GOOD MORNING, EVERYONE.
AND THIS IS THE ANNUAL MEETING
AS THE FIRST ONE WHERE WE CAN
SEE THE EACH OTHER.
I'M DR. INNA BELFER AT THE NCCIH
AND AND BEHALF OF FELLOW NCCIH I
WOULD LIKE TO WELCOME YOU ALL TO
THE FIFTH ANNUAL P.I. MEETING
FOR THE PROGRAM CALLED EXPLORING
MECHANISMS UNDERLYING ANALGESIC
OF MINOR CANNABINOIDS AND WE'LL
BEGIN WITH WELCOME REMARKS FROM
THE LEADER OF THE PROGRAM, DAVID
SHURTLEFF AND MEETING OVERVIEW
AND GOALS BY DR. EMMELINE
EDWARDS DIRECTOR OF NCCIH
DIVISION OF EXTRAMURAL RESEARCH.
>> OKAY.
OKAY.
THANK YOU.
WE'RE STILL WORKING OUT -- WE'RE
NOT USED TO BEING BACK IN PERSON
APE -- ANYMORE IT TAKES LONGER
TO DO THINGS AND THIS IS OUR
FIFTH ANNUAL MEETING, OUR FIRST
IN PERSON AND PROBABLY OUR LAST
P.I. MEETING FOR THE PROGRAM
THAT STARTED IN JANUARY OF 2019
WHEN WE ISSUED A REQUEST FOR
APPLICATIONS FOR INTEREST FOR
CANNABINOID AND PUR TURPINE
RESEARCH AND WE FUNDED $3
MILLION WITH FEEL LIKE WE MOVED
THE NEEDLE ON THERAPEUTICS WITH
CANNABIS.
HOW DID WE GET HERE?
SO AS THE NATIONAL CENTER FOR
COMPLEMENTARY AND INTEGRATIVE
HEALTH, WE REALLY STUDIED THE
RIGOROUS DETERMINATES THROUGH
RIGOROUS SCIENTIFIC
INVESTIGATION THE SAFETY OF
COMPLEMENTARY AND INTEGRATIVE
HEALTH APPROACHES WHICH IS
GREAT.
WE LOOK AT THE WHOLE PERSON AND
THINK OF PHYSICAL APPROACHES AND
PSYCHOLOGICAL AND FOR THE
PURPOSES OF THIS MEETING,
NUTRITIONAL APPROACHES INCLUDING
BIOLOGICAL ACTIVITIES OF NATURAL
PRODUCTS, DIETARY SUPPLEMENTS,
BOTANICALS WHICH OF COURSE
CANNABIS FALLS INTO AND
VITAMINS.
WHEN WE THINK ABOUT WHEN WE'RE
GOING TO INVEST IN A PARTICULAR
AREA OF SCIENCE WE THINK ABOUT
TWO THINGS, IS THERE ENOUGH
RIGOROUS PRE-CLINICAL RESEARCH
TO SUPPORT FURTHER STUDY SECOND
IS IT BEING USED BY THE AMERICAN
PUBLIC AND CANNABIS CHECKS BOTH
BOXES IT'S ESTIMATED 55 MILLION
AMERICANS HAVE USED MARIJUANA
AND 83 MILLION REPORT USING
CANNABIS FOR MEDICAL USE.
CLEARLY WE CHECK THE BOX ON ITS
USE BY THE AMERICAN PUBLIC AND
THERE IS A LOT OF GOOD BASIC
SCIENCE TO SUGGEST WE UNDERSTAND
THE ENDOCANNABINOID SYSTEM AND
KNOW A LOT IN GENERAL AND THE
REASON NCCIH DECIDED TO TAKE A
LEAP INTO STUDYING CANNABIS.
AND TO REITERATE THAT IN FACT
NOW -- ALLERGIES ARE KICKING IN
TODAY.
24 STATE AND THE DISTRICT OF
COLUMBIA LEGALIZED MARIJUANA AND
OTHERS HAVE LEGALIZED IT FOR
MEDICAL USE AND IT'S AN
OPPORTUNITY FOR THE PUBLIC TO
USE IT WIDELY.
IT'S A BIT OF A DICHOTOMY UNDER
FEDERAL LAW IT'S SCHEDULED
MEANING HIGHLY RESTRICTED IN
TERMS OF ACCESS AND AVAILABILITY
WITH AVAILABILITY THROUGH THE
MISSISSIPPI AND NOW NEW GROWERS
HAVE COME ONLINE THE DRUG
ENFORCEMENT AGENCY APPROVED.
THERE'S A VARIETY OF
CANNABIS-BASED PRODUCTS THAT
HAVE MOVED FORWARD TO FDA NOT
SCHEDULED AND NABILONE FOR
TREATING AIDS WASTING AND WITH
THE FARM BILL PASSED CERTAIN
CANNABIS PRODUCTS SUCH AS HEMP
ARE AVAILABLE AND UNSCHEDULED.
THERE ARE SOME CHALLENGES WITH
THE SCHEDULING OF COURSE.
OVERSIGHT AND LICENSING FROM
DEA, SECURITY MEASURES ARE NEED
ED THERE'S GOOD NEWS, AND
SERVICE WAS RECOMMENDED TO THE
DRUG ENFORCEMENT AGENCY CANNABIS
BE RESCHEDULED AS A SCHEDULE 3
COMPOUND MAKING ITS WAY THROUGH
THE DEPARTMENT OF JUSTICE AND
DEA.
WE'RE HOPEFUL THIS WILL HAPPEN.
ANYTHING THAT MOVE RESEARCH
QUICKER, FASTER, BETTER WE'RE
ALL FOR IT AND HOPE THIS WILL
MAKE LIFE EASIER BECAUSE WE
DON'T YET KNOW WHAT THIS WILL
BRING IN BRINGING RESEARCH
QUICKER, BETTER, FASTER BUT
WE'RE HOPEFUL.
REGARDLESS OF THE SCHEDULE IS
NCCIH WE'RE STILL INTERESTED IN
THE PLANT AND COMPLEX MIXTURE OF
MINOR CANNABINOIDS AND TURPINE
AND WE'RE INTERESTED FOR
THERAPEUTIC POTENTIAL AND
PRECLINICAL RESEARCH SHOWED THE
CANNABINOIDS TARGET SITES
RELEVANT TO TREATMENT SUCH AS
FOR STIMULATION AND OTHER THAT
WILL ARE ANTIINFLAMMATORY
PROPERTIES AND ANALGESIC AND
ANTIPSYCHOTIC POTENTIAL
PROPERTIES.
WE LAUNCHED A NOSI TO STUDY THE
ANALGESIC PROPERTIES BUT WE OPEN
THAT UP TO OTHER INSTITUTES AT
THE NIH AND TWO OR DELIGHT
OTHERS SIGNED ON TO THE IN THE
OF INTEREST INCLUDING THE
NATIONAL CANCER INSTITUTE,
NATIONAL EYE INSTITUTE AND
NATIONAL INSTITUTE ON AGING AND
THE NATIONAL INSTITUTE ON
ALCOHOL ABUSE AND ALCOHOLISM AND
THE NATIONAL CENTER FOR
CRANIODENTAL FACIAL RESEARCH AND
NIDA AND THE NATIONAL INSTITUTE
ON NEUROLOGICAL DISEASE OF
STROKE AND THE OFFICE OF
RESEARCH ON WOMEN'S HEALTH.
AND GOOD TO SEE OTHER INSTITUTES
SEE POTENTIAL IN STUDYING
CANNABIS FOR THE THERAPEUTIC
BENEFITS PARTICULARLY THE MINOR
CANNABINOIDS AND STAYING AWAY
FROM THE MOST PSYCH ACTIVE THAT
CAUSES DEPENDENCE AND ADDICTION.
YOU'LL BE HEARING ABOUT INTEREST
IN THERAPEUTIC POTENTIAL FOR
CANNABIS AND IT'S A NICE TO SEE
ALL THIS TAKING PLACE AT THE NIH
NOW THAT WE'RE STARTING TO SEE
CHANGES IN SCHEDULING AND OTHER
ASPECTS THAT MAY MAKE RESEARCH
EASIER ACROSS THE NIH AND
FINALLY TO CONDITION THE EFFORT
AND THE MOMENTUM, JUST THIS YEAR
WE ISSUED AN RFA LOOKING TO
SUPPORT A RESEARCH CENTER FOR
CANNABIS AND CANNABINOID
RESEARCH.
THOSE APPLICATIONS CAME IN AND
WE HAD A VERY ROBUST RESPONSE TO
THIS RFA.
THE APPLICATIONS WILL BE
REVIEWED IN JULY AND WE THINK
THIS CENTER HAS THE OPPORTUNITY
TO FURTHER ADVANCE AND FURTHER
THE RESEARCH THAT NIH SUPPORTS
BY GIVING OPPORTUNITIES TO
RESEARCHERS WHEN MAY BE OUTSIDE
THE CANNABINOID RESEARCH FIELD
TO GET INVOLVED AND GIVE THEM A
HELPING HAND TO GET THE RESEARCH
GOING IN THIS COMPLEX REGULATORY
ENVIRONMENT.
WITH THAT ALL STOP AND THANK YOU
VERY MUCH FOR YOUR ATTENTION.
>> GOOD MORNING I'M THE DIRECTOR
OF EXTRAMURAL DIVISION AT NCCIH
TO SEE EVERYBODY IN PERSON.
DAVID ALREADY GAVE A SUMMARY OF
THE HISTORY OF THE PROGRAM AND
GO MORE GRAN YOU WU
GO MORE GRAN YOU LULAR AND SIX S
ARE COMPLETED AND FIVE OF THE
R01 GOING TO COMPLETE THIS YEAR
AND EARLY 2025.
AND THROUGH THAT EFFORT WITH THE
RFA AND NOSI WE ACTUALLY HAVE
SEEN A GROWTH IN OUR RESEARCH
PORTFOLIO 20 TO 25 GRANTS.
IT'S A BURGEONING EFFORT AND
WE'RE HAPPY TO SEE THIS.
MORE EXCITING IS THE FACT
THROUGH THE P.I. MEETING THE
NUMBER OF COLLABORATIONS HAVE
ALREADY STARTED BETWEEN YOU AND
SO TODAY IT'S GOING TO BE
INTERESTING TO HERE THOUGH IT'S
THROUGH A DATA BLITZ FORMAT
MEANING FIVE-MINUTE
PRESENTATIONS THE ADVANCEMENTS
DONE NOT ONLY IN THE
NON-CLINICAL STUDIES OF PAIN AND
CLINICAL ASPECT.
THE PRESENTATIONS WILL BE SHORT,
FIVE MINUTES EACH.
WE'LL ASK YOU TO HOLD QUESTIONS
TO THE END OF THE SESSION.
THERE'LL BE THREE.
TWO FOCUSSED ON THE NON-CLINICAL
ASPECT AND ONE ON THE CLINICAL
ASPECT AND THEN OPEN IT UP FOR
QUESTION AFTER THE END OF THE
SESSION.
SO WITHOUT FURTHER ADO, I'M
GOING TO TURN IT OVER TO INNA
AND LOOK FORWARD TO HEARING THE
PRESENTATIONS.
THANK YOU VERY MUCH.
>> THANK YOU, DAVID AND EMMELINE
FOR YOUR LEADERSHIP AND FOR THE
NCCIH DIRECTOR.
WE'RE UNDER THIS BIG UMBRELLA
AND NOW WE'LL MOVE TO OUR FIRST
SESSION.
THE FIRST SESSION WILL BE THE
FIRST PORTION OF THE MEETING.
WE'LL HAVE 15 PRINCIPAL
INVESTIGATORS OF THE
NON-CLINICAL STUDIES ON
CANNABINOIDS AND PAIN AND EACH
WILL PRESENT A FIVE-MINUTE
PRESENTATION AND THIS WILL BE
PRESENTATION ON STUDY DESIGN,
MAGIC FINDINGS AND NEXT STEPS
AND NEXT STEPS IS IMPORTANT AND
WE WILL BE TALKING ABOUT IT
AFTER THE THOUGHT SESSION OF THE
P.I.s WE'LL HAVE A BRIEF Q&A
AFTER EIGHT PRESENTATIONS AND
BRIEF Q&A AFTER NEXT SET OF
QUESTIONS THAT CAN'T WAIT.
I'LL BE INTRODUCING THE SPEAKER
ONLY BY THEIR NAME EACH WILL
HAVE FIVE MINUTES WITH A
THREE-MINUTE VERBAL WARNING AND
WHEN THE TIME IS UP ANOTHER
VERBAL WARNING.
WITH THIS, I'M INVITING SURGEON
WARD OF TEMPLE UNIVERSITY TO
PRESENT ON THE HOUSE MODEL.
>> THANK YOU VERY MUCH.
YOU KNOW I CAN HARDLY INTRODUCE
MY NAME IN FIVE MINUTES I'M NOT
ONE ON BREVITY BUT I'LL TRY
HARD.
OUR PROJECT FUNDED THROUGH THE
RFA WAS ENTITLED ANALGESIC
EFFICACY OF CANNABINOIDS AND
TURPENES I'VE BEEN STUDYING THE
NEURALOPATHY AND WE EXTENDED OUR
FINDING OF THE BEHAVIORAL
FINDINGS OF EFFECTS OF NEURAL
PATHIC PANEL TO OTHER
CANNABINOIDS AND TURPENES LIKE
MANY SITTING IN THE AUDIENCE
THERE'S THE IDEA OF THE ENTERAGE
EFFECT.
ONE OF THE FIRST EXPERIMENTS
THAT WE CONDUCTED IN THE
LABORATORY WAS TO LOOK AT
WHETHER THE COMBINED EFFECTS OF
CBD AND DELTA 9THC PRODUCE
EFFECTS IN THE PAIN MODEL AND
FOUND PROFOUND SYNERGISTIC
EFFECTS AND WE EXTENDED THE
RESEARCH INTO POTENTIAL
INTERACTIVE EFFECTS BETWEEN
OTHER MINOR CANNABINOIDS AND
TURPENES AND THE ADDITIONAL GOAL
WAS TO MOVE THE BEYOND THE
NEUROPATHIC PAIN TO OTHER MODELS
AND HAVE A RAT MODEL OF
INFLAMMATORY DENTAL PAIN.
THIS IS MY DATA SLIDE SHOWING
YOU SOME OF THE HIGHLIGHTS OF
THE WORK THAT HAS BEEN CONDUCTED
UNDER THE R01.
THE FIRST THREE ARE
PUBLICATIONS.
I'VE LISTED THE PUBLICATIONS
HERE.
WE SPENT TIME CATEGORIZING CBG
AND WE FIND NUANCED EFFECTS IN
THE MECHANICAL SENSITIVITY.
WE ONLY GET SIGNIFICANT EFFECTS
UNDER SPECIFIC DOSING
CONDITIONS.
WHEN WE LOOK AT THOSE EFFECTS IN
COMBINATION WITH CBD WE FIND
CERTAIN SITUATIONS WHERE WE
CONFINED CBG WITH CBD PRODUCE
OTHER EFFECTS AND FIND SUB
ADDITIVE EFFECTS AND I DIRECT
YOU TO THE MANUSCRIPT IF YOU'RE
INTERESTED IN HEARING ABOUT MY
HYPOTHESIS THAT DIFFERENT
RECEPTOR MECHANISMS MAY UNDERLIE
THE SYNERGISTIC EFFECTS OF CBG
AND C.D.BD AND THE OTHER IS THE
SEX, TIME AND SITE SPECIFIC AND
PREVENTED BY CBG ADMINISTRATION.
THIS GAME A STUDY THAT REALLY
DOVE DOWN INTO THE
NEUROINFLAMMATORY SEX
DIFFERENCES IN THE MOUSE MODEL.
AND SO BEFORE WE CAN ADDRESS
BEFORE THERE'S SEX DIFFERENCES
WITH PHYTO CANNABINOIDS IN THE
ASSAY WE NEED TO UNDERSTAND WHAT
THE SEX DIFFERENCES ARE IN THE
MAIN POLLED ITSELF.
AND WE FOUND THERE ARE SEX
DIFFERENCES AFTER OXALIPLATIN
INVESTIGATION AND WHICH ANOLITES
YOU'RE LOOKING AT AND THE THIRD
IS THE DENTAL PAIN MODEL.
AND WE ANESTHETIZED THE RATS AND
I HAD BRAVE STUDENTS WHO DRILLED
A WHOLE IN THE MOLAR OF THE RAT
AND MEASURE THE SENSITIVITY AND
TREAT THESE RATS WITH PHYTO
CANNABINOIDS AND TERPENES AND WE
GET THE PREVENTION OF NEURAL IF
INFLAMMATION AND SENSITIVITY
WHEN WE TREAT THEM AND ANOTHER
STUDY IS ANTI-INFLAMMATORY
EFFECTS OF BETA CARYOPHYILENE
AND EFFECTS OF BCB THAT LOOK
MORE ROBUST IN OUR HANDS THAN
CBD AND SYNERGISTIC INTERACTION.
LET'S DEFINE THE MECHANISMS OF
ACTION OF ARTHRITIS AND CBD.
>> GOOD MORNING, EVERYONE.
ARE YOU ABLE TO SEE MY SLIDES?
>> YES.
>> GREAT.
THE GOAL OF OUR STUDY IS TO
IDENTIFY THE MECHANISM OF ACTION
FORECBD AND CHRONIC OA AND WE
USE A STUDY TO IDENTIFY NEURAL
CHEMICAL ALTERATIONS INDUCED BY
CHRONIC PAIN IN THE OA MOUSE
MODEL AND LOOK AT THE CBD
MODULATION AND CHANGES WITH THE
ANALGESIC AND AN-XIOLYTIC YOU,
ANTI-INFLAMMATORY PROPERTIES
WITH ANTAGONIST COMBINATION.
IN THIS STUDY WE CONCENTRATE ON
THE TARGETS AND ALSO THE TSP TAR
GET BECAUSE THEY'RE VERY MUCH
RELEVANT TO PAIN MANAGEMENT.
CBD BINDS TO THE RECEPTOR AND
DEMONSTRATED IN THE IMAGING
STUDY THIS IS AT BASELINE THE
REGISTRATION AND YOU CAN SEE
HIGH UPTAKE OF THE TRACER BUT IN
THE ANIMAL TREATED SIGNIFICANT
REDUCTION IN THE BRAIN AND THIS
SUGGESTS THE CBD BLOCK THE
UPTAKE CONSISTENT WITH THE FACT
CBD BINDS AND FOR THE FIRST TIME
WE DEMONSTRATED ON THE IMAGING.
AND NEXT UP IS TO CREATE AND
WE'RE SHOWING WE CREATE THE OA
MODEL AND THE INDUCTION WE FOUND
THE TRACER UPTAKE IN THE MODEL
WAS REDUCED AND SHOWN IN THIS
BAR GRAPH SHOWS THE BRAIN REGION
AT BASELINE, HIGH UPTAKE AND
AFTER OA REDUCED AND THE KNOWN
EFFECT WITH THE TREATMENT IN
BEIGE COLOR AND WITH CBD YOU CAN
SEE THE RESTORATION OF THE TRACE
UPTAKE WAS OBSERVED.
THIS IS CONSISTENT WITH CBD AND
ANDIE
THE ANXIOLYTIC ON DAY 15 AND
HERE THE RATIO REMEMBER INDICATE
THE CBD TREATMENT REDUCE
INFLAMMATION.
AND WE LOOKED AT BASELINE AND
AFTER DRUG TREATMENT AND
BASICALLY THE SENSITIVITY WITH
THE CBD AND FOR THE DARK WE
SHOWED SHE HIGHER ANXIETY AS THE
OA STAGE AND RECOVERS AFTER
DAILY CBD.
AND WE FOUND A DECREASE IN THE
MOTOR ACTIVITY AT OA STAGE AND
RECOVERS IMPROVES WITH CBD.
INTERESTING WE DO SEE THE GENDER
EFFECT SIGNIFICANCE DIFFERENCE
FOR MALE ONLY IN ALL ASPECTS AND
OA WAS AT BASELINE AND OA VERSUS
CONTROL AND CBD.
UNFORTUNATELY FOR THE AGONIST,
ANTAGONIST COMBINATION TREATMENT
STUDY THE DIFFERENCE WERE NOT
OBSERVED.
THIS MAY BE DUE TO THE SMALLER
SAMPLE SIZE OF THE DOSE WE USE
NOT OPTIMAL.
OVERALL WE FINE TUNE THE
MECHANISTIC STUDY IN HUMAN FOR
EXAMPLE IN 5HT1A MODULATION AND
INFLAMMATORY EFFECTS IN HUMAN
BEFORE AND AFTER CBD TREATMENT.
THAT'S MY FIVE MINUTES.
THANK YOU VERY MUCH FOR YOUR
ATTENTION.
>> THANK YOU, DR. DING.
THE NEXT SPEAKER IS PRESENTING
ON SYNTHETIC BIOLOGY FOR THE
MANIPULATION OF PAIN.
>> THANKS TO EVERYONE FOR THE
OPPORTUNITY TO ADDRESS YOU AND
FOR THIS PROGRAM FOR ALLOWING IN
SYNTHETIC BIOLOGY EFFORTS IN
CANNABINOID RESEARCH.
OUR ONGOING GOAL HAS BEEN TO
ESSENTIALLY DISSECT HUMAN NEURAL
RESPONSES BY MOVING INTO THE
RECEPTORS OR DIFFERENT COMPOUNDS
IN THE YEAST.
IN PARTICULAR UNDER THIS PROGRAM
WE WERE ABLE TO MOVE CD1R AND 2R
IN THE YEAST AND HAVE OTHER
OPIOID RECEPTOR AND OVER ALL
IT'S BEEN A REAL ABILITY -- THE
FUNDING HAS ALLOWED US TO MOVE
FORWARD IN PUTTING INDIVIDUAL
RECEPTORS IN YEAST AND GETTING
FUNCTION OUT.
AND THE OPOTHE OSIS IS WE'RE
ABLE TO DISSECT HUNDREDS OF
CANNABINOIDS AND THE GRANT IS
EXPIRED AND WE NO LONGER HAVE
FUNDS FOR THIS AND WHAT WE'VE
DONE SINCE THE EXPIRATION OF THE
FUND IS IT FOR MANY YEAST
RECEPTORS FOR INDIVIDUAL
COMPOUNDS MIMIC THE MAMMALIAN
CELLS AND HAVE SHOWN FOR CB1R
AND 2R YEAST OUR RESULTS IN
YEAST ARE SIMILAR TO THOSE IN
MAMMALIAN CELLS AND ALLOWED US
TO GET THE PAPERS OUT WITH
CONFIRMATION IT WILL BE
PUBLISHED IN THE INTERNATIONAL
JOURNAL OF MOLECULAR SCIENCES
AND THIS WAS ALL LARGELY WORK
DONE BY LIZ GARNER NOW A FACULTY
MEMBER IN HER OWN RIGHT.
WHAT I'D LIKE TO TALK TO YOU
ABOUT BRIEFLY IS ONGOING WORK
WHERE WE'RE USING MACHINE
LEARNING TO UNDERSTAND HOW
CANNABINOIDS RELATE TO THEIR
RECEPTORS.
THE DATABASE FOR THIS IS
ESSENTIALLY PUB MED AND ALL THE
PATENT LITERATURE WHERE IN A
VERY HIGH LEVEL WAY WE CAN TAKE
THE SIGNATURES OF COMPOUNDS LIKE
A SENTENCE AND CORRELATE THOSE
WITH ENGLISH WORDS AND LEARN
FROM HUMAN UNDERSTANDING WHAT A
CANNABINOID IS AND CAN LAY THESE
OUT IN GIGANTIC CORRELATIONS
BETWEEN WORD SPACE SO TO SPEAK
AND CHEMISTRY SPACE AND BECAUSE
OF THAT, WE'RE BECOMING QUITE
CONFIDENT IN OUR ABILITY TO
BOTH, A, PREDICT CANNABINOIDS
AND SOME WORK ON THE HORIZON
WE'RE EXCITED ABOUT IS BEING
ABLE TO DRAW OUT OF TO THE
ENTIRE DATABASE OF CHEMISTRY THE
COMPOUNDS THAT MAY ACT ON CB1R
OR 2R OR FAVOR CB1 OVER CB2 AND
SO FORTH.
AND THAT'S ESSENTIALLY WHAT I
JUST SAID.
BECAUSE WE NOW HAVE YEAST
STRAINS WE CAN TEST ON MACHINE
LEARNING PREDICTION WE CAN
IDENTIFY THE COMPOUNDS ARE IN
FACT CANNABINOIDS AND CAN
IDENTIFY NEW COMPOUNDS USING
MACHINE LEARNING METHODS AND
NEW PHENOTYPES AND LIGANDS AND
GO FROM CHEMISTRY TO POTENTIAL
PHENOTYPES WITH RECEPTORS AND
FROM THERE TO POTENTIAL
PHENOTYPES IN HUMAN SYSTEMS
THEMSELVES.
WITH THAT, I'LL TURN IT OVER TO
THE NEXT SPEAKER.
THANK YOU FOR THE OPPORTUNITY.
>> NOW THE NEXT SPEAKER AND LAST
SPEAK ON THIS PORTION IS
DR. CHUI FROM HARVARD MEDICAL
SCHOOL ON ANALGESIC EFFECTS OF
TERPENES.
>> THANK YOU VERY MUCH.
I WANT TO INTRODUCE THIS WAS A
JOINT PROJECT FUNDED BY AN RF21
BY DR. QUAVE AND MYSELF AT
HARVARD MEDICAL SCHOOL AND
DR. QUAVE IS AN ETHOBOTONIST AN
HOPS WE USE COMMERCIALLY TO MAKE
BEER BUT HAS RICHNESS IN
TERPENES AND TERPINOIDS.
AND THIS MAY AFFECT SENSORY
NEURONS TO MEDIATE PAIN AND CAN
WE CREATE FORMULATIONS RICH IN
TERPENE COMPOUNDS AND TEST
MODULATION OF SEE IF THEY HAVE
DIRECT EFFECTS TO MODULATE PAIN
PRODUCTION.
SORRY, I THINK PARTS OF THE
SLIDE ARE CUT OFF BUT I'LL
SUMMARIZE THE DATA WE FOUND.
SO, FIRST WE USED SIX DIFFERENT
DEFINITIONS AND THESE HOPS WERE
SUBJECT TO MASS SPECTOMETRY AND
THIS IS THE CHEMICAL ANALYSIS
DR. QUAVE CONDUCTED AND USED THE
THREE EXTRACTS MOST DISTINCT IN
NATURE AND THE COMPOUNDS THAT
DEFINES THEM THE MOST AND THEN
WE DR. QUAVE FORM 4R5I9ED A WAY
OF APPLIED THIS AND TESTED THEM
ON DIFFERENT ASSAYS AND HAD THE
BIGGEST EFFECT ON HEAT
SENSITIVITY.
ON HOT PLATE ASSAY YOU CAN SEE
IF YOU COMPARE VEHICLE TO CBD AS
A COMPARISON ALL THREE EXTRACTS
HAD SIMILAR EFFICACY IN BLOCKING
HEAT PAIN AT THE 40, 52 DEGREES
AND THERE'S SOME SEX
DEPENDENCIES.
FEMALES HAVE A GREATER WITH
ABILITY TO BE SILENCED IN TERMS
OF EXTRACTS.
OTHER EFFECTS AND MYRCENE AND
HUMULENE EFFECTS DON'T HAVE
MECHANICO THRESHOLDS THERE MAY
BE SOME SPECIFICITY OF THE HOPS
AND TERPENES AND IT MAY MEDIATE
NOXIOUS HEAT SO, JUST IT'S
INTERESTING TO THINK ABOUT OTHER
RELATED SPECIES WHICH
DR. SHURTLEFF MENTIONED ARE NOT
SCHEDULED PLANT SPECIES AS
POTENTIAL SOURCES OF ANALGESIC
CANNABINOIDS OR TERPENES AND
DEFINE MECHANISMS AND DR. QUAVE
SAID THE SYNERGY OF MANY OF THE
COMPOUNDS TOGETHER COULD BE MORE
EFFECTIVE THAN JUST A SINGLE
ONE.
ALSO THINKING ABOUT THAT.
FOR MANY ANCIENT CULTURES THEY
TAKE THESE EXTRACTS AND
UNDERSTANDING HOW THEY WORK
TOGETHER AND MYRCENE MAY HAVE
THE BIGGEST EFFECT AND MAY ACT
ON THE NEURONS.
WE SEE THAT IN VITRO AND CALCIUM
IMAGING ASSAYS AND THINKING
ABOUT HOPS AND OTHER PLANT AS A
SOURCE OF ANALGESICS.
>> THANK YOU, NOW WE'LL PRESENT
ON SYSTEMATIC INVESTIGATION OF
RARE CANNABINOIDS WITH PAIN
RECEPTORS BY DR. DAS.
>> IT'S NICE TO SEE EVERYBODY.
WE WANTED TO DO A METABOLISM AND
MINOR CANNABINOIDS ARE NOT
REALLY MINOR AS YOU CAN SEE FROM
THE LCMS PRESENTATION THESE ARE
IN THE CANNABIS EXTRACT AND LOOK
AT THEIR MECHANISM.
WE LOOKED AT TWO HERE.
SO CANNABIGEROL AT THE 2, 3
POSITION IT CYCLIZES TO BECOME
FROM STUDIES AND AS WELL AS FROM
THE STUDIES AND THEN ALL THESE
AND THEY'RE ALL SHOWING AN
ANTIINFLAMMATORY EFFECT IN
MICROGLIAL CELLS AND SIMILAR
WITH OTHER MOLECULES WHICH HAS
DOUBLE BOND IN SEVEN POSITIONS
TARGETED WHICH ARE PHASE 1 DRUG
METABOLISM.
AND IT SHOWS EVERYWHERE IN THE
BODY AND THE CANNABINOIDS CAN
FORM THESE DIFFERENT PRODUCTS.
DEPENDING ON THE SITE WE HAD
DIFFERENT PRODUCTS AND THE
PRIMARY PRODUCT WAS THE 6, 7
EPO
EPOXY CANNABICHROMINE AND WE
STUDIED CBC AND CBG AND FOUND
THE PRODUCT THAT WE PREDICTED
WOULD BE FORMED WAS ACTUALLY
FORMED IN THE MICE BLOOD AND WIN
HALF AN HOUR OF THE
DEMONSTRATION AND THEN
DISAPPEARS.
OUR HYPOTHESIS IS IT GETS
TRANSFORMED BY THE ENZYMES AND
THE IT REMAINS IN LARGER
CONCENTRATION BUT FORM DIFFERENT
PRODUCTS WE HAD PREDICTS.
BOTH ARE STRONG METABOLIZING
ENZYME AND THERE COULD BE A DRUG
CANNABIS INFRACTION THE OUTCOME
IS WE ELUCIDATED THE METABOLISM
OF THE CANNABINOIDS BY THE
FEDERAL P450s AND STEROID AND
LIPID SYNTHESIS AND THESE
METABOLITES ARE FORMED BUT BIO
ACTIVE.
FUTURE STUDIES WILL LOOK AT
SELECTIVITY AND UNDERSTAND HOW
THEY SELECT AND BECAUSE THE
MOLECULES ARE TIED AND CAN THE
COMPOUNDS BE USED FOR
THERAPEUTICS AND.
AND WE HAD PEOPLE IN THE
CHEMISTRY FIELD AND THEY LOOKED
HOW WE WERE LOOKING AT THE
CANNABINOID MOLECULES.
THIS IS OUR PROGRESS REPORT.
WE HAVE FOUR PUBLICATIONS FROM
THE WORK AND WORKING ON
CANNABIGEROL AND THE MECHANISM
OF CBD TO FORM CBE AND OTHER
METABOLITES.
THANK YOU MY LABORATORY AND
THANK YOU EVERYBODY.
I HOPE THAT WAS AT FIVE MINUTES.
>> THANK YOU SO MUCH.
>> WE'LL HAVE OUR NEXT SPEAKER.
>> HI, EVERYONE.
FWRAD TO BE HERE.
TODAY I'LL BE TALKING ABOUT MY
LAB AND CHRISTINA'S LAB LOOKING
AT THE MINOR CANNABINOIDS AND
TERPENES AND THE PRECLINICAL
EVALUATION OF ANALGESICS AND
TARGETS INVOLVED AND IMPLICATED
IN PAIN AS WELL AS LOOK AT THEM
IN MOUSE MODELS OF PAIN
BEHAVIOR.
WE'LL BE SEEING DATA FROM STEVE
KINSEY'S LAB AND LOOK AT DATA
FROM MY LABORATORY AS WELL.
OUR HYPOTHESIS IS THE STUDIES
OVER ALL IS MINOR CANNABINOIDS
INTERACT WITH THE RECEPTORS AS
INDICATED IN PAIN AND THIS HAS
BEEN KNOWN AND SUGGESTED FOR
QUITE SOME TIME NOW.
AND THAT IN THE BEHAVIORAL
MODELS WE'LL SEE EFFECTS OR
ANALGESIC LIKE EFFECTS.
SO STEVE KINSEY'S LAB DEVELOPED
THIS ARTHRITIS MODEL USING IN
MICE.
AND WE CAN SEE THERE'S A COUPLE
DIFFERENT WAYS IN WHICH THEY CAN
QUANTIFY ARTHRITIC LIKE EFFECTS
IN MICE.
THE FIRST BEING ARTHRITIS
SEVERITY AND THE SCORE OF
PHYSICAL OR VISUAL SIGNS OF
ARTHRITIS.
HERE IN THE PAW THERE'S REDUCED
COLLAGEN AND REDNESS AND
INFLAMMATION OF THE DIGITS AND A
SCORE CRITERIA AND CAN GET
ARTHRITIS SEVERITY.
YOU CAN SEE IN CONTROL ANIMALS
THEY'RE NOT SHOWING ARTHRITIS
OVER THE TIME COURSE OF THE
STUDY HOWEVER, ANIMALS WITH
COLLAGEN BY DAY NINE, 10, 11 THE
EFFECTS GO UP AND WITH A STEROID
THEY BLOCK OUT THE EFFECT.
LOOKING AT THE COMPOUND DELTA H
AND THE CABBINOL AND ALSO LOOKED
AT THE BIO CHEMICAL ASSAYS AND
CYTOKINE AND REDUCTIONS OCCURRED
AS WELL AS WE SEE A RECOVERY OF
DEPRESSION OBSERVED WITH THE
COLLAGEN IN THE ANIMALS.
IN TERMS OF BEHAVIORAL ASSAYS
HAY -- THEY LOOKED AT GRIP
STRENGTH AND THE AMOUNT OF TIME
THE ANIMAL IS ABLE TO HOLD ON TO
THE GRID AND YOU CAN SEE WITH
THE EXPERIMENT WITH THE OTHER
PHYSICAL MEASURES THEY'RE
OBSERVING WE GET DECREASE IN
LATENCY IN THE FALL SUGGESTING
THE REDUCTION IN THE ABILITY TO
GRIP THE GRID.
THIS IS RECOVERED BY THE
CABBINOL.
IN ADDITIONALLY THERE'S THE
CLIMBINGEST IT AND THIS IS A
DIFFERENT ASSAY AND THE PAIN
DEPRESSED BEHAVIOR.
WHEN YOU ASSAY ANIMALS YOU GET
THE INCREASE IN BEHAVIOR.
AND WE SEE THE POSITIVE CONTROL.
AND SOME RINGS HAVE HIGH OR LOW
TEMPERATURE AND WE CAN LOOK AT
THEIR THERMAL PREFERENCE AND
WITH COLLAGEN INDUCED ARTHRITIS
THEY GET THE INCREASE IN
PREFERENCE IN TEMPERATURE
BROUGHT BACK DOWN TO CONTROL
LEVELS IN COLLAGEN AND IT'S THE
FIRST TIME THIS HAS BEEN DONE TO
SHOW THE ARTHRITIS MODEL.
ADDITIONALLY WE LOOKED AT THE
MOBILITY AND SHOWED THERE'S NOT
A GREAT CHANGE IN MOBILITY TIME
VERSUS THE CONTROL ANIMALS.
AND LOOKING AT THE COMPOUNDS AND
BINDING AND FUNCTION THE DELTA
THC IS SIMILAR TO THE GREEN AND
THE GREEN CURVES AS WELL AS
FUNCTIONALLY IN THE FINDINGS AND
SEE AGONIST ACTIVITY OF THE
RECEPTORS.
IT IS OBVIOUSLY A CANNABINOID 1
AND 2 AGONIST.
ALSO, STEVE KINSEY IS
COLLABORATING WITH UCONN AND
SHOWS THIS DATA.
NEXT STEPS AND FUTURE
OPPORTUNITIES FOR THE STUDIES
WELL CONTINUE TO LOOK AT THE
PHARMACOLOGY OF THE COMPOUNDS
AND OTHER TARGETS AND IT'S BEEN
ONGOING.
I SHOULD MENTION MUCH OF THIS
WORK WAS DONE AND THE BEHAVIORAL
WORK IN ANIMALS WAS DONE AT
UCONN, MOLECULAR WORK WAS DONE
AT RTI WHERE I USED TO BE BUT
NOW AT UPSTATE AND WE'LL BE
LOOKING THE OTHER TARGETS AND
THE PHARMACOLOGY OF THE
COMPOUNDS AND ANOTHER ASSAY
WE'LL GETTING UP AND RUNNING IS
THE PAVLOVIAN DISCRIMINATION
PARADIGM AND LOOK AT THE OBVIOUS
RELATED POTENTIAL EFFECTS AND
WE'VE BEEN LOOKING THE DRUG
DISCRIMINATION BEHAVIOR IN
ANIMALS.
THERE'S A PROCEDURE TO LOOK AT
WHETHER THE DRUG PRODUCE PSYCHO
ACTIVE EFFECTS VERSUS JUST
CANNABINOID EFFECTS AND STEVE
KINSEY WILL LOOK AT THE EFFECTS
IN THE MODEL BUT USING FEMALE
MICE BECAUSE I DIDN'T MENTION
ALL THE MICE WERE MALE MICE BUT
IT'S VERY DIFFICULT IN THE
LITERATURE AND THAT'S
EVERYTHING.
THANK YOU VERY MUCH FOR
LISTENING.
>> THANK YOU SO MUCH.
YOU THANK YOU VERY MUCH.
OUR NEXT SPEAKER IS PRESENTING
ON OPTIMIZATION OF CBD MEDIATED
ANALGESIC EFFECTS.
>> I'M KUAN HONG WANG FROM THE
UNIVERSITY OF RODCHESTER
PRESENTING ON MECHANISM AND
OPTIMIZATION OF CBD MEDIATED
ANALGESIC EFFECTS ON BEHALF OF
MY LABS.
SO OVER ALL OBJECTIVES IS TO
IDENTIFY THE IN VIVO ACTION OF
CBD AND NEURO CIRCUIT MECHANISM
FOR ANALGESIA.
WE CAME TO THIS TOPIC BECAUSE
OUR RECENT STUDIES WHERE WE
COLLABORATED WITH DR. WOLF AT
BOSTON CHILDREN'S HOSPITAL AND
USED THE ANIMAL MODEL OF
NEUROPATHIC PAIN TRIGGERED BY
INJURY IN OUR STUDIES AND
THROUGH A SERIES OF CIRCUIT
TRACING AND NEURAL IMAGING AND
MANIPULATION STUDIES WE
IDENTIFIED CENTRAL SENSITIZATION
ALONG THE NEURAL AXIS AND WE
FOUND THAT THE MAJOR ROLE BY THE
SOMATO SENSORY CORTICAL NEURONS
WHICH COMPLETE SPINAL POSITIVE
FEEDBACK LOOP AND REGULATE THE
TACTILE SENSITIVITY AND
SENSITIVITY TO CLASSIC PAIN WE
THINK IN THE DIRECT SPINE
CONNECTION MAY PROVIDE A
SUBSTRATE FOR HOW OUR MENTAL
STATE MODULATES PAIN AND GIVEN
THE SENSITIVITY IN THE LOOP AND
THINK IT'S LIKELY LIKELY TO BE
MONT
MODULATED BY THE CIRCUIT AND CBD
COULD MODULATE THE INHIBITION
THROUGH THE INTERACTION WITH THE
INHIBITOR TRANSMITTERS AND
THOUGH THE PREVIOUS STUDY MOSTLY
DEPENDS ON THE BIO CHEMICAL AND
IN VITRO APPROACH.
WE HYPOTHESIZED A CBD WILL
EXPRESS THE SPINAL CORTICAL LOOP
TO PROVIDE RELIEF AND OUR
APPROACH IS MAINLY IN VIVO OF
BEHAVIOR AND EPIDEMIOLOGICAL
STUDIES AND TO HIGHLIGHT A KEY
SET OF INTERESTING FINDINGS, WE
FOUND ROBOTS WITH INHIBITOR
ACTION IN PAST PAIN BEHAVIORS
AND SENSORY CIRCUITS.
