MARI JUANA AND K I DS: AN E VI DE NCE -BASE D E XAMI NAT - - PDF document

9/28/2016 1

MARI JUANA AND K I DS: AN E VI DE NCE

• BASE

D E XAMI NAT I ON

T e ri Mo se r Wo o PhD, CNL , CPNP-PC, F AANP

DI SCL OSURE S

• No fina nc ia l d isc lo sure s

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L E ARNI NG OBJE CT I VE S

• Histo ric a l use o f c a nna b is
• Re vie w pha rma c o lo g y o f c a nna b is
• Disc uss c urre nt e vide nc e re g a rding use o f ma rijua na
• Me d ic a l the ra py
• I

llic it use b y c hildre n a nd a do le sc e nts

A HI ST ORY L E SSON

• Ca nna b is use d fo r me dic ina l re a so ns sinc e 2000 BC
• US Pha rma c o pe ia c la ssifie d ma rijua na a a a me d ic a l

c o mpo und in 1851

• Sta ye d o n until 1942
• Crimina lize d in 1937
• Sc he dule I drug

L E GAL I ZAT I ON F OR ME DI CAL USE

• 23 sta te s a nd DC ha ve le g a lize d ma rijua na
• Ra ng e in 1 to 24 o z usa b le
• 4 to 24 pla nts
• Re c re a tio na l use
• Wa shing to n, Co lo ra do , DC
• 11 sta te s like ly to le g a lize d in 2016

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MONI T ORI NG T HE F UT URE (2015) MARI JUANA USE MONI T ORI NG T HE F UT URE (2015) MARI JUANA SURVE Y L E GAL I ZAT I ON AND ADOL E SCE NT USE

• Study o f 8th g ra d e rs in WA b e fo re a nd a fte r le g a liza tio n (Ma so n

e t a l, 2015)

• Inc re a se d use o f ma rijua na
• L
• we r a lc o ho l a nd c ig a re tte use , po ssib ly sub stituting with

ma rijua na

• Mo nta na study o f 17,482, a g e 13 to 19 yrs (F

rie se & Grub e , 2013)

• Inc re a se d life time a nd 30-d a y use
• So c ia l no rms a nd e a se o f a c c e ss
• Mo nito ring the F

uture fro m 1991 to 2014 in sta te s with me dic a l ma rijua na la ws (Ha sin e t a l, 2015)

• No inc re a se with pa ssing la ws
• Ove ra ll a d o le sc e nt use hig he r in sta te s with me d ic a l ma rijua na

la ws

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CANNABI NOI D ME DI CI NE S

• Ca nna b is-de rive d pha rma c e utic a ls
• Dro na b ino l (Ma rino l)
• Sc he dule I

I I

• c o nta ins T

HC

• L

a b e l “pe dia tric do sa g e fo r c he mo -a sso c ia te d e me sis is sa me a s a dults”

• Na b ilo ne (Ce sa me t)
• Se he dule I

I

• Co nta ins T

HC

• L

a b e l “sa fe ty a nd e ffe c tive ne ss no t e sta b lishe d…yo ung e r tha n 18 yrs”

• Na b iximo ls (Sa tive x)
• Ca nna b is-b a se d o ra lmuc o sa l spra y
• Appro ve d in Ca na d a , NZ a nd E

U c o untrie s

• Co nta ins T

HC a nd c a nna b id io l (CBD)

• UK

L a b e l “sa fe ty a nd e ffe c tive ne ss no t e sta b lishe d …yo ung e r tha n 18 yrs”

BOT ANI CAL S

• “Me dic a l” ma rijua na
• Cannabis sativa
• uplifting a nd e ne rg e tic
• b e st suite d fo r da y use
• Cannabis indic a
• re la xing a nd c a lming
• b e st suite d fo r nig ht use
• Cannabis rude ralis
• L
• w in T

HC

• Hig h in c a nna b id io l

PHARMACODYNAMI CS

• Ca nna b ino id s wo rk o n the c a nna b ino id re c e pto rs
• CB

1 fo und o n b a sa l g a ng lia (a ffe c ting mo to r a c tivity), c e re b e llum

(mo to r c o o rdina tio n), hippo c a mpus (sho rt-te rm me mo ry), ne o c o rte x (thinking ), a nd hypo tha la mus a nd limb ic c o rte x (a ppe tite a nd se da tio n)

