The

Endo

cann

abin

oid

Syst

em:

Ther

apeu

tic Im

pact

of C

BDan

d Fu

ll-Sp

ectr

um C

anna

bino

ids

Ale

x C

apan

o, D

NP,

CR

NP,

FN

P-B

CSe

nior

Fel

low

: Ins

titut

e of

Em

ergi

ng H

ealth

Pro

fess

ions

, Th

omas

Jef

fers

on U

nive

rsity

Facu

lty: T

he L

ambe

rt C

ente

r for

the

Stud

y of

M

edic

inal

Can

nabi

s &

Hem

p, T

hom

as J

effe

rson

Uni

vers

ity

Disc

losu

res

Chie

f Scie

nce

Offi

cer

Obj

ectiv

es•

1. D

efin

e th

e te

rm C

BD –

the

phyt

ocan

nabi

noid

sder

ived

from

a

lega

lly g

row

n he

mp

plan

t.•

2. E

xpla

in th

e ph

ysio

logy

of t

he m

amm

alia

n en

doca

nnab

inoi

d sy

stem

(ECS

), pa

rticu

larly

as a

mes

sagi

ng sy

stem

for b

iolo

gica

l ac

tivity

.•

3. Li

st th

e pr

imar

y th

erap

eutic

ben

efits

with

in th

e EC

S th

roug

h th

e us

e of

phy

toca

nnab

inoi

ds.

•4.

Des

crib

e th

e ph

arm

acol

ogy

and

pote

ntia

l effi

cacy

of t

he n

on-

psyc

hoac

tive

phyt

ocan

nabi

noid

cann

abid

iol (

CBD)

as a

ther

apeu

tic

trea

tmen

t, in

cludi

ng sa

fety

pro

file,

dru

g in

tera

ctio

ns, d

ose

reco

mm

enda

tions

.•

5. R

ecog

nize

, sel

ect a

nd a

ssem

ble

the

up-to

-dat

e sc

ient

ific

reso

urce

s on

CBD

ther

apy

to p

rovi

de a

ppro

pria

te p

atie

nt co

unse

ling

and

care

thro

ugh

this

evol

ving

indu

stry

.

Con

tinuo

us u

se fo

r > 8

,000

yea

rs

Doc

umen

ted

use

in C

hina

as

early

as

270

0 BC

E

Indi

a, A

frica

& th

e R

oman

Em

pire

fo

r > 2

000

year

s

Gro

wn

by G

eorg

e W

ashi

ngto

n,

used

by

Thom

as J

effe

rson

In th

e U

S Ph

arm

acop

eia

and

wid

ely

used

in A

mer

ica

until

193

7 af

ter t

he

Mar

ihua

na T

ax A

ct

Act o

ppos

ed b

y Am

eric

an M

edic

al

Asso

ciat

ion

Hist

ory

of H

emp

1936

: Film

“Ree

fer

Mad

ness

” is

rele

ased

to

publ

ic

Acc

ordi

ng to

the

Con

gres

sion

al

Res

earc

h Se

rvic

e:th

is

was

has

tily

enac

ted

in

resp

onse

to th

e in

trodu

ctio

n of

mor

phin

e &

opio

ids

Mar

ihua

na Ta

x Ac

t of 1

937

A C R w re int

op

HEM

P &

CB

D 1

01

WH

AT IS

TH

E D

IFFE

REN

CE

BET

WEE

N

HEM

P A

ND

MA

RIJ

UA

NA

CBD

vs. T

HC

CBD

Not p

sych

oact

ive

Will

not

(and

cann

ot!)

get y

ou h

igh

Ther

apeu

tic p

oten

tial:

Anti-

infla

mm

ator

y, p

ain

relie

ving

, im

mun

omod

ulat

ing,

ant

i-anx

iety

, etc

.Ri

sks:

Min

imal

; Dru

g in

tera

ctio

ns, h

epat

ic to

xicit

y Lo

w a

ffini

ty fo

r CB1

& C

B2 re

cept

ors –

“pot

ent

anta

goni

st” (

Thom

as e

t al.,

200

7)

THC

The

com

poun

d th

at e

licits

the

high

in m

ariju

ana

High

ly re

gula

ted

Fede

rally

ille

gal

Ther

apeu

tic p

oten

tial:

Anti-

nocic

eptiv

e>an

ti-in

flam

mat

ory,

ant

i-pro

lifer

ativ

e, e

tc.

Risk

s: Ca

n in

duce

anx

iety

& p

sych

osis,

dru

g in

tera

ctio

ns, h

epat

ic to

xicit

yBi

nds t

o bo

th C

B1 &

Cb2

rece

ptor

s –pa

rtia

l ago

nist

•Ex

cept

iona

lly ri

ch in

po

lyun

satu

rate

d fa

tty a

cids

•O

meg

a-3

& O

meg

a -6

–Li

nole

nic

Acid

, α-li

nole

nic

acid

, ga

mm

a-lin

olen

ic a

cid*

•An

tithr

ombo

tic•

Anti-

infla

mm

ator

y•

Anti-

asth

mat

ic•

Imm

unom

odul

ator

y (a

utoi

mm

une

diso

rder

s, R

A, e

tc.)

Hem

p Se

ed O

il

(Def

erne

, 199

6; R

ose,

199

1; R

ose,

199

7)

Full

Spec

trum

H

emp

Extr

act

•W

hat i

s th

e di

ffere

nce?

•Th

e be

nefit

s of

hem

p-se

ed o

il PL

US

cann

abin

oids

Wha

t are

Can

nabi

noid

s?

•How

do

they

wor

k?–I

ntro

duct

ion

to th

e En

doca

nnab

inoi

d Sy

stem

s?

Qua

lifyi

ng

Cond

ition

s

•Am

yotr

ophi

c lat

eral

scle

rosis

.•

Autis

m.