SO PARTICULARLY IN THE BEHAVIOR
STUDIES WE PERFORMED A CURVE BY
APPLYING A SERIES OF DIFFERENT
PRESSURES TO THE MOUSE IN THE
PERIPHERAL MODEL.
YOU CAN SEE AND YOU CAN SEE THE
ALLODYNIA AND HYPERALGESIA AND
WHEN WE CONDUCT THE CURVE WE
DIDN'T SEE ALTERATION IN THE
ININNOCUOUS AND INNOCUOUS RANGE
AND WE GET THE REDUCTION OF
ACUTE PAIN.
THE CBD EFFECT IS SELECTED FOR
IMPORTANT THERAPEUTIC
APPLICATION.
THE AND THIS DOESN'T AFFECT THE
ACUTE PAIN AND AT THE NEURAL
LEVEL WE STUDY THE CORTICAL
SENSORY TAR GETS LOOKING AT THE
RELABELLING AND LOOKING AT THE
IN VIVO IMAGING WITH THE CAMERA
AND MONITOR THE NEURONAL
ACTIVITY AND LOOKED AMOUNT THE
BEHAVIORS AND ACTIVITY.
BASICALLY IN THE NEUROPATHIC
PAIN MODEL WE GET HYPERACTIVITY
OF THE SENSORY SPINAL NEURONS
AND THAT IS GREATLY REDUCED BY
CBD AND IN THE INTACT ANIMALS
THE NEURONS WILL ONLY RESPOND
MODESTLY TO THE LOW PRESSURE AND
THIS RESPONSE WAS NOT ALTERED BY
CBD.
BOTH AT THE NEURAL AND
BEHAVIORAL LEVEL WE GET A ROBUST
SUPPRESSION OF PAIN AND SPARED
THE SOMATOSENSORY RESPONSE.
MOVING FORWARD WE THINK THERE'S
THERE'S AN IMPORTANT APPROACH TO
INTEGRATE THE SPECIFICITY OF
CANNABINOIDS AT MULTIPLE LEVELS
TO BETTER OPTIMIZE THE
THERAPEUTIC TRANSLATION.
I DON'T HAVE TIME TO TALK ABOUT
SOME EFFORTS ALREADY DONE SO
WE'VE BEEN LOOKING AT THE BIO
AVAILABILITY OF THE CBD THROUGH
ALTERATIONS AND PERFORMED A
STUDY TO BETTER UNDERSTAND HOW
TO THE COMPOUND CAN ACHIEVE A
STATE DEPENDENT EFFECT LIKE
EXCITABILITY AND CONDUCTED
SPINAL BRAIN-WIDE MAPPING OF THE
DIFFERENT POPULATION OF NEURONS
THAT COULD BE EFFECTED BY CBD.
SO CBD'S ACTION THOUGH I
HIGHLIGHT THE SENSORY NEURONS
IT'S BECAUSE WE HAVE AFFECTED
MULTIPLE TARGETS ALONG THE
CENTRAL NEURAL PATHWAY AND THAT
LEADS TO THE PAIN RELIEVING
BEHAVIOR.
I THINK THIS WILL BE AN
INTERESTING QUESTION WE'LL
CONTINUE TO ADDRESS.
WITH THAT I'LL ACKNOWLEDGE THE
KEY PEOPLE INVOLVED IN THE STUDY
IN BOTH LOCATIONS.
THANK YOU VERY MUCH.
>> THANK YOU.
WE HAVE ONE FINAL SPEAKER,
DR. MYRA RICE.
DR. RICE CANDIDATES WILL PRESENT
ON MOTIVATION OF
HYPERSENSITIVITY BY PREFERENCE
THE CANNABINOID RELEASE IN THE
CENTRAL CIRCUITS AND WE'LL HAVE
TIME MAYBE FOR TWO QUESTIONS SO
THIS WILL BE A RACE TO THE
MICROPHONE.
THE FIRST TWO PEOPLE WILL BE
ABLE TO ASK QUESTIONS.
THANK YOU.
>> I'M MYRA RICE LOOKING AT THE
ROOM MECHANISMS FOR NOCICEPTION
AND MOUSE MODELS OF PAIN.
SO OUTCOME MEASURES I'LL BE
TALKING ABOUT ARE THRESHOLDS IN
MICE OF COURSE AND CBD 1
RECEPTOR IN CELL CULTURE
EXPERIMENTS.
AND MYRCENE HAS BEEN IN
INFLAMMATORY MODELS AND WE
REPLICATE THE FINDINGS IN A
CHRONIC CONSTRUCTION INJURY
NERVE MODEL OF NEUROPATHIC PAIN
AND UNCOVERING MECHANISMS
NOCICEPTION.
SO, I'LL BE DISCUSSING IN VIVO
FINDINGS ON THE TOP ROW AND I
USE A CHRONIC CONSTRICTION
INJURY MODEL WHERE THE MOUSE'S
SCIATIC NERVE HAS TUBING AND
I'LL BE DESCRIBING THE
THRESHOLDS ON THE Y AXIS AND
THIS DESCRIBES THE AMOUNT OF
FORCE THE ANIMAL CAN WITH STAND
ON THE INJURED PAW.
SO FIGURE ONE IS SHOWING A DOSE
RESPONSE CURVE FOR MYRCENE AT
VARIOUS DOSES AND WITH HIGHER
DOSES OF GLYCINE THE ANIMAL CAN
WITH STAND MORE MORSE -- FORCE
AND THE ANTAGONIST PRETREATMENT
OF MYRCENE IS ABLE TO BLOCK
THESE ANTI-ANALGESIC EFFECTS AND
THIS IS DISPLAYED AND THESE ARE
GOING TO BE THE VEHICLE
PRE-TREATED MYRCENE COMPARISON
TO THE UPSIDE-DOWN PRE-TREATED
MYRCENE.
AND ADDITIONALLY IF YOU NOTICE
THAT THE CB1 ANTAGONIST
PRE-TREATMENT GROUP IS NOT
STATISTICALLY SIGNIFICANT
COMPARED TO THE VEHICLE CONTROL
GROUP.
NOW I'M GOING TO BE DESCRIBING
SOME IN VITRO STUDIES THAT WERE
DONE USING CELL CULTURE ASSAYS
USING AT THE PROTEIN ACTIVATION
IN THE ASSAY.
SO I'LL BE DESCRIBING CHANGE IN
THE BIO LUMINESCENCE ENERGY
TRANSFER AND THIS HAPPENS WHEN
THERE'S A DISASSOCIATION OF THE
SUB UNIT WHEN THE RECEPTOR IS
ACTIVATED.
SO FIGURE 4 IS SHOWING MYRCENE
COMPARED TO AN A CB1 AGONIST AND
MYRCENE IS NOT BEHAVING LIKE THE
AGONIST AT ALL.
AND THEN FIGURES 5 AND 6 ARE
SHOWING TWO ENDOGENOUS
CANNABINOIDS WITH AND WITHOUT
THE ADDITION OF 10 MICROMOLARS
OF MYRCENE SO IT'S NOT
MODULATING THE CANNABINOID ON
THE CB1 RECEPTORS.
THE NEXT STEPS ARE TO
INVESTIGATE HOW MYRCENE HAS
THESE ANALGESIC PROPERTIES IN
VIVO BLOCKED BY THE CB1 AGONIST
AND YET IN VITRO IT'S NOT
BINDING OR MODULATING
CANNABINOID ACTIVITY.
SO FUTURE STEPS FOR FIELD AND
FOR MY LAB ARE GOING TO BE TO
USE FIBER PHYTO METRY AND LOOK
AT THE SENSOR AND THIS IS A
MODIFIED CB1 RECEPTOR SO WHEN
IT'S BOUND THERE'S A CHANGE AND
THIS CAN BE MEASURED AND I'M
PARTICULARLY INTERESTED IN THE
VENTROLATERAL PERIAQUEDUCTAL
GRAY AND SEX DIFFERENCES HAVE
BEEN FOUND IN CIRCUITS INVOLVED
I'M FROM IN THE LATERAL
HYPERTHALAMUS TO THE PERILATERAL
PER I AQUA -- PERIAQUADUCTAL
GRAY.
>> THREW FOR STAYING ON TIME.
WE HAVE A COUPLE MINUTES FOR
BURNING QUESTIONS.
AND WE HAVE ONE.
GREAT.
I HAVE A QUESTION FOR DING.
YOU MENTIONED ABOUT BINDING OF
YOUR PET TRACER IN THE BRAIN BUT
DID YOU ALSO SHOW SOME PICTURES
OF THE KNEE?
>> SORRY, DID I SHOW PICTURE OF
WHAT?
>> SOME OF THE PICTURES LOOKED
LIKE THEY WERE NOT TH>LIKE THEY.
>> DID YOU ALSO DO PET IMAGING
KNEE?
>> YES.
THIS SCANNER IS A WHOLE BODY
SCANNER.
SO WE LOOK AT BOTH BRAIN AND
KNEE.
YOU SEE THE KINETICS I SHOWED
WITH THE RIGHT KNEE IS THE
INJECTION SITE OF THE MIA TO
INDUCE THE OA AND FOR THE LEFT
KNEE AND THERE'S A VERY MINOR
INFLAMMATION.
>> YOU SAW THE CBD BINDS TO BOTH
THE RECEPTORS IN THE KNEE AND
THE BRAIN?
>> THIS IS AN INFLAMMATION
TARGET.
>> THE TOP PANEL IS TALKING
ABOUT THE RECEPTOR AND I SHOWED
BUT THE BOTTOM PANEL IS FOR THE
STUDY FOR TSPO.
FOR THAT STUDY I HAVE THE BRAIN
IMAGING SHOWING THAT AFTER THE
INDUCTION OF OA YOU SEE THE
UPREGULATION AND HIGHER UPTAKE
OF THE TRACER PBR28 AND ALSO IN
THE PERIPHERY IN TERMS OF KNEE.
RIGHT KNEE IS MUCH HIGHER
INFLAMMATION COMPARED TO LEFT
KNEE AND IF YOU USE AND USE THE
RATIO FOR THE FOUR STAGE YOU CAN
SEE THE BASELINE HAS NO TO
LITTLE INFLAMMATION BUT DAY SIX
HIGHER THAN DAY 13 AND THE
RESULT WITH REDUCTION OF
INFORMATION WITH CBD.
>> IN THE KNEE.
OKAY.
THANK YOU.
>> THANK YOU.
>> THANK YOU FOR THE QUESTION
AND ANSWER AND NOW MOVING TO THE
SECOND SESSION.
AGAIN IN THE NON-CLINICAL
STUDIES.
AGAIN, BRIEF FIVE-MINUTE
PRESENTATIONS AND NOW DR. RAWLS
IS THE FIRST SPEAKER OF THE
SECOND PORTION.
NOW, ON BEHALF OF CO-P.I.
DR. RAWLS FROM TEMPLE UNIVERSITY
LOOKING AT ROOM MECHANISMS AND
INTERACTIVE EFFECTS IN
NEUROPATHIC PAIN.
>> WONDERFUL, THANK YOU.
SO THIS IS AN R21 AWARDED TO
DR. RAWLS AND I IN AUGUST.
THIS WAS INSPIRED PARTLY BY A
STORE CALLED CBD KRATOM BY MY
CHILDREN'S MIDDLE AND HIGH
SCHOOLS AND THOUGHT I THOUGHT
WRITE A GRANT AND CBD AND KRATOM
ARE SOLD AND THE LARGEST
PREDICTOR OF WHETHER OR NOT
PEOPLE USE KRATO M IS WHETHER
PEOPLE USE ANTIBODY AND FOLKS A
LIKELIHOOD PEOPLE ARE CO-USING
THE PLANT DERIVED PRODUCTS AND
UNCLEAR WHETHER THERE ARE
EFFICACY REASONS FOR CO-USE AND
WHETHER THERE ARE REASONS TO BE
CONCERNED ABOUT THIS.
IT'S TO LOOK AT WHETHER THEY
CO-USE CAN CREATE ADVERSE
EFFECTS.
SO KRATOM IS A PLANT THAT FOLKS
USE FOR VARIOUS REASONS TO TREAT
ANXIETY, TO ALLEVIATE OPIOID
WITHDRAWAL SIGNS AS WELL AS TO
TREAT PAIN THAT IS NOT
RESPONSIVE TO CONVENTIONAL
ANALGESICS.
AGAIN, A LOT OF OVERLAP WITH THE
REASONS WHY SOME FOLKS ENDORSE
USING MEDICAL CANNABIS.
UNLIKE CANNABIS THERE'S
DIFFERENT COMPOUNDS IN KRATOM
ONE OF THE BIO ACTIVE SUBSTANCES
THAT HAS RECEIVE THE MOST
ATTENTION FROM THE RESEARCH
COMMUNITY IS A COMPOUND THAT WE
STARTED OUR RESEARCH ON.
IT HAS ACTIVITY AT OPIOID
RECEPTORS AND MAY BE RESPONSIBLE
FOR SOME OF THE REASONS WHY
FOLKS USE THIS IN DIFFERENT
THERAPEUTIC SETTINGS.
AS WELL AS THERE ARE ROOM
ACTIVITIES OF AND FOUND THE
BEHAVIORAL EFFECTS OF
CANNABINOIDS AND MYTRAGYNINE MAY
COME TO LIGHT.
WE'VE DONE WORK IN THIS AREA AND
WE'RE LOOKING AT CBD, CBG AND
DELTA 9THC IN COMBINATION WITH
MYTRAGYNINE IN MALE AND FEMALE
MICE AND THE PRIMARY MODELS ARE
THE CANNABINOID LOOKING AT
ANTINO RECEPTION AND THE MODEL
OF PAIN AND THE MODEL OF
NEUROPATHIC PAIN.
AND AB -- AND SOME HIGHLIGHT WE
FOUND OF THE POINT 1 IS THAT
MITRAGYNINE IS SHOWING EFFECTS
AND IF WE PRETREAT MICE BEFORE
THEY GET THEIR CHEMO AGENT WITH
MITRAGYNINE PREVENTS THE
DEVELOPMENT OF CHEMOTHERAPY
INDUCED SENSITIVITY AND HER WORK
WILL BE TO LOOK AT WHETHER AND
HOW THIS INTERACTS WITH THE
REVERSAL EFFECTS OF THE
CANNABINOIDS AND MIA IS WORKING
ON THE ASSAY AND SEE CBG AND
MITRAGYNINE ATTENUATE PHASE 2
BEHAVIORS AND AN INTERESTING
EFFECT WE SEE WITH CBG AND MAY
HAVE TO DO WITH THE SEDATIVE
EFFECTS BECAUSE WE ONLY SEE THE
EFFECT AT A HIGH DOSE AND AGAIN
MITRAGYNINE IS EFFECTIVE AT
REDUCING PHASE 2 BEHAVIORS
INDICATIVE OF AN
ANTIINFLAMMATORY EFFECT.
IN THE MANY ASSAY WE'RE SEEING
EFFECTS OF DELTA 9 THC AND
LOOKING AT THE PHYTO
CANNABINOIDS AND DON'T SEE
EFFECTS OF MITRAGYNINE IN THE
HOT PLATE SHOWING IT'S NOT
ACTING AS A VERY ROBUST OPIOID
AGONIST IN THE ASSAY.
HOWEVER, IT DOES REDUCE THE AN
TINNO RECEPTIVE EFFECT OF THC
AND CBG.
MITRAGYNINE IS REPORTED ON
HAVING STIMULANT LIKE PROPERTY
AND INTERESTED WHETHER THE
REDUCTION OF THIS BEHAVIOR ON
THE HOT PLATE HAS SOMETHING TO
DO INTERACTING WITH EFFECTS
OPPOSED TO ANTINOCICEPTIVE
EFFECTS AND THANK YOU FOR THE
FIVE MINUTES OF TIME WITH YOU
ALL.
>> THANK YOU.
THE NEXT SPEAKER IS
DR. STREICHER FROM THE
UNIVERSITY OF ARIZONA AND
RELIEVING CHRONIC PAIN VIA THEA
-- THE A2A RECEPTOR.
>> GOOD TO BE HERE WITH YOU IN
PERSON.
SIME I'VE FLOWN FOR YEARS.
SO WE'RE INTERESTED IN TERPENE
COMPOUNDS AS YOU ARE AND WE HAD
INTERESTED AND THEY HAD BEEN
REPORTED IN THE PRECLINICAL AND
CLINICAL LITERATURE BUT THERE'S
A MECHANISM WE WANTED TO DIG
INTO AND THE PRECURSOR TO OUR
FUNDED WORK WE FOUND THEY WERE
ALL PRODUCING BEHAVIORS AND
SYNERGIZED VIA THE RECEPTOR AND
WE WANTED TO EXTEND BEYOND THAT
AND AND AND WE WORKED THROUGH
THE RECEPTOR NOT THE CANNABINOID
1 RECEPTOR AND LINK THE
ACTIVATION OF THE RECEPTOR TO A
CIRCUIT.
WHAT WE FOUND TERPENES WERE
EFFICACIOUS IN THE PAIN AND USED
THE NEUROPATHY ABOUT EQUIVALENT
TO MORPHINE AND SAW THIS IN THE
RECEPTOR AND THE WORK GETS
PUBLISHED THIS YEAR.
IT'S A HUGE PAPER LIKE 21
FIGURES.
AT THE SAME TIME WE SHOWED IT
HAD A GOOD SIDE EFFECT PROFILE.
WE SHOWED KNOW ABUSE LIABILITY.
SOME TERPENES HAD NOR AVERSION
NOR REWARD WHICH IS WHAT YOU
WANT AND MODERATE TOLERANCE AND
THE ABILITY TO ENHANCE OPIOID
PAIN RELIEF AND USE THEM
TOGETHER YOU GET MORE PAIN
RELIEF THAN EITHER ALONE AND
THAT ENHANCEMENT BECOMES
INTERESTING WHEN YOU GET TO THE
UNPUBLISHED WORKED SHOWING IT
CAN BLOCK THE REWARD AND SHOWING
WHEN YOU COMBINE THEM YOU BLOCK
THAT DOPAMINE ACTIVITY.
WHEN YOU THINK OF THAT IN TERM
OF THIS ABILITY TO DO OPIOID
PAIN RELIEF IT SUGGESTS THE
PERFECT COMBINATION THERAPY AND
MAKE THE PAIN RELIEF BETTER AND
BLOCKING THE REWARD ASPECTS THE
OPIOIDS SO WE'RE EXCITED ABOUT
THAT.
WE'VE ALSO BEEN ABLE TO
VISUALIZE THE CIRCUITS AND
FIGURING OUT HOW TERPENES ACT TO
ACTIVATE NOCICEPTION AND WE'RE
LOOKING AT THE NEURONS HOPING TO
BE THE RIGHT MARKER AND HAVE
OTHER PROJECTS WE'VE BEEN
SUCCESSFUL WITH BUT DON'T HAVE
TIME TO TALK ABOUT AND WORK WITH
MINOR CANNABINOIDS.
THIS PAPER WAS JUST ACCEPTED FOR
PUBLICATION WEEKS AGO AND YOU'LL
BE SEEING THAT SOON AND THE
NON-TERPENE CANNABIS TYPES AND
THE NEXT STEPS, WE NEED TO WORK
MORE ON THE MECHANISM.
WE KNOW THROUGH THE RECEPTOR AND
WE FLOW THEY WORK THROUGH OTHER
RECEPTORS FROM THE TARGETS SOME
ION CHANNELS AND OTHER RECEPTOR
TYPES BUT THE MECHANISMS ARE
REALLY NOT CAREER.
WHERE ARE THE CIRCUITS AND
NEUROLOGICAL CHANGE AND AT THE
RECEPTOR WE'RE NOT HAD SURE
THEY'RE STANDARD AGONISTS AND WE
KNOW THERE'S OTHER MECHANISMS OF
ACTION BUT DON'T KNOW WHAT THAT
IS AND PUTTING IN FAIR EFFORT TO
FIGURE OUT HOW THAT THE
HAPPENING.
WE ALSO NEED TO COMPLETE OUR
THERAPEUTIC WORK.
ASK THE QUESTION WILL TERPENES
MAKE REAL DRUGS AND BLOCK
REWARDING AND OTHER SIDE EFFECTS
AND CAN WE REMEMBER THEM IN A
THERAPEUTICALLY USEFUL DOSE AND
THESE WILL BE SOME OF MY
THOUGHTS MAYBE WE CAN MAKE MORE
IN DETAIL.
DO TERPENES CONTRIBUTE TO THE
RECREATIONAL OR THERAPEUTIC
EFFECTS OF CANNABIS IS THAT
REAL?
I GET THAT ASKED A LOT.
SEVERAL TARGETS HAVE BEEN
REPORTED TO DATE AND THERE'S
BEEN A NUMBER INCLUDING ION
CHANNELS AND WHAT IS THE REAL
MECHANISM OF ACTION AND WE NEED
TO FIGURE THAT OUT AND A CONCERN
IS THE PUBLIC IS WIDELY USING
THE DRUGS AND MANY COMMERCIAL
ACTORS ARE AHEAD OF US AND TAKE
THIS AND IT WILL CURE YOUR
ANXIETY AND THIS MYRCENE WILL
MAKE YOU HAPPY AND CURE ALL YOUR
PROBLEMS AND THERE'S NO BACKING
FOR MOST OF THAT AND NEED TO TRY
TO GET AHEAD OF IT OR AT LEAST
CATCH UP AND INFORM THE PUBLIC
OF WHAT THESE DRUGS ARE DOING
AND MIGHT WE FACE HURDLES TO GET
THESE PATENTED AND IS THERE A
WAY TO SECURE INVESTMENT FUND
AND MAYBE NIH MAY HAVE A LEAD ON
THAT.
AND THERE'S A LOT OF WORK TO DO
BUT THESE ARE PEOPLE WHO DID ALL
THE WORK AND THANK YOU ALL FOR
YOUR ATTENTION.
>> THANK YOU VERY MUCH.
OUR NEXT SPEAKER IS DR. MACKIE
FROM INDIANA UNIVERSITY
PRESENTING ON MODULATION OF PAIN
MECHANISM BY CANNABIS DERIVED
CHEMICALS.
THANK YOU VERY MUCH.
>> GOOD MORNING, EVERYONE.
I'M HERE TO TALK ABOUT THE
PROJECT THE MULTI-PRI WE HAVE
WITH QUEENS MEDICAL CENTER IN
HAWAI'I.
AND THIS WAS A PROJECT THAT HAS
TWO PHASES.
THE FIRST PHASE WAS TO BROADLY
PROFILE MINOR CANNABINOIDS AS
WELL AS SOME MIXTURES AGAINST
THE ION CHANNELS PRESENT IN THE
IMMUNE CELLS AND AGAINST THE
NUMBER OF CELL LINES AND RATHER
LARGE MATRIX SCREENING.
THIS WORK WAS DONE BY THOSE
SITTING IN THE FRONT ROW AND CAN
ANSWER SPECIFIC QUESTIONS ABOUT
THIS PART OF THE WORK.
SO INHIBITING THE CALCIUM
CHANNELS MAY BE ANTIINFLAMMATORY
AND MAYBE THE COMPOUNDS WILL BE
USEFUL FOR TREATING VARIOUS PAIN
STATES.
THE SECOND PHASE OF THE STUDY
WAS TO TAKE THE MOST POTENT
COMPOUNDS AND TEST THEM IN PAIN
MODELS PARTICULARLY INFLAMMATORY
PAIN USING CFA AND PHARMACOLOGIC
NEUROPATHY USING THE MODEL.
SO THE PRIMARY FINDINGS FOR THE
ACIDIC CANNABINOIDS AND
INHIBITING THE CHANNELS AND CBGA
WAS POTENT IN THE LOW NANO MOLAR
RANGES AND THEN ALSO ANOTHER
TARGET WAS TRPM7 AND THIS
REQUIRED THE KINASE DOMAIN OF
TRPM7 AND PHOSPHORYLATION BY THE
KINASE.
IN LOOKING AT CBGA IT'S STRONGLY
ANTI-INFLAMMATORY IN TERMS OF
EXPRESSING IL2 PRODUCTION.
DESPITE THIS VERY GOOD IN VITRO
RESULTS, WE HAVE FOUND NO
EFFICACY IN OUR PAIN MODEL CFA
OR TREATING THE ESTABLISHED PAIN
OR USING IT IN A PROPHYLACTIC
MODE FOR MALES AND FEMALES AND
GOING UP TO HIGH DOSES WILL AT
30 MEGS PER KILO GRAM.
INTERESTINGLY THOUGH WE HAVEN'T
SEEN EFFICACY IN THE PAIN MODELS
CPG IS EFFICACIOUS IN TREATING
TWO MODELS OF KIDNEY DISEASE THE
CHEMOTHERAPY INDUCED MODEL AND
DOSE OF 10 MIGS PER KILOGRAM AND
IS NOT EFFECTIVE ON PAIN MODELS.
WE STRUGGLED WITH THIS QUITE A
BIT AND SOME OF THE REASONS WE
THINK FOR THE LACK OF EFFICACY
IN THE PAIN MODELS ARE POOR BIO
AVAILABILITY AND THESE
PARTICULAR PAIN MODELS MAY BE
LESS SUSCEPTIBLE TO THE
ANTI-INFLAMMATORY EFFECTS AND
ALL THE PAIN ASSAYS MAY NOT
REFLECT THE ANTI-INFLAMMATORY
PROCESS.
SO THE NEXT STEPS THINKING THE
CBG IS EFFECTIVE IN THE KIDNEY
MODELS AND MAYBE THE DOSING
PRESENCE QUESTIONS AND
APPLICATION OF CBGA IN CFA MODEL
AND TEST EFFICACY IN THE NERVE
INJURY MODEL THROUGH EVIDENCE
THAT INHIBITORS ARE PARTIALLY
IVE -- EFFECTIVE IN PART IN
MALES AND WORK ON THIS MAY BE
HELPFUL.
THIS IS KIND OF LED US TO A
PLASMA BINDING CANNABINOIDS AND
MORE DIRECTED METHODS OF THE TRP
CHANNELS AND THE TRPM7 PROJECT
HAS LOOKED AT THESE COMPOUNDS IN
TUMOR MODELS AND RESULTS IN
ADVANCING THESE.
WITH THAT THANK YOU AND MANY GO
ON TO THE NEXT ONE.
>> THANK YOU YOU, VERY MUCH.
NEXT SPEAKER IS DR. LAND FROM
UNIVERSITY OF WASHINGTON IN
SEATTLE.
THANK YOU.
PRESENTING ON CANNABIE WHERE
THEY'LL HAVE EFFICACY IN CHRONIC
PAIN.
>> OUR GOAL IN A MODEL OF
LIGATION CAN WE GIVE A CHRONIC
ADMINISTRATION USING A MODEL WE
DEVELOPED TO PRODUCE THESE HYPER
ANALGESIC EFFECTS.
AND THE AMYGDALA HAS SHOWN TO BE
DESENSITIZED TO PAIN AND
REGULATE SPINAL CONTROL OF PAIN.
AND STARTED WITH THIS MODEL OF
ANIMALS WITH ACCESS AND THESE
ARE THE TWO MOST INTERESTING
GROUPS AND WE GAVE TERPENES AND
GAVE IT HIT WITHOUT THE
PRE-TREATMENT OF TERPENES ALONE
AND GET LIGATION AT DAY ZERO AND
IN THE PURPLE GROUP THEY GET CBD
AND TERPENES AND THE CONTROL
ANIMALS RECEIVE CONTROL OF
GELATIN THE ENTIRE TIME.
YOU CAN SEE A NICE ANALGESIA IS
MAINTAINED FOR 21 DAYS WHEN WE
GIVE THE GELATINS THE DOSES WE
HAVE IN THERE WE COMPLETELY
BLOCK THE ANALGENEIC EFFECT AND
INTERESTING ONE THING WE FOUND
IS WHEN WE GIVE ACUTE CBD AND
TERPENES WE DON'T SEE THIS BLOCK
OF CHRONIC PAIN.
AND WHAT WE SEE IS ACUTE CBD
DOESN'T INHIBIT CHRONIC PAIN AND
IF YOU FOCUS ON THE UPPER LEFT
ONE OTHER THING WE'RE DOING IS
THIS REAL TIME CALCIUM IMAGING
IN THE BASAL LATERAL AMYGDALA
AND THE ANIMAL'S HEAD IS FIXED
AND WE'RE APPLYING A FILAMENT TO
THE BASE OF THE TAIL AND I WANT
TO DRAW YOUR ATTENTION TO THE
TOP LINE AND THE LEFT SET OF
DATA GOING DOWN TO HIGHLIGHT THE
FACT THE NEURONS OF THE BLA
SCALE WITH THE WEIGHT AND THE
LIGHTER WEIGHTS ON THE LEFT YOU
DON'T GET AS MUCH AS A RESPONSE
AND OVER TIME YOU SEE THE
DEVELOPMENT OF A STRONGER
RESPONSE TO THAT.
AND WE'RE NOT SEEING THE EFFECTS
ON BEHAVIOR.
AND ONLY CHRONIC DOSING IN THIS
COMBINATION PROVIDES BENEFIT.
WE'RE TRYING TO LOOK AT MORE
BEHAVIORAL PAIN PROFILE AND WE
HAVE THIS MACHINE LEARNING MODEL
WHERE THE MACHINE LEARNING IS
TRAINED TO STAMP ALL THE SPOTS
ON THE MOUSE AND THE MOUSE DOES
ALL THESE BEHAVIORS AND WE CAN
MEASURE THESE IN THE LINEAR
TRACK IN AN UNBIASSED WAY AND
WHAT WE GET WITH THAT IS JUST A
HUGE AMOUNT OF DATA.
THESE ARE ANIMALS THAT AT
BASELINE AND DAY ONE AND DAY 12
OF CHRONIC PAIN AND YOU SEE A
VARIETY OF METRICS CHANGE AS A
RESULT OF CHRONIC PAIN AND HOW
MUCH THEY MOVE.
WE THINK THIS IS LIKE GIVING US
A WIDER BEHAVIORAL PROFILE TO
USE WITH VON FREY AND HOT PLATE.
AND WE CAN GENERATE WHAT WE CALL
RADAR PLOTS THOUGH I THINK THEY
CAN BE REFINED A LITTLE BIT AND
GIVING US WHAT QUOTE, UNQUOTE,
FINGERPRINT OF WHAT THIS CHRONIC
PAIN LOOKS LIKE AND THE DASH
LINE IS 100% AND THESE ARE HOW
THE METRICS CHANGE AT DAY ONE
AND WHEN WE GIVE THE ACUTE
TREATMENT CBD YOU SEE THE
RECOVERY TO THE DASH LINE AND
WE'RE COLLABORATING WITH GROUPS
THAT WOULD LIKE TO TRY THE
LINEAR TRACK FOR THE BEHAVIORAL
MODELS SO COME AND TALK TO ME IF
YOU'RE INTERESTED.
THANKS.
>> WONDERFUL.
THANK YOU.
THANK YOU, DR. LAND.
OUR NEXT SPEAKER IS DR. VRANA
FROM PENNSYLVANIA STATE
UNIVERSITY PRESENTING ON
A.I.-BASED MAPPING CANNABIS
EXTRACTS IN PAIN PATHWAYS.
>> THANK YOU FOR THE OPPORTUNITY
I'M HERE REPRESENTING AN MPI
PROPOSAL WITH MY P.I. IN
RESEARCH.
THE GOAL IS TO USE AN AND
ARTIFICIAL INTELLIGENCE, MACHINE
LEARNING MECHANISM MAPPING
COMPOUNDS TO TARGETS NOT JUST
CANNABINOIDS BUT IN THIS WE'RE
FOCUSSED ON CANNABINOIDS AND WE
HAVE A LARGE TEAM WITH US
SEVERAL OF WHOM ARE WITH US
TODAY.
SO BENJAMIN SET THIS UP WELL.
THIS WAS A PAPER PUBLISHED IN
OCTOBER INVOLVING CHRONIC
ADMINISTRATION OF CBG AND IT'S
PROVIDING 24-7 ANALGESIA AND WE
USE THE IP ADMINISTRATION NOT
THE GELATIN ADMINISTRATION BUT
WE'RE MOVING THAT WAY NOW.
WE DO SEE ACUTE EFFECTS OF CPG
AS AN ANALGESIC HOWEVER, WHAT'S
REMARKABLE IS WHEN WE GIVE IT TO
MALES AND FEMALES CHRONICALLY
OVER THE COURSE OF 7 OR 14 DAYS
WE SEE HERE'S THE PRE-TREATMENT
STATE, THE NEUROPATHIC STATE AND
SEE A RELIEF FROM THAT.
ACUTELY, THAT RELIEF IS ALMOST
100%.
WE DON'T ACHIEVE THAT BUT HERE'S
THE KEY.
THE DRUG WAS GIVEN 24 HOURS
PRIOR TO THE TEST.
WE'RE GETTING MODEST AND GEESH
YA -- ANALGESIA AND WE ARE
BEGINNING TO EXPLORE CLINICAL
TRIAL IN A CANCER MODEL --
CANCER TREATMENT IN HUMANS THAT
GENERATES CIPN.
THE SECOND PAPER WE JUST
PUBLISHED IN DECEMBER COMES FROM
SOME WHO COULDN'T JOIN US AND
THE DIRECTOR OF MY CANNABIS
CENTER IN THE BACK OF THE ROOM
AND THE DRIFT PROGRAM COMPARES
DIFFERENT CANNABINOIDS AND
TERPENES PREDICT THE TARGETS
THEY'LL HIT AND ASKING IF
THEY'RE SIMILAR OR DIFFERENT IN
THE TARGETS?
OBVIOUSLY THC AND THCV WHICH
VARY IN A CARBON LENGTH ON THE
TAIL ARE HIGHLY CORRELATED.
SO THE PEARSON CORRELATION
COEFFICIENT BUT IN THE
PRELIMINARY SCREENING CPC IS
DIFFERENT FROM OTHER MOLECULES
AND THOUGHT IT MAY HAVE A UNIQUE
CHEMICAL BIOLOGICAL PROFILE AND
TURNED OUT TO BE THE CASE AND
WHILE CBD AND CBG LOOK SIMILAR
CBC PROVIDES ANALGESIA AND
INFLAMMATORY PAIN USING THE
MODEL.
WE THINK CBC HAS POTENTIAL AS A
NOVEL CANNABINOID FOR PAIN.
AND THIS IS AVAILABLE NOW AND
IT'S CANDY DOT D-O-K-H.org.
THEY'RE STILL IN REFINEMENT BUT
HERE'S THE IDEA.
WE HAVE PERHAPS DOZENS OF HEMP
EXTRACTS WITH DIFFERENT PROFILES
IN CBC, CBG AN THEY TAKE THE
LIBRARY OF EXTRACTS AND MINES
THE TEXT WITHIN PUB MED AND THE
PUBLICALLY AVAILABLE DATABASES
TO USE ARTIFICIAL INTELLIGENCE
TO START MAKING PREDICTIONS.
AND WHERE WE WOULD WANT TO BE IN
A COUPLE OF YEARS IS THAT RATHER
THAN AN EARLIER COMMENT TAKE
MYRCENE IT WILL TAKE YOU HAPPY
WE'LL HAVE PROFILES OF ENTOURAGE
EFFECTS TO LOOK AT WHAT
CONDITIONS SHOULD BE TREATED
WITH WHICH EXTRACT.
WE EXCITED ABOUT THIS.
I UNDERSTAND THE PUBLICATION HAS
NEARLY COME OUT NOW.
I'LL POINT OUT THESE ARE THE
PAPERS THAT WERE PUBLISHED IN
THE PAST YEAR SINCE LAST JULY
AND THANK YOU FOR YOUR TIME.
THANK YOU.
THIS IS VERY EXCITING.
THE NEXT PRESENTER IS FROM
OREGON STATE UNIVERSITY,
DR. STEVENS ON DISCOVERY OF
CANNABINOIDS FROM HEMP.
6:
>> THANK YOU VERY MUCH.
CAN YOU HEAR ME IN THE BACK?
>> PRESS THE BIG BUTTON.
>> SO OUR PROJECTI PROJECT IS ON
ASSISTED DISCOVERY OF
CANNABINOIDS FROM THE HEMP.
OREGON IS A BIG STATE AND IN
EAST OREGON THERE'S BIG PHARM
AND THEY EXTRACT CBD FROM THE
HEMP AND DISTILL IT ON A BIG
SCALE AND ISOLATE CBD AND CBG ON
A COMMERCIAL SCALE AND SELL TO
PHARMACEUTICAL COMPANIES.
THEN THEY CRYSTALIZE THOSE
MATERIALS AND WHAT'S LEFT OVER
WE CALL IN CHEMISTRY THE MOTHER
LIQUOR.
THE STUDENTS LAUGH.
IT HAS NOTHING TO DO WITH MOTHER
OR LIQUOR BUT IT'S A RICH SOURCE
OF CANNABINOIDS.
THEY USE THOSE MATERIALS TO DO
OUR IN VITRO STUDIES ON BIO
ACTIVE IN CELL CULTURE ANYTHING
RELATED TO PAIN PERCEPTION AND
LOOK AT CANNABINOIDS IN THE
ASSAYS AND WELL USE MACHINE
LEARNING.
HOW DOES THAT WORK?
WE FIRST HAVE A CLASSIC CALL.
ONE COLUMN SEPARATION STEP AND
OUR MACHINE LEARNING CAN DO
PREDICTION AND IN THE FRACTIONS
WE DO NOT ARE CONCERNED THESE
THINGS APPEAR.
YOU CAN SEE IN THE HEAT MAP HERE
AND EVERY FRACTION THAT IS
DIFFERENT CONCENTRATION AND
COMPOUNDS IS ENOUGH TO DO OUR
MACHINE LEARNING.
THEN FROM THOSE FRACTIONS YOU
HAVE A MASS SPECTRUM AND YOU CAN
SEE THE FRACTIONS AND PEAKS IN
THAT HEAT MAP AND THEN WE DO THE
BIO ASSAY AND CAN BE ANY BIO
ASSAY AND HERE'S THE EXAMPLE AND
THERE'S FLUCTUATIONS ACROSS THE
FRACTIONS.
THEN WE COMBINE THOSE TWO DATA
SETS AND DO PREDICTIONS.
YOU CAN SEE ON THE BLOCK ON THE
BOTTOM THAT THERE ARE ABOUT 10
MAYBE 15 COMPOUNDS IN THAT VERY
COMPLEX MIXTURE THAT PREDICTS
THE ACTIVITY IN THAT BIO ASSAY.
YOU CAN SEE IN THE TOP PREDICT
CDC8 AND ALL OTHER ASSAYS.
WHEN I PRESENT THE RESULTS I GET
THE COMPLAINTS YOU WILL ALWAYS
GET A TOP 10, I AGREE.
BUT IF YOU SCRAMBLE THE DATA AND
DISCONNECT THE BIO ACTIVITY DATA
FROM THE CHEM DATA YOU'LL SEE
THE RED LINE HERE AND THEN
COMPLETELY MOVE THE PREDICTIVE
EFFECTS.
SO THIS MEANS THIS WORKS AND NOW
WE CAN USE THOSE PREDICTORS IN
VALIDATION ASSAYS AND PUBLISH
ONE PAPER MAYBE TWO YEARS AGO
AND IT PREDICTS THE BIO ACTIVE
COMPOUND IN THE HOPS.
LAST SLIDE HERE.
SO WE HAVE THE PIPELINE
DEVELOPED.
WE WILL NOW ALSO WORK WITH THE
CBG DEPLETED FRACTIONS IN THE
SAME AIM SO THE BIO ACTIVITY
ASSAYS RELEVANT TO PAIN
PERCEPTION AND THEN WE STILL
NEED TO WORK ON THE CHEMISTRY
BECAUSE THERE'S HUNDREDS OF
COMPOUNDS AND WE HAVE ABOUT 35
STANDARDS IN HAND AND YOU CAN
SEE IN THE
GMPS NETWORK WE CAN IDENTIFY A
BUNCH OF COMPOUNDS BUT THERE'S
STILL MANY CANNABINOIDS WE DON'T
KNOW THE STRUCTURE OF AND MAYBE
THIS WILL HELP US TO IDENTIFY
NOVEL COMPOUNDS.
AND WE WORK WITH A BOTANICAL
CENTER IN OREGON TO DEVELOP THE
CANNABIS DATABASE AND HE STARTED
THAT BUT IT'S STILL NOT COMPLETE
AND WE WANT TO FILL THE
DATABASE.
