%PDF-1.3
%
12 0 obj
<>>>/BBox[0 0 612 792]/Length 133>>stream
xA0}O1K]G5 z"%>)nf{Z;Uƅˠn*jZI^ n#-!1ʄ}ܖOf]]ǘN"W]zT
\2ko'n
endstream
endobj
6 0 obj
<>>>/BBox[0 0 612 792]/Length 133>>stream
xA0}O1K]G5 z"%>)nf{Z;Uƅˠn*jZI^ n#-!1ʄ}ܖOf]]ǘN"W]zT
\2ko'n
endstream
endobj
11 0 obj
<>>>/BBox[0 0 612 792]/Length 133>>stream
xA0}O1K]G5 z"%>)nf{Z;Uƅˠn*jZI^ n#-!1ʄ}ܖOf]]ǘN"W]zT
\2ko'n
endstream
endobj
7 0 obj
<>>>/BBox[0 0 612 792]/Length 133>>stream
xA0}O1K]G5 z"%>)nf{Z;Uƅˠn*jZI^ n#-!1ʄ}ܖOf]]ǘN"W]zT
\2ko'n
endstream
endobj
10 0 obj
<>>>/BBox[0 0 612 792]/Length 133>>stream
xA0}O1K]G5 z"%>)nf{Z;Uƅˠn*jZI^ n#-!1ʄ}ܖOf]]ǘN"W]zT
\2ko'n
endstream
endobj
3 0 obj
<>>>/BBox[0 0 612 792]/Length 133>>stream
xA0}O1K]G5 z"%>)nf{Z;Uƅˠn*jZI^ n#-!1ʄ}ܖOf]]ǘN"W]zT
\2ko'n
endstream
endobj
4 0 obj
<>>>/BBox[0 0 612 792]/Length 133>>stream
xA0}O1K]G5 z"%>)nf{Z;Uƅˠn*jZI^ n#-!1ʄ}ܖOf]]ǘN"W]zT
\2ko'n
endstream
endobj
5 0 obj
<>>>/BBox[0 0 612 792]/Length 133>>stream
xA0}O1K]G5 z"%>)nf{Z;Uƅˠn*jZI^ n#-!1ʄ}ܖOf]]ǘN"W]zT
\2ko'n
endstream
endobj
13 0 obj
<>>>/BBox[0 0 612 792]/Length 133>>stream
xA0}O1K]G5 z"%>)nf{Z;Uƅˠn*jZI^ n#-!1ʄ}ܖOf]]ǘN"W]zT
\2ko'n
endstream
endobj
9 0 obj
<>>>/BBox[0 0 612 792]/Length 133>>stream
xA0}O1K]G5 z"%>)nf{Z;Uƅˠn*jZI^ n#-!1ʄ}ܖOf]]ǘN"W]zT
\2ko'n
endstream
endobj
1 0 obj
<>>>/BBox[0 0 612 792]/Length 133>>stream
xA0}O1K]G5 z"%>)nf{Z;Uƅˠn*jZI^ n#-!1ʄ}ܖOf]]ǘN"W]zT
\2ko'n
endstream
endobj
8 0 obj
<>>>/BBox[0 0 612 792]/Length 133>>stream
xA0}O1K]G5 z"%>)nf{Z;Uƅˠn*jZI^ n#-!1ʄ}ܖOf]]ǘN"W]zT
\2ko'n
endstream
endobj
15 0 obj
<>stream
2021-02-10T21:09:33+05:30
Arbortext Advanced Print Publisher 9.0.114/W
2021-11-03T10:23:17-07:00
Acrobat Distiller 8.1.0 (Windows); modified using iText 4.2.0 by 1T3XT
application/pdf
CAN-2020-0102-ver9-Sullivan_3P 7..18
uuid:7efeec31-4cd0-4686-bba9-d1381de2fde2
uuid:68f0cfc7-9a34-4dc9-8dd0-27896e399513
endstream
endobj
16 0 obj
<>stream
x+ |
endstream
endobj
17 0 obj
<>stream
xS**T0T0 Bi yJ%
endstream
endobj
18 0 obj
<>stream
x+ |
endstream
endobj
19 0 obj
<>stream
xS**T0T0 Bi yw*
endstream
endobj
20 0 obj
<>stream
x+ |
endstream
endobj
21 0 obj
<>stream
xS**T0T0 Bi y+
endstream
endobj
22 0 obj
<>stream
x+ |
endstream
endobj
23 0 obj
<>stream
xS**T0T0 Bi y,
endstream
endobj
24 0 obj
<>stream
x+ |
endstream
endobj
25 0 obj
<>stream
xS**T0T0 Bi y\'
endstream
endobj
26 0 obj
<>stream
x+ |
endstream
endobj
27 0 obj
<>stream
xS**T0T0 Bi yA$
endstream
endobj
28 0 obj
<>stream
x+ |
endstream
endobj
29 0 obj
<>stream
xS**T0T0 Bi ye(
endstream
endobj
30 0 obj
<>stream
x+ |
endstream
endobj
31 0 obj
<>stream
xS**T0T0 Bih lT
endstream
endobj
32 0 obj
<>stream
x+ |
endstream
endobj
33 0 obj
<>stream
xS**T0T0 Bih uU
endstream
endobj
34 0 obj
<>stream
x+ |
endstream
endobj
35 0 obj
<>stream
xS**T0T0 Bi yS&
endstream
endobj
36 0 obj
<>stream
x+ |
endstream
endobj
37 0 obj
<>stream
xS**T0T0 Bi y8#
endstream
endobj
38 0 obj
<>stream
x+ |
endstream
endobj
39 0 obj
<>stream
xS**T0T0 Bi yn)
endstream
endobj
41 0 obj
<>stream
/GS1 gs
BT
/F6 1 Tf
10.959 0 0 10.959 62.022 348.2078 Tm
0 0 0 rg
0 Tc
0 Tw
[(randomized)-278.6(controlled)-281.3(trials)-278.5(\(RCTs\))-278.6(were)-279.1(rare)-281.4(and)-276.4(in-)]TJ
0 -1.1847 TD
[(cluded)-291.2(elevated)-287.3(transaminases)-289.5(\(related)-288.7(to)-289.5(concomitant)]TJ
0 -1.1795 TD
[(valproate)-402.9(use\),)-399.7(and)-400.6(sedation,)-404.7(lethargy,)-399.4(and)-400.6(upper)-401.8(re-)]TJ
0 -1.1847 TD
[(spiratory)-455.8(tract)-455.2(infections)-454.5(\(all)-453(related)-455.8(to)-449.9(concomitant)]TJ
0 -1.1795 TD
[(clobazam)-391.3(use\).)]TJ
8.2191 0 0 7.3052 128.0126 301.2661 Tm
(8)Tj
10.959 0 0 10.959 136.233 296.3904 Tm
[(After)-392.1(excluding)-387.9(studies)-394.1(in)-388.8(childhood)]TJ
-6.7717 -1.1847 TD
[(epilepsy)-143.1(\(and,)-144.8(therefore,)-139.5(concomitant)-141.1(antiepileptic)-143.9(med-)]TJ
0 -1.1795 TD
[(ications\),)-492.4(the)-494.4(only)-491(adverse)-491.1(outcome)-491.5(associated)-495.1(with)]TJ
T*
[(CBD)-530.7(treatment)-531.1(was)-529.2(diarrhea.)]TJ
8.2191 0 0 7.3052 198.7653 262.3748 Tm
(7)Tj
10.959 0 0 10.959 208.5165 257.5558 Tm
[(Thus,)-531(available)-533.2(data)]TJ
-13.3675 -1.1847 TD
[(from)-371.3(clinical)-372.2(trials)-371.6(suggest)-372(CBD)-370.3(is)-374.4(well)-367.7(tolerated)-372.9(and)]TJ
0 -1.1795 TD
[(has)-525.2(relatively)-522.4(few)-524.9(SAEs;)-520.4(however,)-522.4(interactions)-527.1(with)]TJ
0 -1.1847 TD
[(other)-297.7(medications)-298.7(should)-300(be)-299.7(closely)-299.9(monitored.)]TJ
.9984 -1.1795 TD
[(The)-322.1(therapeutic)-316.8(potential)-320.9(of)-321.2(CBD)-313.4(is)-322.7(being)-318.5(explored)]TJ
-.9984 -1.1847 TD
[(in)-238.8(a)-240.7(wide)-237.7(range)-241.3(of)-238.5(disorders.)-243.4(There)-235.3(are)-241.8(currently)-238.6(nearly)]TJ
0 -1.1795 TD
[(100)-239.1(registered)-237.9(trials)-237.1(investigating)-235.2(CBD,)-240.2(of)-238.5(which)-233.7(21)-237(are)]TJ
0 -1.1847 TD
[(phase)-313.4(3)-312.5(\(relevant)-311.5(patients)-313.7(in)-311.2(large)-309.8(numbers\),)-314.1(covering)]TJ
0 -1.1795 TD
[(chronic)-246.7(back)-242.8(pain,)-243.3(postsurgical)-247.5(pain,)-243.3(anxiety)-247.8(disorders,)]TJ
0 -1.1847 TD
[(infantile)-462.9(spasms,)-464.7(Rett)-461.2(Syndrome,)-462.4(Tuberous)-459.6(Sclerosis)]TJ
0 -1.1795 TD
[(Complex,)-340(bipolar)-340.2(depression,)-343.6(degenerative)-340(hallux)-342.7(dis-)]TJ
T*
[(orders,)-456.2(and)-452.3(Fragile)-450.7(X)-456.9(syndrome.)-452.6(Recently,)-450.7(some)-453.2(re-)]TJ
0 -1.1847 TD
[(searchers)-425.2(have)-423.9(speculated)-422.5(that)-424.9(CBD)-422(might)-420.2(be)-423.9(useful)]TJ
0 -1.1795 TD
-.0138 Tc
[(as)-430.9(an)-435(a)4.2(n)-.5(tiv)4.5(i)-2.1(ral)]TJ
8.2191 0 0 7.3052 125.1779 94.0535 Tm
0 Tc
(9)Tj
10.959 0 0 10.959 133.7385 89.1779 Tm
-.0137 Tc
[(o)5.2(r)-436(an)4.8(ti-in)5.2(amma)4.3(to)5.2(ry)]TJ
8.2191 0 0 7.3052 225.5243 94.0535 Tm
-.0237 Tc
[(10)-6.8(,)-5.7(1).1(1)]TJ
10.959 0 0 10.959 247.0109 89.1779 Tm
-.0146 Tc
[(age)-2.1(n)3.9(t)-436.8(i)2.3(n)-435.8(t)2.9(he)]TJ
-16.8801 -1.1847 TD
-.0135 Tc
[(cu)4.7(rren)5(t)-208.1(c)-1(o)5.4(r)-1.3(o)5.4(n)-.2(av)4.8(irus)-203(dise)4.2(ase-)]TJ
10.8016 0 TD
-.0152 Tc
[(19)-208.7(\(COVID-19\)/coronavirus)]TJ
-10.8016 -1.1795 TD
0 Tc
[(pandemic,)-329.7(as)-326.8(well)-331.4(as)-326.8(being)-328.8(capable)-329.7(of)-326.4(downregulating)]TJ
22.9068 57.9085 TD
[(the)-271.9(expression)-267(of)-269.5(key)-271.7(receptors)-269.7(\(ACE2)-268.3(and)-266.1(TMPRSS2\))]TJ
0 -1.1847 TD
[(for)-438.4(severe)-437.1(acute)-433.5(respiratory)-436.2(syndrome)-432.6(coronavirus)-433.7(2)]TJ
0 -1.1795 TD
[(\(SARS-CoV-2\))-348.4(in)-347.5(human)-345.7(epithelial)-341.4(cells.)]TJ
8.2191 0 0 7.3052 494.3621 676.8565 Tm
(12)Tj
10.959 0 0 10.959 506.0408 671.981 Tm
[(It)-347.9(has)-344.1(also)]TJ
-17.6095 -1.1847 TD
[(been)-372.2(postulated)-364.5(that)-368(CBD)-370.3(might)-368.5(inhibit)-367.2(the)-365(develop-)]TJ
0 -1.1795 TD
[(ment)-391.5(of)-388.5(pulmonary)-383.2(brosis)-391.7(in)-388.8(COVID-19)-381.3(patients.)]TJ
8.2191 0 0 7.3052 544.3085 650.9479 Tm
(13)Tj
10.959 0 0 10.959 313.0582 633.0896 Tm
[(Because)-572.7(of)-569.5(the)-572(growing)-570.2(evidence)-571.4(of)-569.5(the)-572(anxiolytic)]TJ
T*
[(effects)-292.4(of)-290.2(CBD,)-286.8(we)-288.2(suggest)-289.2(CBD)-287.5(could)-292.7(also)-285.5(be)-289.4(a)-287.3(thera-)]TJ
T*
[(peutic)-385.4(option)-377.5(to)-382.7(treat)-377.6(long-lasting)-380.6(COVID-19-relate)5.6(d)]TJ
0 -1.1847 TD
[(anxiety)-558.2(and)-560.9(post-traumatic)-555.9(stress)-557.5(disorder)-556.4(\(PTSD\),)]TJ
0 -1.1795 TD
[(which)-300.9(will)-301.2(be)-294.5(a)-302.8(signicant)-297.6(issue)-300.5(of)-300.5(this)-301.9(pandemic.)]TJ
/F4 1 Tf
10.4607 0 0 10.4607 313.0582 555.3636 Tm
[(COVID-Related)-302.3(Anxiety)-300.4(Disorders)]TJ
/F6 1 Tf
10.959 0 0 10.959 313.0582 542.4377 Tm
[(PTSD)-229.1(is)-229.6(a)-230.3(common)-226.5(consequence)-231(of)-228.1(major)-228.8(disasters,)-229.5(in-)]TJ
T*
[(cluding)-407.9(epidemics.)-402.2(Epidemiological)-402.5(projections)-404(made)]TJ
0 -1.1847 TD
[(by)-325(the)-323.7(World)-326(Health)-320(Organization)-321.7(\(WHO\))-323.4(show)-323.2(that)]TJ
0 -1.1795 TD
[(postdisaster)-356.8(mental)-356.3(health)-352.4(problems)-355.7(range)-355.1(from)-355.8(mild)]TJ
0 -1.1847 TD
[(to)-548.2(very)-549.2(severe)-545.8(distress,)-547.6(affecting)-545.5(between)-549.8(20%)-542.3(and)]TJ
0 -1.1795 TD
[(50%)-345.8(of)-341.9(the)-344.3(population.)-341.4(A)-342.5(minority)-341.5(develops)-342.8(new)-342.2(and)]TJ
0 -1.1847 TD
[(debilitating)-605.2(mental)-604.6(disorders,)-605.5(and)-607.5(those)-602.9(with)-604.5(pre-)]TJ
0 -1.1795 TD
[(existing)-428.1(mental)-423.5(disorders)-425.2(need)-424.6(even)-424.5(more)-427.4(help)-424.7(than)]TJ
0 -1.1847 TD
[(before.)-424.8(In)-424.5(the)-421.9(current)-424.1(pandemic,)-428(the)-421.9(WHO)-419.7(suggests)]TJ
0 -1.1795 TD
[(that)-435.2(levels)-437.8(of)-435(loneliness,)-432.4(depression,)-436.7(harmful)-437(alcohol)]TJ
T*
[(and)-385(drug)-378(use,)-385.7(and)-379.9(self-harm)-381.7(or)-377.6(suicidal)-382.2(behavior)-382.9(are)]TJ
0 -1.1847 TD
[(also)-394.1(expected)-390.4(to)-393(rise.)-390.4(Considering)-391.5(the)-390.9(breadth)-390.9(of)-388.5(the)]TJ
0 -1.1795 TD
[(COVID-19)-407.2(pandemic,)-407.3(and)-405.7(the)-401.3(widespread)-410.2(impact)-403.5(of)]TJ
0 -1.1847 TD
[(quarantine,)-482.4(social)-473.4(isolation,)-475.5(loss)-477.5(of)-476.4(loved)-478.8(ones)-475.9(\(and)]TJ
0 -1.1795 TD
[(the)-494.4(inability)-487.8(to)-491.3(grieve)-488.8(socially\),)-487.4(loss)-493(of)-486.8(income)-490(and)]TJ
0 -1.1847 TD
[(nancial)-363.5(worries,)-365.2(potentially)-357.8(extreme)-365.2(and)-359.2(chronic)-365.6(ill-)]TJ
0 -1.1795 TD
[(nesses)-375.1(\(which)-371.8(themselves)-373.5(impact)-372.5(mental)-371.8(health\),)-370.8(and)]TJ
0 -1.1847 TD
[(frontline)-311.5(working,)-310.8(the)-308.1(current)-310.3(crisis)-310.3(is)-307.2(likely)-308.4(to)-310.2(trigger)]TJ
0 -1.1795 TD
[(large)-304.7(numbers)-295.7(of)-300.5(people)-300.9(with)-299.3(long-lasting)-297.9(anxiety)-299.5(and)]TJ
0 -1.1847 TD
[(PTSD)-415.4(or)-419(post-traumatic)-416.2(stress)-412.6(symptoms)-415.3(\(PTSS\).)-419(In)]TJ
0 -1.1795 TD
[(fact,)-431.2(a)-426.9(recent)-431.7(article)-426.1(suggested)-429.2()42.1(PTSD)-425(as)-430.2(the)-427.1(second)]TJ
T*
[(tsunami)-302.5(of)-300.5(the)-297.8(SARS-CoV-2)-299.7(pandemic.)48.7()]TJ
8.2191 0 0 7.3052 491.5275 275.3007 Tm
(14)Tj
10.959 0 0 10.959 324.0566 257.4991 Tm
[(A)-202.8(systematic)-204.2(review)-202.5(of)-202.3(the)-204.7(evidence)-204.1(on)-205.7(the)-204.7(psychoso-)]TJ
-1.0036 -1.1795 TD
[(cial)-473.5(impact)-470.7(of)-471.3(quarantine)-472.8(measures)-471.5(during)-472(previous)]TJ
0 -1.1847 TD
[(coronavirus)-459.6(outbreaks)-453.5(showed)-452.9(that)-455.9(quarantine)-457.2(mea-)]TJ
0 -1.1795 TD
[(sures)-408.6(were)-408.4(consistently)-402.3(associated)-407.1(with)-402.8(negative)-405.7(psy-)]TJ
0 -1.1847 TD
[(chosocial)-469.8(outcomes,)-473.4(including)-470.9(depressive)-470(symptoms,)]TJ
0 -1.1795 TD
[(anxiety,)-205.7(anger,)-204.4(stress,)-205(post-traumatic)-198.9(stress,)-205(social)-204.4(isola-)]TJ
0 -1.1847 TD
[(tion,)-279.3(loneliness,)-282.4(and)-276.4(stigmatisation.)]TJ
8.2191 0 0 7.3052 467.4896 184.6488 Tm
(15)Tj
10.959 0 0 10.959 478.4314 179.7732 Tm
[(For)-281.8(example,)-280.9(the)]TJ
-15.0901 -1.1795 TD
[(rates)-357(of)-352.3(mental)-351.1(health)-352.4(symptoms)-348(after)-352.4(the)-354.7(SARS)-349.6(out-)]TJ
T*
[(break)-344.4(were)-346.3(between)-337.7(4%)-343.7(and)-343.7(17%,)-345(and)-343.7(were)-341.1(worst)-343.4(for)]TJ
0 -1.1847 TD
[(health)-600.7(care)-601.8(workers.)-596.6(Survey)-601(respondents)-599.4(who)-599.3(had)]TJ
0 -1.1795 TD
[(been)-330.8(isolated,)-328.4(worked)-329.3(in)-326.8(high-risk)-325.8(workplaces,)-330.8(or)-325.8(had)]TJ
0 -1.1847 TD
[(friends)-425.5(or)-424.1(close)-418.2(relatives)-421.5(who)-423.4(contracted)-421.2(SARS)-422(were)]TJ
0 -1.1795 TD
[(two)-373(to)-367.1(three)-371.4(times)-365.4(more)-370.5(likely)-370.5(to)-367.1(develop)-370.5(high)-372.1(levels)]TJ
0 -1.1847 TD
[(of)-300.5(PTSS.)]TJ
8.2191 0 0 7.3052 350.5889 93.9968 Tm
(16)Tj
10.959 0 0 10.959 324.0566 76.1953 Tm
[(In)-212.4(the)-215(current)-212(COVID-19)-210.6(outbreak,)-211.5(an)-211.8(early)-216.7(study)-210.5(of)]TJ
-1.0036 -1.1847 TD
[(residents)-219.1(in)-218.1(Wuhan)-215.6(and)-219.5(surrounding)-216.1(cities)-216.8(asked)-220.9(about)]TJ
ET
62.022 692.56 239.131 .22681 re
f
62.022 439.88 239.131 .28345 re
f
62.022 674.872 239.131 .22681 re
f
BT
/F4 1 Tf
8.9663 0 0 8.9663 62.022 699.2502 Tm
[(Table)-306.5(1.)-500.5(The)-297.1(Polypharmacology)-313.1(of)-296.4(Cannabidiol)]TJ
/F2 1 Tf
7.9702 0 0 7.9702 62.022 681.1085 Tm
[(CBDs)-325.6(rich)-336(pharma)13(cology)]TJ
/F9 1 Tf
0 -2.1268 TD
(Receptors)Tj
.9958 -1.1239 TD
[(Low)-296.4(CB)]TJ
5.9774 0 0 5.3127 95.074 653.8392 Tm
(1)Tj
7.9702 0 0 7.9702 98.0787 655.1998 Tm
(/CB)Tj
5.9774 0 0 5.3127 109.5874 653.8392 Tm
(2)Tj
7.9702 0 0 7.9702 115.0299 655.1998 Tm
[(afnity/poss)8.2(ible)-301(antagon)12.9(ism)]TJ
-5.6549 -1.1239 TD
[(Some)-297.3(\(indirect?\))-290.2(CB)]TJ
5.9774 0 0 5.3127 135.2126 644.8817 Tm
(1)Tj
7.9702 0 0 7.9702 138.2173 646.2424 Tm
(-/CB)Tj
5.9774 0 0 5.3127 152.1637 644.8817 Tm
(2)Tj
7.9702 0 0 7.9702 155.1684 646.2424 Tm
[(-mediated)-291.9(effects)]TJ
-10.691 -1.1239 TD
(5HT)Tj
5.9774 0 0 5.3127 83.0551 635.9243 Tm
(1A)Tj
7.9702 0 0 7.9702 92.0693 637.2849 Tm
(agonist)Tj
-2.7741 -1.131 TD
[(Peroxisome)-292.8(proliferator)8(-activated)-289.2(receptor)-296.7(gamma)-295.2(activator)]TJ
0 -1.1239 TD
[(GPR55)-296.1(antagonist)]TJ
T*
[(GPR18)-296.1(agonist)]TJ
T*
[(Inverse)-295.1(agonist)-294.5(for)-297.1(GPR3,)-296.1(GPR6,)-296.1(and)-299.1(GPR12)]TJ
T*
[(Dopamine)-292.9(D2)-299.3(partial)-294.4(agonist)]TJ
T*
[(Predicted)-292.9(dopamine)-294.4(D3)-292.2(agonist)]TJ
0 -1.131 TD
[(Adenosine)-288.1(receptor)-296.7(agonist)]TJ
0 -1.1239 TD
[(Glycine)-294.5(receptor)-296.7(agonist)]TJ
T*
[(Delta-type)-290.7(opioid)-295.1(receptor)-296.7(agonist)]TJ
-.9958 -1.5009 TD
(Ion)Tj
.9958 -1.1239 TD
[(Activation)-291.5(of)-299(TRPV1,)-298.5(TRPV2,)-291.3(TRPV3,)-298.5(and)-292(TRPM8)]TJ
-.9958 -1.5009 TD
(Channels)Tj
.9958 -1.1239 TD
[(Calcium)-297.7(channel)-288.3(inhibition)]TJ
-.9958 -1.5009 TD
(Enzymes)Tj
.9958 -1.1239 TD
[(FAAH)-299.9(inhibitor)]TJ
T*
[(Inhibits)-294.5(CYP1A1,)-293.6(2B6,)-297.7(2C19,)-297.3(3A4,)-298.7(and)-292(3A5)]TJ
T*
[(Cyclooxygena)9.8(se)-300(inhibitor/a)11(ctivator)]TJ
-.9958 -1.5009 TD
(Other)Tj
.9958 -1.1239 TD
[(Binds)-296(to)-303.6(FABPs)-295.3(\(compe)12.9(titive)-301.9(inhibition)13.6(\))]TJ
T*
[(Adenosine)-288.1(uptake)-300.5(inhibitor)]TJ
.128 -2.2478 TD
(5HT)Tj
5.9774 0 0 5.3127 84.0755 426.7841 Tm
(1A)Tj
7.9702 0 0 7.9702 90.7086 428.0881 Tm
[(,)-343.6(serotonin1)11.2(A;)-344.2(CB)]TJ
5.9774 0 0 5.3127 148.4787 426.7841 Tm
(1)Tj
7.9702 0 0 7.9702 151.5401 428.0881 Tm
[(,)-343.6(cannab)12.3(inoid)-341(receptor)-332.2(type)-338.9(1;)-338.6(CB)]TJ
5.9774 0 0 5.3127 265.1527 426.7841 Tm
(2)Tj
7.9702 0 0 7.9702 268.1574 428.0881 Tm
[(,)-343.6(cannabi-)]TJ
-25.8634 -1.1239 TD
[(noid)-385.1(receptor)-374.9(type)-388.6(2;)-381.3(CBD,)-381.3(cannabidiol;)-376.5(CYP,)-381.2(cytochrome)-383.2(P450;)-381(FAAH,)]TJ
T*
[(fatty)-444(acid)-438.3(amide)-434.3(hydrolase;)-435.5(FABP,)-436.4(fatty)-444(acid)-438.3(binding)-432.4(protein;)-438.3(GPR,)-443.3(g-)]TJ
T*
[(protein)-436.1(coupled)-430.7(receptor;)-434(TRPM,)-430.4(melastatin-)11.3(related)-436.3(transient)-431.3(receptor)]TJ
T*
[(potential)-496.3(cation)-502.9(channels;)-492.9(TRPV1,)-504.7(transient)-495.3(receptor)-502.9(potential)-496.3(cation)]TJ
0 -1.131 TD
[(channel)-295.4(subfamily)-290.7(V)-294.5(member.)]TJ
/F4 1 Tf
9.9626 0 0 9.9626 62.022 754.3557 Tm
(8)Tj
40.6704 0 TD
[(OSULLIVA)-10.2(N)-303.2(E)0(T)-299.4(AL.)]TJ
ET
endstream
endobj
51 0 obj
<>stream
/GS1 gs
BT
/F6 1 Tf
10.959 0 0 10.959 59.7543 697.8896 Tm
0 0 0 rg
0 Tc
0 Tw
[(PTSS)-221.1(and)-214.3(sleep)-217.1(qualities.)-218.8(One)-218.1(month)-216.2(after)-217.9(the)-215(outbreak)]TJ
0 -1.1847 TD
[(\(data)-226.9(were)-222.2(collected)-223.2(in)-223.3(January)-226.7(2020\),)-223.4(the)-220.2(prevalence)-225.3(of)]TJ
0 -1.1795 TD
[(PTSS)-391.8(was)-389.5(about)-384.5(7%.)]TJ
8.2191 0 0 7.3052 152.5039 676.8565 Tm
(17)Tj
10.959 0 0 10.959 164.6362 671.981 Tm
[(A)-389(subsequent)-389.2(study)-386.4(\(1210)-389.7(re-)]TJ
-9.5704 -1.1847 TD
[(spondents)-349.9(from)-350.6(194)-347.8(Chinese)-349.3(cities\))-349.8(found)-354.3(54%)-345.8(of)-352.3(re-)]TJ
0 -1.1795 TD
[(spondents)-722.4(rated)-718.3(the)-722(psychological)-713.4(impact)-724.2(of)-719.6(the)]TJ
0 -1.1847 TD
[(outbreak)-305.4(as)-306.1(moderate)-304.3(or)-305.1(severe,)-301.9(17%)-304.4(reported)-307.2(moder-)]TJ
0 -1.1795 TD
[(ate)-241.8(to)-243(severe)-240.6(depressive)-242.3(symptoms,)-238.7(29%)-237.1(reported)-245.1(mod-)]TJ
T*
[(erate)-470.5(to)-470.6(severe)-468.2(anxiety)-470.2(symptoms,)-471.5(and)-467.8(8%)-467.8(reported)]TJ
0 -1.1847 TD
.0141 Tc
[(moder)-4.7(a)1(te)-526.9(to)-520.5(sever)-4.7(e)-521.8(st)-4.6(ress)-527.2(levels.)]TJ
8.2191 0 0 7.3052 214.0157 599.1306 Tm
.0176 Tc
(18)Tj
10.959 0 0 10.959 227.9054 594.2549 Tm
.0161 Tc
[(Lo)4(oking)-519.1(a)3(t)-525.1(t)2.5(h)3.9(e)]TJ
-15.3436 -1.1795 TD
.0164 Tc
[(me)3(nta)3.3(l)-338.9(he)3(alth)-337.2(effe)3(cts)-338.7(o)4.3(f)-344.4(C)5.1(OV)4.7(ID)5.6(-1)3.9(9)-337.5(i)2.2(n)-342.7(y)3.6(o)4.3(u)-1.6(n)3.9(g)-1.5(e)3(r)-338.7(pe)3(o)4.3(-)]TJ
0 -1.1847 TD
.0145 Tc
[(ple,)-605.6(a)-603.8(c)-4(ros)-4.3(s).9(-sectional)-604.6(sur)-4.3(v)1.7(ey)-603.5(s)-4.3(u)1.7(gges)-4.3(ts)-604.4(that)-604.3(nearly)]TJ
0 -1.1795 TD
[(15%)-394.3(o)2.4(f)-392.9(r).9(es)-4.3(pondent)-4.2(s)-387.1(had)-391.5(P)-2.9(TSD)-389.4(s).9(ymptoms)-392.3(a)-3.7(nd)-391.5(40%)]TJ
0 -1.1847 TD
[(had)-303.7(a)-298.7(te)-4.1(ndenc)-4.1(y)-298.4(to)-303(have)-304.2(psychological)-299.5(p)1.6(r)-4.4(o)2.3(blems.)]TJ
8.2191 0 0 7.3052 277.6251 547.3132 Tm
.0245 Tc
(19)Tj
10.959 0 0 10.959 289.1338 542.4377 Tm
.0136 Tc
(In)Tj
-20.9307 -1.1795 TD
.0144 Tc
[(pati)-5(ent)-4.3(s)-475.2(who)-473.7(c)1(ontracte)-4.1(d)-474.4(COVID-19,)-476.3(t).8(he)-474.9(degr)-4.4(ee)-474.9(of)]TJ
0 -1.1847 TD
.0151 Tc
[(psychological)-360.9(d)2.3(istress)-360.7(m)4.6(ay)-359.8(be)-365.6(related)-365(t)1.5(o)-359.2(t)1.5(he)-360.4(level)-360.9(o)-2.2(f)]TJ
0 -1.1795 TD
[(systemic)-298.2(inammation.)]TJ
8.2191 0 0 7.3052 165.4299 508.4786 Tm
