS AROUND THE WORLD AND
50S AND INTO THE 60S SAW A GREAT
PROLIFERATION OF LSD AND SOME
RELATED COMPOUNDS THAT ARE IN A
VARIETY OF CLINICAL SETTINGS AND
RESEARCH SETTINGS AND CLAN
DEFENDANTINED USE BY
INTELLIGENCE AGENCIES AND 1957 A
RETIRED BANKER AND AMATEUR MICRO
ANTHROPOLOGIST GOREDON WENT TO
SEARCH FOR WHAT IS THE MAGIC
MUSHROOM AND FOUND MARY SABINA A
MUSHROOM IN WA HACKA AND BROUGHT
THAT INFORMATION BACK TO THE
WESTERN WORLD AND EXPERIENCE IS
PUBLISHED IN LIFE MAGAZINE IN
1957 AND MAY HAVE BEEN ONE OF
THE FIRST TIME POINTS THAT
PSYCHEDELICS ARE BROUGHT TO
WESTERN CONSCIOUSNESS WRIT LARGE
AND TURNS OUT TENS OF THOUSANDS
OF RESEARCH SUBJECTS ARE
ADMINISTERED PSYCHEDELICS IN LSD
IN 1950S AND CONTROLLED
SUBSTANCES ACT OF 1971 AND
PRECLINICAL RESEARCH ON
SEROTONIN 2A RECEPTORS AND
PSYCHEDELIC DRUGS AND NUMBER OF
PRECLINICAL RESEARCHERS
CONTINUING PROGRAMS OF RESEARCH
STUDYING CONTINUED EFFECTS OF
PSYCHEDELICS ON THE BRAIN SUCH
AS MIKE AND A NUMBER OF OTHER
FOLKS.
THERE WAS A STUDY IN 1994 BY
RICK STATSMAN AT UNIVERSITY OF
MEXICO STUDYING EFFECTS OF DMT
DIMETHIL TRIPTO MEAN THAT IS A
COMPOUND WITH -- EFFECTS OF
THOSE THAT ARE HEAVY PSYCHEDELIC
USERS AND A FEW STUDIES
INVESTIGATED PSYCHEDELIC MODELS
OF PSYCHOSIS IN EUROPE AND
MOSTLY BY FRANZ AND BY
[INDISCERNIBLE] AND WASN'T UNTIL
THIS STUDY WAS PUBLISHED IN 2006
BY MY MENTOR ROLAND GRIFFITHS
THAT THIS AREA TOOK FLIGHT AGAIN
AND IS A STUDY IN A NUMBER OF
OTHERWISE HEALTHY AND
FUNCTIONING WELL EDUCATED AND
HIGH CS INDIVIDUALS WITH SILO
KRIEBIN ADMINISTRATED IN THE
REPORT AND FOLLOW UP STUDIES ARE
NOT ONLY EXPERIENCES THAT ARE
WELL TOLERATED BY PARTICIPANTS
AND OTHERWISE KIND OF A
COMPLETELY MEDICALLY MANAGEABLE
THAT WAS PSYCHOLOGICALLY
MANAGEABLE AND THESE EXPERIENCES
LED TO ENDURING IMPROVEMENTS
THAT ARE IN WELLBEING IN THESE
INDIVIDU
INDIVIDUALS.
I WANT TO TAKE A MINUTE TO POINT
OUT THAT COMPOUNDS ARE
ABSOLUTELY NOT WITHOUT RISK.
THEIR RISK PROFILE NEEDS SPECIAL
ATTENTION AND SCHEDULING
COMPOUNDS THAT ARE AS FAR AS DEA
IS CONCERNED THAT MEANS THEY
HAVE NO KNOWN MEDICAL VALUE AND
ARE HIGHLY DANGEROUS AND/OR HAVE
GREAT RISK OF USE LIABILITY AND
COMPOUNDS HAVE VERY LITTLE
SIMILARITY TO TYPICAL DRUGS AND
ABUSE ON MANY ANIMAL ASSAYS OF
ABUSE LIABILITY AND THESE DRUGS
BY AND LARGE DON'T REALLY PUSH
THE NEEDLE AND DON'T TYPICALLY
ENGENDER A CRAVING OR WITHDRAWAL
SYMPTOM TYPICAL TO DRUG ABUSE
AND THEY ARE POWERFUL DRUGS WITH
SPECIFIC AND KNOWN RISKS AND ARE
EXPECTED TO RELIABLY AND
DOSE-DEPENDENTLY INCREASE HEART
RATE AND BLOOD PRESSURE
PRESENTING A PARTICULAR RISK FOR
PEOPLE WITH A PERSON OR FAMILY
HISTORY OF PSYCHOSIS AND IN
UNCONTROLLED SETTINGS THESE CAN
BE RISKY DRUGS TO ENCOUNTER AND
CONDUCTED A STUDY OF PEOPLE WHO
REPORTED HAVING HAD A BAD TRIP
OR CHALLENGING EXPERIENCE WITH
SPECIFICALLY SILO KRIEBIN THAT
CONTAINED MUSHROOMS DON'T KNOW
RATES OF BAD TRIPS IN THE WORLD
AND POPULATION FROM THIS STUDY
AND KNOW THAT THOSE REPORTING
HAVING A BAD TRIP THAT 11% PUT
THEMSELVES AT RISK OF PHYSICAL
HARM OVER 7% SAID THEY SOUGHT
TREATMENT FOR ENDURING
PSYCHOLOGICAL SYMPTOMS THAT
DEVELOP AS A WAY TO ATTRIBUTE TO
A BAD TRIP AND NEARLY 3% SOUGHT
AND RECEIVED MEDICAL HELP AND
GOING TO EMERGENCY DEPARTMENT TO
COPE WITH ACUTE EFFECTS OF SILO
KRIEBIN MUSHROOMS AND ARE REAL
RISKS THAT PEOPLE CAN INCREDIBLY
PSYCHOLOGICALLY VULNERABLE
EXPERIENCING DRUGS WITHOUT
PROPER SUPERVISION CAN DO THINGS
TO PUT OTHERS AT RISK OR HARM
AND ARE REASONS THAT WE HAVE
DEVELOPED AND MAINTAINED BEST
PRACTICES FOR ADMINISTRATION OF
COMPOUNDS AND WE ESSENTIALLY ARE
CAREFUL TO SCREEN OUT
INDIVIDUALS WITH CARDIOVASCULAR
RISK WHO WANT TO SCREEN OUT
CLINICAL TRIALS FOR RISKS OF
PSYCHOSIS AND SOME MEDICATIONS
SPECIFICALLY FOR SILO KRIEBIN
AND NOT NECESSARILY A MEDICAL
RISK AND INTERACTING WITH
COMPOUNDS TO MODULATETO MODULAT
AFTER CAREFULLY SCREENING
INDIVIDUALS THEY GO THROUGH
ANOTHER ROUND OF CAREFUL
PREPARATION WITH TYPICALLY ABOUT
6 TO 8 HOURS OF MEETINGS WITH
TWO TRAINED THERAPISTS OR
FACILITATORS WHO ARE TRAINED TO
HELP PEOPLE WITH EXPERIENCES AND
MONITOR PROVIDING CARE FOR
EXPERIENCES AND DURING
PREPARATION PERIOD BIG GOAL OF
PREPARATION IS TO ESSENTIALLY
BUILD TRUST AND REPOIRE BETWEEN
THE STUDY TEAM AND THOSE
PARTICULAR FACILITATORS AND
PARTICIPANT AND IS THOUGHT THAT
TRUST AND REPOIRE THAT IS
DEVELOPED BEFORE DRUG
ADMINISTRATION GOES A LONG WAY
TO HELPING PEOPLE FEEL SAFE AND
COMFORTABLE AND SUPPORTED DURING
EXPERIENCES TO NAVIGATE THEM IF
THEY BECOME CHALLENGING AND IF
STUDY IS BEING CONDUCTED FOR
THERAPEUTIC PURPOSE THIS IS A
TIME THAT UNSTRUCTURED
[INDISCERNIBLE] IS DELIVERED
TYPICALLY AND MOVING TO DRUG
ADMINISTRATION SETTING THAT
LASTS 6 TO 8 HOURS ASKING PEOPLE
TO COME EVERY MORNING HAVING
EATEN LOW FAT AND LOCALE ORREE
BREAKFAST TESTING PARTICIPANTS
TO MAKE SURE THEY DON'T HAVE
MISUSED DRUGS RECENTLY AND FOR
WOMEN WE MAKE SURE TO TEST FOR
PREGNANCY AND AFTER TESTS ARE
CLEARED WE ADMINISTER A CAPSULE
WITH WATER AND ASK PARTICIPANT
TO LIE DOWN ON A COMFORTABLE
COUCH AND ENVIRONMENT WITH
SHADES AND IPHONE WITH PROGRAM
OF MOSTLY WESTERN ART AND TUCK
THEM IN WITH A BLANKET AND
TURNING ATTENTION INWARD AND
BEING PRESENT FOR WHATEVER
ARISES IN CONSCIOUSNESS THAT IS
NOT A GUIDED MEDITATION OR
IMAGERY SESSION OR SESSION WHERE
ACTIVE PSYCHOTHERAPY OCCURS.
IT IS A SESSION WHERE TWO
FACILITATORS AND MONITORS ARE
THERE TO PERIODICALLY MONITOR
PARTICIPANTS HEARTRATE AND BLOOD
PRESSURE AND VITAL SIGNS
FIENTDING THEMSELVES IN
STRESSFUL SITUATIONS WE TALK
THEM THROUGH THAT AND AFTER THAT
EXPERIENCE PARTICIPANTS WHEN
CLARED FOR DISCHARGE WILL GO
HOME AND COMPANY OF LOVED ONE OR
TRUSTED FRIEND AND WILL COME
BACK NEXT DAY TO SIT AND RECOUNT
THEIR EXPERIENCES THEY REMEMBER
IT WITH A STUDY TEAM AND FROM
THAT POINT AFTER CARE
INTEGRATION SESSIONS AND
ESSENTIALLY MORE UNSTRUCTURED
COUNSELING OCCUR FOR DAYS TO
WEEKS AND SOMETIMES MONTHS FOR
POPULATION AND IS PACKAGE WHAT
WE MEAN WHEN WE SAY PSYCHEDELIC
THERAPY OR PSYCHEDELIC ASSISTIVE
THERAPY THAT IS CONTEXT WHICH
EVERYTHING ELSE I WILL TALK
ABOUT OCCURS. IT IS IMPORTANT
TO NOTE THAT ONE OF THE MOST
REMARKABLE EXPERIENCES DURING
THE -- DURING THE EXPERIENCE OF
A HIGH DOSE OF A PSYCHEDELIC
DRUG OR THERAPEUTIC DOSE IS
DIFFICULT TO CAPTURE AND
DIFFICULT TO DESCRIBE.
SOME HAVE CALLED EGO DISSOLUTION
AND OTHERS BROADLY PEEKED
EXPERIENCE AND OPERATIONALIZE
THIS EXPERIENCE AS A MYSTICAL
EXPERIENCE AND MYSTICAL
EXPERIENCE I WILL BE FIRST TO
ADMIT MIGHT BE A FAILURE IN
MARKETING AND SOME THINK IS MIST
THAT CAN'T BE CAPTURED OR
GRABBED THAT IS UNDESCRIBABLE
AND WE WILL GET TO IN A MINUTE
AND OTHERS THINK IT HAS
RELIGIOUS CONNOTATION AND IS IT
MYSTICAL AND SOMETHING THAT ONLY
A FEW CAN ATTAIN AND MYSTICAL
EXPERIENCES MEAN IN
OPERATIONALIZE THE FASHION ARE
EXPERIENCES PUNCTUATED BY
BREAKDOWN OF FELT BOUNDARY
BETWEEN SELF AND OTHER PEOPLE
EXPLAIN AS FEELING OF UNITY WITH
SELF AND SURROUNDINGS AND PEOPLE
IN ROOM AND WITH UNIVERSE AND
FEELING ONE HAVING A BREAKDOWN
OF BOUNDARY AND SELF AND OTHER
AND IS THIS MYSTICAL EXPERIENCE
THAT IS OPERATIONALIZED AND IS A
FEELING OF UNITY AND
TRANSCENDENCE OF TIME AND SPACE
AND WHERE CONCEPTS OF IT BEGIN
TO NO THE HAVE MEANING AFTER
SOME PERIOD OF TIME AND DEEPLY
POSITIVE MOOD AND LAST BUT NOT
LEAST DISTINCT DIFFICULTY IN
TRULY REFLECTING EXPERIENCE AND
WORDS.
WE ASK PEOPLE AT END OF EACH
EXPERIENCE TO FILL OUT A
QUESTIONNAIRE PROBING DIMENSIONS
IN SYSTEMATIC FASHION THAT FROM
THAT WE CAN DERIVE A SCALE SCORE
AND PERCENTAGE OF TOTAL POSSIBLE
SCORE OF MYSTICAL EXPERIENCE.
