9/28/2016 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 1
9/28/2016 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 2
9/28/2016 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 8 th 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 o 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 3
9/28/2016 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 o 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 4
9/28/2016 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 o 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 o 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 o 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 o le ra nc e c a n d e ve lo p in a s fe w a s 4 d a ys • L o 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 5
9/28/2016 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, o 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 o ure tte Syndro me K o 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) 6
9/28/2016 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 o 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 o ure tte Synd ro me : no e vide nc e in c hildre n 7
9/28/2016 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 o 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 8
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