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T*
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[(neur)-4.1(odevelopment,)]TJ
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(16)Tj
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[(cannabis)-453.9(exposure)-453.6(during)-453(adoles-)]TJ
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[(cence)-381.2(m)-.7(ight)-381.4(perturb)-379.9(PFC)-384.3(n)2.5(eurodevel)-4(o)2.9(pment)-381.4(a)-3.2(nd)-380.6(cause)]TJ
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0 -1.1795 TD
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[(ments.)-181.3(Supporti)-4.8(ng)-179.3(t)-4.2(h)2.3(is)-180.2(hypot)-4.2(h)2.3(es)-4.3(is,)-181.3(m)-1.2(any)-179.3(s)-4.3(tudies)-185.4(indicate)-179.9(a)]TJ
T*
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[(verity)2.8(\).)]TJ
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[(17)-8.7(2)-8.6(2)]TJ
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[(Fact)-4.7(or)-4.8(s)-227.2(s).4(uc)-4.5(h)-225.8(a)-4.2(s)-227.2(o)1.9(nset)-227.2(of)-227.8(us)-4.8(e,)-228.4(fr)-4.8(eque)-4.5(ncy)-231.5(o)1.9(f)-227.8(u)-4(se,)]TJ
-4.5938 -1.1847 TD
[(a)-4.2(n)1.5(d)-210.9(t)-4.7(he)-216.6(THC/CBD)-214(r).4(at)-4.7(io)-210.2(i)-5.3(n)-210.6(ca)-4.2(nnabis)-211.7(c)-4.5(o)1.9(nsume)-4.5(d)-210.9(have)-216.6(be)-4.5(en)]TJ
0 -1.1795 TD
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[(sh)-3.9(own)-200.9(t)-5.3(o)-200.5(m)-2.3(od)-4.6(ula)-4.8(t)-.2(e)-201.7(t)-.2(h)-3.9(i)-.8(s)-202(r)-5.4(isk)-4.6(.)]TJ
8.2191 0 0 7.3052 178.4125 159.1369 Tm
-.0309 Tc
[(17)-7.2(,2)-7.1(3,)-6(24)]TJ
10.959 0 0 10.959 205.9653 154.2614 Tm
-.0209 Tc
[(For)-205.3(i)1.1(ns)-3.5(tance,)-196.1(after)-200.1(c)1.9(on-)]TJ
-13.1347 -1.1847 TD
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[(tr)-4.4(oll)-4.6(i).2(ng)-246.7(for)-247.5(c)1(onfounding)-241.5(vari)-4.9(abl)-4.6(e)1(s)-242.4(\()-4.7(e.g.,)-243.5(I).8(Q,)-243.5(ps)-4.4(ychiatric)-247.3(i).2(ll-)]TJ
0 -1.1795 TD
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[(ness)-304(in)-297.8(f)-4.6(a)1.7(mily)-303.2(members\))-4.3(,)-300(a)-298.3(large)-298.6(p)2(opulation-bas)-4(e)1.4(d)-298.1(s)-4(tudy)]TJ
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[(found)-210.8(a)-216.2(dose-)-4.4(d)1.3(ep)-3.9(ende)-4.4(nt)-211.6(r)-4.7(e).7(la)-4.1(ti)]TJ
11.2723 0 TD
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[(ons)-4.2(h)2.4(ip)-215.5(of)-211.7(adoles)-4.2(cent)-211(c)1.2(anna-)]TJ
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[(bis)-277.6(u)-2.6(se)-277.3(and)-281.9(t)1.8(he)-277.3(develo)3.3(pment)-277.5(o)3.3(f)-283.3(s)1.8(chizophrenia.)]TJ
8.2191 0 0 7.3052 256.4787 107.3197 Tm
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(19)Tj
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[(In)-282.8(addi-)]TJ
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[(ti)-4.8(on,)-507.3(t)-4.2(he)-511(ris)-4.3(k)-510.4(of)-511.8(developing)]TJ
11.7224 0 TD
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[(a)-505.1(p)-3.1(sychoti)-4.4(c)-505.4(disorder)-510.9(was)]TJ
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[(sh)-3.9(own)-252.6(t)-.2(o)-247(i)-5.9(ncr)-5.4(e)0(a)-4.8(s)-.2(e)-248.3(t)-.2(h)-3.9(r)-.2(e)-5.1(e)0(fo)-3.9(ld)-252.9(amon)-4.3(g)-247.7(u)-4.6(ser)-5.4(s)-248.5(of)-254.3(hig)-4.5(h)1.2(-)-5.1(p).6(o)-3.9(t)-.2(en)-4.3(cy)]TJ
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[(cannabis)-278.3(compar)-4.1(ed)-277.5(with)-276.8(subj)-4.3(ect)-4(s)-273.1(w)-1.5(ho)-271.6(never)-278.3(u)1.9(s)-4.1(e)1.3(d)-277.5(c)1.3(anna-)]TJ
22.9068 57.8774 TD
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(bis.)Tj