.0176 Tc
(20)Tj
10.959 0 0 10.959 70.7527 490.677 Tm
0 Tc
[(A)-218.3(multinational)-216.5(multicenter)-222.5(study)-220.9(on)-216.1(the)-220.2(psycholog-)]TJ
-1.0036 -1.1847 TD
[(ical)-659.7(outcomes)-655.2(among)-656(health)-657.6(care)-658.7(workers)-654.2(during)]TJ
0 -1.1795 TD
[(COVID-19)-303.7(surveyed)-307(906)-306.4(health)-305.8(care)-307(workers.)]TJ
8.2191 0 0 7.3052 261.8645 469.644 Tm
(21)Tj
10.959 0 0 10.959 273.0897 464.7684 Tm
(Using)Tj
-19.4666 -1.1847 TD
[(the)-515.1(depression,)-514.3(anxiety,)-516.1(and)-509.2(stress)-516.1(scale)-512.2(\(DASS-21\))]TJ
0 -1.1795 TD
[(scoring)-537.2(system,)-532.1(the)-530.6(authors)-536(found)-530.2(anxiety)-537.5(in)-533.7(16%,)]TJ
0 -1.1847 TD
[(depression)-230.5(in)-228.5(11%,)-220.9(and)-229.9(stress)-226.4(in)-228.5(5%)-224.7(of)-228.1(the)-225.4(study)-226(partic-)]TJ
0 -1.1795 TD
[(ipants.)-518.8(Seven)-520.4(percent)-522.1(of)-517.8(the)-515.1(study)-520.9(cohort)-516.8(screened)]TJ
0 -1.1847 TD
[(positive)-355(for)-355.6(clinical)-351.5(concern)-354.8(of)-352.3(PTSD.)-352.6(Another)-352.7(cross-)]TJ
0 -1.1795 TD
[(sectional)-383.6(survey)-389.4(of)-383.3(1257)-380.9(health)-383.4(care)-389.7(workers)-380(treating)]TJ
0 -1.1847 TD
[(COVID-19)-329.6(patients)-334.4(in)-326.8(China)-332.3(found)-333.6(signicant)-328.6(repor-)]TJ
0 -1.1795 TD
[(ted)-308.8(symptoms)-301.5(of)-305.7(depression)-303(\(50%\),)-305.7(anxiety)-304.7(\(45%\),)-300.5(in-)]TJ
T*
[(somnia)-298.6(\(34%\),)-300.5(and)-302.3(distress)-300(\(72%\).)]TJ
8.2191 0 0 7.3052 210.8976 353.0267 Tm
(22)Tj
10.959 0 0 10.959 70.7527 335.2251 Tm
[(Overall,)-691(a)-690.8(systematic)-685.3(review)-694(\(published)-690.6(August)]TJ
-1.0036 -1.1795 TD
[(2020\))-482.8(of)-481.6(the)-478.9(effects)-483.8(of)-481.6(COVID-19)-479.6(on)-479.9(psychological)]TJ
0 -1.1847 TD
[(outcomes)-375.8(found)-380.2(high)-377.2(rates)-377.7(of)-378.1(anxiety)-377.1(\(6%51%\),)-372.2(de-)]TJ
0 -1.1795 TD
[(pression)-395.7(\(15%48%\),)-395(PTSD)-394.7(\(7%54%\),)-392.9(psychological)]TJ
0 -1.1847 TD
[(distress)-346.5(\(34%38%\),)-343.2(and)-343.7(stress)-345.4(\(8%82%\))-341.8(in)-347.4(the)-344.4(gen-)]TJ
0 -1.1795 TD
[(eral)-276.4(population)-274.9(in)-275(China,)-279.9(Spain,)-277.1(Italy,)-273(Iran,)-274.6(the)-277.1(United)]TJ
0 -1.1847 TD
[(States,)-374.5(Turkey,)-376.7(Nepal,)-373.9(and)-374.7(Denmark.)]TJ
8.2191 0 0 7.3052 225.9779 262.3748 Tm
(23)Tj
10.959 0 0 10.959 237.9968 257.4991 Tm
[(Their)-370.6(conclu-)]TJ
-16.2645 -1.1795 TD
[(sion)-575(was)-570.6(that)-569.7()47.3(mitigating)-570.4(the)-572(hazardous)-572.1(effects)-571.7(of)]TJ
T*
[(COVID-19)-267.5(on)-267.8(mental)-263.2(health)-269.6(is)-265.8(an)-268.7(international)-265.4(public)]TJ
0 -1.1847 TD
[(health)-300.7(priority.)44.5()]TJ
1.0036 -1.1795 TD
[(Pharmacologica)6.6(l)-220.8(treatment)-220.7(strategies)-217.6(are)-221.2(likely)-220.5(to)-222.3(in-)]TJ
-1.0036 -1.1847 TD
[(volve)-432.2(selective)-431.9(serotonin)-428.2(reuptake)-431.4(inhibitors)-427.3(\(SSRIs\),)]TJ
0 -1.1795 TD
[(selective)-545.7(noradrenali)5.1(ne)-543.2(reuptake)-540.1(inhibitors)-541.1(\(SNRIs\),)]TJ
0 -1.1847 TD
[(serotonin)-355.8(1A)-349.7(\(5HT)]TJ
8.2191 0 0 7.3052 145.8708 165.033 Tm
(1A)Tj
10.959 0 0 10.959 155.4519 166.8472 Tm
-.0001 Tc
[(\))-355.5(agonists,)-353.3(and)-354.1(benzodiazepines,)]TJ
-8.7323 -1.1795 TD
0 Tc
[(all)-402.9(of)-404(which)-399.2(have)-403.2(side)-405.8(effect)-402.9(proles)-402.1(that)-399(are)-402.2(not)-405.5(al-)]TJ
0 -1.1847 TD
[(ways)-241.9(tolerable)-238(to)-237.8(patients,)-240.6(including)-238.1(signicant)-240.7(adverse)]TJ
0 -1.1795 TD
[(events)-394.8(\(e.g.,)-400(insomnia,)-397(agitation,)-392.5(central)-393.5(nervous)-396.2(sys-)]TJ
0 -1.1847 TD
-.0137 Tc
[(t)-13.7(e)-13.7(m)-252.9(d)4.5(e)-1.2(pressive)-182.3(effe)4(cts,)-183.7(an)4.8(d)-186.9(s)3.7(ex)]TJ
11.531 0 TD
-.0163 Tc
[(ua)-3.5(l)-185.3(d)-3.3(y)-3.2(s)1.1(fu)-3.3(nct)-4(i).6(on\))-4.4(,)-186.3(s)-4.1(y)2(mp)-3.3(tom)]TJ
-11.531 -1.1795 TD
-.014 Tc
[(relapse,)-437.5(drug)-435.4(dep)4.2(e)-1.5(nd)4.2(en)4.5(ce,)-437.5(an)]TJ
11.7121 0 TD
-.015 Tc
[(d)-436.5(w)-.2(ithdrawal)-437.5(s)-2.8(yndromes.)]TJ
-11.7121 -1.1795 TD
-.0157 Tc
[(Mor)-3.5(e)2(over,)-361.6(t)-3.4(hes)-3.5(e)-360.2(tr)-3.5(eatments)]TJ
11.1275 0 TD
-.0147 Tc
[(can)-363.5(s)2.7(how)-356.8(limited)-363.8(o)4.2(r)-364.6(s)2.7(ho)4.2(rt-)]TJ
-11.1275 -1.1847 TD
-.0139 Tc
[(live)3.8(d)-430.2(e)-1.4(fca)4.1(cy)-430.2(in)-435.1(a)-430.5(s)3.5(ig)4.4(nic)3.8(ant)-431(n)4.6(umbe)3.8(r)-431(o)-.2(f)-431.6(p)-.9(a)4.1(t)3.6(ie)3.8(nts,)-432.2(a)4.1(n)-.6(d)]TJ
0 -1.1795 TD
-.0133 Tc
[(th)5.6(eir)-182.1(t)-1(he)4.4(ra)4.7(pe)4.4(utic)-181.9(e)4.4(f)-1.6(fec)4.4(t)-1(s)-182.1(c)4.4(an)-181(ha)4.7(ve)-181.9(a)-181.6(d)-.3(ela)4.7(y)-.2(ed)-181.3(o)5.6(n)0(se)4.4(t)-182.1(o).4(f)-182.7(a)4.7(ctio)5.6(n)]TJ
22.912 57.9085 TD
[(o)5.6(f)-363.8(se)4.4(ve)4.4(ra)4.7(l)-363.4(w)1.5(ee)4.4(ks)-363.2(\(in)-367.3(t)4.2(he)-362.9(c)4.4(a)-.5(s)4.1(e)-362.9(of)-363.8(S)4.6(S)-.5(R)5.8(I)-1(s)-363.2(a)4.7(nd)-362.4(SNR)5.8(I)-1(s)4.1(\))-363.5(\(s)4.1(ee)]TJ
0 -1.1847 TD
-.0139 Tc
[(P)4.9(a)-1.1(pa)4.1(gian)4.6(ni)-416.1(an)4.6(d)-414.7(S)-1.1(tev)4.4(e)-1.4(nson)]TJ
8.2191 0 0 7.3052 425.4235 689.7825 Tm
-.0169 Tc
(24)Tj
10.959 0 0 10.959 438.1227 684.9069 Tm
-.0143 Tc
[(for)-462.5(a)-467.1(prev)4(io)4.6(us)-467.7(rev)4(i)-2.6(ew)-465(on)]TJ
-11.6138 -1.1795 TD
-.015 Tc
[(this)-256.3(topic\).)-252.2(P)-1.4(sychological)-251.3(trea)]TJ
11.2723 0 TD
-.0153 Tc
[(tments)-256.6(\(e.g.,)-252.5(exposure)-256.3(ther-)]TJ
-11.2723 -1.1847 TD
-.0158 Tc
[(apy\))-226.3(a)-3(r)1.6(e)-225.8(a)-3(ls)-3.6(o)-224.5(a)-3(vai)-4.1(l)1.4(able)-3.3(,)-227.2(b)-2.1(ut)-225.9(aga)-3(i)1.1(n)-230.1(t)1.7(hey)-230.3(c)1.9(a)-3(n)-224.9(ha)-3(ve)-230.9(limi)-4.1(te)-3.3(d)-225.2(o)-2.1(r)]TJ
0 -1.1795 TD
-.0144 Tc
[(temp)3.8(orary)-378.9(t)-2.1(h)4.5(e)-1.9(rapeutic)-379.5(effects.)]TJ
8.2191 0 0 7.3052 439.2566 650.9479 Tm
-.0169 Tc
(25)Tj
10.959 0 0 10.959 450.992 646.0723 Tm
-.0139 Tc
[(Thu)4.3(s)-1.7(,)-380.5(n)-.6(ov)4.4(el)-379.5(ag)4.4(ents)-384.5(a)4.1(r)-1.7(e)]TJ
-12.7881 -1.1847 TD
-.0172 Tc
[(re)-4.7(qu)-4.2(ir)-5(e)-4.7(d)-299(t)-4.9(o)-298.4(ma)-4.4(na)-4.4(g)-4.1(e)-299.6(the)-4.7(s).2(e)-304.8(s).2(y)-4.1(m)-1.9(pt)-4.9(oms)-5(.)]TJ
/F4 1 Tf
10.4607 0 0 10.4607 310.8472 607.181 Tm
0 Tc
[(Clinical)-299.7(Studies)-299.9(with)-303.8(CBD)-300.3(in)-296(Anxiety)]TJ
0 -1.2357 TD
[(and)-298.4(Related)-304.5(Disorders)]TJ
/F6 1 Tf
10.959 0 0 10.959 310.8472 581.2723 Tm
[(Over-the-cou)5.4(nter)-353.2(\(OTC\))-352(CBD)-349.6(products)-353.2(have)-351.4(become)]TJ
0 -1.1795 TD
[(very)-306(popular)-313.7(in)-306.1(the)-308.1(health)-311(and)-307.4(wellness)-312.2(markets)-307.9(glob-)]TJ
0 -1.1847 TD
[(ally.)-461.5(One)-456.1(of)-460.9(the)-463.3(features)-459.5(most)-458.6(often)-459(proclaimed)-461(for)]TJ
0 -1.1795 TD
[(C)14.5(B)14(D)-300.5(i)11.7(s)-298.2(i)11.7(t)12.3(s)-298.2(ab)21.3(i)11.7(l)12(i)11.7(t)12.3(y)-297.3(t)12.3(o)-296.7(r)12.2(e)12.5(d)0(u)20.9(c)12.5(e)-297.9(s)12.2(t)12.3(r)12.2(es)19.5(s)-298.2(a)12.8(n)13.3(d)-302.5(a)12.8(n)13.3(x)12.8(i)11.7(e)12.5(t)12.3(y)13.1(.)-304.5(A)-295.9(c)12.5(r)12.2(o)13.7(ss)19.3(-)]TJ
T*
[(s)12.2(e)12.5(c)12.5(t)12.3(i)11.7(o)13.7(na)21(l)-360.4(s)12.2(t)12.3(u)13(d)13(y)-359.4(of)-352.3(O)14.8(T)13.9(C)-363.1(C)14.5(BD)-348.6(u)13(s)12.2(e)12.5(r)0(s)-353.2(f)11.6(o)13.7(u)13(n)13.3(d)-364.6(t)12.3(h)13.7(a)12.8(t)-360.2(t)12.3(h)13.7(e)-360(t)12.3(op)]TJ
0 -1.1847 TD
-.0128 Tc
[(3)-299.4(m)-2.6(edical)-306(condition)-12.8(s)-292.5(for)-305.8(w)2(hich)-304.3(CBD)-302.9(i)-1.1(s)-300.6(u)-12.8(s)7.3(e)-.3(d)-299.8(w)-12.8(e)9.3(r)-.6(e)-300.3(p)-12.8(a)7.8(i)-1.1(n,)]TJ
0 -1.1795 TD
-.0124 Tc
[(anxiety)-12.4(,)-386.6(an)-12.4(d)-384.4(d)-12.4(e)7.9(p).6(ressio)-12.4(n)9.5(.)]TJ
8.2191 0 0 7.3052 416.1826 508.4786 Tm
-.0168 Tc
(26)Tj
10.959 0 0 10.959 428.1448 503.603 Tm
-.013 Tc
[(A)-396.8(m)2.3(or)-13(e)-386.6(r)-.8(e)-13(c)6.8(ent)-399(s)-.8(tudy)-398.2(foun)-13(d)]TJ
-10.7033 -1.1847 TD
0 Tc
[(t)12.3(h)13.7(a)12.8(t)-417.1(t)12.3(h)13.7(e)-411.7(t)12.3(op)-402.6(r)12.2(e)0(a)20.1(s)12.2(o)13.7(n)13.3(s)-417.2(O)14.8(TC)-400.9(CB)23.3(D)-414.3(w)14.8(as)-404.4(u)13(s)12.2(ed)-403.9(we)22.1(r)12.2(e)-411.7(s)12.2(t)12.3(re)19.5(s)12.2(s)]TJ
0 -1.1795 TD
-.0124 Tc
[(relief,)-223.8(r)-12.4(e)7.1(l)-.4(axation,)-228.9(and)-227(s)-.2(leep)-227(improvement.)]TJ
8.2191 0 0 7.3052 485.4613 482.5699 Tm
-.0169 Tc
(27)Tj
10.959 0 0 10.959 495.5526 477.6943 Tm
.2111 Tc
[(A2)224.5(0)211.1(2)232.8(0a)211.1(n)232.1(a)223.9(l)223.1(-)]TJ
-16.8542 -1.1847 TD
-.0128 Tc
[(ysis)-336.8(of)-332.2(so)-12.8(c)8.2(i)-1.1(al)-331.8(media)-336.3(c)-.3(on)-12.8(t)7.7(e)-.3(nt)-331.6(r)-12.8(e)6.7(vealed)-336(that)-336.8(CB)-12.8(D)-325.2(i)-1.1(s)-331.7(m)-2.6(ost)]TJ
0 -1.1795 TD
-.0126 Tc
[(discuss)-12.6(e)6.9(d)-366.9(a).2(s)-372.8(a)-367.1(the)-12.6(r)6.9(apeutic)-372.6(o)1.1(ption)-371.7(f)-.9(or)-372.8(anxiety)-372(d).4(isord)-12.6(e)7.7(rs)]TJ
0 -1.1847 TD
-.0129 Tc
[(and)-356.8(p).1(ain.)]TJ
8.2191 0 0 7.3052 351.7227 443.6786 Tm
-.0169 Tc
(28)Tj
10.959 0 0 10.959 363.2314 438.803 Tm
-.0127 Tc
[(How)-12.7(e)9.4(ver,)-353.4(th)-12.7(e)8.3(r)-.5(e)-352(a).1(re)-357.2(issues)-357.4(with)-350.8(O)-12.7(T)10.8(C)-355.1(C)1.8(B)-12.7(D)11.2(,)]TJ
-4.78 -1.1795 TD
[(includ)-12.6(i)12.1(n)-12.6(g)-348.3(u).4(n)-12.6(r)7.8(eliable)-357.1(q)-12.6(u)8.6(a).2(lity,)-358.5(p)-12.6(o)9(t)-.3(ential)-357.5(p)-12.6(r)7.5(esence)-362.2(of)-357.9(co)-12.6(n)9.3(-)]TJ
T*
-.0125 Tc
[(trolled)-439.2(s)-12.5(u)7.6(b)1.2(stanc)-12.5(e)7.3(s,)]TJ
8.2191 0 0 7.3052 390.5007 417.77 Tm
-.0168 Tc
(29)Tj
10.959 0 0 10.959 402.9164 412.9511 Tm
0 Tc
[(a)12.8(n)0(d)-418.5(l)12(o)13.7(w)0(e)22.1(r)-427.5(d)13(o)13.7(s)12.2(i)11.7(ng)-418.5(o)13.7(p)13(t)12.3(i)11.7(on)21.9(s)12.2(,)-428.6(w)14.8(h)0(i)20.2(c)12.5(h)]TJ
-8.4012 -1.1847 TD
-.0126 Tc
[(limit)-300.3(t)-.3(he)-305.3(use)-300.2(o)1.1(f)-301(C)-12.6(B)10.7(D)-297.5(in)-299.3(s)-12.6(e)6.9(rious)-300.4(a).2(n)-12.6(x)8.3(iety)-299.5(con)-12.6(d)8.6(itions.)]TJ
.9984 -1.1795 TD
0 Tc
[(Alongside)-359.9(the)-354.7(anecdotal)-361(use)-360.6(of)-357.5(CBD)-354.8(for)-360.8(stress)-360.9(and)]TJ
-.9984 -1.1847 TD
[(anxiety,)-210.9(there)-216.2(is)-214.1(a)-214.8(growing)-213.2(body)-210.3(of)-212.6(clinical)-217(studies)-213.1(dem-)]TJ
0 -1.1795 TD
[(onstrating)-286.9(the)-282.3(anxiolytic)-288(effects)-287.2(of)-290.2(CBD)-282.3(across)-286.5(various)]TJ
0 -1.1847 TD
[(patient)-548.4(cohorts)-546(and)-545.4(various)-547.5(pathological)-545(situations.)]TJ
0 -1.1795 TD
[(Several)-315.6(small)-318.4(proof-of-concept)-312.7(randomized)-320(controlled)]TJ
0 -1.1847 TD
[(clinical)-408.4(trials)-407.9(and)-410.9(case)-410.4(series)-407.8(report)-410.3(on)-407.5(the)-411.6(ability)-404.1(of)]TJ
0 -1.1795 TD
[(CBD)-266.8(to)-268.9(have)-268.7(positive)-267.1(effects)-271.7(on)-267.8(anxiety)-268.5(in)-269.9(healthy)-272.1(vol-)]TJ
0 -1.1847 TD
[(unteers)-372.3(or)-372.4(patients)-375.8(with)-371.7(various)-371.7(diagnoses,)-371(and)-374.7(these)]TJ
0 -1.1795 TD
[(studies)-301(are)-298.8(summarized)-304(in)-295.7(Table)-302.4(2.)-301.4(It)-301.3(should)-299.9(be)-299.7(noted)]TJ
T*
[(that)-243.8(the)-246.1(evidence)-245.5(base)-248.8(in)-244(this)-245(area)-244.6(is)-250.3(still)-244.9(of)-243.6(low)-243.9(quality.)]TJ
0 -1.1847 TD
[(Although)-463(there)-469.7(are)-469.5(RCTs)-467.9(showing)-466.1(efcacy)-464.8(of)-471.3(CBD,)]TJ
0 -1.1795 TD
-.0179 Tc
[(seven)-444.3(o)1(f)-446(t)-.4(hese)-445.1(were)-445.1(carried)-444.6(out)-445.3(i)-1(n)-444.3(h)1(ealthy)-444.5(volunteers,)]TJ
0 -1.1847 TD
-.0181 Tc
[(and)-310.3(o).8(nly)-310.2().8(ve)-305.6(were)-310.8(in)-310(relevant)-305.8(patient)-311(c)-.4(ohorts)-305.9(\(Table)-310.8(2\).)]TJ
0 -1.1795 TD
0 Tc
[(All)-204.6(of)-207.4(the)-204.7(trials)-211.3(were)-206.6(also)-202.7(in)-207.8(very)-207.7(small)-204.6(patient)-207(numbers.)]TJ
0 -1.1847 TD
[(Thus,)-350(larger)-344.2(trials)-351(in)-347.4(relevant)-349.3(patients)-349.9(are)-345.3(required)-349.5(to)]TJ
0 -1.1795 TD
[(conrm)-296.9(these)-299(ndings.)]TJ
.9984 -1.1847 TD
[(In)-652.1(healthy)-644.5(volunteers)-649.1(in)-647.5(randomized)-651.1(controlled)]TJ
-.9984 -1.1795 TD
[(studies,)-527.9(acute)-531.8(doses)-531.3(of)-533.3(300)-528.8(or)-527.6(600)-166.7(mg)-530.3(given)-531.2(orally)]TJ
T*
[(reduced)-480.3(the)-484(anxiety)-480.6(caused)-482.7(by)-480.2(public)-482.7(speaking,)]TJ
8.2191 0 0 7.3052 529.9652 158.7401 Tm
(3032)Tj
10.959 0 0 10.959 310.8472 140.9385 Tm
-.0001 Tc
[(and)-276.5(reduced)-273.5(the)-277.2(blood)-270.2(pressure)-277.8(and)-276.5(cardiovascular)-277.6(re-)]TJ
T*
0 Tc
[(sponse)-492.1(to)-496.5(physical)-493.9(and)-493.7(mental)-496(stress)-495.4(\(600)-165.1(mg\).)]TJ
8.2191 0 0 7.3052 529.1148 132.8882 Tm
(33)Tj
10.959 0 0 10.959 542.4376 128.0126 Tm
(A)Tj
-21.1324 -1.1847 TD
-.0001 Tc
[(dose-ascending)-592.4(placebo-controlled)-592.3(study)-593.4(in)-595.9(healthy)]TJ
0 -1.1795 TD
0 Tc
[(volunteers)-328.3(found)-328.4(that)-326.6(a)-333.8(single)-328.7(300)-166.7(mg,)-327.8(but)-328.3(not)-327.9(100)-327.1(or)]TJ
0 -1.1847 TD
[(900)-161.5(mg,)-291.6(dose)-290(of)-285(CBD)-287.5(was)-291.2(effective)-288(at)-290.5(reducing)-286.6(anxiety)]TJ
0 -1.1795 TD
[(in)-399.2(a)-395.9(public)-400(speaking)-400.1(test.)]TJ
8.2191 0 0 7.3052 424.6865 81.0708 Tm
(34)Tj
10.959 0 0 10.959 436.9322 76.1953 Tm
[(Such)-398.1(anxiolytic)-396.6(effects)-401(of)]TJ
-11.5051 -1.1847 TD
[(ac)9.8(ut)9.8(e)-318.6(CBD)-313.4(tr)14.2(ea)9.8(tme)14.2(nt)-315.8(ar)9.5(e)-323.8(a)0(s)9.5(s)0(o)10.4(c)0(i)13.8(ate)11.7(d)-318.1(wit)12.9(h)-322.6(a)0(l)14.5(ter)11.1(ed)-315.9(br)10.4(ain)]TJ
/F4 1 Tf
9.9626 0 0 9.9626 59.7543 753.8455 Tm
[(CBD)-306.5(IN)-306.7(COVID-19)-10.5(-RELATED)-309.1(PTSD)]TJ
48.6485 0 TD
(9)Tj
ET
endstream
endobj
55 0 obj
<>stream
0 0 0 rg
/GS1 gs
62.022 680.712 490.167 .22675 re
f
62.022 663.023 490.167 .22681 re
f
BT
/F4 1 Tf
8.9663 0 0 8.9663 62.022 697.3226 Tm
0 Tc
0 Tw
[(Table)-306.5(2.)-500.5(Published)-304.3(Clinical)-305.2(Evidence)-302.9(of)-302.7(Cannabidiol)-304.7(Efcacy)-305.3(in)-297.8(Anxiety)-305.9(Disorders)-306.5(Through)-300.9(Randomized)-305.4(Controlled)-302.1(Trials)]TJ
0 -1.1128 TD
[(and)-302(Observational)-308.6(Studies)]TJ
/F2 1 Tf
7.9702 0 0 7.9702 144.737 669.203 Tm
[(Study)-329.8(type)-4266.7(Patient)-325.9(cohort)-7057.3(Dose)-14323.3(Findings)]TJ
/F9 1 Tf
-10.3781 -2.1197 TD
[(Randomized)-289.6(controlled)-293.2(trials)]TJ
.9958 -1.1239 TD
[(Zuardi)-295.4(et)-301.9(al.)]TJ
1.003 -1.131 TD
(\(1993\))Tj
5.9774 0 0 5.3127 98.6456 637.9085 Tm
(32)Tj
7.9702 0 0 7.9702 133.7385 643.351 Tm
(Double-blind)Tj
1.003 -1.131 TD
[(design)-325.6(and)]TJ
0 -1.1239 TD
(placebo-)Tj
T*
(controlled)Tj
8.0023 3.3787 TD
[(Four)-329.2(groups)-323.5(of)-334.6(10)]TJ
.9958 -1.131 TD
(subjects)Tj
9.5031 1.131 TD
[(CBD)-329.4(\(300)-159.3(mg\),)-327.9(diazepam)]TJ
.9958 -1.131 TD
[(\(10)-164.3(mg\))-332.8(or)-332(ipsapirone)]TJ
0 -1.1239 TD
[(\(5)-169.3(mg\))-325.7(or)-332(placebo)]TJ
11.004 2.2549 TD
[(CBD)-329.4(decreased)-321(anxiety)-328.1(after)-333.8(the)-326(simulated)-327.3(public)]TJ
.9958 -1.131 TD
[(speaking)-324.6(test)-331.8(\(evaluated)-329.8(through)-324(the)-333.2(visual)]TJ
0 -1.1239 TD
[(analog)-326.3(mood)-332.7(scale)-325.8(and)-334.7(state)-329.3(trait)-331.9(anxiety)]TJ
T*
[(inventory\))-327.8(and)-327.6(was)-331.8(as)-328.1(effective)-331.9(as)-328.1(other)]TJ
T*
[(pharmacolog)10.1(ical)-330.3(agents.)-332(Only)-326(diazepam)-324.9(was)]TJ
T*
(sedative.)Tj
-40.5022 -1.1239 TD
[(Fusar-Poli)-291(et)-301.9(al.)]TJ
1.003 -1.1239 TD
(\(2009\))Tj
5.9774 0 0 5.3127 98.6456 584.1069 Tm
(30)Tj
7.9702 0 0 7.9702 133.7385 589.5494 Tm
[(Double-blind)-325.1(and)]TJ
1.003 -1.1239 TD
(placebo-)Tj
0 -1.131 TD
(controlled)Tj
8.0023 2.2549 TD
[(Fifteen)-320.8(healthy)-326.5(and)]TJ
.9958 -1.1239 TD
[(right-handed)-325.5(men)]TJ
9.5031 1.1239 TD
[(Ten)-329.8(milligrams)-322(THC,)]TJ
.9958 -1.1239 TD
[(600)-162.9(mg)-329.3(CBD)]TJ
0 -1.131 TD
[(or)-332(placebo)]TJ
11.004 2.2549 TD
[(There)-325.8(was)-324.7(a)-331.9(trend)-324.1(for)-332.7(a)-331.9(reduction)-323(in)-328.7(anxiety)-321(after)]TJ
.9958 -1.1239 TD
[(administrati)9.3(on)-336.7(of)-327.4(CBD.)-331.6(CBD)-329.4(attenuated)-322(the)]TJ
0 -1.131 TD
[(blood)-332(oxygenatio)11.3(n)-330(level-depend)14.1(ent)-333.2(signal)-331(in)]TJ
0 -1.1239 TD
[(the)-333.2(amygdala)-322.1(and)-327.5(the)-333.2(anterior)-325.1(and)-334.7(posterior)]TJ
T*
[(cingulate)-239.1(cortex,)-236.1(while)-236.4(subjects)-240.9(were)-232.3(processing)]TJ
T*
[(intensely)-328.8(fearful)-327.4(faces,)-330(and)-327.5(its)-334.4(suppression)-326.7(of)]TJ
T*
[(the)-333.2(amygdala)-322.1(and)-327.5(anterior)-332.3(cingulate)-324.4(responses)]TJ
T*
[(was)-274.9(correlated)-271.5(with)-273.5(the)-269.1(concurrent)-269.6(reduction)-273.2(in)]TJ
0 -1.131 TD
[(skin)-297.9(conductance)-293.4(response)-294.6(uctuatio)8.4(ns.)]TJ
-40.5022 -1.1239 TD
(Bergamaschi)Tj
1.003 -1.1239 TD
[(et)-209.4(al.)-204.7(\(2011\))]TJ
5.9774 0 0 5.3127 115.7102 503.433 Tm
(37)Tj
7.9702 0 0 7.9702 133.7385 508.8188 Tm
[(Double-blind)-3540.3(Twelve)-324.7(healthy)]TJ
10.0011 -1.1239 TD
[(volunteers)-327.9(and)-327.6(24)]TJ
T*
[(patients)-330.7(with)]TJ
T*
[(generalized)-326.4(SAD)]TJ
9.5031 3.3716 TD
[(CBD)-329.4(600)-162.9(mg)-6823.6(Pretreatm)12.5(ent)-333.2(with)-330.4(CBD)-329.4(significantl)10.5(y)-335.8(reduced)]TJ
12.9957 -1.1239 TD
[(anxiety,)-252(cognitive)-239.1(impairment)-246.3(and)-249.3(discomfo)12.1(rt)-252.3(in)]TJ
T*
[(their)-329.9(speech)-330.3(performanc)12(e.)]TJ
-40.5022 -2.2477 TD
[(Zuardi)-295.4(et)-301.9(al.)]TJ
1.003 -1.131 TD
(\(2017\))Tj
5.9774 0 0 5.3127 98.6456 467.5463 Tm
(34)Tj
7.9702 0 0 7.9702 133.7385 472.9889 Tm
(Parallel-group,)Tj
1.003 -1.131 TD
[(double-blind)14.8(,)]TJ
0 -1.1239 TD
[(and)-327.6(placebo-)]TJ
T*
(controlled)Tj
8.0023 3.3787 TD
[(Sixty)-267.5(healthy)-262.5(subjects)]TJ
.9958 -1.131 TD
[(of)-334.6(both)-327.7(genders)]TJ
9.5031 1.131 TD
[(Placebo,)-326.7(clonazepa)12.1(m)]TJ
.9958 -1.131 TD
[(\(1)-169.3(mg\),)-327.9(and)-327.6(CBD)-329.4(\(100,)]TJ
0 -1.1239 TD
[(300,)-335.8(and)-327.5(900)-162.9(mg\))]TJ
11.004 2.2549 TD
[(Subjective)-322.7(anxiety)-328.1(measures)-324.2(in)-335.8(volunte)12.9(ers)-333.7(were)]TJ
.9958 -1.131 TD
[(reduced)-328.9(with)-330.4(CBD)-329.4(300)-162.9(mg,)-331.4(but)-332(not)-327.7(with)-330.4(CBD)]TJ