WE HAVE A MOUSE MODEL AND
NON-INVASIVE USING ACOUSTICS AND
THIS IS SOMETHING WE DO WITH THE
COLLEGE OF ENGINEERING WHEN YOU
PUT A MOUSE IN A BOX IN PAIN
THEY BREATHE DIFFERENTLY AND
MAKE DIFFERENT SOUNDS AND
INSTEAD OF MAKING MOUSE AND PUT
IT IN THE SYSTEM YOU CAN MONITOR
WHILE THEY'RE LIVING IN THE CAGE
AND IT STILL NEEDS TO TO SOME
VALIDATION FOR US BUT IT WOULD
BE A GOOD WAY TO HAVE TOP
PREDICTORS AND TEST THEM IN A
WAY THAT MODEL TO SEE IF THERE
IS ANY EFFECT OF CANNABINOIDS ON
PAIN AND THAT'S MY PRESENTATION.
THANK YOU FOR YOUR ATTENTION.
>> THIS IS FANTASTIC.
THANK YOU, DR. STEVENS.
THE LAST PRESENTATION FOR THIS
PORTION IS DR. LOVE FROM
UNIVERSITY OF CALIFORNIA SAN
DIEGO.
THANK YOU.
PRESENTING ON MECHANISMS OF
MINOR CANNABINOIDS.
>> HI, EVERYONE.
I'M ANNA A POSTDOC IN PROFESSOR
BRAD MOORE'S LAB AT UCSD
REPRESENTING OUR MULTI-P.I.
PROGRAM.
A RECENTLY FUNDED R01 BETWEEN
THE MOORE LAB AND PROFESSOR
CHUNG'S LAB AT THE MEDICAL
DISCOVERY INSTITUTE.
SAN DIEGO'S A VERY RICH AREA FOR
ACADEMIC AND INDUSTRIAL BIO
TECHNOLOGY OUR LABS ARE A 10
MINUTE DRIVE AWAY WHICH HAS
HELPED FOSTER THIS
COLLABORATION.
OUR AWARD WAS FOUNDED ON
DECEMBER 20, 2023 AND THE FIRST
AIM IS TO DISCOVER AND
CHARACTERIZE NEW BIO CATALYSTS
TO CONSTRUCT THE DIVERSE MINOR
CANNABINOIDS AND THEN IN AIM 2
WE'RE LOOKING AT THE
NON-CLASSICAL AND CLASSICAL
CANNABINOID RECEPTOR COMPOUNDS
WE'RE GENERATING IN AIM 1.
THERE'S SYNERGY THAT HELP INFORM
EACH OTHER AND WE CAN GO BACK
AND GENERATE NEW LIBRARIES OF
MOLECULES.
SO OUR INTERESTING RESULTS, WE
HAVE A PAPER OUT THOUGH THE
AWARD WAS RECENTLY FUNDED.
WE HAVE A PAPER OUT EARLIER THIS
YEAR AND YOU MIGHT BE ASKING
WHAT DOES THE OCEAN HAVE TO DO
WITH CANNABIS BUT THIS WAS
SPAWNED FROM A RECENT DISCOVERY
IN BRAD MOORE'S LAB WE FOUND THE
MARINE BACTERIAL ENZYMES
INVOLVED IN THE BIO SYNTHESIS OF
ANTIBIOTICS AND FORM THE SAME
REACTIVE INTERMEDIATE FORMED BY
THE ENZYMES IN THE CANNABIS
PLANT.
YOU CAN SEE HERE ON THE TOP LEFT
THE MARINE BACTERIAL ENZYMES ARE
ABLE TO GENERATE THIS REACTIVE
INTERMEDIATE WHICH IS THE SAME
MADE BY THE OTHER CANNABINOID
FORMING ENZYMES IN THE CANNABIS
PLANT.
ALL THESE ENZYMES LONG TO THE
FAMILY OF ENZYMES AND YOU CAN
SEE IN THE FIGURE IN THE TOP
RIGHT ONE OF THE HALLMARKS IS AN
ATTACHMENT BETWEEN THE RESIDUES
OBSERVED IN BOTH MEMBERS OF THE
FAMILY AND THESE ARE CONSERVED
IN OUR MODELS.
SO IN OUR PAPER THAT WE
PUBLISHED WE WERE ABLE TO TAKE
WILD TYPE.
ENZYMES AND SHOW WE CAN PRODUCE
ACID AND ANALOGS IN VITRO USING
PURIFIED ENZYME AND THROUGH OVER
EXPRESSION AND PRODUCTION IN
BACTERIA.
AND SO THIS IS EXCITING BECAUSE
THE PLANT ENZYMES ARE QUITE
RECALCITRANT AND THIS IS THE
FIRST STEP TOWARDS A PROGRAM
WHERE WE CAN GENERATE ALL KIND
OF DIFFERENT MOLECULES IN
ANALOGS FERMENTATIVELY IN
BACTERIA AND THIS ALLOWS US TO
PRODUCE DIVERSE ANALOGS AND IN
CONTRAST TO THIS PLANT YOU CAN
DIRECTLY ACCESS FROM CBG.
YOU DON'T HAVE TO HAVE ACID AND
PLAYED WITH THE CHAIN LENGTH TO
ANALOGS AND THIS IS OUR EFFORT
TOWARD MINOR TRADITIONAL
CANNABINOID SCAFFOLDS AND THERE
ARE WITH PRESENTATIONS TODAY
SHOWING THERE'S STILL A LOT TO
LEARN ABOUT CBCs SO THEY'RE
EXCITED TO BE ABLE TO ACCESS THE
MOLECULES AND A PERK OF DOING
THIS ENZYMATICLY -- ENZYMA
ENZYMATICALLY FOR CONTROL AND WE
CAN LOOK AT NOT JUST THE
RECEPTORS BUT THE WHOLE FAMILY
WHERE THEY BELONG THE LIPID
SIGNALLING TPCRs.
THERE'S THREE DIFFERENT TYPES OF
RECEPTORS IN THE SIGNALLING
FAMILY AND THE LPA RECEPTORS THE
INDIGENOUS LIGAND HAS THE ACID
AND THE S1P RECEPTORS FOR WHOSE
NATIVE LIGAND IS A FPHOSPHATE AD
THE ENDOGENOUS ENDS OF THE
CANNABINOIDS ARE MOLECULES
EVERYONE SYNTHESISES AND WE'RE
INTERESTED HOW THEY INFLUENCE
SYNTHESIS OF THE
ENDOCANNABINOIDS KNOWN IMPACT
MOOD AND OTHER BIOLOGICAL
EFFECTS.
SO SAM -- SO SOME INTEREST WE
HAVE FROM YOU ALL AND THE FIELD
IS HOW DO THE MINOR CANNABINOIDS
PARTICULARLY CBC AND CBCA FIT IN
THE INFORMATION OF THE BIOLOGY
AND ARE THERE ACTIVITIES AT
OTHER LIPID CBGRs AND SOME LPA
RECEPTORS OR MAYBE METABOLITES
COULD HAVE EFFECTS THERE.
AND ALSO AGAIN THE INTERPLAY
BETWEEN THE PHYTO PHARMACOLOGY
AND EVEN IF SOME DON'T HAVE
ACTIVITY THEY COULD INFLUENCE
BIO SYNTHESIS AND STILL HAVE A
BIOLOGICAL EFFECT.
AND WE HEARD FROM EVERYONE ABOUT
INTEREST IN THE SYNERGY AND
WE'RE INTERESTED IN THIS ANG
SPECIFICALLY HOW THE EFFECT IS
MEDIATED AT A FUNCTIONAL LEVEL.
WHAT ARE THE RECEPTORS THEY'RE
BINDING TO TO MEDIATE THE
ACTIVITY.
THANK YOU SO MUCH FOR THE
OPPORTUNITY TO PRESENT TODAY.
VERY EXCITED TO BE HERE AND
THANK YOU TO OUR P.O. OR THE
GRANT AND THE NIH PEOPLE FOR
ORGANIZING AND BRAD AND GERALD
FOR THE OPPORTUNITY TO COME IN
AND REPRESENT OUR PROGRAM.
THANKS.
>> THANK YOU, DR. LOVE.
THANK YOU ALL NON-CLINICAL
P.I.s.
IT'S AMAZING THE AMOUNT OF DATA
YOU GOT DURING THIS FIVE YEARS
OR LESS OF THE PROGRAM AND
PRESENTING THEM IN SUCH A STRICT
TIME FRAME.
THIS WAS ABSOLUTELY AMAZING.
THANK YOU AND NOW WE'LL GOING TO
OUR BREAK.
WELL DESERVED AND WE'LL KEEP ALL
THE QUESTIONS FOR THE BIGGER Q&A
AND PANEL DISCUSSION WE'LL HAVE
AFTER THE CLINICAL P.I.'S
PRESENTATIONS.
PLEASE PICK UP YOUR NAME TAGS SO
WE'LL RECOGNIZE EACH OTHER BY
NAME AND BY FACE AND EVERYTHING
ELSE AND WE WILL SEE EACH OTHER
AT 11:00.
SO THE BREAK IS A LITTLE
SHORTER.
>> WELCOME TO THE NEXT SESSION
OF OUR MEETING AND THANK YOU FOR
BEING ON TIME.
BY THE WAY WE HAVE OVER 1100
REGISTERED FOR THE NIH VIDEOCAST
FOR THE MEETING.
WE MAY HAVE 1100 PEOPLE WATCHING
US RIGHT NOW.
I'D LIKE TO INTRODUCE DR. SEW
KAY CHIDEYA-CHIHOTA.
>> WE HAVE THE DATA BLITZ AND
I'LL INTRODUCE DR. YURGELUN-TODD
FROM THE UNIVERSITY OF UTAH.
HERE YOU GO.
SHE'S GOING TO BE PRESENTING ON
EXPLORING THE MECHANISMS
UNDERLYING THE ANALGESIC
PROPERTIES OF CANNABIDIOL USE
RESONANCE SPECTROSCOPY.
>> IT'S EXCITING TO HEAR THE
PRE-CLINICAL DATA AND NOW WE'LL
GO IN A DIFFERENT DIRECTION
WORKING WITH HUMAN SUBJECTS HAS
DIFFERENT KINDS OF CHALLENGES.
OUR OVER ALL STUDY AIMS WHICH
EXAMINE THE MECHANISMS WHERE CBD
EXTRACT BRAIN CHEMISTRY THROUGH
PROTON MRS AND IN RECENT YEARS
IT'S BEEN DEVELOPMENTS IN HOW TO
ACQUIRE AND INTERPRET THE MRS
DATA AND GLX WAS LOOKED AT
GLUTAMINE, GLUTAMATE AND GABA
AND LOOK AT THE BRAIN WITH
VARIOUS TECHNIQUES.
HERE WE'RE LOOKING AT MUSC
MUSCULOEMUSC
MUSCULOSKELETAL PAIN AND WE LOOK
AT THE PAIN THAT CAN BE
EXPERIENCED.
IT'S A PLACEBO-CONTROLLED STUDY
AND ENDURES FIVE DAYS AS A DAILY
ADMINISTRATION OF CBD EXTRACT OR
PLACEBO AND LOOKED AT PAIN
INTENSITY AND QUALITY OVERALL.
PRIOR TO THE ADMINISTRATION OF
CBD AND THEN PLACEBO AND 30
MINUTE AFTER.
WE HAVE AN INITIAL SCREEN WE DO
BEFORE ANYONE TALKS TO US AND DO
AN IN-PERSON SCREEN AND THERE'S
INDIVIDUALS BETWEEN THE PHONE
AND IN-PERSON SCREEN AND WHEN WE
INITIATED THE STUDY AT BASELINE
THEY ARE SCANNED AND HAD A
PHYSICAL EXAMINE ON BLOOD WORK
AND EVERYTHING TO MAKE SURE
THERE'S A NORMATIVE CATEGORY AND
IN DAY 1 THEY RECEIVE A SCAN
MEASUREMENTS AND REPEATED ON
DAY, TWO, THREE AND FOUR WITHOUT
A SCAN AND DAY FIVE A FINAL
SCAN.
WE HAVE FOLLOW-UP THE FOLLOWING
WEEK.
WHAT WE CHOSE TO EXAMINE WAS THE
SINGULAR CORTEX AND RIGHT INSULA
AND THIS IS A RADIO LOGIC IMAGE
AND WHAT WE CAN SEE AND THIS IS
A SAMPLE OF OUR DATA ACC
GLUTAMATE LEVELS DECREASED BY
DAY FIVE SIGNIFICANTLY.
WE HAVE CONSIDERABLY MORE DATA
BUT WE'RE IN THE PROCESS OF
ANALYZING IT.
IT'S BEEN A VERY COMPLICATED
STUDY TO DO AND I DO FEEL LIKE I
SHOULD MENTION WITH THE ADVENT
OF THE PANDEMIC WE WERE FROZEN
FOR A YEAR BECAUSE WE COULD NOT
DO HUMAN STUDY IN THIS
ENVIRONMENT BECAUSE IT WAS HARD
TO DISINFECT AND WE HAD THE
OPPORTUNITY TO REGROUP AND MOVE
AHEAD AND THEN OUR STAFF MOVED
ON TO OTHER JOBS AND HAD TO BE
RETRAINED.
THIS HAS BEEN A REAL LABOR OF
LOVE AND PERSEVERANCE.
OUR CURRENT.
FINDING WAS THE GLUTAMATE LEVELS
WERE ASSOCIATED WITH LOWER
SENSITIVITY AND POSITIVE
ASSOCIATION BETWEEN GLUTAMATE
AND PERATI IPHERAL MARKERS IN T
SCAN AND ASSOCIATED WITH REDUCE
INFLAMMATION IN DAY FIVE AND
HAVEN'T LOOKED AT THE DATA YET
BUT LOOKED AT THE RELATIONSHIP
BETWEEN BASELINE DATA AND
GLUTAMATE AND LOWER INTENSITY
PAIN AND PERIPHERAL MARKERS.
WE DID FIND A SIGNIFICANT
RELATIONSHIP RECENTLY PUBLISHED
AND JUST PUBLISHED THE ELEVATING
CIRCULATING SOLUBLE INTERLEUKIN
2 RECEPTOR ASSOCIATED WITH THE
INBALANCE IN INDIVIDUALS WITH
CHRONIC PAIN AND THE FIRST TIME
AS THE BEEN ASSOCIATED WITH
PERIPHERAL BLOOD MARKERS OF
INFLAMMATION.
THAT'S EXCITING TO THINK ABOUT.
WE'RE IN THE PROCESS OF LOOKING
AT A LOT OF OTHER DATA THAT
LOOKS AT BOTH THE SOMATIC
COMPONENTS OF PAIN AND THE
EFFECTIVE COMPONENTS OF PAIN
WHICH WE THINK ARE DIFFERENT IN
TERMS OF THE RESPONSE TO CBD.
AND WE THINK IT'S DIFFERENT IN
TERMS OF UNDERSTANDING ACUTE
VERSUS CHRONIC RESPONSES.
AND I'LL TRY TO RUSH.
WE'RE FINISHING OUR DATA
ANALYSIS AND CONTEMPLATING HOW
IT MAY INDICATE DIFFERENT
INDIVIDUALS WHO MAY BENEFIT FROM
THE TREATMENT OF CBD.
THANK YOU FOR YOUR ATTENTION.
THIS IS ALL THE SAME DATA I
SUMMARIZED.
>> THANK YOU, DR. YURGELUN-TODD.
SO OUR NEXT SPEAKER IS
DR. HELMAN FROM UCSF PRESENTING
ON NEUROIMMUNE MECHANISMS OF
CANNABINOIDS IN INFLAMMATORY AND
NEUROPATHIC PAIN.
>> I'M NOT DR. JUDITH HELL.
-- HELMAN.
I'M MARK SHOEMAKER AND WE USE
MOUSE AND HUMAN CELLS.
BRIEFLY OUR PROPOSAL IS
NEUROIMMUNE MECHANISMS AND OUR
HYPOTHESIS WAS AROUND AND PAIN
WITH MECHANISMS MEDIATED BY THE
CBV AND TRPV1 RECEPTOR AND THE
PRIMARY AIM IS TO HAND EFFECTS
OF MECHANISMS OF MINOR
CANNABINOIDS ON SENSORY NEURONS
AND BRAIN ENDOTHELIAL CELLS AND
WE STUDIED THE CANNABINOIDS
SHOWN HERE AND TAKE A MOMENT TO
SHOW THE RELATIONSHIP AND NEED
TO DRILL DOWN TO THE EFFECTS OF
THE FOUR MINOR CANNABINOIDS ON
CULTURES OF SENSORY NEURONS.
AND THIS DIFFERS FROM A LOT OF
THE PRIOR CHARACTERIZATIONS THAT
OCCURRED FOR INSTANCE TRPV1 IN
THE SYSTEMS OF STUDY.
OUR PRINCIPAL POINT IS WHETHER
THEY ACT IN THE PRIMARY
CULTURES.
SO OUR KEY FINDINGS HERE IS THAT
IN FACT THERE'S GREAT DIVERSITY
IN ACTION OF THESE MINOR
CANNABINOIDS ON THE SENSORY
NEURONS.
AND IN PARTICULAR WE FOCUSSED
PRINCIPALLY ON CVB AND CVN WE
THOUGHT CBD WAS ACTING DIRECTLY
ON THE NEURONS BUT THAT WAS NOT
THE CASE.
IN FACT WE FIND AND OUR EVIDENCE
SHOWS CBD IS ACTING INDIRECTLY
AND IN FACT PROBABLY TRPT PLAYS
A ROLE IN TRPT V1 ACTIVATION.
THERE'S OTHER UNKNOWN SITES OF
ACTION AND WE'RE INVESTIGATING
IN THE RECEPTOR 149.
THE FINAL MOMENT IS CBN IS
DIFFERENT FROM CBD AND EFFECTS A
LARGER DIAMETER OF NEURONS AND
NOT INVOLVED WITH CB1R AND I'LL
TURN IT OVER TO JUDITH TO TALK
ABOUT NON-SENSORY NEURONS AND
THE NON-CENTRAL NERVOUS SYSTEM,
THANK YOU.
>> THE MINOR CANNABINOIDS AFFECT
THE ACTIVATION OF NON NEURAL
CELLS AND HUMAN BRAIN
ENDOTHELIAL CELLS.
WE ACTIVATE THEM WITH BACTERIAL
IL1 BETA IN THE PRESENCE AND
ABSENCE OF THE MINOR
CANNABINOIDS AND THEY MODULATE
CYTOKINE PRODUCTION BY EN
ENDOTHELIAL CELLS AND AFFECT
PERMEABILITY AND ARE
HETEROGENOUS IN HOW THEY EFFECT
THANK YOU LEUKOCYTE AND THERE'S
DIFFERENT EFFECT AND MAGNITUDE
AND EFFECTS UNDER DIFFERENT
INFLAMMATORY CONDITIONS.
WE ALSO ENABLED WHAT I CONSIDER
AN EXCITING DISCOVERY
CANNABINOIDS MODULATE THE
INFLAMMATION VIA CENTRAL NERVOUS
SYSTEM MECHANISMS.
WE USED AN ACUTE MODEL INDUCED
BY LPS ADMINISTRATION.
IN THE EARLY STUDIES ON THE
PROJECT WE FOUND WE FOUND CBG,
CBC AND THC AND OTHERS
DOWNREGULATE CYTOKINES AND
UPREGULATE THE CYTOKINE IL IN
MICE.
FURTHERMORE WE FOUND CANNABINOID
RECEPTOR 1 EXPRESSING CNS
NEURONS AFFECT THIS AND THE TRP
V1 NEURONS MEDIATE THE
INFLAMMATORY ACTIONS IN LPS
TREATED MICE.
CBC AND CBG DO NOT MEDIATE
THROUGH EITHER CB OR TRP V1 IN
OUR MODEL.
AND DR. SHOEMAKER'S GROUP
IDENTIFIED 149 AS A NOVEL
CANNABINOID RESPONSIVE PROTEIN.
SO TO SUMMARIZE OUR STUDIES SHOW
MINOR CANNABINOIDS HAVE MULTIPLE
SITES OF ACTION INCLUDING IN THE
PNS AND NEURONS AND LEUKOCYTES
AND ENDTHELIAL CELLS AND THEY
MODULATE PAIN BIOLOGY AND
INFLAMMATION THROUGH THEIR
DIVERSE ACTIONS ON CELL TYPES
AND WANT TO UNDERSTAND THIS
BRAIN AND THE ROLE OF THE
RECEPTOR 1 IN MODULATING PAIN.
>> THANK YOU, HELLMAN, THANK
YOU.
SO NEXT UP IS DR. COOPER FROM
THE UCLA PRESENTING ON
SUBJECTIVE AND ANALGESIC EFFECTS
ON B CARYOPHYLLENE AND AS WE
KNOW CANNABIS IS USED FOR PAIN
YET THERE ARE MIXED FINDINGS AND
ADVERSE EFFECTS.
THE QUESTION WE'VE BEEN ASKING
ALL MORNING IS CAN CANNABIS
CONSTITUENTS REDUCE HARMS AND
IMPROVE OUTCOMES IN ALLEVIATING
PAIN.
WE HEARD OF THE EVIDENCE
AFFORDING THE USE OF DELTA HYDRO
CANNABINOID FOR PAIN AND THERE'S
EVIDENCE IN POPULATION-BASED
STUDIES AND RANDOMIZED CONTROL
TRIALS HAVE PROVIDED SOME
EVIDENCE THAT CAN BE HELPFUL FOR
CHRONIC PAIN PATIENTS AND WE
HAVE CONTROLLED LABORATORY
SETTINGS DEMONSTRATING IT CAN
REDUCE PAIN RESPONSE IN A
DOSE-DEPENDENT MANNER.
OF COURSE THESE ARE NOT WITHOUT
ADVERSE EFFECTS.
THE QUESTION IS CAN SOME OF
THESE CANNABIS CONSTITUENTS
REDUCE THE DELTA THC LEADING TO
THE GRANT AND THE INTEREST IN
LOOKING AT SOME OF THE TERPENES
ABUNDANTLY PRESENT OR RELATIVELY
PRESENT IN THE CANNABIS PLANT
PARTICUL
PARTICULARLY MYRCENE AND
CARYOPHYLLENE AND UNLIKE THC AND
OTHER ANALGESICS THERE ARE NO
REWARDING EFFECTS OF THE
TERPENES AND CARYOPHYLLENE HE
DEUCES EFFECTS OF DRUGS IN
ANIMAL MODELS AND HUMANS.
THE IDEA WAS TO EXAMINE IN A
SYSTEMATIC CONTROLLED MANNER
WHETHER MYRCENE AND BETA
CARYOPHYLLENE CAN REDUCE PAIN
RESPONSE WITH MINIMAL PSYCHO
ACTIVITY IN HEALTHY PARTICIPANTS
UP OUR CANNABINOID LABORATORY.
NEXT IF THEY CAN ENHANCE DELTA 9
INDUCED ANALGESIA AND REDUCE
EFFECTS.
LOOKING AT THE THC SPARING
EFFECTS OF THE TERPENES.
SOME WAS TALKED ABOUT EARLIER IN
THE ANIMAL MODELS.
THIS WAS A PHASED 1 DOUBLE BLIND
PLACEBO CONTROLLED STUDY WITH
HEALTHY PEOPLE THAT USED
CANNABIS.
THIS WAS CHALLENGING TO GET
THROUGH THE FDA.
TO MY KNOWLEDGE THIS WAS THE
FIRST TIME THIS WAS LOOKED AT IN
HUMANS THESE COMPOUNDS.
WE USED A VAPORIZED MODE OF
ADMINISTRATION BECAUSE THIS IS
HOW MOST PEOPLE ARE EXPOSED TO
THESE AND ECOLOGICALLY RELEVANT
MEANING THE DOSES WE WERE
EXPOSING PEOPLE TO IS WHAT
THEY'RE TYPICALLY EXPOSED TO
WHEN THEY USE CANNABIS BUT
GETTING THE TERPENES AND YOU SEE
7 OF THE 15 OUT-PATIENT
SESSIONS.
THEY WERE ABOUT EIGHT HOURS AND
LOOKED AT ANALGESIC EFFECTS
BEFORE DRUG WAS ADMINISTERED,
AFTER ENSURING PEOPLE HAD NOT
USED ANY CANNABIS THAT MORNING
AND HAD A LOW DOSE, 5 MILLIGRAMS
NOT EXPECTED TO PRODUCE
ANALGESIC EFFECTS ON ITS OWN
UNIVERSITY US A HIGHER DOSE, 15
MILLIGRAMS OF THC EXPECTED TO
PRODUCE EFFECTS AND ROBUST
PSYCHO ACTIVITY WE USED TWO
DOSES OF MYRCENE THE LOWER AND
HIGHER LEVEL SAME FOR BETA
CARYOPHYLLENE AND RANDOMIZED
WITHIN SUBJECT PROTOCOL.
I'M SHOWING YOU HERE A SIMPLI
SIMPLIFIED SCHEDULE AND RELEVANT
TERPENE AND LOOKED AT ANALGESIA
USING THE MODEL OF PAIN AND
ASKED DO YOU LIKE THE DRUG,
WOULD YOU TAKE IT AGAIN AND HOW
STRONG IS THE DRUG.
WE LOOKED AT THC AND MYRCENE AND
BETA CARYOPHYLLENE ITSELF TO
COMPARE THEM TO THC BY
THEMSELVES AND THEN LOOKED AT
THE DOSE COMBINATIONS.
IT'S A LENGTHY STUDY AND WE'RE
COLLECTING BLOOD, PLASMA SAMPLES
TO LOOK AT THE PHARMACO KINETIC
ACTIONS AND ASSOCIATE HOME TO
WITH BEHAVIORAL OUTCOMES.
WE'VE SEEN A LOT OF PARTICIPANTS
AND HAD MANY ENROLLED.
WE'VE ALSO HAD A LOT OF
WITHDRAWALS.
THIS IS A CHALLENGING STUDY IN
PART DUE TO THE LENGTH.
WE HAVE TO MAKE SURE THERE'S
AMPLE TIME FOR WASH OUT AND HAD
EIGHT PEOPLE COMPLETE ONCE
ENROLLED AND HAD A LOT OF
SESSIONS.
APOLOGIZE FOR FORMATTING ISSUES
AND HAD 171 SESSIONS COMPLETED
AND NOT MANY ADVERSE EVENTS.
TO APPEASE THE FDA WE LOOK AT
ADVERSE EVENTS STRINGENTLY AND
HAD FEW MINOR ADVERSE EVENTS
RELATED TO TERPENE
ADMINISTRATION GIVEN ALL THE
SESSIONS WE'VE ADMINISTERED.
STEP 1 IS THE MAXIMUM PAIN
RELIEF AND MINIMAL INTOXICATION
AND RUN PHARMACO KINETIC
ANALYSIS AND ASSESS THE DOSE
COMBINATION TO LOOK AT THE
OPIOID SPARING EFFECTS TO
PERHAPS REDUCE OPIOID DOSES TO
ACHIEVE PAIN RELIEF AND WE HEARD
OF ABOUT WORK IN THIS AREA THIS
MORNING.
AND LASTLY THOUGH NOT PRIOR TO
THE GRANT IS TO CONSIDER
ALTERNATIVE MODES OF
ADMINISTRATION.
VAP
VAPORIZING IS NOT THE BEST
EFFECT AND LOOKING AT ORAL
ADMINISTRATION NEXT.
WE'VE HAD SERIOUS CHALLENGES
WE'VE HAD TO COME UP AGAINST BUT
COOL TO BE ABLE TO DO THIS WORK.
THANK YOU.
>> THANK YOU.
REALLY INTERESTING.
OKAY, DR. HARTE.
>> I'M LOOKING AT PAIN
MECHANISMS IN OSTEOARTHRITIS.
>> THANK YOU.
UNFORTUNATELY DR. HARTE COULDN'T
MAKE IT SO I'M ON THE STUDY AND
LOOKING AT CANNABINOID
INTERACTIONS AND CENTRAL AND
PERIPHERAL PAIN MECHANISMS IN
OSTEOARTHRITIS PAIN AND SEE IF
THEY RESPOND DIFFERENTLY TO CBD,
THC OR THEIR COMBINATION.
I'LL TELL YOU ABOUT OR STUDY
DESIGN AND SUMMARIZE CHALLENGES
IN OUR TRIAL.
IT'S A RANDOMIZED PLACEBO
CONTROLLED DOUBLE-BLIND STUDY
AND HAVE KNEE OSTEOARTHRITIS
PATIENTS AND RANDOMIZED TO ONE
OF FOUR GROUPS EITHER CBC ALONE,
THC ALONE OR COMBINATION OF BOTH
OUR PLACEBO.
THOSE ARE OUR FOUR GROUPS.
OUR PRIMARY OUTCOME IS TO LOOK
AT THE CONNECTIVITY IN THE BRAIN
AND THE OTHER CO-PRIMARY OUTCOME
IS TO LOOK AT CBD LOOKING AT
REDUCING IL6 CONCENTRATION AND
THINK THC WILL BE ACTING MORE
CENTRALLY IN THE BRAIN WHERE CBD
MAY ACT ON IL6.
THAT'S OUR HYPOTHESIS AND WHAT
WE'RE HOPING TO STUDY.
WE LOOKED AT THE STRUCTURE AND
FOUND THAT CONNECTIVITY PATTERN
WAS MORE AMPLIFIED IN
INDIVIDUALS WITH MORE
CENTRALIZED PAIN OR MORE
FIBROMYALGIA LIKE SYMPTOMS ANDIS
THIS THEY MAY BE MORE PREVALENT
IN SOME KNEE OSTEOARTHRITIS
PATIENTS AND MAY BE MORE LIKELY
TO RESPOND TO THC COMPOUNDS AND
PATIENTS THAT DON'T HAVE THOSE
SYSTEMS AND LOW CENTRALIZATION
MIGHT RESPOND BETTER TO CBD AND
HAVE MORE OF AN ANALGESIC EFFECT
ON INFLAMMATION OF THE KNEE.
SO SO FAR WE'VE BASICALLY
RECRUITED OVER 54 PATIENTS IN
THE STUDY AND WE'RE GOING TO
CONTINUE RECRUITING.
WE HAD SIGNIFICANT CHALLENGES AS
MANY HAVE AS WELL SO WE WERE
LAGGING INITIALLY BECAUSE OF
COVID AND STARTED LATE AND THEN
IN ADDITION IN MICHIGAN WE HAVE
RECREATIONAL USE OF CANNABIS
LEGALLY USED RECREATIONALLY AND
PEOPLE ARE LESS LIKELY TO ENROLL
IN A STUDY WHEN THEY CAN GO TO
THE DISPENSARY AND GET SOME.
AND THEN ALSO MANY TIMES THEY
COME TO STUDY THEY HAVE A
SIGNIFICANT LEVEL OF PAIN BEFORE
THEY ENTER IN THE TRIAL AND SO
WE WERE TRYING TO WASH THAT OUT
BEFORE THE ACTUAL ADMINISTRATION
AND HAVE A TWO-WEEK RUN-IN
PERIOD.
IF PATIENTS HAVE LESS THAN THAN
AN ANALOG SCALE FOR THE PAIN
THEY WON'T BE ALLOWED TO
CONTINUE IN THE STUDY.
WE'VE HAD A LOT OF PARTICIPANTS
HAD A STRONG PLACEBO RESPONSE
MAKING THEM UNABLE TO CONTINUE
IN THE STUDY.
ON THE PLUS SIDE WE HAVE PEOPLE
WHO DON'T HAVE A PLACEBO
RESPONSE BUT ON THE NEGATIVE
SIDE IT'S MAKING MORE DIFFICULT
TO RECRUIT BECAUSE WE'VE GOT THE
REGRESSION TO THE MEAN AND
FINALLY THERE'S BEEN SHORTAGE
AND SO THAT HAS ALSO CAUSED US
SOME SLOW UP AS WELL BUT
HOPEFULLY BY THE TIME WE HAVE
OUR NEXT MEETING WE'LL BE ABLE
TO PRESENT THE USE IN DATA AND
SHOW YOU SOME OF OUR FINDINGS WE
HAVE.
SO THANK YOU VERY MUCH.
>> THANK YOU YOU, DR. HARRIS.
DR. BIDWELL FROM UNIVERSITY OF
COLORADO.
THANK YOU.
AND SHE'S GOING TO TO BE
PRESENTING ON SELF-SELECTED
CANNABIS USE AMONG INDIVIDUALS
WITH CHRONIC LOW BACK PAIN.
>> HELLO.
THANK YOU.
THANK YOU FOR THE OPPORTUNITY TO
SPEAK WITH YOU AND I'LL PRESENT
DATA ON OUR HUMAN STUDY OF
SELF-SELECTED EDIBLE CANNABIS
USE AMONG INDIVIDUALS WITH
CHRONIC LOW BACK PAIN AND THIS
WAS FUNDED SIX YEARS AGO AND
RECENTLY WRAPPED UP THE DATA
COLLECTION.
I'M EXCITED TO SHARE PRELIMINARY
FINDINGS WITH YOU ALL FROM THIS
WORK.
THE GOAL WAS TO USE PROSPECTIVE
AND NATURALISTIC DESIGN TO
UNDERSTAND THE THERAPEUTIC
EFFECTS AND PHARMACOLOGY AS
PHARMACOLOGY IN THE WILD FOR
CANNABIS USE FOR CHRONIC PAIN.
WE INVESTIGATED A WIDELY USED
EDIBLE IN OUR COLORADO STATE
LEGAL MARKET.
INTERESTED IN ANALGESIC AND
THERAPEUTIC EFFECTS ON PAIN AND
POTENTIAL NEGATIVE ADVERSE SIDE
EFFECTS OF CANNABIS USE IN THE
POPULATION INITIATED CANNABIS
USE FOR PAIN AND WE'RE
INTERESTED IN THE IDEA THAT
EFFECTS MAY DIFFER DEPENDING ON
DOSE AND RATIO TO CBD IN THE
EDIBLE.
A LITTLE BIT ABOUT OUR DESIGN.
THIS AGAIN IS A PROSPECTIVE
STUDY.
WE BROUGHT IN INDIVIDUALS WHO
HAD CHRONIC PAIN LOW BACK PAIN
WITH SIX MONTHS OF SELF-REPORTED
BACK PAIN AND WERE NOT YET USING
CANNABIS TO USE THAT PAIN.
THEY'RE INTERESTED IN STARTING
AND WE'RE CATCHING THEM AT THE
BEGINNING AND PROVIDING FOR A
BASELINE AND THIS IS FIVE YEARS
OF DATA COLLECTION.
IT TOOK A LOT OF TIME AND AT
BASELINE THEY WENT TO A LOCAL
DISPENSARY AND PURCHASED THEIR
PRODUCT AND WERE ABLE TO SELECT
FROM A RANGE OF CANNABIS
PRODUCTS AVAILABLE IN THE LEGAL
MARKET AND A LITTLE BIT OF WHAT
THAT LOOKS LIKE.
HALF OF THE STUDY POPULATION
SELECTED 47% SELECTED A PRODUCT
THAT WAS BALANCED OR SIMILAR
LEVELS OF THC TO CBD.
38% SELECTED A CBD DOMINANT
PRODUCT WITH LITTLE OR NO THC
AND 15% SELECTED A THC DOMINANT
WITH NUL OR ZERO CBD.
INTERESTING THE GROUPS ARE
SIMILAR IN PAIN LEVELS AND DID
NOT DIFFER DEMOGRAPHICALLY THEY
LOOKED SIMILAR.
THE MAIN DIFFERENCE WAS THOSE
INTERESTED IN A THC PRODUCT HAD
A HIGHER RATIO OF MALES TO
FEMALES THOUGH THE SAMPLE IS
MAINLY FEMALE.
THEY HAD TWO WEEKS TO USE THE
PRODUCT OR LITTLE AS THEY WANTED
AND TRACKED THAT IN DETAIL AND
AT THE TWO-WEEK TIME POINT WE
MET THEM AT THEIR HOME IN OUR
MOBILE LAB.
IT ALLOWED US TO STUDY THE ACUTE
EFFECTS AND USED THE MOBILE LAB
TO GET ASSESSMENTS PRIOR AND
LOOKED AT ONE HOUR AFTER NEWS
AND TWO HOURS AFTER INGESTION.
SOME PRELIMINARY DATA IS WHAT
THIS LOOKS LIKE IN THE MOBILE
LAB.
WHAT DID PEOPLE USE AND WHAT DID
THEIR CANNABINOID EXPOSURE LOOK
LIKE AFTER USE OF THAT LEGAL
MARKET PRODUCT?
YOU CAN SEE ACROSS THE THREE
PRODUCT GROUPS THE INGESTIONS OF
SPECIFIC CANNABINOIDS AS WELL AS
THE EXPOSURE LINE UP NICELY WITH
WHAT YOU'D EXPECT.
ALSO INTERESTING TO HIGHLIGHT
WHAT PEOPLE PREFER TO TAKE AND
THE THC DOSING LINING UP UNDER
10 MILLIGRAMS PER USE ACROSS THE
THC PRODUCT GROUPS AND CBD
LOOKING A LITTLE BIT HIGHER IN
TERMS OF THEIR INGESTED DOSE.
SO THIS IS HOW THEY REPORTED
THEIR SELF-REPORT ONE AND
TWO-HOUR POST USE AND SEE A
TRENDING EFFECT AND THC
CONNECTED PRODUCTS SHOWING A
STRONGER ASSOCIATION WITH PAIN
RELIEF OVER TIME AND FOLLOWED UP
LOOKING AT INDIVIDUAL DOSING
SPECIFICALLY WE SEE A STRONGER
AFFECTS AND WE SEE ASSOCIATIONS
WITH THC SHOWING SLIGHT INCREASE
IN NEGATIVE MOOD ACROSS THE
MOBILE LAB APPOINTMENT AND
SIMILARLY LOOKING AT DRUG
EFFECTS WE SEE INTOXICATION AND
CANNABIS DRUG EFFECTS AND THC
AND NEITHER SEEM TO BE MITIGATED
BY CBD BEING IN THE PRODUCT OR
NOT IS A THC STORY.
WHEN WE THINK ABOUT NEXT STEPS
THIS IS A HUGE DATA SET AND RICH
BEHAVIORAL DATA AND WE HAVE
DAILY DATA AND CIRCULATING
CYTOKINES AND LPS STIMULATING
CYTOKINES AND HAVE WORK TO DO IN
ANALYZING THE DATA AND PRIMARILY
FOR HOW TO IT SEEMS TO BE A THC
STORY AND THIS IDEA THAT CBD ON
BOARD AT THE DOSES PEOPLE ARE
USING IN LEGAL MARKET PRODUCTS
IS NOT ASSIGNED THESE EFFECTS.
THANKS SO MUCH MY COLLABORATORS
ON THE WORK AND WE SPENT A LOT
OF TIME WORKING AND THINKING
ABOUT THE STUDIES TOGETHER.
THANK YOU.
>> THANK YOU.
>> LAST BUT NOT LEAST WE HAVE
DR. RADHAKRISHNAN FROM YALE
SCHOOL OF MEDICINE PRESENTING ON
THE EFFECT OF CANNABIDIOL ON
MICROGLIAL AND PAIN
SENSITIZATION.
>> THANK YOU TO NCCIH FOR
ORGANIZING THIS AND IT'S GREAT
TO SEE EVERYBODY.
WE'RE TALKING ABOUT THE STUDY WE
WERE FUNDED TO DO.
MY CO-INVESTIGATORS
UNFORTUNATELY COULDN'T BE HERE.
WE STUDY THE CANNABIDIOL AND WE
KNOW ACTIVATION IS A TARGET FOR
CHRONIC PAIN AND LOOKING AT
NEUROPATHIC PAIN AND CHRONIC
BACK PAIN AND FIBROMYALGIA AND
LOOK AT PAIN SENSITIZATION A
MECHANISM IN CHRONIC PAIN AND
CONTRIBUTES TO THE TRANSITION
FROM ACUTE TO CHRONIC PAIN.
NOW, IN PRECLINICAL STUDIES TRP
V1 ANTAGONIST AFFECT PAIN
SENSITIZATION AND IN STUDIES
WITH CBD IT'S BEEN SHOWN TO
PREVENT BRAIN AND SPINAL MIC
MICROGLIAL ACTIVATION AND LOOKED
AT THE BIOLOGICAL MECHANISM AND
CENTRAL PAIN MECHANISM
UNDERLYING CHRONIC PAIN.
ONE OF THE CHALLENGES WE HEARD
ABOUT THE PRECLINICAL STUDIES
AND SEE EFFECTS OF CBD ON PAIN
AND RANDOMIZED CONTROL TRIALS ON
HUMANS HAVE NOT BEEN THAT
POSITIVE AND HAS BEEN A
CHALLENGE WE HAVE TO BRIDGE SO
THE STUDY IS PRIMARILY IN
HUMANS.