•Ca

ncer

, inc

ludi

ng re

miss

ion

ther

apy.

•Cr

ohn’

s dise

ase.

•Da

mag

e to

the

nerv

ous t

issue

of t

he ce

ntra

l ne

rvou

s sys

tem

(bra

in-s

pina

l cor

d) w

ith

obje

ctiv

e ne

urol

ogica

l ind

icatio

n of

in

trac

tabl

e sp

astic

ity, a

nd o

ther

ass

ocia

ted

neur

opat

hies

.•

Dysk

inet

ic an

d sp

astic

mov

emen

t diso

rder

s.•

Epile

psy.

•Gl

auco

ma.

•HI

V / A

IDS.

•Hu

ntin

gton

’s di

seas

e.•

Infla

mm

ator

y bo

wel

dise

ase.

•…

ther

e’s m

ore

Qua

lifyi

ng

Cond

ition

s(c

ont’d

)

•In

trac

tabl

e se

izure

s.•

Mul

tiple

scle

rosis

.•

Neur

odeg

ener

ativ

e di

seas

es.

•Ne

urop

athi

es.

•O

pioi

d us

e di

sord

er.

•Pa

rkin

son’

s dise

ase.

•Po

st-tr

aum

atic

stre

ss d

isord

er.

•Se

vere

chr

onic

or in

trac

tabl

e pa

in o

f ne

urop

athi

c orig

in o

r sev

ere

chro

nic o

r in

trac

tabl

e pa

in.

•Si

ckle

cell

anem

ia.

•Te

rmin

al il

lnes

s

“I ca

n’t l

ist a

ll th

e ph

ysio

logi

cal s

yste

ms

and

cond

ition

s af

fect

ed b

y ca

nnab

inoi

ds b

ecau

se

ther

e ar

e to

o m

any.

”

The

Endo

cann

abin

oid

Syst

em

-Dr.

Rap

hael

Mec

houl

am,

the

chem

ist w

ho id

entif

ied

the

endo

cann

abin

oid

syst

em

The

Rece

ptor

sAc

tivat

ion

and

upre

gula

tion

of th

e en

doca

nnab

inoi

d sy

stem

is e

ssen

tial t

o he

alth

y liv

ing

21

CB1

Rece

ptor

s are

pre

dom

inan

t in

the

brai

n.

(Hip

poca

mm

us, C

ereb

ellu

m, a

nd C

ereb

rum

) CB2

Rece

ptor

s are

pre

vale

nt th

roug

hout

the

body

. (Im

mun

e, D

iges

tive,

Mus

cula

r, an

d Va

scul

ar S

yste

ms)

Out

side

Cell

Insid

e Ce

ll

CB1

CB2

Out

side

Cell

Insid

e Ce

ll

Summary

•Tw

o co

nfirm

ed re

cept

or su

btyp

es, m

any

othe

r put

ativ

e•

CB1

ubiq

uito

us, a

bund

ant i

n ne

rvou

s tis

sue

•CB

2 m

ore

loca

lized

, spe

cifica

lly to

im

mun

e ce

lls

•TH

C bi

nds e

qual

ly to

bot

h, C

BD B

INDS

TO

NEI

THER

•Tw

o co

nfirm

ed e

ndog

enou

s lig

ands

(eCB

s),

anan

dam

ide

and

2-AG

, m

any

othe

r put

ativ

e•

Clea

ved

by li

pid

prec

urso

rs o

n de

man

d•

Degr

aded

by

at le

ast t

wo

enzy

mes

Man

y ph

arm

acol

ogica

l effe

cts o

f Can

nabi

s exp

lain

ed b

y ac

tivat

ion

of C

B1 a

nd/o

r CB2

rece

ptor

s

Som

e (e

.g. C

BD e

ffect

s) a

re n

ot C

B re

cept

or m

edia

ted

PAIN

&

INFL

AMM

ATIO

N

•Ch

emica

ls re

leas

ed

arou

nd th

e sit

e of

di

seas

e co

ntrib

ute

to

chro

nic p

ain

cond

ition

s (h

istam

ine,

bra

dyki

nin,

se

roto

nin,

ATP

, pr

osta

glan

dins

, cy

toki

nes,

chem

okin

es

etc.

..)

•Ph

ytoc

anna

bino

ids

gene

rally

-and

CBD

sp

ecifi

cally

-sup

pres

s th

is in

flam

mat

ory

resp

onse

thro

ugh

mul

tiple

mec

hani

sms

The

Endo

cann

abin

oid

Syst

em (E

CS)

Activ

atio

n of

the

ECS

thro

ugh

cann

abin

oids

Endo

geno

us

cann

abin

oids

Anan

dam

ide,

2-

AG

Exog

enou

s Ca

nnab

inoi

ds

Plan

t der

ived

CBD,

THC

, CBG

, CB

N, T

HCV,

etc

.

CBD

& A

nand

amid

eNa

med

afte

r San

skrit

wor

d –

Anan

da -

“blis

s”

Dire

ctly

corr

elat

ed w

ith im

prov

ed

moo

d, re

duct

ion

of d

epre

ssio

n an

d an

xiet

y re

spon

ses.

Endo

geno

us le

vels

are

low

and

th

e ha

lf-lif

e is

rapi

d

Mec

hani

sm th

roug

h FA

AH

inhi

bitio

n Po

tent

ial f

or A

SD re

late

d so

cial

impa

irmen

t (W

ei e

t al.,

201

6)

CBD,

Ana

ndam

ide

& O

xyto

cin

Stud

y at

UC

Irvin

e

Wei

et a

l., 2

015

CBD

&

Infla

mm

atio

n

•M

oder

atio

n of

Mas

t Cel

l act

ivity

and

hist

amin

e re

leas

e•

Redu

ctio

n in

imm

unor

eact

ive

micr

oglia

•De

crea

se in

toll-

like

rece

ptor

resp

onse

s•

Prom

otio

n of

ade

nosin

e re

cept

or A

2A

•He

dge

et a

l., 2

016;

Mar

tin-M

oren

o et

al.,

201

1;

Booz

, 201

7; R

usso

, 200

8.