WE HAVE A FIGURE THAT SUMMARIZES
FINDINGS OF RELATIONSHIP BETWEEN
DOSE OF PSILOCYBIN AND SCORES ON
MYSTICAL EXPERIENCE
QUESTIONNAIRE AND DOSE EFFECT
STUDY OF 18 PARTICIPANTS AND
SUMMARY ACROSS 30 MILLIGRAM
ACROSS THREE STUDIES AND SEE
MYSTICAL EXPERIENCE THAT IS DOSE
DEPENDENT AND FOLLOWS ORDERLY
FASHION IN THAT OF HIGHER DOSE
OF SILO KRIEBIN LEADS TO GREATER
CHANCE OF MYSTICAL EXPERIENCE
AND STRONGER MYSTICAL EXPERIENCE
AND MOST RELIABLY EVOKES
MYSTICAL EXPERIENCE THAT USUALLY
MINIMIZES LIKELIHOOD OF
CHALLENGING EXPERIENCE OR
NEGATIVE EFFECTIVE EXPERIENCES
THAT TURNS OUT THAT MYSTICAL
EXPERIENCES ARE NOT ONLY DOSE
DEPENDENT BUT ALSO PREDICT RATED
MEANINGFULNESS AND SPIRITUAL
EXPERIENCE OF EXPERIENCE THAT
PEOPLE HAD AND REMARKABLE THINGS
THAT CAME OUT OF ROLAND'S FIRST
PAPER OF PSILOCYBIN IN 2006 IS
THAT INDIVIDUALS IN STUDY WERE
ENDORSING EXPERIENCES THEY HAD
WITH SILO KRIEBIN AMONG TOP 5
THAT ARE MEANINGFUL SPIRITUAL
SIGNIFICANTS OF THEIR LIES THAT
IS REMARKABLE YOU MIGHT IMAGINE
SOMEONE SAYING I PASSED BAR AND
GOT APPOINTED AS A FEDERAL JUDGE
OR WHOEVER AND I BECAME A DOCTOR
AND I'M THE CHIEF OF MEDICINE AT
SOME ILUFT TREE OWE US
UNIVERSITY AND I HAD AN
EXPERIENCE ON A COUCH IN EAST
BALTIMORE. THAT IS -- THOSE ARE
-- THAT IS UP THERE AMONG TOP 5
MOST SINGLE MEANINGFUL
EXPERIENCE OF MY LIFE AND THOSE
REMARKABLE EFFECTS SEEMED TO
LEAD TO OTHER REMARKABLE EFFECTS
AND WHAT WE FOUND WAS -- WHAT
ROLAND FOUND WAS IN THE VERY
FIRST SERIES OF STUDIES IS THAT
THESE EFFECTS PERSIST WITH THE
ATTRIBUTION OF THAT EXPERIENCE
PERSISTENT FOR SOME PEOPLE AT
LEAST 14 MONTHS AFTER THE
EXPERIENCE AND NOT ONLY THOSE I
SAY WHAT DO YOU THINK ONCE YOU
GET BACK TO REAL LIFE GETTING
CAUGHT IN TRAFFIC PAYING YOUR
TAXES WHAT DO YOU THINK
HAPPENED? THESE ATTRIBUTIONS
PERSIST AND PEOPLE ENDORSE AN
INCREASE IN WELL-BEING AND LIFE
SATISFACTION AND LESS ANXIETY
ABOUT THE FUTURE AND ABOUT THE
PRESENT AND PROSOCIAL ATTITUDES
AND THESE ENDORSEMENTS ARE NOT
ONLY MADE BY PARTICIPANTS BUT BY
BLINDED INDIVIDUALS IN THE
ENVIRONMENT THAT ARE NOT PART OF
THE STUDY BUT WERE PROBED WEEKS
TO MONTHS OVER A YEAR LATER AND
IN THIS EXPERIENCE SALLY WAS
MORE PROSOCIAL AND SALLY HAD
ANXIETY THAT WAS ESSENTIALLY
CONFIRMED AND VALIDATED BY
COMMUNITY COHORTS AND ANOTHER
REMARKABLE EFFECT OF THESE
COMPOUNDS IS POTENTIAL FOR
THERAPEUTIC EFFECTS IN VAR EYETY
OF CLINICAL POPULATIONS AND ONE
OF THE FIRST CLINICAL STUDIES
PUBLISHED IN MODERN ERA AND ONE
FIRST REALLY RIGOROUS RANDOMIZE
THE CONTROL LEVELS WAS IN LAB IN
HOPKINS AND WE HAD PATIENTS WITH
LATE STAGE CANCER DIAGNOSIS AND
IF YOU EVER HAD A LOVED ONE OR
KNOWN SOMEONE WHO HAS HAD TO
GRAPPLE WITH LATE STAGE CANCER
DIAGNOSIS AND EXISTENTIAL CRISIS
THAT COMPANY COULD BE OF THE
MOST CHALLENGING ASPECTS OF
DIAGNOSIS TO DEAL WITH AND TREAT
ASIDE FROM ACTUAL CANCER AND IN
STUDY PATIENTS WERE RANDOMIZED
TO RECEIVE A TRIVIAL DOSE OF
PSILOCYBIN FIRST OR HIGH DOSE OF
IT FIRST AND SECOND TREATMENT
TIME POINT EVERY WAS CROSSED OWE
EVERY TO TREATMENT THEY DIDN'T
RECEIVE ON FIRST DOSE AND SEE
AFTER THE FIRST SESSION THAT A
REMARKABLE CLINICALLY
SIGNIFICANT RESPONSE IN THOSE
PATIENTS CLINICALLY SIGNIFICANT
RESPONSE REDUCTION IN SEVERITY
OF 50% MORE OF BASELINE AND
INDIVIDUALS IN THAT STUDY
SHOWING CLINICAL RESPONSE AND
60% OF INDIVIDUALS AFTER VERY
FIRST HIGH DOSE OF PSILOCYBIN
THAT WERE IN REMISSION FROM
DEPRESSION AFTER DOSE OF SILO
KRIEBIN AND FINDINGS REMAINED AT
LEAST 6 MONTHS AFTER TREATMENT
AND WAS A STUDY CONDUCTED IN
PATIENTS WITH LATE-STAGE CANCER
DIAGNOSIS AND CONDUCTED FIRST
RIGOROUS CONTROL TRIAL WITH
PATIENTS WITH MAJOR DEPRESSIVE
DISORDER TREATED WITH SILO
KRIEBIN AND FOUND NOT ONLY A
SIMILAR LEVEL OR SOMEWHAT
SIMILAR LEVEL OF EFFICACY AND
OVER 50% OF PEOPLE IN THAT STUDY
FOR MAJOR DEPRESSIVE DISORDER
WERE IN REMISSION AT LEAST A
YEAR AFTER SILO KRIEBIN
TREATMENT AND 70% OF INDIVIDUALS
TREATED FOR MAJOR DEPRESSIVE
DISORDER SHOWED CLINICALLY
SIGNIFICANT RESPONSE AND GRAPH
TO RIGHT SHOWS BASELINE
PRE-TREATMENT GRID MD SCORES OR
BLINDED CLINICIAN RATED HAM
ILLTON DEPRESSION RATING SCALE
SCORES AND ABOVE 8 TA INIS
MODERATELY TO SEVERELY DEPRESSED
AND BELOW 8 IS CONSIDERED IN
REMISSION AND FOO IND THAT AT
LEAST ONE WEEK BUT LASTING FOR
AT LEAST 12 MONTHS AFTER
TREATMENT PATIENTS IN STUDY SHOW
REMARKABLE AND DURING DURABLE
RESPONSE, THERAPEUTIC RESPONSE
FOLLOWED UP BY A STUDY AND
COLLEAGUES AT IMPERIAL COLLEGE
IN LONDON WITH HEAD TO HEAD
COMPARISON COMPARED TO 6 WEEKS
OF STANDARD OF CARE FIRST LINE
FOR TREATMENT OF DEPRESSION OF
SSRI AS TELEPRAM AND THEY
DEMONSTRATED NOT ONLY WHAT I
WOULD INTERPRET AS
NONINFERIORITY FINDING IN STUDY
OF PSILOCYBIN BEING NOT ONLY
INFERIOR 42 DAYS AFTER TREATMENT
AND IS RATINGS ON QUICK
INVENTORY OF DEPRESSIVE SYMPTOMS
SELF RATED DEPRESSION RATING
SCALE IN THIS STUDY EVERYBODY
RECEIVED 42 DAYS OF DAILY PILL.
EVERYBODY RECEIVED AN
EXPERIMENTAL DRUG ADMINISTRATION
SESSION IN PSYCHOACTIVE THERAPY
AND HALF PARTICIPANTS WERE
RANDOMIZED TO RECEIVE SILO
KRIEBIN AND OTHER HALF OF THE
INDIVIDUALS IN THE STUDY WERE
RANDOMIZED TO RECEIVE PLACEBO
DURING EXPERIMENTAL DRUG
ADMINISTRATIONS AND TALI PRAM
DAILY FOR 42 DAYS AND ON THIS
QUICK INVENTORY OF DEPRESSIVE
SYMPTOMS WAS PRE-REGISTERED
PRIMARY OUTCOME AND IN THAT
OUTCOME THERE IS NO SIGNIFICANT
DITCHES AT 42 DAYS BETWEEN
PSILOCYBIN YUP AND MEASURES
EQUAL AND FAVORABLE ABOVE SILO
KRI
KRIEBIN AVOIDANCE AND HEADONIA
FLOURISHING AND ANXIETY WELL
BEING ARE REMARKABLE EFFECTS.
ANOTHER STUDY TO NOTE THAT
RECENTLY CAME OUT WAS
ESSENTIALLY RESULTS OF
MULTINATIONAL PHASE 2B
REGISTRATION TRIAL IN WHICH OVER
75 PEOPLE WERE RANDOMIZED INTO
EACH GROUP AND ONE MILLIDOSE OF
-- 10 MILLIGRAM DOSE OR 25
MILLIGRAM DOSE AND WE HAVE ON
LEFT SIDE SQUARES AND MEAN
CHANGE IN SCORES ON THE
MONTGOMERY A** BERGER DEPRESSION
RATING SCALE AND WHAT WE
ESSENTIALLY SEE IS A RAPID
REDUCTION IN RESPONSE THAT
SOMEWHAT NORMALIZES AT SLIGHTLY
HIGHER LEVELS OF DEPRESSION AND
SEVERITY FROM DAY TO WEEK 12 AND
SEE AT WEEK 12 A SUBSTANTIAL
REDUCTION IN DEPRESSION FOR 25
MILLIGRAM SILO KRIEB BIN GROUP
AND TREATMENT RESISTANT
DEPRESSION THAT ARE DIFFICULT TO
REACH WITH ANY OUTCOME AND ANY
INTERVENTION A FACT THAT THEY
SHOWED A 12 WEEK DURABLE
RESPONSE IN THIS POPULATION THAT
WAS REMARKABLE.
I HAVE SPOKEN ONLY ABOUT MOOD
DISORDERS AND SUBSTANCE USE
DISORDERS AND TREATING THOUSANDS
OF PATIENTS FOR ALCOHOL USE
DISORDER WITH LSD AND WAS A
PAPER PUBLISHED ABOUT I 2012 AND
SCOUR PREVIOUS LITERATURE AND
WERE HUNDREDS OF THOUSANDS OF
STUDIES PUBLISHED WITH A FORM OF
PSYCHEDELIC IN 50S AND 60S AND
VAST MANL ORTD WOULDN'T MEET
MODERN CRITERIA KREBS AND
JOHANNSON IDENTIFIED 6 STUDIES
OUT OF TIME PERIOD THEY HAD
DEFENSIBLE RIGOR AND WHICH LSD
WAS COMPARED WITH TREATMENT OF
PATIENTS WITH ALSO USE DISORDER
AND FINDINGS WITH OVERALL
FAVORABLE EFFECT OF LSD OVER
VARIETY OF CONTROLS SOME OF
WHICH ARE PLACEBO AND SOME ARE
ACTIVE COMPARATIVE DRUGS THAT
ARE PSYCHOACTIVE BUT ARE NOT
PSYCHEDELIC AND SPURRED INTEREST
AND WAS A SIMILAR IMPRESSIVE
STUDY IN THE 70S WITH TREAT
TREATINGENTS PATIENTS WITH --
2014 PUBLISHED OPEN LABEL PILOT
STUDY THAT IS DEMONSTRATING THAT
AFTER 2 TO 3 ADMINISTRATIONS OF
PSILOCYBIN IMBEDDED WITH COURSE
OF COGNITIVE BEHAVIORAL THERAPY
WITH SMOKING CESSATION THAT OVER
80% OF INDIVIDUALS IN TRIAL WERE
BIOLOGICALLY VERIFIED ABSTINNANT
NICOTINE FOR 6 MONTHS AND LONG
TERM FOLLOW UP AND FOUND ONE
MORE INDIVIDUAL LAPSED OAF A
YEAR AND A HALF AFTERWARDS THAT
ARE REMARKABLE EFFECTS WITH
POTENTIALLY COMPARED TO GOLD
STANDARD THAT COULD BE
CONSIDERED [INDISCERNIBLE] AND 6
MONTHS POST TREATMENT YOU SP
EXPECT 30 TO 40% EFFICACY AFTER
TREATMENT AND DR. JOHNSON AND
DR. GARCIA REMOVED FOLLOWING UP
WITH RANDOMIZED CONTROL TRIAL
NOT YET PUBLISHED AND STAY TUNED
AND ABOUT SOMEWHAT THE SAME TIME
A COLLEAGUE AT NEW YORK
UNIVERSITY MICHAEL PUBLISHED
OPEN LABEL CLINICAL TRIAL IN
PATIENTS WITH ALCOHOL USE
DISORDER AND FOLLOWED UP WITH
RANDOMIZE THE CONTROL TRIAL AND
FOLLOWING UP WITH EFFECTS OF
[INDISCERNIBLE] ACTIVE
CONCOMPOUND AND SHOWED SIMILAR
REMARKABLE REDUCTION AND
VARIABLES RELATED TO ALCOHOL USE
DISORDER AND PLOTTED REDUCTIONS
AND DRINKS PER DAY THROUGH
SCREENING ALL THE WAY THROUGH 36
WEEKS PUSH TREATMENT AND WHERE
ARROWS ARE ARE PSILOCYBIN
ADMINISTRATION DAYS AND SAW
REMARKABLE AND DURABLE REDUCTION
IN DRINKS PER DAY AND SAW
SIMILAR EFFECTS IN HEAVY
DRINKING DAYS AND PERCENT
DRINKING DAYS.
I WANT TO REMIND YOU OF THAT
MYSTICAL EXPERIENCE AND QUESTION
COMING INTO THERAPEUTIC EFFECTS
IS, WELL, OKAY. INTERESTING AND
PUZZLING HOW ONE SINGLE
INTERVENTION WOULD LEAD A PERSON
HAVING TREATMENT RESISTANT
DEPRESSION TO HAVE A DURABLE
SPONLSZ OR PATIENT WITH MAJOR
DEPRESSIVE DISORDER AND SMOKING
A PACK OF 10 -- WHEN COMPARING
MEASURES OF THERAPEUTIC EFFICACY
TO MEASURES OF MYSTICAL
EXPERIENCE WE SEE A RELIABLE
RELATIONSHIP HERE.
THESE ARE GRAPHS FROM THE
INITIAL STUDY IN CANCER PATIENTS
PUBLISHED BY LAB IN 2016 AND WE
SHOW A SIGNIFICANT CORRELATION
IN STRENGTH OF MYSTICAL
EXPERIENCE WITH REDUCTION IN
DEPRESSION AND REDUCTION IN
ANXIETY AND SIMILAR STUDY
PUBLISHED ABOUT THE SAME TIME BY
STEVEN ROSS AT NYU SHOWING
SIMILAR EFFECTS AND ALSO SHOWING
A VERY STRONG CORRELATION
BETWEEN STRENGTH OF MYSTICAL
EXPERIENCE CHANGE IN CRAVING AND
EXPERIENCES OF PERSONAL
MEANINGFULNESS PREDICTED BY
MYSTICAL EXPERIENCES STRONGLY
PREDICTING CHANGE AND CONFIDENCE
TO ABSTAIN TO SMOKE AND BELIEVED
IN MYSTICAL EXPERIENCE MAY BE A
CATALYST IN SOME WAY FOR
REMARKABLE CHANGES IN CLINICAL
STATUS WE ARE OBSERVING IN
STUDIES AND THERE IS A GROWING
LITERATURE AROUND WHAT IS
OCCURRING IN THE BRAIN.
QUESTION OF DEEP INTEREST TO
MIND IS WHILE THESE REMARKABLE
EXPERIENCES ARE OCCURRING AND
THEN FOR DAYS AND WEEKS AND
MONTHS AND YEARS AFTERWARDS WHEN
EXPERIENCE SUBSIDED AND FIRST TO
BE PUBLISHED WITH PSILOCYBIN
MAGNETIC RESONANCE TECHNIQUES IN
2012 DEMONSTRATING REMARKABLE
REDUCTION IN OXYGENATION LEVEL
OF [INDISCERNIBLE] AND PROXY AT
SOME LEVEL FOROVERALL BRAIN
FUNCTION AND ACTIVITY WITHIN
DISCRETE BRAIN AREAS AND SAW
REDUCTION IN BALD SIGNALS AS
WELL AS CEREBRAL BLOOD FLOW
MOSTLY RESTRICT TODAY DEFAULT
MODE NETWORK AND MEDIAL TEMPORAL
LOBE AND BASAL GANGLIA REGIONS
INVOLVED IN REWARD RESPONSIVITY
AND MANY FOLLOW UP ANALYSIS OF
DATA SETS AND MANY ON RIGHT THAT
IS A PRETTY WELL-KNOWN FIGURE IN
PSYCHEDELIC TALKS THAT ON THE
LEFT IS A DEPICTION OF
MATHEMATICAL MODELING OF NETWORK
STATE SPACE IN THE BRAIN DURING
NON-DRUG RESTING STATE SCAN AND
TO RIGHT YOU SEE SAME
MATHEMATICAL MODEL APPLIED TO
BRAIN ACTIVITY DURING
PSYCHEDELIC EXPERIENCES
SPECIFICALLY WITH SILO KRIEBIN
AND SEE EMERGENCE OF CONNECTIONS
AND NETWORKS AND EXPANSION OF
NETWORKS STATE SPACE THAT IS
WELL BEYOND THAT WHICH IS
OBSERVED DURING A NORMAL WAKING
CONSCIOUS
CONSCIOUSNESS.