AND WE LOOK AT ACTIVATION AND AS
YOU CAN SEE IN FIGURE 1 THE
BRIGHTER RED IS INDICATE OF
BINDINGS TO THE MICROGLIAL WE
CAN INDUCE AND CAN USE CAPSAICIN
AND AN OBJECTIVE MEASURE AND IN
FIGURE 3 WE'VE SHOWN EARLIER THE
DOSES OF THC CAN MODULATE THIS
EFFECT.
LOW DOSE AND HIGH DOSE OF THC
THERE'S A VARIABLE RESPONSE TO
THE HYPERALGESIA.
IN TERMS OF OUR STUDY SO PBR28
IS A LIGAND THAT BIND TO
ACTIVATION AND THE GENOTYPIC
RESPONSE AND BINDERS CAN BE
INCLUDED IN THE STUDY BUT
EXCLUDE THE BINDERS AND SUBJECT
TO HEALTHY PEOPLE WHO UNDER GO
MRI SCAN AT BASELINE CAPSAICIN
TEST AND HAVE A SCHEDULE OF A
10-DAY REGIMENT OF CANNABIDIOL
AND THE DOSING OF CBD AND THE
RANDOMIZED TRIAL SOME ED CBC AND
IN DAY 10 AND 11 OF THE STUDY
THEY UNDER GO THE PARADIGM WITH
MICROGLIAL ACTIVATION AND
MEASURE AND CONDUCT THE
CAPSAICIN SKIN TEST AND LOOK AT
THE ACTIVATION OF THE THALAMUS
AND WHAT WE CAN DETECT.
AGAIN THE STUDY HAS REGULATORY
CHALLENGES WE HAVE TO OVERCOME
AND SHORTAGES OF LPS AND SOME
REGULATORY ASPECTS WE'RE STILL
TRYING TO OVERCOME BUT ONE OF
THE THINGS THE PRELIMINARY STUDY
OF RESULTS IS THAT OUR MODEL CAN
CAPTURE HYPERALGESIA AND WE
MEASURE SENSITIVE TO THE MEASURE
OF HYPERALGESIA AND MICROGLIAL
ACTIVATION AND YOU GET A
RESPONSE IN THE ACTIVATION AND
WE DRAW EFFECTS AGAINST THE
STRONG SAMPLE SIZE AND IT'S
EARLY DAYS BUT WE STILL ARE
EXCITED ABOUT THIS RESULT.
SO FUTURE STEPS IS STUDY
COMPLETION WHICH IS THE BIGGEST
CHALLENGE.
I THINK IT'S IMPORTANT TO
VALIDATE THE FINDINGS IN
PATIENTS WITH CHRONIC PAIN AND
STUDY HEALTHY PEOPLE AS A
DIFFERENT POPULATION THAN THOSE
IN CHRONIC PAIN.
ONE OF THE THINGS THAT STANDS
OUT IS VARIABILITY AND IT'S
IMPORTANT TO RECOGNIZE
PREDICTORS OF PAIN BECAUSE NOT
EVERYBODY HAS THE SAME RESPONSE
AND THE FOURTH ASPECT I THINK IS
IMPORTANT IS TO CONSIDER
NON-CLINICAL FACTORS AND LOOK AT
SLEEP, ANXIETY AND STRESS AND
THESE ARE THINGS WE ARE
MEASURING.
THANK YOU AGAIN AND THANK YOU TO
NCCIH FOR YOUR SUPPORT FOR WHICH
THE WORK WOULDN'T BE POSSIBLE
WITHOUT THAT AND THANK YOU FOR
ALLOWING ME TO PRESENT TODAY.
>> THANK YOU, DR. RADHAKRISHNAN.
THANK YOU.
SUCH INTERESTING PRESENTATIONS
AND I HONESTLY HAVE QUESTIONS
BUT I'M GOING TO ACTUALLY OPEN
IT UP TO EVERYONE ELSE.
I THINK WE HAVE TIME FOR TWO TO
THREE QUESTIONS.
STEP UP TO THE MIC, ANYONE WITH
QUESTIONS?
DON'T BE SHY.
OTHERWISE I WILL MONOPOLIZE THE
MICROPHONE.
NO?
SOMEONE'S GETTING UP.
ALL RIGHT.
>> ONE THING I NOTICED ABOUT THE
CLINICAL AND PRE-CLINICAL IS THE
COMPARATORS ACROSS THE BOARD IN
DIFFERENT STUDIES.
WE SAW SOME PEOPLE USING
BUPRENORPHINE AND IN HUMAN
STUDIES WE HAD FEWER
COMPETITORS.
IT MAY BE INTERESTING TO THINK
ABOUT THE COMPARATORS IS GOING
TO CHANGE BASED ON THE PAIN
MODEL AND THE CANNABINOID AND
THE MECHANISM OF ACTION.
BUT IT MAY BE INTERESTING TO
THINK ABOUT A UNIFORM WAY OR
SYSTEMATIC WAY WHERE WE CAN HAVE
STANDARD COMPARATORS TO ASSESS
THE DIFFERENT CANNABIS
CONSTITUENTS THAT LOOK AT THEIR
EFFECTIVENESS, EFFICACY,
WHATEVER YOU WANT TO CALL IT
ACROSS THE MODELS.
A GENERAL QUESTION AND
OBSERVATION.
>> THIS IS A WONDERFUL QUESTION
ESPECIALLY BECAUSE WE HAVE A.I.
AND COMPUTATIONAL EXPERTS.
SO CAN WE HAVE SOME OPINIONS OR
PRELIMINARY THOUGHTS ON HOW WE
CAN MAKE IT IN A HIGH THROUGHPUT
COLLEAGUES WHO USE A.I. OR
HIGH-COMPUTATIONAL MODELS.
>> I DON'T HAVE AN ANSWER TO THE
QUESTION BUT I'M GOING TO ADD A
WRINKLE OF COMPLEXITY IS THE
ISSUE OF BLINDING IN HUMAN
STUDIES PEOPLE KNOW WHAT THEIR
PLACEBO IS BECAUSE OF THE SIDE
EFFECTS.
AND AND.
THE OTHER ASPECT WE NEED TO
THINK ABOUT IS SOMETHING THAT
CAN BE BLINDING AND IMPROVED.
>> WHEN WE SEARCH FOR TARGETS
AND BIND MANY TARGETS SO I
HAVEN'T SEEN A DRUG THAT EFFECTS
ONLY ONE RECEPTOR.
IT'S A BIO AVAILABILITY AND
BINDING ABILITY.
SO WHEN YOU LOOK AT FORMULATION
IT BECOMES A GAME OF HOW TO PUT
THINGS TOGETHER SO YOU TARGET A
PARTICULAR SET OF RECEPTORS
VERSUS LIKE OTHER UNDESIRABLE
EFFECTS.
SO I THINK AT LEAST LISTENING TO
THE MEETING IS AMAZING BECAUSE
THERE'S INFORMATION ABOUT ALL
THE STUDIES AND I THINK IT'S
TIME TO CONNECT ALL OF THIS TO
SMALL MOLECULE TO THE EFFECTS.
MAYBE THERE CAN BE AN INITIATIVE
TO PUT THINGS TOGETHER AS A SORT
OF MAJOR DATA BANK WE CAN USE
FOR THE MODELS BASED FROM SMALL
MOLECULES TO THE EFFECTS.
>> GREAT SUGGESTION.
WE HEAR YOU.
ESPECIALLY NOW BECAUSE NOW WE
HAVE THE GRANTS.
WE HAVE A NEW SMSP POLICY.
YOU HAVE TO SHOW WHICH DATABASES
YOU WILL BE STORING YOUR DATA
IN.
IT HAS TO BE PUBLIC ACCESS
FOREVER IN A STANDARDIZED WAY SO
EVERYBODY CAN USE THE FORM OF
THE DATA COLLECTION.
SO IT WILL BE AVAILABLE FOR
EVERYBODY.
THIS IS A TIME TO THINK ABOUT
THE STANDARDIZED BIG DATA SET.
>> OKAY.
HOPEFULLY --
>> SOMEONE IS ON ZOOM.
>> YES.
>> THANK YOU.
TWO COMMENTS.
ONE HAS TO DO WITH MACHINE
LEARNING HAS APPLIED TO MOUSE
BEHAVIOR AND THERE'S DATA ON
USING VON FREY FILAMENT TESTING
AND WE HAVE THE BLACK BOX OF
MACHINE LEARNING AND FOUND A
DIVERGENCE IN FINDINGS BETWEEN
THE VON FREY AND WHAT WE CAN
DETECT IN CHANGES IN THE
APPLICATION OF SOME OF THESE
AGENTS LIKE CBD FOR EXAMPLE WE
CANNOT SEE A SIGNAL ON ONE HAND
WITH VON FREY BUT REVERSAL OF
HYPERSENSITIVITY AND AS THE
KNEELED GOES FORWARD MAYBE
THERE'S UNIFORMITY IN BRINGING
TOGETHER WHAT WOULD BE STANDARDS
FOR SOME OF THESE EMERGING
TECHNIQUES.
AND THE FINAL POINT IS ABOUT CBC
OR POINTED OUT AS BEING UNIQUE
IN THE STUDIES AND WE DID A DEEP
DOSE RESPONSE IN THE SENSORY
NEURONS AND CBC WAS UNIQUE
AMONGST THE FOUR WE STUDIES
SHOWING A DISCREET DOSE RESPONSE
RELATIONSHIP WHICH PREDICTED A
SINGLE SITE OF ACTION DESPITE
THE DRUG TO EVERYONE WORKING ON
CBC.
>> FOR DR. COOPER I HAD A
QUESTION BECAUSE I THINK DURING
YOUR PRESENTATION IF I HEARD YOU
CORRECTLY YOU MADE A COMMENT
ABOUT THE FACT THAT YOU'RE USING
VAPORIZED PRODUCT AND IN SOME
WAYS THAT WAS NOT IDEAL AND
EXPAND WHY IT'S NOT IDEAL.
I GUESS I'M THINKING FROM THE
CLINICAL LENS ALWAYS ABOUT HOW
DO THESE STUDIES -- HOW WOULD
THEY BE TRANSLATED TO HUMAN USE
AND MY UNDERSTANDING STILL IS
POST PEOPLE'S USE OF CANNABIS
PRODUCT THE MAJORITY STILL
INHALE THOUGH THERE'S A GROWING
BODY OF PEOPLE USING EDIBLES.
WHY WAS IT UNDESIRABLE WHEN IT'S
CLOSELY TO HOW PEOPLE USE
CANNABIS FOR RECREATION OR PAIN
MANAGEMENT IS TRUE VAPOR.
IT'S PROBABLY GOING TO BE A LONG
DISCUSSION BUT CURIOUS WHY IT'S
NOT IDEAL AND WHY YOU THINK MORE
INVESTIGATORS DON'T USED
VAPORIZED PRODUCTS.
>> IT'S INTERESTING ON THE HEELS
OF THE ARTICLE OF WHAT'S
HAPPENING IN CANADA AND THE
NUMBER OF OLDER ADULTS THAT ARE
GOING TO THE EMERGENCY ROOM
AFTER USING EDIBLE CANNABIS
PRODUCTS.
THIS IS SOMETHING WE'RE BECOMING
INCREASINGLY AWARE OF AS MORE
STATES ARE LEGALIZING AND MORE
PEOPLE ARE USING EDIBLE PRODUCTS
THERE'S RISK ASSOCIATED WITH
ORAL USE.
AND IN MY HEAD I'M VERY TRAINED
TO THINK INHALED CANNABIS
BECAUSE OF THE POTENTIAL TOXIN
THAT ARE INHALED WHEN IT'S
COMBUSTED THERE'S THE ISSUES
WITH THAT AND THE QUESTION ABOUT
VAPORIZED CANNABINOIDS I THINK
IS STILL A BIG QUESTION AND HOW
IF WE'RE SEEING THIS BEING
TRANSLATED TO SOME CLINICALLY
USEFUL THERAPEUTIC THAT IS GOING
THROUGH SOME FDA PROCESS.
IN MY HEAD I DON'T HAVE A GOOD
TEMPLATE FOR THAT RIGHT NOW.
SO I KNOW THAT SOME PEOPLE ARE
LOOKING AT METERED DOSE INHALERS
BUT I THINK I'M USED TO THINKING
INHALED CANNABINOIDS ARE
PROBABLY NOT THE BEST WAY TO GO.
ALSO IF YOU THINK OF PHARMACO
KINETIC EFFECTS WE KNOW INHALED
DELTA 9THC THOUGH IT'S BETTER
TRITATABLE THAN ORAL YOU'LL HAVE
BETTER PAIN RELIEF THAT WON'T BE
SUSTAINED FOR LONGER PERIOD OF
TIME.
AT LEAST WE'VE SHOWN IT'S
ACCOMPANIED BY HIGHER RATES OF
INTOXICATION THAN ORALLY
ADMINISTERED DELTA9 THC WHERE
THE INTOXICATION IS NOT AS GREAT
AND FEWER LIABILITIES ARE AT
WORK BUT THESE ARE IMPORTANT
QUESTIONS AND THINK NCCIH IS
ABLE TO ANSWER THESE QUESTIONS
WITH THE FUNDING YOU'RE
PROVIDING.
>> THANK YOU.
BEFORE YOU STEP AWAY I'M CURIOUS
AND PERHAPS THIS IS SOMETHING
YOU DISCUSSED AT PREVIOUS
MEETINGS, WHY DID YOU CHOOSE
VAPORIZED?
>> I DIDN'T CHOOSE VAPORIZED, IT
CHOSE ME.
>> AH.
>> I'M SURE THE CLINICAL
RESEARCHERS HAVE THE SAME
EXPERIENCE WHERE A LOT OF THE
TIMES I DEVELOPED GRANT IDEAS
BASED OFF WHAT'S AVAILABLE AND
WHAT'S FEASIBLE.
SO WHAT WAS AVAILABLE WAS
INHALED TERPENES AND WHAT WAS
FEASIBLE FROM AN FDA PERSPECTIVE
AT THAT POINT IN TIME AT LEAST
THE PATH OF LEAST RESISTANCE WAS
INHALED BECAUSE PEOPLE ARE
EXPOSED BASED OFF THE
CONCENTRATIONS OF TERPENES AND
PUBLISHED IN PEER-REVIEWED
PUBLISH LITERATURE AND USED THE
CONCENTRATIONS.
I WAS ABLE TO SAY WE'RE NOT
INTRODUCING ADDITIONAL RISK TO
THE PARTICIPANTS BY EXPOSING
THEM TO THE DOSES AND THAT'S
PART OF THE REASON WHY.
IT'S NOT VERY SOPHISTICATED
REASONING.
>> IT MAKES SENSE.
THANK YOU.
>> MAYBE ONE LAST QUESTION.
>> MAYBE A REMARK.
>> IF YOU LOOK AT DOSE EFFECT
WHEN YOU LOOK AT WHAT'S BETWEEN
THE DOSE AND EFFECT IS THE
CONCENTRATION AND IT DEPENDS ON
THE FORMULATION YOU'RE USING.
I WAS WONDERING ALL THE PEOPLE
PUTTING MONEY IN CLINICAL TRIALS
ALSO DO PHARMACO KINETICS AND
YOU CAN DETERMINE BASED ON THE
CONCENTRATION IF SOMETHING WORKS
OR NOT.
AND ALSO WHY THERE ARE PEOPLE
THAT DO NOT RESPOND TO TO THE
DOSING AND PEOPLE THAT DO AND IF
YOU HAVE A NUMBER ON THE
CONCENTRATION YOU COULD LEARN
SOMETHING.
I'VE DONE A COUPLE NOT WITH
CANNABIS BUT WITH MANY STUDIES,
PRE CLINICAL AND MOUSE MODELS
AND HUMAN STUDIES AND WE ALWAYS
MEASURE PLASMA LEVELS BECAUSE WE
LEARN ABOUT ABSORPTION AND THE
METABOLISM BECAUSE SOME HAVE
DIFFERENT EFFECT.
IT'S JUST A COMMENT.
THANK YOU.
>> GOOD COMMENT.
GREAT.
THANK YOU.
I THINK -- YES.
>> SO ACTUALLY IF YOU COME UP
WITH MORE QUESTIONS, THIS IS
GREAT AND MORE THAN FINE.
WHAT WE PLANNED FOR THIS NEXT 40
MINUTES WOULD BE A COMBINATION
OF THE QUESTIONS THAT YOU CAN
ASK EACH OTHER PRE-CLINICAL AND
CLINICAL AND WHAT WE DID.
WE'RE ASKING EACH OF YOU TO
PROVIDE NEXT STEP FOR THE FIELD
FOR THE CELLS AND FOR THE FIELD.
AND THEN WE'LL SYNTHESIZE THEM
IN SEVERAL SLIDES SO ALL THE
SLIDES THAT YOU WILL SEE RIGHT
NOW THERE IS NOTHING NEW.
YOU ALREADY SAW ALL THE STEPS OR
DIRECTIONS YOU PROPOSED.
WE WOULD LIKE TO DO IN THE NEXT
40 MINUTES IS TO DISCUSS HOW WE
CAN ADDRESS IT.
WHAT ARE PRIORITIES TO PLAN
AHEAD FOR THE PROGRAM AND FOR
THE FIELD AND HOPEFULLY FOR YOUR
FUTURE COLLABORATIONS.
SO I HAVE THREE SLIDES THAT
SYNTHESIZE THE NEXT STEPS FOR
MORE CLINICAL STUDIES.
SO BASED ON WHAT YOU PROPOSED,
THESE ARE THE DIRECTIONS AND
PLANS FOR STUDIES THAT WILL BE
BASIC STUDIES OR PHARMACOLOGICAL
STUDIES.
SO YOU CAN SEE SOME OF THEM ARE
USING THE MODEL ON WHAT WOULD BE
THE BIGGEST GAP SO YOU CAN SEE
THESE AGAIN AND I WILL BE
SHOWING THEM BACK AND FORTH.
SO THE NEXT SLIDE IS YOUR
SUGGESTIONS FOR THE NEXT STEPS
RELATED TO THE POTENTIAL NEW
MODELS AND THINGS THAT CAN BE
GREATER RESOURCES IN THE FIELD.
SO HERE YOU CAN SEE ALL OTHER
PLANS BEYOND CANNABIS THAT CAN
BE SOURCE OF POTENTIAL
ANALGESICS.
THIS GREAT NEW DATABASE THAT I
THINK YOU WILL HAVE QUESTIONS
WITH IT AND CONSIDERING CREATORS
IN THE ROOM IS REALLY GREAT.
THE MOUSE MODELS.
THESE ARE THE THINGS YOU
PROPOSED AND WE CAN START
DISCUSSION ON HOW TO ADDRESS THE
STEPS.
HOW TO MAKE IT NOT 10 YEARS
PLANNED BUT THREE YEARS PLANNED
AND MECHANISTIC STUDIES.
FOR THE MECHANISTICS YOU CAN SEE
ALL THE POTENTIAL MECHANISMS
THAT ARE STILL UNDER STUDIED OR
COMPLETED NEW.
AND YOU CAN SEE THOR THE
SYNERGIES BETWEEN THE DIFFERENT
COMPONENTS OF THE HEMP MAYBE AND
HOW YOU CAN USE THEM AS DOSE
DEPENDENT AND TIME DEPENDENT FOR
RELATIONS IN RELATION TO PAIN.
IT'S STILL THE PROBLEM IS STILL
ABOUT NEW ANALGESICS.
COMPARE THE EFFECTS OF DIFFERENT
COMPOUNDS AND START THINKING
ABOUT WHAT DO WE MISS?
SO WE ALL HAVE SOME STUDIES
INVESTIGATING MINOR CANNABINOIDS
BETWEEN THEMSELVES AND THE
COMBINATION BETWEEN THE TWO.
IS THERE ANYTHING ELSE YOU WOULD
LIKE TO INVESTIGATE?
THE LAST WOULD BE TRANSLATION.
SO THESE ARE ALL SUGGESTIONS FOR
POTENTIAL TRANSLATIONAL STUDIES.
HOW YOU CAN INVESTIGATE THE
EFFICACY TO OPTIMIZE THE
THERAPEUTIC TRANSLATION.
WHAT POTENTIAL EVENTS FOR
CANNABIS CONSTITUENTS CAN OR
CANNOT BE USED IN HUMANS.
THE QUESTION IS IF THE
TRANSLATION POTENTIAL IS LOW
SHOULD WE STILL FUND THOSE
STUDIES?
HOW MUCH OF THE BASIC EFFECTS
ARE VARIABLE IF WE ARE NOT SURE
WHICH ONE CAN BE TRANSLATED TO
HUMAN STUDIES AND ANSWERING
OTHER QUESTIONS DO THEY CONTINUE
TO HAVE EFFECTS OF CANNABIS.
HOW WE CAN BETTER ADDRESS THE
INTERACTION EFFECTS.
SO THESE WOULD BE POTENTIAL
STEPS AND DIRECTIONS FOR
NON-CLINICAL.
THEN FROM OUR CLINICAL WE HEARD
ABOUT ALL THESE GREAT NEXT STEPS
AND SOME ARE ALL ABOUT
INDIVIDUALIZED PAIN THERAPY.
WE KNOW MANY OF THE CONSTITUENTS
HAVE SHOWN ANALGESIC PROPERTIES
ARE THEY FOR EVERYONE?
CAN THEY BE SEX-GENDER
DEPENDENT?
AGE DEPENDENT?
CAN THEY WORK DIFFERENTLY IN
DIFFERENT RACIAL OR ETHNIC
GROUPS DEPENDING ON BIOLOGY?
DEPENDING ON PURPOSES OF THE
CONSTITUENTS?
HOW TO ADDRESS THEM?
CAN WE PREDICT WHO WILL BE
RESPONDING BETTER TO THE DRUG
THAT IS A MAJOR PRODUCT AND SO
HOW THEY HAVE MANY PAIN
MECHANISMS AND WHAT WOULD BE THE
BEST WAY TO INVESTIGATE CANNABIS
IN THE BRAIN AND THE EFFECT ON
BRAIN VERSUS PERIPHERY?
P.K. STUDIES?
ALTERNATIVE MODES OF
ADMINISTRATION?
SO WE JUST STARTED THINKING
ABOUT VAPORIZED CANNABINOIDS
VERSUS EDIBLES.
MAYBE THERE'S OTHER INTERESTS.
UNDERSTANDING THE RELATIONSHIP
BETWEEN CHRONIC PAIN AND RELATED
FACTORS SUCH AS SLEEP, FATIGUE,
ANXIETY STRESS IN THE CONTEXT OF
CANNABINOIDS.
SO THESE ARE ALL INTERESTING
NEXT STEPS FOR CLINICAL STUDIES
THAT CAN BE ON THE PRE-CLINICAL
LEVEL AND FOR CLINICAL STUDIES
WE HAVE SO MANY CHALLENGES.
PATIENT COMMITMENT, PATIENT
ENGAGEMENT, DRUG RELIABILITY AND
TESTING.
WE HAVE HERE IN ONE PARTICULAR
STUDY THAT HAD TWO ISSUES WITH
FDA CLINICAL HOPES.
TWO, NOT ONE.
WE WILL HAVE RECORDINGS AT THE
NEXT PORTION OF THE MEETING WITH
QUESTIONS THAT WE CAN START
ADDRESSING.
PLACEBO EFFECTS AND REGRESSION
TO THE MEAN AS A CHALLENGE IN
THE CLINICAL STUDIES AND OF
COURSE DRUG SHORTAGES.
WE WILL HAVE AT LEAST TWO
OPINIONS ON HOW TO ADDRESS THEM
FROM THE PROGRAM.
THESE ARE THE CHALLENGES AND NEW
DIRECTIONS THAT YOU ALL
SUGGESTED?
WE HAVE TWO MICROPHONES AND MORE
MICROPHONES AT THE TABLE.
SO IT WOULD BE GREAT IF THROWS
WHO HAVE OPINIONS, SUGGESTIONS
CAN COME TO THE MICROPHONE.
DON'T BE SHY.
THIS IS YOUR MEETING AND THE
FINAL MEETING SO IF YOU WANT
THIS PROGRAM TO ADDRESS NEW
DIRECTION AND COME UP WITH NEW
STEPS, PLEASE SUGGEST THEM NOW.
SO THESE ARE CHALLENGES AND
STEPS FOR CLINICAL STUDIES.
IDEAS FOR POTENTIAL TRANSLATION
AND IDEAS ON POTENTIAL NEW
MECHANISMS.
IDEAS ON RESOURCES AND BASIC AND
PHARMACOLOGIC STUDIES.
AND NOW I WELCOME YOU ALL.
PLEASE JUST START THE COVERING.
-- CONVERSATION.
>> THIS RELATES TO ZIVA'S
QUESTION AND I WAS TALKING TO A
COLLEAGUE AND TELLING ME ABOUT A
PROGRAM WITH PRE-CLINICAL STROKE
RESEARCHERS AND STROKE
SCIENTISTS THROUGHOUT THE
COUNTRY ARE STANDARDIZING THEIR
ASSAYS IN A WAY WHERE FOLKS ARE
TRAINED AT DIFFERENT SITES.
SAY I DO CIP N AND HE TRAINS ON
CIPN AND WE DECIDE A WAY TO DO
IT WITH VON FREY OR OTHER COOL
SOPHISTICATED WAYS.
WE STANDARDIZED THE SEX WHETHER
MALE OR FEMALE AND CBD IS
PROVIDED AND TESTED AND
ELIMINATE THE VARIABILITY.
HALF OF ME THINKS THAT'S VERY
COOL AS A WAY TO ADD STRENGTH TO
OUR RESEARCH AND TRANSLATE IT
ACROSS LABS BUT THEN I ALSO FEEL
LIKE IT TAKES AWAY PERHAPS SOME
OF THE NOVELTY AND INNOVATION
AND DOING THINGS IN A DIFFERENT
WAY.
I HAVE THOSE TWO IDEAS BOUNCING
AROUND IN MY HEAD AND TO ADDRESS
ZIVA'S POINT, WITH CONTROL
COMPOUNDS TO LOOK AT HOW SIMILAR
OUR COMPOUNDS AND WHAT DOES THE
DOSE MORPHINE LOOK LIKE AND
THOUGH WE CAN AGREE WE DO OUR
ASSAYS A LITTLE BIT DIFFERENTLY
WE CAN LOOK AT THIS ASSAY WHERE
MORPHINE LOOKS LIKE THIS AND
THESE ARE THINGS I WAS THINKING
ABOUT.
>> APRIL.
>> I SPENT THE LAST 20 YEARS AND
I WAS STRUCK BY IS HOW
HETEROGENOUS THE VIEWS ARE AND
MY EXPERTISE AND BRINGING TO THE
TABLE INVESTIGATOR ENVIRONMENT
AND HOW THEY ARE USED
CLINICALLY.
IT'S GREAT AND IF YOU'RE GOING
TO DO THAT YOU'RE GOING TO ASK
DIFFERENT QUESTIONS TO DEVELOP A
BETTER METHOD FOR AND DRUG
COMPANIES LOOK AT THIS ALL THE
TIME AND LIKELY TO LOOK AT THE
MAJORITY OF THE FUNDING RELATED
TO DISEASE OR TREATMENT
RESPONSE.
>> YOU CAN'T ANSWER THE QUESTION
WITHOUT BEING CLEAR OF WHAT THE
GOAL IS AND YOU FUND STUDIES
INVOLVING BASIC SCIENCE AND
CLEARLY THAT HAVE A LONG-TERM
GOAL IN THE TREATMENTS BEING
AVAILABLE ACROSS THE BOARD, HOW
DO YOU FEEL WHEN YOU GET
APPLICATIONS THAT HAVE THESE
DIFFERENT END POINTS GIVEN YOU
HAVE SO MANY DIFFERENT
PERSPECTIVES YOU MUST CONSIDER
AND I'LL TURN MY QUESTION BACK
TO YOU.
>> OKAY.
SO JUST KEEP IN MIND WE'LL BE
NOT THE FIRST TO SEE
APPLICATION.
WE WILL HAVE THE STUDY SECTION
WITH YOUR COLLEAGUES AND EXPERTS
IN THE FIELD AND THEY WILL
REVIEW MANY ASPECTS OF THE
STUDY.
AS ALWAYS YOU ALL KNOW THEY'LL
BE LOOKING AT THE THREE MAIN
CATEGORIES.
ONE IS THE NOVELTY OF THE IDEAS.
LOOK AT WHAT WAS ALREADY FUNDED
FOR THE SPECIFIC AREA YOU'RE
INTERESTED.
SO NOVELTY IF IT'S THE MECHANISM
THEN IT SHOULD BE SOMETHING
INNOVATIVE WITHIN THE MECHANISM.
IT COULD BE NOVELTY ASPECTS.
ANOTHER THEME WOULD BE WHO IS
YOUR TEAM OF INVESTIGATORS AND
THE EXPERTISE FOR DIFFERENT
EXPERIMENTS AND AIMS THAT YOU
PROPOSE IN THE STUDY AND DO YOU
HAVE THE HISTORY OF
COLLABORATION.
WHO WILL BE DOING THE WORK?
THIS IS ANOTHER ASPECT AND THE
THIRD IS HOW THE EXPERIMENTS
THAT YOU PROPOSE ARE FEASIBLE
AND CAN YOU DO IT IN THREE OR
FIVE YEARS AND HOW THEY'LL BE
ADDRESSING THE MAIN AIMS YOU
PROPOSE.
AND THEN IT COMES TO US AND THEN
AT THE LAST SESSION WE'LL HAVE
COLLEAGUES FROM NCCIH TALKING
ABOUT THEIR PARTICULAR INSTITUTE
OR CENTER PRIORITIES IN FUNDING
CANNABIS RESEARCH THAT WILL BE
DIFFERENT AND WE'RE MOSTLY
INTERESTED IN THE ANALGESIC
PROPERTIES OF MINOR CANNABINOIDS
AND WE ALLOW STUDIES ON THC ON
CANNABINOIDS AND THIS IS
DIFFERENT FROM EACH INSTITUTE.
WE STILL HAVE AN ACTIVE NOSI OF
SPECIAL INTEREST WITH SUBMISSION
BY JULY 2025.
I WOULD SAY IT'S A GREAT TIME
BECAUSE AFTER THIS MEETING YOU
WILL BETTER UNDERSTAND THE
POTENTIAL GAPS AND OPPORTUNITIES
THAT MAY PROPOSE THE INNOVATIVE
THING THAT WILL BE BRIDGING THE
THINGS THAT WERE ALREADY FUNDED
AND INVESTIGATED.
SO IF YOU THINK ABOUT POTENTIAL
COLLABORATION THIS WOULD BE A
GREAT CHANCE TO START AT IT AT
THE MEETING AND LET'S TALK ABOUT
NEXT STEPS AT THE CLINICAL OR
NON-CLINICAL STUDIES.
I KNOW GIVEN YOUR THOUGHTS MAYBE
RISKY BUT THIS IS THE BEST ROOM
BECAUSE YOU HAVE YOUR PEERS
DOING THE GREAT STUDIES THAT CAN
BETTER ADVISE YOU.
PLEASE GO AHEAD, YES.
>> ONE OF THE RUNNING PREVAILING
THEMES IS MYSELF INCLUDED IS
HARNESSING MACHINE LEARNING
ACROSS A VARIETY OF SPECTRA FROM
COMPOUND DEVELOPMENT AND TARGET
DISCOVERY AND BEHAVIOR.
POINTING TOWARDS THAT SECOND ONE
A BOTTLENECK FOR ME AAS A
TRAINED BEHAVIORALIST IS THE
PAIN BEHAVIOR AND DEVELOPING
TARGETS HOW TO TEST THAT IN AN
EFFICACIOUS MANNER WHEN
TYPICALLY WE'VE BEEN USING THE
MOUSE AS THE MODEL.
I WANTED TO HIGHLIGHT THOSE WHO
USE ZEBRAFISH AS A MODEL AND
THEY RESPOND TO PAIN AND
SENSITIZED PAIN AND YOU CAN
BREED THEM EN MASSE AND TEST
THEM EN MASSE.
THERE'S A DECENT AMOUNT OF
GENETIC MODELS YOU CAN GENERATE
WITH THEM.
THEY'RE EASY TO CRISPR AND
DEVELOP MUTANT FISH.
WHEN WE TALK ABOUT HIGH
THROUGHPUT ASSAYS IT'S DIFFICULT
TO THINK ABOUT PAIN BEHAVIORS.
THERE'S POTENTIALLY OTHER THINGS
TO THINK ABOUT BUT THAT WOULD BE
A BIG BOTTLENECK IN MY MIND
PRECLINICALLY IS LOOK AT THE
THINGS WE'RE DEVELOPING AND
COMING UP WITH AND DO THEY WORK
FOR PAIN.
>> THANK YOU SO MUCH.
IDEAS, COMMENTS, FEEDBACK?
>> I WAS HOPING TO GO BACK TO
THE VAPORIZED AND HOW MUCH DO WE
KNOW ABOUT OF THE METABOLISM OF
CANNABINOIDS WHEN GIVEN THROUGH
THE LUNGS WHERE THEY DON'T PASS
THROUGH THE LIVER VERY QUICKLY
VERSUS ORALLY?
I WONDER WHETHER THERE'S GOING
TO BE DIFFERENT SITUATION WITH
ORAL OR ENTERAL ADMINISTRATION
AND INHALE AND HOW THAT MIGHT
IMPACT.
>> I AGREE.
IT'S WORTH EXPLORING MORE IN
DEPTH.
GIVEN WHAT WE UNDERSTAND ABOUT
CANNABINOID USE IN THE UNITED
STATES WHERE MOST PEOPLE STILL
DO PREFER THE ORAL -- I MEAN THE
INHALED VERSION TYPE-
>> I WANTED TO ADD SOMETHING TO
THE VAPORIZATION.
THIS WAS A STUDY WHERE VITOL WAS
TOXIC AND WE SAW THIS THROUGH
INHALATION AND VITAMIN E ACETATE
AND ACUTE LUNG INFECTIONS
ASSOCIATED WITH THAT AND BECAUSE
THERE'S AN IDEA TERPENES ARE
GRASS IT'S THE SAME IF THEY'RE
INHALED WHERE I DON'T THINK
THAT'S THE CASE.
I THINK ZIVA WAS INTELLIGENT TO
USE SOMETHING TYPICALLY EXPOSED
BUT WE DO SEE IN THESE WHERE
PEOPLE ARE ADDING HIGHER LEVELS
OF TERPENES.
MAYBE FINE IN EDIBLE BUT WHEN
IT'S ADULTERATED IT MAY BE TOXIC
AND PART OF THE GOAL IS TO FIND
OUT ARE THESE EFFECTIVE TO TREAT
PAIN AND THERE'S INTERESTING
STUDIES BUT MY QUESTION IS AS
YOU TRANSITION FROM ANIMALS TO
HUMANS HOW DO THEY LOOK AT THEM
IN TERMS OF SAFETY?
BECAUSE THE EXPOSURE LEVEL FOUND
IN TYPICAL CANNABIS IS LOW.
IS THERE CONSIDERATION TO
FUNDING OR LOOKING INTO GENERAL
TOX STUDIES THAT WOULD SUPPORT
THE USE IN CLINICAL.
WE HAVE SOME STUDIES WITH CPG
NOW AND IN TOX STUDIES SUGGEST
YOU MAY GO TO LEVELS YOU WOULD
SAY THE HUNDREDS IF NOT
THOUSANDS OF MILLIGRAM DOSES.
I DON'T KNOW IF THERE'S ENOUGH
SUPPORTING EFFORTS TO SAY CAN WE
GIVE 300 OR 500 MILLIGRAMS TO
CBC IN CHRONIC DOSING AND IS IT
SAFE BECAUSE IT'S CANNABIS?
THAT WOULD BE GOOD START TOE SAY
THERE'S EVIDENCE.
>> THIS IS A GREAT QUESTION.
AND WE DO ALLOW THE COMPONENT
FOR THE TEXAS IN THE STUDY THAT
WOULD BE MAINLY FOCUSSED ON
THERAPEUTIC POTENTIAL.
YOU CAN HAVE BOTH.
ALSO THE REASON FOR POTENTIAL
TOXICITY OR ADVERSE AFFECTS AND
IF IT'S MOSTLY FOR ANALGESIC
POTENTIAL THAT WOULD BE ALIGNING
BETTER WITH THE END STABLE IF
THE MAIN FOCUS IS ON THE TOX
STUDY THAT WOULD POTENTIALLY GO
TO NIDA.
>> THE COMPUTATIONAL PREDICTIONS
ARE BASICALLY A FANTASY WORLD
UNTIL IT'S TESTED.
AND THE WE'RE TESTING THE
COMPOUNDS AND GETTING THE
INFORMATION AND GOING BACK AND
FORTH IT'S IN A SENSE USELESS.
COMPUTATION GENERATES SOME
HYPOTHESIS AND SO I THINK IT'S
AN INCREDIBLE RESEARCH BECAUSE
IF YOU HAVE A GAZILLION
COMPOUNDS AND PRIORITIZE THE
COMBINATIONS IT COULD BE A HUGE
RESOURCE.
ONE THING THAT COULD BE REALLY
HELPFUL AND HAS BEEN HELPFUL IN
OTHER FIELD LIKE PROTEIN
DATABASE CREATED AND WAS A HUGE
RESOURCE IN THE G BANK AND
INTEGRATED RESOURCE OF GROSS AL
DATA AND COMPUTATIONAL DATA THAT
CAN PLAY OFF EACH OTHER.
AND WE CAN ENHANCE THE SPACE OF
COMPOUNDS PARTICULARLY RECEPTORS
THROUGH TOOLS THAT HAVE BEEN
RECENTLY DEVELOPED THAT HAVE
SCREENINGS OF BILLIONS OF
COMPOUNDS A DAY AND IF YOU'RE
LOOKING FOR NEW CANNABINOIDS
IT'S NOT HARD TO DO BUT YOU
GENERATE A LIST OF MANY
COMPOUNDS THAT WE NEED TO SCREEN
AND A GOOD WAY TO MOVE FORWARD
TO TRANSLATION IS TO CREATE A
GENERAL RESOURCE THAT WILL
COMBINE EXPERIMENTAL AND
COMPUTATIONAL DATA AND BRING
COMMUNITIES TOGETHER.
>> GREAT SUGGESTION.
>> THERE'S A NEW POLICY THAT WAS
WHAT IT WAS SUPPOSED TO DO AND
THE CHALLENGE IS NO ONE CAN
AGREE WHERE TO PUT THE DATA.
ALL YOU OF YOU IN THE FIELD MAY
BE SHARING DATA BUT I GUARANTEE
YOUR NOT STORING IN THE SAME
PRAISE BUT THERE'S EXISTING
REPOSITORIES IF YOU CAN AGREE
WHICH TO PUT IT IN YOUR PROBLEM
WOULD BE SOLVED BUT NO ONE CAN
AGREE WHAT TO HAVE FOR LUNCH LET
ALONE WHERE TO PUT THEIR DATA
AND THEY CREATED THE DATA
MANAGEMENT SHARING POLICY WITH
THE HOPE THERE WOULD BE MORE
DATA CONGREGATING IN THE SAME
PLACE.
WE SEE HOW WELL IT PLAYS OUT.
>> THANK YOU, DR. HOFF.
ALSO TODAY THERE WILL BE A
SPECIAL PRESENTATION FROM THE
COLLEAGUE ABOUT THE NCCIH
RESOURCE CENTER INITIATIVE.
THESE ARE INTERESTING
SUGGESTIONS AND VERY HELPFUL FOR
NEXT DIRECTIONS.
ANY OTHER THOUGHTS ON
NON-CLINICAL?
SFWR I
>> I WANT TO ECHO WHAT DR. HARTE
AND I WOULD LOVE IF EVERYONE
ACCEPTS THE METHODS MY LAB DOES
AND I SOO -- SEE THE MACHINE
LEARNING AND THEY SAY USE THIS
AND IT'S NOT EASY AND IT'S
CHANGING AND THE SOFTWARE'S
CHANGING.
EVEN IF WE WERE TO AGREE ON WHAT
FACTORS WE WANT THE BLACK BOX TO
OUTPUT FOR US WHICH IS LIMITED,
IT'S ALSO CHANGING AS WE'RE
USING IT.
THOSE ARE OTHER TYPES OF THINGS
WE'LL NEED TO THINK ABOUT AND
TRYING TO PUSH FOR CONSISTENCY
HERE AND MAKE HELPFUL
SUGGESTIONS AS WE'RE REVIEWING
EACH OTHER'S WORK BECAUSE I'M
NOT SURE HOW THE BEHAVIORAL
ASSAYS WILL CHANGE OVER TIME.