CBD

& M

ood

Mul

tiple

bas

ic sc

ienc

e st

udie

s

Hum

an so

cial p

hobi

a st

udy

(use

d iso

late

at h

igh

dose

600

mg,

Be

rgam

asch

i et a

l., 2

011)

Seco

ndar

y ou

tcom

es

Activ

ity o

n 5H

T1-A

sero

toni

n re

cept

or

PTSD

CBD

&

Neur

opro

tect

ion

Atte

nuat

ion

of

hipp

ocam

pal

neur

ogen

esis

Mod

ulat

ion

of ce

ll de

ath

path

way

s

Decr

ease

in

dege

nera

ting

neur

ons

and

incr

ease

in v

iabl

e ne

uron

s afte

r hyp

oxic-

ische

mia

.

•Ind

ivid

ually

and

syne

rgist

ically

•Inc

reas

e in

glu

tath

ione

•Dec

reas

e hi

gh le

vels

of g

luta

mat

e to

redu

ce

oxid

ativ

e st

ress

• • •An

tioxi

dant

pot

entia

l

•Ani

mal

stud

ies:

incr

ease

in sy

napt

ic pr

otei

ns in

pr

efro

ntal

cort

ex &

hip

poca

mpu

s•P

rolo

nged

effe

cts

• •

Neur

oreg

ener

ativ

e po

tent

ial

Cam

pos e

t al.,

201

3; Ju

nkat

et a

l., 2

013;

Tum

a&

Ste

ffens

, 20

12; F

erna

nez-

Lope

z et a

l., 2

013;

Alv

arez

et a

l., 2

008

THE

ENTO

UR

AG

E EF

FEC

T:

IT’S

NO

T O

NLY

AB

OU

T C

BD

!W

HAT

IS F

ULL

-SPE

CTR

UM

HEM

P EX

TRA

CT?

The

Ento

urag

e Ef

fect

: W

hy W

hole

-Pla

nt, F

ull-S

pect

rum

Mat

ters

Terp

enes

Dose

Res

pons

e Cu

rve

02468101214161820

12

34

56

78

910

1112

1314

1516

1718

1920

2122

2324

25

Full

Spec

trum

vs.

Isol

ate

Serie

s1Se

ries2

ISO

LATE

Full-

Spec

trum

CANN

ABIN

OID

S, P

AIN,

&

OPI

OID

RED

UCTI

ON

Opi

oid

Redu

ctio

n:

Why

CBD

?

•Ef

ficac

y•

Safe

ty•

With

draw

al•

Subs

titut

e or

Trea

tmen

t?

CA

NN

AB

INIO

IDS

AN

D P

AIN

JAM

A’s s

yste

mat

ic re

view

of c

anna

bino

ids a

nalg

esia

.1

•28

rand

omize

d cli

nica

l tria

ls (R

CTs)

com

plet

ed o

ver 6

7 ye

ars.

•Th

e re

view

con

clude

d th

at ca

nnab

is th

erap

y fo

r mar

ked

pain

relie

f and

sp

astic

ity re

duct

ion

is su

ppor

ted

by h

igh-

qual

ity e

vide

nce.

39

Met

a-An

alys

is fro

m th

e N

atio

nal A

cade

mie

s of S

cien

ce, E

ngin

eerin

g &

Med

icin

e•

“Con

clusiv

e or

subs

tant

ial e

vide

nce”

of ca

nnab

inoi

ds’ e

ffica

cy in

pai

n re

lief,

spas

ticity

, sei

zure

s.•

Wel

l tol

erat

ed

Petz

ke’s

Syst

emat

ic R

evie

w o

n Ca

nnab

inoi

ds &

Pai

n•

15 R

CTs

•Co

nclu

sion:

Can

nabi

noid

s effe

ctiv

e fo

r pai

n re

lief

•Si

de e

ffect

s of i

ntox

icatio

n w

ith h

igh

THC*

CB

D fo

r Opi

oid

Red

uctio

n:

With

draw

al

–CB

D &

Fen

tany

l Ph

arm

acok

inet

ic St

udy

–No

incr

ease

d ris

k of

re

spira

tory

dep

ress

ion

–No

incr

ease

d ca

rdio

vasc

ular

risk

•Pr

eclin

ical

and

pilo

t stu

dies

hav

e sh

own

CBD

may

redu

ce o

pioi

d cr

avin

gs a

nd a

llevi

ate

opio

id w

ithdr

awal

sym

ptom

s.

•C

BD d

oes

not p

ose

a ris

k fo

r add

ictio

n or

dep

ende

nce

•In

hum

ans:

Dou

ble-

blin

d, p

lace

bo c

ontro

lled

RC

T:–

CBD

was

saf

e w

hen

used

in c

onju

nctio

n w

ith o

pioi

ds–

No

incr

ease

d ris

k of

resp

irato

ry d

epre

ssio

n or

car

diov

ascu

lar

issu

es–

Stat

istic

ally

sig

nific

ant r

educ

tion

in h

eroi

n cr

avin

gs a

fter o

ne

dose

of C

BD a

t 1 h

r, 24

hrs

& 7

days

–C

BD d

ecre

ased

cig

aret

te u

se a

mon

g de

pend

ent p

artic

ipan

ts.

–C

BD re

duce

d an

xiet

y in

the

patie

nts

who

rece

ived

it

CB

D fo

r Opi

oid

Red

uctio

n

•Pr

eclin

ical

and

pilo

t stu

dies

hav

e sh

own

CBD

may

redu

ce o

pioi

d cr

avin

gs a

nd a

llevi

ate

opio

id w

ithdr

awal

sym

ptom

s.