IN THIS MODEL THEY PROPOSED THAT
UNDER A NORMAL WAKING
CONSCIOUSNESS WHEN WE RECEIVE
SENSORY INPUT THAT SENSE YRY
INPUT IS INTERPRETED HEAVILY AND
HIGHLY WEIGHTED BASED ON TOP
PREDICTIONS THAT YOU CAN
CONSIDER BAYESIAN PRIORS ABOUT
THE WORLD AND HAVE MODELS HOW
THE WORLD SHOULD WORK AND APPLY
THEM IN UNDERSTANDING TO INPUTS
WE RECEIVE ON A REGULAR BASIS
AND IN MODELS PSYCHEDELICS
ESSENTIALLY FLATTEN ENERGY
LANDSCAPE OF PREDICTIONS AND
MODELS THAT YOU CAN IMAGINE A
REDUCTION IN WEIGHT OF PRIORS OR
REDUCTION IN WEIGHT OF MODELS
HELPING YOU TO INTERPRET THE
WORLD AND THEN ALLOWS FOR
DIFFERENT PREDICTIONS AND
PREDICTION ERRORS TO PUSH AROUND
AND BEGIN TO MODULATE YOUR BRAIN
STATE GOING FORWARD AND
PSYCHOLOGICAL STATE GOING
FORWARD AND THIS IS ONE MODEL OF
HOW PSYCHEDELICS MAY BE ALTERING
BRAIN FUNCTION ACUTELY DURING
EXPERIENCES AND ANOTHER MODEL
THAT COMES OUT OF A VAST AMOUNT
OF WORK ON PSYCHOSIS AND
[INDISCERNIBLE] FOCUSES IN ON A
KIND OF RECURRENT CIRCUIT
BETWEEN THALAMIC NUCLEI AND
CORTICAL SITES AND WITHIN THIS
CIRCUIT IT IS KNOWN AND EXPECTED
THAT PREFRONTAL BRAIN REGIONS
WILL EXERT TOP-DOWN INFLUENCE
OVER THALAMUS THAT WILL EXERT
SIL AMIC NUCLEI AND CONTROL OVER
AMOUNT OF SENSORY INFORMATION
PASSING FROM THALAMUS TO HIGHER
AREAS FOR PERCEPTION AND
COGNITION TO OCCUR AND TURNS OUT
THROUGHOUT THIS CIRCUIT AND
SOMEWHAT RECURRENT AND
SELF-REGULATING CIRCUIT MANY
SEROTONIN RECEPTORS AND
PSYCHEDELIC DRUGS AND IDEA IN
PLAIN LANGUAGE GOES WHEN YOU
HAVE A PSYCHEDELIC EXPERIENCE
DRUGS ARE DISRUPTING THE CIRCUIT
LEADING TO OVERFLOW OF SENSORY
INFORMATION MAKING IT TO CORTEX
THAT LEADS TO FURTHER BREAK DOWN
CIRCUIT LEADING TO SENSORY
INFORMATION LEADING TO CORTEX
AND THEN EVERYTHING PROCEEDS
FROM THAT AND FROM THAT STATE.
THIS IS HEAVILY RELIANT ON WORK
FROM MARK AND [INDISCERNIBLE]
WHO APPLIED THIS MODEL THAT HAS
BEEN DEVELOPED IN STUDY OF
PSYCHOSIS TO UNDERSTANDING OF
PSYCHEDELIC EXPERIENCES.
AND THESE -- THESE MODELS TO
THIS POINT, THEY EXPLAIN WHAT IS
OCCURRING CUTELY DURING
PSYCHEDELIC EXPERIENCES THAT
DON'T GO FAR IN EXPLAINING WHAT
HAPPENS AND CHANGES AFTER THE
FACT AND MODELS PREDICTING BRAIN
[INDISCERNIBLE] AND WHAT HAPPENS
NEXT AND WORKING ON DATA AND
[INDISCERNIBLE] SUGGESTS
PSYCHOLOGICAL FLEXIBILITY
COGNITIVE FLEXIBILITY AND NEURAL
FLEXIBILITY ALTERED IN ENDURING
FASHION AFTER PSYCHEDELIC
EXPERIENCES THAT IS IMPORTANT
BECAUSE COGNITIVE EXPERIENCES
ARE TARGETS IMPAIRED IN MOOD AND
SUBSTANCE USE DISORDERS AND IN
OTHER DISORDERS POSSIBLY THAT IS
PICTURE OF ALLAN DAVIS FIRST
AUTHOR IN PUBLICATION AND LEAD
AUTHOR POST DOCTORAL FELLOW
GOING ON TO LEAD RESEARCH CENTER
AT OHIO UNIVERSITY AND SURVEY
AND INDIVIDUALS IN WORLD THAT
CLAIM TO RECOVER FROM DEPRESSION
AFTER TAKING MUSHROOMS AND ASKED
HIM TO COMPLETE QUESTIONNAIRES
AND OF COURSE CAVEATS ABOUND AND
SURVEY SAMPLE AND ALMOST
CERTAINLY RESPONSE AND
SELECTIVITY BIAS AND
RECOLLECTION AND POSITIVITY BIAS
AND OF DATA WE COLLECTED WE
FOUND THAT THERE WASN'T
NECESSARILY ACCUSE MYSTICAL
EXPERIENCES PREDICTING
INCREASING IN DEPRESSION THAT
PERSON EXPERIENCED AFTER
PSYCHEDELIC EVENT AND RATHER
MYSTICAL EXPERIENCES STRONGLY
PREDICTED OCCURRENCE OF ACUTE
PSYCH LONL INSIGHTS PEOPLE
GAINING INSIGHTS TO THEMSELVES
MRAPSD IN WORLD AND
RELATIONSHIPS DURING EXPERIENCES
THAT THEN PREDICT INCREASES IN
PSYCHOLOGICAL FLEXIBILITY THAT
SEEM TO FINALLY PREDICT
DECREASES IN DEPRESSION AND
ANXIETY CENTERING FLEXIBILITY
AND INCREASED CAPACITY FOR
FLEXIBILITY AS POTENTIAL
THERAPEUTIC TARGET OF
PSYCHEDELIC DRUGS AND UNDER
SURVEY BRINGING UNDER TIGHT
EXPERIENCE AND CONTROL AND STUDY
OF PATIENTS WITH MAJOR
DEPRESSIVE DISORDER WE ASK
PATIENTS TO COMPLETE
[INDISCERNIBLE] AND THIS IS A
DEPICTION OF THE TASK WE USE AND
IS ADAPTATION OF WISCONSIN
[INDISCERNIBLE] CALLED PEN
CONDITIONAL EXCLUSION TASK AND
IN TASK YOU ARE TOLD TO CLICK ON
OBJECT THAT DOESN'T BELONG AND
YOU SEE OH, WELL. WHAT IS THE
RULE?
IS SQUARE AN OBJECT THAT DOESN'T
BELONG AND IT IS DIFFERENT THAN
OBJECT IN THE STARS AND BOLD
STAR THAT STNT BELONG IN LINE
WITH WEIGHT FROM FIGURES AND
FIRST FIGURE SMALL STAR BECAUSE
SMALLER THAN OTHER THREE FIGURE
ERRS AND PERSON COMPLETING TASK
HAS TO CLICK THROUGH AFTER EACH
CLICK ON OBJECT TO SELECT AND
THIS IS ONE I THINK DOESN'T
BELONG GIVEN FEEDBACK IT HAS
INCORRECT AND ALONG WAY YOU
LEARN RULE AND CHUG ALONG
PLAYING WITH RULE AND TOLD
CHANGES AND START TO BE TOLD
THAT RESPONSE IS INCORRECT AND
YOU HAVE TO SWITCH SEARCH AND
EXPLORE AND FIND NEW RULE AND
BEGIN TO RESPOND TO THAT RULE
AND CHUG ALONG FOR A WHILE UNTIL
THAT RULE CHANGES AND FIX YOUR
RESPONDING AND DEGREE TO WHICH
YOU PERCEIVERATE ON PREVIOUS
RULE AFTER RULE HAS CHANGED IS A
MEASURE OF COGNITIVE
INFLEXIBILITY AND REDUCTION IN
PERSEVERATIVE RORS IS INCREASE
IN COGNITIVE FLEXIBILITY AND --
RERECEIVE REDUCTION IN
BEHAVIORAL CONTROL HERE AND
ALONG THAT SAME STUDY WE ALSO
HAD PEOPLE SCANNED WITH
FUNCTIONAL MRI BEFORE AND AFTER
THEIR TREATMENT AND SAW INCREASE
IN DYNAMIC FUNCTIONAL
CONNECTIVITY AND VARIANCE,
MOMENT TO MOMENT VARIANCE IN
CONNECTIVITY AND COMMUNICATION,
IF YOU WILL, OF POSTERIOR
SINGLET AND ANTERIOR SINGLET
INVOLVED HEAVILY IN PROCESS OF
EXECUTIVE AND COGNITIVE CONTROL
AND FLEXIBILITY AND SEEING
INCREASE IN DYNAMIC CONNECTIVITY
AND NEURAL FLEXIBILITY OF BRAIN
REGION THAT PREDICTED CHANGE AND
DEPRESSION A MONTH AFTER
TREATMENT AND SEEING EVIDENCE
FOR PSYCHOLOGICAL AND COGNITIVE
AND NEURAL FLEXIBILITY INCREASES
PREDICTIVE OF THERAPEUTIC
OUTCOMES THAT COULD BE AN
EXPLANATION OF WHY PSYCHEDELICS
MAY BE THERAPEUTICALLY EFFECTIVE
IN MOOD AND SUBSTANCE USE
DISORDERS THAT IN ITSELF MIGHT
BE REMARKABLE DON'T THINK OF
MOOD DISORDERS TO BE FOR THERAPY
FOR TOBACCO USE DISORDERS TO BE
FIRST LINE OF THERAPY FOR
ALCOHOL USE DISORDER AND SO ON
AND SO FORTH.
IF WE CAN DETERMINE THESE TYPES
OF POTENTIAL TRANSDIAGNOSTIC
THERAPEUTICS FOR PSYCHEDELIC
DRUGS WE WILL HAVE GONE A LONG
WAY TO UNDERSTAND BETTER HOW TO
OPTIMIZE DELIVERY OF THERAPIES
AND WE HAVE ONE OTHER HYPOTHESIS
HERE WE ARE WORKING ON THAT IS
PSYCHEDELICS CHANGING BALANCE OF
COGNITIVE FLEXIBILITY AND
STABILITY LEADING TO LONG-TERM
EFFECTS THAT THIS IS MY POST
DOCTORAL FELLOW AND
[INDISCERNIBLE] IS LEADING THE
CHARGE ON THIS AND ACKNOWLEDGING
POST DOCTORAL FELLOW WHO LED
CHARGES ON BRAIN ANALYSIS AND
WANT TO GIVE A NOD AND HANDOFF
TO DAVID OLSON'S WORK AND
DAVID'S WORK IS REMARKABLE
LEADING WAY DEMONSTRATING
POTENTIAL FOR MOLECULAR NEURONAL
BASIS FOR EFFECTS I DESCRIBED
AND POSSIBLE THAT NEURAL
PSYCHOLOGICAL FLEXIBILITY ARE
UNDERLAYED BY INCREASE OF SPINE
DENSITY AND SNAPPO GENESIS THAT
MAY BE POSSIBLE AFTER THE
ADMINISTRATION OF VARIETY OF
PSYCHEDELIC COMPOUNDS AND THINK
THAT I SHOULD NOW PAUSE TO
ACKNOWLEDGE THE VERY LARGE AND
DIVERSE TEAM OF PROFESSIONALS AT
MANY LEVELS OF ACADEMIC CAREER
AND WITH WHOM I HAVE HAD THE
PRIVILEGE TO WORK AT JOHNS
HOPKINS UNIVERSITY FOR CENTER
FOR PSYCHEDELIC RESEARCH AND OF
WHICH NONE WILL HAVE SHOWED YOU
AND HAVE OCCURRED AND WANT TO
ALSO THANK YOU FOR YOUR TIME AND
ATTENTION. NOW, I WILL
OFFICIALLY HAND OFF THE MIC TO
DR. OLSON.
>>THANK YOU VERY MUCH, FRED,
FOR AN EXCITING PANORAMIC VIEW
OF THIS FIELD AND TURNING TO
DAVID OLSON WHO WILL DISCUSS
PSYCHEDELICS AND RELATED
PLASTICITY PROMOTING
NEUROTHERAPEUTICS. DAVID?
>>CAN EVERYONE SEE SLIDES AND
HEAR ME?
>>GREAT. FANTATASTIC
FRED AND NOW TALKING ABOUT HOW
DRUGS MIGHT IMPACT THE BRAIN AND
BEFORE I GET INTO THIS I HAVE TO
TELL NEW ADIDITION TO -- DELLIX
LICENSES TECHNOLOGY FROM UC
DAVIS AND HOPE YOU COME AWAY
WITH A BETTER UNDERSTANDING OF
-- AND HOPE YOU GAIN KNOWLEDGE
ABOUT MECHANISMS BY WHICH
PSYCHEDELICS CAN PRO NONOTE
STRUCTURAL NEUROPLASTICITY AND
TALK ABOUT THE POSSIBILITY OF
SEPARATING HALLUCINOGENIC
EFFECTS ON NEUROPLASTICITY AND
LONG TERM BENEFICIAL EFFECTS AND
OUR GROUP IS FINDING TREATMENTS
IN STRESS RELATED
NEUROPSYCHIATRIC DISEASES THAT
ARE CONDITIONS THAT ARE
PRECIPITATED OR EXACERBATED BY
CHRONIC STRESS LIKE DEPRESSION
AND POST-TRAUMATIC STRESS
DISORDER AND SUBSTANCE USE
DISORDER AND HALLMARK OF
ILLNESSES ARE PHYSICAL CHANGES
IN STRUCTURE OF THE BRAIN AND
PARTICULARLY AT TROE FEEING OF
NEURONS IN PART OF THE BRAIN
THAT IS PREFRONTAL CORTEX
SITTING HERE AND PFC IS CRITICAL
BRAIN REGION THAT GOES TO
SUBCORTICAL REGIONS DOING THINGS
LIKE CONTROLLING MOOD AND
MOTIVATION AND FEAR AND REWARD
THAT IS PERHAPS UNSURPRISING
THAT STRESS INDUCED CHANGES IN
STRUCTURE OF BRAIN REGION LEADS
TO SYMPTOMS OF MANY OF THE
NEUROPSYCHIATRIC CONDITIONS.