>> I'M GOING TO JUMP IN AGAIN
WITH A THOUGHT QUESTION NOT TO
PERSERVERATE BUT GOING TO THE
CLINICAL TRIALS AND FROM A
CLINICAL CLINICIAN VIEW POINT.
I THINK WE'D BE REMISS AND
PEOPLE TALK TOPICAL PRODUCTS AND
I HAVEN'T HEARD RESEARCH ON
TOPICAL VERSIONS IN TERMS OF
ROOT OF ADMINISTRATION AND
CURIOUS AND PEOPLE RUB THINGS IN
TO THEIR SKIN IN ADDITION TO
ORALLY.
HAS ANYONE HERE THOUGHT ABOUT
STUDYING TOPICALLY ADMINISTERED
CANNABINOIDS OR CANNABIS
PRODUCTS OR IS THAT SOMETHING
THAT AGAIN IS TOO MESSY TO DO A
REALLY GOOD CLINICAL TRIAL OR
NON-CLINICAL TRIAL?
PLEASE.
IS
>> WE'VE BEEN USING IN
OSTEOARTHRITIS IN MICE AND
FRACTURING HEALING IN RODENTS.
I THINK IT'S A REMARKABLY RICH
AREA TO EXPLORE AND TELL ONE
STO
STORY FOLKS THAT WENT TO OUR
MEDICAL PROGRAM IN PENNSYLVANIA
WOULD COME INTO THE CLINICAL
RESEARCH CENTER AND WE WOULD ASK
A SIMPLE QUESTION HOW MUCH
TOPICAL GETS IN THE CIRCULATION
AND WILL I FAIL A DRUG TEST AND
MY IRB BOUGHT IT AND THE FDA
SAID I NEEDED INVESTIGATIONAL
NEW DRUG APPLICATION.
RESCHEDULING SHOULD HELP BUT
GIVEN THE FELICITY OF THE
MOLECULES THEY'LL BE USING FOR
IN A TOPICAL FORM.
AS LONG AS I WANTED THE MIC IF I
CAN CHANGE THE SUBJECT FOR A
SECOND, ONE THING WE'RE IGNORING
IS PHARMACO GENOMICS AND THE THC
IN THE PLANT REACHED THE UPPER
LIMIT 30% TO 35% BY WEIGHT WE'RE
SEEING THE SIDE EFFECTS AND
ACUTE PSYCHOSIS AND CANNABIS
SYNDROME AND THESE DRUGS ARE
METABOLIZED BY 2C9 AND 3A4 AND
FOR 3A4 THERE'S FOUR ALLELES
THAT COMPRISE THE ACTIVITY AND
HAVE ULTRA METABOLIZERS AND
NON-METABOLIZERS AND WE HAVE NO
IDEA.
IT WILL ADD ANOTHER DIMENSION TO
THE BIG DATA OF THE GENOTYPES OF
OUR SUBJECTS AND HOW DOES THAT
INFLUENCE HOW THEY'LL RESPOND
AND WHETHER THEY'LL HAVE SIDE
EFFECTS.
DOES IT WORK FOR THEM IF THEY'RE
AN ULTRA METABOLIZER OR DO THEY
HAVE SIDE EFFECTS BECAUSE OF
COMPRISED EFFECTS.
THIS GOES TO THE COMPLEXITIES OF
THE CLINICAL TRIALS.
ON THE OTHER HAND, THINKING
ABOUT THERAPEUTIC BIOMARKERS,
THINKING ABOUT HOW TO PREDICT
WHO WILL BE RESPONDING BETTER
PROBABLY FOR THE INDIVIDUALIZED
APPROACH GENETICS AND PHARMACO
GENOMICS WOULD BE ESSENTIAL WILL
STEPS IN CLINICAL TRIALS.
>> AS I LISTEN TO THE BASIC
STUDIES WITH ELEGANT HABIT --
LABORATORY METHODS I'M CURIOUS
ABOUT THE TRANSLATIONAL
QUESTION.
IT SEEMS THE STUDIES USED
SYNTHETIC CANNABINOIDS AND
THAT'S NOT WHAT OUR PARTICIPANTS
BUY AT DISPENSARIES AND DO WE
HAVE GOOD EVIDENCE THE
SYNTHETICS WORK THE SAME WAY IN
TERMS OF PHARMACO DYNAMICS AND
WHETHER THEY IMPACT SYMPTOMS
WHETHER SYNTHETIC OR NATURAL
VERSIONS AND DOSE.
I LOOK AT SOME OF THE DOSES IN
THE DIFFERENCE STUDIES AND THEY
SEEM TO BE ALL OVER THE PLACE.
AND VERY DIFFERENT FOR ANIMAL
MODELS VERSUS HUMANS, LOW DOSES
IN SOME STUDIES, SUPER HIGH IN
OTHERS.
THAT'S ANOTHER QUESTION IS HOW
DO WE FIGURE OUT IN TERPENES AND
WHAT CLINICAL DOSES SHOULD BE.
>> I OFTEN WISH THERE WAS A
DATABASE AND A MOUSE IS MY MAGIC
CBD DOSE AND THAT THE AN
EXCELLENT POINT.
I DON'T KNOW THE BIG DIFFERENCE
IN OUR WORK IS THE PRE CLINICAL
FOLKS ARE USING SYNTHETIC VERSUS
A CRYSTALLIZED POWDER
FORMULATION WE CAN THEN MAKE UP
IN DIFFERENT CONCENTRATIONS AND
ADMINISTER.
I THINK THAT'S THE BIGGER
DIFFERENCE RATHER THAN SYNTHETIC
THAT WE'RE NOT USING EXTRACTS,
FOR EXAMPLE.
>> I'M SAYING THIS FROM THE
PERSPECTIVE OF HAVING DONE WORK
ON THE FOOTBALL TEAM AT TO THE
UNIVERSITY OF UTAH WHO NEVER
HAVE PAIN AND SOME ARE VETERANS
AND HAVE EXPOSURE TO PTSD AND
CHRONIC PAIN AND SOME OF THE
NEWER WORK ONE OF MY COLLEAGUES
WHO IS HERE IS ESTABLISHING WITH
THE NATIVE AMERICAN POPULATION.
INDIGENOUS POPULATIONS AND HOW
IMPORTANT CULTURE IS FOR
ASSESSING PAIN AND LIFE
EXPERIENCE IN TERMS OF PAIN
TOLERANCE GOALS.
AND AGAIN I AGREE WITH THE
COMMENTS PRESENTED TODAY BUT WE
WEEN TO THE NECESSARY AGREE IN
STUD
STUDIES.
>> THANK YOU.
>> THERE'S A CANNABIS HEALTH
RESEARCH INITIATIVE AND TIME TO
GET AT A COUPLE THINGS YOU
TALKED ABOUT AS FAR AS PUTTING
INFORMATION TOGETHER TO WE'RE
LEARNING FROM EACH OTHER BECAUSE
WE HAVE DIFFERENT PEOPLE DOING
DIFFERENT THINGS AND THE ONLY
WAY THEY HAVE THE ABILITY TO DO
THEM IS WE REALIZE IS VERY
DIFFICULT AND SO ONE OF THE
PURPOSES OF THE PROJECT THAT
JUST CAME ONLINE THROUGH JOHNS
HOPKINS IS THEY'RE HOPING TO
GATHER PATIENT-CENTERED
INFORMATION USEFUL FOR THOSE IN
A CLINICAL CENTER TO LEARN FROM
EACH OTHER THIS IS THE DATA
WE'VE BEEN COLLECTING IN OUR
CLINICAL POPULATION AND HAVE IT
IN ONE PLACE TO BE DISSEMINATED
AND THE DATA COLLECTION HAS
DIFFERENT PARTS BUT URGE THOSE
INTERESTED IN THE
PATIENT-FOCUSSED SIDE OF THINGS
TO TAKE A LOOK AND IF YOU NEED
HELP FINDING IT, I'M MARCIA.
SEEK ME OUT AND I'LL HELP YOU
FIND IT.
>> THANK YOU SO MUCH, MARCIA.
>> WE MAY HAVE TIME FOR ONE
QUESTION BEFORE THE LUNCH.
YOUR CHANCE FOR ONE QUESTION, IF
NOT, WE CAN HAVE THIS MINUTE
ADDED TO THE LUNCH BREAK.
SO THAT WAS AN ABSOLUTELY
PHENOMENAL PART OF THE DAY 21
PRESENTATIONS.
WONDERFUL DATA.
AND GREAT IDEA SO WE CAN
CONTINUE DISCUSSING IT OVER THE
LUNCH LUX WILL BE NETWORKING AND
IT WILL BE OPEN IN TWO MINUTES
AND YOU'RE WELCOME TO GO THERE
AND WE ENCOURAGE YOU TO START
THE CONVERSATION ABOUT POTENTIAL
COLLABORATIONS AND BRINGING
EXPERTISE TO POTENTIAL
APPLICATIONS TO NIH.
THANK YOU VERY MUCH FOR THE
GREAT HALF OF THE DAY AND WE'LL
SEE YOU BACK AT 1:30 SHARP.
THANK YOU.
WELCOME TO DR. PIOMELLI AFTER
WORKING AT THE NEURO SCIENCE
INSTITUTE IN SAN DIEGO AND
JOINED THE UNIVERSITY OF IRVINE
THE CHAIR IN NEURO SCIENTISTS
AND PHARMACOLOGY AND BIOLOGICAL
CHEMISTRY.
DR. PIOMELLI IS THE AUTHOR OF
OVER 450 PEER-REVIEWED ARTICLES
IN NATURE OF NEUROSCIENCE AND
HAS TWO FULL-LENGTH BOOKS AND 34
PATENTS.
HIS RESEARCH IS FOCUSSED ON
UNDERSTANDING HOW
ENDOCANNABINOID SUBSTANCES AND
OTHER LIPID SINGLING MOLECULES
AFFECT THE FUNCTION OF THE BRAIN
AND ALERT ORGANS AND
INVESTIGATED BIO CHEMICAL
PATHWAYS INVOLVED IN THE
FORMATION AND DEACTIVATION OF
ENDOCANNABINOID TRANSMITTERS AND
UNCOVERED ROLES PLAYED IN THE
MOLECULES AND WELL PROVIDE AN
OVERVIEW OF SAFETY AND EFFICACY
OF CANNABIS BASED STRATEGIES IN
ANIMAL MODELS AND HUMAN-BASED
STUDIES.
>> THANK YOU FOR THE KIND
INTRODUCTION AND FOR HAVING ME.
>> THE TOPIC IS AS I'M SURE YOU
REALIZE VERY LARGE, TOO LARGE
FOR A 30, 35 MINUTE PRESENTATION
AND WHAT I THOUGHT I'D DO
INSTEAD IS FOCUS ON TWO
PARTICULAR SUB TOPICS OR POINTS.
ONE IS TO DEVELOP METHODOLOGICAL
ISSUES REGARDING CANNABIS
RESEARCH AND BIAS, CAUSALITY AND
CONFOUNDERS AND THE OTHER IS TO
PRESENT EXAMPLES OF THIS
METHODOLOGICAL ISSUES TO CASE
STUDIES.
ONE CANNABIS IN PSYCHOSIS AND
THE OTHER CANNABIS AS AN
ANALGESIC.
LET'S LOOK AT THE METHODOLOGICAL
ISSUES FIRST.
WHEN I SPEAK OF BIAS IN THIS
CASE I DO NOT MEAN GENDER BIAS
OR RACE BIAS.
I MEAN SOMETHING THAT IS
ACTUALLY AS PERNICIOUS BUT MORE
INSIDIOUS AND WOULD LIKE TO GO
OVER WITH YOU IN A MINUTE AND
TALK ABOUT CAUSALITY AND WHAT
ISSUES PRESENT WITH CANNABIS AND
CONFOUNDERS.
AND ALL OF US RECOGNIZE IT'S A
VERY DICHOTOMOUS DEBATE AND
POLARIZED DEBATE.
YOU CAN HEAR OPINIONS THAT RANGE
FROM CANNABIS AS ONE OF THE MOST
TOXIC SUBSTANCES ON THE PLANET
EXEMPLAIFIED BY THE CAMPAIGN JUT
SAY NO TO DRUGS AND WE HAVE THE
OPPOSITE SIDE AND FOLKS WHO
BELIEVE CANNABIS IS BASICALLY A
CURE-ALL AND PANACEA FOR ALL
POSSIBLE AILMENTS.
AND OF COURSE THE PROBLEM IS WE
SCIENTISTS ARE SITTING RIGHT IN
THE MIDDLE OF THIS AND SO WE'RE
LITERALLY BETWEEN A ROCK AND A
HARD PLACE.
NOW, THIS IS NOT JUST AWKWARD,
IT'S ALSO PROBLEMATE IC US BECAE
US UNDERSTANDING THAT.
THAT DICHOTOMY IS ALSO LARGELY
UNIQUE TO CANNABIS AND IT HAS
ALSO VERY DEEP ROOTS AND THE
CONSEQUENCES ARE THOSE THAT I'M
WORRIED ABOUT.
THIS IS AN AUDIENCE OF
PHARMACOLOGISTS AND SCIENTISTS
AND YOU ALL KNOW THERE'S
MULTIPLE PSYCHO ACTIVE AND
PSYCHO TROPIC DRUGS AND WE HAVE
COCAINE IF AND MORPHINE AND
SCOPOLAMINE AND WE CAN HAVE
CONVERSATIONS ABOUT THIS DRUGS
AS WE DO ABOUT CANNABIS.
WE JUST DON'T.
AND FOR WHATEVER HISTORICAL
REASON THAT'S IMPORTANT.
AND THE IMPORTANT BECAUSE IT'S
DEEPLY ROOTED AND YOU HAVE SEEN
THESE TYPES OF SLIDES IN THE
PAST.
CANNABIS WAS AN APPROVED
MEDICATION IN THE UNITED STATES
OF AMERICA IN 1860 AND
INTRODUCED IN THE UNITED STATES
PHARM
PHARMACO BOOKS AND A CAMPAIGN
STARTED WITHOUT STRONG MEDICAL
OR EVEN WEAK MEDICAL BACKGROUND
THAT COMPLETELY MOVED IT IN THE
OPPOSITE DIRECTION.
AND THIS IS ACTUALLY DRUGS THAT
MAKE YOU CRAZY AND YOU WOULD SEE
MOVIES LIKE REEFER MADNESS WHICH
IF YOU HAVE NOT SEEN I RECOMMEND
YOU SPENT 30 MINUTES SEEING
BECAUSE IT'S ENTERTAINING AND
HEAR CANNABIS IS PUBLIC ENEMY
NUMBER ONE AND THAT LED TO THE
ILLEGALIZATION OF CANNABIS WITH
THE CONTROLLED SUBSTANCE ACT.
AGAIN, AS SCIENTISTS AND OUR
COMMON PERSPECTIVE HERE HOW DO
WE LOOK AT THIS?
IS IT MEDICINE OR PUBLIC ENEMY
NUMBER ONE?
THERE'S THE FACT THAT THEY
HIDDEN CONSEQUENCES AND BRING
BIASSED OPINIONS AND ESPECIALLY
IF THEY'RE HIDDEN CANNOT BE
UNDERESTIMATED AND THIS POSTER
SAYS A TRUTH AND I WANT TO GIVE
AN EXAMPLE OF THIS.
SO I BRING THIS INTO A MORE
CONCR
CONCRETE GROUND SOME HAVE SEEN
THIS PAPER PERSISTENT CANNABIS
USERS SHOW NEURAL PSYCHOLOGICAL
DECLINE AND PUBLISHED IN 2012
AND IS AND THE COHORT IS NORTH
OF NEW ZEALAND WHICH FOLLOWED A
COUPLE RESIDENTS FROM BIRTH TO
38 AND THEY ASSESSED I.Q. AND
INTELLIGENT QUOTIENT I.Q. AND
DR. MIER CAME TO THE CONCLUSION
THAT THOSE INDIVIDUALS WHO USE
CANNABIS PERSISTENTLY HAD LOWER
I.Q.
SO THERE IS A LOT THAT CAN BE
SAID ABOUT THIS BUT I BET THAT
YOU HAVEN'T SEEN THIS PARTICULAR
PAPER.
THIS PARTICULAR PAPER WAS
PUBLISHED BY A NORWEGIAN
ECONOMIST WHO LOOKED AT THE DATA
AND THE SAME DATA MIER'S WORKED
WITH AND FOUND THE SAME RESULTS
COULD BE CONFOUNDED BY THE
SOCIAL ECONOMIC STATUS.
IN THIS SUGGESTED THE SOCIO
ECONOMIC STATUS IN CANNABIS WAS
RESPONSIBLE FOR THE LOWER I.Q.
IN THIS PARTICULAR POPULATION.
THE POINT I WANT TO MAKE NOW IS
NOT WHETHER MIER IS RIGHT,
THAT'S NOT THE POINT BUT THE
POINT IS I THINK WE ALL KNEW THE
PAPER AND VERY FEW HEARD OF THIS
PAPER AND WE HAVE NUMBERS FOR
THAT BECAUSE THE PAPER HAS BEEN
CITED ALMOST 2,000 TIMES AND
THIS PAPER HAS BEEN BARELY 132
TIMES.
SO THAT'S THE POINT I WANT TO
MAKE IS THAT IT'S NOT ONE OR THE
OTHER IS RIGHT BUT IT SHOULD
HAVE BEEN CITED APPROXIMATELY
THE SAME AMOUNT OF TIMES BECAUSE
THEY CAME OUT AT THE SAME TIME
SAYING TWO OPPOSITE THINGS
LOOKING AT THE SAME DATA.
THIS SHOWS A BIAS.
I FEEL THIS IS A WAY I DO IT
MYSELF.
I'M NOT CLAIMING IT'S SOMETHING
YOU SHOULD BE DOING BUT WHAT I
INTEREST I TRY TO MODIFY MY
BEHAVIOR AND SELF-AWARENESS AND
THE BIASES REFLECT AND SEEK
FEEDBACK.
THAT'S ALL SIMPLE IN THEORY.
EDUCATION AND LEARNING AND LEARN
OF DIFFERENT BIASES AND THE CASE
WE HAVE SEEN MEIER EXAMPLE IS A
CASE OF WHAT SOME PEOPLE CALM
BIAS AND YOU FEEL LIKE YOU KNOW
KIND OF THIS IS BAD FOR YOU SO
WHEN YOU SEE A PAPER THAT SAYS
IT'S BAD FOR YOU, IF YOU SEE A
PAPER THAT SHOWS OPPOSITE IT
RAISES YOUR DECISION AND MINDFUL
DECISION MAKING AND PAUSE AND
REFLECT AND CONSIDER
ALTERNATIVES AND AND IF YOU'RE
AN ADVOCATE FOR CANNABIS TALK TO
A PHYSICIAN THEY HAVE DIFFERENT
OPINIONS.
IF YOU'RE A PHYSICIAN TALK TO AN
ADVOCATE AND IF YOU'RE A
SCIENTIST LIKE I HAPPEN TO BE
TALK TO BOTH BUT PLEASE BUT THE
DATA FIRST BECAUSE AT THE END OF
THE DAY ALL WE NEED TO DO IS
LOOK AT THE DATA AND EVERYTHING
THAT WE INTERPRET FROM THE DATA
IS NARRATIVE.
THE DATA ARE THE EMPIRICAL
GROUND IN WHICH WE ALL STAND.
AND CULTIVATE AN OPEN MIND SET.
IF THE STUDY CHALLENGES YOUR
FURTHER IDEA, DON'T IGNORE IT
AND THAT IS UNFORTUNATELY WHAT
HAPPENED WITH THE MEIER PAPER.
I WANT TO GO BACK TO THIS TO
HIGHLIGHT SOMETHING ABOUT THE
TITLE OF THE TWO TALKS ONE HAS
ALMOST AN IMPLICIT CAUSALITY AND
CAUSALITY IS IMPLIED NOT IN SO
MANY WORDS BUT CLEARLY IMPLIED.
WHEREAS THE PAPER AND
CORRELATION IS IN THE TITLE.
AND THAT IS MY SEGUE FOR GOING
TO ISSUE OF CAUSAL EVIDENCE.
SO WE ALL KNOW CORRELATION IS
NOT CAUSATION.
WE FEEL CORRELATION IS NOT WILL
A POSITION BUT SOMEWHAT SIMILAR
TO CAUSATION.
LET ME TELL YOU OFF THE BAT, HE
WAS WRONG.
CONTINGENCY IS NOT CAUSE.
WE HAVE TWO VERY DIFFERENT
THINGS.
ACCORDING TO THIS GUY.
SO IF CAUSATION WERE THE SAME AS
CAUSATION IN THESE HEADLINES
WOULD BE AND WELL, IF YOU RUN A
CROSS-SECTIONAL ANALYSIS IN MANY
PLACES YOU WOULD SEE MOST PEOPLE
ARE BORN OF CUBAN DISSENT AND
PEOPLE WHO OF JEWISH DESCENT AND
HOW DO WE ESTABLISH CAUSALITY IN
OUR WORK?
MOST KNOW CAUSALITY HAS BEEN IB
A BIG TOPIC FROM SINCE ARISTOTLE
AND WILL SAY FROM MY MODEST
WHICH I HAVE NOT COLLABORATED IN
ANY WAY, SHAPE OR FORM AND WE
SCIENTISTS USE DAILY A VIEW OF
CAUSALITY THAT IS RADICALLY NEW
AND THE VIEW OF CAUSALITY WAS IN
THE BOOK CALLED THE DISCOURSE OF
FLOATING BODIES AND GALILEO
WROTE THE EFFECT FOLLOWS AND
REMOVED THE EFFECT WILL IS
REMOVED.
WHAT HE MEANS IS SIMPLE.
WE DO THIS ALL THE TIME YOU WANT
TO SHOW THE ACTIVATION OF
CANNABINOIDS IN THE BRAIN CAUSES
HYPERTHERMIA, CAUSALITY?
THE CANNABINOID RECEPTOR AGONIST
AND GIVE THE ANTAGONIST AND
BLOCK THE AFFECT AND REMOVE THE
CAUSE AND THE AFFECT IS REMOVED.
THAT'S ESSENTIALLY WHAT
PHILOSOPHERS CALL AN
INTERVENTIONIST APPROACH TO
CAUSALITY.
AND IT'S VERY SIMPLE.
WE HAVE CAN PLAN EXPERIMENTS
THAT ARE MORE CONE OF CONTROLLED
AND HARD FOR OBSERVATION AND
STUFF FROM ASTRONOMY AND
OBSERVATION PLAYS AN IMPORTANT
ROLE IN CANNABIS RESEARCH.
SO HOW DO WE ADDRESS THE ISSUE
OF CAUSALITY IN CANNABIS
RESEARCH?
THERE ARE WAYS TO DO THAT AND I
THINK ARE PRETTY STRONG.
FOR EXAMPLE WE CAN USE
DISCORDANT SIBLING/TWIN DESIGN
AND COMPARE OUTCOMES WHEN HO
HOMOZYGOTIC TWINS ARE DISCORDANT
IN THEIR CANNABIS USE AND THIS
APPROACH HAS BEEN USED
CLASSICALLY TO DEFINE THE
GENETIC COMPONENT OF
SCHIZOPHRENIA IN THE 1960s.
SO THERE'S AN AREA OF
OPTIMIZATION AND TAKES ADVANTAGE
OF THE FACT THAT NEXT IS SINGLE
NUCLEOTIDE POLYMORPHISMS OCCUR
RANDOMLY.
THAT'S THE RANDOM CONTROL IN A
WIDE POPULATION AND SO WE CAN
USE THE GENETIC VARIANTS
ASSOCIATED WITH CANNABIS USE AS
A VARIABLE TO TEST THE CAUSAL
EFFECT OF CANNABIS ON A SPECIFIC
OUTCOME AND WE'RE LUCKY BECAUSE
THE RESEARCH IS GENETIC VARIANCE
ASSOCIATED WITH CANNABIS USE AND
THE RECEPTOR VARIANTS AND THE
AND THE FATTY ACID GENE
RECOGNIZED.
AND THEN THERE IS INTERVENTIONS.
PAUSE INTERVENTIONS ARE A COOL
WAY OF DOING THAT AND MAYBE SOME
LOOK INTO THAT AND CAN
CAPITALIZE AND THE FACT THAT AN
EXTERNAL EVENT OR PUBLIC
INTERVENTION AFFECTS IT ONE ONE
POPULATION AND SAY IN THE STATE
OF COLORADO AND NOT IN THE STATE
OF NORTH DAKOTA OR SOMETHING
LIKE THAT.
THEY HAVE TO BE DEMOGRAPHICALLY
SIMILAR AND YOU GET THE DRIFT.
AND FINALLY WHAT I DO
EXPERIMENTAL STUDIES WE CAN RUN
CONTROLLED STUDIES TO PERMIT
RANDOM ASSIGNMENT OF SUBJECTS
AND COULD BE HUMAN SUBJECTS FOR
THE ADMINISTRATION OF A DEFINED
QUANTITY AND TYPE OF CANNABIS OR
CANNABINOID AND INCLUDES PLACEBO
CONTROL RANDOMIZED CLINICAL
TRIALS.
AND THIS WAS MY SEGUE TO THE
NEXT AND THE CONFOUNDER AND THE
NEXT ISSUE I WANTED TO DISCUSS
AND LOOK AT THE CANNABIS AND
CANNABINOID.
AND I WAS GOING TO GO OVER THAT
IN SOME DETAIL.
WE ALL RECOGNIZE THE PLAN
DIVERSITY IS THE CONFOUNDER IN
OUR STUDIES AND IF YOU GO TO ANY
DISPENSARY IN THE STATE OF
CALIFORNIA YOU FIND HUNDREDS OF
PRODUCTS AND YOU HAVE YOUR DABS
AND YOUR PRE-ROLL, ETCETERA.
DIFFERENT NAMES, DIFFERENT
PRICES, DIFFERENT MARKET
PRESENTATION.
THIS MAY BE OVERWHELMING TO SOME
BUT IT WAS NOT OVERWHELMING TO
ME WHEN I FIRST SAW ITS.
I REMEMBER WHEN I FIRST ARRIVED
IN THIS COUNTRY A LONG TIME AGO
I REMEMBER THIS.
TO ME THIS WAS LIKE ALIEN.
WHY DO THEY NEED SO MANY POTATO
CHIPS?
I STILL HAVEN'T GOTTEN USED TO
IT, I HAVE TO ADMIT.
SO THE THING IS DIFFERENT
CANNABIS PRODUCTS DIFFER AND
THAT'S IMPORTANT.
THEY'RE NOT JUST THE SAME.
YOU CAN'T TREAT THEM AS IF THEY
WERE THE SAME.
THEY'RE DIFFERENT BUT IN WHAT?
MODE OF VIEWS WE DISCUSSED
BEFORE AND IN THE EXCIPIENTS AND
LIKE POTATO CHIPS ARE ABOUT
POTATOES, SALT AND OIL THIS IS
ABOUT THC.
IF THERE WERE NO THC WE WOULDN'T
BE HERE.
AND WE'RE HERE IN THE MEETING
THANKS TO THC AND I WENT TO AN
EVENT IN SAN BERNARDINO AND SEE
DIFFERENT TYPES OF CANNABIS AND
SOME ARE SHORT AND SOME ARE
FULLY AND SOME ARE FULL OF
FLOWERS AND RICH IN A PARTICULAR
OIL AND SMELL STRONGLY.
IT'S VERY INTERESTING WE HAVE
DIFFERENT TYPES OF CANNABIS
NAMES THROWN AROUND ALL THE TIME
BUT WHAT'S THE SCIENCE BEHIND
IT?
LET ME TAKE YOU TO A PAPER THAT
GOES SPECIFICALLY TO THE
QUESTION OF THE SCIENCE BEHIND
THE VARIETY.
SO IN THIS PAPER A GROUP OF
RESEARCHERS IN THE NETHERLANDS
TOOK A HUNDRED VARIETIES OF
CANNABIS AND FOR PLANT PEOPLE
PREFER TO USE VARIATALS AND
STRAINS AND THERE'S COMMENTARIES
ABOUT THAT.
AND THEY DID TWO THINGS.
YOU CAN SEE HERE.
THEY LOOKED AT THE GENOME AND
THEN THEY LOOKED AT TERPENE AND
CANNABINOID COMPOSITION AND YOU
SEE THE COMPONENT ANALYSIS AND
YOU CAN SEE THE CULTIVARS ARE
CLUSTERED TOGETHER.
SOME HAVE 100% SATIVA AND SOME
I
INDICA AND ACCORDING TO
CANNABINOID COMPOSITION.
THIS MEANS THEY'RE THE SAME
GENETICALLY AND CHEMICALLY THE
SAME.
YOU CAN'T TAKE THIS TO YOUR LAB
AND I COULD HAVE A LONG
EDITORIAL ON THIS BUT THE
CANNABIS CULTIVARS AND HERE'S MY
TWO CENTS.
FIRST, PLEASE IGNORE MARKETING
GOALS.
DON'T LISTEN TO THE CANNABIS
INDUS
INDUSTRY, INDICA AND SATIVA ARE
VERNACULAR TERMS.
THEY'VE BEEN HIGH JACKED FOR
MARKETING PURPOSE AND PAINS ME
TO HEAR COLLEAGUES USING THE
WORDS NOT BECAUSE THEY'RE WRONG
BUT WE'RE BORROWING THEM FROM
THE INDUSTRY AND PUT THERE FROM
THE INDUSTRY TO SELL STUFF.
WE HAVE NAMES FOR THIS,
SYNERGISM AND ALL KIND OF THINGS
TO USE AND ENTOURAGE EFFECT IS
NOT HELPFUL TO THE ROOM
DISCOURSE AND NOT A GOOD IDEA IF
YOU'RE A SCIENTIST.
I DON'T WANT TO SOUND EXTREME IN
MY POSITION BUT WE CANNOT IGNORE
CANNABIS IS TASTING A CERTAIN
WAY TO THE USER IS IMPORTANT TO
THE USER NOT JUST THE HUMAN USER
BUT ANIMALS.
IF YOU CAN SMELL IT, I CAN
PROMISE A RAT CAN SMELL BETTER
THAN YOU CAN AND DON'T IGNORE
THE AROMA.
THERE'S CONSEQUENCES, FOR
EXAMPLE, THEY ARE CAN MAKE THE
DIFFERENCE BLIND OR NOT BLUE
LINE OR HAVE A PLACEBO JUST
CONSIDER IS THAT.IUE
LINE OR HAVE A PLACEBO JUST
CONSIDER IS NUE
LINE OR HAVE A PLACEBO JUST
CONSIDER IS DUE
LINE OR HAVE A PLACEBO JUST
CONSIDER IS THAT.E
LINE OR HAVE A PLACEBO JUST
CONSIDER IS THAT.INE
OR HAVE A PLACEBO JUST CONSIDER
IS THAT.NE
OR HAVE A PLACEBO JUST CONSIDER
IS THAT.E
OR HAVE A PLACEBO JUST CONSIDER
IS TH OR
HAVE A PLACEBO JUST CONSIDER IS
THAT.
THERE'S SUCH A THING AS THE DOSE
OF THE DRUG AND THC IS A 1
MILLIGRAM, 10 MILLIGRAM AND
THOSE ARE DIFFERENT ANIMALS.
PAY ATTENTION TO WHERE IT'S
DOING IT'S JOB IF IT'S THE BRAIN
OR IMMUNE CELLS.
AND FINALLY PAY TENSION TO
EXCIPIENTS THE STUFF INDUSTRY
PUTS.
FOR EXAMPLE, THE POLY ETHYLENE
RECALL OR VITAMIN A WAS
MENTIONED BEFORE.
THESE CAN INTERACTION
FUNCTIONALLY WITH THC AND HAVE
EFFECTS ON THEIR OWN.
I'LL QUICKLY OVER TWO CASE
STUDIES.
CANNABIS AND PSYCHOSIS AND
CANNABIS AS AN ANALGESIC.
THAT'S THE CAUSED PSYCHOSIS.
THIS IS A BRUTE WAY OF PUTTING
IT BUT THE WAY I THINK WE SHOULD
ADDRESS IT SO WE DON'T HIDE
BEHIND WORDS.
SO THAT'S CANNABIS CAUSED
PSYCHOSIS.
LET'S REFINE THE QUESTION TO TWO
RELATED QUESTIONS.
THAT'S CANNABIS CAUSE ACUTE
PSYCHOTIC SYMPTOMS AND THERE'S
PERCEPTUAL DISTURBANCES SUCH AS
ALTERATIONS IN SPACE AND TIME
AND VISUAL ILLUSION, ETCETERA.
WE CAN SPEAK OF CANNABIS INDUCED
PSYCHOSIS AND IF WE ASK THE
PERSON, OKAY, SO YOU'RE SEEING
EVERYTHING IN THAT PARTICULAR
COLOR AND SEEMS LIKE IT'S GOING
SLOWLY, WHY?
WELL, BECAUSE I'M HIGH.
IF THAT'S THE PERSON YOU HAVE
INTACT REALITY AND THE CAN'T BE
TALKING ABOUT PSYCHOSIS AND WHAT
MATTERS TO US REGARDLESS OF
WHETHER WE'RE PARENTS OR NOT
CLEARLY IT'S IMPORTANT TO KNOW
WHETHER USE OF CANNABIS AND WHEN
THERE'S YOUNG WOMEN AND MEN
SUSCEPTIBLE TO DEVELOPING
PSYCHOSIS AND THAT IS THE
QUESTION I WOULD LIKE TO RECALL
FOCUS QUICKLY ON.
AND REALLY THIS ALL STARTED WITH
THIS PARTICULAR PAPER THE FACE
THAT LAUNCHED A THOUSAND SHIPS
THE FAMOUS PAPER FROM SWEDISH
STUDY OF 1987 WHERE
COLLABORATORS SHOWED STARTING
FROM A COHORT OF 45,000 USING
CANNABIS DURING ADOLESCENTS WAS
RECALL ASSOCIATED SIX TIMES MORE
IN DEVELOPING PSYCHOSIS IN
ADULTHOOD.
LET'S LOOK AT THE CONTEXT.
THE CONTEXT, THE BACKGROUND IS
AT THAT POINT WE'RE ALREADY
EVERYONE INCLUDING THE
SCIENTISTS WE DON'T LIVE IN AN
IVORY TOWER, WE'RE HEARING
THINGS ABOUT CANNABIS MAKING
PEOPLE CRAZY.
WHAT I BROUGHT UP HERE IS MAYBE
THE QUOTE, UNQUOTE, FUN EXAMPLE
BUT FUN EXAMPLE BECAUSE IT'S SO
EXTREME.
THIS IS AN ARTICLE THAT APPEARED
IN THE 1940s IN A NEWSPAPER.
ENTITLED EVIL MEXICAN PLANT THAT
DRIVE YOU INSANE AND A MEXICAN
OF THE LOWER CLASS WHO SMOKED AN
MARIJUANA CIGARETTE BECAME
INSANE AND KILLED A POLICEMAN
AND BADLY WOUNDED THREE OTHERS.
IT'S WRONG ON SO MANY LEVELS I
DON'T EVEN WANT TO START BUT TO
POINT OUT IF YOU THINK THIS IS
SOMETHING THAT HAPPENED IN THE
1940s ISN'T HAPPENING NOW, YOU'D
BE WRONG BECAUSE I HEARD THE
SAME PHRASE ON FOX NEWS TWO
YEARS AGO.
THIS IS STILL WITH US.
ANYWAY, LET'S REVIEW THE
EVIDENCE.
THIS IS DONE BY NATIONAL
ACADEMIES OF SCIENCES WHO PUT
FORTH THIS HEFTY REPORT AND WHEN
THE COMMITTEE REVIEWED THE
EVIDENCE ISSUED THEIR
CONCLUSIONS, THESE WERE THEIR
CONCLUSIONS.
THE FIRST CONCLUSION IS I'LL
READ FOR YOU, THIS IS
SUBSTANTIAL EVIDENCE OF A
STATISTICAL ASSOCIATION BETWEEN
CANNABIS USE AND THE DEVELOPMENT
OF SCHIZOPHRENIA OR OTHER
PSYCHOSIS WITH THE HIGHEST RISK
AMONG THE HIGHEST USERS AND IT
WAS ACCURATE, SUBSTANTIAL NOTE
CONCLUSIVE.
STATISTICAL ASSOCIATION NOT
CAUSAL.
IT'S A CAREFUL STATEMENT AND THE
REASON IT WAS CAREFUL AND THERE
WERE DISCUSSION ON THIS BECAUSE
WHEN YOU LOOK AT THE DATA
CAREFULLY THINGS AND THERE'S
MODERATE EVIDENCE AMONG
INDIVIDUALS WITH PSYCHOTIC
DISORDERS THERE'S A STATISTICAL
ASSOCIATION BETWEEN A HISTORY OF
CANNABIS USE AND BETTER
COGNITIVE PERFORMANCE WHICH IS
SUGGESTIVE OF CAUSAL AND THOSE
WHO USE CANNABIS IT SOMEHOW
MAKES THEM FEEL IN SOME WAYS
BETTER.
I'M NOT PROPOSING THAT THEORY
BUT SAYING THERE'S ENOUGH IN THE
DATA TO SUGGEST IT WOULD BE MORE
COMPLEX THAN JUST CANNABIS MAKES
YOU CRAZY.
THE ISSUE OF CAUSALITY WAS
EXPLICITLY RAISED IN THE STUDY
PUBLISHED IN 2021 AND CAUSALITY
WAS AT THE CENTER OF THE PAPER
AND THIS IS A LONGITUDINAL
DISCORDANT PAPER AND IN THE
STUDY US OF 262 TWINS REPORTING
GREATER CANNABIS USE REPORTED
HIGHER LEVEL OF PSYCHOLOGY AND
POORER ECONOMIC OUTCOME AND IT
HAD BEEN SHOWN AND THIS IS THE
KICKER CANNABIS USE REMAINS
RELATED WITH SOCIAL OUTCOMES,
EDUCATION AND OCCUPATIONAL
OUTCOMES AND IN OTHER WORDS
CANNABIS USE ON THE PAPER
APPEARS TO BE CAUSATIVE FOR
NEGATIVE SOCIO ECONOMIC OUTCOMES
BUT NOT FOR LOWER I.Q. OR
SCHIZOPHRENIA AND THE PAPER HAS
BEEN CITED 38 TIMES SINCE 2021.
THAT'S NOT A LOT.
WHAT NEXT?
HOW DO WE ADDRESS THE LINK
BETWEEN CANNABIS AND
SCHIZOPHRENIA?
I THINK WE'RE IN A GREAT PLACE
TO DO THAT BECAUSE WE HAVE SEEN
ABCD AND ALL OF US.
WE CAN USE MENDELIAN
RANDOMIZATION ON THE LARGE HUMAN
COHORT AND ASK WHAT IS CAUSATIVE
AND WHAT IS NOT.
WE CANNOT DO THEM BECAUSE
SCHIZOPHRENIA IS SO COMPLEX WE
DON'T HAVE ANYTHING CLOSE TO A
MODEL THERE.
I'LL QUICKLY CONCLUDE AND GO
OVER MY SECOND CASE STUDY.
WHETHER CANNABIS IS A SAFE AND
EFFECTIVE ANALGESIC.
THE FACE THAT LAUNCHED A
THOUSAND SHIPS WAS THIS PAPER
PUBLISHED IN 2007.
WHAT THE PAPER SHOWED WAS THAT
SMOKING LOW LEVELS OF CANNABIS
IN A SMALL NUMBER OF PATIENTS
WITH HIV ASSOCIATED SENSORY
NEUROON -- NEUROPATHY HAD LOWER
PAIN AND THIS WAS BASED ON A
BACKGROUND CONTRARY TO THE
PREVIOUS ONE WAS THE FIRST THEY
FOUND EUROPEAN ACCOUNT AND
CANNABIS AS AN ANALGESIC AND
READ THE TEXT AND THERE WAS AN
APPENDIX TO THE PAPER AND THIS
COMMENTARY ON THE PHARMACOPEIA
AROUND I FOUND SECESSION OF PAIN
AND PLEASANT NUMBNESS IN THE
LIMBS AND GIDDINESS AND
IMPOSSIBILITY TO FOLLOW TRAIN OF
THOUGHT AND SLIGHT INCREASE IN
THE FORCE OF THE PULSE.
THIS IS AN ACCURATE DESCRIPTION
OF WHAT CANNABIS DOES.
VERY ACCURATE AND TELLS YOU WE
TO THINGS.