•C

BD d

oes

not p

ose

a ris

k fo

r add

ictio

n or

dep

ende

nce

•In

hum

ans:

Dou

ble-

blin

d, p

lace

bo c

ontro

lled

RC

T:–

CBD

was

saf

e w

hen

used

in c

onju

nctio

n w

ith o

pioi

ds–

No

incr

ease

d ris

k of

resp

irato

ry d

epre

ssio

n or

car

diov

ascu

lar

issu

es–

Stat

istic

ally

sig

nific

ant r

educ

tion

in h

eroi

n cr

avin

gs a

fter o

ne

dose

of C

BD a

t 1 h

r, 24

hrs

& 7

days

–C

BD d

ecre

ased

cig

aret

te u

se a

mon

g de

pend

ent p

artic

ipan

ts.

–C

BD re

duce

d an

xiet

y in

the

patie

nts

who

rece

ived

it

CB

D fo

r Opi

oid

Red

uctio

n

•St

ates

with

med

ical

can

nabi

s la

ws:

24.

8% lo

wer

mea

n an

nual

opi

oid

over

dose

mor

talit

y ra

te c

ompa

red

to s

tate

s w

ithou

t med

ical

can

nabi

s ac

cess

•M

edic

are

pres

crip

tions

for d

rugs

to tr

eat p

ain,

dep

ress

ion,

anx

iety

, na

usea

, psy

chos

es, s

eizu

res

and

slee

p re

duce

d in

sta

tes

with

ca

nnab

inoi

ds

•M

ichi

gan:

retro

spec

tive

surv

ey re

veal

ed a

64%

dec

reas

e in

opi

oid

use,

a d

ecre

ase

in s

ide

effe

cts,

and

an

over

all i

mpr

oved

qua

lity

of li

fe

in th

ose

who

use

d ca

nnab

inoi

ds

•C

alifo

rnia

, a s

urve

y of

2,8

97 re

veal

ed th

at 9

7% o

f opi

oid

user

s re

porte

d th

at th

ey “s

trong

ly a

gree

d/ag

reed

” tha

t can

nabi

noid

s re

duce

d th

eir o

pioi

d us

e

CB

D fo

r Opi

oid

Red

uctio

n

•M

aine

Med

ical

Cen

ter:

1,50

0 op

ioid

use

rs:

patie

nts

opio

ids

for c

hron

ic p

ain.

•Re

duct

ion

in:

–O

pioi

ds: 7

6.7%

–

Anxi

ety

med

s: 71

.8%

–

Depr

essio

nm

eds:

37%

–

Slee

p m

eds:

65.2

%

–M

igra

ine

med

s: 66

.7

–Al

coho

l: 42

%

CB

D fo

r Opi

oid

Red

uctio

n

Self-

repo

rt fro

m o

ver 1

,300

fibr

omya

lgia

pat

ient

s on

tre

atm

ent e

ffica

cy o

f Cym

balta

, Lyr

ica,

Sav

ella

& C

BD

Cym

balta

: 8%

“ve

ry e

ffect

ive”

32%

“it h

elps

a li

ttle”

60%

“did

not

wor

k at

all”

Lyric

a: 10%

“ver

y ef

fect

ive”

29%

“it h

elps

a li

ttle”

61%

“did

not

wor

k at

all

Save

lla:

10%

“ver

y ef

fect

ive”

22%

“it h

elps

a li

ttle”

68%

“did

not

wor

k at

all”

Can

nabi

noid

s:62

% “v

ery

effe

ctiv

e”33

% “h

elps

a li

ttle”

5% “d

id n

ot h

elp

at a

ll”

Nat

iona

l Pai

n Fo

unda

tion

Stud

y on

Fib

rom

yalg

ia

•Se

lf-re

port

•Va

riabl

e do

sage

•So

me

may

be

usin

g hi

gher

TH

C–

“Mic

rodo

se” o

f TH

C

belie

ved

to b

e su

ffici

ent

–Pr

oper

ties

of C

BD

Lim

itatio

ns

Opi

oid

Subs

titut

e or

Add

ictio

n Tr

eatm

ent?

–De

crea

ses r

ewar

d fa

cilita

ting

effe

ct &

seek

ing

beha

vior

in

opi

oid

depe

nden

ce, b

ut n

ot co

cain

e (K

atsid

onie

t al.,

201

3)•

CBD

inhi

bite

d de

crea

se o

f the

ICSS

thre

shol

d by

mor

phin

e•

No m

otor

impa

irmen

t•

Acitv

ityon

5-H

T1A

–De

crea

sed

opio

id se

ekin

g be

havi

or (R

en e

t al.,

200

9)•

Inhi

bits

cue-

indu

ced

hero

in-s

eeki

ng b

ehav

ior.

Pos

sibly

thro

ugh

alte

red

CB1

expr

essio

n in

nuc

leus

acc

umbe

ns•

Effe

cts l

aste

d up

to 2

wee

ks

–Po

tent

ial f

or re

laps

e pr

even

tion

in co

cain

e &

alco

hol

addi

ctio

n (G

onza

lez-

Cuev

as e

t al,

2018

)•

Redu

ctio

n in

anx

iety

, im

pulsi

vity

, dru

g-se

ekin

g be

havi

ors p

rovo

ked

by st

ress

&

dru

g cu

es•

CBD

clear

ed fr

om b

rain

with

in 3

day

s•

Effe

cts p

ersis

ted

5 m

onth

s lat

er

–Tr

ansla

tiona

l risk

s

Anim

al S

tudi

es: C

BD e

valu

ated

for treatmento

f dr

ug a

ddict

ion

Eval

uatin

g th

e ef

fect

s of

fu

ll-sp

ectru

m h

emp

extra

ct

on o

pioi

d us

e an

d qu

ality

of

life

indi

cato

rs in

chr

onic

pa

in p

atie

nts

OB

SERV

ATIO

NA

L ST

UD

Y

This

obse

rvat

iona

l stu

dy a

imed

to in

vest

igat

e th

e ef

fect

s of a

ca

nnab

idio

l (CB

D) ri

ch fu

ll-sp

ectr

um h

emp

extr

act p

rodu

ct o

n op

ioid

use

, qua

lity

of li

fe (Q

OL)

mea

sure

s, an

d w

illin

gnes

s to

dow

n tit

rate

opi

oids

in ch

roni

c pa

in p

atie

nts i

n on

e pa

in m

anag

emen

t cli

nic

in ru

ral I

ndia

na.