NOW, THE CURRENT THERAPEUTIC
APPROACH TO TREAT ILLNESSES HAVE
RELIED ON TRYING TO RECTIFY
SO-CALLED CHEMICAL IMBALANCES IN
THE BRAIN THROUGH USE OF THINGS
LIKE SELECTIVE SEROTONIN
REUPTAKE INHIBITORS AND HAVE
LARGELY EFFECTIVE ANYONE KNOWING
ABOUT SSRIS KNOWS IT TAKES WEEKS
TO MONTHS FOR THAT TYPE OF
MEDICINE TO DEMONSTRATE CLINICAL
EFFICACY AND 1/3 OF ALL PATIENTS
WILL NEVER RESPOND TO MORE
TRADITIONAL ANTIDEPRESSANT
TREATMENTS AND OUR GROUP IS
INTERESTED REALLY IN TRYING TO
PUSH FORWARD A NEW APPROACH AND
ONE THAT INVOLVES USE OF SMALL
MOLECULE DRUGS TO SELECTIVELY
MODULATE SPECIFIC CIRCUITS IN
THE BRAIN TO PRODUCE
LONG-LASTING CHANGES IN
BEHAVIOR. WE REASON ONE BEST
WAY TO IMPACT NEURAL CIRCUIT IS
PHYSICALLY CHANGING STRUCTURE OF
NEURONS WITHIN CIRCUIT AND
PURPOSES OF TODAY'S TALK I WILL
FOCUS ON THESE LAYER 5 PARAMETAL
NEURONS OF CORTEX THAT TEND TO
ATROPHY IN RESPONSE TO CHRONIC
STRESS.
WE STARTED STUDYING A CLASS OF
COMPOUNDS CALLED PSYCHOMRAFTI
GENERALS THAT ARE STIMULI
INDUCING STRUCTURAL FUNCTIONAL
NEURAL PLASTICITY AND YOU WILL
SEE COMPOUNDS PROMOTE GROWTH OF
NEW DENDRITES AND IF YOU ZOOM IN
ON ONE OF THE DENDRITES YOU WILL
SEE GROWTH OF THE LITTLE TINY
NUMBERS CALLED DENDRITIC SPINES
THAT ARE SITES OF EXCITATORY
SYNAPSES IN THE BRAIN AND
CHANGES IN NEURONAL STRUCTURE
OFTEN MANIFEST AS FUNCTIONAL
CHANGES YOU CAN MEASURE WITH
TRADITIONAL TECHNIQUES LIKE
ELECTROPHYSIOLOGY.
NOW, ONE OF THE BEST KNOWN
PSYCHOMRAFTI GENERALS IS
MOLECULE KETAMINE THAT IS
DISASSOCIATIVE ANESTHETIC THAT
IS IN MEDICINE FOR MANY YEARS
AND IS KNOWN AS SPECIAL K ON
STREET WHEN IT IS ABUSED AND
MORE RECENTLY FDA HAS APPROVED
KETAMINE FOR TREATMENT RESISTANT
DEPRESSION AND BELIEVE THAT
KETAMINE'S ANTIDEPRESSIVE
EFFECTS STEM FROM NEURAL
PLASSISTY AND SHOWING NEURONS
THAT ARE CULTURED IN A DISH AND
ON LEFT NEURONS ARE TREATED WITH
VEHICLE CONTROL AND ON RIGHT
NEURONS ARE TREATED WITH
KETAMINE THAT KETAMINE TREATED
NEURONS HAVE MORE DENDRITIC
BRANCHES IF YOU LOOK BELOW GREEN
DOTS ARE REPRESENTING SYNAPSES
AND KETAMINE PROMOTES GROWTH OF
NEURITES AND NEUR EATO GENESIS
AND PROMOTES NEUROGENESIS OR SIN
APTO GENESIS AND SHOWING IN VIVO
DATA FROM LATE [INDISCERNIBLE]
AND THEY REALLY DEMONSTRATED
THAT CHRONIC STRESS COULD LEAD
TO CORTICAL ATROPHY IN LOSS OF
DENDRITIC SPINES I TOLD YOU
ABOUT BEFORE AND LOSS OF
DENDRITIC SPINES MANIFEST AS
SYNAPTIC DEFICITS YOU CAN
MANIFEST WITH ELECTROPHYSIOLOGY
AND WHAT IS REMARKABLE ABOUT
KETAMINE IS SINGLE
ADMINISTRATION OF THE DRUG
RAPIDLY IN 24 HOURS CAN REGROW
LOST DENDRITIC SPINES
REESTABLISHING SYNAPTIC
CONNECTIVITY IN THE CORTEX AND
KETAMINE IS A REALLY INTERESTING
DRUG THAT IS PUSHING
NEUROPSYCHIATRY IN NEW
DIRECTIONS AND IN DIRECTION
TOWARDS HEALING DANL NEURAL
BRAIN CIRCUITRY SIMPLY THAN
TREATING SYMPTOMS AND KETAMINE
IS A DRUG AND MMDA RECEPTOR
FOUND BROADLY ACROSS ENTIRE
BRAIN AND GETTING INTO THE FIELD
WE ARE REALLY INTERESTED IN
TRYING TO FIND MOLECULES THAT
MIGHT HAVE MORE CIRCUIT-LEVEL
SEA ACTIVITY CONTROLLING WHERE
NEURAL PLASTICITY HAPPENS IN THE
BRAIN AND REMEMBER THAT NEURAL
PLASTICITY EVERYWHERE IS NOT A
GOOD THING PROMOTING NEURAL
PLASTICITY IN ADDICTION
CIRCUITRY ADDICTIVE COMPOUNDS
LIKE COCAINE DO AND PROMOTING
NEURAL PLASTICITY PAIN SENSING
NEURONS IN PERATIVERY CAN LEAD
TO CHRONIC PAIN AND WE THINK
DEEPLY ABOUT GENETICS OF BRAIN
TRYING TO FIND A TARGET
SELECTIVELY EXPRESSED IN NEURONS
IN CORTEX THAT ATROPHY IN
NEUROPSYCHIATRIC DISEASES LIKE
DEPRESSION STUDYING SEROTONIN
A
AND 5-HT2A RECEPTORS AND VERY
HIGH EXPRESSION IN THE ANTERIOR
PARTS OF THE BRAIN AND LESS
EXPRESSION MOVING TOWARDS BACK
OF THE BRAIN AND VERY LITTLE
EXPRESSION IN STRUCTURES LIKE
HIPPOCAMPUS AND STRIATUM AND IF
YOU ARE THINKING OF TRYING TO
MODULATE SEROTONIN 2A RECEPTOR
CLASSIC MOLECULES ARE
PSYCHEDELICS MOLECULES LIKE LSD
AND SILO SIL COMING FROM
MUSHROOMS AND FIRST EXPERIMENT
WE DID IS TOOK NEURONS TREATING
THEM WITH PSYCHEDELIC COMPOUNDS
YOU SEE COMPARED TO NEURONS
TREATED WITH VEHICLE CONTROL
NEURONS TREATED WITH
PSYCHEDELICS DMT AND LSD THAT
HAVE SUBSTANTIALLY MORE COMPLEX
DENDRITIC HARBORS AND DOG SUPER
RESOLUTION MICROSCOPY ZOOMING IN
ON DENDRITES YOU SEE GROWTH OF
DENDRITIC SPINES AND
FILLOPODIA-LIKE STRUCTURES AND
TO DEMONSTRATE THIS IN VIVO WE
RELIED ON A VERY FAST ACTING
RAPIDLY CLEARED PSYCHEDELIC DIE
MENLIL TRIPTO MEAN AND HALF LIFE
ERODANT IS ABOUT 10 MINUTES AND
FOR THIS EXPERIMENT WE GAVE
SYSTEMIC ADMINISTRATION OF DMT
AND WAITED 24 HOURS AND TIME
PERIOD WHEN ALL OF THE DRUG IS
CLEARED FROM THE BODY AND WE
SACRIFICED ANIMAL AND TOOK
TISSUE LOOKING AT NEURONAL
STRUCTURE VIA GOLGI STAINING AND
ELECTROPHYSIOLOGY AND LOOKING AT
STRUCTURE OF THE CORTEX AND WE
SEE A LARGE INCREASE IN
DENDRITIC SPINE DENSITY THAT
STRUCTURAL CHANGES ARE
ACCOMPANIED BY FUNCTIONAL
CHANGES AND SEE INCREASE IN BOTH
AMMRITTUDE AND FREQUENCY OF
SPONTANEOUS EXCITATORY
POSTSYNAPTIC CURRENTS AND NOW
SINCE WE PUBLISHED THIS STUDY
WAY BACK IN 2018, IT HAS BEEN
REPLICATED AND EXTENDED BY A
NUMBER OF GROUPS AND WANT TO
HIGHLIGHT ONE GROUP IN
PARTICULAR AND WORK FROM ALEX
QUAN'S GROUP WHO WAS AT YALE AND
MOVED TO CORNELL AND ALEX WAS
INTERESTED IN SEEING HOW LONG
EFFECT ON STRUCTURAL
NEUROPLASTICITY LASTS AND TOLD
YOU EARLIER THAT EFFECTS OF
THERAPEUTICS OF PSYCHEDELICS ARE
ENDURING AND COUPLE OF DOSES
WITH THERAPEUTICS LASTING WEEKS
TO MONTHS AND ALEX FOUND SINGLE
DOSE OF SILO KRIEBIN TO RODENTS
IN MALE AND FEMALE RODENTS LED
TO INCREASE IN CORTEX LASTING
FOR AT LEAST A MONTH THAT IS
QUITE REMARKABLE.
NOW, IN ADDITION TO THEIR
ENDURING EFFECTS AND SOMETHING
ELSE IS UNIQUE ABOUT
PSYCHEDELICS AND IT IS THAT THEY
HAVE A PANACEA-LIKE PROPERTY AND
TEND TO WORK ACROSS INDICATIONS
AND EMPHASIZING THAT DRUGS ARE
NOT PANACEAS AND ONE HYPOTHESIS
FOR WHY THEY SEEM TO HAVE
EFFICACY FOR DISORDERS LIKE
DEPRESSION AND SUBSTANCE USE
DISORDERS AND POST-TRAUMATIC
STRESS DISORDER IS THEY ARE
TARGETING A CRITICAL HUB IN THE
BRAIN OF PREFRONTAL CORTEX AND
KNOW FROM OPTOAND KINETIC
REVOLUTIONS THAT ARE
CIRCUMSTANCE CUTS ORIGINATING
FROM PREFRONTAL CORTEX DOG
THINGS LIKE REGULATING DRUG
SEEKING BEHAVIOR AND CONTROLLING
EXPRESSION OF FEAR AND ENHANCED
MOTIVATION FOR INSTANCE AND I
WILL SUMMARIZE LOTS OF WORK
QUICKLY AND WILL SAY IN GENERAL
PSYCHOMRAFTO GINS WILL HAVE LONG
LASTING BEHAVIORAL EFFECTS SUCH
AS ENHANCEMENT OF FEAR EXTENSION
LEARNING RELEVANT TO TREATMENT
OF POST-TRAUMATIC STRESS
DISORDER OR ANTIDEPRESSANT-LIKE
[INDISCERNIBLE] AND
ANTIDEPRESSANTS THAT PROMOTE A
SWIMMING BEHAVIOR IN THIS TEST
OUR GROUP WAS INTERESTED IN --
PROMOTING NEUROPLASTICITY AND
PRODUCE THERAPEUTIC EFFECTS AND
START BY DOING SELECTIVE
PHARMACOLOGY AND THIS IS MEASURE
OF STRUCTURAL NEUROPLASTICITY
AND SEE FROM PSYCHEDELICS FROM
THREE DISTINCT CHEMICAL
SCAFFOLDS LIKE LSD AND TRIPTO
MEANS AND AMPHETAMINES ARE GOOD
AT PROMOTING GROWTH OF COURTI CO
NEURONS USING ANTAGONIST OF
5HT2A RECEPTORS HAVE BLOCKS WE
CHOSE THIS BECAUSE THERE IS LOTS
OF LITERATURE SHOWING THIS
MEDIATES HAG USE KNOW GENIC
EFFECTS OF PSYCHEDELICS AND
LOOKED AT A COUPLE DOWNSTREAM
KINASES KNOWN TO BE INVOLVED IN
KETAMINE NEUROINDEESED PLASSISTY
AND HIGH AFFINITY RECEPTOR FOR
BRAIN [INDISCERNIBLE] AND
ANOTHER IS MTOR THAT IS
PRODUCTION FOR PROTEINS
NECESSARY FOR PLASTICITY AND
STRUCTURAL PROTEINS -- ION
CHANNELS ALLOWING THEM TO CHANGE
SYNAPTIC [INDISCERNIBLE] AND
BLOCKING MTOR OR TRACK B YOU
BLOCK PSYCHEDELIC INDUCED
NEUROPLASTICITY AND IN THIS
STAGE ANTAGONIST USING TO BLOCK
5HT2A RECEPTOR IS NOT A PERFECT
DRUG TO BE REALLY CERTAIN THAT
2A RECEPTOR IS MEDIATING EFFECTS
TO RELY ON GENETIC KNOCKOUTS AND
HERE WE ARE GIVING PSYCHEDELIC
DRUG 5 METH OXY [INDISCERNIBLE]
TO WILD TYPE ANIMALS AND
INCREASE IN DENDRITIC INCREASE
IN CORTEX AND THIS IS COMPLETELY
GONE IN 5-HT2A -- PRODUCING LONG
LASTING CHANGES IN FUNCTIONAL
PLASTICITY AND AGAIN EFFECTS ARE
COMPLETELY GONE 5HT2A KNOCKOUT
ANIMALS IN TERMS OF BEHAVIORAL
EFFECTS WE RELIED ON VERSION OF
SWIM TEST THAT IS A LITTLE MORE
CHALLENGING AND TRADITIONAL
ANTIDEPRESSANT DON'T TYPICALLY
WORK IN AND NEUROMRAFTINS LIKE
KETAMINE GO IN AND RUN A SWIM
TEST DAY 1 PROVIDING A LITTLE
STRESS TO ANIMALS MAKING SURE
ALSO THAT ALL GROUPS HAVE EQUAL
RESPONSES AND WE THEN GIVE A
SINGLE DOSE OF 5MEODMT AND DO A
BEHAVIORAL MEASURE TO MAKE SURE
THAT ANIMALS GOT APPROPRIATE
DOSE AND 24 HOURS LATER AFTER
DRUG IS CLEARED FROM SYSTEM WE
LOOK FOR ANTIDEPRESSANT EFFECTS
AND SEE 5MDOT ON ITS OWN YOU CAN
SEE A ROBUST ANTIDEPRESSANT
RESPONSE AND IF YOU PRETREAT
ANIMALS WITH ANTAGONIST OF
5HT2AR RECEPTOR YOU SEE THIS IS
COMPLETELY BLOCKED AND IN
ADDITION LOOKING TO SWIM TEST
YOU LOOK AT MEASURE OF
ANADON'TIA AND ANIMALS LIKE
MYSELF WILL PREFER A SUGARLY
DRINK OVER PLAIN OLD WATER AND
GIVE OPTION OF DRINKING A BOTTLE
OF WATER THAT CONTAINS SUCROSE
THEY WILL PREFER SUCROSE AND
MEASURE THIS IN SUCROSE
PREFERENCE TEST AND HERE WE ARE
SHOWING AT BASELINE WILD TYPE
AND 5HT2A KNOCKOUT ANIMALS HAVE
ROBUST PRECHS FOR SOLUTION AND
PRODUCE THIS LIKE PHENOTYPE
DOING ANIMALS CHRONIC COURTI CO
STEROID AND CHRONIC STRESS
HORMONE AND AFTER 10 DAYS OF
THAT RUNNING ANOTHER SUCROSE
PREFERENCE TEST AND SEE WILD
TYPE AND KNOCKOUT HAVE REDUCTION
IN PREVENS FOR SUCROSE SUGGEST
THEY HAVE ANHEADONIA AND SINGLE
ADMINISTRATION OF SIGNO SIEL
ABIN COME BACK 24 HOURS LATER
AND DO ANOTHER TEST YOU SEE IT
IN WILD TYPE ANIMALS RESCUES
DEFICIT AND DOES NOTHING IN
5HT2A KNOCKOUT ANIMALS THAT
SUGGESTED TO US THAT 5H2TA
RECEPTOR IS CRITICAL FOR
PSYCHEDELIC INDUCED STRUCTURAL
NEUROPLASTICITY IN THE CORTEX
AND IS RESPONSIBLE FOR SOME
ANTIDEPRESSANT-LIKE BEHAVIORAL
EFFECTS AND NOW AT THIS POINT WE
HAVE ONE RESULT THAT REALLY LEFT
US SCRATCHING OUR HEAD THAT WAS