0 -1.1239 TD
[(100)-326.5(and)-327.6(900)-162.9(mg,)-324.3(in)-328.6(the)-326(postspeech)-317(phase)-321.7(after)]TJ
T*
[(a)-331.9(test)-331.8(of)-334.6(public)-332.2(speakin)12.5(g)-337.1(i)0(n)-328.6(a)-331.9(real)-326.5(situation.)]TJ
-40.5022 -1.1239 TD
[(Jadoon)-297.1(et)-294.8(al.)]TJ
1.003 -1.1239 TD
(\(2017\))Tj
5.9774 0 0 5.3127 98.6456 431.6597 Tm
(33)Tj
7.9702 0 0 7.9702 133.7385 437.1022 Tm
(Placebo-)Tj
1.003 -1.1239 TD
(controlled,)Tj
T*
[(double-blind)14.8(,)]TJ
T*
[(and)-327.6(crossover)]TJ
8.0023 3.3716 TD
[(Nine)-325(healthy)-326.5(males)-2372.5(CBD)-329.4(600)-162.9(mg)-329.3(or)-332(placebo)-1979.3(C)24.3(B)21.7(D)-233.1(l)22.7(o)21.7(w)17.7(e)23.4(r)23.2(e)16.3(d)-227.6(B)21.7(P)-230.1(\()24.9(e)16.3(s)25.1(p)21.4(e)16.3(c)20.2(i)22.7(a)23.8(l)15.6(l)22.7(y)-229.1(b)21.4(e)23.4(f)20.7(o)21.7(r)16.1(e)-225.5(a)16.6(n)25.6(d)-227.6(a)16.6(f)20.7(t)23.2(e)16.3(r)-225.7(s)18(t)23.2(r)16.1(e)23.4(s)18(s)25.1(\))17.8(,)]TJ
23.4947 -1.1239 TD
-.0214 Tc
[(i)-5.8(n)4.2(cr)-5.3(eased)-249(H)-2.4(R,)-251.2(decr)-5.3(eased)-249(s)-3.4(t)-5.3(r)1.8(oke)-246.9(v)-4.7(olume)-5.1(,)-251.2(and)]TJ
T*
-.0216 Tc
[(ca)-5(use)-5.3(d)-178(a)-182.8(b)-.2(lunte)-5.3(d)-178(for)-5.5(e)1.8(ar)-5.5(m)-177.3(s)-3.6(kin)-180.9(b)-.2(lood)-185.1(flow)-181.8(r)-5.5(e)1.8(sponse)]TJ
T*
-.0226 Tc
[(t)-6.5(o)-249.8(is)-4.6(omet)-6.5(ri)-7(c)-251.3(e).8(x)-5.6(e).8(rci)-7(s)2.5(e)-6.3(.)-252.4(In)-253(res)-4.6(p)-1.2(onse)-255.3(to)-256.9(cold)-250.2(s)-4.6(t).6(r)-6.5(e).8(s)-4.6(s)2.5(,)]TJ
0 -1.131 TD
-.0224 Tc
[(s)-4.4(u)-.7(bject)-6.3(s)-246.2(w)-4.7(h)3.2(o)-256.7(h)3.2(a)-5.8(d)-250(ta)-5.7(ken)-252.8(C)1.9(BD)-255.5(had)-257.1(b)-1(lunted)-257.1(BP)-252.5(and)]TJ
0 -1.1239 TD
-.0188 Tc
[(in)6.8(cre)4.6(a)5(se)4.6(d)-161(H)7.4(R,)-156.1(with)-156.8(low)6(e)-2.5(r)-159.2(t)4.4(ota)5(l)-159.7(pe)4.6(r)4.5(i)-3.2(ph)6.8(er)4.4(a)5(l)-159.7(re)4.6(sist)4.4(a)5(n)-.3(ce)4.6(.)]TJ
-40.5022 -1.1239 TD
0 Tc
(Bhattacharyya)Tj
1.003 -1.1239 TD
[(et)-209.4(al.)-204.7(\(2018\))]TJ
5.9774 0 0 5.3127 115.7102 377.8582 Tm
(40)Tj
7.9702 0 0 7.9702 133.7385 383.3007 Tm
(Parallel-group,)Tj
1.003 -1.1239 TD
[(double-blind)14.8(,)]TJ
T*
[(and)-327.6(placebo-)]TJ
T*
(controlled)Tj
8.0023 3.3716 TD
[(Thirty-thr)10.4(ee)]TJ
.9958 -1.1239 TD
[(medication-n)14(aive)]TJ
T*
[(participant)9.5(s)-337.7(a)0(t)]TJ
T*
[(CHR-P)-328.3(and)-327.6(19)-331.5(HC)]TJ
9.5031 3.3716 TD
[(CBD)-329.4(600)-162.9(mg)-6823.6(P)18.9(a)16.6(r)16.1(t)16.1(i)0(c)28.7(i)15.6(p)14.3(a)16.7(n)18.5(t)16.1(s)-238.1(r)16.1(e)16.3(c)0(e)29.4(i)15.6(v)16.6(i)15.6(n)18.5(g)-237.6(p)21.4(l)15.6(a)16.7(c)0(e)29.4(b)14.3(o)-234.3(h)18.5(a)16.6(d)-234.7(r)16.1(e)16.3(d)14.3(u)14.6(c)20.2(e)16.3(d)]TJ
12.9957 -1.1239 TD
[(a)16.6(c)0(t)29.2(i)15.6(v)16.7(a)16.6(ti)24.6(o)21.7(n)-237.6(r)16.1(e)16.3(l)15.6(a)16.6(t)16.1(i)15.6(v)16.6(e)-232.7(to)-225.3(c)20.2(o)14.6(n)18.5(t)0(r)25.2(o)21.7(ls)-222.5(i)15.6(n)-230.4(th)27.5(e)-232.6(r)16.1(i)15.6(g)0(h)29.9(t)-232.8(ca)29.7(u)14.6(d)21.4(at)25.7(e)]TJ
T*
[(d)14.3(u)14.6(r)16.1(i)15.6(n)18.5(g)-237.6(e)16.3(n)18.5(co)27.7(d)21.4(i)15.6(ng)-219(a)16.7(n)18.5(d)-234.7(i)15.6(n)-237.6(t)16.1(h)18.5(e)-232.7(p)14.3(a)16.6(r)16.1(a)16.6(hi)27(p)21.4(p)14.3(o)14.6(c)0(a)29.7(m)22.1(p)14.3(a)16.6(l)]TJ
T*
-.0167 Tc
[(g)-16.7(y)14.6(rus)-254.8(a)-.1(nd)-251.4(mid)4.7(b)-2.4(rain)-16.7(.)-242.2(W)1.2(ithin)-254.3(t)-.6(hese)-256.5(three)-249.4(r)-.6(eg)-16.7(i)10.3(o)-2.1(ns,)]TJ
0 -1.131 TD
0 Tc
[(a)16.6(c)0(t)29.2(i)15.6(v)16.7(a)16.6(ti)24.6(o)21.7(n)-152.2(i)15.6(n)-145.1(t)16.1(h)18.5(e)-147.3(C)0(B)31.8(D)-147.8(gr)27.5(o)14.6(u)21.7(p)-149.3(w)17.7(a)16.7(s)-152.7(g)18.5(r)16.1(e)16.3(a)16.7(t)16.1(e)16.3(r)-147.5(t)0(h)27.5(a)16.6(n)-145.1(i)15.6(n)-145.1(t)0(h)27.5(e)]TJ
0 -1.1239 TD
-.0156 Tc
[(plac)-15.6(e)13.8(b)-1.3(o)-164.6(g)2.9(roup)-164.9(but)-163.1(l)0(ower)-170.2(tha)-15.6(n)-151.2(in)-167.8(th)-15.6(e)-151.5(c)-15.6(o)12.1(n)2.9(trol)-163.6(g)-15.6(r)11.9(oup)5.8(.)]TJ
-40.5022 -1.1239 TD
0 Tc
(Masataka)Tj
1.003 -1.1239 TD
(\(2019\))Tj
5.9774 0 0 5.3127 98.6456 324.0566 Tm
(38)Tj
7.9702 0 0 7.9702 133.7385 329.4991 Tm
(Placebo-)Tj
1.003 -1.1239 TD
(controlled)Tj
8.0023 1.1239 TD
[(Thirty-sev)10.6(en)]TJ
.9958 -1.1239 TD
(Japanese)Tj
T*
[(teenagers)-323.7(with)]TJ
T*
[(SAD)-328(and)-334.7(avoidan)13.4(t)]TJ
T*
(personality)Tj
0 -1.131 TD
(disorder)Tj
9.5031 5.6265 TD
[(Cannabis)-319.9(oil)-338.3(containin)12.1(g)]TJ
.9958 -1.1239 TD
[(300)-162.9(mg)-329.3(CBD)-329.4(or)]TJ
T*
(placebo)Tj
11.004 2.2477 TD
[(CBD)-329.4(significantl)10.5(y)-335.8(decreas)11.2(ed)-332.2(anxiety)-328.1(during)-329.1(a)]TJ
.9958 -1.1239 TD
[(simulated)-327.3(public)-332.2(speakin)12.5(g)-337.1(test.)]TJ
-40.5022 -5.6265 TD
[(Linares)-298.6(et)-294.8(al.)]TJ
1.003 -1.1239 TD
(\(2019\))Tj
5.9774 0 0 5.3127 98.6456 270.3117 Tm
(31)Tj
7.9702 0 0 7.9702 133.7385 275.6975 Tm
[(Double-blind)-325.1(and)]TJ
1.003 -1.1239 TD
[(parallel)-328.4(group)]TJ
8.0023 1.1239 TD
[(Fifty-seven)-320(healthy)]TJ
.9958 -1.1239 TD
[(male)-327.7(subjects)]TJ
9.5031 1.1239 TD
[(CBD)-329.4(150,)-328.7(300,)-328.7(and)]TJ
.9958 -1.1239 TD
[(600)-162.9(mg)-329.3(or)-332(placebo)]TJ
11.004 1.1239 TD
[(CBD)-329.4(significantl)10.5(y)-335.8(reduced)-321.8(anxiety)-328.1(during)-329.1(a)]TJ
.9958 -1.1239 TD
[(simulated)-327.3(public)-332.2(speakin)12.5(g)-337.1(test.)]TJ
-40.5022 -1.1239 TD
[(Hurd)-298.7(et)-301.9(al.)]TJ
1.003 -1.1239 TD
(\(2019\))Tj
5.9774 0 0 5.3127 98.6456 252.3401 Tm
(43)Tj
7.9702 0 0 7.9702 133.7385 257.7826 Tm
[(Double-blind)-325.1(and)]TJ
1.003 -1.1239 TD
(placebo-)Tj
T*
(controlled)Tj
8.0023 2.2478 TD
[(Drug-abst)12.5(inent)]TJ
.9958 -1.1239 TD
[(individuals)-322.5(with)]TJ
T*
[(heroin)-327.1(use)]TJ
0 -1.131 TD
(disorder)Tj
9.5031 3.3787 TD
[(CBD)-251.1(400)-262.5(or)-253.8(800)-162.9(mg,)-260.3(once)]TJ
.9958 -1.1239 TD
[(daily)-309.2(for)-311.3(3)-308(consecut)10.6(ive)]TJ
T*
(days)Tj
11.004 2.2478 TD
[(B)14.6(o)21.7(th)-157.4(d)14.3(o)14.6(s)18(e)16.3(s)-166.9(o)14.6(f)-171.4(C)17.2(B)14.6(D)-169.1(si)26.5(g)18.5(n)18.5(i)15.6(f)13.6(i)15.6(ca)29.7(n)18.5(t)16.1(l)15.6(y)-172.2(r)16.1(e)16.3(d)14.3(u)14.6(c)20.2(e)16.3(d)-170.7(b)14.3(o)14.6(t)16.1(h)-166.4(c)0(r)29.2(a)16.6(v)16.6(i)15.6(ng)]TJ
.9958 -1.1239 TD
[(a)16.6(n)0(d)-180.6(a)16.6(n)18.5(x)17(i)15.6(e)16.3(t)16.1(y)-193.5(i)15.6(n)18.5(d)14.3(u)14.6(ce)29.4(d)-192(b)21.4(y)-193.5(t)16.1(he)-178.6(p)14.3(r)16.1(e)16.3(s)18(e)16.3(n)18.5(ta)25.7(t)16.1(i)15.6(o)14.6(n)-187.8(o)14.6(f)-192.7(s)18(a)16.6(l)15.6(i)15.6(e)16.3(nt)]TJ
T*
[(d)14.3(r)16.1(u)14.6(g)-230.4(cu)27.7(e)16.3(s)18(,)-236.9(w)17.7(hi)27(c)20.2(h)-237.6(p)21.4(e)16.3(rs)27(i)15.6(s)18(te)25.3(d)-227.6(7)-236.9(d)14.3(a)16.6(y)19.9(s)-238.1(a)16.6(f)13.6(t)16.1(e)16.3(r)-232.8(t)16.1(he)-221.2(f)13.6(i)15.6(n)18.5(a)16.6(l)]TJ
0 -1.131 TD
-.0159 Tc
[(C)-15.9(B)15.9(D)-185(e).4(xposure.)-181.7(C)-15.9(B)15.9(D)-185(r).2(educ)4.3(ed)-186.6(the)-184.5(d)-1.6(rug)-182.3(c)-15.9(u)18.9(e).4(-)-15.9(i)10.1(ndu)5.8(c)-15.9(e)13.5(d)]TJ
0 -1.1239 TD
-.0168 Tc
[(c)-16.8(h)14.8(an)-16.8(g)13.1(e)-.5(s)-247.8(i)-1.2(n)-254.4(H)2.2(R)-254(a)-.2(nd)-251.5(sa)-16.8(l)8.3(i)-1.2(vary)-253(c)3.4(ortis)-16.8(o)8.7(l)-250.2(l)-1.2(evels.)]TJ
-40.5022 -1.1239 TD
0 Tc
[(Sultan)-297.3(et)-294.8(al.)]TJ
1.003 -1.1239 TD
(\(2020\))Tj
5.9774 0 0 5.3127 98.6456 207.496 Tm
(36)Tj
7.9702 0 0 7.9702 133.7385 212.9385 Tm
(Placebo-)Tj
1.003 -1.1239 TD
[(controlled)-328.8(and)]TJ
T*
(double-blind)Tj
8.0023 2.2478 TD
[(Healthy)-326(males)-323.9(\()]TJ
/F11 1 Tf
6.5654 0 TD
(n)Tj
/F10 1 Tf
.6971 0 TD
(=)Tj
/F9 1 Tf
.7113 0 TD
(13)Tj
-6.978 -1.1239 TD
[(per)-301.8(group\))]TJ
9.5031 1.1239 TD
[(CBD)-329.4(600)-162.9(mg)-329.3(or)-332(placebo)]TJ
.9958 -1.1239 TD
[(orally)-335.4(for)-325.5(1)-336.5(week)]TJ
11.004 1.1239 TD
[(In)-328.6(response)-330.2(to)-332(stress,)-326.4(volunteers)-327.9(who)-326.2(had)-334.7(taken)]TJ
.9958 -1.1239 TD
[(CBD)-329.4(had)-334.7(lower)-325.1(systolic)-331.4(BP)-329.3(after)-333.8(acute)-328.6(and)]TJ
T*
[(repeated)-328.8(dosing.)]TJ
-40.5022 -1.1239 TD
(Appiah-Kusi)Tj
1.003 -1.1239 TD
[(et)-209.4(al.)-204.7(\(2020\))]TJ
5.9774 0 0 5.3127 115.7102 180.6236 Tm
(41)Tj
7.9702 0 0 7.9702 133.7385 186.0661 Tm
(Placebo-)Tj
1.003 -1.1239 TD
[(controlled)-328.8(and)]TJ
0 -1.131 TD
(double-blind)Tj
8.0023 2.2549 TD
[(Thirty-two)-326.2(CHR-P)]TJ
.9958 -1.1239 TD
[(patients)-266.7(and)-270.6(26)-274.6(HC)]TJ
9.5031 1.1239 TD
[(CBD)-329.4(600)-162.9(mg)-329.3(or)-332(placebo)]TJ
.9958 -1.1239 TD
[(for)-332.7(1)-336.5(week)]TJ
11.004 1.1239 TD
[(The)-329.8(change)-325.2(in)-328.7(cortisol)-331.4(associate)9.9(d)-334.3(with)]TJ
.9958 -1.1239 TD
[(experimental)-225.9(stress)-231.7(exposure)-228.4(was)-232.2(greates)11.3(t)-239.9(i)0(n)-229.1(H)0(C)]TJ
0 -1.131 TD
[(and)-334.7(least)-329.9(in)-328.7(CHR-P)-328.3(patients,)-325.8(with)-330.4(CHR-CBD)]TJ
0 -1.1239 TD
[(patients)-330.7(exhibitin)12.4(g)-337.1(a)0(n)-327.6(intermedia)11.1(te)-330.3(response.)]TJ
T*
[(Changes)-324.5(in)-335.8(anxiety)-328.1(and)-327.6(experience)-323.9(of)-327.4(public)]TJ
T*
[(speaking)-310.4(stress)-310(were)-310.6(greates)11.3(t)-318.2(i)0(n)-307.3(the)-311.8(CHR-P)-314.1(and)]TJ
T*
[(least)-329.9(in)-335.8(the)-326(HC,)-335.8(with)-330.4(CHR-CB)11.9(D)-332.7(participants)]TJ
T*
[(demonstratin)10.9(g)-294.5(a)0(n)-284.9(intermedia)11.1(te)-287.7(level)-282.3(of)-291.9(change.)]TJ
-40.5022 -1.131 TD
[(de)-296.6(Faria)-295.3(et)-301.9(al.)]TJ
1.003 -1.1239 TD
(\(2020\))Tj
5.9774 0 0 5.3127 98.6456 108.907 Tm
(42)Tj
7.9702 0 0 7.9702 133.7385 114.2928 Tm
[(Double-blinde)11.3(d,)]TJ
1.003 -1.1239 TD
(placebo-)Tj
T*
[(controlled,)-323.8(and)]TJ
T*
(crossover)Tj
8.0023 3.3716 TD
[(Twenty-)11.7(four)-332.3(patients)]TJ
.9958 -1.1239 TD
[(with)-330.4(Parkinsons)]TJ
T*
(disease)Tj
9.5031 2.2477 TD
[(CBD)-244(300)-162.9(mg)-251(or)-253.8(a)-246.5(placebo)-1495.6(Acute)-324.6(CBD)-329.4(administratio)9.7(n)-337.1(decreas)11.2(ed)-332.2(anxiety)-328.1(in)]TJ
12.9957 -1.1239 TD
[(patients)-252.5(with)-252.2(Parkinson)12.3(s)-259.4(disease,)-249.8(and)-249.3(there)-250.9(was)]TJ
T*
[(also)-333.5(decreased)-321(tremor)-332.5(amplitude)-323.9(in)-328.7(an)]TJ
T*
[(anxiogenic)-326.4(situation.)]TJ
15.4355 -2.3758 TD
(\()Tj
/F11 1 Tf
.2774 0 TD
(continued)Tj
/F9 1 Tf
4.0118 0 TD
(\))Tj
/F4 1 Tf
8.9663 0 0 8.9663 302.1732 26.2488 Tm
(10)Tj
ET
endstream
endobj
61 0 obj
<>stream
/GS1 gs
BT
/F6 1 Tf
10.959 0 0 10.959 59.7543 283.4645 Tm
0 0 0 rg
0 Tc
0 Tw
[(ac)9.8(tiv)11.2(it)13.6(y)-374.9(i)0(n)-373.3(c)0(o)10.7(r)0(t)14.2(ico)12(li)13.4(mbi)14.9(c)-375.5(r)0(e)9.2(gio)17.8(ns)-372.8(\(e.)14.8(g.,)-363.1(cin)11.6(gu)10.6(lat)16.4(e)-375.5(c)0(o)10.7(rte)16.3(x)]TJ
0 -1.1847 TD
[(an)10.6(d)-390.5(a)0(m)12.6(ygd)13.4(ala)16.9(\))-391.6(t)0(h)10.5(a)0(t)-383.6(m)0(e)12.3(d)0(i)9.2(ate)-376.3(co)10.7(gn)10.9(iti)15(on)-386.8(an)10.6(d)-385.3(emo)15.7(tio)17(nal)]TJ
0 -1.1795 TD
[(re)9.2(gu)10.6(lat)11.3(io)15.1(n.)]TJ
8.2191 0 0 7.3052 105.9023 262.4314 Tm
[(30,)17.2(35)]TJ
10.959 0 0 10.959 127.6157 257.5558 Tm
[(In)-393.4(he)10.6(alt)16.4(hy)-392.2(vo)11.3(lu)9.5(nt)10.1(ee)9.5(rs,)-388.7(7)-395.3(day)13.1(s)-396.5(o)0(f)-393.7(tre)16.3(at-)]TJ
-6.1923 -1.1847 TD
[(men)15.3(t)-329.1(w)0(i)11(t)0(h)-325.8(C)0(B)12.9(D)-326.3(\(6)9.8(00)-154.2(mg/)14.2(da)10.3(y\))-326.8(al)14.5(so)-325.8(re)9.2(du)10.5(ce)9.5(d)-328.4(t)0(h)10.5(e)-328.9(he)10.6(mo)13.5(-)]TJ
0 -1.1795 TD
[(dy)10.6(nam)15.6(ic)-291.4(re)9.2(sp)9.7(on)11.5(se)-290.9(to)-289.5(ac)9.8(ut)9.8(e)-292.7(phy)13.9(sic)15.7(al)-290.7(str)16(es)9.2(s.)]TJ
8.2191 0 0 7.3052 243.496 236.5228 Tm
(36)Tj
10.959 0 0 10.959 70.7527 218.6645 Tm
[(In)-274.4(medication-naive)-276.3(patients)-277.5(with)-273.4(generalized)-280.9(social)]TJ
-1.0036 -1.1795 TD
[(anxiety)-454.7(disorder,)-457.4(acute)-454.2(oral)-456.2(doses)-453.7(of)-455.7(300)-456.4(or)-455.2(600)-161.5(mg)]TJ
T*
[(reduced)-407.9(anxiety)-408.2(caused)-405.1(by)-407.7(public)-405.1(speaking)-405.3(in)-404.4(a)-406.2(ran-)]TJ
0 -1.1847 TD
[(domized)-585.9(controlled)-581.4(study.)]TJ
8.2191 0 0 7.3052 180.907 184.7054 Tm
(37)Tj
10.959 0 0 10.959 195.1936 179.8298 Tm
[(Similarly,)-584(in)-585.4(teenagers)]TJ
-12.3587 -1.1795 TD
[(with)-439(social)-437.2(anxiety)-434(disorder,)-436.7(an)-439.5(RCT)-433.6(showed)-437.4(that)-435.2(4)]TJ
0 -1.1847 TD
[(weeks)-312.6(CBD)-308.2(\(300)-165.1(mg/day\))-312.7(treatment)-308.7(decreased)-311(anxiety)]TJ
0 -1.1795 TD
[(measures)-295.6(using)-293.6(the)-297.8(Fear)-296.1(of)-290.2(Negative)-295.6(Evaluation)-290.6(Ques-)]TJ
0 -1.1847 TD
[(tionnaire)-310.7(and)-307.5(the)-308.1(Liebowitz)-302.5(Social)-307.3(Anxiety)-308.2(Scale.)]TJ
8.2191 0 0 7.3052 276.0944 132.8882 Tm
(38)Tj
10.959 0 0 10.959 287.3763 128.0126 Tm
(As)Tj
-20.7703 -1.1795 TD
[(with)-340.7(healthy)-339.3(volunteers,)-338(the)-344.3(anxiolytic)-339.7(effects)-338.9(of)-341.9(CBD)]TJ
0 -1.1847 TD
[(in)-202.6(anxiety)-201.2(disorders)-202.8(are)-200.5(also)-202.7(linked)-198.6(to)-201.6(alterations)-198.4(in)-202.6(cor-)]TJ
0 -1.1795 TD
[(ticolimbic)-540.2(activity.)]TJ
8.2191 0 0 7.3052 143.3196 94.0535 Tm
(39)Tj
10.959 0 0 10.959 157.1527 89.1779 Tm
[(Moreover,)-540.1(in)-538.9(medication-naive)]TJ
-8.8875 -1.1847 TD
[(participants)-507.1(at)-497.4(clinical)-506.7(high)-501.4(risk)-499.2(of)-502.3(psychosis,)-505.7(CBD)]TJ
0 -1.1795 TD
[(\(600)-165.1(mg\))-430.4(partially)-426(normalized)-429.6(the)-427.1(alterations)-426(in)-430.2(lim-)]TJ
22.912 20.0926 TD
[(bic,)-452.8(striatal,)-454.5(and)-457.5(midbrain)-454.9(function)-452(in)-456.1(an)-455(RCT.)]TJ
8.2191 0 0 7.3052 529.5117 288.3401 Tm
(40)Tj
10.959 0 0 10.959 542.381 283.4645 Tm
(A)Tj
-21.1272 -1.1847 TD
[(follow-up)-343.8(study)-350.2(by)-350.8(the)-344.4(same)-350.7(group)-348.8(showed)-349.4(7)-348.7(days)-347.2(of)]TJ
0 -1.1795 TD
[(treatment)-200(with)-201(CBD)-204.8(\(600)-165.1(mg/day\))-198.8(in)-207.8(patients)-199.9(at)-202.5(clinic)16.8(a)18(l)]TJ
0 -1.1847 TD
-.0182 Tc
[(high)-377(risk)-377.6(of)-379(psychosis)-378.4(partially)-377.6(restored)-377.6(the)-378.2(c)-.5(ortisol)-378.6(r)-.8(e-)]TJ
0 -1.1795 TD
-.0178 Tc
[(sponse)-507.1(el)4.6(icited)-506.6(duri)4.2(n).7(g)-506.5(t)-.3(he)-507.1(Trier)-502.2(S).1(ocial)-507.6(S).1(tres)4.8(s)-507.4(T)1.3(est)-507.3(t)-.3(o)]TJ
0 -1.1847 TD
-.0184 Tc
[(that)-218.2(observed)-217.5(i)-1.5(n)-217.2(t)-.9(he)-218(control)-218.5(g)-.1(roup.)]TJ
8.2191 0 0 7.3052 455.0172 223.5401 Tm
-.0238 Tc
(41)Tj
10.959 0 0 10.959 464.8818 218.6645 Tm
-.0179 Tc
[(In)-216.7(this)-212.6(study,)-218.9(t)-.4(he)-217.5(ex-)]TJ
-14.0555 -1.1795 TD
[(perie)4.8(n)-4.7(ce)-196.9(of)-202.9(anxiety)-201.5(i)-1.1(n)-196.1(r)-.6(esponse)-202.1(t)-.5(o)-195.7(t)-.5(he)-202.1(st)4.7(ress)-202.4(t)4.6(e)-.3(st)-202.3(was)-197.2(g).3(reat-)]TJ
T*
-.0181 Tc
[(est)-414.5(i)-1.2(n)-418.6(t)-.6(he)-419.5(high-risk)-418.9(p).1(atients)-419.7(a)-.1(nd)-418.9(lowest)-414.5(in)-418.6(the)-419.5(h).8(ealthy)]TJ
0 -1.1847 TD
-.0179 Tc
[(control)4.5(s)-.5(,)-358.6(w)2.1(ith)-350.8(t)-.4(hose)-357.2(a).1(t)-352.2(h)1(igh)-356(r)-.5(i)4.1(s)-.5(k)-356.6(w)2.1(ho)-356(were)-352(treated)-356.6(w)2.1(ith)]TJ
0 -1.1795 TD
-.0176 Tc
[(CBD)-297.4(f)-.8(or)-300.2(7)-299.1(d).6(ays)-300.2(e).1(xhibiting)-299.4(a).4(n)-299.1(i)4.4(nt)5(ermedia)5.5(t)-.1(e)-300(r)-.2(esponse.)]TJ
.9984 -1.1847 TD
0 Tc
[(Anxiety)-287.5(is)-286.5(often)-283.1(comorbid)-287.3(with)-283.8(other)-282.2(presentations,)]TJ
-.9984 -1.1795 TD
[(and)-307.5(the)-308.1(anxiolytic)-308.7(effects)-313.1(of)-310.9(CBD)-308.2(in)-306.1(other)-308.1(pathologies)]TJ
0 -1.1847 TD
[(has)-302.7(also)-306.2(been)-304.9(tested)-302.8(in)-306.1(randomized)-304.5(controlled)-302(studies.)]TJ
0 -1.1795 TD
[(In)-383.1(patients)-386.1(with)-382.1(Parkinsons)-388.4(disease,)-383.1(a)-385.5(single)-385.6(dose)-383.1(of)]TJ
0 -1.1847 TD
[(CBD)-411.7(\(300)-165.1(mg\))-409.7(attenuated)-411.2(the)-411.6(anxiety)-413.3(experimentally)]TJ
0 -1.1795 TD
[(induced)-278.2(by)-278.4(a)-282.1(Simulated)-277.7(Public)-280.4(Speaking)-280.6(Test)-280.2(in)-280.2(a)-282.1(ran-)]TJ
0 -1.1847 TD
[(domized)-368.7(double-blinded)-368.5(placebo-controlled)-369.9(crossover)]TJ
0 -1.1795 TD
(trial.)Tj
8.2191 0 0 7.3052 330.9164 68.1449 Tm
(42)Tj
10.959 0 0 10.959 343.2188 63.2692 Tm
[(In)-409(drug-abstinent)-406.5(individuals)-410.8(with)-402.8(heroin)-409.2(use)]TJ
ET
59.754 341.008 490.167 .22678 re
f
59.754 692.504 490.167 .28345 re
f
59.754 674.589 490.167 .22675 re
f
BT
/F4 1 Tf
8.9663 0 0 8.9663 262.8849 699.2502 Tm
[(Table)-338.1(2.)-500.5(\(Continued\))]TJ
/F2 1 Tf
7.9702 0 0 7.9702 142.4693 680.825 Tm
[(Study)-329.8(type)-4266.7(Patient)-325.9(cohort)-7057.3(Dose)-14330.4(Findings)]TJ
/F9 1 Tf
-10.3781 -2.5038 TD
[(Uncontrolled)-291.2(trials/case)-294.4(reports)-293.8(and)-299.1(series)]TJ
1.003 -1.1239 TD
[(Shanno)13.9(n)-301.6(and)]TJ
1.003 -1.1239 TD
(Opila-)Tj
T*
(Lehman)Tj
T*
(\(2016\))Tj
5.9774 0 0 5.3127 96.4346 628.5542 Tm
(48)Tj
7.9702 0 0 7.9702 131.5275 651.9116 Tm
[(Case)-330.2(report)-4152.9(A)-327.8(10-year-old)-325.3(girl)]TJ
9.994 -1.1239 TD
[(with)-330.4(PTSD)]TJ
T*
[(secondary)-329.1(to)]TJ
T*
[(sexual)-328.6(abuse)]TJ
9.5031 3.3716 TD
[(CBD)-329.4(\(25)-164.3(mg\))-325.7(at)-337.1(bedtime,)]TJ
1.003 -1.1239 TD
[(and)-327.5(612)-160.9(mg)-329.3(of)-334.6(CBD)]TJ
T*
[(sublingua)11.3(l)-332.9(spray)]TJ
T*
[(during)-322(the)-333.2(day)-333.3(as)]TJ
T*
[(needed)-323.7(for)-332.6(anxiety)]TJ
10.9969 4.4955 TD
[(A)-334.9(gradual)-321.5(increase)-331.8(in)-328.7(sleep)-324.9(quality)-328.3(and)-334.7(quantity)]TJ
1.003 -1.1239 TD
[(and)-284.9(a)-289.2(decrease)-285.5(in)-286(her)-290.5(anxiety)-285.4(were)-289.2(noted.)-285.1(After)]TJ
T*
[(5)-329.3(months,)-328.2(the)-326(patient)-334.5(was)-324.7(sleeping)-329.2(in)-328.7(her)-333.2(own)]TJ
T*
[(room)-273.9(most)-270.6(nights)-271.7(and)-277.8(handling)-269.3(the)-276.3(new)-274.7(school)]TJ
T*
[(year)-329.4(with)-330.4(no)-329.6(difficulties)11.3(.)]TJ
-40.5022 -1.131 TD
[(Shanno)13.9(n)-301.6(e)0(t)-301.9(al.)]TJ
1.003 -1.1239 TD
(\(2019\))Tj
5.9774 0 0 5.3127 96.4346 601.6818 Tm
(44)Tj
7.9702 0 0 7.9702 131.5275 607.0676 Tm
[(Case)-330.2(series)-4380.9(Seventy-tw)11(o)-333.9(adults)]TJ
9.994 -1.1239 TD
[(with)-330.4(concerns)-327(of)]TJ
T*
[(anxiety)-328.1(\()]TJ
/F11 1 Tf
3.6206 0 TD
(n)Tj
/F10 1 Tf
.6971 0 TD
(=)Tj
/F9 1 Tf
.7113 0 TD
[(47\))-299.5(or)]TJ