A to

tal o

f 97

part

icipa

nts c

ompl

eted

the

8-w

eek

stud

y.O

f the

m, 9

4 pa

rtici

pant

s use

d th

e he

mp-

extr

act.

Thre

e ch

ose

not t

o us

e he

mp

extr

act.

Addi

tiona

l dat

a co

llect

ion

occu

rred

at w

eek

12 w

ith 3

7 pa

rtici

pant

s. O

f tho

se w

ho

took

the

hem

p pr

oduc

t, 53

% (N

=50)

to 5

8% (

N=55

) red

uced

opi

oid

use

at w

eeks

8 a

nd 1

2 re

spec

tivel

y, an

d94

%(N

=89)

repo

rted

im

prov

ed Q

OL o

utco

mes

.No

ne (N

=0) o

f the

par

ticip

ants

who

did

no

t tak

e th

e he

mp

prod

uct r

educ

ed o

pioi

ds o

r rep

orte

d im

prov

ed

QO

L out

com

es.

Qua

ntita

tive

Stat

istica

l Ana

lyse

s usin

g AN

OVA

was

co

mpl

eted

with

SPS

S.Im

prov

emen

ts in

scor

es fr

om b

asel

ine

to

wee

k 8

wer

e st

atist

ically

sign

ifica

nt o

n th

e PE

G sc

ale,

the

PSQ

I, an

d th

e PD

I.Sc

ore

chan

ges o

n th

e PH

Q-4

and

the

Will

ingn

ess V

AS

sugg

este

d a

dow

nwar

d tr

end

but w

ere

not s

tatis

tical

ly

signi

fican

t.Th

is st

udy

sugg

ests

that

CBD

-rich

hem

p ex

trac

t is

effe

ctiv

e in

redu

cing

opio

id u

se a

nd im

prov

ing

qual

ity o

f life

ou

tcom

es in

chro

nic

pain

pat

ient

s, bu

t it i

s not

effe

ctiv

e in

im

prov

ing

patie

nts’

will

ingn

ess t

o do

wn

titra

te o

pioi

ds.

Stat

istica

lly si

gnifi

cant

, p=.

003

Stat

istica

lly si

gnifi

cant

, p=.

006

*sta

tistic

ally

sign

ifica

nt, p

=.09

8*N

ot st

atist

ically

sign

ifica

nt

Conc

lusio

nsLim

itatio

nsNe

ed fo

r clin

ical e

duca

tion

Drug

scre

enin

g ad

apta

tions

Futu

re R

esea

rch

Gen

eva:

Aug

ust 1

7, 2

018

In a

n hi

stor

ic re

solu

tion,

the

Wor

ld H

ealth

O

rgan

izat

ion

(WH

O) E

xper

t Com

mitt

ee o

n D

rug

Dep

ende

nce

just

rec

omm

ende

d th

at “

prep

arat

ions

co

nsid

ered

to b

e pu

re C

BD s

houl

d no

t be

sche

dule

d w

ithin

the

Inte

rnat

iona

l Dru

g C

ontr

ol C

onve

ntio

ns.”

Som

e ke

y fin

ding

s fro

m th

e W

HO

:“T

here

are

no

case

rep

orts

of a

buse

or

depe

nden

ce r

elat

ing

to th

e us

e of

pur

e C

BD

.”“N

o pu

blic

hea

lth p

robl

ems

have

bee

n as

soci

ated

w

ith C

BD

use

.”“C

BD

has

bee

n fo

und

to b

e ge

nera

lly w

ell t

oler

ated

w

ith a

goo

d sa

fety

pro

file.

”“T

here

is n

o ev

iden

ce th

at C

BD

is li

able

to s

imila

r ab

use

and

sim

ilar i

ll-ef

fect

s as

sub

stan

ces…

such

as

can

nabi

s or

TH

C.”

1.M

ay 2

018:

FD

Asc

ient

ists

con

clud

eth

atC

BD h

as n

o ab

use

pote

ntia

l and

doe

s no

t pos

e a

risk

to p

ublic

he

alth

.

2.In

the

hour

s fo

llow

ing

the

2018

Far

m B

ill si

gnin

g, th

e ag

ency

issu

ed tw

o gr

ound

-bre

akin

g st

atem

ents

: (1

)opi

ning

that

hul

led

hem

p se

ed, h

emp

seed

pro

tein

po

wde

r and

hem

p se

ed o

il ar

e ge

nera

lly re

cogn

ized

as

safe

(GR

AS) u

nder

thei

r int

ende

d co

nditi

ons

of u

se;

and

(2) t

hat t

he a

genc

yis

serio

usly

con

side

ring

usin

g its

aut

horit

y to

issu

e a

regu

latio

n th

at w

ill sp

ecifi

cally

al

low

hem

p-de

rived

CBD

ingr

edie

nts

in fo

ods

and

supp

lem

ents

, and

that

it w

ill re

ach

out t

o th

e in

dust

ry

and

the

publ

ic fo

r inp

ut.

