Offi ci al Titl e: Usi n g C a n n a bi n oi ds t o E n h a n c e O pi oi d Analgesic Effects in Hu mans N C T: 02901275 Docu ment Date: February 12, 2018 J H MIRB eF or m A 0 1 V ersi o n 3 D at e d: 06/2007 P a g e 1 of 2 0 D at e: February 12, 2018 Pri n ci p al I n v esti g at or: K ell y D u n n, P h. D. Application Nu mber: I R B 00097937 J H M I R B - e For m A – Protocol • Us e t he sectio n hea dings to write t he J H M I R B e For m A, inserting the appropriate material in each. If a s e cti o n is n ot a p pli c a bl e, l e a v e h e a di n g i n a n d i ns ert N/ A. • When sub mitting J H M I R B e F or m A (ne w or revised), enter the date su b mitted to the field at the top of J H M I R B e F o r m A. ********************************************************************************************** 1. A bstract a. Provide no more than a one page research abstract briefly stating the proble m, the research hypothesis, a n d t h e i m p ort a n c e of t h e r es e ar c h. T his st u d y will s yst e m ati c all y e v al u at e w h et h er c a n n a bi n oi ds c a n e n h a n c e t h e a n al g esi c effi c a c y of o pi oi ds, w hi c h will advance the use of cannabinoids for the treat ment of acute and/or chronic pain. Chronic pain affects over 100 milli o n A m eri c a ns. O pi oi ds ar e u n a ni m o usl y r e c o g ni z e d as t h e m ost eff e cti v e dr u gs f or t h e r eli ef of p ai n a n d s uff eri n g, b ut t h e U S is n o w s uff eri n g fr o m a n e pi d e mic of a b us e, a d di cti o n a n d a c ci d e nt al d e at hs r es ulti n g fr o m t h e i n cr e as e d s al e a n d us e of o pi oi ds. T h er e is l e giti m at e v al u e i n i d e ntif yi n g a dj u n cts t h at mi g ht r e d u c e r eli a n c e o n o pi oi ds w hil e m ai nt ai ni n g a d e q u at e p ai n r eli ef. Pr e cli nic al st u di es r e p ort t h at c o- a d mi nist eri n g c a n n a bi n oi ds wit h o pi oi d a g o nists si g nifi c a ntl y a n d r eli a bl y r e d u c e t h e a m o u nt of o pi oi ds r e q uir e d f or a n al g esi a b ut t his h y p ot h esis h as n ot b e e n ri g or o usl y e v al u at e d i n h u m a ns. T his pr o p os al will e v al u at e t h e eff e ct of dr o n a bi n ol o n o pi oi d-i n d u c e d a n al g esi a. T h e st u d y will e nr oll 6 0 h e alt h y a d ults ( 3 0 me n/ w o m e n) t o c o n d u ct a wit hi n-s u bj e ct, d os e-r es p o ns e e v al u ati o n of c a n n a bi n oi ds o n t h e a n al g esi c eff e ct of h y dr o m or p h o n e ( Dil a u di d). S u bj e cts will c o m pl et e 5 e x p eri m e nt al s essi o ns t h at will o c c ur at l e ast o n c e w e e kl y a n d will e n a bl e s u bj e cts t o a d mit t h e ms el v es i nt o a cli ni c al r es e ar c h u nit t h e ni g ht b ef or e t h e s essi o n t o c o m pl et e t he st u d y s essi o n. S u bj e cts will r e c ei v e a d os e of hydro morphone (4 m g, oral) and a double-blind oral dose of study drug or placebo the morning of each experi mental s essi o n, a n d will u n d er g o q u a ntit ati v e s e ns or y t esti n g ( Q S T; a c o m pr e h e nsi v e p ai n t esti n g b att er y), pr o vi d e s elf- r e p ort r ati n gs of dr u g eff e cts, a n d c o m pl et e a n e ur o c o g niti v e b att er y. Q S T t esti n g will c o m pr e h e nsi v el y a n d s yst e m ati c all y m e as ur e p ai n s e nsiti vit y, a n d pr o vi d e i nf or m ati o n o n t h e f ull r a n g e of a n al g esi c eff e cts p ossi bl e a cr os s a wide variety of pain measures, including threshold responses (ther mal, pressure), te mporal su m mation, cold pr ess or, c o n diti o n e d p ai n m o d ul ati o n, a n d c a ps ai ci n s e nsiti z ati o n. Pri m ar y o ut c o m es will b e m a g nit u d e a n d d ur ati o n of p ai n as a f u n cti o n of st u d y dr u g d os e. A d diti o n al pri m ar y ai ms i n cl u d e pr o x y m e as ur es of a b us e li a bilit y a n d n e ur o c o g niti v e p erf or m a n c e. All m e as ur es will b e ass ess e d as a f u n cti o n of s e x, d u e t o s u bst a nti al e vi d e n c e t hat men/ wo men differ with regard to pain perception, endogenous cannabinoid receptor density, and opioid response. We hypothesize that cannabinoids will shift the analgesic curve of hydro morphone and enhance analgesia effects. T his will b e t h e 1 st hu man laboratory study to evaluate co mbinations of cannabinoids and opioids using QS T, and r es ults will i d e ntif y w h et h er a si g n al f or t his m e di c ati o n c o m bi n ati o n e xists t h at s h o ul d b e a d v a n c e d i nt o r a n d o mi z e d c o ntr oll e d tri al e v al u ati o ns wit h cli ni c al p ai n p o p ul ati o ns. T his st u d y will als o ass ess as p e cts t h at w o ul d i m p a ct dr u g d e v el o p m e nt ( a b us e li a bilit y, n e ur o c o g niti v e i m p air m e nt), as w ell as t h e eff e cts of s e x a n d c a n n a bi n oi d t y p e o n o ut c o m es.