-5.029 -1.1239 TD
[(poor)-303.1(sleep)-289.4(\()]TJ
/F11 1 Tf
5.029 0 TD
(n)Tj
/F10 1 Tf
.6971 0 TD
(=)Tj
/F9 1 Tf
.7113 0 TD
(25\))Tj
3.0658 3.3716 TD
[(25-175)-156.9(mg)-336.4(in)-328.7(the)]TJ
1.003 -1.1239 TD
[(morning)-324.1(\(anxiety\))-320.9(or)]TJ
T*
[(evening)-320.6(\(sleep\))]TJ
10.9969 2.2477 TD
[(Anxiety)-238.6(and)-235.1(sleep)-239.6(improved)-232.8(for)-247.3(most)-235(patients,)-240.4(and)]TJ
1.003 -1.1239 TD
[(these)-327.3(improveme)11.8(nts)-331.5(were)-324.8(sustained)-328.5(over)-327.5(time.)]TJ
-40.5022 -3.3716 TD
[(Elms)-294.6(et)-294.8(al.)]TJ
1.003 -1.1239 TD
(\(2019\))Tj
5.9774 0 0 5.3127 96.4346 565.7952 Tm
(47)Tj
7.9702 0 0 7.9702 131.5275 571.2377 Tm
[(Case)-330.2(series)-4380.9(Eleven)-323.9(adult)-328.2(patients)]TJ
9.994 -1.1239 TD
[(with)-330.4(DSM-5-)]TJ
T*
[(diagnosed)-329.8(PTSD)]TJ
9.5031 2.2477 TD
[(Mean)-327.3(starting)-326.7(dose)]TJ
1.003 -1.1239 TD
[(33)-160.8(mg)-329.3(and)-327.6(the)-333.2(mean)]TJ
T*
[(total)-326.3(dose)-328(at)-337.1(the)-326(8-)]TJ
0 -1.131 TD
[(week)-328.2(follow-up)-324.2(was)]TJ
0 -1.1239 TD
[(49)-160.8(mg)-329.3(\(range:)-325(2100\))]TJ
10.9969 4.5026 TD
[(Ten)-251.5(of)-249.2(11)-253.3(patients)-245.4(experienced)-238.4(a)-253.7(decrease)-249.9(in)-250.4(PTSD)]TJ
1.003 -1.1239 TD
[(symptom)-271.2(severity.)-279.7(Four)-272.3(patients)-280.9(continued)-270.9(CBD)]TJ
T*
[(for)-304.2(36)-303(weeks)-295.9(or)-303.6(more.)-302.9(They)-302.8(had)-299.1(an)-306.3(initial)-298.9(mean)]TJ
0 -1.131 TD
[(PCL-5)-327.1(score)-327.3(of)-334.6(57.75)-330.9(with)-330.4(a)-331.9(mean)-324.8(score)-327.3(at)-337.1(36)]TJ
0 -1.1239 TD
[(weeks)-324.4(of)-334.6(29.25.)-325.9(CBD)-329.4(also)-333.5(offered)-329.1(relief)-326.1(in)-335.8(a)]TJ
T*
[(subset)-329.4(of)-327.4(patients)-330.7(who)-326.2(reported)-331(frequent)]TJ
T*
[(nightmar)14.1(es.)]TJ
-40.5022 -1.1239 TD
[(Laczkovics)-193.8(et)-202.3(al.)]TJ
1.003 -1.1239 TD
(\(2020\))Tj
5.9774 0 0 5.3127 96.4346 503.0361 Tm
(45)Tj
7.9702 0 0 7.9702 131.5275 508.4786 Tm
[(Case)-330.2(report)-4152.9(Teenager)-324.1(with)]TJ
9.994 -1.1239 TD
[(multiple)-332.1(substance)]TJ
0 -1.131 TD
[(use)-335.2(disorder,)]TJ
0 -1.1239 TD
[(severe)-334.2(depression)12.7(,)]TJ
T*
[(social)-333.2(phobia,)-327.9(and)]TJ
T*
(narcissistic)Tj
T*
(personality)Tj
T*
(disorder)Tj
9.5031 7.8742 TD
[(CBD)-329.4(with)-330.4(an)-327.6(initial)]TJ
1.003 -1.1239 TD
[(dosage)-278.6(of)-284.8(50)-160.8(mg)-286.6(twice)]TJ
0 -1.131 TD
[(daily,)-325.6(gradually)-328.7(to)]TJ
0 -1.1239 TD
[(300)-162.9(mg)-329.3(twice)-326.6(daily)]TJ
10.9969 3.3787 TD
[(By)-335.4(their)-329.9(request)12.2(,)-336.5(the)-333.2(patient)-327.4(discontinu)9.6(ed)]TJ
1.003 -1.1239 TD
[(sertraline)-254.3(after)-262.6(3)-265.3(weeks)-260.4(of)-263.4(CBD)-258.3(treatment.)-260.3(There)]TJ
0 -1.131 TD
[(were)-324.8(no)-329.6(side)-334.1(effects)-326.9(regarding)-325.9(HR,)-327.1(BP,)-331.5(and)]TJ
0 -1.1239 TD
[(weight.)-326.2(The)-329.8(patient)-327.4(improved)-325.3(regarding)]TJ
T*
[(depressiv)10.4(e)-332.2(a)0(s)-328.1(well)-333.1(as)-328.1(anxiety)-328.1(symptoms,)]TJ
T*
[(includin)12(g)-337.1(simple)-324.9(phobias)-329.1(and)-327.6(symptoms)-324.3(of)]TJ
T*
[(paranoia)-326.1(and)-327.5(dissociatio)8.6(n.)]TJ
-40.5022 -2.2478 TD
[(Klier)-291.6(et)-301.9(al.)]TJ
1.003 -1.131 TD
(\(2020\))Tj
5.9774 0 0 5.3127 96.4346 431.3196 Tm
(46)Tj
7.9702 0 0 7.9702 131.5275 436.7621 Tm
[(Case)-330.2(report)-4152.9(Fourteen-)11.6(year-old)]TJ
9.994 -1.131 TD
[(patient)-327.4(with)]TJ
0 -1.1239 TD
[(Crohns)-333.1(disease)]TJ
T*
[(with)-330.4(social)-333.2(phobia)]TJ
9.5031 3.3787 TD
[(CBD)-329.4(with)-330.4(an)-327.6(initial)]TJ
1.003 -1.131 TD
[(dosage)-321.3(of)-334.6(100)-162.9(mg)-329.3(per)]TJ
0 -1.1239 TD
[(day,)-328.4(gradually)-328.7(to)]TJ
T*
[(600)-162.9(mg)-329.3(per)-330.3(day)-326.2(for)-332.7(19)]TJ
T*
(weeks)Tj
10.9969 4.5026 TD
[(CBD)-329.4(reduced)-328.9(the)-326(Clinical)-327.4(Global)-331(Impression)]TJ
1.003 -1.131 TD
[(Severity)-325.8(Scale)-324.3(from)-331.9(5)-336.5(t)0(o)-332(3)0(,)-331.5(and)-327.5(reduced)-328.9(the)]TJ
0 -1.1239 TD
[(severity)-327.4(of)-327.4(symptoms)-331.5(of)-327.4(needle)-329.5(phobia,)-327.9(fear)-328.6(of)]TJ
T*
[(medica)12.7(l)-332.9(intervention,)-329.5(and)-327.6(social)-326.1(phobia.)]TJ
-40.5022 -2.2478 TD
[(Gulbra)11(nsen)]TJ
1.003 -1.1239 TD
[(et)-202.3(al.)-204.7(\(2020\))]TJ
5.9774 0 0 5.3127 113.4425 386.4755 Tm
(49)Tj
7.9702 0 0 7.9702 131.5275 391.918 Tm
[(Audit)-6740.1(Two)-332.3(hundre)13(d)-334.3(fifty-)]TJ
9.994 -1.1239 TD
[(three)-329.2(patients)]TJ
0 -1.131 TD
[(presenting)-329.6(to)]TJ
0 -1.1239 TD
[(Cannabis)-327(Care,)]TJ
T*
[(New)-334.3(Zealand)]TJ
9.5031 4.5026 TD
[(CBD)-329.4(oil)-8902.5(Four)-286.5(hundred)-278.6(patients)-280.9(were)-282.1(assessed)-284.1(for)-282.9(CBD)-286.7(and)]TJ
13.0028 -1.1239 TD
[(397)-326.5(received)-323.4(a)-331.9(prescription.)-332.7(Follow-)12.7(up)-333.9(was)]TJ
0 -1.131 TD
[(complet)12.6(ed)-332.2(on)-329.6(253)-333.7(patients.)-325.8(Patients)-326.2(with)]TJ
0 -1.1239 TD
[(noncanc)13.4(er)-337.4(pain)-326.2(and)-327.6(mental)-328.6(health)-325.1(symptoms)]TJ
T*
[(achieve)13.5(d)-334.3(improveme)11.8(nts)-331.5(to)-332(patient-repor)9.4(ted)]TJ
T*
[(pain,)-328.3(depression)-321.6(and)-327.6(anxiety)-328.1(symptoms.)]TJ
-40.3742 -2.2406 TD
[(Studies)-291(are)-299.5(presente)11.1(d)-298.7(i)0(n)-300.2(chronologi)10.5(cal)-303.2(order)-292.4(in)-300.2(each)-291.1(section.)]TJ
0 -1.131 TD
[(BP,)-203.4(blood)-196.9(pressure;)-199.6(CHR-P,)-202.4(clinical)-203.4(high)-199.2(risk)-200.7(for)-204.6(psychosis;)-200.7(HC,)-207.8(healthy)-198.5(controls;)-202.6(HR,)-199(heart)-200.8(rate;)-207.3(PCL-5,)-201.3(PTSD)-203.7(Checklist)-198.2(for)-204.6(DSM-5;)-195.1(PTSD,)-205.9(post-trau)8.9(m)]TJ
58.8975 0 TD
(atic)Tj
-60.0285 -1.1239 TD
[(stress)-302.9(disorder;)-289.4(SAD,)-301.8(social)-290.5(anxiety)-299.6(disorder;)-289.4(THC,)-302.1(tetrahydroca)9.6(nnabinol.)]TJ
/F4 1 Tf
9.9626 0 0 9.9626 59.7543 753.8455 Tm
[(CBD)-306.5(IN)-306.7(COVID-19)-10.5(-RELATED)-309.1(PTSD)]TJ
48.0965 0 TD
(11)Tj
ET
endstream
endobj
65 0 obj
<>stream
/GS1 gs
BT
/F6 1 Tf
10.959 0 0 10.959 62.022 697.8896 Tm
0 0 0 rg
0 Tc
0 Tw
[(disorder,)-359.1(CBD)-354.8(\(either)-358.1(400)-358.1(or)-356.9(800)-161.5(mg)-359.6(for)-355.6(3)-359.1(days\))-356(also)]TJ
0 -1.1847 TD
[(reduced)-314.8(the)-313.3(anxiety)-315.1(and)-312.6(cortisol)-313.5(responses)-310.3(to)-315.4(the)-313.3(pre-)]TJ
0 -1.1795 TD
[(sentation)-320.4(of)-321.2(a)-318.3(drug)-321.1(cue)-318.9(in)-321.6(a)-318.3(double-blind)-316.4(randomized)]TJ
0 -1.1847 TD
-.0002 Tc
[(placebo-controlled)-302.7(trial.)]TJ
8.2191 0 0 7.3052 167.0173 663.8738 Tm
0 Tc
(43)Tj
10.959 0 0 10.959 72.9637 646.0723 Tm
[(Several)-253.6(case)-255.2(reports)-253.2(also)-249.3(document)-251.3(the)-256.4(anxiolytic)-251.8(ef-)]TJ
-.9984 -1.1847 TD
[(fects)-202.7(of)-207.4(CBD.)-204(In)-202(adults)-204(with)-201(concerns)-202.9(of)-207.4(anxiety)-201.2(or)-206.9(poor)]TJ
0 -1.1795 TD
[(sleep,)-366.4(CBD)-359.9(treatment)-365.6(\(25175)-161.2(mg)-364.7(per)-365.8(day\))-363(improved)]TJ
T*
[(anxiety)-330.6(and)-333.3(sleep)-330.9(improved)-330(for)-329.7(most)-329.3(patients)-329.2(in)-331.9(a)-328.6(re-)]TJ
0 -1.1847 TD
[(cent)-239.1(case)-239.7(series.)]TJ
8.2191 0 0 7.3052 129.8834 599.1306 Tm
(44)Tj
10.959 0 0 10.959 140.3716 594.2549 Tm
[(For)-240.4(a)-240.7(16-year-old)-236.3(patient)-238(with)-237.2(multi-)]TJ
-7.1493 -1.1795 TD
[(ple)-469.4(substance)-464.8(use)-464.1(disorder,)-467.7(severe)-468.2(depression,)-467.8(social)]TJ
0 -1.1847 TD
[(phobia,)-236.2(and)-235(narcissistic)-235.5(personality)-233.6(disorder,)-240.1(treatment)]TJ
0 -1.1795 TD
[(with)-242.4(CBD)-241(\(100600)-168.4(mg/day)-241.8(for)-241.8(8)-245.2(weeks\))-243.7(improved)-242(de-)]TJ
0 -1.1847 TD
[(pressive)-671.4(and)-669.6(anxiety)-672(symptoms.)]TJ
8.2191 0 0 7.3052 214.3558 547.3132 Tm
(45)Tj
10.959 0 0 10.959 229.6062 542.4377 Tm
[(CBD)-665.2(treatment)]TJ
-15.2919 -1.1795 TD
[(\(up)-339.7(to)-336.1(600)-166.7(mg)-338.9(per)-334.7(day)-338.7(for)-340.1(19)-335.3(weeks\))-336.9(in)-342.3(a)-339(14-year-old)]TJ
0 -1.1847 TD
[(patient)-605.3(with)-604.5(Crohns)-602.5(disease)-606.3(and)-607.5(anxiety)-604.7(disorder)]TJ
0 -1.1795 TD
[(\(social)-358(phobia\))-359.5(reduced)-361.3(the)-359.9(severity)-360.8(of)-357.5(anxiety)-361.6(symp-)]TJ
T*
(toms.)Tj
8.2191 0 0 7.3052 86.0598 495.4959 Tm
(46)Tj
10.959 0 0 10.959 97.0015 490.677 Tm
[(A)-275.2(case)-275.9(report)-275.8(and)-276.4(case)-275.9(series)-278.5(in)-275(PTSD)-275.7(patients)]TJ
-3.1918 -1.1847 TD
[(treated)-233.1(with)-237.2(CBD)-230.6(\(2100)-164.2(mg/day)-236.6(for)-236.6(8)-234.9(weeks\))-233.4(reported)]TJ
0 -1.1795 TD
[(improvements)-360.1(in)-363(anxiety)-361.6(and)-359.2(sleep)-361.9(quality.)]TJ
8.2191 0 0 7.3052 255.685 469.644 Tm
(47,48)Tj
10.959 0 0 10.959 277.2283 464.7684 Tm
[(A)-358(re-)]TJ
-19.6374 -1.1847 TD
[(cently)-332.9(published)-330(study)-334.7(of)-331.6(an)-336(audit)-330.3(of)-336.8(CBD-prescrib)6.2(ed)]TJ
0 -1.1795 TD
[(patients)-220.6(was)-218.8(completed)-219.4(on)-221.3(253)-218.4(patients.)]TJ
8.2191 0 0 7.3052 234.1417 443.7353 Tm
(49)Tj
10.959 0 0 10.959 244.4598 438.8597 Tm
[(Patients)-220(with)]TJ
-16.6473 -1.1847 TD
[(noncancer)-266.6(pain)-259.6(and)-266.1(mental)-263.2(health)-264.5(symptoms)-260.1(achieved)]TJ
0 -1.1795 TD
[(signicant)-659.7(improvement)5.3(s)-660.3(t)0(o)-656.8(patient-reported)-656.8(pain,)]TJ
0 -1.1847 TD
[(depression,)-302.2(and)-297.1(anxiety)-299.5(symptoms.)]TJ
/F4 1 Tf
10.4607 0 0 10.4607 62.022 374.0597 Tm
[(CBDs)-300.7(Mechanism)-296.7(of)-303.6(Action)-300.3(in)-301.4(Anxiety)]TJ
/F6 1 Tf
10.959 0 0 10.959 62.022 361.1338 Tm
[(Many)-312.2(pre-clinical)-316.8(studies)-311.4(have)-315.2(investigated)-315.1(the)-313.3(anxio-)]TJ
T*
[(lytic)-336.7(and)-333.3(mnemonic)-337.2(effects)-333.8(of)-336.8(CBD)-334.1(in)-337.1(animal)-335.9(models)]TJ
0 -1.1795 TD
[(of)-279.9(anxiety)-278.8(and)-276.4(learned)-278.9(fear)-281.9(when)-276.8(CBD)-277.2(is)-276.1(administered)]TJ
0 -1.1847 TD
[(systemically)-251.7(or)-253.4(directly)-257.6(into)-254.2(the)-251.2(brain,)-256.3(revealing)-254.1(poten-)]TJ
0 -1.1795 TD
[(tial)-328.8(mechanisms)-323.7(of)-331.6(action)-327.2(for)-324.5(CBD)-328.9(in)-326.8(these)-324.8(models.)]TJ
8.2191 0 0 7.3052 293.2723 314.192 Tm
(50)Tj
10.959 0 0 10.959 62.022 296.3338 Tm
[(Several)-253.6(receptors)-249(have)-253.2(been)-248(implicated)-250.8(to)-253.3(be)-248(molecular)]TJ
T*
[(sites)-311.6(of)-310.9(action)-311.7(of)-316.1(CBD.)-307.5(The)-311.7(5HT)]TJ
8.2191 0 0 7.3052 206.8157 281.5936 Tm
(1A)Tj
10.959 0 0 10.959 219.8551 283.4078 Tm
[(receptor)-307.7(and)-312.6(tran-)]TJ
-14.4021 -1.1795 TD
[(sient)-331.1(receptor)-328.4(potential)-331.2(vanilloid)-326.3(1)-333.2(channel)-328.9(have)-325.6(been)]TJ
0 -1.1847 TD
[(implicated)-276.7(in)-280.2(the)-277.1(anxiolytic)-277.6(effects)-276.9(of)-279.9(CBD.)]TJ
8.2191 0 0 7.3052 251.3196 262.3748 Tm
(51,52)Tj
10.959 0 0 10.959 271.9558 257.4991 Tm
(Perox-)Tj
-19.1563 -1.1795 TD
-.0001 Tc
[(isome)-208.8(proliferator-activated)-209.5(receptor)-209.6(gamma)-210.1(activation)]TJ
0 -1.1847 TD
0 Tc
[(is)-219.2(also)-218.2(thought)-213.4(to)-217.1(be)-216.9(involved)-213.1(in)-218.1(the)-220.2(underpinning)-218.9(anti-)]TJ
0 -1.1795 TD
-.0001 Tc
[(inammatory/antioxidant)-338.1(effects)-333.9(that)-337(help)-331.7(resolve)-336(the)]TJ
0 -1.1847 TD
0 Tc
[(pathological)-332.9(effects)-333.8(that)-331.7(can)-339(lead)-332.5(to)-336.1(anxiety.)]TJ
8.2191 0 0 7.3052 257.6692 210.5574 Tm
(53)Tj
10.959 0 0 10.959 269.1779 205.6818 Tm
(Activa-)Tj
-18.9028 -1.1795 TD
[(tion)-274.9(of)-274.7(the)-277.1(CB)]TJ
8.2191 0 0 7.3052 124.5543 190.9417 Tm
(1)Tj
10.959 0 0 10.959 131.5275 192.7559 Tm
[(receptor)-271.5(has)-276.9(been)-273.9(implicated)-276.7(in)-275(the)-277.1(fa-)]TJ
-6.3423 -1.1847 TD
[(cilitatory)-320.6(effect)-325.3(of)-326.4(CBD)-318.6(on)-324.7(fear)-323.3(extinction,)-328.5(possibly)-322.5(as)]TJ
0 -1.1795 TD
[(an)-465.3(indirect)-459.5(consequence)-463.8(of)-460.9(enhancing)-463.2(endocannabi-)]TJ
T*
[(noids)-365.4(within)-357(the)-365(brain.)]TJ
8.2191 0 0 7.3052 165.1464 158.7401 Tm
(5456)Tj
10.959 0 0 10.959 189.1275 153.9212 Tm
[(Fear)-363.3(extinction)-360.2(is)-364.1(a)-359.7(form)]TJ
-11.5983 -1.1847 TD
[(of)-590.2(inhibitory)-592(learning)-592.2(that)-590.4(suppresses)-588.8(learned)-594.5(fear)]TJ
0 -1.1795 TD
[(and)-410.9(forms)-410.8(the)-406.4(theoretical)-410.2(basis)-413.3(for)-407.3(exposure)-410.2(therapy)]TJ
0 -1.1847 TD
[(in)-207.8(the)-209.8(treatment)-210.4(of)-207.4(certain)-212.7(anxiety)-206.4(disorders.)]TJ
8.2191 0 0 7.3052 253.8141 119.9055 Tm
(25)Tj
10.959 0 0 10.959 263.9621 115.0299 Tm
(Interest-)Tj
-18.4268 -1.1795 TD
[(ingly,)-401.6(a)-401.1(study)-407.1(in)-399.2(humans)-400.7(showed)-401.2(that)-404.2(CBD)-401.3(also)-399.3(en-)]TJ
0 -1.1847 TD
[(hanced)-330.9(fear)-323.3(extinction)-329.2(in)-326.8(healthy)-329(volunteers,)]TJ
8.2191 0 0 7.3052 260.2204 93.9968 Tm
(57)Tj
10.959 0 0 10.959 271.729 89.1212 Tm
(raising)Tj
-19.1356 -1.1795 TD
[(the)-230.5(possibility)-224.7(that)-228.3(CBD)-230.6(might)-223.6(enhance)-230.1(the)-230.5(therapeutic)]TJ
0 -1.1847 TD
[(effects)-302.7(of)-300.5(psychologic)6.7(al)-301.1(treatments.)]TJ
23.9104 57.9137 TD
[(In)-295.1(pre-clinical)-296.1(studies,)-295.1(CBD)-292.7(has)-297.6(also)-290.7(been)-294.6(shown)-294.3(to)]TJ
-1.0036 -1.1847 TD
[(decrease)-422.3(dopamine)-422.3(\(DA\))-417.4(transmission,)]TJ
8.2191 0 0 7.3052 488.9196 689.7825 Tm
(58)Tj
10.959 0 0 10.959 501.392 684.9069 Tm
[(5HT)-418(trans-)]TJ
-17.1853 -1.1795 TD
(mission)Tj
8.2191 0 0 7.3052 347.0739 676.8565 Tm
(59)Tj
10.959 0 0 10.959 359.6598 671.981 Tm
[(and)-436.8(to)-429.2(modulate)-433.3(synaptic)-431.9(plasticity)-429.9(in)-435.4(the)]TJ
-4.2523 -1.1847 TD
-.0002 Tc
[(amygdala)-521.2(and)-519.8(hippocampus.)]TJ
8.2191 0 0 7.3052 444.1321 663.8738 Tm
0 Tc
(60)Tj
10.959 0 0 10.959 457.7385 658.9983 Tm
[(CBD)-515.1(can)-520.1(also)-518.3(block)]TJ
-13.2019 -1.1795 TD
[(the)-339.2(formation)-338.5(of)-336.8(associative,)-337.7(fear-related)-337.2(memories)-339.4(in)]TJ
0 -1.1847 TD
[(specic)-377.5(neural)-374.2(regions,)-376.1(including)-372.6(the)-375.4(nucleus)-377(accum-)]TJ
0 -1.1795 TD
-.0168 Tc
[(be)-4.3(ns)-439.1(\(NAc)-4.3(\))-434.3(a)-4(nd)-438.3(v)-3.7(e).9(n)-3.5(t).7(r)-4.6(a)1.2(l)-439.3(h)2.1(i)-5.1(p)1.4(p)-3.8(o)-3.1(ca)-4(mpu)-3.8(s)-439.1(\(v)-3.7(HI)-4.5(PP\))-4.9(.)-435.1(Thus)-4.6(,)]TJ
T*
-.0146 Tc
[(Norris)-338.6(et)-338.6(al.)-339.8(r)-2.4(epo)4.3(r)-2.4(ted)-337.8(t)2.9(hat)-333.4(d)-1.6(irect)-338.6(i)2.3(nfusio)4.3(ns)-338.6(o)4.3(f)-339.2(CBD)-335.8(i)2.3(nto)]TJ
0 -1.1847 TD
0 Tc
[(the)-313.3(rodent)-316.1(NAc)-310.1(potently)-316.7(blocked)-307.8(the)-313.3(formation)-312.6(of)-316.1(as-)]TJ
0 -1.1795 TD
[(sociative)-591.1(fear)-587.2(memories)-582.6(through)-586(a)-587.3(5HT)]TJ
8.2191 0 0 7.3052 502.5826 579.4581 Tm
(1A)Tj
10.959 0 0 10.959 512.1636 581.329 Tm
(-receptor)Tj
-18.1682 -1.1847 TD
[(dependent)-582.9(mechanism.)]TJ
8.2191 0 0 7.3052 418.0534 573.2219 Tm
(58)Tj
10.959 0 0 10.959 432.2267 568.3463 Tm
[(These)-576.7(effects)-582.1(of)-574.7(CBD)-577.2(on)]TJ
-10.874 -1.1795 TD
[(fear-memory)-502.8(formation)-498.9(were)-501.5(also)-497.6(dependent)-505.3(on)-500.6(its)]TJ
0 -1.1847 TD
[(ability)-342.1(to)-341.3(dampen)-339(the)-339.2(activity)-340.3(of)-341.9(DA)-337.7(neurons)-344.2(directly)]TJ
0 -1.1795 TD
[(in)-347.4(the)-349.5(ventral)-346.3(tegmental)-344.3(area,)]TJ
8.2191 0 0 7.3052 444.6991 534.3873 Tm
(58)Tj
10.959 0 0 10.959 456.3778 529.5117 Tm
[(an)-346.3(effect)-346(that)-347.3(is)-348.6(simi-)]TJ
-13.0778 -1.1847 TD
[(larly)-512(thought)-508.3(to)-506.8(underlie)-510.1(the)-509.9(putative)-509.7(antipsychotic)]TJ
0 -1.1795 TD
[(properties)-397.1(of)-398.8(CBD.)]TJ
8.2191 0 0 7.3052 398.4944 508.4786 Tm
(61)Tj
10.959 0 0 10.959 410.7401 503.603 Tm
[(CBD)-396.2(has)-395.9(also)-394.1(been)-398(reported)-395.1(to)]TJ
-8.9134 -1.1795 TD
[(mitigate)-265.6(the)-266.8(anxiogenic)-260.6(effects)-266.5(of)-264.3(THC.)]TJ
8.2191 0 0 7.3052 484.5542 495.4959 Tm
(62)Tj
10.959 0 0 10.959 495.3826 490.677 Tm
[(For)-261.1(example,)]TJ
-16.6369 -1.1847 TD
[(coadministration)-535.2(of)-538.5(CBD)-535.8(with)-532.1(THC)-535.9(in)-538.9(the)-535.8(rodent)]TJ
0 -1.1795 TD
[(vHIPP)-382.4(was)-379.2(shown)-377.1(to)-382.7(block)-379.9(the)-375.4(ability)-383.4(of)-378.1(THC)-380.7(alone)]TJ
0 -1.1847 TD
[(to)-330.9(induce)-332.6(potentiation)-328.4(of)-331.6(fear-related)-332.1(memory)-331.7(forma-)]TJ
0 -1.1795 TD
[(tion.)-450(This)-445.1(effect)-444.3(was)-446.4(dependent)-448.4(on)-443.7(CBDs)-445.3(ability)-445.5(to)]TJ
0 -1.1847 TD
-.0001 Tc
[(block)-478.3(hyperstimulatio)5.2(n)-478.2(o)-.1(f)-476.5(extracellular-signal-related)]TJ
0 -1.1795 TD
0 Tc
[(kinase)-359(1-2)-348.6(phosphorylation)-354.1(states)-349.9(induced)-355.8(by)-356(THC.)]TJ
8.2191 0 0 7.3052 544.3085 417.8267 Tm
(63)Tj
10.959 0 0 10.959 313.0582 399.9684 Tm
[(Thus,)-432.7(the)-427.1(therapeutic)-430.6(ability)-430(of)-424.7(CBD)-432.4(in)-425(anxiety)-428.9(and)]TJ
T*
[(stress)-366.1(management)-363.4(is)-358.9(not)-364.2(reliant)-363.2(on)-360.9(a)-364.8(single)-364.9(molecu-)]TJ
0 -1.1847 TD
[(lar)-625.1(target)-618(and)-623(involves)-617.4(many)-623.1(biological)-618(processes.)]TJ
0 -1.1795 TD
[(This)-538.3(might)-539.2(also)-533.8(explain)-537.8(why)-537.8(CBD)-535.8(is)-534.8(anxiolytic)-536.3(in)]TJ
T*
[(many)-245.5(different)-241(types)-247.3(of)-238.5(anxiety)-247.8(disorders.)-243.4(Accordingly,)]TJ
0 -1.1847 TD
[(there)-288.6(is)-286.5(an)-284.3(urgent)-285.7(need)-290.1(to)-284.4(map)-284.8(and)-286.8(validate)-287.8(these)-283.4(pre-)]TJ
0 -1.1795 TD
[(clinical)-439.5(molecular)-437.4(biomarkers)-434.4(associated)-438.2(with)-433.8(CBDs)]TJ
0 -1.1847 TD
[(anxiolytic)-707(properties)-707.5(onto)-702.2(translational)-705.6(studies)-704.5(in)]TJ
0 -1.1795 TD
[(human)-299.1(populations.)]TJ
/F4 1 Tf
10.4607 0 0 10.4607 313.0582 270.4818 Tm
[(CBD)-300.3(and)-303.8(Sleep)-297.5(Disorders)]TJ
/F6 1 Tf
10.959 0 0 10.959 313.0582 257.4991 Tm
[(As)-588.9(alluded)-584.1(to)-579.2(earlier,)-585.9(sleep)-584.4(disturbances)-583.1(are)-588.4(often)]TJ
T*
[(reported)-503.8(in)-502.6(those)-504.7(suffering)-499.1(with)-501(anxiety,)-505.7(PTSS)-500.5(and)]TJ
0 -1.1847 TD
(PTSD,)Tj
