Cause and effect essay

VIEWPOINT A ndrew A. M o n te, M D D e p a rtm e n t o f Emergency Medicine, U nive rsity o f Colorado.

Aurora: and Rocky M ountain Poison and D rug Center, Denver, Colorado.

Richard D. Zane, M D D e p a rtm e n t o f Emergency M edicine, U nive rsity o f Colorado, Aurora.

Kennon J. Heard, MD, PhD D e p a rtm e n t o f Emergency M edicine, U nive rsity o f Colorado, Aurora; and Rocky M o un tain Poison and Drug Center, Denver, Colorado.

A u th o r Reading at jama.com Corresponding Author: A n d re w A.

M o nte , MD, D e p a rtm e n t o f Emergency Medicine, U nive rsity o f Colorado, Leprino Bldg, Seventh Floor, Campus Box B-215,12401 E 17th Ave, Aurora, CO 8 0 0 4 5 (a nd re w .m o nte @ucdenver.edu).

jam a.comThe Implications of Marijuana Legalization in Colorado The leg aliza tion o f m arijuana in C olorado has had com p le x e ffe c ts on th e he alth o f its citizens. Physi­ cians have th e re s p o n s ib ility t o pre se n t a balanced p e rs p e c tiv e , id e n tify in g b o th th e p o te n tia l h e a lth b e n e fits and risks associated w ith marijuana use. In th is V ie w p o in t, w e discuss th e h is to ry o f marijuana policy in Colorado and th e expected and unexpected e f fe c ts o f in c re a s e d m a riju a n a a v a ila b ility . O th e r states considering marijuana policy liberalization may learn fro m th e experiences in Colorado.

History o f Colorado Marijuana Policy In N ovem ber 2 0 0 0 , th e Colorado state c o n s titu tio n was amended to allow fo r the use o f medical marijuana b y p a t i e n t s w i t h " c h r o n i c d e b i l i t a t i n g m e d ic a l conditions."' Few patients used medical marijuana until O ctober 2 0 0 9 , w hen th e US A tto rn e y General d is trib ­ uted guidelines f o r federal prosecution o f th e posses­ s io n and use o f m a riju a n a , c e d in g j u r i s d i c t i o n o f marijuana law enforcement to state governments. The c o m b in a tio n o f perm issive local la w and th e federal policy change effectively liberalized the sale and use o f medical marijuana in Colorado. Anyone w ith one o f the conditions outlined by Colorado law could be issued a medical marijuana license w ith no expiration date. The number o f licenses increased from 4819 on December 3 0 ,2 0 0 8 , to 116 287 on September 30,2014.

In Novem ber 2012, A m en dm e nt 64, wh ich legal­ iz e d th e r e t a il sale, p u rc h a s e , and p o s s e s s io n o f marijuana fo r state residents and visitors older than 21 years, was approved by 55% o f voters. During th e f o l­ lowing year, the state legislature appointed policy advi­ sors t o de te rm in e a ta x s tructure , o u tlin e dispensary regulations, and d e term in e th e public health im plica­ tions o f th e legalization. Retail marijuana stores began sales t o consumers on January 1, 2014. Medical and retail marijuana products are th e same, although regu­ lations vary between the 2 marketplaces. For example, there is no minim um age restriction, and only state resi­ dents can legally buy medical marijuana in Colorado. As o f November 3, 20 14 ,4 97 medical marijuana dispensa­ rie s and 2 9 2 r e t a il d is p e n s a rie s w e re lic e n s e d in Colorado.2 Expected Health System Effects o f Legalization Increased availability led to increased health care u tili­ zation related t o marijuana exposure.3 Exacerbation o f chronic health c on ditions was expected. Tetrah ydro­ cannabinol (THC) is associated w ith psychosis, anxiety, and depression symptoms, making exacerbation o f un­ derlying psychiatric disorders inevitable. However, it is d iff ic u lt t o fu lly q u a n tify th e scope o f th is increased health care utilization because marijuana use is often co­incident w ith o th e r behaviors th a t c o n trib u te to health care visits. For example, th e com bin ation o f marijuana plus ethanol increases th e risk o f m o to r vehicle c o lli­ sions more than either substance alone. Serum THC con­ centrations are n o t readily available, so assessing cau­ sality is d ifficu lt.