FACT THAT THIS MOLECULE HERE ON
THE LEFT SEROTONIN COULD NOT
PRODUCE PSYCHEDELICLIKE EFFECTS
ON STRUCTURAL NEURAL PLASTICITY
AND BOTHERED US SPENDING LAST
FEW SLIDES SAYING THAT SEROTONIN
RECEPTOR IS CRITICAL FOR
PSYCHEDELIC BASED
NEUROPLASTICITY AND DIDN'T
UNDERSTAND IT UNTIL WE SAW A
STRUCTURE OF ACTIVITY
RELATIONSHIP STUDY AND FOUND
THAT IF WE STARTED TO METHYLATE
SEROTONIN TO PRODUCE COMPOUNDS
LIKE THIS OR PSYCHEDELIC
COMPOUNDS LIKE ONES ON RIGHT WE
SAW INCREASE IN THEIR ABILITY TO
PROMOTE GROWTH OF CORTICAL
NEURONS THAT LED US TO
HYPOTHESIS THAT SEROTONIN NOT
THAT IT CAN'T ACTIVATE TARGET WE
KNOW IT CAN. MAYBE IT CAN'T
ACTUALLY ACCESS THE TARGET AND
MAYBE TARGET OF G PROTEIN
COUPLED RECEPTOR NOT FOUND ON
CELL SURFACE LIKE MOST GCPCRS IS
ON INSIDE OF THE CELL AND THAT
VERY POLAR MOLECULES LIKE
SEROTONIN CAN'T SIMPLY CROSS
MEMBRANES TO ACCESS THAT TARGET
AND WE TRY TO CORRELATE EFFICACY
IN NEURAL PLASTICITY ASSAYS TO
ACTIVATION OF 5HT2A RECEPTOR AND
SAW NO CORRELATION AND IN FACT
WE IS A YOU A SLIGHT
ANTI-CELATION AND THEN WHEN WE
JUST TRIED TO CORRELATE LIPO
PHALLUSTY OF THE DRUG AND HOW
GREASY IT IS WE SAW A NICE
CORRELATION AND VERY POLAR DRUGS
THAT CAN'T CROSS CELL MEMBRANES
LIKE SEROTONIN ARE NOT GOOD AT
PROMOTING COURTI CO GROWTH AND
THESE ARE VERY GOOD AT PROMOTING
CORTICAL NEURON GROWTH AND NEXT
WE WANTED LOOK AND SEE WHERE
RECEPTORS ARE LOCALIZED AND FOR
THESE STUDIES WE EXPRESSED 2
DIFFERENT GCPRS IN AN EXCEL LINE
AND CONTROL SHOWING CFP GOES
EVERYWHERE IN THE CELL AND THEY
ARE PRIMARILY LOCALIZED TO THE
CELL MEMBRANE AND WHITE LINES
HERE ARE A MARKER FOR PLASMA
MEMBRANE AND WHAT YOU WOULD
EXPECT FOR GCPR AND LOOKING IN
NEURONS WE SEE SOMETHING
DIFFERENT AND -- THIS IS
PRIMARILY LOCALIZED INSIDE OF
THE CEMAND THIS IS STILL VISIBLE
ON THE CELL SURFACE AND WE WERE
NOT THE FIRST TO DISCOVER THIS
AND MANY OTHER GROUPS HAVE FOUND
THAT IN CORTICAL NEURONS
SEROTONIN A RECEPTORS SEEMS TO
LIVE ON INSIDE OF THE CELL AND
NO ONE UNDERSTOOD WHAT
FUNCTIONAL RELEVANCE OF THIS
LOCALIZATION WAS.
SO, AT THIS POINT WE -- WE
ASSUMED THAT IF SEROTONIN COULD
ACCESS TARGET ON INSIDE OF THE
CELL, IT SHOULD BE ABLE TO
PROMOTE PSYCHEDELICLIKE EFFECTS
ON NEURAL PLASTICITY AND TO GET
IT ON INSIDE OF THE CELL WE -- A
SPARSELY TRANCE FEKTED AND A
TRANSPORTER FOR SEROTONIN THAT
IS A SEROTONIN TRANSPORTER THAT
IS A COUPLE NEURONS IN SAME DISH
SIDE BY SIDE AND ONE NEURON HAS
A TRANSPORTER TO IMPORT
SEROTONIN AND OTHER NEURON LACKS
TRANSPORTER AND CANNOT AND ON
RIGHT SIDE HERE NEURON ON RIGHT
HAS TRANSPORTER AND ONE ON LEFT
DOES NOT WE FIND COMPARING
GENOTYPES VEHICLE DOES NOTHING
AND COMPOUND THAT CAN CROSS
MEMBRANE PROMOTES CORTICAL
NEURON GROWTH IN BOTH GENOTYPES
AND SEROTONIN CAN ONLY PROMOTE
NEURON GROWTH IN NEURONS THAT
CAN IMPORT MONOAMEAN.
WE SAW SOMETHING SIMILAR LOOKING
AT DENDRITIC SPINE DENSITY AND
DMT PROMOTES GROWTH IN BOTH
GENOTYPES AND SEROTONIN PROMOTES
GROWTH IN NEURONS IMPORTING
SEROTONIN.
NOW, TO DEMONSTRATE THIS IN
VIVO, WE RELIED ON EXPRESSING
SEROTONIN TRANSPORTER IN
PREFRONTAL CORTEX USING VIRUS
AND THREE WEEKS TO ALLOW
EXPRESSION OF TRANSPORTER AND
GAVE A DOSE OF THIS COMPOUND
HERE CALLED PARACOLORA
AMPHETAMINE THAT CAUSES RELEASE
OF SEROTONIN AND COMING BACK 24
HOURS LATER AND MEASURE SPINE
DENSITY WE FIND THAT NEURONS
WITH TRANSPORTER FOR SEROTONIN
WE SEE GROWTH EFFECTS AND
NEURONS LACKING TRANSPORTER WE
SEE NO EFFECT OF RELEASED
SEROTONIN AND IF STRUCTURAL
PLASTICITY IS IMPORTANT FOR
BEHAVIORAL EFFECT WE SEE
ANTIDEPRESSANT RESPONSE AS WELL
AND RAN A SIMILAR TYPE OF
EXPERIENCE FOR THIS ONE AFTER WE
EXPRESSED TRANSPORTER AND DO
NOVELTY INDUCE THE LOCOMOTION
ASSAY TO SHOW NO DIFFERENCE
BETWEEN TWO GENOTYPES AND THERE
IS NOT AND RUN PRETEST FOR THIS
TEST AND AGAIN SHOWING NO
DIFFERENCE BETWEEN TWO GENOTYPES
AND GIVE A SINGLE ADMINISTRATION
OF SEROTONIN RELEASING COMPOUND
AND RELEASING ANTIDEPRESSANTS 24
HOURS LATER IN THE SWIM TEST AND
FIND THAT ONLY NEURONS AND IN
ANIMALS THAT HAVE NEURONS IN PFC
EXPRESSING TRANSPORTER, THOSE
ANIMALS EXHIBIT ANTIDEPRESSANT
EFFECTS IN PARACHLOROFEEN AND
OTHER ANIMALS DO NOT.
AT THIS POINT WE FEEL CONFIDENT
THAT 5H2A RECEPTOR IS
RESPONSIBLE FOR HALLUCINOGENIC
AND ELASTICITY PROMOTING
PSYCHEDELIC AS AND RECREPTOR IS
KNOWN TO EXHIBIT FUNCTIONAL
SELECTIVITY AND TWO AGONISTS
COMBINED TO ECREPTOR CAUSING TWO
DIFFERENT DOWNSTREAM PATHWAYS
AND NO KNOWN AGONISTS OF 52HC
RECEPTORS THAT ARE
NONHALLUCINOGENIC AND WANT TO
ASK QUESTION WHETHER ORE NOT IT
IS POSSIBLE TO SEPARATE
HALLUCINOGENIC EFFECTS FROM
EFFECTS OF NEUROPLASTICITY AND
BENEFICIAL BEHAVIORAL EFFECTS
AND I'M HOPEFUL FOR THE DAY WHEN
PSYCHEDELICS WILL RECEIVE FDA
APPROVAL FOR VARIOUS CONDITIONS
AND THINK IT IS IMPORTANT TO
REALIZE THAT IN ORDER FOR DRUGS
TO BE SAFELY ADMINSTERED THEY
HAVE TO BE GIVEN UNDER CARE OF
HEALTH CARE PROFESSIONALS THAT
DRASTICALLY INCREASE COSTS AND
COMPLEXITY OF TREATMENT AND WHEN
YOU CONSIDER FACT THAT 1 IN 5
PEOPLE WILL SUFFER FROM
NEUROPSYCHIATRIC DISORDER
SOMETIME IN THEIR LIFETIME YOU
REALIZE THAT PSYCHEDELIC
PSYCHOTHERAPY AND MIGHT HELP
SOME PATIENTS AND HOPEFUL IT
WILL IT WON'T ADDRESS MASSIVE
ISSUES WE HAVE WITH MENTAL
HEALTH CARE WE HAVE TODAY BY
PRODUCING NONHALLUCINOGENIC
VARIANTS WE ARE HOPING TO REACH
A LARGER PATIENT POPULATION AND
TO DEVELOP NONHALLUCINOGENIC
PSYCHOMRAFTO GENERALS -- WE TURN
TO RODENT BEHAVIOR ON LEFT
CALLED THIS HEAD-TWITCH RESPONSE
ASSAY. IT IS A RAPID ROTATIONAL
MOVEMENT OF THE HEAD
CHARACTERISTIC OF PSYCHOCONTINUE
URGIC PSYCHEDELICS AND BEAUTIFUL
WORK FROM CO-WORKERS HAS SHOWN
ACROSS 30 STRUCTURALLY
PSYCHEDELIC COMPOUNDS THERE IS
CORRELATION BETWEEN POTENCY
TOWARDS RESPONSE ASSAY AND NOW
THIS RESPONSE IS HIGHLY
PREDICTIVE NOT AMENABLE TO DRUG
DISCOVERY BECAUSE IT IS NOT HIGH
THROUGH PUT ENOUGH AND TACKLING
THIS PROBLEM DEVELOPING IN VITRO
ASSAY FOR HALLUCINOGENIC
POTENTIAL WE DID SOMETHING
SIMPLE. WE LOPPED OFF
INTRACELLULAR LOOP OF GCPR AND
FUSE THE ON GREEN FLUORESCENT
PROTEIN THESE WORK CUT IN BETA
BARREL THAT IS OPEN AND ALLOWS
WATER TO GET IN QUENCHING FOR
ESSENCE OF FLOR OE FLOR AND WHEN
LYINGAND BINDS TO RECEPTOR
CONFIRMATIONAL CHANGE CLOSING
BETA BARREL PROTECTING IT
ALLOWING IT TO TURN ON AND
TREATING WITH AGONIST LIKE CER
TONIN YOU SEE A NICE
CONCENTRATION DEPENDENCE
INCREASE IN -- YOU SEE NO CHANGE
OR SLIGHT DECREASE IN
FLUORESCENCE INTENSITY AND GOT
EXCITED WHEN FINDING THIS
BIOASSAY CORRELATED WITH HUMAN
HALLUCINOGENIC POTENCY AND
CALLED THIS BIOCENSOR
[INDISCERNIBLE] AND I WAS MOST
EXCITED WHEN SEEING THESE DATA
WE SAW CYCLIC DIFFERENTIATED
BETWEEN TWO CLOSELY RELATED
STRUCTURAL ANALOG AND COMPOUNDS
LSD AND IN PURPLE SHOWING
NONHALLUCINOGENIC COMPOUNDS
[INDISCERNIBLE] AND 6MDMT AND
YOU FLIP THIS AND INSERT THAT
NITROGEN AND 6MDOMT COMPARED TO
5MEO YOU MOVE THIS ONE CARBON
OVER AND THAT IS IT AND
HALLUCINOGENIC COMPOUNDS TURN
THIS OVER NICELY AND
NONHALLUCINOGENIC COMPOUNDS
DON'T AND MIGHT ASK YOURSELF IF
THESE COMPOUNDS SIMPLY DON'T
BIND TO CENSOR AND WE CAN
ADDRESS THAT QUESTION RUNNING
ASSAY IN ANTAGONIST MODE AND CAN
GIVE A BIT OF AGONIST TO TURN ON
CENSOR AND TIGHT TRAIT IN
INCREASING QUANTITIES OF
NONHALLUCINOGENIC LYINGAND AND
WATCH FLUORESCENCE INCREASE ON
THE RIGHT AND COMPOUNDS ON
AGONIST MODE ON X AXIS AND
ANTAGONIST MODE ON Y AXIS AND
POINTING EYE TO BLACK DOT THERE
THAT IS VEHICLE CONTROL AND
COMPOUNDS INCREASING CYCLIC
FLUORESCENCE FROM ONE STANDARD
DEVIATION FROM THE VEHICLE THESE
ARE COMPOUNDS IN RED AND KNOWN
HALLUCINOGENIC COMPOUNDS THAT --
MORE THAN ONE STANDARD DEVIATION
FROM THE VEHICLE CONTROL ARE
MOLECULES IN BLUE HERE AND ARE
NONHALLUCINOGENIC LIGANDS OF
52HC RECEPTOR AND COMBINING
ANTAGONIST MODE DATA PRODUCING
LYING YAPD SCORES HERE ON LEFT
AND COMPOUNDS WITH BLACK
LYINGAND SCORE ARE MOLECULES
CLUSTERING AROUND CONTROL NOT
PREDICTED TO BIOCENSOR AND
COMPOUNDS IN BLUE ARE LIGANDS
PREDICTED TO BE
NONHALLUCINOGENIC YOU SEE
INTERESTING COMPOUNDS IN HERE
AND YOU SEE CLASSIC ANTAGONISTS
LIKE MDL AND [INDISCERNIBLE] AND
YOU SEE ANTIPSYCHOTICS LIKE HALO
PERIDOLL AND SEE AGONISTS LIKE
LISTERIDE AND WILL TELL YOU
ABOUT INTERESTING COMPOUNDS NOW
AND STARTING WITH THIS ONE 5
BROMO-DMT AND WE ARE INTERESTED
IN THIS BECAUSE WE MADE FIVE
HALO GENERATED SERIES GOING FROM
FLOR OE TO CHLORO TO BROEM OE
AND DIFFERENCE HERE IS YOU ARE
INCREASING VANEDER WALL RADII OF
THAT ATOM AND PREDICTING
FLUOROAND CHLOROCOMPOUND SHOULD
BE HALLUCINOGENIC AND THIS
SHOULD BE NONHALLUCINOGENIC AND
SAW TO RESPONSE OF ASSAY AND
THIS TWITCHES AT ALL DOSES AND
NICE DEPENDENT INCREASE AND THIS
COMPOUND DID NOT PRODUCE HEAD
TWITCHES AT ANY DOSE. WE USE
THE PSYCH LIED TO IDENTIFY A
BUNCH OF NONHALLUCINOGENIC
MRAFTO JENS AND WILL TURN YOU TO
ONE CALLED -- WE SAW NO HEAD
TWITCHES UP TO MASSIVE 100 MEG
DOSE AND THIS DOSE OF AAZ IS
AROUND 10MIGS PER KEG AND IS
REMASHABLE IT PRODUCED
PSYCHOGENIC EFFECTS STRUCTURE OF
NEUROPLASTICITY AND PRODUCES
RAPID AND ENDURING EFFECTS ON
BEHAVIORS RELEVANT TO DEPRESSION
AND VERSION OF FOUR SWIM TESTS
SHOWING AFTER 30 MINUTES
KETAMINE AND AAZ PRODUCE RAPID
RESPONSE THAT EFFECT IS MAINTAIN
THE FOR A WEEK FOR BOTH OF THESE
COMPOUNDS AND LOOKING AT THAT
MEASURE OF ANODON'TIA WE TALKED
ABOUT EARLIER AND SUCROSE
PREFERENCE WE ARE USING A
GENETIC MODEL OF DEPRESSION
FOLLOWED BY BILL WECHLEL'S GROUP
AT DUKE AND WE KNOW IN HUMANS IF
YOU INHIBIT THIS YOU CAN INDUCE
PHENOTYPES AND THESE ANIMALS
HAVE BASE LINE DEPRESSIVE
PHENOTYPES AND ONE IS ANODON'TIA
AND IN WHITE ARE WILD TYPE
ANIMALS WITH NICE SUCROSE
PREFERENCE AND THESE
HETEROZYGOTE ANIMALS DON'T AND
SINGLE DOSE OF AAZ CAN RESCUE
ANHEADONIA RESPONSE AND EFFECT
LASTS FOR AT LEAST TWO WEEKS
BEFORE THE GENOTYPES START TO
DIVERGE.