BA

BY

BO

OM

ERS

FIR

ST

USE

D C

AN

NA

BIN

OID

S TO

BE

AN

TI-E

STA

BLI

SHM

ENT…

NO

W T

HEY

USE

TH

EM T

O B

E A

NTI

-INFL

AM

MAT

ORY

!-R

onal

d Tu

ma,

PhD

The

Brig

htfie

ld S

tudy

: A

third

-par

ty m

arke

t an

alys

is e

valu

ated

the

mar

ket f

or h

emp-

deriv

ed

CBD

with

ove

r 1,4

00

parti

cipa

nts

•To

p C

ondi

tions

for C

BD u

se:

depr

essi

on, i

nsom

nia,

anx

iety

, pa

in, m

igra

ines

, arth

ritis

and

na

usea

•84

% re

porte

d he

mp-

deriv

ed

CBD

was

ver

y ef

fect

ive

or

extre

mel

y ef

fect

ive

in re

duci

ng

thei

r clin

ical

con

ditio

ns.

(13%

m

oder

atel

y, 3

% s

light

ly, 0

% n

ot

at a

ll)

•42

% s

ubst

itute

d C

BD c

ompl

etel

y an

d el

imin

ated

use

of t

radi

tiona

l m

edic

atio

ns.

Key

Tak

eaw

ays

from

the

Brig

htfie

ld S

tudy

•69

% o

f hem

p-de

rived

CBD

use

rs

repo

rted

CBD

was

eith

er m

ore

effe

ctiv

e or

“muc

h m

ore

effe

ctiv

e”

than

oth

er O

TC p

rodu

cts

they

’ve

tried

.

•56

% re

porte

d th

e sa

me

over

pr

escr

iptio

n m

eds.

•90

% re

porte

d th

at th

ey w

ere

likel

y to

buy

aga

in.

•Pr

os: r

elie

f with

out s

ide

effe

cts,

no

t psy

choa

ctiv

e

•C

ons:

lack

of a

vaila

bilit

y, n

ot

psyc

hoac

tive

•Ab

out 6

7% o

f CBD

use

rs b

ough

t bet

wee

n 1

& 3

prod

ucts

in

the

last

two

wee

ks

•C

BD u

sers

are

“sig

nific

antly

mor

e lik

ely

to p

urch

ase

bran

ded

prod

ucts

via

lega

l and

offi

cial

cha

nnel

s”

•Sp

lit a

lmos

t eve

nly

betw

een

gend

ers

(55%

fem

ale,

44%

m

ale)

•Sp

anne

d ac

ross

all

age

grou

ps.

Key

Tak

eaw

ays

from

the

Brig

htfie

ld S

tudy

The

Prob

lem

with

Sta

tes’

Med

icina

l Ca

nnab

is Pr

ogra

ms

Have

hum

an p

atie

nts

or cl

ient

s? W

hat y

ou

need

to k

now

•Do

sing

•In

tera

ctio

ns•

Mon

itorin

g•

Prod

uct S

elec

tion

Dos

ing

and

Del

iver

ySu

blin

gual

vs.

Ora

l vs.

Topi

cal

Find

the

peak

Derm

atom

es

•CB

D in

tera

cts w

ith

CYP

450

–Po

tent

ial i

nhib

ition

at

CYP3

A4, C

YP2C

9,

CYP2

C19,

CYP

2D6*

•Th

ink

grap

efru

it ju

ice,

but

…•

Clin

ical

ly s

igni

fican

t?

•Fo

llow

-up

& C

ouns

elin

g

Dru

g / D

rug

Inte

ract

ions

GW

Pha

rmac

eutic

als:

40m

g sa

tivex

(1:1

ratio

)•

No

inte

ract

ion

with

oth

er C

YP 4

50, o

ther

dr

ugs

Pedi

atric

Evi

denc

e:•

Inte

ract

ion

with

ant

i-epi

lept

ic d

rugs

at

35m

g C

BD•

Res

ulte

d in

incr

ease

d si

de-e

ffect

s fro

m

anti-

epile

ptic

dru

gs•

Red

uced

dos

e of

ant

i-epi

lept

ic d

rugs

to

reve

rse

adve

rse

effe

cts

•M

aint

aine

d ov

eral

l red

uctio

n in

sei

zure

ac

tivity

•70

% o

f par

ticip

ants

had

50%

redu

ctio

n in

ove

rall

seiz

ures

But

Will

I Fa

il a

Dru

g Te

st?

•O

rigin

al F

ull S

pect

rum

pro

duct

s (0

.3%

TH

C) –Un

likel

y, b

ut p

ossib

le.

–In

divi

dual

met

abol

ism v

arie

s–

False

pos

itive

on

imm

unoa

ssay

ur

ine

drug

scre

en•

Full

spec

trum

, THC

-free

pro

duct

s–

THC

leve

l is z

ero

–N

o ch

ance

of a

TRU

E po

sitiv

e–

May

trig

ger f

alse

pos

itive

with

UD

S*

Use

in P

regn

ancy

&

Brea

stfe

edin

g•

Anim

al D

ata:

•O

ral a

dmin

istra

tion

of ca

nnab

idio

l (0,

75,

150

, or 2

50 m

g/kg

/day

) to

preg

nant

rats

thro

ugho

ut

the

perio

d of

org

anog

enes

is re

sulte

d in

em

bryo

feta

l mor

talit

y at

the

high

est d

ose

test

ed.

Ther

e w

ere

no o

ther

dru

g-re

late

d m

ater

nal o

r dev

elop

men

tal e

ffect

s. Th

e hi

ghes

t no-

effe

ct

dose

for e

mbr

yofe

tal t

oxici

ty in

rats

was

ass

ocia

ted

with

mat

erna

l pla

sma

cann

abid

iol

expo

sure

s (AU

C) a

ppro

ximat

ely

16 ti

mes

that

in h

uman

s at t

he re

com

men

ded

hum

an d

ose

(RHD

) of 2

0 m

g/kg

/day

.