IN ALL THE WARNING PEOPLE ONLY
RATE CESSATIONAL PAIN AND THE
COMMITTEE OF THE NATIONAL
ACADEMIES ARRIVED TO THE
CONCLUSION THERE WAS SUBSTANTIAL
EVIDENCE CANNABIS IS AN
EFFECTIVE TREATMENT FOR CHRONIC
PAIN IN ADULTS AND THERE WAS
STRONG RATIONALE SO WHEN NON
HUMAN SCIENTISTS CONVENED THEY
BASICALLY ARRIVED TO THE SAME
CONCLUSION.
AND THEY LOOKED AT THE
CO-PRESSURE TEST ON HUMAN
VOLUNTEERS TO STUDY AND EXAMINE
WHETHER THC WAS ANALGESIC OR NOT
AND IT'S AN INTERESTING STUDY.
YOU CAN SEE THE RESULTS HERE.
BASICALLY THE CONCLUSION WAS
THAT IN BOTH MEN AND WOMEN THC
PRODUCED AN ANALGESIC EFFECT ON
PAIN SENSITIVITY AND PAIN
TOLERANCE.
SO, LEADS US TO CONCLUDE BOTH
HUMAN AND ANIMAL DATA SUPPORT
THE NOTION CANNABIS CAUSES
ANALGESIA.
I'M USING A WORD NOT IN THE
PAPER BUT I THINK YOU
UNDERSTAND.
SO WHAT NEXT AND HOW DO YOU
ADDRESS THE CAUSAL NATURE OF THE
LINK BETWEEN CANNABIS AND A
ANALGESIA AND IS IT SAFETY
ANDES
ANDESQUE -- SAFE AND EFFECTIVE
AS AN ANALGESIC AND LOOK AT
PLACEBO CONTROLS OF CP --
CHRONIC PAINS IN ADULTS AND WE
CAN HAVE HUMAN TRIALS TO AID US
IN THE SELECTION OF ONE OR MORE
SUITABLE CHRONIC PAIN CONDITIONS
BECAUSE CHRONIC PAIN IS A
HETEROGENOUS CONSTRUCT AND
CONTAINS MANY THINGS.
I'LL START BY SUGGESTING YOU
DOWNLOAD THIS AND IT'S 486
PANELS PAGES BUT IT'S USEFUL
FOR A VARIETY OF THINGS.
UNFORTUNATELY IT'S STILL
UPDATED.
I WISH I COULD SAY IN FOUR OR
SIX YEARS OR WHATEVER AND FIVE
YEARS WHATEVER.
WE HAVE SO MANY MORE DATA IT'S
STILL QUITE UPDATED AND WITH
THAT I'LL STOP AND THANK YOU.
>> THANK YOU, PIOMELLI FOR THE
PROVOCATIVE TALK.
WE HAVE TIME FOR THREE OR FOUR
QUESTIONS.
>> I LOVED THE COMMENT ABOUT
DON'T LET THE MARKETERS USE THE
VOCABULARY AND I HATE SOME THAT
POP UP.
SECOND I WOULD ADD THAT TO YOUR
LIST OF THINGS NOT TO USE.
>> PEOPLE DO WHAT PEOPLE DO.
ALL WE CAN DO IS MAKE
SUGGESTIONS.
>> SO, I APPRECIATE THE FACT YOU
SAID THIS IS A CANNABIS ISSUE
BUT I'M THINKING THE BRAIN
DOESN'T KNOW WHETHER THE DRUG IS
ELICIT OR LEGAL AND IT'S
BIOLOGICAL AND CAN WE EXTRACT
FROM CANNABIS OTHER DRUGS OF
ABUSE AND THINKING THE OPIOID
PROCESS IS A RELATIVELY
EFFECTIVE ANALGESIC BUT HAS
RESPIRATORY DEPRESSION AND HIGH
RISK FOR OVERDOSE AND DEATH AND
ABUSE.
SO, TRYING TO GET AT THE SENSE
OF RISK BENEFIT HERE REGARDLESS
OF TALKING ABOUT CANNABIS OR ANY
PHARMACEUTICAL AT THIS POINT OR
CAN YOU EXTRACT WHAT YOU'RE
SAYING TO OTHER DRUGS OF ABUSE?
>> I THINK WE CAN LOOK AT DRUGS
AS CULTURAL PHENOMENA AND I
THINK WE SHOULD.
IT'S COMPLEX BUT EVERY DRUG HAS
TO BE TREATED DIFFERENTLY AND
THERE'S A CASE IN THE GOOD AND
BAD BECAUSE WE HAVE SHAPED OUR
VIEW OF AN ANALGESIC BASED ON
THE OPIOIDS.
WHEN WE LOOK FOR A NEW ANALGESIC
WE LOOK FOR SOMETHING THAT DOES
WHAT THE OPIOIDS DO BUT THEY'RE
VERY PECULIAR IN THE WAY THEY
PRODUCE ANALGESIA AND LIKEWISE
WE'RE SHAPED TO HAVE NEGATIVE
VIEWS BASED ON OPIOIDS BECAUSE
OF CULTURAL FACTORS.
AND THERE'S HIGHLY ADDICTIVE
DRUGS AND CAN KILL PEOPLE.
HAVING A CONVERSATION ABOUT THE
CULTURAL SIGNIFICANCE OF DRUGS
AND THIS HAPPENED FOR EXAMPLE
WITH PROZAC MANY YEARS AGO.
WE AS SCIENTISTS SHOULD BE
SOMETIMES PART OF THE
CONVERSATION THOUGH OF COURSE IT
BECOMES QUICKLY SOMETHING WE
DON'T FEEL COMFORTABLE WITH
BECAUSE IT DOESN'T HAVE DATA
MORE INTERPRETATION AND
ITERATION OF THE DATA BUT I FEEL
IT'S ALSO IMPORTANT TO CONSIDER.
>> MY PRESENTATION WAS VERY
[OFF-MIC]
>> THE QUESTION IS DO YOU THINK
THERE IS A REASON TO STUDY
CANNABIS USE IN HEALTHY
INDIVIDUALS AND IMPACT ON THEIR
HEALTH RATHER THAN JUST HOW TO
MITIGATE SOME DISEASE?
>> EXCELLENT QUESTION AND HOW
HEALTHY IS A HEALTHY INDIVIDUAL?
ONE DEMOGRAPHIC HAS SEEN IN
RECENT YEARS AN INCREASE IN
CANNABIS USE AND THAT'S MY
DEMOGRAPHIC 55 YEARS AND OLDER
BUT MY DEMOGRAPHIC HAS INCREASED
AND WHY IS THAT SO?
PEOPLE HAVE DONE SURVEYS AND
FIND CANNABIS IS USED IN MY AGE
GROUP TO BASICALLY ALLEVIATE
LITTLE PAINS OR FACILITATE
SLEEP.
THE HEALTH CHANGES OUR
PERCEPTION AND HEALTH CHANGES
OVER TIME AND CANNABIS NOT JUST
CANNABIS ANY OTHER RECREATIONAL
SUBSTANCE INCLUDING ALCOHOL AND
COFFEE ARE USED IN THE CONTEXT.
YEAH, I USE COFFEE DAILY BUT I
UNDERSTAND WHY SOMEONE WOULD
SAY, OKAY, LOOK, IF I SMOKE A
JOINT IF I'M GOING TO BED I'M
GOING TO SLEEP BETTER OR TAKE AN
EDIBLE.
I UNDERSTAND THAT.
OF COURSE WHAT I LIKE TO SEE THE
DATA SHOWING THAT IS BACKED BY
EMPIRICAL EVIDENCE?
YES, I WOULD, OF COURSE.
BUT IT'S A DIFFERENT BALLPARK.
>> OKAY.
THE OTHER THING WE'RE NOT
TALKING ABOUT AS A
PHARMACOLOGIST IT'S ALL ABOUT
CONCENTRATION AND CONCENTRATION.
THE DATA WAS WITH 5% TO 7% BY
WEIGHT THC.
HOW MUCH DO WE REQUIRE WHEN WE
HAVE PLANT MATERIAL KNOW THAT'S
30%, 35% OF EXTRACTS PUSHING
100?
WE DON'T TALK ABOUT THAT OTHER.
STUDIES THAT SAY WHEN THE FDA
APPROVES A DRUG YOU VA -- HAVE
TO SHOW A DOSE RESPONSE CURVE IN
THE DATA AND WE DON'T EVEN
CONSIDER IT.
>> IT'S VERY HARD.
THIS IS IN ITSELF A TOPIC FOR A
SEPARATE CONVERSATION.
I CAN'T DEVELOP THAT BUT IT'S
TRULY A VERY HARD PROBLEM
BECAUSE AND WE'RE DEALING WITH
THE PROBLEM OF HIGH POTENCY
CANNABIS PRODUCTS.
AND EVEN DEFINING HIGH POTENCY
IS AN EXAMPLE.
SAY WE'RE LOOKING AT A FLOWER
THAT CONVEYS 26% THC IS AVERAGE
NOW.
LET'S LOOK AT THAT.
THE QUESTION IS HOW MUCH OF THAT
26% WILL GO IN THE PERSON?
HOW MUCH IS THE REAL DOSE.
DOES THE PERSON TITRATE OR NOT?
I HAVE NOT SEEN DATA SHOWING
TITRATION OR NOT.
MAYBE IN COLORADO THERE WAS A
STUDY AND I DON'T KNOW IF THEY
CAN ILLUMINATE US BUT IT'S A
STEP WISE APPROACH.
SO HOW MUCH THC DO PEOPLE
ACTUALLY USE?
AFTER THAT, THEN I THINK POLICY
DECISIONS CAN BE MADE AS TO
WHETHER FOR EXAMPLE TAX HIGH THC
PRODUCTS OR NOT.
>> GREAT TALK.
YOU STARTED BY SAYING THAT WE
ARE HERE BECAUSE OF THC.
FOR THE FIRST HALF OF THE DAY WE
WERE TALKING SPECIFICALLY ABOUT
CANNABIS CONSTITUENTS NOT THC.
YOU SKIRTED AROUND THE TOPIC OF
OTHER CONSTITUENTS MAY OR MAY
NOT BE AND HOW IT'S SHAPING THE
CULTURAL CONVERSATION IN THE
UNITED STATES WHERE THERE'S A
VARIETY OF PRODUCTS AVAILABLE
THAT ARE NOT THC.
I'M WONDERING IF YOU CAN THINK
ABOUT WHAT WILL HAPPEN IN THE
NEXT 10 YEARS WILL THE
CONVERSATION TO CONSTITUENTS
SHIFT OR THINK IT'S THC?
>> IF YOU'RE THINKING ABOUT WHY
MOST PEOPLE WE KNOW, OUR TEENAGE
KIDS OR MY 70-YEAR-OLD NEIGHBOR
USE CANNABIS BECAUSE IT HAS THC
MY ANSWER IS WELL 90% OF THE
CASES IT'S BECAUSE OF THC.
THE KNOWN MEDICAL USE REQUIRES
THC OTHERWISE WHY WOULD YOU EVEN
DO IT AND IT'S NOT PROVIDING YOU
THE EUPHORIA AND FEELING OF
RELAXATION AND THE CHANGES AND
SENSES AND THE INCREASED SENSORY
EXPERIENCE THAT THC PROVIDES.
THAT FEELS GOOD JUST LIKE A
GLASS OF RED WINE FEELS GOOD.
THAT IS THC.
NOW WHAT HAPPENED WITH CANNABIS
WHICH I FEEL IS GREAT, THE
CORRELATES OF THAT THANKS TO
CANNABIS WE'RE DOING TWO THINGS.
FIRST IS WE HAVE AN
ENDOCANNABINOID SYSTEM IN THE
BRAIN AND HAD NO IDEA ABOUT THAT
25 YEARS AGO AND THAT'S A MAJOR
THING SO IF ANYTHING WE SHOULD
BE GRATEFUL BECAUSE THE
DISCOVERY IN THE BRAIN AND,
SECOND, CANNABIS ITSELF IS A
FANTASTIC PLANT.
IT'S A CHEMICAL FACTORY.
IF YOU LOOK AT THE TERPENE AND
THE VARIOUS REACTION THAT
FOLLOWS YOU HAVE 140, 150
MOLECULES THERE THAT ARE BASED
ON A SCAFFOLD THAT IS WHAT US IN
DRUG DISCOVERY WE CALL IT A
PREFERRED SCAFFOLD.
IT'S EFFICACIOUS BUT NOT
PARTICULARLY TOXIC.
THAT IS WHERE ALL OF YOU GUYS
WERE TODAY.
NOT ME, I DON'T DO THAT A LOT
BUT ALL YOU GUYS TODAY CAN HELP.
IF THAT SCAFFOLD IS PROMISING AS
I THINK IT IS, STUFF WILL COME
UP THAT HAS NOTHING TO DO WITH
CANNABIS.
LET'S FACE IT IT BARELY LOOKS
LIKE THC.
IT LOOKS MORE LIKE ANOTHER
TERPENE BUT COULD HAVE AN
INTERESTING SERIES OF EFFECTS
AND CANNOT BE VARYING AND ALL
THE DIFFERENT KIND.
IF WE LOOK AT THEM AND LOOK AT
CANNABIS AS A CHEMICAL PLANT IN
THE NOT SENSE OF VEGETABLE, THE
SENSE OF CHEMICAL PLANT, THEN WE
JUST USE IT TO CREATE NEW
MEDICATIONS AND IT'S
HAPPENSTANCE AS A LUCKY
DISCOVERY.
THAT'S ALL I CAN SAY.
THANK YOU SO MUCH.
>> THANK YOU SO MUCH FOR THE
KEYNOTE DR. PIOMELLI AND FOR
LEADING THE SESSION.
NOW, WE ARE STARTING OUR FOURTH
SESSION WITH THE MODERATOR THE
DEPUTY DIRECTOR OFF THE DIVISION
FOR EXTRAMURAL RESEARCH
DR. CRAIG HOPP ON THE KNEW
INITIATIVES AND RESOURCES FOR
CANNABIS RESEARCH.
>> THANK YOU FOR THE
INTRODUCTION, INNA.
WE'RE GOING TO TALK NOW FOR THE
NEXT HOUR OR SO ABOUT OR HALF
OUR ABOUT SOME OF THE NEW THINGS
GOING ON AND START OFF WITH ONE
OF MY CLOSE COLLEAGUES AND
FELLOW NATURAL PRODUCTS CHEMIST
DR. PATRICK STILL TO TALK ABOUT
A NEW INITIATIVE I THINK DAVID
REFERENCED THE CANNABIS RESOURCE
CENTER AND TELL US WHAT THAT
WILL PROVIDE FOR EVERYBODY.
>> GOOD AFTERNOON, EVERYONE.
SO I'M NOT SURE IF THE SLIDE SET
IS ON ITS WAY UP OR --
>> APOLOGIES FOR THE TECHNICAL
DIFFICULTY WE'LL DO IT VERBALLY
IN THE INTEREST OF TIME.
GOOD AFTERNOON, EVERYONE.
MY NAME IS PATRICK STILL.
I'M A PROGRAM DIRECTOR AT THE
BASIC AND MECHANISTIC BRANCH
HERE AT NCCIH AND I ADMINISTER
A
PORTFOLIO ON PART OF OUR NATURAL
PRODUCT AREAS WE COVER.
AND I WANT TO THANK EVERYONE
VIRTUALLY AND IN PERSON FOR
ATTENDING AND WE'RE EXCITED DO
HAVE YOU HERE.
I'LL BE DISCUSSING AN RFA THAT
WAS PUBLISHED JUST LAST OCTOBER
FOR A RESOURCE CENTER FOR
CANNABIS AND CANNABINOID
RESEARCH.
AND THIS WAS LED BY NCCIH IN
PARTNERSHIP WITH NIDA, NIA AND
NCI AND WALK YOU THROUGH
VERBALLY IN THE ABSENCE OF OUR
SLIDES THIS AFTERNOON.
WE KNOW THAT CANNABIS AND ITS
CONSTITUENTS HAVE A WIDE VARIETY
OF PHARMACOLOGIC EFFECTS AND THE
PUBLIC POLICY AND LEGALIZATION
LANDSCAPE HAS BEEN CHANGING
QUITE RAPIDLY AND DESPITE THIS
WIDESPREAD AVAILABILITY OF
VARIOUS CANNABIS PRODUCTS AND
ESTABLISHED PHARMACEUTICAL
POTENTIAL THERE'S STILL
SIGNIFICANT BARRIERS TO
CONDUCTING RESEARCH IN THE AREA.
THE PURPOSE OF THE RESOURCE
CENTER YOU SEE IN YOUR AGENDA.
THE PURPOSE OF THE PROPOSED
RESOURCE CENTER AND THE TO BE
FUNDED RESOURCE CENTER WOULD BE
TO ADDRESS BARRIERS TO
CONDUCTING RESEARCH IN THE FIELD
OF CANNABIS AND GENERATE DATA
ACROSS THE DOMAINS DISCUSSED
TODAY BASIC AND CLINICAL.
SO OVER THE PAST SEVERAL YEARS
NCCIH AND OTHER PARTNER
INSTITUTIONS HAVE ORGANIZED A
VARIETY OF PRINCIPLE
INVESTIGATOR MEETINGS LIKE THE
ONES WE'RE HERE FOR TODAY AND
THERE'S BEEN HIGHLIGHTED
BARRIERS AND CHALLENGES TO
RESEARCH IN THIS FIELD AND IN
2022, NCCIH ISSUED A REQUEST FOR
INFORMATION TO SOLICIT THE
COMMUNITY TO IDENTIFY BARRIERS
IN RESEARCH OF THE FIELD AND THE
RESULT OF THE RFI WERE SCHEDULE
1 STATUS AND CHALLENGES IN
OBTAINING AND MAINTAINING
LICENSING AS WELL AS ISSUES FOR
INDs AND CHALLENGES.
TO ADDRESS THE CHALLENGES WE
ISSUED THE RFA FOR THE RESOURCE
CENTER.
AND SO THE SERVICES THAT ARE TO
BE PROVIDED BY THIS AND HOW IT
WOULD HELP THE COMMUNITY ARE
ENVISIONED IN THREE CORE
COMPONENTS THAT APPLICATIONS
THAT ARE APPLY TO THIS
INITIATIVE HAD TO HAVE INCLUDING
THE REGULATORY GUIDANCE CORPS,
RESEARCH STANDARDS CORPS AND
RESEARCH SUPPORT CORPS.
THE REGULATORY GUIDANCE CORE IS
TO LINK TO EXISTING FDA GUIDANCE
FOR EXAMPLE.
RESEARCH STANDARD CORPS WOULD
PROVIDE FOR STANDARDS
APPROPRIATE FOR RESEARCH AND THE
SUPPORT CORPS WOULD PROVIDE SEED
FUNDING FOR REGULATORY SUPPORT
IN RESEARCH APPLICATION
DEVELOPMENT.
SO THERE'S A NUMBER OF A LA
CARTE RESEARCH AREAS FOR US AND
OUR PARTNER INSTITUTIONS THAT
RESOURCE APPLICANTS CAN RESPOND
TO AND SOLICIT APPLICATIONS FOR
SEED FUNDING PROPOSALS I
ENCOURAGE TO LOOK AT WITHIN THE
RFA.
WE'RE EXCITED AT NCCIH ABOUT THE
CENTER AND THE POTENTIAL TO
SERVE AS A FOCAL POINT FOR
CANNABIS RESEARCH AND HAPPY TO
ANSWER QUESTIONS AND THREW FOR
YOUR ATTENTION.
>> LIKE YOU SAID, IF WANT TO
HAVE MORE CONVERSATIONS REACH
OUT.
NEXT IS DR. ARCHING LA ARENSDORF
TALKING ABOUT TRANS GROUP WE
CALL T CREW THIS IS COMPOSED OF
MANY I.C.s AND ANGELA WILL TELL
US WHAT THEY'VE BEEN UP TO.
BEAUTIFUL PRESENTATION.
>> I'M ALSO GOING TO PUT A PLUG
IN FOR NASEM REPORT AND I READ
IT AND IT'S A LOT THERE.
I'M NOT GOING TO BELABOR THE
POINT HERE.
THE TAKE HOME MESSAGE IS THAT WE
NEED MORE RESEARCH INTO THE
HEALTH EFFECTS OF THIS BUT I
RECOMMEND EVERYBODY LOOK AT THIS
BECAUSE IT'S A GREAT DATA
SOURCE.
THIS IS WHERE WE STARTED WITH
THE REPORT AND SAW THE NEED FOR
MORE AFFECTS INTO THE POTENTIAL
AND THERE'S A GRAPH OF NIH
FUNDING FOR CANNABIS AND
CANNABINOID RELATED RESEARCH
FROM 2018 TO 2022.
AND SADLY I DID NOT GET THE
UPDATED DATA FOR 2023 BY THE
TIME WE NEEDED IT.
IF THE KEY WAS THERE, THE BLUE
LINE WOULD BE HOW MUCH
COLLECTIVELY WE HAVE BEEN
SPENDING ON THERAPEUTIC
CANNABINOID RESEARCH AND THE RED
IS ALL OTHER CANNABINOID
RESEARCH AND YOU CAN SEE THAT
WE'RE STILL NOT INVESTING AS
MUCH AS IN THE THERAPY AS IN THE
OTHER.
BUT WE'RE GOING UP SO THAT IS
NICE.
WE'RE TRYING TO FIGURE OUT HOW
TO WORK ACROSS THE NIH TO
CONTINUE THE TRAJECTORY OF
THERAPEUTIC POTENTIAL RESEARCH
GOING UP.
I BELIEVE IN 2022 WE ESTABLISHED
A TRANS-NIH WORKING GROUP
BECAUSE WE LOVE OUR GROUPS.
AND WE HAVE AFFECTIONATELY
REFERRED TO IT AS T CREW WHICH
STANDS FOR THERAPEUTIC
CANNABINOID RESEARCH WORKING
GROUP.
THE GOAL FOR THE GROUP WAS THAT
WE WORK TOGETHER TO FIGURE OUT
HOW TO EXPAND CANNABINOID
RESEARCH AND THE RESEARCH
COMMUNITY.
WE DO A VARIETY OF ACTIVITIES
THESE ARE THE BIG FOUR AND
TRYING TO FIGURE OUT HOW TO
STRATEGIZE TO WORK WITHIN THE
DIETARY GUIDELINES AND RESEARCH
IN THE SPACE AND COLLABORATE AND
SHARE IMPORTANT INFORMATION AND
DEVELOP AND STRENGTHEN
I.C.-SPECIFIC INTEREST IN THE
SPACE.
ON THE RIGHT ARE THE NUMBER OF
NIH INSTITUTES AND CENTERS THAT
FORM THE RESEARCH.
AND THE ONES IN RED I WANT TO
HIGHLIGHT THOSE ARE THE ONES
THAT ARE T CREW MEMBERS.
THERE'S INTEREST ACROSS THE NIH.
IT ISN'T JUST US OR NIDA.
THERE'S A LOT OF POTENTIAL
FUNDING THERE.
SO WHAT HAVE WE ACCOMPLISHED
THUS FAR?
WITH HAVE DONE A GOOD JOB OF
INCREASING COMMUNICATION BETWEEN
THE I.C.s.
PATRICK MENTIONED THE RFI THAT
LED TO THE DEVELOPMENT OF THE
RESOURCE CENTER AND I'LL TALK
ABOUT THE GREAT RESOURCE THAT I
COUNT WHENEVER I CAN THAT ALSO
CAME OUT OF T CREW WHICH IS A
WEB PAGE DESIGN SPECIFICALLY FOR
RESEARCHERS.
WE TRIED TO MAKE IT A ONE-STOP
SHOP AND HAVE FOUR AREAS THE
FIRST IS SHOWING THE RESEARCH
INTERESTS AND IF YOU HAVE A
SPECIFIC INTEREST YOU CAN GO AND
TRY TO SEE WHAT II.C.OPPORTUNIT
AND THESE ARE SPECIFIC TO
CANNABIS AND CANNABINOID
RESEARCH.
THE NEXT IS A LIST OF THE
PROGRAM OFFICERS AND CONTACT
INFORMATION AND LASTLY LINKS TO
OTHER RESOURCES SUCH AS NIH
RESOURCES, FDA RESOURCES, DEA
RESOURCES.
THERE'S A LOT OF GREAT
INFORMATION HERE ALSO THERE'S
LINK TO REPORTER AND ALL THE
GRANTS THAT HAVE BEEN FUNDED AND
SEE WHAT HAS BEEN DONE WHEN YOU
PROPOSE YOUR IDEA.
THIS IS MY LAST SLIDE.
I WANT TO PUT IN ANOTHER PLUG.
RARITY ON THERE WILL BE A
SESSION ON THE SPECIFIC INTEREST
WE T CREW MEMBERS.
WITH THAT I WILL STOP AND NOT
SURE IF I MADE UP TIME.
>> NEXT WE HAVE A COLLEAGUE FROM
OUTSIDE NCCIH AND WE'LL HEAR
FROM MARY MacDONALD TELL US
ABOUT THE NIDA DRUG SUPPLY
PROGRAM AN OTHER RESOURCES THAT
MAY BE BENEFICIAL FOR YOUR
RESEARCH.
THANK YOU, MARY.
>> GOOD AFTERNOON I'M FROM NIDA
AND HERE TO UPDATE YOU ON THE
NIDA DRUG SUPPLY PROGRAM.
THE PROGRAM HAS BEEN IN
EXISTENCE SINCE THE EARLY 1980s
TO PROVIDE PRODUCTS TO
RESEARCHERS FREE OF CHARGE AND
OUR INVENTORY IS COMPRISED OF
ITEMS CONTROLLED BY THE FDA
EITHER COMMERCIALLY UNAVAILABLE
OR HARD TO GET OR EXPENSIVE FOR
RESEARCHERS AND THE PROGRAM IS
ADMINISTERED THROUGH A SERIES OF
CONTRACTS AND THE CONTRACTS
COVER THE PROCUREMENT OR
SYNTHESIS OF SMALL MOLECULE AND
PEPTIDES AND THEIR ANALYSIS AND
STORAGE AND ALSO A CONTRACT WITH
A MARIJUANA FARM FOR OUR
CANNABIS PRODUCTS.
THE PROGRAM COVERS A LOT OF
ACTIVITIES.
WE PRIMARILY REVIEW REQUESTS TO
THE DRUG SUPPLY PROGRAM AND
COMMUNICATE WITH THE RESEARCHERS
TO UNDERSTAND THEIR NEEDS OTHER
ARE REPORTS FROM THE DEA AND
FORENSICS TO FIND OUT EMERGING
COMPOUNDS THAT COULD BE OF USE
TO RESEARCHERS AND WE CAN GET
FOR THE INVENTORY.
THE PROGRAM ALSO PROVIDES AN --
ANALYTICAL CRYSTALLOGRAPHY AND
DO A METHOD DEVELOPMENT FOR
STUDIES AND CAN DO STABILITY
STUDIES FOR PLANT-BASED
MATERIALS FOR DRUG SUBSTANCES
AND PRODUCTS.
SO OUR INVENTORY COMPRISES
STIMULANTS, SEDATIVES, AND OTHER
PRODUCTS AND IF YOU DON'T SEE IT
YOU CAN CONTACT US WITH THE
QUESTION AND THE E-MAIL IS
LISTED.
AND THE SHOULD GET BACK TO YOU
QUICKLY TO LET YOU KNOW IF YOUR
COMPOUND IS IN THE INVENTORY AND
YOU CAN MOVE ON FROM THERE.
WE GET OUR CANNABIS THROUGH OR
CONTRACT WITH THE UNIVERSITY OF
PLIS MISS.
-- MISSISSIPPI AND FOR A LONG
TIME WE WERE THE ONLY PROVIDER
OF MARIJUANA RESEARCH AND THEY
RECENTLY APPROVED OTHERS AND
RESEARCHERS WHO RECEIVEFUL
FUNDING FOR THEIR WORK CAN ONLY
PROCURE MATERIALS THROUGH ONE OF
THESE FEDERALLY APPROVED
PROVIDERS.
OUR CANNABIS CONTRACT PROVIDES
CANNABIS FOR HUMAN USE AND
EXTRACTS AN CANNABINOIDS AND
ONCE AGAIN THESE MATERIALS ARE
ALSO AVAILABLE FREE OF CHARGE TO
RESEARCHERS WHO SUBMIT COMPLETE
REQUEST PACKAGES APPROVED.
AND THE GROUP MAINTAINS THE DRUG
MASTER FILES AND KEEP A
COLLECTION OF THE GERMPLASMS FOR
THE VARIOUS PLANT VARIETIES AND
ALSO RUN A POTENCY MONITORING
PROGRAM IN WHICH THEY ANALYZE
SAMPLES THAT ARE CONFISCATED BY
LAW ENFORCEMENT.
THE SPECIFIC PRODUCTS WE GET
FROM THE UNIVERSITY OF
MISSISSMISS
INCLUDE HOMOGENIZED PLANT
MATERIALS AND GET BULK PLACEBO
PLANT MATERIAL FOR HUMAN USE.
THERE'S A NUMBER OF PURIFIED
CANNABINOIDS INCLUDING DELTA 9,
THC AND DELTA 8 AND CDC, CBG AND
THERE'S NCBD RICH EXTRACT FOR
HUMAN USE AND MAKE CANNABIS
CIGARETTES AVAILABLE IN PLACEBO
AND ACTIVE FORMS.
THEY USE THE STRAIGHT ROLL
CIGARETTES BUT WE CAN MAKE THEM
USING THE CONE-SHAPED ROLLERS.
THE HUMAN USE PRODUCTS ARE
PRODUCED UNDER GMP CONDITIONS AN
SHOW THEY MEET THE
SPECIFICATIONS SET BY THE FDA.
THE CERTIFICATES OF ANALYSIS
INCLUDE THE PERCENTAGES OF
CANNABINOIDS AND PRESENCE OF
PESTICIDES AND AFLATOXINS AND
MICROORGANISMS AND BECAUSE IT'S
DIFFICULT TO GROW PLANT MATERIAL
UNDER STERILE CONDITIONS THEY
ADDED AN ERADICATION PROCESS AND
CHECK IT BEFORE AND AFTER TO
LOOK AT THE MOISTURE CONTENT
REMAINS THE SAME AND THEY DO.
SO IF YOU ARE INTERESTED IN
SUBMITTING A REQUEST TO THE DRUG
SUPPLY PROGRAM, YOU CAN CONTACT
THE MAILBOX AT THE E-MAIL SHOWN
ABOVE AND THE FOLKS WILL SEND
YOU A LIST OF REQUIRED DOCUMENTS
YOU'LL NEED FOR A COMPLETE
REQUEST PACKAGE AND SOME OF THE
ITEMS HERE STATE WHAT YOU WANT
AND HOW MUCH YOU NEED AND THE
REVIEW PROCESS IS REALLY TO
JUSTIFY THE AMOUNT THAT YOU'RE
REQUESTING.
SO THE PROTOCOL IS TO PUT
EVERYTHING IN CONTEXT AND WE
LIKE TO SEE CAL CLAYING --
CALCULATIONS AND IF YOU GO TO
THE SOURCE OF FUNDING YOU DO NOT
NEED TO HAVE NIH FUNDING TO
OBTAIN PRODUCTS FROM THE
PROGRAM.
IF YOU HAVE EXTERNAL FINDING,
WE'LL SEND THE REDACTED PACKAGE
OUT TO TWO EXTERNAL REVIEWERS
WHO WILL REVIEW IT TO JUSTIFY
THE AMOUNT OF PRODUCTS YOU'RE
ASKING FOR AND WE'LL GO ON FROM
THERE.
BUT IN OTHER KEY PIECES OF
INFORMATION ARE A COPY OF YOUR
DEA LICENSE OR A COPY OF YOUR
LICENSE FOR RADIO ACTIVITY.
IF YOU'RE DOING IN VIVO STUDIES
AN WANT TO AN APPROVED IRB AND
WE SAY THE REVIEW PROCESS TAKES
FOUR TO SIX WEEKS BECAUSE THERE
ARE MULTIPLE LEVELS OF REVIEW.
SO WITH THAT SAID, THANK YOU FOR
YOUR ATTENTION AND I'M WILLING
TO TAKE ANY QUESTIONS
AFTERWARDS.
>> THANK YOU SO MUCH.
THE LAST SPEAKER IS SOMEBODY
WHO'S LOGO YOU MAY HAVE SEEN IN
A PRIOR SLIDE, HUNTER LAND WHO
WORKS WITH THE PHARMACEUTICAL
RESEARCH AND WILL TALK ABOUT
COMMERCIAL SUPPLIERS FOR
CANNABINOIDS.
>> THANK YOU.
I'M HUNTER LANCE, VICE PRESIDENT
OF RESEARCH AND DEVELOPMENT AT
BRC AND THANK YOU TO THE
ORGANIZERS FOR INVITING PE IING
TODAY.
I DON'T THINK IT WILL TAKE FIVE
MINUTES BUT I'LL INTRODUCE WHO
BRC IS.
WE'RE A SCHEDULE 1 PRODUCER OF
CANNABIS AND CANNABINOIDS AND
OUR MISSION IS TO SEE IF
CANNABINOIDS CAN WORK IN CERTAIN
DISEASE STATES.
WE DO PROVIDE AN API OR
FORMULATIONS FOR RESEARCHERS TO
WORK WITH US IN COLLABORATION OR
ON THEIR OWN.
MANY DIFFERENT PROCESSES TO
CONSIDER.
THESE ARE OUR DEA REGISTRATIONS.
WE HAVE SIX AND CAN IMPORT AND
EXPORT AND FORMULATE AND
ETCETERA.
WE HAVE MANY FORMULATIONS WITH
ACCELERATED STABILITY UP TO TWO
YEARS NOW WITH MANY DIFFERENT
CANNABINOIDS THAT COULD
POTENTIALLY BE AVAILABLE.
WE DO MANUFACTURE UNDER GMP AND
WE DO NOT BREAK FEDERAL LAW
WHATSOEVER SO YOU'LL NEVER SEE
PROMOTIONAL MATERIAL FROM US AND
EVEN OUR NAME DOESN'T HAVE COOL
NIFTY CANNABINOID CONNECTION.
IT'S JUST BRC.
SO I THINK THAT PRETTY MUCH SUMS
THAT PART UP.
WE ARE DEDICATED TO COMPLIANCE
AND QUALITY.
WE BELIEVE IN GMP.
WE HAVE SYSTEMS FOR CORRECT
MANAGEMENT AND WE'VE GOT SEVERAL
INDs OPEN AND ENROLLING HUMAN
PATIENTS AND HAVE DONE
PRE-CLINICAL WORK AS WELL AND
HAVE A REPUTABLE TEAM.
OUR CEO IS A FORMER NAVY SEAL
AND ALSO A STANFORD BUSINESS
GRAD.
WE HAVE A WHOLE LIST OF
RESEARCHERS WITH CANNABINOID
BACKGROUNDS.
FORMER DEA, FORMER SCIENTISTS
AND CHEMISTS THAT KNOW HOW TO
MANUFACTURE AND FOLLOW
ESTABLISHED PATHWAYS FOR
CANNABINOIDS AND DRUG
DEVELOPMENT.
WE HAVE INDUSTRY EXPERIENCE AND
KEY ADVISORS TO MAKE SURE WE
STAY ON THE STRAIGHT AND NARROW
PANEL.
YOU MAY RECOGNIZE SOME OF THESE
PEOPLE HERE.
AS WELL AS FORMER COLLEAGUES
LIKE KATHERINE MAIR WE WORKED
TOGETHER AT GWU AND MANY MAY
KNOW BRIAN THOMAS INVOLVED WITH
US AS WELL.
THAT CONCLUDES MY VERY SHORT
INTRODUCTION TO BRC BUT IF
YOU'RE INTERESTED IN
COLLABORATING OR API, FEEL FREE
TO REACH OUT.
THANKS.
>> ALL RIGHT.
WE HAVE A FEW MINUTES FOR
QUESTIONS.
WE ARE ACTUALLY QUITE GOOD ON
TIME AT THE MOMENT.
SO PLENTY OF TIME FOR QUESTIONS.
YOU LINE UP EVERYBODY.
ALICE, FIRST QUESTION OF HUNTER.
DO YOU GUYS HAVE JUST THE CRUDE
MATERIAL OR PLANT EXTRACTS?
>> WE CAN POTENTIALLY SUPPLY
[OFF-MIC]
WE DON'T HAVE A STOCK OF EVERY
MINOR CANNABINOID IN A NEUTRAL
FORMAT AND EVERY SIMULATION.
WE HAVE A VARIETY OF THINGS TO
PRODUCE OR CAN COLLABORATE WITH
ON RESEARCH.
>> THANK YOU.
ANY OTHER QUESTIONS FOR THE NIDA
FOLKS ON ONGOING RESOURCES AND
ACTIVITIES.
IT MUST BE GETTING LATE IN THE
DAY.
PEOPLE HAVE FLIGHTS TO CATCH.
ZIVA WILL CATCH ONE RIGHT NOW.
>> I'LL ASK A GENERAL QUESTION
BASED ON THE U24 AND NIDA DRUG
SUPPLY.
WHAT IS RESCHEDULING POTENTIALLY
REDO TO THOSE THINGS.
THAT TOOK PLACE AFTER.
>> WE WERE AFRAID YOU'D ASK THAT
QUESTION.
I DON'T THINK IT'S BAD
NECESSARY.
>> I THINK AS WE WERE THINKING
ABOUT THIS OBVIOUS ELEPHANT IN
THE ROOM I THINK WHAT WE CAME
TO -- WE ALL KNOW IS THE ANSWER.
AND THEY HAVEN'T ACTUALLY
CHANGED IT YET.
NOTHING HAS CHANGE.
WE'RE STILL IN THE EXACT SAME
REGULATORY ENVIRONMENT AS WHEN
THIS WAS ANNOUNCED.
IT WILL TAKE AT LEAST A YEAR TO
CHANGE AND THEN THE DETAILS --
WHAT EXACTLY IS GOING TO CHANGE?
I WOULD SUSPECT THERE'S LOTS OF
INDICATIONS FOR WHAT THIS MEANS
AND I DON'T HAVE ANSWER UNLESS
MARY WANTS TO CHIME IN THERE.
NIDA MEETS SCHEDULE 1 CRITERIA.
I SUSPECT THOSE WHO HAVE A
SCHEDULE 1 WILL HAVE MATERIAL
AND THERE WILL STILL BE TRACKING
OF PLANT AND API.
BECAUSE IT'S SCHEDULE 3 DOESN'T
MEAN YOU CAN JUST GO GET IT.
THERE'S STILL KETAMINE AND
THINGS LIKE THAT ON SCHEDULE 1
YOU CAN'T JUST GET.
ANYBODY IN THAT SITUATION NOW
WILL STILL BE ABLE TO APPLY MORE
QUICKLY.
>> TO POINT OUT THAT THE NOTICE
OF PROPOSED RULE MAKING HAS BEEN
PUBLISHED AND THERE'S A 60 DAY
OPEN PERIOD FOR COMMENTS.
IF YOU READ THROUGH THAT, YOU
WILL NOTICE THERE'S ATTENTION
MADE TO WHAT THE IMPACT WILL BE
IN RESEARCH.
WE'LL SEE ABOUT CHANGES IN VERY
LITTLE ABOUT RESEARCH AND SO
ANYBODY COULD COMMENT AND PEOPLE
IN THE ROOM WILL BE MOST
EFFECTED AND YOU HAVE AN
OPPORTUNITY TO WEIGH IN AND SAY
I HOPE YOU MAKE IT EASIER TO DO
RESEARCH.
IT'S POSSIBLE.
THERE'LL BE A LONG LIST OF RULES
SIMULATIONS THAT COME OUT IN THE
PROCESS AND THE DEVIL IS ALWAYS
IN THE DETAIL AND WHAT IT WILL
MEAN FOR RESEARCHERS TO GET
REGISTERED AND WHAT IT WILL MEAN
FOR ACCESS TO DISPENSARY
PRODUCTS IS STILL UP IN THE AIR
AND THE DEA CAN MAKE IT EASIER
BUT WE'LL NEED TO HEAR FROM
PEOPLE HOW IT WILL BE AFFECTIVE.
>> THE QUESTION WHETHER YOU CAN
NOW USE YOUR LOCAL DISPENSARY
FOR YOUR FEDERALLY FUNDED
RESEARCH.
YOU CAN'T DO IT NOW FOR SURE BUT
WILL YOU BE ABLE TO WHEN IT'S
SCHEDULE 3?
I GUESS THAT DEPENDS ON HOW THEY
WRITE THE RULE.
ANYBODY ELSE HAVE QUESTIONS OR
COMMENTS?
WE STILL HAVE 15 MINUTES IN THE
SESSION.