8.2191 0 0 7.3052 341.4613 236.4661 Tm
(64)Tj
10.959 0 0 10.959 351.9495 231.5905 Tm
[(and)-235(case)-234.5(series)-237.1(data)-233.6(suggest)-232.3(sleep)-237.8(disturbances)]TJ
-3.5488 -1.1795 TD
[(are)-288.4(improved)-283.4(by)-288.7(CBD)-282.3(in)-285.4(patients)-282.7(with)-288.9(PTSD,)]TJ
8.2191 0 0 7.3052 513.5242 223.5401 Tm
(47,48)Tj
10.959 0 0 10.959 534.2172 218.6645 Tm
-.013 Tc
[(pa)-13(r)6.8(-)]TJ
-20.1805 -1.1847 TD
0 Tc
[(t)12.3(i)11.7(cu)20.3(l)12(a)12.8(r)12.2(l)12(y)-199(i)11.7(n)-198.8(t)12.3(h)13.7(e)-199.6(r)12.2(e)12.5(du)20.9(c)12.5(t)12.3(i)11.7(o)13.7(n)-198.8(o)13.7(f)-200.5(n)0(i)25(g)0(h)21.6(t)12.3(m)15.3(a)0(r)19.8(e)12.5(s)-199.9(\()11.9(s)12.2(e)12.5(e)-199.6(T)13.9(a)12.8(b)0(l)20.6(e)-194.4(3)-203.9(for)-210.7(a)]TJ
0 -1.1795 TD
[(summary)-278.5(of)-279.9(studies)-280.3(that)-274.8(report)-275.8(improvements)-277.3(in)-280.2(sleep)]TJ
0 -1.1847 TD
[(with)-371.7(CBD)-365.1(in)-373.3(humans\).)-367.4(One)-368.1(placebo-controlled)-369.9(dose-)]TJ
0 -1.1795 TD
[(ranging)-495(clinical)-486(study)-489.9(found)-494(that)-486.9(a)-494.2(dose)-486.6(of)-492(160)-166.7(mg)]TJ
T*
-.0191 Tc
[(CBD)-257.5(w).9(as)-255.2(effe)3.7(ctiv)4.4(e)-260.1(a)-1.1(t)-255.1(i)-2.2(mp)4.3(rov)4.4(i)-2.2(n)4.6(g)-259.5(slee)3.7(p)-259.6(duration)-259.2(i)2.9(n)-259.2(i)-2.2(n)4.6(s)-1.7(om-)]TJ
0 -1.1847 TD
-.0204 Tc
[(niac)-370(volunteers.)]TJ
8.2191 0 0 7.3052 379.6156 145.8141 Tm
-.0306 Tc
(65)Tj
10.959 0 0 10.959 391.0676 140.9385 Tm
-.0218 Tc
[(In)-370.6(pr)-4.4(e-)-4.1(cl)-4.6(inic)-4.1(al)-366.7(st)]TJ
6.4354 0 TD
-.0221 Tc
[(ud)-3.9(ie)-4.4(s,)-373.2(CBD)-369.1(h)-3.2(as)-366.8(be)-4.4(en)]TJ
-13.5537 -1.1795 TD
-.0207 Tc
[(s)-3.3(h)-1.8(own)-586.8(t)1.9(o)-586.4(b)-1.8(lock)-587(anxie)-3(t)1.9(y-r)-3.3(e)2.1(l)-3.5(a)2.4(t)-3.2(e)2.1(d)-587.1(r)1.9(apid)-587.1(eye)-582.4(m)-.2(oveme)-3(n)3(t)]TJ
0 -1.1847 TD
[(s)-3.2(l)1.8(eep)-561.1(al)-3.4(terati)-3.7(ons)-3.2(.)]TJ
8.2191 0 0 7.3052 385.1716 119.9055 Tm
-.0238 Tc
(66)Tj
10.959 0 0 10.959 398.7778 115.0299 Tm
-.0208 Tc
[(Observat)-3.3(ional)-562.3(u)-2.6(ncontr)-3.4(ol)-3.6(led)-561.3(c)-3.1(linical)]TJ
-7.8218 -1.1795 TD
-.019 Tc
[(studies)-539.6(inv)4.5(e)-1.3(stiga)4.1(t)-1.5(ing)-543.9(t)3.6(he)-539.3(effe)3.8(cts)-544.8(o)-.1(n)-543.7(s)3.6(leep)-538.8(fo)5.1(und)-544(C)5.9(BD)]TJ
0 -1.1847 TD
-.0194 Tc
[(\(25)4.4()-.9(30)4.4(0)-166.4(m)1.1(g/day\))-292(to)-290.2(have)-291.4(positi)]TJ
11.9707 0 TD
-.0185 Tc
[(ve)-290.5(effe)4.3(cts)-296(o)5.6(n)-294.9(s)4.1(le)4.3(ep)-290(qua)4.6(l)-1.3(ity)]TJ
-11.9707 -1.1795 TD
-.019 Tc
[(and)-218.1(t)-1.5(o)-217.4(d)-.8(ec)3.8(re)3.8(ase)-223.8(s)3.6(le)3.8(ep)-218.1(disturb)5.1(a)-1(nc)3.8(es)-218.9(in)-222.9(pa)4.1(tien)4.7(ts)-218.9(with)-217.4(autism)]TJ
0 -1.1847 TD
-.0226 Tc
[(s)-5.2(p)-4.4(ec)-4.9(tr)-5.2(um)-648.7(di)-5.7(sor)-5.2(d).8(e)-4.9(r)0(,)]TJ
8.2191 0 0 7.3052 395.7731 68.0882 Tm
-.0307 Tc
[(67)-7(,)-5.8(6)-.1(8)]TJ
10.959 0 0 10.959 419.244 63.2126 Tm
-.02 Tc
[(Parkinsons)-644.1(d)-1.8(isease,)]TJ
8.2191 0 0 7.3052 505.814 68.0882 Tm
-.0237 Tc
(69)Tj
10.959 0 0 10.959 520.3274 63.2126 Tm
-.0206 Tc
[(chr)-3.2(o)3.5(nic)]TJ
/F4 1 Tf
9.9626 0 0 9.9626 62.022 754.3557 Tm
0 Tc
(12)Tj
40.6704 0 TD
[(OSULLIVA)-10.2(N)-303.2(E)0(T)-299.4(AL.)]TJ
ET
endstream
endobj
69 0 obj
<>stream
/GS1 gs
BT
/F6 1 Tf
10.959 0 0 10.959 59.7543 179.8298 Tm
0 0 0 rg
-.0192 Tc
0 Tw
(pain,)Tj
8.2191 0 0 7.3052 80.3338 184.7054 Tm
-.0237 Tc
(70)Tj
10.959 0 0 10.959 93.4866 179.8298 Tm
-.0197 Tc
[(and)-518.8(i)-2.8(n)-518.5(p)-1.5(atients)-524.8(w).3(ith)-518.2(i)-2.8(n)4(s)-2.3(omn)4(i)-2.8(a)3.4(.)]TJ
8.2191 0 0 7.3052 232.8377 184.7054 Tm
-.0306 Tc
[(44)-6.9(,)-5.7(7)0(1)]TJ
10.959 0 0 10.959 255.0047 179.8298 Tm
-.0201 Tc
[(Again,)-526.3(al-)]TJ
-17.8164 -1.1847 TD
.5309 Tc
[(t)548.4(h)549.8(o)555(u)549.1(g)554.4(h)-3.8(t)553.5(h)549.8(ee)548.6(v)554.4(i)547.8(d)554.3(e)548.6(n)549.4(c)553.7(eb)549.8(a)548.9(s)553.5(ei)547.8(so)555(fl)548.1(o)555(w)-2.6(q)554.6(u)549.1(a)548.9(l)553.3(i)552.9(t)548.4(y)549.2(,)4(t)548.4(h)549.8(e)553.7(r)548.3(ei)552.9(s)]TJ
0 -1.1795 TD
-.0193 Tc
[(sufcient)-622.6(d)-1.1(ata)-627.3(t)3.4(o)-626.4(s)3.3(upport)-627.8(t)3.3(he)-622.4(hypoth)4.7(esis)-622.7(th)4.7(at)-622.6(CBD)]TJ
0 -1.1847 TD
-.0196 Tc
[(would)-203.2(b)-.7(e)-203.7(b)4.5(en)4.1(ec)3.2(i)-2.7(a)3.5(l)-204.1(in)-202.8(sleep)-203.1(d)3.8(i)-2.7(sorders)-204(a)-1.6(sso)4.5(c)-1.9(iated)-203.2(w).4(ith)-202.5(a)3.5(nx-)]TJ
0 -1.1795 TD
-.0177 Tc
[(ie)5.1(ty)5.8(,)-301.5(w)2.3(h)6.3(i)-.8(c)5.1(h)-298.9(mer)4.9(i)4.3(ts)-295.2(te)5.1(st)4.9(ing)5.8(.)]TJ
/F4 1 Tf
10.4607 0 0 10.4607 59.7543 102.3874 Tm
0 Tc
[(Current)-303.3(and)-298.4(Future)-301.6(Approaches)-301.7(for)-297.1(Clinical)]TJ
0 -1.2357 TD
[(Research)-230.6(with)-222.5(CBD)-229.8(in)-225.5(Anxiety-Related)-227.8(Disorders)]TJ
/F6 1 Tf
10.959 0 0 10.959 59.7543 76.1953 Tm
[(Based)-287.3(on)-283.3(this)-281.2(positive)-282.6(background)-283.4(of)-285(pre-clinical)-285.7(data,)]TJ
0 -1.1847 TD
[(anecdote)-285.4(and)-281.6(case)-281.1(reports,)-283.6(and)-286.8(small)-277(RCTs,)-286.2(numerous)]TJ
22.912 10.6412 TD
[(larger)-302.8(clinical)-310.2(trials)-304.4(are)-303.9(currently)-311(registered)-305.1(and)-307.4(ongo-)]TJ
0 -1.1847 TD
-.0001 Tc
[(ing)-515.5(\(see)-520(clinicaltrials.gov\))-520.1(assessing)-513.8(the)-520.3(potential)-512.4(of)]TJ
0 -1.1795 TD
0 Tc
[(CBD)-380.6(in)-378.5(anxiety-related)-380.7(disorders,)-383.1(which)-383.7(are)-381.5(summa-)]TJ
0 -1.1847 TD
[(rized)-201.9(in)-197.4(Table)-198.9(4.)-203.1(These)-199.1(trials)-200.9(cover)-199.8(relevant)-199.3(patient)-196.6(pop-)]TJ
0 -1.1795 TD
[(ulations,)-637.9(including)-641.6(PTSD,)-642.3(anxiety)-641(\(comorbid)-637.5(with)]TJ
T*
[(breast)-332.9(cancer)-338.1(or)-331(Parkinsons)-336.7(disease\),)-335(and)-333.3(generalized)]TJ
0 -1.1847 TD
[(an)15.8(xi)19.3(et)14.4(y)-307.6(d)0(i)14.4(s)0(o)15.6(r)12.2(de)15.2(r,)-302.6(us)14.9(i)11.7(n)0(g)-299.5(c)0(l)14.2(i)0(n)14.7(i)11.7(ca)14.9(ll)13.7(y)-302.5(r)0(e)14.4(l)0(e)14.2(v)0(a)15.6(n)0(t)-295.1(p)0(r)14.9(i)0(m)16.7(a)0(r)14.7(y)-307.6(en)15.5(d-)]TJ
0 -1.1795 TD
[(po)16.4(i)11.7(n)0(t)15.3(s)0(.)-349.2(I)0(n)15.3(t)0(e)14.5(r)0(e)14.4(s)12.2(ti)13.6(ng)16.1(ly)20(,)-361.4(t)12.3(he)15.8(re)-352.9(i)11.7(s)-360.2(a)-354.5(r)0(e)14.4(c)0(e)14.6(n)0(t)20.5(l)0(y)-352.5(r)12.2(eg)15.2(is)13.6(te)19.6(re)14.4(d)-359.4(t)12.3(ri)13.6(al)]TJ
0 -1.1847 TD
[(specically)-306.9(to)-310.2(assess)-308.7(the)-313.3(use)-308.9(of)-310.9(CBD)-308.2(\(300)-165.1(mg)-307.8(daily)-309.8(for)]TJ
0 -1.1795 TD
[(28)-387(days\))-392.2(in)-388.8(the)-390.9(treatment)-386.3(of)-388.5(burnout)-389.8(and)-390.2(distress)-387.9(in)]TJ
ET
59.754 682.583 490.167 .28345 re
f
59.754 232.668 490.167 .28348 re
f
59.754 655.937 490.167 .22675 re
f
BT
/F4 1 Tf
8.9663 0 0 8.9663 59.7543 699.2502 Tm
[(Table)-306.5(3.)-500.5(Published)-304.3(Clinical)-305.2(Evidence)-302.9(of)-302.7(Cannabidiol)-304.7(Efcacy)-305.3(in)-304.1(Sleep)-303.8(Disorders)-300.2(Through)-300.9(Randomized)-305.4(Controlled)-308.4(Trials)]TJ
0 -1.1128 TD
[(and)-302(Observational)-308.6(Studies)]TJ
/F2 1 Tf
7.9702 0 0 7.9702 162.1417 662.1731 Tm
[(Study)-329.8(type)-5988(Patient)-325.9(cohort)]TJ
21.0833 1.1239 TD
[(Dose)-331.7(and)-329.2(length)-323.7(of)]TJ
2.077 -1.1239 TD
[(treatment)-10786.1(Findings)]TJ
/F9 1 Tf
-36.0067 -2.1268 TD
(RCTs)Tj
1.003 -1.1239 TD
[(Carlini)-290.2(and)-299.1(Cunha)]TJ
1.003 -1.1239 TD
(\(1981\))Tj
5.9774 0 0 5.3127 96.4346 630.8219 Tm
(65)Tj
7.9702 0 0 7.9702 139.2377 636.2644 Tm
[(Double-bli)12(nd)-330(and)]TJ
.9958 -1.1239 TD
(randomized)Tj
10.4705 1.1239 TD
[(Fifteen)-327.9(insomniac)]TJ
1.003 -1.1239 TD
(volunteers)Tj
10.4634 1.1239 TD
[(40,)-333.7(80,)-333.7(and)-327.6(160)-162.9(mg)-329.3(CBD)]TJ
1.0029 -1.1239 TD
[(compared)-327.8(with)]TJ
T*
[(placebo)-329.1(and)-327.5(5)-165.7(m)0(g)]TJ
T*
(nitrazepam)Tj
10.4705 3.3716 TD
[(Subjects)-324.8(receiving)-329.9(160)-162.9(mg)-329.3(CBD)-329.4(reporte)10.3(d)]TJ
.9958 -1.1239 TD
[(having)-329.5(slept)-332.2(significan)14.3(tly)-332.5(more)-329.2(than)]TJ
T*
[(those)-329(receiving)-329.9(placebo)12.4(;)-336.5(the)]TJ
T*
[(volunteers)-327.9(also)-333.5(reporte)10.3(d)-334.3(significantl)10.5(y)]TJ
0 -1.131 TD
[(less)-323.3(dream)-320(recall)-312.1(with)-323.3(the)-318.9(three)-314.9(doses)]TJ
0 -1.1239 TD
[(of)-334.6(CBD)-329.4(than)-328.5(with)-330.4(placebo.)]TJ
-44.3717 -1.1239 TD
[(Linares)-291.5(et)-301.9(al.)]TJ
1.003 -1.1239 TD
(\(2019\))Tj
5.9774 0 0 5.3127 96.4346 577.0203 Tm
(31)Tj
7.9702 0 0 7.9702 139.2377 582.4628 Tm
[(Crossover)-328.9(and)-327.6(double-)]TJ
.9958 -1.1239 TD
[(blind)-334.3(design)]TJ
10.4705 1.1239 TD
[(Twenty-seven)-322.2(healthy)]TJ
1.003 -1.1239 TD
(subjects)Tj
10.4634 1.1239 TD
[(CBD)-308(\(300)-159.3(mg\))-304.3(or)-310.7(placebo)-962.1(Unlike)-329(other)-323.7(anxiolytic)-328.1(and)]TJ
12.4693 -1.1239 TD
[(antidepress)9.5(ant)-332.8(drugs,)-333.2(acute)]TJ
T*
[(administrati)9.3(on)-294.1(of)-291.9(an)-284.9(anxiolytic)-285.4(dose)-285.3(of)]TJ
T*
[(CBD)-251.1(did)-254.6(not)-249.5(seem)-254.5(to)-253.8(interfere)-246.2(with)-252.2(the)]TJ
0 -1.131 TD
[(sleep)-332.1(cycle)-327.5(of)-334.6(healthy)-326.5(volunteers.)]TJ
-45.3747 -1.4938 TD
[(Uncontrolled)-291.2(trials/case)-294.4(reports)-293.8(and)-299.1(series)]TJ
1.003 -1.131 TD
[(Chagas)-292.8(et)-294.8(al.)]TJ
1.003 -1.1239 TD
(\(2014\))Tj
5.9774 0 0 5.3127 96.4346 520.2708 Tm
(69)Tj
7.9702 0 0 7.9702 139.2377 525.6566 Tm
[(Case)-330.2(series)-6849.2(Four)-329.2(Parkinsons)-325.3(disease)]TJ
12.4693 -1.1239 TD
(patients)Tj
10.4634 1.1239 TD
[(CBD)-336.5(\(75)-157.2(mg/day)]TJ
1.0029 -1.1239 TD
[(\(3)-332.9(patients\))-327.1(or)]TJ
T*
[(300)-162.9(mg/day)-272.7(\(1)-276(patient\))]TJ
T*
[(for)-332.7(6)-329.4(weeks)]TJ
10.4705 3.3716 TD
[(Four)-329.2(patients)-323.6(treated)-329.1(with)-330.4(CBD)-329.4(had)-327.6(a)]TJ
.9958 -1.1239 TD
[(substantial)-317.7(reduction)-315.9(in)-321.5(the)-318.9(frequency)]TJ
T*
[(of)-334.6(rapid)-292.9(eye)-303.2(movem)13.5(ent)-297.6(sleep)]TJ
T*
[(behaviour)-290.5(disorder-rela)8.4(ted)-301.8(events.)]TJ
-44.3717 -1.1239 TD
[(Vigil)-293.2(et)-294.8(al.)-304.2(\(2018\))]TJ
5.9774 0 0 5.3127 123.5905 493.3416 Tm
(71)Tj
7.9702 0 0 7.9702 139.2377 489.8266 Tm
[(Mobile)-323.7(software)]TJ
.9958 -1.1239 TD
(application)Tj
10.4705 1.1239 TD
[(Four)-329.2(hundred)-328.4(nine)]TJ
1.003 -1.1239 TD
[(people)-328.3(with)-323.3(insomnia)]TJ
10.4634 1.1239 TD
[(Mean)-277.5(THC)-285.7(level)-275.2(was)-282(20%)]TJ
1.0029 -1.1239 TD
[(and)-327.6(the)-333.2(mean)-324.8(CBD)]TJ
0 -1.131 TD
[(level)-332.1(was)-324.7(5.7%)]TJ
10.4705 2.2549 TD
[(Releaf)-322.4(App)]TJ
/F10 1 Tf
4.5809 0 TD
()Tj
/F9 1 Tf
1.2163 0 TD
[(users)-329.5(showed)-327.4(an)-327.6(average)]TJ
-4.8014 -1.1239 TD
[(symptom)-328.1(severity)-327.4(reduction)-330.1(of)]TJ
/F12 1 Tf
13.33 0 TD
()Tj
/F9 1 Tf
.7682 0 TD
(4.5)Tj
-14.0982 -1.131 TD
[(points)-301.2(on)-294.1(a)-296.3(010)-296(point)-297.8(visual)-294.1(analog)]TJ
0 -1.1239 TD
[(scale.)-228.4(CBD)-229.8(was)-232.2(associate)9.9(d)-227.6(with)-230.8(greater,)]TJ
T*
[(statistically)-299.1(signicant,)-291.8(symptom)-292.6(relief)]TJ
T*
[(than)-300.1(THC.)]TJ
-44.3717 -1.1239 TD
[(Barchel)-287.4(et)-301.9(al.)]TJ
1.003 -1.1239 TD
(\(2019\))Tj
5.9774 0 0 5.3127 96.4346 430.5826 Tm
(68)Tj
7.9702 0 0 7.9702 139.2377 436.0251 Tm
[(Prospectiv)10.3(e)-332.2(and)]TJ
.9958 -1.1239 TD
(uncontrolled)Tj
10.4705 1.1239 TD
[(Fifty-three)-329.4(children)-320.1(with)]TJ
1.003 -1.1239 TD
[(autism)-323.7(spectrum)]TJ
T*
(disorder)Tj
10.4634 2.2477 TD
[(CBD)-336.5(median)-323.3(daily)-330.6(dose)]TJ
1.0029 -1.1239 TD
[(was)-331.8(90)-331.5(\(45143\))-321.6(mg.)]TJ
T*
[(Median)-325.9(duration)-321.6(of)-334.6(66)]TJ
0 -1.131 TD
[(\(30588\))-328.7(days)]TJ
10.4705 3.3787 TD
[(Reports)-326.7(on)-329.6(21)-331.5(patients)-330.7(with)-323.3(sleep)]TJ
.9958 -1.1239 TD
[(problems)-331(were)-324.8(recorded.)-329.1(Of)-330.8(21)]TJ
T*
[(reports,)-331.6(71%)-330.1(improved,)-327.4(24%)-330.1(had)-327.6(no)]TJ
0 -1.131 TD
[(change,)-327.4(and)-327.5(worsening)-329.8(of)-327.4(symptoms)]TJ
0 -1.1239 TD
[(was)-331.8(reported)-331(in)-328.7(one)-327.6(patient.)]TJ
-44.3717 -1.1239 TD
[(Fleury-Tei)11.6(xeira)]TJ
1.003 -1.1239 TD
[(et)-294.8(al.)-297.1(\(2019\))]TJ
5.9774 0 0 5.3127 114.9165 385.7385 Tm
(67)Tj
7.9702 0 0 7.9702 139.2377 391.181 Tm
[(Observation)10.5(al)-330.5(study)-3082.4(Eighteen)-237.6(autistic)-251.2(patients)-956.7(Pure)-332.4(CBD)-329.4(and)-327.6(CBD-)]TJ
23.9357 -1.1239 TD
[(enriched)-326.5(extract)]TJ
10.4705 1.1239 TD
[(The)-329.8(strongest)-324.2(improveme)11.8(nts)-331.5(with)-330.4(CBD)]TJ
.9958 -1.1239 TD
[(were)-331.9(reported)-323.9(for)-332.6(seizures,)-328(attention)]TJ
T*
[(deficit/hyperac)11.9(tivity)-333.9(disorder,)-324.9(sleep)]TJ
T*
[(disorders,)-328.3(and)-334.7(commun)12.6(ication)-330.8(and)]TJ
0 -1.131 TD
[(social)-333.2(interactio)9.4(n)-337.1(deficits.)-327.7(Sleep)]TJ
0 -1.1239 TD
[(disorders)-333.2(were)-324.8(improved)-325.3(by)]TJ
/F8 1 Tf
12.2488 0 TD
(*)Tj
/F9 1 Tf
1.0029 0 TD
(40%.)Tj
-57.6235 -1.1239 TD
[(Shanno)13.9(n)-301.6(e)0(t)-301.9(al.)]TJ
1.003 -1.1239 TD
(\(2019\))Tj
5.9774 0 0 5.3127 96.4346 331.9369 Tm
(44)Tj
7.9702 0 0 7.9702 139.2377 337.3794 Tm
[(Case)-330.2(series)-6849.2(Seventy-tw)11(o)-333.9(adults)-331.5(with)]TJ
12.4693 -1.1239 TD
[(concern)10.7(s)-337.7(o)0(f)-327.4(anxiety)]TJ
T*
(\()Tj
/F11 1 Tf
.2774 0 TD
(n)Tj
/F10 1 Tf
.6971 0 TD
(=)Tj
/F9 1 Tf
.7184 0 TD
[(47\))-292.4(or)-303.6(poor)-296(sleep)]TJ
-1.6929 -1.1239 TD
(\()Tj
/F11 1 Tf
.2774 0 TD
(n)Tj
/F10 1 Tf
.6971 0 TD
(=)Tj
/F9 1 Tf
.7184 0 TD
(25\))Tj
8.7705 3.3716 TD
[(Twenty-five)-324.5(to)-332(175)-162.9(mg)]TJ
1.0029 -1.1239 TD
[(per)-330.3(day)-333.3(in)-328.7(the)]TJ
T*
[(morning)-324.1(\(for)-336.2(anxiety\))]TJ
T*
[(or)-332(evening)-327.7(\(for)-329.1(sleep\))]TJ
10.4705 3.3716 TD
[(On)-311.7(average,)-311.8(anxiety)-313.9(and)-320.4(sleep)-310.7(improved)]TJ
.9958 -1.1239 TD
[(for)-332.7(most)-334.6(patients)10.7(,)-336.5(and)-327.5(these)]TJ
T*
[(improvement)10.9(s)-337.7(were)-324.8(sustained)-328.5(over)]TJ
T*
(time.)Tj
-44.3717 -1.1239 TD
[(Capano)-293.3(et)-294.8(al.)]TJ
1.003 -1.131 TD
(\(2020\))Tj
5.9774 0 0 5.3127 96.4346 296.107 Tm
(70)Tj
7.9702 0 0 7.9702 139.2377 301.5495 Tm
[(Prospectiv)10.3(e)-332.2(cohort)-333.7(study)-969.8(One)-330.9(hundred)-321.2(thirty-one)]TJ
12.4693 -1.131 TD
[(patients)-259.6(from)-260.8(a)-260.8(private)]TJ
0 -1.1239 TD
[(pain)-326.2(managemen)16.3(t)]TJ
T*
(centre)Tj
10.4634 3.3787 TD
[(Hemp)-333.7(extract)-329.6(CBD)-3651.2(More)-324.6(than)-328.5(half)-334(of)-334.6(chronic)-324.3(pain)-326.2(patients)]TJ
12.4693 -1.131 TD
[(\(53%\))-330(reduced)-328.9(or)-332(eliminated)-323.7(their)]TJ
0 -1.1239 TD
[(opioids)-334(within)-324.7(8)-329.3(weeks)-331.5(with)-330.4(CBD-ric)10.3(h)]TJ
T*
[(hemp)-327.1(extract.)-331.8(There)-325.8(was)-331.8(a)-331.9(significant)]TJ
T*
[(relationship)-323.3(between)-325.5(CBD)-329.4(and)]TJ
T*
[(Pittsburgh)-331.1(Sleep)-323.4(Quality)-331.3(Index)]TJ
T*
(\()Tj
/F11 1 Tf
.4481 0 TD
(p)Tj
/F10 1 Tf
.69 0 TD
(=)Tj
/F9 1 Tf
.7113 0 TD
[(0.003\),)-301(and)-292(Pain)-293.2(Intensity)-300.6(and)]TJ
-1.8494 -1.131 TD
(Interference.)Tj
-44.2437 -2.2406 TD
[(Studies)-291(are)-299.5(presente)11.1(d)-298.7(i)0(n)-300.2(chronologi)10.5(cal)-303.2(order)-292.4(in)-300.2(each)-291.1(section.)]TJ
/F4 1 Tf
9.9626 0 0 9.9626 59.7543 753.8455 Tm
[(CBD)-306.5(IN)-306.7(COVID-19)-10.5(-RELATED)-309.1(PTSD)]TJ
48.0965 0 TD
(13)Tj
ET
endstream
endobj
75 0 obj
<>stream
0 0 0 rg
/GS1 gs
91.219 63.213 .22678 707.697 re
f
117.865 63.213 .22678 707.697 re
f
BT
/F4 1 Tf
0 8.9663 -8.9663 -0 84.7559 63.2126 Tm
0 Tc
0 Tw
[(Table)-306.5(4.)-500.5(Registered)-303.4(and)-302(Active)-300.6(Clinical)-305.2(Trials)-303.2(Examining)-303.8(the)-303.4(Potential)-308.9(of)-296.4(Cannabidiol)-311(in)-297.8(the)-303.4(Treatment)-303.5(of)-302.7(Anxiety)-299.6(Disorders)]TJ
/F2 1 Tf
0 7.9702 -7.9702 -0 111.8551 63.2126 Tm
-.0001 Tc
[(NCT)-329.5(no.)-7403.4(Title)-6726.9(Status)-5335.5(C)6.7(ondition)6.7(s)-6981.8(O)6.9(utcome)-336.6(meas)6.9(ures)-4531.5(Spons)8.1(or/coll)5.1(abor)7.2(ators)-3458.7(Phase)]TJ
/F13 1 Tf
70.982 0 TD
0 Tc
(N)Tj
/F2 1 Tf
3.7842 0 TD
[(St)6.5(art)-332.3(date)]TJ
7.9952 1.1239 TD
[(Comple)9.1(tion)]TJ
1.5578 -1.1239 TD
(date)Tj
/F9 1 Tf
-84.3191 -2.1268 TD
[(NCT03)5.5(518801)-745.5(Cann)6.8(abidio)5.7(l)-332.9(and)]TJ
7.5399 -1.1239 TD
[(Pr)6.5(olonge)5.7(d)-334.3(Expos)5.2(ure)]TJ
10.25 1.1239 TD
[(Recr)7.5(uiting)-2532.9(PTS)8.1(D)-9089(Clinicia)6.9(n-admin)9.3(istered)-328.2(PTSD)-331.7(scale)]TJ
18.9992 -1.1239 TD
-.0005 Tc
[(DS)6.4(M)-336.6(5)-329.8(\(CAPS-5\))]TJ
/F12 1 Tf
7.0135 0 TD
0 Tc
(j)Tj
/F9 1 Tf
.6046 0 TD
[(PTS)8.1(D)-332.7(checkli)5.4(st)]TJ
-7.6182 -1.1239 TD
[(\(PCL-)5.8(5\))]TJ
14.7455 2.2477 TD
[(Univers)6.4(ity)-332.5(of)-334.5(Californ)7(ia,)]TJ
1.0029 -1.1239 TD
[(San)-329.4(Diego)]TJ
10.25 1.1239 TD
-.0002 Tc
[(Phase)-324.4(2)-4462.3(136)-746.4(Ma)7.5(rch)-336.6(1,)-331.7(201)7.6(9)-2947.2(S)-.2(e)7.2(ptember)-330.5(2023)]TJ
-62.7876 -3.3787 TD
0 Tc
[(NCT04)5.5(197102)-745.5(Use)-330.8(of)-334.6(CBD)-329.4(Oil)-327.4(in)-335.8(th)6.2(e)]TJ
7.5399 -1.1239 TD
[(Treat)6.5(men)7.1(t)-339.5(o)7.5(f)]TJ
T*
[(Postt)5.5(raum)5.5(atic)-336.9(St)7.2(ress)]TJ
T*
[(Dis)6.7(order)]TJ
10.25 3.3716 TD
[(Recr)7.5(uiting)-2532.9(PTS)8.1(D)-9089(CAPS-5)]TJ
/F12 1 Tf
21.3323 0 TD
(j)Tj
/F9 1 Tf
.6046 0 TD
(CGI)Tj
/F12 1 Tf
1.7783 0 TD
(j)Tj
/F9 1 Tf
.6046 0 TD
[(PC)7.6(L-5)-334.7(QID)7.1(S)]TJ
/F12 1 Tf
5.1001 0 TD
(j)Tj
/F9 1 Tf
.6046 0 TD
[(SD)6.9(S)]TJ
/F12 1 Tf
1.9632 0 TD
(j)Tj
/F9 1 Tf
-12.9886 -1.1239 TD
[(WHO)5.5(QOL)6.8(-BSEF)]TJ
14.7455 1.1239 TD
[(Univers)6.4(ity)-332.5(of)-334.5(Texas)-332.2(at)]TJ
1.0029 -1.1239 TD
[(Aust)5.5(in)]TJ
10.25 1.1239 TD
[(Phase)-324.2(2)-4462.1(120)-746.2(Jan)7.9(uary)-331.1(15,)-333.7(2020)-1829.6(Jan)7.9(uary)-331.1(5,)-331.5(2023)]TJ
-62.7876 -4.4955 TD
[(NCT04)5.5(504877)-745.5(Burnout)-331.7(and)-327.6(Distre)5.5(ss)]TJ
7.5399 -1.1239 TD
[(prev)6.5(ention)-327.1(with)]TJ
0 -1.131 TD
[(caNn)7.2(abidio)5.7(l)-332.9(i)0(n)-328.7(Front-)]TJ
0 -1.1239 TD
[(lin)7(e)-332.2(Healt)5.5(h)-337.1(Car)7.3(e)]TJ
T*
[(wor)5.8(kerS)-333.6(deA)8.6(ling)-330.1(with)]TJ
T*
[(CO)7.1(VID)-334.2(19)]TJ
10.25 5.6265 TD
[(Recr)7.5(uiting)-2532.9(CO)7.1(VID-19)6.2(/Burn)]TJ
7.7462 -1.1239 TD