• CB

2 fo und o n immune c e lls a nd tissue s, b ra in

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CANNABI DI OL(CBD)

• T

he ma jo r no n-psyc ho tro pic c o mpo und in c a nna b is

• L
• w a ffinity fo r CB1 o r CB2 re c e pto rs
• Do e s no t pro duc e e upho ria o r into xic a tio n
• Anima l stud ie s: a nti-se izure , a ntio xid a nt, ne uro pro te c tive ,

a nti-infla mma to ry, a na lg e sic , a nti-tumo r, a nti-psyc ho tic , a nd a nti-a nxie ty pro pe rtie s

• E

pid io le x

• a purifie d CBD e xtra c t

Vo lko w, 2015; Re ddy & Go lub , 2016

PHARMACOK I NE T I CS

• Ab so rptio n
• Ra pidly a b so rb e d fro m lung s
• L
• we r b io a va ila b ity whe n ta ke n o ra lly
• T

HC ½ life fo r d istrib utio n is 0.5 hr a nd te rmina l ½ life is 30 hrs

• Ca nnib id io l te rmina l ½ life is 9 hrs
• Hig hly lipo philic
• T

HC a c c umula te s in the b ra in

DRUG-DOSE RE L AT I ONSHI P

• Wide va ria tio n in re po rte d d o se s to g e t d e sire d e ffe c t
• T
• le ra nc e to T

HC

• Do wnre g ula tio n o f CB1 re c e pto rs a nd G-pro te in a c tiva tio n
• T
• le ra nc e c a n d e ve lo p in a s fe w a s 4 d a ys
• L
• w d o se : < 7 mg
• Me dium do se : 7-18 mg
• Hig h do se : > 18 mg
• Se rum c o nc e ntra tio ns d o no t c o rre la te with physio lo g ic

e ffe c t

Bo rg e lt e t a l, 2013

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DI F F E RI NG RE SPONSE S T O CANNABI S

• L

H, F SH, pro la c tin a nd g ro wth ho rmo ne a ll d e c re a se with lo ng -te rm use

• F

e ma le s with hig he r e stro g e n a re mo re se nsitive to e ffe c ts o f c a nna b is o n pa in, b e ha vio r a nd re wa rd

• Pa tie nts with he a rt pro b le ms ma y ha ve inc re a se d he a rt ra te
• Co mplic a te d b y me dic a tio ns tha t a lso inc re a se he a rt ra te

(a mphe ta mine s)

• De c re a se d a le rtne ss whe n use d with b e nzo d ia ze pine s,
• pia te s a nd T

CAs

ME DI CAL USE OF CANNABI S

• Na use a a nd vo miting fro m c he mo the ra py
• Appe tite stimula tio n in HIV/ AI

DS

• Chro nic pa in
• Spa stic ity due to multiple sc le ro sis
• Ga stro inte stina l diso rde rs
• Psyc hia tric diso rde rs (de pre ssio n/ a nxie ty)
• HIV-a sso c ia te d se nso ry ne uro pa thy
• Se izure diso rde r/ e pile psy
• Pa rkinso n dise a se
• T
• ure tte Syndro me

K

• ppe l e t a l, 2015; Whiting e t a l,

2015; Go dse y & Grundma nn, 2016

E VI DE NCE I N CHI L DRE N: SE I ZURE S

• Ma rijua na -De rive d E

pile psy Drug in Clinic a l T ria l fo r Child re n with Unc o ntro lle d Se izure s

• Multic e nte r (11 site s) tria l
• E

pidio le x, a purifie d c a nna b ino id tha t c o me s in a liq uid fo rm c o nta ining no te tra hydro c a nna b ino l (T HC) fo r 12 we e ks

• 36.5% re duc tio ns in mo to r se izure s (De vinsky e t a l, 2016)

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E VI DE NCE I N CHI L DRE N: SE I ZURE S

• Pa re nt re po rt studie s
• Hussa in e t a l (2015): o nline surve y o f pa re nts who a d ministe r

CBD o il to c hild re n with infa ntile spa sms o r L e nno x-Ga sta ut

• 85% re po rte d re duc tio n in se izure s, 14% se izure fre e
• Pre ss e t a l (2015): re tro spe c tive study o f 75 pts with se izure s
• n o ra l c a nna b is the ra py (OCT