>> SO THE RESOURCE FUNDED BY
NCCIH, HOW DOES NCCIH ENVISION
THE RESEARCH CENTER WILL BE
SERVED FOR RESEARCHERS?
FOR EXAMPLE, AT THE MEETINGS IN
THE FUTURE, WILL THERE BE
REPRESENTATIVES FROM THE
RESEARCH CENTER THAT WILL BE
ABLE TO ANSWER ANSWER QUESTIONS
OR GUIDE RESEARCHERS ON HOW TO
SUBMIT INDs OR PROCURE PRODUCT?
HOW WOULD -- WHAT'S THE VISION
FOR HOW IT WILL ALL COME
TOGETHER TO BE ABLE TO PROVIDE
THIS REALLY IMPORTANT RESOURCE
AS YOU CAN SEE FROM THE TALKS
EARLIER TODAY.
I THINK ACROSS THE BOARD PEOPLE
ARE HAVING A HARD TIME WITH
THIS.
>> THE RESOURCE CENTER UP WAS IN
DIRECT RESPONSE TO WHERE CAN I
GO TO THIS PARTICULAR
CANNABINOID AND WHEN THEY'RE
STOOD UP AND RUNNING WILL HAVE
READY ANSWERS AND GUIDE ANCESS
-- GUIDANCES.
THEY WON'T BE TESTING YOUR
PRODUCT OR SUBMITTING ON YOUR
BEHALF BUT HOPEFULLY BE ABLE TO
TELL YOU HOW TO NAVIGATE THE
REGULATORY FRAMEWORK THAT YOU
HAVE TO NAVIGATE TO DO
CANNABINOID RESEARCH.
>> I FEEL LIKE IF WE WERE TO
TALK TO FDA TO GET GUIDANCE FROM
THEM -- I'M WONDERING WILL THERE
BE AN INFRASTRUCTURE THROUGH
NCCIH TO WORK WITH THE DIFFERENT
AGENCIES OR JUST A RESOURCE
CENTER TRYING TO FIGURE IT OUT?
>> IT'S A COOPERATIVE AGREEMENT.
THERE'LL BE A LOT OF NCCIH AND
WITH FUNDING PARTNERS, NCI AND
NIA AND NIDA AND AS WRITTEN WE
DID ANTICIPATE THIS GROUP AND
THERE'LL AB A STEERING COMMIT
GROUP THERE WILL HAVE OPEN LINES
OF COMMUNICATION WITH FDA AND
DEA TO PROVIDE GUIDES.
WE CAN'T SPEAK FOR DEA OR FDA
BUT HOPEFULLY WE CAN BE
COMMUNICATIVE WITH THEM SO WE'RE
TALKING THE SAME HANG --
LANGUAGE AND PROVIDE IF FDA HAS
A RESOURCE IF YOU TRIED TO
NAVIGATE THEIR WEBSITE IT'S
HARDER THAN NIH AND HOPEFULLY
THE GROUP CAN FIND IT FOR YOU
AND POINT IT OUT TO YOU AND HAVE
IT READY IN THE LIBRARY
SOMEWHERE OF THINGS THEY WOULD
BE ABLE TO SHARE.
AND THIS IS MEANT FOR I WANT TO
GET IN THIS FIELD BUT DON'T KNOW
HOW TO START.
YOU GUYS ARE MORE OF THE
ADVANCED GROUP IN THE FIELD AND
HAVE ALREADY DONE IT AND YOU
GUYS HAVE YOUR OWN SET OF
CHALLENGES.
BUT THIS IS GEARED TO PEOPLE
TRYING TO BREAK INTO THE
CANNABINOID FIELD OR TRYING TO
EXPAND THE ROSTER OF PEOPLE WHO
CAN DO CANNABINOID RESEARCH BUT
THERE'S HIGH BARRIERS TO GET
PEOPLE INTO THE FIELD AND HOPING
THE RESOURCE CENTER WILL HELP
BREAK SOME OF THOSE DOWN.
>> THANK YOU.
ALL RIGHT, WELL WE CAN MOVE ON
TO THE NEXT SESSION.
THANK YOU TO ALL THE SPEAKERS
AND TO EVERYONE ELSE.
WE'LL GO TO THE NEXT ONE.
THANK YOU, DR. HOPP.
I WILL THANK OUR GREATER
SPEAKERS.
A PARTICULAR THANKS TO NON-NIH
AND NON-P.I. SPEAKERS.
SO NOW WE'LL HAVE A BREAK
ACTUALLY.
I WANTED TO LET YOU KNOW THAT
ONE SESSION THAT WILL BE VERY
IMPORTANT FOR YOU SO WE WILL
HAVE OUR FDA SPEAKER AND HAVE
OUR CANNABIS POLICY AND IMPACT
ON RESEARCH TALKS SO PLEASE BE
PREPARED WITH YOUR QUESTIONS SO
WE WILL HAVE THIS SESSION AFTER
THE BREAK AND THE FINAL SESSION
WILL BE WITH MY COLLEAGUES FROM
DIFFERENT INSTITUTES AND NOW
ENJOY THE BREAK.
THANK YOU.
I WILL SEE YOU AT 3:30 IN THE
ROOM.
THANK YOU.
CAPTIONS RETURN SHORTLY
SCHOOL-BASED STUDY AND FOUND 11%
OF 12th GRADE STUDENT IN THE
STUDENTS HAVE USED DELTA 8 IN
THE PAST YEAR AND WE WERE
SURPRISED HOW HIGH THE NUMBER
WAS AND UNDER SCORES HOW
IMPORTANT IT IS TO DO RESEARCH
AND HOW PEOPLE ARE USING THE
SUBSTANCES AS WELL AS THE IMPACT
ON PUBLIC HEALTH.
SO BEYOND DELTA 8 WE TALKED
ABOUT OTHER COMPOUNDS, THC A AND
DELTA 8 AND OTHERS AND THESE
PRODUCTS MAY BE HEMP OR NON-HEMP
DERIVED AND IMPACTS THE CONTROL
STATUS AS WE'LL TALK ABOUT IN A
LITTLE BIT.
I'M NOT CAUSING THAT.
ANYBODY ONLINE AND JOINED THE
ZOOM COULD YOU PLEASE MAKE SURE
YOU MUTE YOURSELF, YOU.
CANNABIS PRODUCTS CONTAINING
DELTA 9 ON -- THES THIS IS FOR
SUBSTANCES WITH HIGH USE AND IN
2019 CONGRESS PASSED THE ACT TO
DECONTROL -- CANNABIS LESS THAN
OR EQUAL TO -- OKAY, WELL THEN
SO IMPORTANTLY THE A.I. OR FARM
BILL DID NOT IMPACT THE THCs AND
IMPACTS REGULATING FOR THE
COSMETICS ACT AND 38 STATES AND
THE DISTRICT OF COLUMBIA PASSED
MEDICAL CANNABIS RAISE AND
THEY'RE HIGHLY VARIABLE IN TERMS
OF ALLOWABLE CONDITIONS FOR
WHICH MEDICAL CANNABIS CAN BE
USED AND WHETHER IT'S AVAILABLE
IN DISPENSARIES AND WHETHER
STATES HAVE REGISTRIES AND
TESTING AND REGULATORY
ENVIRONMENTS.
AND AT THE STATE LEVEL THE
LEGALITY THERE'S VARIABILITY IN
HOW STATES TREAT THEM IT'S A
PATCH WORK.
WHAT ARE REGULATORY CHALLENGES
FOR CONDUCTING CANNABIS AND
CANNABINOID RESEARCH THE BIGGEST
RELATE TO THE CONTROL STATUS OF
COURSE.
MARIJUANA FOR CANNABIS WITH MORE
THAN 4.3% THC REMAINS A SCHEDULE
1 DRUG AND THIS CONTRIBUTES TO
REAL CHALLENGES FOR RESEARCHERS
IN TERMS OF GETTING THAT
SCHEDULE 1 REGISTRATION
ADMINISTRATIVE AND COST
CHALLENGES.
AND WE HEARD IT CAN TAKE UP TO A
YEAR TO GET SCHEDULE 1
REGISTRATION AND MAY BE REQUIRED
FOR EACH RESEARCHER IN YOUR LAB
OR WITHIN DEPARTMENT.
IF YOU HAVE MULTIPLE LABS YOU
MAY BE REQUIRED TO REGISTER EACH
SITE AND THERE'S VARIABILITY IN
TERMS OF HOW IT'S TREATED.
WE HEARD IT'S EXPENSIVE TO
IMPLEMENT THE RIRT -- REQUIRES
CAMPUS TO MAKE ROOM AND COULD BE
TIME CONSUMING AND POSE A
CHALLENGE WITH THOSE WITH LESS
RESOURCES AND THERE'S
VARIABILITIES.
STATES HAVE THEIR OWN CONTROLLED
SUBSTANCES REGULATIONS AND
DIFFERENT UNIVERSITIES MAY HAVE
DIFFERENT REQUIREMENTS AND YOU
MAY HAVE TO ENROLL OR NOT AND
ALL THAT SERVES AS A COMPLICATED
REGULATORY FRAMEWORK FOR
INVESTIGATORS TO NAVIGATE.
THERE'S ALSO BEEN CONFUSION OVER
THE REGULATORY STATUS OF
CANNABIS PRODUCTS.
I MENTIONED EARLIER HEMP DERIVED
CANNABINOIDS WITH LESS THAN THAT
.3% THC ARE NOT CONTROLLED UNDER
THE CSA BUT IF THE PRODUCTS ARE
NON-HEMP DERIVED THEY MAY IN
CONTROLLED AND YOU HAVE A
SITUATION WHERE AN IDENTICAL
CHEMICAL MAY BE CONTROLLED OR
DE-CONTROLLED DEPENDING ON THE
PROMINENCE.
THJ ANOTHER EXAMPLE IN THE NEWS
A PRECURSOR THAT CONVERTS TO
DELTA 9 READILY WHEN HEATED AND
WE -- THE NEWS REPORTS
INDICATING SENIOR DEA OFFICIALS
INDICATED THC A LEVEL HAS TO BE
TAKEN INTO ACCOUNT WHEN
CONSIDERING THE DELTA 9 LEVEL
MEETS THE THRESHOLD AND
CONTROLLING THE THCA AND THIS IS
SOMETHING A POTENTIAL REGISTRANT
COMMUNICATED ABOUT THIS AND THIS
CAME OUT IN THE NEWS.
IT'S COMPLICATED FOR RESEARCHERS
TO NAVIGATE AS IS PROBABLY NO
SURPRISE TO PEOPLE IN THE ROOM.
AND DISPENSARY PRODUCTS CAN BE
REGULATED AND UNTIL RECENTLY
NIDA WAS THE ONLY DOMESTIC
SOURCE FOR MARIJUANA FOR
RESOURCE AND HAVE NEWLY
REGISTERED MANUFACTURERS BUT I
THINK IT'S A QUESTION OF HOW
WIDELY THEY'RE PROVIDING
PRODUCTS TO EXTRAMURAL
RESEARCHERS.
AND LATELY THERE'S BEEN IN AN
CLEAR PATH TO DRUG DEVELOPMENT
BECAUSE THE NIDA DRUG SUPPLY
HASN'T BEEN ABLE TO SUPPLY
SUFFICIENT DEVELOPMENT AND SCALE
UP AND THE PRODUCT REQUIRED IN
MONITORING HAS TO BE EQUIVALENT
TO THE PRODUCT USED FOR THE IND.
THAT CREATED CHALLENGES FOR
MEDICAL PRODUCT DEVELOPMENT.
ALSO NOTE THAT LAST YEAR
CONGRESS PACKED THE CANNABINOID
ACT AND EXPANDING RESEARCH ON
CANNABIS AND CANNABIS PRODUCTS
INCLUDING BY INCREASING THE
NUMBER OF AND VARIETY OF
MANUFACTURERS AUTHORIZED TO
PROVIDE MARIJUANA FOR RESEARCH
AND FACILITATING THE PROCESS OF
OBTAINING A SCHEDULE 1
REGISTRATION TO CANNABIS
RESEARCH.
IT WOULD NOT, DID NOT ADDRESS
ACCESS TO STATE DISPENSARY
PRODUCTS.
THE LAW MUST BEING IMPLEMENTED
BY THE D.A. AND HAVEN'T SEEN
REGISTRATION FOR THE PROCESS AND
REMAINS TO BE SEEN HOW IT WILL
IMPACT THE SCHEDULE 1 PROCESS
AND WHETHER IT WILL MAKE IT
EASIER TO GET THE REGISTRATION.
WE HAVE FREQUENTLY ASKED
QUESTIONS ON OUR WEB PAGE AND
LINKED FROM THE RESOURCES THAT
ANGELA TOLD YOU ABOUT.
IT HELPS FROM NAVIGATE AND
ADDRESSES ISSUES LIKE WHEN IS A
SCHEDULE 1 REGISTRATION
REQUIRED.
THAT IS A VERY SHIFTING
LANDSCAPE AND YOUR BEST BET
ABOUT THE CONTROL STATUS OF A
PRODUCT IS TO CONTACT THE DEA.
AND WE PROVIDE THE GUIDANCE BUT
THAT'S THE ULTIMATE BOTTOM LINE
AND ADDRESSES WHERE RESEARCHERS
CAN OBTAIN CANNABIS PRODUCTS FOR
RESEARCH AND THE DRUG SUPPLY AND
DEA MANUFACTURERS AND WHETHER
FEDERAL OR NON-FEDERAL FUNDS CAN
BE USED TO HANDLE THE PRODUCTS
IF YOU'RE AN NIH RESEARCHER.
THE SHORT ANSWER IS NO.
IT DISCUSSES WHAT RESEARCH IS
PERMISSIBLE WITH PRODUCTS
OBTAINED BY DISPENSARIES AS WELL
AS WHETHER AN IND IS NEEDED AND
FOR THAT WE DIRECT YOU TO THE
FDA.
AGAIN, IF YOU HAVE REGULATORY
QUESTIONS IT'S BEST TO CONTACT
THE REGULATORY AGENCIES AND WE
HAVE CONTACT INFORMATION FOR THE
FDA AND YOU CAN ACCESS THAT VIA
THE QR CODE OR LINK BELOW AND I
WANT TO MENTION THAT NIDA AND
NATIONAL CANCER INSTITUTE ARE
SPONSORING THIS STUDY FROM THE
NATIONAL ACADEMIES ON THE PUBLIC
HEALTH CONSEQUENCES OF CHANGES
IN THE CANNABIS POLICY LANDSCAPE
AND THE COMMITTEE IS ADDRESSING
CANNABIS AND CANNABINOID
AVAILABILITY AND LOOKING AT
FRAMEWORK FOR THE CANNABIS
INDUSTRY AND OUTLINING
RECOMMENDATIONS TO MINIMIZE
POTENTIAL HARMS AND INFORM
POLICY RESEARCH OVER THE NEXT
FIVE YEARS.
THAT REPORT SHOULD COME BY THE
END OF THE YEAR AND WILL BE A
USEFUL RESOURCE TO ALL OF YOU.
THAT'S IT AND THANK YOU VERY
MUCH.
>> THANK YOU SO MUCH.
WE'LL MOVE ON TO OUR NEXT
SPEAKER AND AFTER I'LL INVITE
YOU TO JOIN ME WHERE YOU GOT
MICS AVAILABLE TO ANSWER
QUESTIONS.
SO, OUR NEXT SPEAKER IS
DR. REISSIG AT THE CENTER FOR
DRUG EVALUATION AND RESEARCH AT
THE U.S. FOOD AND DRUG
ADMINISTRATION.
HE HAS BEEN A PHARMACOLOGIST AT
FDA FOR 15 YEARS AND LEADS THE
PHARMACOLOGY TEAM IN THE REVIEW
AND EVALUATION OF DRUGS OF
ABUSE.
PRIOR TO JOINING THIS GROUP, HE
SERVED AS THE BEHAVIORAL AND
CLINICAL PHARMACOLOGY BRANCH
CHIEF AT THE CENTER FOR TOBACCO
PRODUCTS AT FDA AND WILL BE
PRESENTING CURRENT PRACTICES IN
REVIEWING THE INVESTIGATIONAL
NEW DRUG APPLICATIONS INVOLVING
CANNABIS AND HEMP PRODUCTS.
I'LL TURN THINGS OVER TO YOU.
>> WHAT A FLATTERING
INTRODUCTION.
I'M A PHARMACOLOGIST WITH FDA AT
THE CONTROLLED SUBSTANCE STAFF
AND THE TITLE'S RIGHT THERE.
I'LL BE TALKING ABOUT OUR
CURRENT PRACTICES IN REVIEWING
INDs THAT INVOLVE CANNABIS AND
HEMP PRODUCTS.
THIS IS THE STANDARD FDA
DISCLAIMER.
THE TALK IS GOING TO BE MY VIEWS
ALONE AND NOT THOSE OF FDA
ESPECIALLY IF I MISS SPEAK FOR
SAY THAT OFFENDS YOU AND I
CONSIDER MYSELF A BEHAVIORAL
PHARMACOLOGIST AND THAT'S THE
LENS I REVIEW UNDER.
FDA'S A BIG PLACE AND ABOUT
18,000 PEOPLE WORK THERE AND
REGULATE A NUMBER OF PRODUCTS
AND WE REVIEW PRODUCTS AND WE
LOOK AT BOTH PRESCRIPTION AND
NON-PRESCRIPTION.
IF YOU WANT TO RESEARCH AND
DEVELOP CANNABIS PRODUCTS IT
STARTS WITH SUBMISSION AS AN IND
AND MOST PROBABLY KNOW IT
INCLUDES A LOT OF INFORMATION
AND INCLUDES THE CHEMISTRY AND
MANUFACTURING AND QUALITY
CONTROLS CALL THE CMC DATA AND
TOXICOLOGY AND YOU CAN REQUEST A
PREMEETING WITH THE FDA TO GET
OVERVIEW OF YOUR IND AND WE CAN
HELP YOU GET IT TOGETHER AND
SUBMIT IT.
WE HAVE SEEN A LOT OF GUIDANCES
TODAY THIS ARE THE MOST RELEVANT
ONES AND COMPOUNDS AND RECENT
ONES AND TALK ABOUT SOURCING AND
THE SAME MANUFACTURING QUALITY
CONTROLS AND HAD GUIDELINES FOR
ESTIMATING YOUR THC TO DETERMINE
WHETHER OR NOT YOU'LL MEET THE
HEMP DEFINITION AND THE CONTROL.
OF THE OLDER BOTANICAL DRUG
GUIDANCE FROM 2016 FOCUSES ON
QUALITY CONTROLS AND HAS
INFORMATION ON GROWING
CONDITIONS FOR YOUR RAW
BOTANICAL MATERIAL.
THERE'S THREE BASIC TYPES OF
INDs.
THE FIRST IS INVESTIGATOR IND
FAR AND AWAY THE MOST COMMON ONE
WE GET.
THAT IS SUBMITTED BY AN
INDIVIDUAL THAT WILL INITIATE
AND CONDUCT RESEARCH AND LOOK AT
THE INDs ADMINISTERED.
FOR EXAMPLE, PHYSICIAN OR
INVESTIGATOR COULD PROPOSE
STUDYING AN UNAPPROVED DRUG
BRAND NEW OR APPROVED PRODUCT OR
NEW INDICATION, A NEW PATIENT
POPULATION OR DOSE AND AN IND.
THERE'S EMERGENCY USE INDs THAT
ALLOWS US TO AUTHORIZE
EXPERIMENTAL DRUGS IN EMERGENCY
SITUATIONS AND APPLIES TO
PATIENTS THAT DON'T MEET
CRITERIA FOR EXISTING PROTOCOLS
BUT ARE PRETTY RARE RELATIVELY
SPEAKING AND THEN THERE'S DRUGS
THAT SHOW PROMISING TESTING FOR
SERIOUS AND LIFE-THREATENING
CONDITIONS.
INTERNALLY WE BREAK THEM IN
COMMERCIAL INDs WHERE WE THINK A
SPONSOR DECLARES THAT THEY WILL
BE USING THE IND TO SEEK
MARKETING APPROVAL AND A GENTLE
REMINDER FOR THOSE THAT DON'T
KNOW, PHASES 1 THROUGH 3 OF
CLINICAL TRIALS NEED TO BE
COMPLETED UNDER IND AND SPONSORS
HAVE TO SUBMIT AN NDA TO
FORMALLY PROPOSE US, FDA, TO
REVIEW THE PROPOSED DRUG TO GET
A MARKETING APPROVAL.
THE RESEARCH THAT PROBABLY
BROUGHT MANY OF YOU HERE IS
OPPOSITE.
WHERE THE SPONSOR INDICATES NO
MARKET APPROVAL AND THE REQUIRED
INFORMATION.
WE USE IN CLINICAL TRIALS
EVERYONE HAS TO MEET FDA
REQUIREMENTS AND THERE'S THREE
VERY BROAD AREAS.
THE FIRST TOXINS.
THIS HELPS DETERMINE WHETHER IT
IS REASONABLY SAFE FOR INITIAL
TESTING IN HUMANS.
THAT OFTEN INCLUDES ANY PREVIOUS
HUMAN EXPERIENCE, PRE-CLINICAL
STUDIES, IN VITRO STUDIES,
ETCETERA.
THEN THE BIG ONE, THE
MANUFACTURING INFORMATION, THE
CMC AND CHEMISTRY MANUFACTURING
AND CONTROLS.
THIS SECTION HAS INFORMATION
PERTAINING TO COMPOSITION, THE
MANUFACTURER, THE STABILITY AND
CONTROL FOR MANUFACTURING THE
DRUG SUBSTANCE IN THE DRUG AND
THE DRUG PRODUCT.
WE HEARD ABOUT THAT IN THE LAST
TALK ABOUT THE NIDA DRUG SUPPLY.
FDA USES THE INFORMATION TO
ENSURE THE COMPANY OR
INVESTIGATOR CAN ADEQUATELY
PRODUCE CONSISTENT REPRODUCIBLE
BATCHES OF THE DRUG.
SO SPONSORS MUST SUBMIT THIS
INFORMATION FOR OUR REVIEWERS TO
ENSURE IDENTIFY, QUALITY,
PURITY, POTENCY, EVERYTHING
ABOUT THE PRODUCT TO BE
ADMINISTERED.
AND IMPROVED QUANTITATIVE DATA
AND PHYTE SCRO -- PHYTO
CHEMICALS AND GUIDELINES TO HELP
ASSIST SPONSORS IN THEIR
ANALYTICAL METHODOLOGY FOR
PROVIDING THIS INFORMATION.
ANOTHER WAY TO MEET THE CMC
REQUIREMENTS IS THROUGH
AUTHORIZATION.
THAT ALLOWS THE REFERENCE TO A
DIFFERENT SPONSOR CMC THAT HAS
ALREADY BEEN ALLOWED BY FDA.
WE SEE THIS WITH A NUMBER OF
DRUGS WHERE IF AN INDs ALLOWED
TO PROCEED, ANOTHER ENTITY CAN
REFERENCE THE SAME IND.
AND YOU CAN ALSO SUBMIT A LETTER
OF AUTHORIZATION ALLOWING FOR
THE DRUG MASTER FILE HELD BY A
DIFFERENT ENTITY.
THE DMFs ARE SUBMITTED TO FDA
AND PROVIDE CONFIDENTIAL AND
DETAILED INFORMATION ABOUT THE
SUBSTANCE, INTERMEDIATES,
GROWING CONDITIONS,ING YOU CAN
INCLUDE THINGS LIKE PACKAGING
MATERIAL, EXCIPIENT COLUMN AND
OTHER REFERENCE INFORMATION.
AND FINALLY THE CLINICAL
PROTOCOL.
THE CLINICAL PROTOCOL NEEDS TO
BE DETAILED.
WE ASK FOR DETAILED PROTOCOLS
AND ALLOWS US TO DETERMINE THE
RISK SUBJECTS MAY BE FACING.
WE ALSO ASK FOR QUALIFICATIONS
OF CLINICAL INVESTIGATORS.
WE WANT TO GENERATE THE
EXPERIENCE OF THE INVESTIGATOR
AND THEY ARE AT AN ACCREDITED
INSTITUTION.
WE ALSO ASK FOR INFORMED CONSENT
AND COMMITMENT THAT SPONSORS
HAVE THEIR CLINICAL STUDIES
REVIEWED BY AN IRB AND THEY'RE
GOING TO ADHERE TO IND
REGULATIONS.
SO, IMPORTANT BULLET, FOLLOWING
REVIEW OF THE IND, FDA GETS 30
DAYS TO DETERMINE IF A STUDY CAN
PROCEED OR GETS PLACED ON HOLD
AND WE'LL FOLLOW UP WITH A
DETAILED LETTER EXPLAINING THAT
HOLD.
IF AUTHORIZED TO PROCEED FOR
STUDIES USING SCHEDULE 1
CANNABIS MATERIAL THEN SPONSORS
CAN PROCEED WITH DEA PROTOCOL
REGISTRATION.
AND UNFORTUNATELY DEA IS NOT
HERE TO TALK ABOUT THAT VERY
IMPORTANT COMPONENT.
SOURCES.
WE HEARD ABOUT SOURCES OF
CANNABIS.
AND I THINK THE TAKE HOME HERE
IS THAT THEY'RE HELD TO THE SAME
REGULATORY STANDARDS AS ANY
OTHER BOTANICAL RAW MATERIAL AND
DRUG SUBSTANCE OR ANY OTHER
BOTANICAL DRUG PRODUCT.
SO SPONSORS MUST MEET ALL THE
FDA REQUIREMENTS REGARDLESS OF
THE SOURCE AND SO WE'VE HEARD
EARLIER TRADITIONAL SOURCES,
NIDA, THE NIDA DRUG SUPPLY
PROGRAM.
HISTORICALLY IT'S BEEN THE ONLY
DOMESTIC LEGAL SOURCE FOR
CANNABIS FOR CLINICAL RESEARCH
AND IT'S PROVIDED BY THE
UNIVERSITY OF MISSISSIPPI.
I WON'T GET INTO THAT SINCE WE
JUST HEARD ABOUT THAT BUT WE
HERE FROM NEW DEA REGISTRANTS
AND NOW PRODUCING CANNABIS
RELATED COMPOUNDS THAT CAN BE
USED FOR AUTHORIZED
MANUFACTURING AND RESEARCH.
SO THERE'S A LINK THERE TO SOME
OF THE DEA INFORMATION.
SO MORE GENERAL DRUG BOTANICAL
DRUG DEVELOPMENT GUIDANCE, WE
ISSUED OURS IN 2016 TAKING INTO
ACCOUNT WHAT IS NECESSARY AND
GIVES CURRENT THINKING LIKE ANY
OTHER GUIDANCE AND THAT IS
EXTENDED TO 2024 FROM 2016 AND
HAS ALL THE INFORMATION YOU SEE
THERE INCLUDING AGAIN YOU'LL SEE
THE CHEMISTRY MANUFACTURING AND
CONTROLS AND IF YOU'RE REALLY
INTERESTED YOU CAN GOOGLE ALL
THE FEDERAL REGULATIONS AND READ
THEM TO YOUR HEART'S CONTENT.
BUT THIS IS OUR MAIN REGULATORY
STANDARD AND THE MAIN ONE IS
DMP.
SO CURRENT MANUFACTURING
PRACTICE FOR HUMAN
PHARMACEUTICALS.
SO THAT'S OUR RECOMMENDATION FOR
EVERYONE WHO WANTS TO OR IS
INTERESTED IN DEVELOPING
BOTANICAL COMPOUNDS.
HERES SOME WONDERFUL IMAGES OF
THE GUIDANCE AND MORE SPECIFIC
RECOMMENDATIONS OF PHASED
DEVELOPMENT AND THE LATER YOU
GET IN DEVELOPMENT, THE MORE
INFORMATION YOU'RE GOING TO NEED
AND THAT'S IN ANTICIPATION IF A
DRUG OR COMPOUND IS APPROACHED
IT WILL BE DISPENSED TO A WIDER
AND LARGER SET OF INDIVIDUALS.
SO WE WANT A LITTLE BIT MORE
SPECIFIC INFORMATION.
THE NEW GUIDANCE ALSO REPUBLICS
A TOTALITY OF EVIDENCE
APPROACH -- RECOMMENDS A
TOTALITY OF EVIDENCE APPROACH
BEFORE A BOTANICAL DRUG PRODUCT
IS APPROVED.
WE HEARD ABOUT THE CANNABIS
DEVELOPMENT FINAL GUIDANCE AND
MORE RECENT, 2023.
THAT OUTLINES A LOT OF THE WAYS
WHICH CANNABIS RESEARCH CAN BE
DONE UNDER IND AND STATEMENTS ON
SOURCES, RESOURCES FOR
INFORMATION ON QUALITY
CONSIDERATIONS AND OTHER
CONSIDERATIONS UNDER THE CSA.
HERE'S THE SUMMARY, WE NEED YOU
NEED TO OBTAIN THE EXCEPTION TO
BE APPROVED OF A MARKETING
APPLICATION BEFORE TRANSPORTED
OR DISTRIBUTED.
WHAT THAT MEANS AND WE TALK
ABOUT INTERSTATE COMMERCE AND
ONLY APPROVED DRUGS WHEN YOU
LOOK AT THE FOOD DRUG AND
COSMETIC ACT CAN BE INTRODUCED
TO INTERSTATE COMMERCE AND THE
IND ALLOWS THE EXCEPTION TO
SHIFT AND TRANSPORT THE DRUG.
THERE'S THREE TYPES, THE
INVESTIGATOR, THE BULK OF THEM
BUT THERE ARE EMERGENCY USE
TREATMENT INDs.
THE TWO BASIC CATEGORIES,
COMMERCIAL AND RESEARCH.
AND THE REQUIRED INFORMATION IS
LISTED THERE.
IT'S PRIMARILY ANIMAL
PHARMACOLOGY AND TOXICOLOGY
STUDIES AND CNC INFORMATION AND
ANYTHING CRITICAL.
THERE ARE LINKS RIGHT THERE IF
YOU SUBMIT YOUR INDs AND YOU
HAVE TO WAIT 30 DAYS OR HERE
EARLIER AND AT THE END OF THE
SLIDES AFTER THE ADDITIONAL
RESOURCES THERE'S A WHOLE BUNCH
OF LINKS FOR ANY QUESTIONS AND I
ENCOURAGE YOU TO VISIT ALL THOSE
LINKS TO HELP FACILITATE YOUR
WONDERFUL EXPERIENCE WITH FDA.
>> I'M GOING TO ASK OUR SPEAKERS
TO COME UP HERE AND FOR PEOPLE
TO GET READY FOR QUESTIONS.
UNFORTUNATELY OUR FINAL SPEAKER
FOR THIS SESSION FROM THE DRUG
ENFORCEMENT ADMINISTRATION WAS
UNABLE TO JOIN US AT THE LAST
MOMENT AND SO DR. HEUETT THE
CHIEF OF SCHEDULE 1 RESEARCH AND
INTERNATIONAL CONTROL UNIT AT
THE DRUG AND CHEMICAL EVALUATION
SECTION WAS NOT ABLE TO JOIN US
BUT LET US KNOW THEIR GOAL IS TO
SUPPORT RESEARCHERS AS THEY
NAVIGATE THE REGISTRATION
PROCESS AND PROVIDE THE SUPPORT
AND HE PROVIDED AN E-MAIL LINK
THAT WE'LL TRY TO PUT IN THE
MEETING MINUTES OF A CONTACT FOR
ANYONE WHO IS INTERESTED IN
CONDUCTING RESEARCH WITH
SCHEDULE 1 CONTROLLED SUBSTANCES
AND TO REACH OUT AND HAPPY TO
ANSWER QUESTIONS AND HELP
PEOPLE.
I'LL START US OFF WITH QUESTIONS
AS PEOPLE START COMING UP TO ASK
THEIR QUESTIONS WE'VE GOT
MICROPHONES AVAILABLE.
JENNIFER FOR WHY YOUTH ARE USING
AND WHERE THE INFORMATION IS AND
IN TERMS OF HOW QUICKLY THE
PUBLIC IS SHIFTING IN WHAT
THEY'RE DOING RELATED TO
CANNABIS AND CANNABIS-RELATED
COMPOUNDS.
>> I WAS REFERRING TO THE NIDA
SUPPORTED MODERN FUTURE STUDY WE
HAVE A PROGRAM OFFICER TO ANSWER
BETTER THAN I CAN BUT THAT'S AN
ANNUAL SURVEY OF YOUTH IN
EIGHTH, NINTH AND 12th GRADE AND
COLLECTS INFORMATION ON A WIDE
RANGE OF DRUGS USED BY KIDS AS
WELL AS THEIR ATTITUDES AND
PERCEPTIONS OF DRUG USE AND
OTHER SOURCES OF DATA WE OFTEN
SITE ARE THE SURVEY ON DRUG USE
AND HEALTH SUPPORTED BY SAMHSA
AND USUALLY COMES OUT IN THE
FALL TIME AND HAS INFORMATION ON
CANNABIS USE.
I DON'T RECALL THE EXTENT TO IN
WHICH IT BREAKS DOWN TO
DIFFERENT KINDS OF CANNABINOIDS
AND BEYOND DELTA 8 I'M NOT SURE
BEYOND THAT WHAT IT DOES SO
MAYBE YOU WANT TO COMMENT.
>> THEY ADDED DELTA 8 FOR THE
FIRST TIME SINCE 2023 AND
THEY'RE SOCIOLOGISTS MOST OF
THEM AND IT'S AN EPIDEMIOLOGIC
STUDY AND HAVE A SCIENTIFIC
ADVISORY BOARD OR WHATEVER
THEY'RE CALLING IT THESE DAYS
WHO COMES AND MEETS ONCE A YEAR
AND TALK ABOUT ALL RIGHT THIS IS
WHAT WE'RE SEEING.
MAYBE YOU SHOULD CONSIDER ADDING
IT AND BALANCE GIVING IDEAS TO
CHILDREN ABOUT THINGS THEY
SHOULD USE VERSUS TRYING TO
CAPTURE INFORMATION THAT IS
GOING TO BE USEFUL AND THEY USED
THIS ON 12th GRADERS BECAUSE
THEY ADDED IT TO THE 2024 SURVEY
BECAUSE OF THE PREVALENCE AND
WE'LL HAVE IT FOR THE YOUNGER
STUDENTS BUT THEY EVALUATE
WHAT'S GOING ON AND DECIDE IT'S
A LARGE SURVEY SO ALL THE THINGS
THAT GO ALONG WITH A SURVEY.
SO AT ANY POINT THOSE WHO ARE
WORK IN COMMUNITIES, IF YOU SEE
SOMETHING GOING ON YOU THINK IS
PREVALENT THE INVESTIGATORS ARE
OPEN TO HAVING CONVERSATION
ABOUT WHAT SHOULD BE ADDED.
QUESTIONS FROM THE GROUP?
>> YOU MUST GO TO FDA TO HAVE TO
THE QUESTIONS ANSWERED AND
THEY'RE ALWAYS EXCITED TO DO SO
AND THEY OFTEN AND IT STARTS A
CONVERSATION BASICALLY ABOUT
WHETHER OR NOT IND DATA BUT I'VE
HEARD A THIRD OPTION WHICH IS
YOU AN FORMALLY REQUEST AN IND
WAIVER, IS THAT REAL OR NOT?
>> START WITH THE DIVISION AND
REACH OUT TO THEM AND ASK THEM
THEIR VIEW.
I'M WELL VERSED IN IND
EXCEPTIONS.
MY OPINION IS THEY'RE RARE BUT
WHETHER OR NOT YOU GET 90 GETS
TO BE COMPLICATED AS YOU MIGHT
EXPECT.
BECAUSE IT DEPENDS ON HOW A DRUG
OR COMPOUND IS USED.
GENERALLY DRUGS ARE DEFINED AS
CLAIMS ANYTHING INTENDED TO
MITIGATE OR TREAT DISEASE.
THERE'S LIKE FOUR OR FIVE WORDS
IN THERE.
THOSE ARE CONSIDERATIONS THE
AGENCY HAS IN ADDITION TO
WHETHER SOMEONE IS CLASSIFIED AS
A FOOD OR DIETARY SUPPLEMENT.
>> THERE'S A LOT OF INTEREST IN
THE MINOR CANNABINOIDS WITH
PRECLINICAL RESEARCH AND WHAT'S
IN THE CLEAR TO ME I THINK IT'S
AMBIGUOUS AND MAYBE CASE BY
CASE.
WHAT TYPE OF -- THOUGH IT MAY
NOT BE SUFFICIENT FOR NDA WHAT
PRECLINICAL TOX DATA THAT IS
EXISTING OR NEEDS TO BE
CONDUCTED THAT WOULD MEET A
MINIMUM STANDARD AND EXPLORATORY
PILOT AND CBC.
WHAT WOULD YOU GUYS LOOK FOR?
>> SURE.
THE TOXICOLOGY TEAM IS PROBABLY'
BETTER SOURCE TO ANSWER THAT
QUESTION BUT SOME OF THE
STANDARD ICH GUIDELINE THE
30-DAY, 60-DAY TOX STUDIES BUT
IT DEPENDS ON WHAT IS EXISTING
IN THE LITERATURE AS WELL.
IF YOU COULD COME IN AND
DEMONSTRATE WHAT YOU WANT TO
ADMINISTER IN YOUR CLINICAL
TRIAL WILL NOT EXPOSE SUBJECTS
TO RISK OR HARM BASED ON
EXISTING LITERATURE ARE THE CASE
BY CASE DECISIONS FDA MAKES.
>> THANKS VERY MUCH.
>> WITH THAT COULD THEY
POTENTIALLY CITE REFERENCES THAT
USE CANNABIS AS A WHOLE BUT
BEING ABLE TO SPECIFY THE AMOUNT
OF THE INDIVIDUAL CONSTITUENTS
AND WHAT THE DOSE IS IN THAT
RANGE IS THAT A POTENTIAL
REFERENCE THEY CAN LOOK AT?
>> ONE OF THE CHALLENGES I FOUND
WITH BOTANICAL PRODUCTS IS
ISOLATED COMPOUNDS VERSUS BULLET
POINT.
THE QUESTION IS NOW THAT YOU'VE
ISOLATED THAT VERY SPECIFIC
COMPOUND, HAVE YOU ELIMINATED
THE PROTECTIVE ENTOURAGE EFFECT
OR SOME OTHER EFFECT?
AND I WILL SAY I'VE RAN A STUDY
ON KRATOM WHICH I'M HAPPY TO
TALK ABOUT BUT WE RAN INTO
SIMILAR SITUATIONS LIKE THAT.
>> AND OFTEN TIMES WHEN YOU'RE
STUDYING A SINGLE COMPONENT,
YOU'RE USING IT IN HIGHER DOSES
THAN GIVEN OR TAKEN BY
INDIVIDUALS IN OTHER STUDIES
GIVING HIGHER DOSES.
>> AND DEPENDS ON THE STANDARD
DESIGN AND SOME HAVE MORE
CONFIDENCE IF YOU START LOW AND
GO UP.
YOU CAN SEE THEM INCREASE IN THE
DOSE-DEPENDENT MANNER.
HOPEFULLY YOU'LL HAVE SOME
SAFETY THERE.
>> THE FACT THAT IN THE
LEGISLATION I'M AWARE OF THERE'S
ALWAYS A DISTINCTION BEING MADE
BETWEEN NATURALLY DERIVED
CANNABINOIDS AND SYNTHETIC
CANNABINOIDS.
I DON'T MEAN MAN CANNABINOIDS
BUT THC MADE IN THE LAB OPPOSED
TO THC EXTRACTED FROM THE PLANT
AND CBC EXTRACTED FROM THE
PLANT.
IS THERE SOMETHING I DON'T KNOW?
ARE THEY REALLY DIFFERENT?
I WAS TALKING TO A GROUP OF
STAFFERS AND ONE PERSON RAISED
THEIR HAND AND SAID IS SYNTHETIC
THC DIFFERENT AND IT'S THE SAME
MOLECULE SO HOW CAN IT BE
DIFFERENT.
MY THOUGHT PROCESS IS THEY DON'T
KNOW.
IS THERE ANYTHING WE CAN DO TO
CONVINCE THEM THE MOLECULE IS
THE MOLECULE.
LIKE WATER IS WATER AND H2O AND
IT'S HOT OR COLD BUT IT'S WATER.
>> THERE'S A REAL NEED FOR
CLARITY AND EDUCATION OF POLICY
MAKERS AROUND SOME OF THIS STUFF
AND TO STEVE'S POINT THERE'S
OPPORTUNITIES FOR THE RESEARCH
COMMUNITY TO WEIGH IN ON RULE
MAKING.