[(Out/PTS)6.1(D)]TJ
10.25 1.1239 TD
-.0002 Tc
[(aMBI-HS)8.5(S:)-338.5(Ab)6.4(breviated)-332.4(Ma)7.5(slach)]TJ
1.003 -1.1239 TD
[(Burn)6.8(out)-331.8(Inven)7.1(toryHuman)]TJ
0 -1.131 TD
-.0004 Tc
[(Servi)5.6(ces)-330(Survey)]TJ
/F12 1 Tf
6.8144 0 TD
0 Tc
(j)Tj
/F9 1 Tf
.6046 0 TD
-.0003 Tc
[(Post-)6.5(traumatic)]TJ
-7.419 -1.1239 TD
0 Tc
[(stres)6.3(s)-316.3(disorder)-315.6(checkli)5.4(st)-314.4(for)-318.4(DS)6.9(M-)]TJ
T*
[(5)-329.4(\(PCL-)5.8(5\))]TJ
/F12 1 Tf
4.1114 0 TD
(j)Tj
/F9 1 Tf
.6046 0 TD
-.0003 Tc
[(Brief)-329.5(measure)-332.5(for)]TJ
-4.716 -1.1239 TD
0 Tc
[(as)6.2(sessing)-332.3(gener)7.5(alize)7.5(d)-334.3(anxiet)7.7(y)]TJ
T*
[(diso)5.6(rder:)-330.5(The)-329.8(GAD7)]TJ
/F12 1 Tf
8.5713 0 TD
(j)Tj
/F9 1 Tf
.6046 0 TD
[(PHQ)6.5(-9:)]TJ
-9.1759 -1.1239 TD
[(Pa)7(tients)-278.5(Healt)5.5(h)-280.2(Quest)5.2(ionnai)7(re-9)]TJ
/F12 1 Tf
13.7284 0 TD
(j)Tj
/F9 1 Tf
-13.7284 -1.1239 TD
[(Chan)6.8(ge)-328(in)-335.8(proin)8(flamma)7.1(tory)]TJ
0 -1.131 TD
-.0002 Tc
[(cytok)5.1(ine)-333.9(co)6.2(ncentration)]TJ
/F12 1 Tf
9.9797 0 TD
0 Tc
(j)Tj
/F9 1 Tf
.6046 0 TD
[(No.)-334.5(of)]TJ
-10.5843 -1.1239 TD
-.0002 Tc
[(part)6.1(icipants)-327.6(with)-330.6(treatment-)]TJ
T*
0 Tc
[(rela)7.8(ted)-337.4(adve)7(rse)-326.6(events)-332(as)]TJ
T*
[(as)6.2(sessed)-333(by)-328.6(CTCAE)-332.7(v5)7.4(.0)]TJ
14.7455 13.5007 TD
-.0001 Tc
[(Univers)6.3(ity)-332.6(of)-334.6(Sao)-333.4(Pa)6.9(ulo)-1463.2(Phase)-324.3(2/Phase)-327.8(3)-834.5(102)-746.3(Jun)5.8(e)-332.3(16,)-333.8(202)7.7(0)-3082.2(S)-.1(e)7.3(ptember)-330.4(2020)]TJ
-51.5347 -14.6246 TD
0 Tc
[(NCT04)5.5(267679)-745.5(Cann)6.8(abidio)5.7(l)-332.9(for)-332.7(Anxiety)-1326.9(Not)-330.4(yet)]TJ
18.7858 -1.1239 TD
-.0003 Tc
(recruiting)Tj
5.7545 1.1239 TD
0 Tc
[(Anxi)7.8(ety)-8120.7(Generali)6.1(zed)-239.5(Anxi)7.8(ety)-246.4(Dis)6.7(order)-242.6(7-ite)6.5(m)]TJ
12.2488 -1.1239 TD
[(scal)6.4(e)]TJ
/F12 1 Tf
2.3758 0 TD
(j)Tj
/F9 1 Tf
.6046 0 TD
-.0003 Tc
[(Perception)-328.6(of)-334.9(chang)6.7(e)]TJ
/F12 1 Tf
9.4036 0 TD
0 Tc
(j)Tj
/F9 1 Tf
-12.384 -1.131 TD
[(Pro)6.9(tocol)-331.4(Compl)5.5(iance)]TJ
/F12 1 Tf
9.0692 0 TD
(j)Tj
/F9 1 Tf
.6046 0 TD
[(Sl)6.7(eep)]TJ
-9.6739 -1.1239 TD
[(quali)5.6(ty)]TJ
14.7455 3.3787 TD
(CB)Tj
0 5.9774 -5.3127 -0 309.4865 482.8534 Tm
(2)Tj
0 7.9702 -7.9702 -0 308.1259 488.2959 Tm
[(Insig)8(hts/G)6.3(reen)-295.5(Lotus)]TJ
-.7967 -1.1239 TD
[(Hem)7.7(p)]TJ
10.25 1.1239 TD
[(Phase)-324.2(2)-4462.1(100)-746.2(Jan)7.9(uary)-331.1(10,)-333.7(2020)-1829.6(Jan)7.9(uary)-331.1(2,)-331.5(2021)]TJ
-62.7876 -4.5026 TD
[(NCT04)5.5(286594)-745.5(A)-334.9(Clinica)5.5(l)-332.9(Trial)-329(of)-334.6(a)]TJ
7.5399 -1.1239 TD
[(He)6.9(mp-De)7.7(rived)]TJ
T*
[(Cann)6.8(abidio)5.7(l)-332.9(Produ)7.4(ct)]TJ
T*
[(for)-332.7(Anxi)7.8(ety)]TJ
10.25 3.3716 TD
[(Not)-330.4(yet)]TJ
.9958 -1.1239 TD
-.0003 Tc
(recruiting)Tj
5.7545 1.1239 TD
0 Tc
[(Anxi)7.8(ety)-8120.7(Chan)6.8(ge)-335.1(from)-331.9(B)7.5(aseline)-331.2(in)-328.6(Self-)]TJ
12.2488 -1.1239 TD
-.0002 Tc
[(Rep)6.6(orted)-328.2(Anxiety)-331.3(as)-328.3(Assessed)-334.5(b)-.2(y)]TJ
T*
0 Tc
[(th)6.2(e)-332.2(Beck)-334.4(Anxi)7.8(ety)-331.8(Inven)7.3(tory)-331.6(\(BAI\))]TJ
14.7455 2.2477 TD
[(Mclean)-327.1(Hospit)5.2(al)-4520.2(Phase)-324.2(2)-4967.1(7)0(5)-751.2(A)0(p)6.5(ril)-336.8(1,)-331.5(202)7.8(0)-3601.4(M)0(a)7.7(rch)-329.3(2022)]TJ
-51.5347 -4.4955 TD
[(NCT03)5.5(549819)-745.5(Cann)6.8(abidio)5.7(l)-332.9(for)-332.7(the)]TJ
7.5399 -1.131 TD
[(Treat)6.5(men)7.1(t)-339.5(o)7.5(f)-335(Anxiety)]TJ
0 -1.1239 TD
[(Dis)6.7(orders:)-333.5(An)-330.7(8-We)6.8(ek)]TJ
T*
[(Pil)7.4(ot)-332(Study)]TJ
10.25 3.3787 TD
[(Not)-330.4(yet)]TJ
.9958 -1.131 TD
-.0003 Tc
(recruiting)Tj
5.7545 1.131 TD
0 Tc
[(Ge)6.9(nerali)6.3(zed)-332(Anxiety)]TJ
.9958 -1.131 TD
-.0003 Tc
[(Disorder/Soc)4.9(ial)]TJ
0 -1.1239 TD
-.0002 Tc
[(Anxiety)-281.5(Disorder/Pa)7.4(nic)]TJ
T*
[(Disorder/Agor)6.4(aphob)7(ia)]TJ
10.25 3.3787 TD
0 Tc
[(Hamilt)5.5(on)-329.6(Anxiety)-331.1(Ra)7(ting)-329.6(Scale)]TJ
1.003 -1.131 TD
[(\(HA)7.8(M-A\))]TJ
/F12 1 Tf
3.8411 0 TD
(j)Tj
/F9 1 Tf
.6046 0 TD
[(Clinica)5.5(l)-332.9(Glob)6.7(al)]TJ
-4.4457 -1.1239 TD
[(Impre)6.2(ssion)6.5(Sev)6.8(erity)-335.6(\(C)6.5(GI-S\))]TJ
/F12 1 Tf
12.3057 0 TD
(j)Tj
/F9 1 Tf
-12.3057 -1.1239 TD
[(Clinica)5.5(l)-332.9(G)0(l)6.2(obal)-330.1(Impression)5.6()]TJ
T*
[(Improv)6.9(emen)9.2(t)-332.4(\(CGI-I\))]TJ
/F12 1 Tf
8.863 0 TD
(j)Tj
/F9 1 Tf
-8.863 -1.1239 TD
[(Ge)6.9(neraliz)6.5(ed)-332.2(Anxiety)-331.1(Dis)6.7(order-7)]TJ
T*
[(\(GA)7.8(D-7\))]TJ
/F12 1 Tf
3.6064 0 TD
(j)Tj
/F9 1 Tf
.5975 0 TD
[(Liebow)5.9(itz)-330.8(Social)]TJ
-4.2039 -1.131 TD
[(Anxi)7.8(ety)-331.8(Scale)-331.4(Self-R)8.9(eport)-335.1(\(LS)7.4(AS)]TJ
0 -1.1239 TD
(SR\))Tj
/F12 1 Tf
1.6289 0 TD
(j)Tj
/F9 1 Tf
.6046 0 TD
[(Panic)-329.8(and)-327.6(Agor)6(aphobia)]TJ
-2.2335 -1.1239 TD
[(Sca)6.6(le)-330.9(\(PAS\))]TJ
/F12 1 Tf
4.9863 0 TD
(j)Tj
/F9 1 Tf
.6046 0 TD
[(Qui)5.9(ck)-336.9(Inv)8.1(entory)-332.3(of)]TJ
-5.5909 -1.1239 TD
[(Depr)5.6(essiv)6.3(e)-246.9(Sympt)6.6(omolog)7.6(y)-243.3(\(QIDS\))]TJ
/F12 1 Tf
T*
(j)Tj
/F9 1 Tf
.6046 0 TD
[(Shee)6.6(han)-330.4(Dis)6.7(ability)-327.3(Scale)-331.4(\(SDS\))]TJ
/F12 1 Tf
13.0668 0 TD
(j)Tj
/F9 1 Tf
-13.6714 -1.1239 TD
[(Wor)6(ld)-332.9(Healt)5.5(h)-337.1(O)0(r)6(ganiza)7.9(tion)]TJ
0 -1.131 TD
[(Dis)6.7(ability)-334.4(Ass)6.9(essme)5.4(nt)-335.2(Sca)6.6(le)]TJ
0 -1.1239 TD
[(\(WHO)9.1(DAS)-235.6(2.0)7.8(\))]TJ
/F12 1 Tf
6.16 0 TD
(j)Tj
/F9 1 Tf
.4979 0 TD
[(Insomnia)-230.3(Se)7.4(verity)]TJ
-6.6579 -1.1239 TD
[(Inde)7.8(x)-331.6(\(ISI\))]TJ
14.7455 16.8795 TD
[(McMaste)5.5(r)]TJ
1.0029 -1.131 TD
-.0001 Tc
[(Unive)7.8(rsity/Tilray)]TJ
10.25 1.131 TD
0 Tc
[(Phase)-324.2(3)-4967.1(5)0(0)-751.2(Jan)7.9(uary)-331.1(7,)-331.5(2019)-2341.7(Jan)7.9(uary)-331.1(8,)-331.5(2020)]TJ
21.439 -19.2553 TD
(\()Tj
/F11 1 Tf
.2774 0 TD
-.0004 Tc
(continued)Tj
/F9 1 Tf
4.0118 0 TD
0 Tc
(\))Tj
/F4 1 Tf
8.9663 0 0 8.9663 302.1732 26.2488 Tm
(14)Tj
ET
endstream
endobj
80 0 obj
<>stream
0 0 0 rg
/GS1 gs
528.491 63.213 .22675 707.697 re
f
72.34 63.213 .22676 707.697 re
f
99.213 63.213 .28346 707.697 re
f
BT
/F4 1 Tf
0 8.9663 -8.9663 -0 65.8771 375.1369 Tm
0 Tc
0 Tw
[(Table)-331.8(4.)-500.5(\(Continued\))]TJ
/F2 1 Tf
0 7.9702 -7.9702 -0 93.2598 63.2126 Tm
-.0001 Tc
[(NCT)-329.5(no.)-7403.4(Title)-6726.9(Status)-5335.5(C)6.7(ondition)6.7(s)-6981.8(O)6.9(utcome)-336.6(meas)6.9(ures)-4531.5(Spons)8.1(or/coll)5.1(abor)7.2(ators)-3458.7(Phase)]TJ
/F13 1 Tf
70.982 0 TD
0 Tc
(N)Tj
/F2 1 Tf
3.7842 0 TD
[(St)6.5(art)-332.3(date)]TJ
7.9952 1.1239 TD
[(Comple)9.1(tion)]TJ
1.5578 -1.1239 TD
(date)Tj
/F9 1 Tf
-84.3191 -2.1268 TD
[(NCT04)5.5(482244)-745.5(RCT)-250.3(of)-249.2(CBD)-251.1(f)6.5(o)0(r)-253.8(Anxi)7.8(ety)-253.6(in)]TJ
7.5399 -1.1239 TD
[(Ad)6.6(vanced)-331.3(Brea)6.8(st)]TJ
T*
[(Canc)8.5(er)]TJ
10.25 2.2477 TD
[(Not)-330.4(yet)]TJ
.9958 -1.1239 TD
-.0003 Tc
(recruiting)Tj
5.7545 1.1239 TD
0 Tc
[(Ad)6.6(vanced)-331.3(B)7.5(reast)]TJ
.9958 -1.1239 TD
[(Cancer)5.4(/Anxi)6.5(ety)-331.8(CBD)]TJ
10.25 1.1239 TD
[(Chan)6.8(ge)-335.1(in)-328.6(Anxiety)-331.1(Scor)6.5(e-Visual)]TJ
1.003 -1.1239 TD
[(Anal)7.5(og)-329.6(Mood)-328.1(Scale)-331.4(\(VAMs)9.2(\))]TJ
T*
[(anxiet)7.7(y)-335.8(subs)8(cale)]TJ
/F12 1 Tf
7.2056 0 TD
(j)Tj
/F9 1 Tf
.6046 0 TD
[(No.)-334.5(of)]TJ
-7.8102 -1.1239 TD
[(Pa)7(rticipan)5.1(ts)-335.8(with)-330.4(Treat)6.5(ment-)]TJ
T*
[(Rel)8.1(ated)-335(Ad)6.6(verse)-329.2(Events)-328.8(\(PRO-)]TJ
T*
[(CTCAE)8.8(a)]TJ
2.8168 .0285 TD
()Tj
.3841 -.0285 TD
[(,,)-331.5(\))-332.9(5.)]TJ
/F12 1 Tf
2.8879 0 TD
(j)Tj
/F9 1 Tf
.6046 0 TD
[(Moo)6.1(d)-334.3(C)0(h)7.2(anges)]TJ
/F12 1 Tf
6.7006 0 TD
(j)Tj
/F9 1 Tf
-13.394 -1.131 TD
[(Naus)8.2(ea)-336.9(Ra)7(te)]TJ
/F12 1 Tf
5.534 0 TD
(j)Tj
/F9 1 Tf
.6046 0 TD
[(Pain)-328.7(Rate)]TJ
/F12 1 Tf
4.2821 0 TD
(j)Tj
/F9 1 Tf
.6046 0 TD
[(Pa)7(in)]TJ
-11.0254 -1.1239 TD
[(inten)6.8(sity)-335.8(scal)6.4(e)-332.2(\(PINS\))]TJ
14.7455 7.8742 TD
[(Dana-)6.8(Farber)-330.7(Cancer)]TJ
1.0029 -1.1239 TD
[(Insti)5.6(tute/Ha)5.1(ns)-333.4(and)]TJ
T*
[(Mavis)-326.1(Lopate)5.4(r)]TJ
T*
[(Foun)7.5(dation)]TJ
10.25 3.3716 TD
-.0003 Tc
[(Phase)-324.5(2)-4967.4(5)-.3(0)-751.5(S)-.3(e)7.1(ptember)-330.6(18,)]TJ
11.0254 -1.1239 TD
0 Tc
(2020)Tj
7.9525 1.1239 TD
[(Febr)6.5(uary)-331(202)7.8(3)]TJ
-81.7655 -8.9981 TD
[(NCT03)5.5(248167)-745.5(Cann)6.8(abidio)5.7(l)-332.9(a)0(s)-335.2(a)]TJ
7.5399 -1.1239 TD
[(Treat)6.5(men)7.1(t)-339.5(f)6.5(or)-332(AUD)]TJ
T*
[(Comor)6.4(bid)-332.8(Wit)6.9(h)-337.1(PTS)8.1(D)]TJ
10.25 2.2478 TD
[(Recr)7.5(uiting)-2532.9(Al)7.9(cohol)-329(Use)]TJ
7.7462 -1.1239 TD
-.0003 Tc
(Disorder/PTSD)Tj
10.25 1.1239 TD
0 Tc
[(No.)-334.5(of)-327.4(drinks)-331.5(per)-330.3(day)]TJ
/F12 1 Tf
9.304 0 TD
(j)Tj
/F9 1 Tf
.6046 0 TD
[(Wee)7.8(kly)]TJ
-8.9056 -1.1239 TD
-.0002 Tc
[(percentage)-326.7(of)-334.8(hea)8.6(vy)-333.6(drink)6(ing)]TJ
T*
0 Tc
(days)Tj
/F12 1 Tf
2.198 0 TD
(j)Tj
/F9 1 Tf
.5762 0 TD
-.0002 Tc
[(Wee)7.6(kly)-300.5(percentage)-298.2(of)-299.2(ver)6.2(y)]TJ
-2.7741 -1.1239 TD
-.0003 Tc
[(hea)8.5(vy)-333.7(drinking)-330.3(days)]TJ
/F12 1 Tf
8.8274 0 TD
0 Tc
(j)Tj
/F9 1 Tf
.6046 0 TD
[(Week)6.3(ly)]TJ
-9.432 -1.1239 TD
-.0002 Tc
[(percentage)-326.7(of)-334.8(subjec)9.2(ts)-335.9(that)-331.1(are)]TJ
0 -1.131 TD
0 Tc
[(presen)7.1(t)-332.4(and)-327.6(clean)]TJ
/F12 1 Tf
7.9383 0 TD
(j)Tj
/F9 1 Tf
.6046 0 TD
[(Wee)7.8(kly)]TJ
-8.5429 -1.1239 TD
-.0002 Tc
[(percentage)-326.7(of)-334.8(day)7.9(s)-337.9(abs)6.1(tinent)]TJ
/F12 1 Tf
12.6969 0 TD
0 Tc
(j)Tj
/F9 1 Tf
-12.6969 -1.1239 TD
[(Wee)7.8(kly)-335.9(ave)6.9(rage)-330.7(severi)6.5(ty)-333.9(of)]TJ
T*
[(alcoh)7.4(ol)-289.9(craving)]TJ
/F12 1 Tf
6.6437 0 TD
(j)Tj
/F9 1 Tf
.5619 0 TD
[(PTSD)-289(symp)10.2(toms)]TJ
/F12 1 Tf
-7.2056 -1.1239 TD
(j)Tj
/F9 1 Tf
.6046 0 TD
-.0002 Tc
[(Psy)6.7(chophy)6.2(siologi)5.7(cal)-331.9(arousal-)]TJ
-.6046 -1.1239 TD
0 Tc
[(rela)7.8(ted)-337.4(hea)8.8(rt)-337.6(rat)6.2(e)]TJ
/F12 1 Tf
7.6964 0 TD
(j)Tj
/F9 1 Tf
-7.6964 -1.131 TD
-.0002 Tc
[(Psy)6.7(chophysiologic)6.5(al)-337.8(arou)4.9(sal-)]TJ
0 -1.1239 TD
[(rela)7.6(ted)-337.6(skin)-326.5(conductance)]TJ
/F12 1 Tf
10.9258 0 TD
0 Tc
(j)Tj
/F9 1 Tf
-10.9258 -1.1239 TD
[(Trauma)-328.2(indu)6.1(ced)-333.3(crav)5.6(ing)]TJ
/F12 1 Tf
10.5772 0 TD
(j)Tj
/F9 1 Tf
-10.5772 -1.1239 TD
[(Trauma)6.1(-ind)9(uced)-332.9(negat)7.9(ive)]TJ
T*
[(emoti)6.5(on)]TJ
14.7455 16.8724 TD
[(NYU)-330.4(Langon)7.1(e)]TJ
1.0029 -1.1239 TD
[(Healt)5.5(h/Na)7(tional)]TJ
T*
[(Insti)5.6(tutes)-331.4(of)-334.6(Healt)5.5(h)]TJ
T*
(\(NIH\))Tj
10.25 3.3716 TD
-.0002 Tc
[(Phase)-324.4(1/Phase)-327.9(2)-1339.6(4)-.2(8)-751.4(S)-.2(e)7.2(ptember)-330.5(16,)]TJ
11.0254 -1.1239 TD
0 Tc
(2019)Tj
7.9525 1.1239 TD
[(Au)6.9(gust)-331.1(2020)]TJ
-81.7655 -17.9962 TD
[(NCT02)5.5(548559)-745.5(Sublin)5.7(gual)-333(Cann)6.8(abidio)5.7(l)]TJ
7.5399 -1.1239 TD
[(for)-332.7(Anxi)7.8(ety)]TJ
10.25 1.1239 TD
[(Recr)7.5(uiting)-2532.9(Anxi)7.8(ety)-8120.7(Chan)6.8(ge)-335.1(from)-331.9(B)7.5(aseline)-331.2(in)-328.6(Self-)]TJ
18.9992 -1.1239 TD
-.0002 Tc
[(Rep)6.6(orted)-328.2(Anxiety)-331.3(as)-328.3(Assessed)-334.5(b)-.2(y)]TJ
0 -1.131 TD
0 Tc
[(th)6.2(e)-282.4(Bec)8.5(k)-278.9(Anxiety)-274.2(Inven)7.3(tory)-274.7(\(BAI\))]TJ
/F12 1 Tf
13.7284 0 TD
(j)Tj
/F9 1 Tf
-13.7284 -1.1239 TD
[(Chan)6.8(ge)-328(from)-331.9(Baselin)8.6(e)-332.2(i)0(n)-335.8(Anxi)7.8(ety)]TJ
T*
[(Ass)6.9(essed)-329.7(by)-335.7(th)6.2(e)-332.2(Hamilt)5.5(on)]TJ
T*
[(Anxi)7.8(ety)-331.8(Scale)-331.4(\(HA)7.8(M-A\))]TJ
/F12 1 Tf
9.7734 0 TD
(j)Tj
/F9 1 Tf
.6046 0 TD
[(Chan)6.8(ge)]TJ
-10.3781 -1.1239 TD
-.0002 Tc
[(from)-332.1(B)7.3(aseline)-331.4(in)-328.8(Self-Reporte)5.7(d)]TJ
T*
0 Tc
[(Anxi)7.8(ety)-331.8(Asses)5.7(sed)-335.5(by)-328.6(the)-333.2(State)6.5(-)]TJ
0 -1.131 TD
-.0002 Tc
[(Trait)-328.7(Anxiety)-324.2(Inventory)-336(\(ST)6.9(AI\))]TJ
14.7455 9.0052 TD
-.0004 Tc
[(Staci)-331.9(Gruber,)]TJ
1.0029 -1.1239 TD
0 Tc
[(PhD/M)7.4(clean)-325.3(Hospital)]TJ
10.25 1.1239 TD
[(Phase)-324.2(2)-4967.1(1)0(6)-751.2(A)0(u)6.9(gust)-331.1(14,)-333.7(2018)-2078.5(Jan)7.9(uary)-331.1(8,)-331.5(2021)]TJ
-62.7876 -10.1291 TD
-.0001 Tc
[(NCT04)5.4(075435)-745.6(Cann)6.7(abidio)5.6(l)-333(Solution)-337.2(f)6.4(or)]TJ
7.5399 -1.1239 TD
0 Tc
[(th)6.2(e)-332.2(Treatmen)6.5(t)-332.4(o)0(f)]TJ
T*
[(Beh)6.8(avioral)-329.1(Sympt)6.6(oms)]TJ
T*
[(in)-328.6(Older)-331.9(Ad)6.6(ults)-334(With)]TJ
T*
[(Alz)8.1(heimers)-327.3(Dement)5.6(ia)]TJ
10.25 4.4955 TD
[(Recr)7.5(uiting)-2532.9(Al)7.9(zheimer)]TJ
7.7462 -1.1239 TD
[(Disease/)8.7(Anxiety/)]TJ
T*
[(Agitati)5.5(on,)]TJ
T*
-.0004 Tc
(Psychomotor)Tj
10.25 3.3716 TD
0 Tc
[(Anxiety)-331.1(Dom)9.9(ain)-333.3(on)-329.6(the)]TJ
1.003 -1.1239 TD
[(Neur)6(opsych)5.9(iatric)-333.6(Inven)7.3(tory-)]TJ
T*
[(Clinicia)6.9(n)-237.6(scale)]TJ
/F12 1 Tf
6.0391 0 TD
(j)Tj
/F9 1 Tf
.5121 0 TD
[(Total)-237.6(score)-241.9(on)-237.2(the)]TJ
-6.5512 -1.1239 TD
[(Ge)6.9(neraliz)6.5(ed)-332.2(Anxiety)-331.1(Dis)6.7(order)-335.1(7)]TJ
T*
[(scal)6.4(e)]TJ
/F12 1 Tf
2.3402 0 TD
(j)Tj
/F9 1 Tf
.569 0 TD
[(Safety)-296.3(defined)-296.6(b)7.2(y)-300.2(absence)]TJ
-2.9093 -1.1239 TD
[(of)-291.9(serious)-285(advers)5.5(e)-296.7(even)10.9(ts)]TJ
/F12 1 Tf
10.8902 0 TD
(j)Tj
/F9 1 Tf
.5619 0 TD
(Safety)Tj
-11.4521 -1.131 TD
-.0002 Tc
[(as)-328.3(defined)-325.2(by)-335.9(lack)-333.3(o)7.3(f)-335.2(treatment)]TJ
0 -1.1239 TD
0 Tc
[(emer)6.8(gent)-328.9(cogniti)5.4(ve)-329.8(impai)6(rment)]TJ
T*
-.0002 Tc
[(as)-328.3(measured)-332.4(by)-328.8(the)-333.4(Mini)-329.3(Me)7.2(ntal)]TJ
T*
[(Status)-330.7(Examinat)6.8(ion)-335.6(\()-82(MMS)8.6(E\))]TJ
T*
0 Tc
[(Saf)7.1(ety)-331.8(defined)-332.1(as)-328.1(absence)-327.9(of)]TJ
T*
[(tre)5.9(atment)-328.1(emerge)6.1(nt)-335.2(d)7.2(elirium)-332.1(as)]TJ
0 -1.131 TD
-.0002 Tc
[(meas)8.8(ured)-330.1(by)-335.9(th)6(e)-332.4(Confusion)]TJ
0 -1.1239 TD
0 Tc
[(Ass)6.9(essme)5.4(nt)-335.2(Me)7.4(thod)-334.8(\(CA)5.9(M\))]TJ
0 7.9702 -7.9702 -0 406.0912 473.9526 Tm
[(Mclean)-327.1(Hospit)5.2(al/Spier)]TJ
1.0029 -1.1239 TD
[(Fami)7(ly)-334.4(Foun)7.5(dation)]TJ
10.25 1.1239 TD
[(Early)-331.9(Phas)8(e)-332.2(1)-2648.2(12)-751.2(Ma)7.7(rch)-336.4(1,)-331.5(202)7.8(0)-2947(N)0(o)9.1(vembe)7.4(r)-339.5(202)7.8(1)]TJ
/F4 1 Tf
8.9663 0 0 8.9663 299.9054 26.2488 Tm
(15)Tj
ET
endstream
endobj
84 0 obj
<>stream
/GS1 gs
BT
/F6 1 Tf
10.959 0 0 10.959 62.022 697.8896 Tm
0 0 0 rg
0 Tc
0 Tw
[(frontline)-389.1(health)-388.6(care)-394.9(professionals)-385.1(who)-392.3(participate)-390.9(in)]TJ
0 -1.1847 TD
[(the)-339.2(care)-338(of)-336.8(patients)-339.6(with)-335.5(COVID-19)-334.8(\(NCT04504877\).)]TJ
0 -1.1795 TD
[(Emerging)-200.3(data)-202.6(from)-200.6(these)-205.8(studies)-202.7(will)-197.7(establish)-202.4(whether)]TJ
0 -1.1847 TD
[(there)-386.9(is)-389.9(potential)-388.1(for)-386.6(a)-390.7(licensed)-386.5(CBD)-391(product)-386.1(in)-388.8(this)]TJ
0 -1.1795 TD
(space.)Tj
/F4 1 Tf
10.4607 0 0 10.4607 62.022 619.8801 Tm
[(Summary)-299.3(and)-298.4(Conclusion)]TJ
/F6 1 Tf
10.959 0 0 10.959 62.022 606.9542 Tm
-.0124 Tc
[(Symptoms)-212.3(of)-212.9(anx)-12.4(i)6.9(ety)-211.4(a).4(nd)-211.5(p)-12.4(o)9.2(st-traumatic)-212(stress)-212.3(ar)-12.4(e)-205(g).7(oing)]TJ
0 -1.1847 TD
-.0131 Tc
[(to)-252.9(be)-254.1(prev)-13.1(a)7.6(l)-1.1(ent)-254.3(a)-.3(s)-254.4(a)-248.6(co)-13.1(n)8.8(s)-.9(equ)-13.1(e)7.2(nce)-254.1(o).6(f)-254.9(t)-.8(he)-254.1(CO)-13.1(V)10.6(I)-.8(D)-13.1(-)9.4(19)-253.2(pan-)]TJ
0 -1.1795 TD
-.0124 Tc
[(demic,)-291(p)-12.4(a)8.2(rticularly)-294.2(in)-293.9(those)-294.8(m)2.9(ost)-295(c).1(losely)-294.2(affected)-294.2(by)-294.2(the)]TJ
0 -1.1847 TD
0 Tc
[(disease,)-352.1(and)-348.8(in)-347.4(those)-349.5(with)-351(pre-existing)-346.8(anxiety)-351.3(condi-)]TJ
0 -1.1795 TD
[(tions.)-520.6(Unlike)-517.2(CBD,)-514.4(current)-522.4(antianxiety)-513.3(medications)]TJ
0 -1.1847 TD
[(possess)-346.4(signicant)-344.2(unwanted)-345(side)-343.7(effects,)-348.6(and)-343.7(delayed)]TJ
0 -1.1795 TD
[(onset)-210.1(of)-207.4(action,)-207.5(limited)-206.3(efcacy)-211.4(in)-207.8(some)-204.9(patients,)-209.5(strong)]TJ
T*
-.0001 Tc
[(drug)-367.8(dependence,)-366.7(and)-364.5(withdrawal)-361.4(syndromes.)-368(Unlike)]TJ
0 -1.1847 TD
0 Tc
[(THC,)-286.9(studies)-290.7(have)-289.4(shown)-289.2(that)-285.2(CBD)-287.5(lacks)-289.2(any)-286.7(reward-)]TJ
0 -1.1795 TD
[(ing)-246.4(effects)-245.8(of)-243.6(its)-243.1(own)-247.8(given)-241.5(that)-243.8(it)-245(fails)-244.8(to)-248.2(induce)-244.7(condi-)]TJ
0 -1.1847 TD
[(tioned)-544.2(place)-542.4(preference)-542.5(or)-543.1(enhance)-545.7(the)-540.9(reinforcing)]TJ
0 -1.1795 TD
-.0001 Tc
[(effects)-344.2(of)-342(electrical)-337.5(brain)-345(self-stimulation.)]TJ
8.2191 0 0 7.3052 245.3102 469.3605 Tm
0 Tc
(7274)Tj
10.959 0 0 10.959 269.0078 464.4849 Tm
[(CBD)-339.3(is)]TJ
-18.8873 -1.1847 TD
[(already)-242.6(being)-240.9(evaluated)-237.7(as)-244(a)-240.7(potential)-238.1(treatment)-241.4(during)]TJ
0 -1.1795 TD
[(the)-401.3(active)-406.2(coronavirus)-402.7(disease)-399.4(phase,)-405.8(and)-400.6(we)-402.1(suggest)]TJ
0 -1.1847 TD
[(that)-223.1(the)-225.4(pre-clinical)-223.6(and)-224.7(clinical)-227.4(evidence)-224.8(base)-223(supports)]TJ
0 -1.1795 TD
[(the)-339.2(hypothesis)-332.3(that)-336.9(CBD)-334.1(could)-339.2(be)-335.9(a)-333.8(novel)-338.8(pharmaco-)]TJ
0 -1.1847 TD
[(logical)-300.1(option)-299.9(for)-298.7(treating)-298.1(COVID-related)-300.1(anxiety)-299.5(dis-)]TJ
0 -1.1795 TD
[(orders)-782.9(that)-781.8(merits)-782.5(testing)-781.7(through)-782.6(well-designed)]TJ
T*
[(clinical)-237.7(trials.)-236.4(CBD)-235.8(could)-235.8(be)-237.6(more)-230.8(preferable)-237(compared)]TJ
0 -1.1847 TD
[(with)-439(some)-437.7(of)-435.1(the)-442.6(medicines)-438.8(currently)-435.2(available)-440.1(with)]TJ
0 -1.1795 TD
[(respect)-207.7(to)-206.8(its)-201.8(safety)-210(and)-204(side)-204.1(effect)-211.5(prole,)-201.5(although)-206.1(pre-)]TJ
0 -1.1847 TD
[(scribers)-242.2(need)-243.5(to)-243(be)-242.8(aware)-245.3(of)-243.6(potential)-243.3(drug)-243.5(interactions)]TJ
0 -1.1795 TD
[(with)-361.4(concomitant)-358.3(medication)-362.6(because)-360.8(of)-357.5(the)-365(effect)-361.5(of)]TJ
0 -1.1847 TD
[(CBD)-297.9(on)-298.9(liver)-300.6(enzymes.)]TJ
/F4 1 Tf
10.4607 0 0 10.4607 62.022 280.1763 Tm
[(Authors)-298.3(Contribution)]TJ
/F6 1 Tf
10.959 0 0 10.959 62.022 267.1936 Tm
[(The)-472.1(article)-477.9(was)-472.3(written,)-474(reviewed,)-476.4(and)-473(approved)-470.8(by)]TJ
0 -1.1795 TD
[(S.E.O.,)-302.6(C.W.S.,)-300.3(and)-302.3(S.R.L.)]TJ