) fo r se izure s

• 57% re po rte d a ny impro ve me nt in sz, 33% re po rte d > 50% re duc tio n

in sz

• 45.3% mo ve d to Co lo ra d o fo r OCT

E VI DE NCE I N CHI L DRE N: SPAST I CI T Y

• Sma ll study in Ge rma ny (N = 16, me a n a g e 12.7 yrs)
• 2.5% o ily te tra hydro c a nna b ino l so lutio n (dro na b ino l)
• Do sa g e ra ng e d fro m 0.08 to 1.0 mg / kg / d a y (me a n 0.33 mg / kg / d a y)
• Me a n le ng th o f tre a tme nt 181 d a ys
• Wo rke d we ll to impro ve tre a tme nt re sista nt spa stic ity
• Minima l side e ffe c ts

K uhle n e t a l, 2016

E VI DE NCE I N CHI L DRE N

• Ca nc e r tre a tme nt: no e vid e nc e fo und
• Ong o ing studie s
• ADHD: no e vid e nc e
• T
• ure tte Synd ro me : no e vide nc e in c hildre n

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ADVE RSE E F F E CT S: T HE E VI DE NCE

• De c re a se d c e re b ra l b lo o d flo w in a d o le sc e nts he a vy use rs

(Ja c o b us e t a l, 2012)

• No rma l a fte r 4 we e ks o f a b stine nc e
• Ba ta lla e t a l (2013) Syste ma tic re vie w o f func tio na l studie s in

a d o le sc e nts a nd a d ults

• Struc tura l a nd func tio na l c ha ng e s fo und in a do le sc e nts who use

c a nna b is

ADOL E SCE NT USE AND PSYCHOSI S

• Inc re a se d inc id e nc e o f psyc ho sis in he a vy c a nna b is use rs
• L
• ng itud ina l stud ie s -> inc re a se d sc hizo phre nia
• ? Se lf me dic a ting
• E

nd o c a nna b ino id syste m pla ys a n impo rta nt ro le in fund a me nta l b ra in d e ve lo pme nta l pro c e sse s

• Use during a do le sc e nc e c a n a ffe c t b ra in func tio ns a nd b e ha vio r

Ma lo ne e t a l, 2010

ADVE RSE E F F E CT S I N ST UDI E S

• De vinsky e t a l (2016)
• so mno le nc e 25%, de c re a se d a ppe tite 19%, dia rrhe a 19%, fa tig ue

13%, c o nvulsio n 11%, sta tus e pile ptic us 6%

• Pre ss e t a l (2015)
• I

nc re a se d se izure s (13%) a nd so mno le nc e / fa tig ue (12%)

• Ra re a dve rse e ve nts inc lud e d d e ve lo pme nta l re g re ssio n,

a b no rma l mo ve me nts, sta tus e pile ptic us

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E VI DE NCE NE E DE D!

• Pre va le nc e o f pa re nts tre a ting c hild re n with c a nna b ino id s
• T
• ure tte Synd ro me in c hild re n a nd a d o le sc e nts
• Spa stic ity in c hildre n
• L
• ng te rm e ffic a c y a nd a d ve rse e ffe c ts

QUE ST I ONS?

• wo o tm@ plu.e du

RE F E RE NCE S

• Ba te la e t a l (2013). Struc tio na l a nd func tio na l ima g ing studie s in c hro nic c a nna b is

use rs: A syste ma tic re vie w o f a do le sc e nt a nd a dult finding s. PL OS One , 8(2), e 55281-

• Bo rg e lt, L

.M., F ra nso n, K .L ., Nussb a um, A.M. & Wa ng , G.S. (2013). Pha rma c o lo g ic a nd c linic a l e ffe c ts o f me d ic a l c a nna b is. Pharmac o the rapy, 33(2), 195-209.

• De vinsky, O e t a l. (2016). Ca nna b idio l in pa tie nts with tre a tme nt-re sista nt e pile psy: a n
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e ye s, K M, e t a l (2015). Me dic a l ma rijua na la ws a nd a do le sc e nt ma rijua na use in the USA fro m 1991 to 2014: re sults fro m a nnua l, re pe a te d c ro ss se c tio na l surve ys. L anc e t Psyc hiatry Pub lishe d o nline 16 June 2015 http:/ / dx.do i.o rg / 10.1016/ S2215-0366(15)00217-5

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