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(25)Tj
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[(In)-406.9(thi)-5(s)-402.8(st)-4.4(udy,)-404(dail)-4.7(y)-402(u)-3.7(se)-407.7(of)-403.4(high-pot)-4.4(ency)-402(cannabis)]TJ
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[(c)335.8(o)342.2(n)336.6(f)340.1(e)340.9(r)335.5(r)340.7(e)335.8(da)341.3(ne)340.9(v)336.4(e)340.9(nh)337(i)340.1(g)341.6(h)337(e)340.9(r\()]TJ
/F7 1 Tf
10.4653 0 TD
0 Tc
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[(vefold\))-341.1(r)-4.5(i).1(sk)-339.9(for)-340.8(d)1.5(e)-4.2(v)1.6(el)-4.7(oping)]TJ
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[(sc)3.8(hiz)3.8(o)-.1(p)4.4(h)-.1(r)3.6(e)3.8(nia.)]TJ
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(25)Tj
10.959 0 0 10.959 324.0566 658.9983 Tm
0 Tc
[(A)-404.5(causal)-410.9(relationship)-407.5(between)-405(adolescent)-406(cannabis)]TJ
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[(use)-293.4(and)-286.8(an)-289.4(increased)-290.8(risk)-287.1(for)-288.3(schizophrenia)-289.8(is)-291.7(unlikely)]TJ
0 -1.1847 TD
[(to)-341.3(be)-346.3(proven)-341.1(given)-339.8(ethical)-341.9(constraints.)-341.8(Thus,)-339.6(research)]TJ
0 -1.1795 TD
[(utilizing)-369.8(animal)-366.9(models,)-370.6(rigorously)-364.4(controlled)-369.3(experi-)]TJ
T*
[(mental)-433.9(design,)-435.6(and)-436.8(examination)-432(of)-429.9(specic)-434.4(cannabis)]TJ
0 -1.1847 TD
[(components)-240.5(can)-235.6(identify)-237(potential)-238.1(mechanisms)-235.8(linking)]TJ
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[(frequent)-261.3(adolescent)-261.1(cannabis)-254.6(use)-262.3(and)-255.7(an)-258.4(increased)-259.7(risk)]TJ
0 -1.1847 TD
[(for)-453.9(schizophrenia.)-449.4(Furthermore,)-446.3(examining)-452.6(the)-447.8(vari-)]TJ
0 -1.1795 TD
[(ables)-407.5(involved)-404.5(in)-409.5(producing)-401.7(schizophrenia-associated)]TJ
0 -1.1847 TD
[(phenotypessuch)-341.4(as)-342.3(impairment)-340.6(of)-341.9(working)-342.6(and)-338.5(ob-)]TJ
0 -1.1795 TD
[(ject)-416.3(recognition)-413.5(memory,)-413.7(anxiety,)-412.6(and)-416.1(repetitive)-414.2(and)]TJ
0 -1.1847 TD
[(compulsive)-295.1(behaviorsmight)-293.9(provide)-293.6(valuable)-291.2(insight)]TJ
0 -1.1795 TD
[(into)-290.4(schizophrenias)-287.2(etiology.)-285.1(Working)]TJ
8.2191 0 0 7.3052 483.4203 508.4786 Tm
(2629)Tj
10.959 0 0 10.959 506.4943 503.603 Tm
[(and)-291.9(object)]TJ
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[(recognition)-780.8(memory)]TJ
8.2191 0 0 7.3052 408.3589 495.4959 Tm
(3032)Tj
10.959 0 0 10.959 436.8755 490.677 Tm
[(decits)-776(are)-779.9(frequent)-778.6(in)]TJ
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[(schizophrenia.)-247.7(Furthermore,)-249.8(repetitive)-248.7(and)-245.4(compulsive)]TJ
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(behaviors)Tj
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(33,34)Tj
10.959 0 0 10.959 377.4613 464.7684 Tm
[(as)-445.7(well)-445.2(as)-440.6(anxiety)]TJ
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(35,36)Tj
10.959 0 0 10.959 481.0959 464.7684 Tm
[(are)-443.6(common)-443.8(in)]TJ
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(schizophrenia.)Tj
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[(vented)-300.9(by)-299.1(concurrent)-301.8(CBD)-297.9(treatment.)]TJ
/F5 1 Tf
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[(Materials)-302.5(and)-303.8(Methods)]TJ
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(Subjects)Tj
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10.959 0 0 10.959 313.0582 309.3164 Tm
0 0 0 rg