/F4 1 Tf
10.4607 0 0 10.4607 62.022 224.844 Tm
[(Author)-303.3(Disclosure)-299.8(Statement)]TJ
/F6 1 Tf
10.959 0 0 10.959 62.022 211.9181 Tm
[(S.E.O.)-220.5(is)-219.2(a)-220(paid)-223.6(scientic)-218.7(advisor)-221.6(for)-215.9(Artelo)-222.8(Biosciences.)]TJ
0 -1.1847 TD
[(C.W.S.)-233.8(and)-235(S.R.L.)-231.7(receive)-239(research)-230.5(funding)-236.8(from)-231.6(Artelo)]TJ
0 -1.1795 TD
[(Biosciences,)-346.8(who)-345.8(have)-351.4(developed)-345(a)-349.3(CBD)-344.4(cocrystal)-347.1(for)]TJ
T*
[(solid-state)-209.3(delivery.)-209.5(Cocrystals)-208.7(are)-210.8(dened)-211.7(as)-207.8(crystalline)]TJ
0 -1.1847 TD
[(materials)-341.4(composed)-338.9(of)-341.9(two)-342(or)-341.4(more)-344.6(molecules)-339.4(within)]TJ
0 -1.1795 TD
[(the)-385.7(same)-381.7(crystal)-388.8(lattice)-384.7(\(FDA)-380(Guidance)-387.8(for)-386.6(Industry,)]TJ
0 -1.1847 TD
[(2016\).)-228.6(The)-228.9(Artelo)-233.2(CBD)-225.4(cocrystal)-233.3(uses)-229.4(the)-230.5(coformer)-227.3(tet-)]TJ
0 -1.1795 TD
[(ramethylpyrazine)-333(\(TMP\),)-335.5(which)-332(itself)-336.3(has)-333.8(evidence)-338.6(of)]TJ
0 -1.1847 TD
[(activity)-298.9(in)-300.9(anxiety-related)-297.9(disorders)-301(or)-300(PTSD.)]TJ
8.2191 0 0 7.3052 262.148 113.159 Tm
(75,76)Tj
/F4 1 Tf
10.4607 0 0 10.4607 62.022 82.3748 Tm
[(Funding)-301.1(Information)]TJ
/F6 1 Tf
10.959 0 0 10.959 62.022 69.4488 Tm
[(Funding)-302.6(was)-296.4(provided)-301.2(by)-299.1(Artelo)-300.4(Biosciences.)]TJ
/F4 1 Tf
10.4607 0 0 10.4607 313.0582 698.2297 Tm
(References)Tj
/F9 1 Tf
7.4718 0 0 7.4718 316.7999 688.2518 Tm
[(1.)-507(Alves)-304.5(P,)-296.3(Amaral)-309.1(C,)-300.9(Teixeira)-307.1(N,)-300.3(et)-301(al.)]TJ
/F11 1 Tf
16.0704 0 TD
[(Cannab)-12.8(is)-298.2(sativa)]TJ
/F9 1 Tf
6.457 0 TD
[(:)-296.2(much)-305.5(more)-307.9(beyond)]TJ
/F8 1 Tf
-21.3134 -1.1988 TD
(D)Tj
/F9 1 Tf
.6677 0 TD
[(9-tetrahydrocannabi)-19.1(nol.)-302.1(Pharmacol)-306.6(Res.)-304.3(2020;157:104)-14.7(822.)]TJ
-1.8817 -1.1988 TD
[(2.)-507(Lattanzi)-303.4(S,)-308(Brigo)-303.8(F,)-302.8(Trinka)-298.8(E,)-308(et)-301(al.)-301.4(Efcacy)-303.8(and)-303.9(safety)-306.9(of)-298.6(can)-9.2(nabidiol)]TJ
1.214 -1.2064 TD
[(in)-296.4(epileps)-12.6(y:)-298.6(a)-302.5(systematic)-306.8(review)-306.4(and)-303.9(meta-analysis.)-309.8(Drugs.)-303.8(2018;78:)]TJ
0 -1.1988 TD
(17911804.)Tj
-1.214 -1.1988 TD
[(3.)-507(Ibeas)-301(Bih)-301.8(C,)-308.4(Chen)-297.6(T,)-308(Nunn)-301.6(AVW,)-300.4(et)-301(al.)-301.4(Molecu)-13(lar)-297.8(targets)-310(of)-298.6(cannab)-9.6(idiol)]TJ
1.214 -1.1988 TD
[(in)-296.4(neuro)-10(logical)-306.3(disorders.)-307.6(Neurotherapeut)-17.2(ics.)-302.7(2015;12:699730.)]TJ
-1.214 -1.1988 TD
[(4.)-507(Bian)-300.8(Y)-303.6(min,)-298.4(He)-304.2(X)-303(bing,)-305.7(Jing)-298.6(Y)-303.6(kang,)-301.5(et)-301(al.)-301.4(Comp)-11.1(utational)-304.7(systems)-303.8(ph)-9(ar-)]TJ
1.214 -1.1988 TD
[(macology)-303.3(an)-8.5(alysis)-301.4(of)-306.1(cannabidiol:)-306.5(a)-302.5(combination)-305.2(of)-306.1(chemogenomics)-13.2(-)]TJ
T*
[(knowledgebase)-313.1(network)-306.7(analysis)-302.3(and)-303.9(integrated)-311.3(in)-296.4(silico)-304.9(modeling)-304.2(and)]TJ
0 -1.2064 TD
[(simulation.)-309.2(Acta)-302.9(Pharmaco)-12(l)-294.5(Sin.)-308.5(2019;40:374386.)]TJ
-1.214 -1.1988 TD
[(5.)-507(OSullivan)-305.1(SE.)-304.6(An)-300.8(update)-304.3(on)-303.1(PPAR)-306.9(activation)-306.7(by)-305.4(cannabinoids.)-309.4(Br)-297.9(J)]TJ
1.214 -1.1988 TD
[(Pharmacol.)-306.9(2016;173)-11.7(:18991910.)]TJ
-1.214 -1.1988 TD
[(6.)-507(Muller)-305.9(C,)-300.9(Morales)-305.8(P,)-303.9(Reggio)-304.6(PH.)-303.9(Cannabinoid)-305.9(ligands)-302.7(targe)-10.3(ting)-302.6(TRP)]TJ
1.214 -1.1988 TD
[(channels.)-308.2(Front)-303.1(Mol)-302.2(Neurosci.)-307.3(2019;11:)-13.6(487.)]TJ
-1.214 -1.1988 TD
[(7.)-507(Chesney)-308(E,)-300.4(Oliver)-300.8(D,)-307.9(Green)-303.6(A,)-299.2(et)-301(al.)-301.4(Adverse)-310.5(effects)-304.3(of)-298.6(can)-9.2(nabidiol:)]TJ
1.214 -1.2064 TD
[(a)-302.5(systematic)-306.8(review)-306.4(and)-303.9(meta-analysis)-309.6(of)-298.6(rando)-10(mized)-302(clinical)-300.3(trials)-12(.)]TJ
0 -1.1988 TD
[(Neuropsycho)-14.1(pharmacology.)-308.3(2020;45:1799)-14.7(1806.)]TJ
-1.214 -1.1988 TD
[(8.)-507(dos)-300.3(Sant)-9.4(os)-300.8(RG,)-303.9(Guimara)]TJ
10.9261 .0152 TD
()Tj
.387 -.0152 TD
[(es)-296.3(FS,)-307(Crippa)-301.5(JAS,)-303.6(et)-301(al.)-309(Serious)-306.4(adverse)-306.5(effects)]TJ
-10.099 -1.1988 TD
[(of)-298.6(canna)-10.1(bidiol)-303.7(\(CBD\):)-302.2(a)-302.5(review)-306.4(of)-298.6(randomized)-312(controlled)-307.6(trials.)-308.2(Expert)]TJ
T*
[(Opin)-299.4(Drug)-303.9(Metab)-309.4(Toxicol.)-306.2(2020;16:5175)-15.5(26.)]TJ
-1.214 -1.1988 TD
[(9.)-507(Hill)-299.4(KP.)-309.2(Cannabinoids)-305.5(and)-303.9(the)-302.9(coronavirus.)-311.9(Cannabis)-307.7(Cannabinoid)-305.9(Res.)]TJ
1.214 -1.1988 TD
(2020;5:118120.)Tj
-1.7148 -1.2064 TD
[(10.)-505.4(Byrareddy)-313.5(SN,)-304.5(Mohan)-298.8(M.)-306.1(SARS-CoV2)-304.1(induced)-309.8(respiratory)-310.7(distress:)-309.9(can)]TJ
1.7224 -1.1988 TD
[(cannab)-9.6(inoids)-299.4(be)-303.8(added)-301.8(to)-305.5(anti-viral)-308.5(therapies)-304.7(to)-305.5(reduce)-307.3(lung)-303.7(inamma-)]TJ
T*
[(tion?)-305.6(Brain)-305.1(Behav)-302(Immun.)-305.4(2020;87:)-13.6(120121.)]TJ
-1.7224 -1.1988 TD
[(11.)-505.4(Costiniuk)-309.1(CT,)-305.1(Jenabian)-304.5(MA.)-301.5(Acute)-310(inammation)-311.5(and)-296.3(patho)-10(genesis)-299.1(of)]TJ
1.7224 -1.1988 TD
[(SARS-CoV-)-11.3(2)-301.9(infection:)-305.7(cannabidio)-11.7(l)-294.5(a)0(s)-302.1(a)-302.5(potential)-308.3(anti-inamm)-11.8(atory)]TJ
T*
[(treatment)-13.7(?)-295.5(Cytokin)-12.1(e)-296.7(Growth)-311.1(Factor)-300.9(Rev.)-303.7(2020;53:)-13.6(6365.)]TJ
-1.7224 -1.2064 TD
.0221 Tc
[(1)22.1(2)22.1(.)-483.3(Wa)-7.3(ng)-306.1(B)-6(,)-304.4(Ko)-6(valchuk)-306.6(A,)-304.4(Li)-302.8(D)-4.8(,)-304.4(et)-308.4(al.)-304.4(I).7(n)-306.1(s)-.2(ear)-4.9(c)-1.3(h)-306.1(o)1.6(f)-309.1(p)-.1(revent)-4.9(ative)-312.5(s)-.2(tr)-4.9(ategies:)]TJ
1.7224 -1.1988 TD
.0238 Tc
[(novel)-399.7(a)2(nt)4.4(i-)7.1(inammat)4.4(o)-4.3(r)4.4(y)-403.5(h)6.7(i)2.4(gh-CBD)]TJ
/F11 1 Tf
15.5848 0 TD
.0236 Tc
[(C)6.5(a)-2.7(nnabis)-295.3(s).6(ativa)]TJ
/F9 1 Tf
7.0564 0 TD
.0249 Tc
[(ex)4.9(tr)5.5(a)3.1(c)1.5(ts)-300.9(m)8.1(o)-3.2(du)4.4(-)]TJ
-22.6412 -1.1988 TD
.0218 Tc
[(lat)-5.2(e)-297.7(ACE)-5.2(2)-302.8(expr)-5.2(e)5.9(s)-8.1(sion)-298.8(i)-7.2(n)-298.8(CO)-4.4(VID-19)-302.8(gateway)-306.9(t)2.4(issu)-6.3(es.)-297.2(P)-1.1(r)-5.2(e)-1.7(print)-5.2(.)-297.2(20)-6.9(20;0:)]TJ
T*
.0223 Tc
[(11)-6.4(2)1.2(.)]TJ
-1.7224 -1.1988 TD
0 Tc
[(13.)-505.4(Esposito)-281.9(G,)-273.4(Pesce)-267.5(M,)-275.7(Seguella)-274.9(L,)-268.3(et)-270.6(al.)-278.7(The)-264.9(pote)-9.9(ntial)-268(of)-275.8(cannabidiol)-275.9(in)-273.7(the)]TJ
1.7224 -1.1988 TD
[(COVID-19)-307(pandem)-9.9(ic:)-303.1(a)-294.9(hypothesi)-14.3(s)-295.5(letter.)-309.2(Br)-305.5(J)-296.1(Pharmaco)-12(l.)-294.8(2020.D)-13.1(OI:)]TJ
T*
[(10.1111/b)-13.7(ph.15157.)]TJ
-1.7224 -1.2064 TD
[(14.)-505.4(Dutheil)-309.6(F,)-302.8(Mondillon)-300.5(L,)-306.2(Navel)-305.1(V.)-298.1(PTSD)-308.6(as)-294.5(the)-302.9(second)-311.2(tsunami)-306.3(of)-298.6(the)]TJ
1.7224 -1.1988 TD
[(SARS-Cov2)-308.8(pandem)-9.9(ic.)-303.1(Psychol)-304.6(Med.)-306.4(2020;12.)-302.7(DOI:)]TJ
T*
[(10.1017/S00)-15.1(33291720001336.)]TJ
-1.7224 -1.1988 TD
[(15.)-505.4(Ro)]TJ
2.3825 .0076 TD
()Tj
.4173 -.0076 TD
[(hr)-203.4(S,)-201.8(Mu)]TJ
2.8984 0 TD
[()-118.7(ller)-207.2(F,)-204.2(Jung)-206.6(F,)-204.2(et)-202.3(al.)-202.8(Psychosocial)-209.2(impact)-208.6(of)-207.5(quarantine)-204.3(mea)-9.1(sures)]TJ
-3.9759 -1.1988 TD
[(during)-208.8(serious)-203.1(cor)-10.3(onavirus)-202.8(outbreak)-13.3(s:)-197.1(a)-203.9(rapid)-205.8(review.)-200.5(Psy)-9.7(chiatr)-206.1(Prax.)-205.9(2020;)]TJ
T*
[(47:17918)-12.5(9.)]TJ
-1.7224 -1.2064 TD
.0216 Tc
[(1)21.6(6)21.6(.)-483.8(Wu)-401(P,)-396(Fang)-405.2(Y)6.3(,)-403.6(G)-1.1(uan)-397.6(Z)4.5(,)-403.6(e)5.7(t)-400(a)-.2(l.)-396(T)-5.4(h)4.5(e)-396.5(p)-.6(sychological)-394.3(impa)7.4(ct)-400(of)-400.6(the)]TJ
1.7224 -1.1988 TD
.0214 Tc
[(SA)-4.4(RS)-392.5(epidemic)-396.6(on)-397.8(hospital)-394.5(employees)-395.5(i)0(n)-397.8(C)-6(hina)7.2(:)-403.8(E)2(xposure,)-396.2(r)-5.6(i)7.6(sk)-405.9(p)6.7(e)-2.1(r-)]TJ
T*
.0212 Tc
[(cep)6.5(t)-5.8(ion,)-396.4(and)-395.6(a)-.6(ltruistic)-396.8(a)-.6(cc)5.4(eptance)-396.9(o).7(f)-393.4(r)1.8(isk.)-396.4(Can)-398(J)-396.3(P)5.9(s)-1.1(yc)5.4(hiatry.)-388.8(2009;54:)]TJ
T*
.0214 Tc
(302311.)Tj
-1.7224 -1.1988 TD
0 Tc
[(17.)-505.4(Liu)-302.3(N,)-307.9(Zhang)-302.6(F,)-295.2(Wei)-309.7(C,)-300.9(et)-301(al.)-301.4(Prevalence)-309.6(and)-296.3(predi)-10.3(ctors)-302.4(of)-306.1(PTSS)-301.1(during)]TJ
1.7224 -1.1988 TD
[(COVID-19)-238.7(outbreak)-241(in)-228.1(China)-233.8(hardest-h)-12.7(it)-230.5(areas:)-238.2(gender)-236.8(differences)-236.8(matter.)]TJ
T*
[(Psychi)-10.9(atry)-298.3(Res.)-304.3(2020;287)-11.7(:112921.)]TJ
-1.7224 -1.2064 TD
[(18.)-505.4(Wang)-305.6(C,)-300.9(Pan)-304.6(R,)-303.9(Wan)-303.7(X,)-295.7(et)-301(al.)-309(A)-298.9(longitudinal)-309.6(study)-307(on)-295.5(the)-302.9(mental)-309.8(health)]TJ
1.7224 -1.1988 TD
[(of)-306.1(general)-303.2(population)-305.7(during)-307.4(the)-302.9(COVID-19)-307(epidemic)-303.7(in)-304(China.)-302.3(Brain)]TJ
T*
[(Behav)-302(Imm)-9.5(un.)-303.4(2020.)-304.9(DOI:)-302.4(10.1016/j.bbi.2020)-17.3(.04.028.)]TJ
-1.7224 -1.1988 TD
[(19.)-505.4(Liang)-307.4(L,)-298.6(Ren)-306.3(H,)-296.2(Cao)-304.9(R,)-303.9(et)-301(al.)-301.4(The)-302.8(effect)-304.7(of)-306.1(COVID-19)-307(on)-303.1(youth)-300(mental)]TJ
1.7224 -1.1988 TD
[(health.)-310.3(Psychiatr)-306.9(Q.)-299.7(2020.)-304.9(DOI:)-302.4(10.1007/s)-13.7(11126-020-09744-)-13.8(3.)]TJ
-1.7224 -1.1988 TD
[(20.)-505.4(Guo)-306.5(Q,)-299.7(Zheng)-304.3(Y,)-303.9(Shi)-300.7(J,)-304(et)-301(al.)-301.4(Immediate)-308.4(psychological)-308.2(distress)-309.7(in)]TJ
1.7224 -1.2064 TD
[(quaranti)-12(ned)-298.1(patients)-311.5(with)-300.1(COVID-19)-307(and)-303.9(its)-298.4(assoc)-11.7(iation)-303.7(with)-300.1(peripheral)]TJ
0 -1.1988 TD
[(inammatio)-13.7(n:)-298.1(a)-302.5(mixed-method)-308.7(study.)-307.3(Brain)-305.1(Behav)-302(Immun.)-305.4(2020.)-304.9(DOI:)]TJ
T*
[(10.1016/j.bb)-17.3(i.2020.05.038.)]TJ
-1.7224 -1.1988 TD
[(21.)-505.4(Chew)-211.6(NWS,)-212.7(Lee)-208.9(GKH,)-210.4(Tan)-210(BYQ,)-206.5(et)-209.9(al.)-202.8(A)-207.9(mult)-9.9(inational,)-212.5(multicentre)-210.9(study)-215.9(on)]TJ
1.7224 -1.1988 TD
[(the)-249.8(psycholo)-13.3(gical)-249.3(outcomes)-258.1(and)-243.2(asso)-11(ciated)-245.7(phys)-11(ical)-247.4(symptoms)-256.8(amongst)]TJ
T*
[(healthcare)-231.3(workers)-228.5(during)-224(COVID-19)-223.5(outbre)-11.9(ak.)-221.8(Brain)-221.6(Behav)-226.1(Immun.)-229.5(2020.)]TJ
0 -1.2064 TD
[(DOI:)-302.4(10.1)-10.6(016/j.bbi.2020.04.049.)]TJ
-1.7224 -1.1988 TD
[(22.)-505.4(Lai)-220.1(J,)-220.5(Ma)-213.8(S,)-216.9(Wang)-222.1(Y,)-212.9(et)-217.5(al.)-218(Fact)-10.6(ors)-214(assoc)-11.7(iated)-214.7(with)-216.7(mental)-226.3(health)-219(outcomes)]TJ
1.7224 -1.1988 TD
[(among)-305.7(health)-302.4(care)-308.3(workers)-304.4(exposed)-306.2(to)-305.5(coronavirus)-311.7(disease)-301.4(2019.)-304.9(JAMA)]TJ
T*
[(Netw)-304.5(Open.)-301.9(2020;3:e2)-14.4(03976.)]TJ
-1.7224 -1.1988 TD
[(23.)-505.4(Xiong)-265.2(J,)-258.5(Lipsitz)-258.9(O,)-261.7(Nasri)-256(F,)-264.9(et)-255.4(al.)-255.9(Impact)-269.3(of)-253(COVID-19)-269.1(pandemic)-259.7(on)-257.6(mental)]TJ
1.7224 -1.1988 TD
[(health)-294.8(in)-288.9(the)-295.3(general)-295.7(population:)-298.4(a)-294.9(systematic)-299.2(review.)-291.6(J)-296.1(Affect)-291.8(Dis.)-298.5(2020;)]TJ
T*
[(277:5564)-12.5(.)]TJ
-1.7224 -1.2064 TD
[(24.)-505.4(Papagianni)-310.8(EP,)-300.5(Stevenson)-306.1(CW.)-307.7(Cannabinoid)-305.9(regula)-9.9(tion)-298.4(of)-306.1(fear)-297.3(and)]TJ
1.7224 -1.1988 TD
[(anxiet)-9.5(y:)-298.6(an)-304.4(update.)-304.6(Curr)-306.9(Psychiatry)-309.3(Rep.)-304.2(2019;21:38.)]TJ
/F4 1 Tf
9.9626 0 0 9.9626 62.022 754.3557 Tm
(16)Tj
40.6704 0 TD
[(OSULLIVA)-10.2(N)-303.2(E)0(T)-299.4(AL.)]TJ
ET
endstream
endobj
88 0 obj
<>stream
/GS1 gs
BT
/F9 1 Tf
7.4718 0 0 7.4718 59.7543 700.2707 Tm
0 0 0 rg
0 Tc
0 Tw
[(25.)-505.4(Singewald)-307.5(N,)-300.3(Schmucker)-14.4(mair)-299.5(C,)-300.9(Wh)-8.7(ittle)-302.5(N,)-300.3(et)-301(al.)-301.4(Pharmaco)-12(logy)-296.6(of)]TJ
1.7224 -1.2064 TD
[(cognitive)-307.1(enhancers)-306.8(for)-302.8(expos)-10(ure-based)-306.2(therapy)-308.1(of)-298.6(fear,)-305.2(anxiety)-307.8(and)]TJ
0 -1.1988 TD
[(trauma-re)-12.6(lated)-298.1(disorders.)-315.2(Pharmacol)-306.6(Ther.)-307.4(2015;149:150190.)]TJ
-1.7224 -1.1988 TD
[(26.)-505.4(Corroon)-311.8(J,)-296.4(Phi)-8.3(llips)-298.4(JA.)-307(A)-298.9(cross-secti)-14.8(onal)-300.8(study)-307(of)-298.6(cannab)-9.6(idiol)-296.6(users.)]TJ
1.7224 -1.1988 TD
[(Cannabis)-307.7(Cannabinoid)-305.9(Res.)-304.3(2018;3:1)-13.6(52161.)]TJ
-1.7224 -1.1988 TD
[(27.)-505.4(Wheeler)-309.9(M,)-298.5(Merten)-302.7(JW,)-303.2(Gordon)-312.2(BT,)-298.1(et)-301(al.)-309(CBD)-302.4(\(cannabidiol\))-305.7(product)]TJ
1.7224 -1.1988 TD
[(attitudes,)-311.8(knowledge,)-306.9(and)-303.9(use)-301.6(among)-305.7(young)-305.2(adults.)-302.5(Subst)-308.8(Use)-303.8(Misuse.)]TJ
0 -1.2064 TD
[(2020;55:1138)-14.7(1145.)]TJ
-1.7224 -1.1988 TD
[(28.)-505.4(Tran)-305.3(T,)-300.4(Kavuluru)-310.6(R.)-303.9(Social)-302.4(media)-303.1(surveillance)-310.8(for)-302.8(perceived)-307.5(therapeutic)]TJ
1.7224 -1.1988 TD
[(effects)-304.3(of)-306.1(cannabidiol)-306.3(\(CBD\))-309.5(products.)-307(Int)-300.7(J)-303.7(Drug)-303.9(Policy.)-309.6(2020;77:)]TJ
T*
(102688.)Tj
-1.7224 -1.1988 TD
[(29.)-505.4(Liebling)-283.2(JP,)-289(Clarkson)-281.4(NJ,)-285.4(Gibbs)-285.5(BW,)-285.6(et)-278.2(al.)-278.7(An)-285.6(analysis)-287.1(of)-283.4(over-the-counter)]TJ
1.7224 -1.1988 TD
[(cannab)-9.6(idiol)-243.5(products)-253.6(in)-243.3(the)-249.8(United)-247.8(Kingdom.)-249.7(Cannabis)-254.6(Cannabinoid)-252.8(Res.)]TJ
T*
[(2020;can.20)-15.2(19.0078.)-301.9(DOI:10)-10.9(.1089/can.2019.0078)]TJ
-1.7224 -1.2064 TD
[(30.)-505.4(Fusar-Poli)-284.6(P,)-281.2(Crippa)-278.7(JA,)-276.7(Bhattachary)-14.6(ya)-274.6(S,)-277.6(et)-278.2(al.)-278.7(Distinct)-285.2(effects)-281.5(of)-275.8({delta}9-)]TJ
1.7224 -1.1988 TD
[(tetrahydr)-13.2(ocannabinol)-300.2(and)-288.7(cannabidio)-11.7(l)-287(o)0(n)-295.5(neural)-290.7(activation)-299.1(during)-299.8(emo-)]TJ
T*
[(tional)-303.7(processing.)-315.9(Arch)-298.2(Gen)-306.1(Psychiatry.)-309.6(2009;66:9510)-15.5(5.)]TJ
-1.7224 -1.1988 TD
[(31.)-505.4(Linares)-264.6(IM,)-259.2(Zuar)-10.5(di)-256.1(AW,)-260.5(Pereira)-265.9(LC,)-265.4(et)-255.4(al.)-263.5(Cannabidiol)-264.7(present)-11.1(s)-257.5(a)0(n)-258.9(inverted)]TJ
1.7224 -1.1988 TD
[(U-shaped)-305.2(dose-r)-10.9(esponse)-303.3(curve)-306(in)-304(a)-294.9(simula)-10.4(ted)-300.5(public)-305.7(speaking)-307.2(test.)]TJ
T*
[(Revista)-305(brasileira)-305.8(de)-303.8(psiquiat)-12(ria)-297.8(\(Sao)-304.2(Paulo,)-304.6(Brazil:)-307.6(1999\).)-304.6(2019;41:)]TJ
0 -1.2064 TD
(914.)Tj
-1.7224 -1.1988 TD
[(32.)-505.4(Zuardi)-304.6(AW,)-306(Cosme)-307.9(RA,)-299.4(Graeff)-309.8(FG,)-302.8(et)-301(al.)-301.4(Effects)-307.7(of)-298.6(ipsapi)-10(rone)-300.6(and)-303.9(canna-)]TJ
1.7224 -1.1988 TD
[(bidiol)-303.7(on)-303.1(human)-305.7(experimental)-311(anxiety.)-300.5(J)-303.7(Psychophar)-14.7(macol.)-301.5(1993;7:)]TJ
T*
(8288.)Tj
-1.7224 -1.1988 TD
[(33.)-505.4(Jadoon)-307.2(KA,)-304.5(Tan)-301(GD,)-300.3(OSullivan)-312.6(SE.)-304.6(A)-298.9(single)-304.9(dose)-301.1(of)-306.1(cannabidiol)-306.3(reduces)]TJ
1.7224 -1.1988 TD
[(blood)-220.7(pressure)-218.9(in)-213(healthy)-221.4(volunteers)-217.2(in)-213(a)-219.1(randomized)-220.9(crossover)-223.7(study.)-216.2(JCI)]TJ
0 -1.2064 TD
[(Insight.)-310.6(2017;2:e93760.)]TJ
-1.7224 -1.1988 TD
[(34.)-505.4(Zuardi)-304.6(AW,)-306(Rodrigues)-311.3(NP,)-300.5(Silva)-303(AL,)-301.7(et)-301(al.)-301.4(Inverted)-305.1(U-sh)-10.5(aped)-302.3(dose-)]TJ
1.7224 -1.1988 TD
[(response)-307.6(curve)-306(of)-298.6(the)-302.9(anxio)-9.7(lytic)-300.6(effect)-304.7(of)-306.1(cannabidiol)-306.3(during)-307.4(public)]TJ
T*
[(speaking)-307.3(in)-304(real)-298.6(life.)-306.8(Front)-303.1(Pharmacol.)-306.9(2017;8:2)-13.6(59.)]TJ
-1.7224 -1.1988 TD
[(35.)-505.4(de)-296.2(Souza)-300.1(Crippa)-293.9(JA,)-299.4(Zuardi)-297(AW,)-298.5(Garrido)-299.3(GEJ,)-293(et)-293.4(al.)-301.4(Effects)-300.1(of)-291(cannab)-9.6(idiol)]TJ
1.7224 -1.1988 TD
[(\(CBD\))-241.2(on)-234.8(regional)-245.7(cerebral)-243.2(blood)-235.9(ow.)-243.8(Neuropsychopharmacolo)-21.8(gy.)-232.3(2004;)]TJ
T*
[(29:41742)-12.5(6.)]TJ
-1.7224 -1.2064 TD
[(36.)-505.4(Sultan)-309.3(SR,)-300.5(OSullivan)-305.1(SE,)-304.6(England)-303(TJ.)-308.2(The)-302.8(effects)-304.3(of)-298.6(acute)-306(and)-303.9(sustained)]TJ
1.7224 -1.1988 TD
[(cannab)-9.6(idiol)-296.6(dosi)-10.6(ng)-299.7(for)-302.8(seven)-305.6(days)-304(on)-295.5(the)-302.9(haemody)-10.6(namics)-305(in)-304(healthy)]TJ
T*
[(men:)-308.1(a)-294.9(rando)-10(mised)-303.6(controlled)-307.6(trial.)-301(Br)-305.5(J)-303.7(Clin)-299.7(Pharmaco)-12(l.)-294.8(2020;86)-13.3(:1125)]TJ
T*
(1138.)Tj
-1.7224 -1.1988 TD
[(37.)-505.4(Bergamas)-11.6(chi)-289.5(MM,)-293.2(Queiroz)-288.9(RHC,)-293.4(Chagas)-294.4(MHN,)-295(et)-293.4(al.)-286.3(Cannabidiol)-295.1(redu)-9.9(ces)]TJ
1.7224 -1.1988 TD
[(the)-302.9(anxiety)-307.8(induced)-302.2(by)-305.4(simulated)-310.9(public)-298.2(speaking)-307.3(in)-304(treatment-nave)]TJ
0 -1.2064 TD
[(social)-305.4(phobia)-307.4(patients.)-304.2(Neurop)-11.7(sychopharmacology.)-318.2(2011;36:12191226)-16.6(.)]TJ
-1.7224 -1.1988 TD
[(38.)-505.4(Masataka)-308.2(N.)-300.3(Anxiolyt)-11.5(ic)-295.2(effects)-311.9(of)-298.6(repeated)-312.4(cannabidiol)-306.3(treatment)-309.6(in)]TJ
1.7224 -1.1988 TD
[(teenage)-9.5(rs)-299.7(with)-300.1(socia)-10.8(l)-294.5(anxiet)-9.5(y)-298.3(disorders.)-307.6(Front)-310.7(Psychol.)-304.9(2019;10:2466)-14.7(.)]TJ
-1.7224 -1.1988 TD
[(39.)-505.4(Crippa)-309.1(JAS,)-303.6(Derenusson)-304.3(GN,)-307.9(Ferrari)-306.2(TB,)-305.7(et)-301(al.)-301.4(Neural)-300.5(basis)-307.4(of)-298.6(anxio)-9.7(lytic)]TJ
1.7224 -1.1988 TD
[(effects)-304.3(of)-306.1(cannabidiol)-306.3(\(CBD\))-309.5(in)-296.4(generalized)-307.7(social)-305.3(anxiety)-307.8(disorder:)-308(a)]TJ
T*
[(prelimina)-10.6(ry)-302.6(report.)-307(J)-296.1(Psyc)-10.4(hopharmacol.)-305.8(2011;25:)-13.6(121130.)]TJ
-1.7224 -1.1988 TD