WE HAVE DONE IT A NUMBER OF
TIMES AND WANT TO TELL YOU ABOUT
ONE COMPOUND ABOUT
NONHALLUCINOGENIC
[INDISCERNIBLE] AND YOU CAN SEE
SMALL STRUCTURAL CHANGES
REQUIRED TO TWEAK A PSYCHEDELIC
COMPOUND TO MAKE IT A SAFER AND
MORE SCALEABLE ALTERNATIVE AND
THIS IS POTENT HALLUCINOGEN
PRODUCING ROBUST HEAD TWITCH
RESPONSE AND CONFIRMATION ALLEY
RESTRICTING THIS GROUP TO
PRODUCE THIS MOLECULE YOU SEE
YOU REDUCE HEAD TWITCH RESPONSE
AND MOVING THIS ONE POSITION
OVER HERE YOU HAVE COMPLETELY
ELIMINATED THE HEAD TWITCH
RESPONSE AND IMPORTANTLY TCHLTD
BG IS A POTENT PSYCHOMRAFTO
GENERAL AND FOR THIS STUDY WE
RELIED ONL MICE WITH NEURONS IN
CORTEX PLACED WITH PROTEINS TO
VISUALIZE DENDRITES AND ON FIRST
DAY WE CAN REMOVE A PART OF THE
SKULL AND PUT IN A GLASS WINDOW
AND USE A TWO PHOTON MICROSCOPE
TO PEER INSIDE OF THE BRAIN AND
COUNT DENDRITIC SPINES ON A
BRANCH GIVING DOSE OF TBG GIVING
24 HOURS GIVING SECTION OF
DENDRITE ALLOWING TO QUANTIFY
NUMBER OF SPINES FORMED LIKE
THIS ONE IN BLUE AND NUMBER OF
SPINES ELIMINATED IN RED AND TBG
DOESN'T IMPACT [INDISCERNIBLE]
AND DOES PROMOTE SPINE FORMATION
AND DOES SO IN COMPARABLE EXTENT
TO HALLUCINOGENIC DRUG DOI AND
IF OUR HYPOTHESIS IS CORRECT
THAT STRUCTURAL PLASTICITY IN
THE CORTEX IS CRITICAL FOR
THERAPEUTIC EFFECTS ACROSS
INDICATIONS WE EXPECT TO SEE
BROAD EFFECTS OF TBG AND WHAT WE
SEE AND ANTIDEPRESSANT EFFECTS
IN SWIM TEST AND ANTI-ADDICTIVE
EFFECTS IN ASSAY RELEVANT TO
ALCOHOL USE DISORDER AND SEE
EVERY ANIMAL IN STUDY REDUCED
ALCOHOL CONSUMPTION AFTER
ADMINISTRATION OF TBG AND
EFFECTS OF BEHAVIOR RELEVANT USE
DISORDER AND DOESN'T MATTER WHEN
WE ADMINISTER TBG DURING EARLY
STAGES OF WITHDRAWAL AND
IMMEDIATELY PRIOR TO
REINSTATEMENT AND TIME POINTS
THAT TBG HAD LONG LASTING
PROTECTIVE EFFECT ON HER WIN
SEEKING BEHAVIOR AND LAST TO
MENTION IS TBG HAS POTENTIAL TO
HEAL DAMAGED NEURAL CIRCUITS AND
SHOWING YOU HERE CALCIUM IMAGING
FROM SOMATOSENSORY
[INDISCERNIBLE] FROM MICE THAT
ARE TACTILE CREATURES THAT
ENVIRONMENT FROM WHIS KERS AND
YOU SEE A NICE COORDINATED
RESPONSE IN SOMATOSENSORY CORTEX
AND YOU WILL NOTICE
UNPREDICTABLE MIELTD STRESS
COMPLETELY DISRESULTS THIS
COORDINATED RESPONSE AND SINGLE
DOSE OF TBG CAN RESCUE
COORDINATOR RESPONSE EVEN AFTER
DRUG HAS BEEN CLEARED FROM THE
SYSTEM AND TO SUMMARIZE WHAT I
TRIED TO TELL YOU ABOUT TODAY IN
HEALTHY BRAIN AND CORTEX NEURONS
HAVE LOTS OF DENDRITIC BRANCHES
AND DENDRITIC SPINES HELPING
COMMUNICATE WITH NEIGHBORS AND
IN MANY BRAIN DISORDERS IT THAT
ARE INCLUDING NEUROSTRESS
DISORDERS LIKE DEPRESSION YOU
SEE PHYSICAL ATROPHYING LOSS OF
NEURONS AND DEN DRIDIC SPINES
AND MRAFTO JENS LIKE
PSYCHO-DELLICS AND
NONHALLUCINOGENIC VARIANCE ARE
GOOD AT PROMOTING GROWTH OF
CORTICAL NEURONS AND SUMMARIZING
I TOLD YOU TODAY THAT
PSYCHO-DELLICS -- ACTIVATION OF
INTRACELLULAR POPULATION OF 5H2A
RECEPTORS AND THAT IS A
BIOCENSOR THAT IS GOOD AT
PREDICTING HALLUCINOGENIC
[INDISCERNIBLE] IN VITRO THAT
ARE POTENTIALLY SAFER
PSYCHOMRAFTO JENS AND THANKING
FUNDING AGENCIES ON RIGHT AND
KEY COLLABORATORS IN PARTICULAR
AND WOULD LIKE TO THANK LYNNE
WHO WAS A REALLY GREAT
COLLABORATION WORKING WITH HER
GROUP ON DEVELOPMENT OF
[INDISCERNIBLE] AND THANKING
INCREDIBLE STUDENTS WORKING WITH
TODAY AND HARD WORKING BUNCH AND
PASSIONATE ABOUT SCIENCE AND
WHAT THEY DO AND INCREDIBLY
CREATIVE AND HIGHLIGHTING NAMES
AND A FEW STUDENTS WHOSE WORK I
TALKED ABOUT TODAY AND THANKS
FOR YOUR ATTENTION.
>>I WANT TO THANK BOTH OF YOU
FOR THESE EXTRAORDINARY AND
EXCITING PRESENTATIONS.
WE HAVE A SLEW OF QUESTIONS I
WILL TRY TO DIRECT AND STARTING
AT THE BEGINNING ANY WANT TO
COMMENT WHAT FUNCTION OF
PSYCHOBIOME IN THE MUSHROOM IS?
>>WHAT IS FUNCTION OF
PSILOCYBIN IN THE MUSHROOM? WE
DON'T KNOW IN TERMS OF EVOLUTION
OF THE MUSHROOM, GREAT QUESTION
AND UNCLEAR WHETHER PSILOCYBIN
IS ADAPTABLE CHANGE IN MUSHROOMS
AND UNCLEAR WHETHER IT CONFERRED
EVOLUTIONARY ADVANTAGE IN
DEVELOPMENT AND EVOLUTION OF THE
MUSHROOMS AND SEE MUSHROOMS ARE
SLIGHTLY DIFFERENT THAN I DO
ANIMAL SPECIES.
IT SEEMS MUSHROOMS THEMSELVES
OUTSIDE OF PSYCHOACTIVE
MUSHROOMS ARE REMARKABLE FORMS
OF LIFE AND THEY ARE LITTLE
CHEMICAL FACTORIES AND THERE ARE
LOTS OF DIFFERENT SPECIES OF
MUSHROOMS WITH LOTS OF DIFFERENT
RELATIONSHIPS WITH PLANTS AND
MICROBUY OATA IN NATURAL
ENVIRONMENTS AND SOME MUSHROOMS
ARE SACK ROW PHILIC AND EXIST IN
SYMBIOTIC RELATIONSHIP WITH
DIFFERENT PLANTS AND
ENVIRONMENTS IN WHICH THEY
OPERATE AND SOME FORM TO KIND OF
RECYCLE CERTAIN TYPES OF
CHEMICALS AND COMPOUNDS IN THEIR
ENVIRONMENT AND OTHERS HELP AS
REALLY KIND OF DECOMPOSERS IN
THE FOREST AND THIS IS ME
DANCING AROUND THE ANSWER I
DON'T REALLY KNOW AND IS NOT
CLEAR THAT PSILOCYBIN HAS TO
NECESSARILY PROVIDE SOME KIND OF
EVOLUTIONARY ADVANTAGE TO THE
SPECIES THAT CARRY IT. IT COULD
BE ITS PRESENCE COULD BE A
BYPRODUCT OF ENVIRONMENT THEY
FIND THEMSELVES IN AND
PARTICULAR RELATIONSHIPS THEY
HAVE WITH OTHER PLANTS AND
THINGS IN THEIR ENVIRONMENT.
>>PARDON ME?
>> GO AHEAD.
>>FOLLOWING UP ON WHAT FRED WAS
SAYING AND SOMETHING THAT WILL
SURPRISE LISTENERS IS
PSYCHEDELICS ARE FOUND BROADLY
ACROSS SPECIES IN MANY, MANY
PLANTS AND ARE OF COURSE EVEN
PRODUCED BY ANIMALS LIKE HUMANS
AND LOTS OR MANY PEOPLE KNOW OF
PSYCHEDELIC MUSHROOMS FOUND IN
VERY COMMON PLANTS TOO AND YOU
CAN FIND PSYCHEDELICS IN
ORANGES, FOR INSTANCE.
>>JUST AN INCREDIBLY LOW
CONCENTRATIONS; RIGHT?
>>CORRECT.
>>DESERVING TO KEEP PREDATORS
AWAY AND ALL RIGHT A VERY
IMPORTANT QUESTION THAT POPPED
UP.
INITIAL RESPONSE TO A
PSYCHEDELIC COMPOUND IS
SOMETHING THAT OCCURS WITHIN A
MATTER OF MINUTES THROUGH A VERY
SHORT PERIOD OF TIME.
AND THEN WE HAVE THESE PROLONGED
EFFECTS AS MANIFESTED AND
EXPERIMENTALLY AND CLINICALLY.
ARE THEY BY THE SAME AND IN
THINKING BY THE SAME MECHANISM?
IMPLICATION THAT YOU COULD
DEVELOP A COMPOUND THAT IS
NONHALLUCINOGENIC BUT HAS
THERAPEUTIC IMPLICATIONS THAT
SORT OF IMPLIES THAT THE -- THEY
MAY BE DIFFERENT. I DON'T KNOW.
WHAT ARE YOUR -- THIS HAS POPPED
UP IN SEVERAL QUESTIONS.
>>YOU KNOW, IT IS A REALLY
INTERESTING QUESTION. I THINK
THAT IT REALLY SPEAKS TO THE
COMPLEXITY OF G PROTEIN COUPLED
RECEPTOR BIOLOGY THAT ARE
INCREDIBLE MACHINES AND AS I
MENTIONED IN THE TALK, THEY
EXHIBIT FUNCTIONAL SELECTIVITY
AND TWO COMPOUNDS BINDED TO
RECEPTOR GETTING DIFFERENT
DOWNSTREAM EFFECTS AND WHY THAT
IS THE CASE IS VARIETY OF
DIFFERENT HYPOTHESES AND ONE
HYPOTHESIS IS RELATED TO
EFFECTORS AND THINGS G PROTEIN
ECREPTOR COUPLES TO IS COUPLED
TO BIAS AGNIX AND FUNCTIONAL
SELECTIVITY CALLED LOCATION BIAS
AND LOCATION OF RECEPTOR
DICTATES DOWNSTREAM FUNCTION AND
ANOTHER HYPOTHESIS COULD BE
NEURAL CIRCUITS IT THAT
DIFFERENT POPULATIONS THAT THEY
EXIST IN MIGHT PLAY DIFFERENT
ROLES AND FINALLY YOU HAVE TO
CONSIDER POLYPHARMACOLOGY AND
COULD BE DRUGS ARE ACTIVATING
OTHER ADDITIONAL RECEPTORS THAT
MODULATE THERAPEUTIC RESPONSE.
I THINK THIS IS A LONG WAY OF
SAYING IT THAT I THINK THAT THE
FIELD DOESN'T KNOW EXACTLY WHY
THIS IS POSSIBLE JUST YET AND
PHENOMENON SEEMS TO BE REAL AND
SOME COMPOUNDS AND
NONHALLUCINOGENIC AGONISTS ARE
TESTED IN PEOPLE AND KNOWN TO BE
DEFINITIVELY NONHALLUCINOGENIC
AND SOME USED AS THERAPEUTICS
FOR INSTANCE LIKE PARKINSON'S
DISEASE OR SOMETHING LIKE THIS
AND WHY YOU CAN CREATE
NONHALLUCINOGENIC AGONIST IS A
MYSTERY TO THE FIELD STILL.