However, th e re has been an increase in visits fo r pure marijuana in to xica tion. These w ere previo usly a rare occurrence, b u t even th is increase is d iffic u lt to quantify. Patients may present t o emergency de p a rt­ ments (EDs) w ith anxiety, panic attacks, public intoxica­ tion, vomiting, or o th er nonspecific symptoms precipi­ tated by marijuana use. The University o f Colorado ED sees a p p ro x im a te ly 2 0 0 0 p a tie n ts p e r w e ek; each week, an estim ated 1 to 2 pa tien ts present solely f o r m a r iju a n a i n t o x i c a t i o n a n d a n o t h e r 10 t o 15 f o r marijuana-associated illnesses.

Medical Marijuana Use Patients w ith some seizure disorders may b e n e fit from th e cannabidiol com p o n e n t in marijuana, and several clinical trials w ill soon enroll patients (NC T02224690, N C T 0 2 2 2 4 5 6 0 , N C T 0 2 2 2 4 7 0 3 , N C T 0 2 0 9 1 3 7 5 , NCT02224573). Marijuana likely has a n ti-in fla m m a ­ to r y e ffe cts4 and may b e n e fit some pa tien ts w ith in ­ flam m a to ry bowel disease.5 Marijuana may have a safer therapeutic w in d o w than opioids fo r pain control, and an o b s e rv a tio n a l s tu d y fo u n d fe w e r o p io id -re la te d deaths in states w ith liberal marijuana laws.6 However, it is unlikely th a t marijuana is effective fo r the w ide range o f health problems approved under Colorado law.1 Legalization o f marijuana has increased o p p o rtu n i­ ties fo r clinician scientists to study the positive health ef­ fects o f marijuana due t o increased availability; h o w ­ ever, federal designation o f marijuana as a Schedule I drug continues to lim it investigators' ab ility t o conduct high-quality, nationally funded clinical trials. The use o f medical marijuana fo r a w ide range o f disorders is incon­ sis tent w ith th e science su p p o rtin g its effectiveness, highlightin g th e need fo r high-quality research.

Unexpected Health System Effects o f Legalization Experimentation w ith new ways to use and produceTHC products has resulted in unexpected health effects, in­ cluding an increased prevalence o f burns, cyclic v o m it­ ing syndrome, and health care visits due t o ingestion o f edible products.

The University o f Colorado burn center has experi­ enced a substantial increase in the number o f marijuana- related burns. In th e past 2 years, th e burn center has had 31 admissions f o r marijuana-related burns; some cases involve more than 70 % o f body surface area and 21 required skin grafting. The majority o f these were flash JAMA January 2 0 ,2 0 1 5 Volu m e 313, N um b e r 3 241 b u rn s t h a t o c c u rre d d u rin g THC e x tra c tio n fr o m m ariju a n a p la n ts u sin g b u ta n e as a s o lv e n t.

The fre q u e n t use o f high THC co n c e n tra tio n p ro d u c ts can lead t o a c y c lic v o m i t i n g s y n d r o m e . P a t ie n t s p r e s e n t w i t h s e v e re a b d o m in a l pain, v o m itin g , and diaphoresis; t h e y o fte n re p o r t re lie f w it h h o t showers. A small s tu d y a t 2 Denver-area hosp itals revealed an increase in cyclic v o m itin g p re se n ta tio n s fr o m 41 p e r 113 2 6 2 ED visits t o 8 7 pe r 125 0 9 5 ED vis its (prevale nce ratio , 1.92) a fte r m e d i­ cal m a riju a n a lib e r a liz a tio n (A. A. M o n te , MD, u n p u b lis h e d d ata, D ecem ber 2014).