[(Male)-308.9(CD1)-308.8(mice)-310.1(\()]TJ
/F10 1 Tf
7.0303 0 TD
(n)Tj
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(=)Tj
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[(221\))-310(were)-310.1(bred)-305.5(and)-312.6(housed)-309.8(three)]TJ
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[(to)-330.9(four)-327(per)-329.6(cage)-326.8(under)-329.1(a)-328.6(standard)-327.7(reversed)-329.1(light)-330.4(cycle)]TJ
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[(housing)-369.7(facility)-367.9(\(lightdark)-367.8(cycle)-366.8(of)-367.8(12)-164.6(h:)-368.4(lights)-369.9(on)-366.1(at)]TJ
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/F10 1 Tf
17.2577 0 TD
[(ad)-485.4(libitum)]TJ
/F11 1 Tf
4.3455 0 TD
(.)Tj
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0 -1.1795 TD
[(Universitys)-522(Bloomington)-510.8(Institutional)-519.9(Animal)-515.3(Care)]TJ
T*
[(and)-302.3(Use)-301.6(Committee.)]TJ
/F8 1 Tf
10.4607 0 0 10.4607 313.0582 205.7385 Tm
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(Drugs)Tj
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10.959 0 0 10.959 313.0582 192.7559 Tm
0 0 0 rg
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[(Injection)-337.9(s)-2.7(olutions)-339(were)-338.7(made)-338.7(by)-338.1(di)-3.3(ssolving)-338.1(THC,)-340.1(CBD,)]TJ
T*
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[(or)-441.5(CBD)]TJ
/F7 1 Tf
3.316 0 TD
0 Tc
(+)Tj
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[(T)4.4(H).4(C)-439.9(i)-3(n)-441(1)3.9(00%)-439(ethanol)-442.3(t)2.8(o)-440.6(a)-441.6(concentration)-441(o)-.9(f)]TJ
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[(6)-166.5(m)1(g/mL)-300.7(for)-302.2(e)-1.9(ach)-300.7(d)-1.3(rug.)-303.3(In)-301.1(a)-301.6(s)-2.1(econ)4.2(d)-306.5(t)3.1(ube,)-303.3(Kollipho)4.5(r)]TJ
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()Tj
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(EL)Tj
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[(\(synonym:)-396.7(C)-.1(remophor)]TJ
/F7 1 Tf
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0 Tc
()Tj
/F11 1 Tf
10.959 0 0 10.959 420.5479 153.9212 Tm
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[(EL;)-391.8(Sigma-Aldrich\))-396.1(was)-401(m).5(ixed)]TJ
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[(wi)-3(th)-399.3(sterile)-400.5(0)-1.2(.9%)-397.6(s)-2.4(aline.)-396.7(The)-400.5(d)-1.6(issolved)-400(cannabinoid)-400(w).2(as)]TJ
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0 -1.1847 TD
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[(nal)-633.5(ratio)-631.9(o)-.7(f)-633.9(1)-1(:1:18)-632.2(\()-2.5(cannabi)]TJ
12.1518 0 TD
-.024 Tc
[(noid/eth)5.2(ano)5.2(l)-1.6(:Cre)4(moph)5.2(or:)]TJ
-12.1518 -1.1795 TD
0 Tc
[(sa)14.7(l)12(i)0(n)14.7(e)12.5(\).)-354.7(Th)17.2(e)-360()0(n)16.7(a)0(l)-352.8(c)12.5(on)16.7(ce)19.8(nt)15.3(r)12.2(a)0(t)14.8(i)11.7(on)-355.8(o)13.7(f)-366(e)12.5(a)0(c)14.9(h)-358.8(co)15.9(m)10.2(p)0(o)21.6(n)0(e)15.5(n)0(t)-352(i)11.7(n)]TJ
T*
[(th)15.6(e)-282.4(i)11.7(nj)15(e)12.5(c)0(t)19.6(i)0(o)15.1(n)-281.5(s)12.2(o)0(l)15.4(u)13(ti)18.8(on)16.7(s)-282.6(w)0(a)22.4(s)-282.6(0.)19.3(3)-157.3(m)10.2(g/)14.4(m)10.2(L)-281.2(c)12.5(a)0(n)15.8(n)0(a)21(b)0(i)15.1(n)0(o)21.9(i)0(d)14.4(,)-278.6(5%)]TJ
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0 -1.1795 TD
[(in)14.7(j)12(e)0(c)14.6(t)12.3(ed)-584.9(i)11.7(n)0(t)20.5(r)0(a)14.7(p)0(e)20.3(r)0(i)18.7(t)0(o)15.7(n)0(e)20.6(a)0(l)19.6(l)0(y)-580.1(\()0(i)13.2(.)11.1(p.)18.9(\))-593.3(w)0(i)21.3(t)0(h)-579.3(3)-157.3(m)10.2(g)0(/)14.4(k)13.1(g)-592.2(o)0(f)-579.9(t)0(h)20.8(e)]TJ
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