•O

ral a

dmin

istra

tion

of ca

nnab

idio

l (0,

50,

80,

or 1

25 m

g/kg

/day

) to

preg

nant

rabb

its

thro

ugho

ut o

rgan

ogen

esis

resu

lted

in d

ecre

ased

feta

l bod

y w

eigh

ts a

nd in

crea

sed

feta

l st

ruct

ural

var

iatio

ns a

t the

hig

hest

dos

e te

sted

, whi

ch w

as a

lso a

ssoc

iate

d w

ith m

ater

nal

toxic

ity. M

ater

nal p

lasm

a ca

nnab

idio

l exp

osur

es a

t the

no-

effe

ct le

vel f

or e

mbr

yofe

tal

deve

lopm

enta

l tox

icity

in ra

bbits

wer

e le

ss th

an th

at in

hum

ans a

t the

RHD

.

•W

hen

cann

abid

iol (

75, 1

50, o

r 250

mg/

kg/d

ay) w

as o

rally

adm

inist

ered

to ra

ts th

roug

hout

pr

egna

ncy

and

lact

atio

n, d

ecre

ased

gro

wth

, del

ayed

sexu

al m

atur

atio

n, n

euro

beha

vior

al

chan

ges (

decr

ease

d ac

tivity

), an

d ad

vers

e ef

fect

s on

mal

e re

prod

uctiv

e or

gan

deve

lopm

ent

(sm

all t

este

s in

adul

t offs

prin

g) a

nd fe

rtili

ty w

ere

obse

rved

in th

e of

fspr

ing

at th

e m

id a

nd h

igh

dose

. The

se e

ffect

s occ

urre

d in

the

abse

nce

of m

ater

nal t

oxici

ty. T

he n

o-ef

fect

dos

e fo

r pre

-an

d po

stna

tal d

evel

opm

enta

l tox

icity

in ra

ts w

as a

ssoc

iate

d w

ith m

ater

nal p

lasm

a ca

nnab

idio

l ex

posu

res a

ppro

ximat

ely

9 tim

es th

at in

hum

ans a

t the

RHD

. 8.2

•La

ctat

ion

Risk

Sum

mar

y Th

ere

are

no d

ata

on th

e pr

esen

ce o

f can

nabi

diol

or i

ts m

etab

olite

s in

hum

an m

ilk, t

he e

ffect

s on

the

brea

stfe

d in

fant

, or t

he e

ffect

s on

milk

pro

duct

ion.

The

de

velo

pmen

tal a

nd h

ealth

ben

efits

of b

reas

tfeed

ing

shou

ld b

e co

nsid

ered

alo

ng w

ith th

e m

othe

r’s c

linica

l nee

d fo

r EPI

DIO

LEX

and

any

pote

ntia

l adv

erse

effe

cts o

n th

e br

east

fed

infa

nt

from

EPI

DIO

LEX

or fr

om th

e un

derly

ing

mat

erna

l con

ditio

n.

NAV

IGAT

ING

TH

E W

ILD

WES

T O

F TH

E C

BD

MA

RK

ET

FDA:

91%

of p

rodu

cts d

o no

t mat

ch

pack

agin

g (2

016)

JAM

A: 7

0% o

f CBD

pro

duct

s do

not

mat

ch la

bel (

Bon

Mill

er e

t al.,

201

7)

Solu

tion?

Ask

for a

Cer

tifica

te o

f An

alys

is (C

OA)

Cert

ifica

te o

f An

alys

is

•Sh

ould

:–

Be d

one

by a

th

ird p

arty

lab

–In

clude

ca

nnab

inoi

d co

nten

t–

Inclu

de te

sts f

or

pest

icide

s, m

icrob

es,

chem

icals

–Be

lot s

pecif

ic

VER

IFY

THE

CER

TIFI

CAT

E O

F A

NA

LYSI

S

•30m

l bot

tle

•Lab

eled

300

mg

•Is

this

cor

rect

?

•Is

this

full-

spec

trum

?

• • • •

CO

A fo

r a C

BD

“A

rous

al”

Prod

uct

•30m

l bot

tle

•How

man

y m

g of

CBD

?

•Is

it fu

ll-sp

ectru

m?

Anal

yst:

JDP

Test

Dat

e: 3

/4/2

018

The

clie

nt sa

mpl

e w

as a

naly

zed

for p

lant

-bas

ed c

anna

bino

ids b

y C

onve

rgen

ce C

hrom

atog

raph

y (C

C).

The

col

lect

ed d

ata

was

com

pare

d to

dat

a co

llect

ed fo

r cer

tifie

d re

fere

nce

stan

dard

s at k

now

n co

ncen

tratio

ns.

2695

2-CN

CN: C

anna

bino

id P

rofil

e &

Pot

ency

[WI-

10-0

4]

Can

-Tek

Lab

s Llc

.81

07 S

outh

I-35

serv

ice

rd.

Okl

ahom

a C

ity, o

k 7

3149

Att

n: K

orbi

n H

and

Cer

tific

ate

ID: 2

6952

Clie

nt S

ampl

e ID

: 250

-60%

Mat

rix: T

inct

ure

- MC

T O

ilD

ate

Rec

eive

d:2/

16/2

018

This

test

met

hod

was

per

form

ed in

acc

orda

nce

with

the

requ

irem

ents

of I

SO/IE

C 1

7025

. The

sam

ple

was

pro

vide

d to

the

labo

rato

ry b

y th

e cl

ient

an

d te

sted

as r

ecei

ved.

The

se re

sults

rela

te o

nly

to th

e te

st a

rticl

e lis

ted

in th

is re

port.

Rep

orts

may

not

be

repr

oduc

ed e

xcep

t in

thei

r ent

irety

.

CB

D0.