The m o s t c o n c e r n in g h e a lth e f f e c ts h a ve b e e n a m o n g c h il­ dre n . The n u m b e r o f c h ild re n eva lu a te d in t h e ED f o r u n in te n tio n a l m a r iju a n a in g e s t io n a t t h e C h ild r e n 's H o s p ita l o f C o lo r a d o i n ­ creased fr o m 0 in th e 5 years p re c e d in g lib e ra liz a tio n t o 14 in t h e 2 years a fte r m ed ica l lib e ra liz a tio n .3 This n u m b e r has increased f u r ­ t h e r sin ce le g a liza tio n ; as o f S e p te m b e r 2 0 1 4 ,1 4 c h ild re n had been a d m itte d t o t h e h o s p ita l th is year, and 7 o f th e se w e re a d m itte d to t h e in te n s iv e care u n it. T he va st m a jo r ity o f in te n s iv e care a d m is ­ sio ns w e re re la te d t o in g e s tio n o f e d ib le THC p ro d u c ts .

Challenges o f Edible M arijuana Products Edib le p ro d u c ts are re s p o n sib le f o r t h e m a jo r ity o f h e a lth care v is ­ its d u e t o m ariju a n a in to x ic a tio n f o r all ages. This is lik e ly d u e t o fa il­ ure o f a d u lt users t o a p p re cia te t h e dela yed e ffe c ts o f in g e stio n c o m ­ pa re d w it h in h a la tio n . P ro lo n g e d a b s o rp tio n c o m p lic a te s dosin g , m a n u fa c tu rin g in co n siste ncies lead t o d o se va ria b ility , and t h e a p ­ p e a lin g p r o d u c t fo rm s lead t o u n in te n tio n a l in g e s tio n b y c h ild re n .

S m o k in g m ariju a n a re su lts in clin ica l e ffe c ts w it h in 10 m in u te s, peak b lo o d c o n c e n tra tio n s o ccu r b e tw e e n 3 0 and 9 0 m in u te s , and cle arance is c o m p le te w it h in 4 ho u rs o f in h a la tio n .7 Oral THC does n o t reach s ig n ific a n t b lo o d c o n c e n tr a tio n u n til a t least 3 0 m in u te s , w it h a peak a t a p p ro x im a te ly 3 ho u rs, and cle arance a p p ro x im a te ly 12 h o u rs a fte r in g e s tio n .7 Ten t o 3 0 m g o f THC is re co m m e n d e d fo r in to x ic a tio n d e p e n d ­ in g o n t h e e x p e rie n c e o f t h e user; each p a ckage, w h e t h e r i t is a sin gle co o kie o r a package o f g u m m y bears, th e o r e tic a lly c o n tains 1 0 0 m g o f THC. Because m a n y f in d it d i f f ic u lt t o e a t a t e n t h o f a cookie , u n in te n tio n a l o v e rd o s in g is c o m m o n . F u rth e rm o re , m a n u ­fa c tu rin g practices f o r marijuana e d ib le p ro d u c ts are n o t s ta n d a rd ­ ized. This results in e d ib le p ro d u c ts w it h in c o n s is te n t THC c o n ce n ­ t r a t io n s , f u r t h e r c o m p lic a t in g d o s in g f o r use rs. A c c o r d in g t o a re p o r t in t h e Denver Post, p ro d u c ts describ e d as c o n ta in in g 1 0 0 m g o f THC a ctu ally c o n ta in e d fr o m 0 t o 146 m g o f THC.8 In itia lly, n o n m e d ica l e d ib le p ro d u c ts w e re re q u ire d t o be sold in a c h ild p r o o f package, a lth o u g h m ed ica l m ariju a n a d id n o t have th is re q u ire m e n t. C h ild p r o o f p a cka ging r e q u ire m e n ts are n o w c o n ­ s is te n t across b o th re ta il an d m ed ica l p ro d u c ts , b u t t h e re is no d o s ­ in g r e c o m m e n d a tio n f o r m ed ica l m arijuana. To c o m p lic a te m a tte rs fu rth e r , t h e p a cka ging is in c o n s is te n tly e f fe c tiv e an d n o t a p p lie d t o a d o sin g u n it. This m eans t h a t a p ro d u c t m a y be sold in a c h ild p r o o f con taine r, b u t once th e package is o p e n e d , th e p ro d u c t is rea d ily ac­ cessible t o ch ild re n . A lth o u g h in g e stio n o f 1 0 0 m g o f THC in an a d u lt m ay re s u lt in d e liriu m o r severe p h y s io lo g ic im p a irm e n t, th is dose is u n lik e ly t o cause re s p ir a to ry a rre st, w h ic h m ay o ccu r in c h ild re n a t th is dose.