>>RELATED TO THAT IS MORE
MOLECULAR NATURE OF THE
RESPONSE. FOR EXAMPLE
EXTRAORDINARY EFFECTS OF
NEURONAL PLASTICITY AND SPINES
AND EXTENSIONS AND ARE THESE
BASICALLY DUE TO TRANSCRIPTIONAL
EFFECTS OR TRANSLATIONAL?
DO WE HAVE AN UNDERSTANDING OF
THAT?
>>YEAH. I DID MY POST DOCTORAL
WORK AND GENE EXPRESSION THAT
MUST LEAD TO LONG LASTING
CHANGES AND TO BE HONEST WE
HAVEN'T SEEN MANY ROBUST CHANGES
IN GENE EXPRESSION OF
PSYCHEDELIC AND PEOPLE HAVE
LOOKED ACROSS THE BRAIN AND DONE
TRANSCRIPTOMICS YOU SEE
IMMEDIATE CHANGES IN EARLY GENES
BUT NOT MASSIVE CHANGESES IN
GENE EXPRESSION AND SOME
INDICATIONS MAY BE EPIGENETICS
THAT ARE CHANGE THE AND MAYBE IF
YOU CAN FOCUS ON VERY SPECIFIC
CELL POPULATIONS YOU MIGHT SEE
TRANSCRIPTIONAL CHANGES THAT
STILL IS WORK THAT IS ONGOING
AND CURRENTLY HYPOTHESIS IS THAT
THIS LARGELY RELIES ON
TRANSLATION.
WHAT IS KNOWN IS IF YOU ACTIVATE
M4 PATHWAY AND START PRODUCING
PROTEINS FOR NEUROPLASTICITY IT
IS FEEDBACK LOOP AND WILL
PRODUCE BRAIN DERIVED -- YOU CAN
GET A LONG LASTING EFFECT ON
NEURONAL GROWTH THAT IS
STIMULATING IN A SHORT PERIOD OF
TIME.
>>IN ELAITION TO INCREASED
SPINES AND AXONAL GROWTH IS THAT
NEW PROTEIN SYNTHESIS OR RE --
IN SOME WAY ASSEMBLY AND
ORGANIZATION OF BUILDING BLOCKS
THAT ARE ALREADY THERE?
>>WE BELIEVE A LARGE PART OF IT
IS NEW PROTEIN SYNTHESIS.
>>THAT CAN OCCUR IN -- IN
MATTER OF MINUTES WITH
ADMINISTRATION OF PSYCHEDELIC?
>>NO. WE KNOW TIME COURSE FOR
WHICH THIS HAPPENS AND LOTS OF
WORK DONE IN VIVO WITH KETAMINE
AND SILO KRIEBIN AND OUR GROUP
HAS DONE WORK IN VITRO AND WE
FOUND THAT SPINES TEND TO GROW
OVER COURSE OF ABOUT 24 HOURS.
YOU DON'T SEE SPINE GROWTH UNTIL
6 TO 24 HOURS AND THEY REACH
MAXIMUM AND PERSIST OVER A
PERIOD OF TIME. YOU CAN PULSE
FOR DIFFERENT AMOUNTS OF TIME
AND GET STRUCTURAL PLASTICITY
EFFECTS AND FOR INSTANCE YOU CAN
PUT DRUGS ON CORTICAL NEURONS
AND YOU CAN PUT THEM ON NEURONS
FOR 15 MINUTES TAKE DRUG AWAY
AND WAIT THREE DAYS AND COMING
BACK THREE DAYS LATER THEY WILL
HAVE GROWN BUT DON'T GROW IN
FIRST 15 MINUTES BUT TAKE A FEW
DAYS TO GROW FRIEND IN VARIOUS
STUDIES YOU AND OTHERS PERFORM
AND MENTIONED TODAY ROLONGED
CLINICAL EFFECTS OF DOSES OF
PSYCHEDELICS AND PATIENTS
RECEIVED PSYCHOTHERAPY AND MAYBE
YOU WILL COMMENT ABOUT MUSIC.
WHAT ROLE DOES THAT SUPPORTIVE
THERAPY HAVE.
IS PSYCHEDELIC MAKING PEOPLE
RESPONSIVE TO TRADITIONAL WAYS
OF TREATMENT? WHAT IS
RELATIONSHIP BETWEEN THEM?
>>MOST HONEST ANSWER IS WE
DON'T KNOW REALLY. THE MORE
INFORMED CLINICALLY INFORMED
ANSWER IS THAT WE DO BELIEVE
THAT PSYCHOTHERAPEUTIC ASPECT OF
PSYCHEDELIC THERAPY IS A REAL
AND ACTIVE INGREDIENT YOU MIGHT
RECALL BACK IN SLIDES AND SLIDE
I SHOWED FROM FIRST CLINICAL
STUDY IN CANCER PATIENTS THAT
PEOPLE WERE RANDOMIZED TO
RECEIVE A VERY HIGH DOSE OF
PSILOCYBIN FIRST OR TRIVIAL DOSE
OF PSILOCYBIN FIRST.
PREPARATION AND MONITORING
INTEGRATION AND AFTER CARE AND
WHILE THOSE WHO RECEIVED HIGH
DOSE OF PSILOCYBIN FIRST SHOWED
EMARKETABLE REDUCTION IN --
THOSE SHOWING PSILOCYBIN SHOWED
HALF EFFECT SIZE THAT IS
REMARKABLE EFFECTS PERFECT
EXAMPLE OF EFFECT OF FARM COLONL
CAL PACKAGING AROUND IT AND TO
CONSIDER IS IN STUDY THAT
[INDISCERNIBLE] HARRIS CONDUCTED
WILL YOU SEE FIGURE AND PANEL
FOR THOSE GETTING TELO PRAM WAS
COUPLED TO PATH OF THOSE
RECEIVING PSILOCYBIN AND
SEVERITY 7 DAYS AFTER INITIATION
OF THERAPY THAT IS NOT WHAT YOU
EXPECT AND PATIENT RECEIVING
THIS AND TAKES LONGER FOR
EFFECTS TO KICK IN THAT MIGHT BE
EXAMPLE OF EFFECT OF ALL OTHER
STUFF AND PSYCHOTHERAPY AROUND
IT TWO OTHER WAYS TO THINK ABOUT
THIS WITH YOU. ONE, LOTS OF
PEOPLE TOOK LSD IN 50S AND 60S
AND DIDN'T BECOME DEPRESSED AND
STOP SMOKING OR DRINKING AND
DOING OTHER THINGS AND BELIEVE
THAT CONTEXT AND FRAMING AROUND
EXPERIENCES HAVE HUGE EFFECT AND
LAST WAY TO THINK ABOUT THIS IS
BECAUSE IF YOU TAKE BROAD
EXAMPLE OR SENSE OR HEURISTIC
KNOWLEDGE THAT MAYBE DRUGS ARE
SOMEHOW LEANING TO
NEUROPLASTICITY AND I DON'T
THINK WE SHOULD EXPECT THE BRAIN
TO NATURALLY EVOLVE TO A MORE
ADAPTIVE STATE BECAUSE WE MADE
IT MORE PLASTIC AND THINK THAT
WE HAVE TO IF WE MAKE BRAIN
PLASTIC WE DO SOMETHING WITH
PLASTICITY AND THE PREPARATION
AND MONITORING AND AFTER CARE WE
PROVIDE PROVIDES A REAL MOLD
WITHIN WHICH YOU CAN PUT PLASTIC
BRAIN TO HELP IT INTO A MORE
ADAPTIVE STATE AFTERWARDS.
>>WE HAVE SEVERAL QUESTIONS TO
THE RELATIONSHIP BETWEEN SLEEP
AND RESPONSE TO A PSYCHEDELIC.
HAVE THERE BEEN ANY STUDIES
WHERE PSYCHEDELICS HAVE BEEN
ADMINISTERED TO SLEEPING
PATIENTS?
>>NOT THAT I'M AWARE OF AND A
NUMBER OF FOLKS TALKED ABOUT
CONDUCTING STUDIES AND PATIENTS
THAT ARE ENASSISTHETIZE THE AND
[INDISCERNIBLE] AT UNIVERSITY OF
WISCONSIN MADISON AND BORIS HYPE
AT STANFORD AND NOT SURE IF THEY
CONDUCTED STUDIES OR PUBLISHED
IT YOU ARE IN GEOGRAPHY. WHAT
IS UP?
>>WE ARE COLLABORATING ON THAT
AND NOT READY FOR STUDY YET. WE
ARE STILL WORKING ON IT AND NO
ONE HAS GIVEN A PSYCHEDELIC TO
SOMEONE WHILE THEY ARE SLEEPING
BUT BELIEVE THAT PSYCHEDELICS
HAVE BEEN ADMINSTERED BEFORE
SOMEONE GOES TO SLEEP AND ARE
EFFECTS.
FOR INSTANCE THERE IS SOME
SUPPRESSION THAT IS A GOOD
HALLMARK ACTUALLY OF MANY
ANTIDEPRESSANT COMPOUNDS THAT
SUPPRESS ANTIDEPRESSION.
>>WHAT DO YOU THINK.
>>HE GAVE DURING SLEEP I DON'T
KNOW WAS SUBJECT OF ONE OF MY
PROPOSALS GOING TO UC DAVIS BUT
NEVER HAD A CHANCE TO TRY IT.
FRED, HAVE ANY THOUGHTS?
>>I THINK IT IS POSSIBLE YOU
MAY GET MUCH MORE VIVID DREAM
STATES AND PEOPLE LIKE TO
COMPARE PSYCHEDELIC STATES TO
DREAMLIKE STATES THAT OFFER REM
SUPPRESSION.
>>I SUSPECT WHAT MIGHT HAPPEN
IS PATIENTS MIGHT WAKE UP.
>>POSSIBLE.
>>I CAN SAY IT IS UNLIKELY FOR
PATIENTS TO FALL ASLEEP UNDER
EFFECTS OF HIGH DOSE OF SOOILO
KRIEBIN.
>>THERE IS EVIDENCE PLAYING A
ROLE IN WAKING CONSCIOUSNESS.
YOU KNOW?
>>SLEEP BY WHATEVER ITS
MECHANISM IS MAY ACTUALLY HAVE A
PROFOUND EFFECT ON THE
PSYCHEDELIC COMPOUND. MAYBE
DELAY ACTION.
>>THERE HAS BEEN A HYPOTHESIS
FOR A LONG TIME DREAMING STATES
MIGHT BE IN RELEASE OF
PSYCHEDELICS IN A WAY, SHAPE OR
FORM THAT HAS NEVER BEEN
RIGOROUSLY TESTED IN LARGE PART
BECAUSE IT IS EXTREMELY HARD TO
MEASURE MOLECULES WITH TEMPORAL
PRECISION THAT IS REQUIRED AND
WITH SENSITIVITY BECAUSE THEY
ARE PRODUCED IN LOW QUANTITIES.
>>COULD WE IMAGINE A HEALTHY
DOSE OF ANOTHER 2A AGONIST
BEFORE SLEEP IN A FEW WEEKS FOR
PEOPLE TO SEE IF THEY DREAM?
>>INTERESTING QUESTION.
ARE THERE PEOPLE WHO CAN TAKE 5
OR 10 MILLIGRAM DOSE AND
ACTUALLY HAVE NO PSYCHIC
EXPERIENCE?
IS THERE SOME SORT OF
PSYCHOLOGICAL RESIDUAL OR
WHATEVER IT IS?
DO THESE PEOPLE EXIST?
>>I THINK THOSE WHO FORM
PSYCHOLOGICAL RESISTANCE TO
EFFECTS HAVE BAD TRIPS BECAUSE
THEY TRY TO CONTROL EXPERIENCE
AND EFFECT. I HAVE HAD ONE
PARTICIPANT IN A STUDY WHERE IT
WAS OPEN DOSE AND HIGH DOSE OF
PSILOCYBIN AND EFFECTS AND VERY
FEW AND FAR BETWEEN AND DON'T
BELIEVE ARE WELL CHARACTERIZE AT
ALL HARD TO FIND CAN'T PREDICT
IT YET BUT BELIEVE THAT PEOPLE
EXIST.
>>YEAH.
>>INTERESTING TO KNOW IF SUCH
INDIVIDUALS HAVE EMILORATION OF
CLINICAL PHENOTYPE.
>>THIS IS ANECDOTAL AND GOT AN
E-MAIL ONCE FROM A PERSON WHO
CLAIMS THAT HE AND HIS DAUGHTERS
HAVE TAKE N EXTREMELY HIGH DOSE
OF PSYCHEDELICS NEVER
EXPERIENCED HALLUCINOGENIC
EFFECTS BUT HAVE HIGHLY
ANTIDEPRESSANT EFFECTS AND
WANTED GENOTYPE THEM AND SEE
WHAT IT WAS ABOUT THEIR
RECEPTORS THAT HAS TO DO WITH
RECEPTOR DENSITY IN BRAINS AND
MAYBE HAVING TO DO WITH SMALL
SINGLE NUCLEOTIDE POLYMORPH ISMS
AND KNOWN THAT GENETIC
MODIFICATIONS TO RECEPTOR COULD
IMPACT RESPONSE AND FRED SAID
THEY ARE NOT WELL CHARACTERIZED
IF OUT THERE WANTING TO
VOLUNTEER FOR STUDIES LET US
KNOW. REALLY INTERESTING
QUESTION PLANS TO TAKE
INDIVIDUALS WITH LOW EXPRESSION
OF PSYCHEDELIC EFFECT AND SOME
WITH HIGH EXPRESSION OF TOX TIS
AND DO ACTUALLY GENE SEQUENCING
ON PEOPLE OR.
>>I THINK FINDING PEOPLE HAS
BEEN HARD AND WE DON'T HAVE
ENOUGH OF THEM TO BE ABLE TO YOU
KNOW HAVE THINGS THAT WOULD BE
STATISTICALLY SIGNIFICANT.
>>YEAH.
>>SO, NEXT QUESTION, IS THERE A
RELATIONSHIP BETWEEN NATURE AND
MAGNITUDE OF PSYCHEDELIC
EXPERIENCE AND CLINICAL EFFECT?