WE CAN'T PROACTIVE GO TO
CONGRESS ON THESE THINGS BUT YOU
AS RESEARCHERS CERTAINLY CAN AND
I KNOW THERE ARE SCIENTIFIC
SOCIETIES THAT ARE INTERESTED IN
THESE QUESTIONS AND HAVE
ADVOCACY ARMS THAT ENGAGE WITH
CONGRESS ON THESE AND I'M
ENCOURAGING YOU TO REACH OUT
BECAUSE THERE'S OPPORTUNITIES
FOR EDUCATION ON THIS.
>> WERE HEMP DERIVED CBC
PRODUCTS SO THANK YOU.
AND MY QUESTION IS SAY MY
UNDERSTANDING IS IF I WERE TO
CONDUCT AN EXPERIMENTAL STUDY
FROM THE NIDA DRUG SUPPLY WITH
THE THC PRODUCT AND IT'S NOT ON
A THERAPEUTIC INDICATION BUT
MORE RISK OR ABUSE LIABILITY
PHENOTYPE.
IT'S AN EXPERIMENTAL STUDY.
I STILL HAVE TO GO TO THE FDA.
HOW DOES THE FDA CONSIDER THAT
IF I WERE TO DO AN ALCOHOL
ADMINISTRATION STUDY IN MY LAB
THAT IS PRETTY MUCH EXEMPT
RELATIVELY QUICKLY.
HOW DOES THE FDA TREAT THOSE
TYPES OF STUDIES AND ANY ADVICE
FOR INVESTIGATORS TRYING TO
NAVIGATE THAT?
>> YEAH.
I THINK THE EASIEST ANSWER IS
THC IS A DRUG SO THAT FALLS
UNDER THE FDA PURVIEW ARE OTHERS
MAY NOT.
>> ARE THERE TIMES STUDIES GET
EXEMPT CONSIDERING THEY'RE
EXPERIMENTAL STUDIES IN LAB
WITHOUT FOCUS ON A THERAPEUTIC
INDICATION?
OR IS THERE TYPICALLY THE GAMUT
FOR THE PROCESS.
>> THE OUTCOME MEASURES WOULD
PROBABLY BE A STRUCTURE
FUNCTION.
IT'S ADMINISTERING IS THE DRUG
TO SEE HOW IT AFFECTS THE
STRUCTURE FUNCTION.
>> AND THAT KEEPS IT UNDER THE
FDA PURVIEW?
>> IT PUTS IT INTO THE DRUG
TRIAL THAT REQUIRES 90 --
>> CAN HAVE YOU THC-BASED
STUDIES THAT MEET THE CRITERIA
FOR EXEMPTION?
>> IF YOU HAVE AN FDA APPROVED
PRODUCT IN THE INDICATED
POPULATION -- YEAH.
>> WE FUND BOTANICALS AND THE
DIFFERENCE HERE IS THAT THIS SET
OF COMPOUNDS AND PRODUCT IS
CURRENTLY SCHEDULE 1 AND IN THE
PROCESS OF POTENTIALLY BEING
RESCHEDULED AND THE SAME PROCESS
COMES INTO PLAY WHERE WHAT YOUR
USING THE PRODUCT FOR IS THE
CONVERSATION I HAVE.
I WON'T GET ALL FIVE BUT TREAT,
MITIGATE, PREVENT, CURE OR
DIAGNOSIS.
ARE THE FIVE ARE -- IF YOU'RE
USING IT FOR ANY OF THOSE
REASONS, THEN WHETHER YOU PLAN
TO TAKE IT FORWARD FOR MARKETING
PURPOSES AND BRING IT TO AN NDA
SOMEONE ELSE WHEN YOU PUBLISH
THE RESULTS OF THAT WORK COULD
USE THAT INFORMATION TO MAKE AN
INDICATION IS HOW WE THINK ABOUT
IT.
THERE'S SOME ELEMENTS UNIQUE THE
HEMP DERIVED VERSUS NOT AND
FALLS IN THE BOTANICAL CATEGORY
AND ALL THE SAME RULES APPLY AS
ANY OTHER BOTANICALS.
>> DESCRIBE HOW THE BOTANICAL
AND DIVISION STAFF COORDINATE IN
AN IND REVIEW.
>> SURE.
>> IT'S A -- ASSIGNED WITH THE
DIVISION OF PSYCHIATRY AND
ANALGESIA AND ADDICTION PRODUCTS
AND DIVISION OF NEUROLOGY
PERHAPS AND THEY'LL PUT TOGETHER
A LARGE INTERNAL TEAM OF
INDIVIDUALS.
PHYSICIANS, CHEMISTS,
TOXICOLOGISTS, STATISTICIANS AND
CALL THE CONTROL SUBSTANCE STAFF
AS WELL AND GENERALLY THERE'S A
MEETING AND ANYWHERE FROM 15 TO
20 MULTI-DISCIPLINARY REVIEWERS
WILL SIT IN A ROOM AND SAY,
OKAY, HERE'S THE PROTOCOL.
WHAT DO WE THINK?
IT CAN RANGE FROM EVERYTHING
FROM SPLB SAW SOMETHING WORDED
FUNNY IN INFORMED CONSENT FORM
OR THE TEAM MAY NOTICE THE LEVEL
OF METAL IN HERE OR A LINE ITEM
THAT'S MISSING.
THE STATISTICAL TEAM MAY HAVE
QUESTIONS ABOUT THE STUDY
DESIGN, THE POWER, USUALLY THE
INITIAL MEETINGS DETERMINE
WHETHER THERE'S A HOLD ISSUE AND
HOLD ISSUES FT. LAUDERDALELY
SPEAKING ARE SAFETY.
AND THE PROTOCOL COULD BE PLACED
ON HOLD AND THE HOLD LETTER
DRAFTED IMMEDIATELY AND WE'RE
AWIRE WE ONLY HAVE 30 DAYS AND
GOES OUT AND WHEN THE RESPONSE
TO THE WHOLE COMES BACK IN TO
FDA SOMETIMES DEPENDING ON THE
ISSUE THE WHOLE GROUP WILL GET
BACK TOGETHER OR ONLY THE IS
SPECIFIC DISCIPLINE.
FROM A CSS PROSPECTIVE AND
CONTROLLED SUBSTANCES STAFF,
MARIJUANA, THC ARE ALL FROM OUR
PERSPECTIVE ARE ABUSE LIABILITY
IS PRETTY WELL CHARACTERIZED.
SO USUALLY CSS SPECIFICALLY
DOESN'T RAISE A LARGE AMOUNT OF
ISSUES.
OUR LANGUAGE IS WE WANT TO
NOTIFY YOU COULD BE USING A
SCHEDULE 1 SUBSTANCE AND AS OF
LATE OUR HEMP BILL OFTEN IT'S WE
GOT A SUBSTANCE OR PRODUCT THAT
LOOKS KIND OF FUNKY AND ON THE
.3% LINE SO TALK TO DEA AND SEE
IF YOU'RE SCHEDULED OR NOT.
BUT THAT'S GENERALLY HOW THE
PROCESS WORK AND FOR NDA THE
SIMILAR PROCESS AND OVER AND
OVER AGAIN FOR A YEAR LONG
REVIEW.
>> IS THERE A STANDARD FORMAT
AND THOUGHT FDA AND NIH CREATED
ONE TO MAKE IT EASIER TO DO
REVIEWS?
THEY ALL TEND TO LOOK DIFFERENT
TO MY EYE.
AFTER DOING IT SO LONG I START
TO RECOGNIZE SPECIFIC P.I.s BY
THEIR FONT AND LETTERHEAD.
SO IT'S GENERALLY NOT SUPER
STANDARDIZED BUT IT'S A CLINICAL
PROTOCOL SO GENERALLY SPEAKING
THEY HAVE THE INFORMATION YOU
EXPECT.
>> ANY OTHER ADVICE YOU HAVE FOR
RESEARCHERS OR OTHERS ONLINE
LISTENING IN AND WANTING TO DO
RESEARCH IN THIS SPACE.
>> I DON'T THINK I HAVE A LOT.
THE SCHEDULE 1 AND GOOGLE 1301.8
AND YOU'LL SEE BOLDED SECTIONS
THAT SAY, SCHEDULE 1 PROTOCOL
MUST CONTAIN -- NAME OF
INVESTIGATOR, AMOUNT USED, WHERE
YOU GOT IT FROM, SYNOPSIS OF THE
PROTOCOL, ETCETERA.
BY THE TIME WE GET THAT I
CREATED THIS WONDERFUL TEMPLATE
THAT OH, MY GOODNESS HAS THE
SAME HEADING.
WE LOOK AT THAT AND THE IND AND
PROTOCOLS GENERALLY REVIEWED BY
THE DIVISION BUT FOR THE
SCHEDULE 1 PORTION SPECIFICALLY,
CSS REVIEWS THOSE QUICKLY AND
GET IT BACK TO DEA AND WHAT
HAPPENS BEFORE THAT AND AFTER
THAT WE DON'T PARTICULARLY KNOW.
>> IF YOU HAVE QUESTIONS ABOUT
NAVIGATING THE PROCESS, DEA IS
YOUR BEST BET.
>> I WONDER IF ANYONE HAS AN
OPINION ON THE NINTH CIRCUIT'S
OPINION ON DELTA 8 AND AS A
PHARMACOLOGIST AND CHECKIST IT'S
WHAT DANIELE SAID THE COMPOUND
IS THE COMPOUND.
DELTA 8 IS PHARMACOLOGY EQU
EQUIVALENT AND ANY THOUGHTS ON
THAT?
>> THE PERSONAL THOUGHT IS A
MOLECULE IS A MOLECULE AND WHEN
YOU GET PLANT EXTRACTED OR
DERIVED AND ANY IMPURITIES ON
THE EXTRACTION ITSELF I DON'T
BELIEVE I'VE EVER SEEN EVIDENCE
AN EXTRACTED MOLECULE PERFORMS
DIFFERENT THAN A SYNTHETIC.
>> I'M NOT A PHARMACOLOGIST SO I
WON'T COMMENT.
>> THANK YOU SO MUCH TO OUR
SPEAKERS AND THE WONDERFUL
QUESTIONS AND I WILL INVITE INNA
UP TO MOVE US UP TO THE NEXT.
THANK YOU SO MUCH.
>> THANK YOU VERY MUCH FOR THE
SPEAKERS AND FOR THE MODERATORS.
I CAN'T BELIEVE IT BUT WE'RE AT
THE LAST SESSION OF TODAY.
WE HAVE SOME RESOURCES FROM FDA.
WONDERFUL RESOURCES.
AND TALK ABOUT THE OVERVIEW OF
NIH SUPPORT OF CANNABIS RESEARCH
AND INSTITUTE SPECIFIC
PRIORITIES AND I'LL INVITE
PROGRAM OFFICERS FROM OTHER
INSTITUTES AND CENTERS.
I THINK WE HAVE THREE IN THE
ROOM.
COULD YOU PLEASE JOIN THE
PODIUM.
SO AND YOUR NAMES SHOULD BE
HERE.
WE HAVE SEVERAL ON THE ZOOM
JOINING US AND WE HAVE THREE IN
THE ROOM.
WHEN YOU APPLY AND SUBMIT YOUR
APPLICATION TO NIH IT WILL GO TO
THE SPECIFIC INSTITUTE BASED ON
THE PRIORITIES AND MISSION OF
THE INSTITUTE.
SO I WILL START WITH NCCIH
INTERESTS AND THESE IS WHAT WE
GOT.
THE PURPOSE OF OUR PROGRAM THAT
IS CALLED CANNABIS RESEARCH
PROGRAM IS TO ENCOURAGE RESEARCH
ON TERPENES AND ORGANOIDS IN
ORGANISMS OR HUMAN SUBJECTS AS
IT RELATES TO PAIN, NOCICEPTION
AND AND AND GEE -- ANALGESIA AN
USE IT FOR PAIN RELIEF AND GOES
TO NATURAL PRODUCTS AN CANNABIS
CANNABINOID IS A NATURAL PRODUCT
INTERVENTION.
SO WE HAVE FOUR HIGH-PRIORITY
AREAS.
ONE AREA IS MECHANISMS BY WHICH
MINOR CANNABINOIDS AFFECT
SIGNALLING PASS WAY DURING
INTERACTIONS OR OTHER PATHWAYS.
THIS IS ONE BIG AREA AND THE
OTHER IS INTERACTION BETWEEN THE
MICROBIOME AND.
TERPENES.
THE THIRD IS HOW SPECIFIC
TERPENES MAY INFLUENCE POTENTIAL
ANALGESIC MECHANISMS OF UNDER
STUDIED MINOR CANNABINOIDS AND
NUMBER FOUR, MULTIMODAL
APPROACHES TO ANALGESIA
INCLUDING MINOR CANNABINOIDS AND
TERPENES.
THE GOAL IS TO BRING EXPERTISE
FROM MANY AREAS AND FACILITATE
COLLABORATIONS BY EXPERTS AND
IMMUNOLOGY AND CHEMISTRY AND
PAIN AND NEUROSCIENCE.
THIS IS NCCH PROGRAM ON
CANNABINOIDS AND PAIN.
WE PUBLISHED THE NOTICE OF
SPECIAL INTEREST AND PROMOTE
MECHANISTIC RESEARCH OF
THERAPEUTIC AND OTHER BIOLOGICAL
PROPERTIES OF THERAPISTS
TOGETHER WITH 10 INSTITUTES AND
CENTERS OF NIH SO AUTHOR DEFINED
AS COMBINES FROM THE CANNABIS
PLANT OTHER THAN THC AND MAY
INCLUDE MANY THAT WERE DISCUSSED
TODAY SUCH AS OTHERS.
THIS NOTICE OF SPECIFIC INTEREST
SUPPORT HIGHLY INNOVATIVE BASIC
AND MECHANISTIC STUDIES AND
HUMAN SUBJECTS AIMING TO
INVESTIGATE THE IMPACT OF MINOR
CANNABINOIDS ON MECHANISMS
UNDERLYING THE THERAPEUTIC
EFFECTS.
SO THE NOSI IS BUT CLINICAL
STUDIES ARE ENCOURAGED FOR
COMBINATIONS OF MINOR
CANNABINOIDS OR OTHER NATURAL
PRODUCTS SUCH AS KRATOM THAT MAY
ENHANCE THE THERAPEUTIC BENEFITS
OR ADVERSE EFFECT AFFECT.
THE EXPIRATION DATE IS JULY 1,
2025.
SO IN THIS WE HAVE MANY
INSTITUTIONS AND THE NEXT ONE
WILL BE MY COLLEAGUE FROM THE
NATIONAL EYE INSTITUTE.
ONE OF THE PROPERTIES IS STUDIES
AND SEE THE PROGRAM AT THE
NATIONAL EYE INSTITUTE AND
PROVIDED THIS SLIDE AND
CANNABINOIDS FOR GLAUCOMA AND
DRY EYE AND DIABETIC ON THES AND
THE PRIORITIES FOR THE NATIONAL
EYE INSTITUTE.
OKAY.
NEXT ONE I WELCOME THE DIVISION
OF RESEARCH NATIONAL INSTITUTE
OF MENTAL HEALTH.
>> GOOD AFTERNOON, THREW SO
MUCH.
-- THANK YOU SO MUCH.
IT LOOKS LIKE THE SLIDE NEEDS TO
BE CLICKED MULTIPLE TIMES.
I'M THE BRANCH CHIEF IN ONE OF
THE EXTRAMURAL DIVISIONS OF T
THEIBILITY NATIONAL INSTITUTE OF
MENTAL HEALTH AND LOOK AT HOW
ENDOGENOUS CANNABINOIDS
INFLUENCE CIRCUIT BASED
MECHANISM AND IMPLICATE MENTAL
HEALTH BEHAVIORS AND TESTING
TARGETING ACTING ON THIS SYSTEM.
THE PRECLINICAL RESEARCH WOULD
NOT STUDY MARIJUANA AND
COMPOUNDS IN PRE-CLINICAL
RECEIVER.
IN THE AREA OF CLINICAL
RESEARCH, THE FOCUS WOULD BE ON
STUDYING HOW PHARMACOLOGIC
MANIPULATION OF CANNABINOID OR
CANNABINOID RECEPTORS CAN
INFLUENCE FUNCTION OF THE
CENTRAL NERVOUS SYSTEM
SPECIFICALLY IN PSYCHIATRIC
DISORDERS AND THE CAUSE OF THE
TARGET-BASED ORIENTATION OF OUR
CLINICAL TRIAL SYSTEM THAT WOULD
READ TO THE ACCESS OF THE
PHARMACOLOGIC AGENTS WITH
SPECIFICITY AND TEST EARLY STAGE
PHARMACO KINETIC TRIALS USING
TRIAL DESIGNS THAT INCORPORATE A
CENTRAL NERVOUS SYSTEM AND
ASSOCIATED WITH THE
PRE-SPECIFIED PHARMACOLOGIC
TARGET.
THAT'S IT.
>> THANK YOU VERY MUCH.
NOW WE'RE MOVING TO DR. YU AT
THE DIVISION OF METASCIENCE AND
BEHAVIOR OF THE NATIONAL
INSTITUTE OF ALCOHOL ABUSE AND
ALCOHOLISM.
NO.
I THINK I HAVE THE WRONG ORDER
TE NEXT PRESENTER IS DR. LIN
FROM NIDA.
>> I'M HAPPY TO OPPORTUNITY TO
COME HERE AND FOLLOW MY
COLLEAGUE'S PREVIOUS
PRESENTATIONS AND NIDA IS NOT A
STRANGER TO THE AUDIENCE HERE
TODAY.
WHAT I'D LIKE TO SAY IS THAT
MANY PRESENTATIONS HERE
INCLUDING WILL WHAT INNA
DESCRIBED ABOUT THE NCCIH
PRIORITY WE SHARE THE SAME
INTEREST, FOR EXAMPLE PAIN
RESEARCH AS THE MAIN TOPIC OF
TODAY'S SYMPOSIUM AND SHOWED
INTEREST IN TERMS OF IMMUNOLOGY
AND IN TERMS OF THE NEUROIMMIMM
INTERACTS AND IN NYE -- NIDA
AND IN TERMS OF CANNABINOID WE
DID RESEARCH FOR 10 YEARS NOW.
WHAT I WANT TO POINT OUT THE
DIVISION OF NEUROSCIENCE AND
BEHAVIOR WE FOCUS ON BRAIN
INTERACTIONS AND WE LIST SEVERAL
PRIORITIES LIKE NOSIs MORE
SPECIFIC AND THESE ARE EXAMPLES.
EVERY YEAR WE HAVE THE
OPPORTUNITY TO DEVELOP NEW IDEAS
AND YOU'LL SEE NEW INITIATIVES
COME OUT.
SOME HAVE ACTIVE IN THERE AND
EVEN FOR THOSE NOT EXPIRED AND
I'D ENCOURAGE YOU TO LOOK TO THE
IF THE AREA AS TO YOUR INTEREST
THE REASON IS FOR THE NOSI AND
NOFO, THOSE MECHANISM FOR NIH TO
SHARE WITH YOU THE PROGRAM
IDENTIFIED SO EVERY YEAR WE PUT
SEVERAL NEW BUT FOR THOSE TO
YOUR AREA OF INTEREST AND LOOK
TO THAT AND YOU CAN CONTINUE TO
SHARE INTEREST WITH NCCIH AND
INTEREST WITH NIDA AND WE WORK
WITH NCCIH AND SHARE THE
PERSPECTIVES OF NCCIH WE WORK
CLOSELY TOGETHER AND IF YOU HAVE
QUESTIONS WORK WITH US.
>> I'M PLEASED TO INTRODUCE
DR. OSHINSKY PROGRAM DIRECTOR
FROM NINDS.
>> I'M THE DIRECTOR THE OFFICE
OF PRECLINICAL PAIN RESEARCH AT
NINDS AND HAVE A CENTRAL ROLE IN
MANAGING THE PAIN PORTION OF THE
HEAL INITIATIVE.
NINDS' ROLE IS NOT FOCUSSED ON
THE CANNABINOID ITSELF BUT
REALLY ON THE THERAPEUTIC
CONDITIONS AND PATHOLOGICAL
CONDITIONS THAT FALL IN NINDS'
MISSION AND THERE'S EPILEPSY,
ALZHEIMER'S DISEASE, ALS,
PARKINSON'S DISEASE AND PAIN AND
HEADACHE AND WE'VE HAD
APPLICATIONS COME IN FOR
CANNABINOID RESEARCH AND
RESEARCH FOR THE THERAPEUTIC
CONDITIONS.
THERE'S A FEW OTHER POINTS I
WANT TO MAKE.
I WATCHED THE PRESENTATIONS
EARLIER TODAY AND THE DATA
BLITZ' AND THERE'S GREAT WORK ON
HERE.
THERE'S RESTRICTED AMOUNT OF
TYPE OF WORK THAT CAN HAPPEN
INSIDE OF AN R&R 21 AND
ENCOURAGE YOU TO
AN R21 AND NOT THERE'S LY --
THERE'S NOT NECESSARILY LOOK FOR
THE WORD CANNABINOID AND IF IT'S
IN NINDS' MISSION IT DOESN'T
HAVE TO HAVE A FUNDING
ANNOUNCEMENT TO LIST
CANNABINOIDS TO PUT IT ON THE
PARENT R01.
I WANT TO ENCOURAGE YOU TO DO
THAT.
THE SECOND THING IS AT NINDS AND
THIS IS A TRANS-NIH PROGRAM BUT
CAU IN SEE THEN ON THE WEBSITE
WE SUPPORT THE USE OF THE DATA
TRANSPARENCY AND RIGOR ICONS.
I WAS SURPRISED THERE WERE FEW
DOSE RESPONSES DONE IN THE
ANIMALS, DESCRIPTION OF THE
BLINDING, WHAT THE
INCLUSION/EXCLUSION CRITERIA
WERE AND I UNDERSTAND THE R21
IT'S TOUGH TO DO THAT BUT INSIDE
THE R01s MAY GIVE RIGOR ASPECT
FOR THE RESEARCH AND WE HAVE THE
DIVISION OF TRANSLATIONAL
RESEARCH TO HELP YOU AND WE HAVE
SEVERAL PROGRAMS NOT R01
MECHANISMS AND MILESTONE
MECHANISMS TO HELP YOU WITH YOUR
IND SUBMISSION AND PHASE 1
CLINICAL TRIALS AND HAVE A SLEW
OF NET FOR DISORDERS AND ONE IS
FOR PAIN AND THE OTHER IS
NEURONEXT AND ENCOURAGE YOU TO
USE THEM FOR YOUR CANNABINOID
RESEARCH.
THAT'S THE MISSION OF THE
TRANSLATIONAL RESEARCH WHICH IS
WHERE INSIDE OF NINDS WE HAVE
THE CLINICAL RESEARCH THAT RUNS
THE CLINICAL TRIAL NETWORKSES
AND REACH OUT IF YOU HAVE
QUESTIONS HOW TO TAKE ADVANTAGE
OF NINDS' FUNDING ANNOUNCEMENT
OR HAVE AN IDEA FOR A PROJECT
INSIDE THE MISSION.
HAPPY TO ENTERTAIN THAT.
AGAIN, GREAT MEETING.
THANK YOU.
>> THANK YOU, MICHAEL.
THIS IS GREAT.
NOW I INVITE MY COLLEAGUE FROM
THE NIAA ALCOHOL APEWS AND
ALCOHOLISM INSTITUTE, DR. LIU.
>> GOOD AFTERNOON.
MY NAME IS QI-YING LIU AT THE
DIVISION OF NEUROSCIENCE AND
BEHAVIOR NATIONAL INSTITUTE ON
ALCOHOL ABUSE AND ALCOHOLISM.
NIAAA.
SUBSTANCE USE DISORDER INSTITUTE
IS FOCUS ON ALCOHOL USE DISORDER
AND WE'RE INTERESTED IN
COMORBIDITY AND LOOKING AT
STUDIES RELEVANT TO THIS MEETING
SUCH AS THE AFFECT OF CANNABIS
USE ON ALCOHOL CRAVING AND
CONSUMPTION AND THE STUDY OF PRE
NATAL ALCOHOL EXPOSURE AND FETAL
BRAIN DEVELOPMENT.
SO NIAAA'S PORTFOLIO IN THIS
AREA IS QUITE SMALL WITH LESS
THAN 10 ACTIVE RESEARCH FINDS.
A
AND CANNABIS EXPERTS AND WE
EXPLORE THE ROLE OF
ENDOCANNABINOID RECEPTORS IN
ALCOHOL MISUSE AND AUD.
NIAAA'S PRIORITY IN THIS AREA
INCLUDE RESEARCH EXPLORING THE
ROLE OF CANNABINOID MISUSE AND
TO STUDY MECHANISMS OF
CANNABINOID AND ALCOHOL
PREFERENCE AND CONSUMPTION AND
INTOXICATION AND WITHDRAWAL AND
ETCETERA.
SECONDLY, WE'RE INTERESTED IN
EXPLORING THE SIGNAL SYSTEM AS
POTENTIAL TARGETS FOR ALCOHOL
PHARMACO THERAPY AND DEVELOP
MEDICATIONS FOR AUD MEDICATED BY
THE RECEPTORS.
SO WE'RE INTERESTED IN THE
POTENTIAL FOR USING CBD FOR THE
TREATMENT OF AUD AND LASTLY
STATUS IN EX MORGUE BRAIN
MECHANISMS SHARED BY ALCOHOL USE
DISORDER AND OTHER SUBSTANCE USE
DISORDERS INCLUDING CANNABIS USE
AS SUPPORTED BY NIAA.
I'LL STOP THERE.
>> THANK YOU.
THANK YOU, DR. LIU, GREAT.
THE NEXT PRESENTER IS
DR. FREEDMAN.
>> I'M FROM THE NATIONAL CANCER
INSTITUTE.
THERE WAS A STUDY FROM
WASHINGTON STATE SHOWING 1 IN 4
CANCER PATIENTS WERE USING
CANNABIS OR CANNABINOID DURING
TREATMENT.
SO NCI TOOK NOTICE AND DEVELOPED
THE CANCER RESEARCH GROUP ACROSS
ALL OF NCI AND CO-LEAD THIS AND
OUR GOALS ARE TO ASSESS CANCER
PATIENT'S USE OF CANNABIS AND
IDENTIFY BENEFITS AND HARMS AND
LOOK AT TOBACCO CO-USE AND LOOK
AT THE ACTION IN CANCER AND
CONTRIBUTE EVIDENCE TO
CLINICIANS AND PATIENTS AND
PROVIDE INFORMATION DESIGN AND
CONDUCT CLINICAL TRIALS.
FIRST THING WE DID WAS DEVELOP A
SYMPOSIUM IN 2020 THAT I THINK
WAS A TWO OR THREE-DAY SYMPOSIUM
AND WERE ABLE TO PUBLISH A YEAR
LATER WITH THE HIGHLIGHTS FROM
THE SYMPOSIUM AND USED IT TO
IDENTIFY THE GAPS IN THE
RESEARCH.
AT THE SAME TIME WE WERE ABLE TO
FUND COMPREHENSIVE CANCER
CENTERS TO DO A CROSS-SECTIONAL
SURVEY OF THE THOUSAND CANCER
PATIENTS ON THEIR USE OF
CANNABIS, HOW THEY USE IT AND
WHY AND DO THEY THINK IT MAKES A
DIFFERENCE AND WE'RE JUST ABOUT
TO PUBLISH ANOTHER MONOGRAPH IN
GNCI WITH ABOUT 14 ARTICLES
BASED ON THE RESULTS.
THOSE RESULTS RIGHT NOW ARE
SHOWING THAT IT'S NOT 1 IN 4
CANCER PATIENTS BUT 1 IN 3 USE
CANNABIS DURING THEIR TREATMENT.
WE DEVELOPED A FEW INITIATIVES.
ONE IS ADMINISTRATIVE SUPPLEMENT
LOOKING AT TOBACCO AND CANNABIS
CO-USE.
WE HAVE A NOTICE OF SPECIAL
INTEREST OR NOSI STILL ACTIVE ON
BASIC MECHANISM OF CANNABIS IN
CANCER AND LAST YEAR WE WERE
ABLE TO FUND AN RFA ON CANNABIS
AND CANNABINOID USE ON ADULT
PATIENTS DURING ACTIVE TREATMENT
AND BENEFITS AND HARMS.
WE FUNDED FIVE CANCER CANNABIS
COHORTS.
ALL COHORTS WILL LOOK AT
PATIENTS IN THE ACT MUCH
TREATMENT AND LOOKING AT THOSE
USING CANNABIS AND NOT USING
CANNABIS.
IN TOTAL WE'LL HAVE OVER 4,000
CANCER PATIENTS AND WE'LL BE
FOLLOWING THEM FOR UP TO TWO OR
THREE YEARS.
SO HOPEFULLY WITH THIS RFA WE'LL
GET EVIDENCE ON SOME BENEFITS
AND HARMS AND NOT JUST
CROSS-SECTIONAL.
SO IF YOU HAVE ANY QUESTIONS
ABOUT ANYTHING WE'RE FUNDING, OR
ANYTHING WE'RE DOING, PLEASE
FEEL FREE TO CONTACT ME OR JOE
AT ANY TIME.
THANKS.
>> THANK YOU VERY MUCH.
AND NOW OUR FINAL PRESENTER, I'D
LIKE TO INTRODUCE ONE MORE SLIDE
AND THIS IS FROM MY COLLEAGUE
DR. ALEXIS BACKOS COULDN'T JOIN
US BUT WANTED ME TO SHOW HER
SLIDE ON THE NATIONAL INSTITUTE
OF AGING AND LOOKING AT THE
POTENTIAL CONTRIBUTIONS OR
ADVERSE OF CANNABINOIDS TO
RELIEF SYMPTOMS AND IMPROVE
QUALITY OF LIFE IN OLDER ADULTS
EXPERIENCING PAIN, AGE-RELATED
COGNITIVE DECLINE AND INSOMNIA
AND FOR END OF LIFE CARE.
SO IF YOU HAVE ANY INTEREST IN
THOSE AREAS, PLEASE CONTACT HER
DIRECTLY.
AND FINALLY, WE HAVE A PRESENTER
IN THE ROOM, DR. LORENA
BACCAGLINI AT THE CENTER FOR
CLINICAL RESEARCH, NATIONAL
INSTITUTE OF DENTAL AND
CRANIOFACIAL RESEARCH.
>> YOU ALREADY GAVE SUCH A GOOD
PRESENTATION SO MY TWO MINUTES I
MAY ONLY NEED ONE MINUTE.
I'M HERE FOR THE NATIONAL
INSTITUTE OF DENTAL AND
CRANIOFACIAL RESEARCH.
I'M THE DIRECTOR OF THE CLINICAL
RESEARCH AND EPIDEMIOLOGICAL
PROGRAM AND WE'VE BEEN WORKING
WITH INNA AND THIS IS AN EXAMPLE
OF THE TYPE OF COLLABORATION WE
HAVE WITH OUR OTHER COLLEAGUES.
AND IF YOU HAVE AN INTEREST IN
THE DENTAL CRANIOFACIAL OUTCOMES
COME TO OUR INSTITUTE AND THE
CANNABINOID RECEPTOR SPREAD
THROUGHOUT THE AREA AND WE FIND
IT IN THE TEMPORAL MANDIBULAR
JOINT AND CONSIDER IDEAS IN THAT
AND THE STUDIES FOR THIS FUNDING
OPPORTUNITY COULD BE PRECHIN --
PRE CLINICAL AND MECHANISTIC
STUDIES AND STUDY ANALGESIA BUT
ALSO IMMUNE EFFECT AND
ANTIINFLAMMATORY AND OTHER
THERAPEUTIC THOUGHTS.
AS LONG AS IT'S DENTAL OR
CRANIOFACIAL YOU CAN CONSIDER
THESE.
AS OTHER COLLEAGUES HAVE
MENTIONED YOU DON'T HAVE TO GO
THROUGH A PARTICULAR FUNDING
OPPORTUNITY BUT YOU CAN APPLY
THE GENERAL MECHANISMS.
IF YOU'RE THINKING ABOUT AN
OBSERVATIONAL OR BASIC SCIENCE
STUDY YOU CAN APPLY THROUGH THE
REGULAR R01 OR R21 MECHANISMS
THEY'RE AVAILABLE ALL THE TIME.
YOU CAN KEEP AN EYE ON THE NOSI
EXPIRED BUT IF IT'S NOT RENEWED
YOU CAN APPLY THROUGH THE
GENERAL MECHANISMS.
IF YOU'RE THINKING OF AN
INTERVENTIONAL TYPE OF STUDY YOU
WOULD APPLY THROUGH THE UH3 --
UG3, UH3 MECHANISM WHERE THERE'S
AN INITIAL PHASE WHERE YOU
DEVELOP THE COMPONENTS AND THE
UG3 WHERE YOU DO THE
IMPLEMENTATION OF THE
INTERVENTION.
AND IF YOU HAVE ANY QUESTIONS,
FEEL FREE TO CONTACT ME OR MY
COLLEAGUE THE DIRECTOR OF THE
NEUROSCIENCE AND TEMPORAL
MANDIBULAR DISORDER PROGRAM AND
WE'LL BE HAPPY TO SPEAK WITH YOU
AND ANSWER ANY QUESTIONS.
>> THANK YOU.
THANK YOU, SO MUCH LORENA.
WE'RE A LITTLE BIT BEHIND FOR
THE Q&A DO WE HAVE BURNING
QUESTION FROM ZOOM OR IN THE
ROOM?
IF YOU HAVE ANY QUESTIONS WE CAN
ACCOMMODATE ONE OR TWO, IF NOT
YOU HAVE THE CONTACT INFORMATION
AND PLEASE DO NOT HESITATE TO
FIND THE PROGRAM OFFICER AND YOU
KNOW THIS IS THE KEY FOR
SUCCESS.
OKAY.
SO THANK YOU SO MUCH TO MY
WONDERFUL COLLEAGUES.
OF COURSE THIS IS WE CAN DO THIS
RESEARCH TOGETHER.
THANK YOU SO MUCH.
NOW I'D LIKE TO WELCOME
DR. SHURTLEFF FOR THE CLOSING
REMARKS.
>> FIRST, I WANT TO SAY WHAT A
GREAT DAY IT WAS.
IT'S GREAT TO SEE EVERYBODY IN
PERSON AFTER FOUR OR FIVE LONG
YEARS OF DEALING WITH COVID AND
OTHER THINGS.
AND TAKE LONG VIEW OF THIS WE'VE
COME A LONG WAY AS AN INSTITUTE
WE DIDN'T HAVE A CANNABIS
RESEARCH PROGRAM FIVE YEARS AGO
AND NOW HAVE A BURGEONING
GROWING DEVELOPING PROGRAM.
A LOT MORE TO DO.
YOU LAID THE FOUNDATION FOR
SOMETHING REALLY IMPORTANT WE
STARTED NOW AND CANNABIS IS A
MANUFACTURING MACHINE OF A
VARIETY OF NATURAL PRODUCTS AND
CANNABINOIDS AND TERPENES AND
OTHER CHEMICALS THE PLANT
PROVIDES A WEALTH OF OPPORTUNITY
TO DEVELOP AND THC GOT US HERE
BUT I THINK THC NEEDS TO BE PUT
ASIDE AND FOCUS ON OTHER
COMPOUNDS THAT MAY HAVE
POTENTIAL THERAPEUTIC BENEFIT AS
WE LEARNED OVER THE LAST FOUR OR
FIVE YEARS ACTUALLY WITH YOUR
GOOD WORK.
SO I'D LIKE TO ALSO THANK OUR
NIH COLLEAGUES.
I THINK THIS IS A TEAM EFFORT
NOT JUST NCCIH BUT ALL OF NIH
THAT NEEDS TO GET ON BOARD AND
MAKING PROGRESS IN THAT DOMAIN
AS YOU HEARD FROM THE LAST PANEL
AND CERTAINLY THROUGH OUR
PROGRAM WE'RE MAKING GREAT
STRIDES TO INCLUDE EVERYONE IN
THE TO FURTHER RESEARCH FUNDING
AND OPPORTUNITIES FOR STUDYING
MINOR CANNABINOIDS AND OTHER
ASPECTS OF THE CANNABIS PLANT
FOR THERAPEUTIC DEVELOPMENT
ACROSS A WIDE RANGE OF
CONDITIONS NOT JUST PAIN AND
ANALGESIA AND MANY CONDITIONS AS
YOU LEARNED FROM MY COLLEAGUES
ACROSS NIH AND THAT WILL
CONTINUE TO GROW.
I THINK WE LEARNED A LOT WHERE
THE NEXT STEPS TO BE.
PHARMACO GENETICS CAME UP AND
ARTIFICIAL INTELLIGENCE AND
OTHER NEW TECHNOLOGIES THAT
COULD BE BROUGHT TO BEAR TO
STUDY CANNABINOIDS IS WE'LL TAKE
SERIOUSLY AS WE THINK OF NEXT
STEPS AT NIH.
AND THANK YOU AGAIN FOR SPELT
US -- SETTING US UP AND THANK
YOU INNA BELFER WHO ORGANIZED
THE MEETING.
SHE HAS A DAY JOB.
THESE ALSO A PROGRAM OFFICER AND
NOT A MEETING ORGANIZER SO THANK
YOU INNA AND THE NIH STAFF THAT
HELPED SUPPORT THIS EFFORT
INCLUDING CERTAINLY THE P.I.s
AND THE GENEROUS CONTRIBUTIONS
AND RESEARCH AND IDEAS, THE NIH
I.C.s AND FDA.
WE COULDN'T DO IT WITHOUT FDA.
THANK YOU, FDA.
YOU PLAY AN IMPORTANT ROLE AND
D.A. AND WE KNOW THE ROLE THEY
PLAY IN HELPING REGULATE THE
RESEARCH WE DO AND PLAY AN
IMPORTANT ROLE IN ALL THAT.
SPECIAL THANKS TO NIH STAFF WHO
ORGANIZED AND RAN THE MEETING.
THE PEOPLE BEHIND THE SCENES.
MANY PEOPLE DIDN'T SEE AND
DR. PETERSON AND THE OVERVIEW.
I HOPE YOU ENJOYED COMING TO THE
NIH.
I HOPE YOU HAD FUN AND FOUND
OPPORTUNITIES TO SPEAK TO FELLOW
COLLEAGUES AND HAVE A FEW
COLLABORATIONS STARTED BECAUSE
OF THIS MEETING.
WE ALWAYS LIKE TO SEE THAT
HAPPEN.
IF YOU HAVE QUESTIONS YOU KNOW
WHERE TO FIND ME AND INNA AND
ALL OUR GREAT STAFF, PATRICK AND
WENDY AND CRAIG AND EVERYONE
INVOLVED IN THE CANNABIS PROGRAM
AT NCCIH AND FIND COLLEAGUES AT
NIDA AND OTHER PLACES.
I HOPE YOU'LL KEEP IN TOUCH AND
LOOK FORWARD TO THE FUTURE OF
CANNABINOID RESEARCH AND GREAT
THINGS AHEAD SO THANK YOU AGAIN.
>> THANK YOU SO MUCH.
I WOULD LIKE TO EXTENT THIS
THANKS OF COURSE TO OUR KEY NOTE
SPEAKERS AND GREAT AND
PROVOCATIVE TALKS AND TO NCCIH
OFFICE OF COMMUNICATION AND HAVE
OUR SCIENTIFIC WRITER TAKING
NOTES.
HOPEFULLY THERE WILL BE AN
EXECUTIVE SUMMARY ON THE NCCIH
WEB PAGE AT SOME POINT AND WE
HAD SO MANY REGISTRANTS FOR THIS
VIDEOCAST OF THE MEETING THANKS
TO THE FRAET WORK AND TO ALL THE
COLLEAGUES AND TO YOU ALL AND
TRAINEES AND CO-P.I.s AND
EVERYBODY WHO HELPS YOU WITH THE
IMPORTANT WORK.
THANK YOU SO MUCH.
THIS MEETING IS NOW OFFICIALLY
ADJOURNED.
AND BEFORE WE GO, THOSE WHO STAY
AT THE PRESIDENT HOTEL WILL HAVE
A SHUTTLE COMING AT 5:30 TO THE
GETAWAY TO BE DROPPED OFF.
5:30 PLEASE BE THERE FOR THE
PICK UP FOR YOUR HOTEL AND IT'S
A SHORT WALK TO BETHESDA WITH
LOTS OF GREAT RESTAURANTS AND
LITTLE CAFES.
SO WE ENCOURAGE YOU TO CONTINUE
COLLABORATING AND WORKING AND
EXHANG
EXHANGING -- EXCHANGING IDEAS
AND WE HOPE YOU WILL ENJOY YOUR
EVENING.
THANK YOU.