Edib le o r capsule fo rm u la tio n s m ay be a p re fe ra b le r o u te o f a d ­ m in is tra tio n w h e n co m p a re d w it h in h a la tio n f o r in d iv id u a ls w it h le ­ g itim a te m ed ica l in d ic a tio n s f o r t h e d ru g . H ow ever, t h e re is no rea ­ son th e se p ro d u c ts should be packaged in a m an n e r t h a t is appealing t o c h ild re n o r m akes th e m easily co n fu se d w it h n o n m a riju a n a p r o d ­ u cts. F u r th e rm o re , t h e c o n c e n tr a tio n o f THC m u s t be s y s te m a ti­ cally m ea su re d an d re p o r te d . No o n e w o u ld to le ra te a m e d ic a tio n t h a t c o n ta in e d a v a riab le a m o u n t o f t h e a ctive in g re d ie n t. S ta n d a rd ­ izin g t h e p ro d u c tio n and p re m a rk e t te s tin g o f e d ib le p ro d u c ts m ay h e lp lim it in a d v e rte n t overdoses.

Conclusions W h ile m any users fe e l th e y have b e n e fite d fr o m m arijuana legaliza­ t io n in C o lo rad o , th e r e h a ve also been u n t o w a r d a d v e rs e h e a lth e f f e c t s . T h e r is k s o f use m u s t b e c o n s is t e n t ly c o m m u n ic a t e d th ro u g h h e a lth care p ra c titio n e rs and p u b lic h e a lth o fficia ls, e sp e ­ cia lly f o r e d ib le p ro d u c ts t h a t pose u n iq u e risks f o r exposed a d u lts and c h ild re n . U ltim a te ly, a d d itio n a l research is n eeded t o q u a n tify t h e b e n e fits and risks o f m arijuana u tiliz a tio n so h e a lth care p ro fe s ­ sionals can have w e ll-in fo rm e d discussions w it h m edical and recre ­ a tio n al users.

ARTICLE INFORMATION Published Online: D ecember 8 ,2 0 1 4 .

doi:10.1001/jama.2014.17057.

Conflict o f In tere s t Disclosures: All a uthors have c o m ple te d and s u b m itte d th e ICMJE Form fo r Disclosure o f Pote ntial C on flicts o f In te rest. Dr M o nte re p o rte d th a t he sits on th e Colorado Retail Marijuana Public Health A d vis o ry C om m ittee co ord in ated th ro u g h th e Colorado D e p a rtm e n t o f Public H ealth and En viro n m e nt. Dr Heard re p o rte d having received grants fro m McNeil Consumer Healthcare. No o th e r disclosures w ere re po rte d .

Funding/S upport: Dr M onte's w o rk is s u pp o rte d by grants fro m th e National In stitu te s o f Health (1K23GM110516-01, U L1TR 001082, and 1R 56D A038366-01).Role o f th e Funder/Sponsor: The fu n d e r had no role in th e p reparation, review, o r approval o f th e manuscript.

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