>>THERE HAVE BB A NUMBER OF
STUDIES AND ANALYSIS CONDUCTED
ACROSS NUMBER OF SITES AND
INSTITUTIONS SUGGESTING IN FACT,
YES. EXACT NATURE OF
RELATIONSHIP IS SOMETHING THAT
IS VERY AMENABLE TO DEEPER
INVESTIGATION AND INTERROGATION
AND AT MOMENT SEEMS TO BE CASE
AND SOME CAVEATS HERE COULD BE
EVERYBODY READ MICHAEL COLLIN'S
BOOK AND EVERYBODY THINKS THEY
SHOULD HAVE A BIGAMIST CAL
EXPERIENCE THAT WILL HEAL THEM
AND FIGHTING AGAINST EXPECTANCY
OF SORTS OF TYPES AND MANNER AND
ONE DATA POINT IS IN CONTRAST IS
THAT YOU CAN -- WE ASK PEOPLE
OFTEN TO RATE OVERALL STRENGTH
OF DRUG EFFECT ON SCALE AND HAVE
DIFFERENT RATING SCALES TO TRY
TO INTERROGATE ASPECTS OF
SUBJECTIVE EXPERIENCE THAT IS
NOT OVERALL STRENGTH OF DRUG
EFFECT AND NOT GOOD OR BAD DRUG
EFFECTS NECESSARILY AND SEEMS TO
BE MORE SPECIFICALLY PECULIAR
ASPECTS EXPERIENCING MYSTICAL
EXPERIENCE AND CORRELATED TO
THERAPEUTIC OUTCOMES AND MAY BE
IT IS NOT JUST A MYSTICAL
EXPERIENCE THAT IS PREDICTIVE OF
PSYCH LONL INSIGHT THAT PEOPLE
GAIN DURING EXPERIENCES THAT
LEAD TO THERAPEUTIC OUTCOME AND
AGAIN ARE EARLY STAGE STUDIES
STILL. LOTS OF EFFECTS HAVE TO
BE FULLY REPLICATED ACROSS ALL
SITES.
>>ANOTHER INTERESTING QUESTION,
YOU FOCUS ON SEROTONIN RECEPTOR
BASED ON ELEGANT WORK YOU HAVE
DONE AND IS THERE A ROLE OF
OTHER CENTRAL NERVOUS SYSTEM
RECEPTORS THAT DO THEY
PARTICIPATE?
IS THERE ANY EVIDENCE OF THERE
BEING INTRINSICALLY INVOLVED OR
SECONDARILY?
WHAT IS STATUS OF THAT?
WHAT --
>>I WOULD SAY IT DEPENDS ON
DRUG. YOU KNOW, PSYCHEDELICS
AND CLASSIC PSYCHEDELICS THAT
FRED MENTIONED ARE 5HT2A
AGONISTS THAT HAVE UNIQUE
POLYPHARMACOLOGY PROFILE AND
AMPHETAMINE PROFILES ARE
SELECTED FOR 2HC AND 2P AND
TRIPTO MEANS ARE LESS SELECTIVE
HITTING SEROTONIN RECEPTORS AND
[INDISCERNIBLE] ARE LESS THAN
THAT HITTING DOPAMINE RECEPTORS
AND [INDISCERNIBLE] RECEPTORS
AND YOU CAN DO A TEST IN RODENTS
WHERE BASICALLY YOU TRAIN THEM
TO PRESS A LEVER WHEN YOU GIVE
THEM A PSYCHEDELIC DRUG. YOU
CAN USE IT TO TEASE OUT
MECHANISM WITH SUBJECTIVE
EXPERIENCE AND LSD AND DOPAMINE
EARTHIC SYSTEM THAT SEEMS TO BE
IMPORTANT FOR THAT PARTICULAR
EXPERIENCE OF THOSE ANIMALS THAT
ARE ADMINISTERED LSD.
>>FRED, THERE IS A QUESTION
ABOUT I MENTIONED IN
INTRODUCTION THE WORD MUSIC.
YOU DIDN'T COMMENT ABOUT IT.
DO YOU -- SOMEONE ASKED WHAT IS
RELATIONSHIP THAT IS BETWEEN
MUSIC AND PSYCHEDELIC EFFECTS
AND TREATMENT?
>>I'M SORRY FOR NOT PICKING UP
ON THAT. I KNOW I HEARD YOU SAY
THAT. I CAN SPEAK FOR ANOTHER
HOUR AND A HALF ABOUT
RELATIONSHIP BETWEEN MUSIC AND
PSYCHEDELICS AND DIDN'T WANT TO
BEHAVIOR THE POINT.
>>YOU CAN TALK AS LONG AS YOU
WANT. WE CAN GO HOME IN 10
MINUTES.
>>OKAY. I WILL TRY TO SEE WHAT
I CAN DO WITH THIS.
SO SOME OF EARLIER STUDIES WITH
LSD IN CLINIC AND RESEARCH LAB
WERE SET BY A NUMBER OF PROBLEMS
MOSTLY DOO YOU TO IGNORANCE
ABOUT SUBJECTIVE EFFECTS OF
DRUGS AND SOME ADMINISTRATIONS
OF LSD THAT OCCURRED EARLY ON IN
HISTORY OF USE OF COMPOUNDS IN
CLINIC AND LAB. THEY OCCURRED
WITHOUT MUCH PSYCHOLOGICAL
SUPPORT IF AT ALL AND STORIES
BEING STRAPPED TO GURNEY
SUBJECTED WITH LSD WITHOUT PRIOR
PREPLATION THAT LEFT HOURS ON
ENDS AND NOT ENDING WELL AND
THROUGH RECEIVED KNOWLEDGE FROM
INDIGENOUS PRACTICE OR
EXPERIMENTATION AND NATURAL
EVOLUTION OF THIS EXPERIENCE
PEOPLE REALIZED CREATING
COMFORTABLE ENVIRONMENT THIS
COULD BE BETTER RECEIVED THAN
CHAOTIC OR UNCONTROLLED OR
UNCOMFORTABLE ENVIRONMENT AND IS
ACTUALLY A CIRCUIT LEVEL
NEUROSCIENCE HERE TO BE EXPLORED
AND 2A RECEPTORS EXPRESSED ALONG
AUDITORY PATHWAY NOT ON COCHLEAR
NERVE BUT IN GENETIC NUCLEI AND
IN BRAINSTEM NUCLEI THAT LEAD TO
PRIMARY AUDITORY CORTEX AND ARE
EARLIER ANIMAL STUDIES THAT ARE
DEMONSTRATING ACTIVATION OF
SEROTONIN 2A RECEPTOR CHANGING
FIELDS OF CERTAIN AUDITORY
NEURONS IN THIS PATHWAY AND ALSO
YOU KNOW RESPONSE PROFILES AND
FREQUENCY RESPONSE PROFILES FOR
NEURONS AND IS A BASIC AUDITORY
NEUROSCIENCE PLAYING IN
PSYCHEDELIC EXPERIENCES THAT
CHANGES FUNDAMENTAL WAY THAT YOU
HEAR SOUND AND IN PARTICULAR
MUSIC.
THERE ARE LOTS OF STUDIES THAT
COULD BE DONE TO TRY TO
DETERMINE BASIC AUDITORY
NEUROSCIENCE THAT HAVE BY AND
LARGE NOT BEEN DONE AND PEOPLE
COME ING OUT OF EXPERIENCES AND
ALONG WAY WHEN FOLKS REALIZE
TUNING SETTING OR CONTEXT OF
ENVIRONMENT OF EXPERIENCE THAT
CAN HELP PROVIDE STABLE PLATFORM
FOR PEOPLE TO HAVE EXPERIENCES
THAT IS MUCH MORE COMFORTABLE
ENVIRONMENT AND PEOPLE REALLY
PLAYED WITH MUSIC AND BEGAN TO
FIND THAT PSYCHEDELICS CAN
REALLY, REALLY DEEPEN AND CHANGE
HOW YOU EXPERIENCE MUSIC PEOPLE
COMING OUT OF HYDROPSILOCYBIN
MUSICIANS SAID THEY BECAME AND
WERE INSEPARABLE FROM THE MUSIC
AND THEY FELT EVERY NOTE PLAYED
AND CLAIMING RADICAL THINGS SUCH
AS I UNDERSTOOD WHAT THE
COMPOSER MEANT WHEN THEY TRIED
TO EXPRESS AND COMPOSE THIS
PIECE AND THAT IS UNVERIFIABLE
AND BEST LEFT TO SPECULATION BUT
SEEMS TO ME INCONTROVERTIBLE
THAT PSYCHEDELICS REALLY OPEN A
PERSON UP IN A PROFOUND WAY TO
DEEPLY IMMERSING THEMSELVES AND
BECOMING ABSORBED IN AESTHETIC
EXPERIENCES THAT HAVE BEEN
ATTEMPTS TO UNDERSTANDING THIS.
IN FACT INTERESTING STORY TO
TELL ABOUT A WOMAN NAMED HELEN
BONNIE WHO WAS A PSYCHIATRIC
NURSE AT MARYLAND PSYCHIATRIC
INSTITUTE IN SPRING GROVE
RESEARCH CENTER IN MARYLAND WHO
WAS A PRIMARY PSYCHIATRIC NURSE
INVOLVED IN [INDISCERNIBLE]
THERE AND CONCERT VIOLINIST AND
MUSICAL PROFILE AND BACK IN DAY
PEOPLE WOULD -- SIT WITH BOX OF
VINYL AND THEY ARE
GETTINGAGETATED AND I WILL PUT
ON SOMETHING CALM AND THEY ARE
GETTING TOO CALM I WILL PUT
SOMETHING ON TO STIR THE POT AND
GET THEM ENGAGED PSYCHOLOGICALLY
AND HELEN CAME UP WITH A METHOD
GUIDED MUSIC DIFFERENT PHASES OF
PSYCHEDELIC EXPERIENCE AND
CONTROLLED SUBSTANCE ACT WAS
PASSED AND THIS WENT AWAY DIDN'T
STOP BEING A MUSIC FILE --
GUIDED IMAGERY WITH WITH NEW
MUSIC THAT EXISTS OUTSIDE OF
PSYCHEDELICS AND TO SAY THERE IS
A WHOLE WORLD HERE TO EXPLORE --
>>AND YES. WE ARE SLOWLY
RUNNING OUT OF TIME. HERE WE
WANT TO END WITH TWO REALLY
CRITICAL QUESTIONS.
ONE, IS THE FREQUENT OR
LONG-TERM USE OF PSYCHEDELICS
SAFE?
>>DEPENDS. DEPENDS.
PSYCHEDELICS ARE MEDICALLY SAFE
FOR THE RIGHT PROPERLY SCREENED
INDIVIDUALS WHEN ADMINISTERED IN
A CONTROLLED ENVIRONMENT THAT WE
DON'T HAVE A LOT OF INFORMATION
ABOUT CHRONIC USE OF
PSYCHEDELICS AND CONCERN ABOUT
MICRO DOSING MOVEMENT IS DUE TO
POTENTIAL BINDING OF VARIOUS
PSYCHEDELIC DRUGS TO SEROTONIN
2B RECEPTORS EXPRESSED ON WALLS
OF THE HEART AND CHRONIC
ADMINISTRATION DRUG AND DISEASE
AND CARDIO MYOPATHY THAT IS
HYPOTHETICAL RISK NOT BORED OUT
BY EVIDENCE BUT A CONCERN.
>>OKAY. AND ANOTHER CRITICAL
QUESTION, GIVEN HUGE PUBLIC HYPE
ABOUT PSYCHEDELICS, HOW DOES
THAT INFLUENCE SELECTION OF
PATIENTS FOR YOUR STUDY?
CAN YOU HAVE A REAL CONTROL IF
THE EXPERIENCE IS REQUIRED FOR
LONG TERM EFFECTS? IS THAT A
PRACTICAL PROBLEM IN TRYING TO
DO CLINICAL STUDIES THAT HAVE
PEOPLE THAT ALREADY HAVE
ANTICIPATION AND ALL KINDS OF
INFORMATION THAT I SUSPECT IS
VERY MISLEADING.
SO, MAYBE A BRIEF FINAL COMMENT
ABOUT THAT, DAVID.
WHAT IS YOUR VIEW?
>>I THINK THAT FRED PROBABLY
WOULD BE A BETTER PERSON TO
ANSWER THIS QUESTION.
I WILL SAY THAT, YOU KNOW,
EXPECTATIONS ARE A HUGE ISSUE
FOR CLINICAL TRIALS.
IN DESIGNING PLACEBO CONTROLLED
CLINICAL TRIALS IS INCREDIBLY
CHALLENGING AND MAYBE IMPOSSIBLE
IN SOME WAYS AND WAYS TO GET
EFFICACY WITHOUT DOING STANDARD
PLACEBO CLINICAL TRIAL AND FDA
PUSHED FOR DOSE RESPONSE STUDIES
SEEING NICE DOSE ESCALATION, YOU
KNOW, YOU CAN FILL IN FOR THE
DRUG THAT IS EFFICACIOUS. FRED,
WANTING TO PICK UP ON THIS?
>>YEAH. JUST TO SAY THAT THE
QUESTION OF HOW DO YOU BLIND A
MYSTICAL EXPERIENCE. IS IT A
PERTINENT ONE OR STRUGGLE FOR
FIELD AND VERY IMPERFECT ACT OF
CONTROL CONDITIONS THAT HAVE
BEEN ATTEMPTED LIKE NIEOCENE AND
METHO FEN ADATE AND SOMETHING
THAT THE FIELD CONTINUES TO
STRUGGLE WITH FOR SURE.
>>SO, IS IT A CONTROLLED
SUBSTANCE?
>>YES.
>>YES, IT IS.
>>IN SAME WAY AS PEOPLE THAT
ARE GROWING MARIJUANA PLANTS
THEY CAN GET THEIR OWN
MUSHROOMS. IS THAT A PRACTICAL
ISSUE YOU THINK FROM PRACTICAL
HEALTH STANDPOINT OR SHOULDN'T
WE BE CONCERNED ABOUT THAT?
>>MY CONCERN LIKE FRED
MENTIONED WHEN COMPOUNDS ARE
GIVEN IN A SAFE ENVIRONMENT AND
SUPPORTIVE ENVIRONMENT THEY
COULD BE ADMINISTERED AND BE
SAFE AND INCREDIBLY HELPFUL FOR
PATIENTS WHEN ADMINISTERED IN
UNCONTROLLED ENVIRONMENTS THOUGH
THERE ARE GREATER RISKS OF
COURSE AND DECRIMINALIZATION
EFFORTS AND GREATER ACCESS TO
MOLECULES IN GENERAL PUBLIC WE
HAVE TO BE CONCERNED ABOUT THOSE
TYPES OF ADVERSE EVENTS.
>>GOOD. WELL, LISTEN, ON
BEHALF OF THE HUNDREDS OR MAYBE
THOUSANDS OF PEOPLE AROUND THE
WORLD, I FORGOT TO MENTION THAT
FOLKS IN 38 DIFFERENT COUNTRIES
NOW DOWNLOAD THESE PROGRAMS
EITHER LIKE NOW OR FROM THE
VIDEO ARCHIVE.
ON BEHALF OF EVERYBODY, WE WANT
TO REALLY THANK YOU FOR VERY
EXCITING AND INSIGHTFUL
PRESENTATIONS OF THE STATE OF
THE SITUATION.
IT IS OBVIOUSLY EVOLVING AND WE
WILL HEAR MUCH, MUCH MORE ABOUT
IT.
BOTH FROM A CLINICAL
INVESTIGATIVE STANDPOINT AND
ALSO BRIDGING THE THEME OF THE
COURSE TO A REDUCTION
UNDERSTANDING OF WHAT IS GOING
ON.
SO, THANK YOU ALL VERY MUCH.
THERE ARE SOME ADDITIONAL
QUESTIONS THAT I WILL LOOK
THROUGH.
PERHAPS I CAN SEND THEM OFF TO
YOU IF YOU WISH TO ANSWER TO THE
INDIVIDUAL WHO PRESENTED THEM.
SO, THANK YOU ALL AGAIN.
WE APPRECIATE VERY MUCH YOUR
PARTICIPATING.