26TH

CV

-Δ9

-TH

C-

CB

C-C

BN-

CB

G-TH

CA

-C

BD

A-

CB

GA

-C

BD

V-

Aut

horiz

atio

n:Si

gnat

ure:

Dat

e:

3/5/

2018

Mat

thew

Silv

a, C

hem

ical E

ngin

eer

Max

TH

C (a

nd M

ax C

BD

) are

cal

cula

ted

valu

es fo

r tot

al c

anna

bino

ids a

fter h

eatin

g, a

ssum

ing

com

plet

e de

carb

oxyl

atio

n of

the

acid

to th

e ne

utra

l fo

rm. I

t is c

alcu

late

d ba

sed

on th

e w

eigh

t los

s of t

he a

cid

grou

p du

ring

deca

rbox

ylat

ion:

M

ax T

HC

= (0

.877

x T

HC

A) +

TH

C.

ND

= N

one

dete

cted

abo

ve th

e lim

its o

f det

ectio

n (L

LD)

IDW

eigh

t %C

onc.

Δ9-T

HC

ND

ND

THC

VN

DN

DC

BD

0.26

wt %

2.51

mg/

mL

CB

DV

ND

ND

CB

GN

DN

DC

BC

ND

ND

CB

NN

DN

DTH

CA

ND

ND

CB

DA

ND

ND

CB

GA

ND

ND

0.26

wt%

2.51

mg/

mL

Tota

l-

-M

ax T

HC

0.26

wt%

2.51

mg/

mL

Max

CB

D

FM-1

0-05

, Rev

. 1, D

CN

:14-

0001

Page

1 o

f 142

0 Fo

rtun

e B

lvd.

• M

ilfor

d, M

A 0

1757

• 61

7-22

1-33

56w

ww

.Pro

Ver

deL

abs.c

om

•30

ml b

ottle

•La

bele

d “5

00m

g” o

f C

BD

•Is

it c

orre

ct?

•Is

it fu

ll-sp

ectru

m?

8107

Sout

h I-

35se

rvi

ND

ND

ND

ND

ND

ND

222.551

mg/

mLLL

VER

IFY

THE

CER

TIFI

CAT

E O

F A

NA

LYSI

S

CBD

for P

ets

•Co

rnel

l Stu

dies

*•

Phar

mac

okin

etics

•Ef

ficac

y•

Safe

ty•

Dosin

g (2

mg/

kg

bid)

*

Law

s & Le

galit

y

2018

Farm

Bill

•He

mp-

deriv

ed C

BD is

no

long

er a

cont

rolle

d su

bsta

nce

unde

r fed

eral

law

.

As a

cons

eque

nce

of th

e 20

18 F

arm

Bill

, hem

pis

now

pe

rman

ently

rem

oved

from

the

Cont

rolle

d Su

bsta

nces

Act

(C

SA).

It is

now

dee

med

an

agric

ultu

ral c

omm

odity

, no

long

er a

ble

to b

e cla

ssifi

ed a

s a co

ntro

lled

subs

tanc

e, li

ke

mar

ijuan

a.

Furt

herm

ore,

by

rede

finin

g he

mp

to in

clude

its “

extra

cts,

cann

abin

oids

and

der

ivat

ives

,” Co

ngre

ss e

xplic

itly

rem

oved

pop

ular

hem

p pr

oduc

ts –

such

as h

emp-

deriv

ed

CBD

--fro

m th

e pu

rvie

w o

f the

CSA

.Ac

cord

ingl

y, th

e Dr

ug

Enfo

rcem

ent A

dmin

istra

tion

(DEA

) no

long

er h

as a

ny cl

aim

to

inte

rfere

with

the

inte

rsta

te co

mm

erce

of h

emp

prod

ucts

, so

as lo

ng a

s the

THC

leve

l is a

t or b

elow

0.3

%.

This

shou

ld g

ive

com

fort

to fe

dera

lly re

gula

ted

inst

itutio

ns

–ph

arm

acie

s, ba

nks,

mer

chan

t ser

vice

s, cr

edit

card

co

mpa

nies

, e-c

omm

erce

site

s and

adv

ertis

ing

plat

form

s --

to co

nduc

t com

mer

ce w

ith th

e he

mp

and

hem

p CB

D in

dust

ry.

FAQ

s

Drug

Tes

ting

1

Preg

nanc

y &

Br

east

feed

ing

2

Drug

inte

ract

ions

3

Dosin

g

4

Pedi

atric

Use

5

“Can

I us

e it

for…

?”

6

Que

stio

ns?

Ale

x C

apan

o, D

NP,

CR

NP,

FN

P-B

CSe

nior

Fel

low

: Ins

titut

e of

Em

ergi

ng H

ealth

Pro

fess

ions

, Th

omas

Jef

fers

on U

nive

rsity

Facu

lty: T

he L

ambe

rt C

ente

r for

the

Stud

y of

M

edic

inal

Can

nabi

s &

Hem

p, T

hom

as J

effe

rson

Uni

vers

ity

•O

VER

TH

E CO

UNTE

R•

LEG

AL•

AVAI

LAB

LE A

T YO

UR

LO

CAL

PH

ARM

ACY

Vert

ical I

nteg

ratio

n fro

m F

arm

-to-P

harm

acy

for S

uper

ior Q

ualit

y

Form

ulat

ion

and

pack

agin

g is

com

plet

ed in

a ce

rtifi

ed cG

MP

facil

ity

Supe

rior q

ualit

y tin

ctur

es, s

oft g

els a

nd sa

lves

Hem

p se

ed le

gally

is im

port

ed to

the

USA

from

Eco

fibre

in

Aust

ralia

Gold

en o

il is

test

ed b

y an

inde

pend

ent l

ab to

ver

ify co

nsist

ency

and

pur

ity

Hem

p cr

ops a

re g

row

n on

com

pany

-ow

ned

farm

s in

Kent

ucky

and

cr

ops a

re fu

lly-c

ompl

iant

und

er S

ectio

n 76

06 o

f the

201

4 Fa

rm B

ill

•O

VER

TH

E CO

UNTE

R•

LEG

AL•

AVAI

LAB

LE A

T YO

UR

LO

CAL

PH

ARM

ACY