[(40.)-505.4(Bhattachary)-14.6(ya)-297.4(S,)-300.4(Wilson)-306.8(R,)-303.9(Appiah-Kusi)-307.8(E,)-300.4(et)-308.6(al.)-301.4(Effect)-300.5(of)-306.1(cannabidiol)-306.3(on)]TJ
1.7224 -1.2064 TD
[(medial)-301.7(tempo)-11.5(ral,)-298.1(midbr)-11.1(ain,)-295.8(an)-8.5(d)-295.4(striatal)-311.2(dysfunction)-312.8(in)-296.4(people)-308(at)-299.2(clinical)]TJ
0 -1.1988 TD
[(high)-285.1(risk)-278.1(of)-283.4(psychosis:)-288.2(a)-279.8(randomized)-281.6(clinical)-285.1(trial.)-285.9(JAMA)-281.7(Psychiatry.)-286.8(2018;)]TJ
T*
[(75:11071)-12.5(117.)]TJ
-1.7224 -1.1988 TD
[(41.)-505.4(Appiah-Kus)-13.3(i)-271.8(E)0(,)-270(Petros)-279.9(N,)-277.6(Wilson)-276.4(R,)-273.6(et)-270.6(al.)-278.7(Effects)-277.3(of)-275.8(short-term)-278.2(cannab)-9.6(idiol)]TJ
1.7224 -1.1988 TD
[(treatment)-309.6(on)-303.1(response)-307.6(to)-297.9(socia)-10.8(l)-294.5(stress)-311.5(in)-296.4(subject)-13.9(s)-295.5(a)0(t)-306.8(clinical)-300.3(high)-307.8(risk)]TJ
T*
[(of)-306.1(developing)-301.9(psych)-11.7(osis.)-299.3(Psyc)-10.4(hopharmacology.)-307.9(2020;23)-13.3(7:1121)]TJ
0 -1.2064 TD
(1130.)Tj
-1.7224 -1.1988 TD
[(42.)-505.4(de)-303.8(Faria)-303.5(SM,)-302.7(de)-303.8(Morais)-305(Fabr)]TJ
13.4224 .0228 TD
()Tj
.258 -.0228 TD
[(cio)-308.1(D,)-300.3(Tumas)-305.7(V,)-298.1(et)-301(al.)-301.4(Effect)-12.2(s)-295.5(o)0(f)-306.2(acute)-306(can-)]TJ
-11.958 -1.1988 TD
[(nabidio)-10.1(l)-294.5(administra)-14.1(tion)-298.4(on)-303.1(anxiety)-307.8(and)-303.9(tremors)-308.5(induced)-302.2(by)-305.4(a)-294.9(simula)-10.4(ted)]TJ
T*
[(public)-305.7(speaking)-307.3(test)-304.8(in)-304(patients)-303.9(with)-300.1(Parkinson)-13.2(s)-303.3(disease.)]TJ
T*
[(J)-303.7(Psychopharmacol.)-316.3(2020;34:189196.)]TJ
-1.7224 -1.1988 TD
[(43.)-505.4(Hurd)-221.5(YL,)-215.3(Sprigg)-10.4(s)-212(S)0(,)-216.9(Alishayev)-223.1(J,)-220.5(et)-209.9(al.)-218(Cannabid)-11.7(iol)-215(for)-219.4(the)-219.4(reduction)-217.9(of)-222.7(cue-)]TJ
1.7224 -1.1988 TD
[(induced)-309.8(craving)-301.4(and)-303.9(anxiety)-307.8(in)-296.4(drug-a)-11.5(bstinent)-306.7(individuals)-301.9(with)-307.7(heroin)]TJ
0 -1.2064 TD
[(use)-301.6(disorder:)-308(a)-302.5(double-)-10.6(blind)-301.6(randomized)-304.4(placebo)-11(-controlled)-309.1(trial.)]TJ
0 -1.1988 TD
[(Am)-300.6(J)-303.7(Psychiatry.)-309.6(2019;176)-11.7(:911922.)]TJ
-1.7224 -1.1988 TD
[(44.)-505.4(Shannon)-243.8(S,)-239.7(Lewis)-236.1(N,)-239.6(Lee)-239.2(H,)-235.4(et)-240.3(al.)-240.7(Cannabidiol)-242(in)-235.7(anxiet)-9.5(y)-237.6(and)-235.6(sleep:)-242.4(a)-234.2(large)]TJ
1.7224 -1.1988 TD
[(case)-303.5(series.)-307.4(Perm)-302.8(J.)-304(2019;23:18041.)]TJ
-1.7224 -1.1988 TD
[(45.)-505.4(Laczkovics)-309.2(C,)-300.9(Kothg)-11.1(assner)-301(OD,)-303.8(Felnhofer)-305.9(A,)-306.8(et)-301(al.)-301.4(Cannabidiol)-310.2(treatment)]TJ
1.7224 -1.1988 TD
[(in)-304(an)-296.8(adoles)-10.4(cent)-303.6(with)-300.1(multiple)-303.3(subs)-11.5(tance)-302.6(abuse,)-308(social)-305.4(anxiety)-300.2(and)]TJ
0 -1.2064 TD
[(depress)-11.6(ion.)-302(Neuropsychiatrie.)-310.6(2020.)-304.9(DOI:)-310(10.1007/s40211-)-14.7(020-00334-0.)]TJ
-1.7224 -1.1988 TD
[(46.)-505.4(Klier)-303.6(CM,)-303.2(de)-303.8(Gier)-299.6(C,)-308.4(Felnhofer)-305.9(A,)-299.2(et)-301(al.)-301.4(A)-306.5(case)-303.5(report)-306.7(of)-298.6(cannabidio)-11.7(l)]TJ
1.7224 -1.1988 TD
[(treatment)-309.6(of)-298.6(a)-302.5(crohns)-309.8(disease)-301.4(patie)-9.8(nt)-302.1(with)-300.1(anxiety)-307.8(disorder.)-308(J)-303.7(Clin)]TJ
T*
[(Psychophar)-14.7(macol.)-301.5(2020;40:9092)-15.5(.)]TJ
-1.7224 -1.1988 TD
[(47.)-505.4(Elms)-262(L,)-260.7(Shann)-8.9(on)-257.6(S,)-262.5(Hughes)-267.4(S,)-254.9(et)-263(al.)-263.5(Cannabidiol)-264.7(in)-266.1(the)-257.3(treatment)-271.7(of)-260.6(post-)]TJ
1.7224 -1.1988 TD
[(traumatic)-290.3(stress)-288.8(disorder:)-292.9(a)-279.8(case)-288.4(series.)-284.6(J)-280.9(Altern)-286(Comp)-11.1(lement)-281.2(Med.)-283.6(2019;)]TJ
T*
[(25:39239)-12.5(7.)]TJ
31.8829 85.2005 TD
[(48.)-505.4(Shannon)-281.7(S,)-277.6(Opila-Lehman)-289.2(J.)-281.2(Effectiveness)-285.6(of)-283.4(cannabidiol)-283.5(oil)-283.3(for)-280.1(pediatric)]TJ
1.7224 -1.2064 TD
[(anxiety)-300.2(and)-303.9(insomnia)-310.1(as)-294.5(par)-10.4(t)-300.2(o)0(f)-298.6(posttrauma)-14.6(tic)-299.5(stress)-303.9(diso)-10.6(rder:)-305(a)-294.9(case)]TJ
0 -1.1988 TD
[(report.)-307(Perm)-302.8(J.)-296.4(201)-10.3(6;20:16-005.)]TJ
-1.7224 -1.1988 TD
[(49.)-505.4(Gulbransen)-246.1(G,)-235.5(Xu)-240(W,)-242.3(Arroll)-241.8(B.)-240.8(Cannabidiol)-249.5(prescription)-244.9(in)-243.3(clinical)-239.6(practice:)]TJ
1.7224 -1.1988 TD
[(an)-296.8(audit)-302.7(on)-303.1(the)-302.9(rst)-307.6(400)-298.6(patie)-9.8(nts)-301.6(in)-296.4(New)-307.8(Zealand.)-304.6(BJGP)-301.5(Open.)-309.5(2020;4:)]TJ
T*
(bjgpopen20X101010.)Tj
-1.7224 -1.1988 TD
[(50.)-505.4(Lee)-299.9(JLC,)-303.5(Bertoglio)-305.2(LJ,)-306.4(Guimara)]TJ
13.9611 .0076 TD
()Tj
.387 -.0076 TD
[(es)-303.8(FS,)-299.4(et)-301(al.)-301.4(Cannabid)-11.7(iol)-298.5(regulation)-308.4(of)]TJ
-12.6257 -1.2064 TD
[(emotion)-306.2(and)-296.3(emoti)-10.7(onal)-300.8(memory)-304.5(processing:)-308.3(releva)-10.1(nce)-299.3(for)-302.8(treating)]TJ
0 -1.1988 TD
[(anxiety-related)-248.3(and)-235.6(subs)-11.5(tance)-241.9(abuse)-239.4(disorders.)-246.9(Br)-244.8(J)-235.4(Pha)-8.7(rmacol.)-245.1(2017;174:)]TJ
T*
(32423256.)Tj
-1.7224 -1.1988 TD
[(51.)-505.4(Campos)-298(AC,)-296.3(Moreira)-295.4(FA,)-298.2(Gomes)-295.6(FV,)-297.1(et)-293.4(al.)-293.9(Mult)-10.5(iple)-293.5(mechanisms)-301.3(involved)]TJ
1.7224 -1.1988 TD
[(in)-288.9(the)-295.3(large-spectrum)-302.9(therapeutic)-300.2(potential)-293.1(of)-298.6(cannabidiol)-298.7(in)-288.8(psychiatric)]TJ
T*
[(disorders.)-307.6(Philos)-307.7(Trans)-297.3(R)-303.6(Soc)-306.1(Lond)-305.1(B)-301.2(Biol)-303.8(Sci.)-299.7(2012;367)-11.7(:33643378.)]TJ
-1.7224 -1.1988 TD
[(52.)-505.4(Szkudlarek)-302.9(HJ,)-304(Desai)-305.7(SJ,)-300.6(Rena)-9.4(rd)-299.7(J,)-304(et)-301(al.)]TJ
/F8 1 Tf
18.3846 0 TD
(D)Tj
/F9 1 Tf
.6677 0 TD
[(-9-Tetrahydrocann)-15.7(abinol)-298.9(and)]TJ
-17.3299 -1.2064 TD
[(cannabidiol)-306.3(produce)-303.7(dissociabl)-14.2(e)-296.7(effects)-311.9(on)-295.5(prefro)-11.5(ntal)-299.7(cortical)-307.4(executive)]TJ
0 -1.1988 TD
[(function)-303.7(and)-303.9(regulation)-308.4(of)-298.6(affec)-10.3(tive)-298.6(behaviors.)-311.8(Neuropsychopharmac)-20.1(ol-)]TJ
T*
[(ogy.)-298.3(2019;44:)-13.6(817825.)]TJ
-1.7224 -1.1988 TD
[(53.)-505.4(Sonego)-300.2(AB,)-304.5(Prado)-304.2(DS,)-304.5(Vale)-303.8(GT,)-300.4(et)-301(al.)-301.4(Cannabid)-11.7(iol)-298.5(prevent)-10.6(s)-295.5(haloperido)-12.9(l-)]TJ
1.7224 -1.1988 TD
[(induced)-256.7(vacuos)-251.7(chewing)-255.6(moveme)-9.2(nts)-248.5(and)-250.8(in)-8.1(ammatory)-256.4(changes)-256.2(in)-250.9(mice)]TJ
T*
[(via)-300.2(PPAR)]TJ
/F14 1 Tf
3.6875 0 TD
(c)Tj
/F9 1 Tf
.736 0 TD
[(receptors.)-308.1(Brain)-305.1(Behav)-302(Imm)-9.5(un.)-295.8(201)-10.3(8;74:241251.)]TJ
-6.1459 -1.2064 TD
[(54.)-505.4(Song)-301.7(C,)-300.9(Stevenson)-306.1(CW,)-307.7(Guimaraes)-304.2(FS,)-307(et)-301(al.)-301.4(Bidirectional)-311.5(effects)-304.3(of)]TJ
1.7224 -1.1988 TD
[(cannabidiol)-306.3(on)-303.1(contextual)-305.8(fear)-304.9(memory)-304.5(extinction)-13.7(.)-296.2(Front)-303.1(Pha)-8.7(rmacol.)]TJ
T*
(2016;7:493.)Tj
-1.7224 -1.1988 TD
[(55.)-505.4(Bitencourt)-303.9(RM,)-306.2(Pamplona)-308.7(FA,)-298.2(Takahashi)-309.2(RN.)-300.5(Facili)-9.8(tation)-301.7(of)-298.6(contextu)-12.2(al)]TJ
1.7224 -1.1988 TD
[(fear)-297.3(memo)-9.4(ry)-302.6(extinction)-302(an)-8.5(d)-295.4(anti-anx)-11.1(iogenic)-303.8(effects)-304.3(of)-306.1(AM404)-303.9(and)]TJ
T*
[(cannabidiol)-306.3(in)-296.4(conditio)-14.2(ned)-298.1(rats.)-303.3(Eur)-309.7(Neuropsychopharmacol.)-320.3(2008;18:)]TJ
0 -1.2064 TD
(849859.)Tj
-1.7224 -1.1988 TD
[(56.)-505.4(do)-255.2(Monte)-265(FH,)-264.8(Souza)-262.2(RR,)-258.5(Bitenc)-11.6(ourt)-262(RM,)-260.7(et)-263(al.)-255.9(Infus)-10.3(ion)-256.2(of)-260.6(cannab)-9.6(idiol)-258.7(into)]TJ
1.7224 -1.1988 TD
[(infralimbic)-226.5(cortex)-225(facilitates)-228.5(fear)-221.5(extinction)-226.1(via)-224.3(CB1)-220.8(receptors.)-224.6(Behav)-226.1(Brain)]TJ
T*
[(Res.)-296.7(2013;25)-13.3(0:2327.)]TJ
-1.7224 -1.1988 TD
[(57.)-505.4(Das)-298.6(RK,)-301.7(Kambo)-10.8(j)-299.7(SK,)-298.1(Ram)-8.4(adas)-300.6(M,)-306.1(et)-301(al.)-301.4(Cannabidiol)-310.3(enhances)-302.5(consolida-)]TJ
1.7224 -1.1988 TD
[(tion)-298.4(of)-306.1(explicit)-301.9(fear)-304.9(extinction)-309.6(in)-304(humans.)-305.6(Psychopharmacology.)-318.3(2013;)]TJ
T*
(226:781792.)Tj
-1.7224 -1.2064 TD
[(58.)-505.4(Norris)-304.5(C,)-300.9(Loureiro)-307.1(M,)-306.1(Kramar)-301.9(C,)-300.9(et)-308.6(al.)-301.4(Cannabidiol)-302.7(modul)-10.4(ates)-299.6(fear)]TJ
1.7224 -1.1988 TD
[(memory)-304.4(formation)-306.1(through)-305.6(inter)-9.9(actions)-305.3(with)-300.1(serotonerg)-13.2(ic)-302.8(transmission)]TJ
T*
[(in)-296.4(the)-302.9(mesolimbi)-12(c)-296.6(system.)-312.1(Neuropsychopharmacolo)-21.8(gy.)-300.5(2016;41:2839)]TJ
T*
(2850.)Tj
-1.7224 -1.1988 TD
[(59.)-505.4(de)-296.2(Gregorio)-308.8(D,)-300.3(McLaug)-11.7(hlin)-297(RJ,)-304.1(Posa)-307.5(L,)-298.6(et)-301(al.)-301.4(Cannabid)-11.7(iol)-298.5(modulates)]TJ
1.7224 -1.1988 TD
[(serotonergic)-308.5(transmission)-310.2(and)-303.9(reverses)-305(both)-306.9(allodynia)-306.6(and)-303.9(anxiety-)]TJ
0 -1.2064 TD
[(like)-296.4(beha)-8.8(vior)-303.2(in)-296.4(a)-302.5(model)-301.8(of)-306.1(neuropathic)-309.9(pain.)-302.8(Pain.)-303.5(2019;160:)]TJ
0 -1.1988 TD
(136150.)Tj
-1.7224 -1.1988 TD
[(60.)-505.4(Uhernik)-305.8(AL,)-301.7(Montoya)-308.9(ZT,)-302.3(Balkissoon)-304(CD,)-305(et)-301(al.)-301.4(Learning)-306.8(and)-303.9(memory)-304.4(is)]TJ
1.7224 -1.1988 TD
[(modulated)-302.3(by)-305.4(cannabidiol)-306.3(when)-307.5(administered)-304.4(during)-307.4(trace)-305(fear-)]TJ
T*
[(conditioning.)-307.2(Neurobiol)-310.2(Learn)-304.3(Mem.)-300.9(2018;149)-11.7(:6876.)]TJ
-1.7224 -1.1988 TD
[(61.)-505.4(Renard)-301.5(J,)-304(Loureiro)-307.1(M,)-298.5(Rosen)-303.6(LG,)-306.2(et)-301(al.)-301.4(Cannabid)-11.7(iol)-298.5(counteracts)]TJ
1.7224 -1.1988 TD
[(amphetamine-induced)-312.9(neuronal)-305.5(and)-303.9(behavioral)-309.6(sensitization)-306.3(of)-306.2(the)]TJ
0 -1.2064 TD
[(mesolimbic)-308.5(dopamine)-302.2(pathway)-309.1(through)-305.6(a)-302.5(novel)-301.6(mTOR/p70S6)-312.7(kinase)]TJ
0 -1.1988 TD
[(signaling)-305.6(pathway.)-301.8(J)-303.7(Neurosci.)-307.3(2016;36:5160)-14.7(5169.)]TJ
-1.7224 -1.1988 TD
[(62.)-505.4(Karniol)-301.4(IG,)-302.4(Carlini)-309.3(EA.)-303.4(Pharmacological)-310.8(interaction)-308(between)-303.4(can)-9.2(nabidiol)]TJ
7.4718 0 0 7.4718 323.7164 260.9007 Tm
(and)Tj
/F14 1 Tf
1.8893 0 TD
(d)Tj
/F9 1 Tf
.5008 0 TD
[(9-tetrahydroc)-19.1(annabinol.)-302(Psychophar)-14.8(macologia.)-306.4(1973;33:)]TJ
-2.3901 -1.1988 TD
(5370.)Tj
-1.7224 -1.1988 TD
[(63.)-505.4(Hudson)-299.9(R,)-303.9(Renard)-309.1(J,)-296.4(Norr)-10.4(is)-301.7(C,)-300.9(et)-301(al.)-301.4(Cannabidiol)-310.2(counteracts)-314.4(the)]TJ
1.7224 -1.2064 TD
[(psychotropic)-310.4(side-effects)-311.8(of)]TJ
/F14 1 Tf
11.8745 0 TD
(d)Tj
/F9 1 Tf
.5008 0 TD
[(-9-tetrahydr)-14.6(ocannabinol)-307.8(in)-296.4(the)-302.9(ventr)-10.3(al)]TJ
-12.3753 -1.1988 TD
[(hippocampus)-306.5(through)-305.6(bidirecti)-12.5(onal)-300.8(control)-308.7(of)-298.6(ERK1-2)-303.8(ph)-9(osphorylation.)]TJ
T*
[(J)-296.1(Neurosc)-12.5(i.)-294.8(2019;39)-13.3(:87628777.)]TJ
-1.7224 -1.1988 TD
[(64.)-505.4(Miller)-299.2(KE,)-305.7(Brownlow)-307.9(JA,)-299.4(Gehrman)-305.4(PR.)-304.1(Sleep)-307.4(in)-296.4(PTSD:)-308.9(treatment)]TJ
1.7224 -1.1988 TD
[(approaches)-305.5(and)-303.9(outcomes.)-311.5(Curr)-306.9(Opin)-299.4(Psychol.)-304.9(2020;34)-13.3(:1217.)]TJ
-1.7224 -1.1988 TD
[(65.)-505.4(Carlini)-301.7(EA,)-303.4(Cunha)-301.1(JM.)-306.3(Hypnotic)-308.6(and)-303.9(antiepileptic)-308.8(effects)-304.3(of)-306.1(cannabidiol.)]TJ
1.7224 -1.1988 TD
[(J)-296.1(Clin)-307.3(Pharmacol.)-306.9(1981;21:417S427)-16.5(S.)]TJ
-1.7224 -1.2064 TD
[(66.)-505.4(Hsiao)-298.4(YT,)-308.1(Yi)-302.3(PL,)-298.8(Li)-304.6(CL,)-303.3(et)-301(al.)-301.4(Effect)-308.1(of)-298.6(cannab)-9.6(idiol)-304.2(on)-295.5(sleep)-310.4(disruption)]TJ
1.7224 -1.1988 TD
[(induced)-302.2(by)-305.4(the)-302.9(repeated)-304.8(combination)-312.7(tests)-304.4(consisting)-308.3(of)-298.6(open)-303.4(eld)]TJ
T*
[(and)-296.3(elevat)-10.1(ed)-296.2(plus-maz)-10.7(e)-296.7(i)0(n)-304(rats.)-303.3(Neuropharmaco)-16(logy.)-304.5(2012;62:373)]TJ
T*
(384.)Tj
-1.7224 -1.1988 TD
[(67.)-505.4(Fleury-Teixeira)-311.5(P,)-296.3(Caixeta)-307.2(FV,)-304.7(Ramires)-307.6(da)-302(Silva)-303(LC,)-303.3(et)-301(al.)-301.4(Effects)-307.7(of)]TJ
1.7224 -1.1988 TD
(CBD-enriched)Tj
/F11 1 Tf
6.0397 0 TD
[(Cannabis)-311(sativa)]TJ
/F9 1 Tf
6.7529 0 TD
[(extract)-306.5(on)-303.1(autism)-304.4(spectrum)-311.9(disorder)]TJ
-12.7926 -1.2064 TD
[(symptoms:)-310.2(an)-296.8(observational)-311.2(study)-307(of)-306.1(18)-300.2(participants)-312.8(undergoing)]TJ
0 -1.1988 TD
[(compassionate)-311.2(use.)-301.9(Front)-303.1(Neurol)-10.9(.)-296.2(2019;10:1145)-14.7(.)]TJ
-1.7224 -1.1988 TD
[(68.)-505.4(Barchel)-230.7(D,)-232(Stolar)-235.8(O,)-231.4(De-Haa)-12(n)-229.5(T)0(,)-232.1(e)0(t)-232.7(al.)-233.2(Oral)-233(cannabidiol)-238(use)-233.3(in)-228.1(children)-233.9(with)]TJ
1.7224 -1.1988 TD
[(autism)-258.8(spectrum)-266.4(disorder)-269.8(to)-260(treat)-263(related)-265.3(symptoms)-264.3(and)-258.4(Co-mo)-10.9(rbidities.)]TJ
T*
[(Front)-303.1(Pharmacol.)-306.9(2019;9:1521.)]TJ
-1.7224 -1.1988 TD
[(69.)-505.4(Chagas)-302(MHN,)-302.6(Eckeli)-308.9(AL,)-301.7(Zuardi)-304.6(AW,)-306(et)-301(al.)-301.4(Cannabidiol)-310.2(can)-297.5(improve)]TJ
1.7224 -1.1988 TD
[(complex)-299.7(sleep-rel)-12.1(ated)-299.5(behaviours)-309.3(associated)-309.9(with)-307.7(rapid)-304.4(eye)-299.9(movement)]TJ
/F4 1 Tf
9.9626 0 0 9.9626 59.7543 753.8455 Tm
[(CBD)-306.5(IN)-306.7(COVID-19)-10.5(-RELATED)-309.1(PTSD)]TJ
48.0965 0 TD
(17)Tj
ET
endstream
endobj
93 0 obj
<>stream
OEGNHC+AdvPSMP10 q
AdvPSMP10 D jI_V!QBg5fqu!@`w|wsbm\a[18$;t~ri{w~~yy`U6_Sv(AL5]hğ>VlF?^RCnQvGGhhfPG89"4&tMEF|qux,
endstream
endobj
96 0 obj
<>stream
0 0 0 rg
/GS1 gs
1 i
q 1 0 0 1 62.022 435.968 cm 0 0 m
.113 1.077 l
.461 3.485 2.551 5.502 4.932 5.896 c
6.009 6.009 l
6.009 4.989 l
5.102 4.932 l
2.98 4.455 1.512 3.081 1.077 .907 c
1.02 0 l
f*
Q
q 1 0 0 1 295.143 441.978 cm 0 0 m
1.02 -.113 l
3.628 -.574 5.318 -2.396 5.896 -4.932 c
6.009 -6.009 l
4.989 -6.009 l
4.932 -5.102 l
4.433 -2.979 3.016 -1.504 .85 -1.077 c
0 -1.02 l
f*
Q
68.031 440.957 227.112 1.0205 re
f
q 1 0 0 1 68.031 392.145 cm 0 0 m
-1.077 .113 l
-3.207 .243 -5.766 2.802 -5.896 4.932 c
-6.009 6.009 l
-4.989 6.009 l
-4.932 5.102 l
-4.51 2.993 -3.025 1.472 -.907 1.077 c
0 1.02 l
f*
Q
q 1 0 0 1 301.153 398.154 cm 0 0 m
-.113 -1.077 l
-.7 -3.615 -2.34 -5.382 -4.932 -5.896 c
-6.009 -6.009 l
-6.009 -4.989 l
-5.159 -4.932 l
-2.996 -4.586 -1.566 -2.973 -1.077 -.907 c
-1.02 0 l
f*
Q
68.031 392.145 227.112 1.0205 re
f
62.022 398.154 1.0205 37.814 re
f
300.132 398.154 1.0204 37.814 re
f
q 1 0 0 1 313.058 699.364 cm 0 0 m
.113 1.02 l
.595 3.471 2.504 5.45 4.989 5.896 c
6.009 5.953 l
6.009 4.989 l
5.159 4.876 l
3.116 4.586 1.44 2.856 1.077 .85 c
1.02 0 l
f*
Q
q 1 0 0 1 546.236 705.316 cm 0 0 m
1.02 -.057 l
3.204 -.362 5.663 -2.708 5.839 -4.932 c
5.953 -5.953 l
4.932 -5.953 l
4.876 -5.102 l
4.573 -3.084 2.869 -1.38 .85 -1.077 c
0 -.964 l
f*
Q
319.068 704.353 227.168 .96381 re
f
q 1 0 0 1 319.068 391.975 cm 0 0 m
-1.02 .057 l
-3.658 .614 -5.338 2.295 -5.896 4.932 c
-6.009 5.953 l
-4.989 5.953 l
-4.932 5.102 l
-4.644 3.23 -2.794 1.218 -.85 1.077 c
0 .964 l
f*
Q
q 1 0 0 1 552.189 397.927 cm 0 0 m
-.113 -1.02 l
-.397 -3.474 -2.568 -5.449 -4.932 -5.896 c
-5.953 -5.953 l
-5.953 -4.989 l
-5.102 -4.876 l
-3.252 -4.717 -1.287 -2.76 -1.077 -.85 c
-1.02 0 l
f*
Q
319.068 391.975 227.168 .96378 re
f
313.058 397.927 1.0205 301.436 re
f
551.168 397.927 1.0204 301.436 re
f
BT
/F9 1 Tf
7.4718 0 0 7.4718 74.8913 700.2707 Tm
0 Tc
0 Tw
[(sleep)-302.8(behaviour)-309.7(disorder)-307.7(in)-296.4(Parkinson)-13.2(s)-303.3(disease)-301.4(patients:)-311.7(a)-294.9(case)-303.5(series)-11.2(.)]TJ
0 -1.2064 TD
[(J)-296.1(Cli)-9.5(n)-297.8(Pharm)-302.9(Ther.)-307.4(2014;39:564566.)]TJ
-1.7224 -1.1988 TD
[(70.)-505.4(Capano)-305.3(A,)-299.2(Weaver)-306.7(R,)-303.9(Burkman)-308.3(E.)-300.4(Evaluation)-311.3(of)-298.6(the)-302.9(effects)-304.3(of)-306.1(CBD)-302.4(hemp)]TJ
1.7224 -1.1988 TD
[(extract)-306.5(on)-303.1(opioid)-302.8(use)-301.6(and)-303.9(quality)-303.7(of)-306.1(life)-298.9(indicator)-12.2(s)-303.1(i)0(n)-296.4(chronic)-309.3(pain)]TJ
T*
[(patients:)-304.2(a)-302.5(prospective)-308.2(cohort)-310.1(study.)-307.3(Postgrad)-309.9(Med.)-298.8(2020;13)-13.3(2:)]TJ
T*
(5661.)Tj
-1.7224 -1.1988 TD
[(71.)-505.4(Vigil)-303.2(J,)-304(Stith)-301.6(S,)-300.4(Diviant)-309.1(J,)-296.4(et)-301(al.)-309(Effectiveness)-308.4(of)-298.6(raw,)-306.5(natural)-308.4(medical)]TJ
1.7224 -1.2064 TD
[(cannabis)-303.7(ower)-309.3(for)-302.8(treating)-303.4(insomnia)-310.1(under)-300.1(naturali)-11.1(stic)-299.1(conditio)-14.2(ns.)]TJ
0 -1.1988 TD
[(Medicines.)-306.6(2018;5:75.)]TJ
-1.7224 -1.1988 TD
[(72.)-505.4(Vann)-300.6(RE,)-300.5(Gamage)-305.9(TF,)-307(Warner)-305.4(JA,)-299.4(et)-301(al.)-309(Divergent)-304.1(effects)-304.3(of)]TJ
1.7224 -1.1988 TD
[(cannabidiol)-222.8(on)-219.7(the)-219.4(discriminat)-14.4(ive)-218.5(stimulus)-225.4(and)-220.4(place)-218.7(conditioning)-231(effects)]TJ
T*
(of)Tj
/F8 1 Tf
1.1305 0 TD
(D)Tj
/F9 1 Tf
.6677 0 TD
[(9-tetrahydroca)-18.1(nnabinol.)-303(Drug)-303.9(Alcohol)-309.4(Depend.)-302.8(2008;94:)]TJ
-1.7982 -1.1988 TD
(191198.)Tj
-1.7224 -1.1988 TD
[(73.)-505.4(Parker)-306.9(LA,)-301.7(Burton)-307.1(P,)-303.9(Sorge)-304.8(RE,)-300.5(et)-301(al.)-301.4(Effect)-308.1(of)-298.6(low)-306.9(doses)-300.6(of)]TJ
/F8 1 Tf
1.7224 -1.2064 TD
(D)Tj
/F9 1 Tf
.6677 0 TD
[(9-tetrahydrocannabi)-19.1(nol)-301.8(and)-296.3(can)-9.2(nabidiol)-304.6(on)-303.1(the)-302.9(extinction)-302(of)]TJ
-.6677 -1.1988 TD
[(cocaine-induced)-310.8(and)-303.9(amphetamine-)-10.7(induced)-302.2(conditioned)-312.4(place)]TJ
T*
[(preference)-307(learning)-303(in)-304(rats.)-303.3(Psychophar)-14.7(macology.)-303.6(2004;17)-13.3(5:)]TJ
T*
(360366.)Tj
-1.7224 -1.1988 TD
[(74.)-505.4(Katsidoni)-308.1(V,)-298.1(Anagnosto)-14.6(u)-301.2(I)0(,)-294.8(Pan)-8.7(agis)-302.6(G.)-296.2(Cannabi)-12.3(diol)-298(inhibits)-306.5(the)-302.9(reward-)]TJ
1.7224 -1.1988 TD
[(facilitating)-306.4(effect)-304.7(of)-306.1(morphine:)-310.2(involvement)-307.9(of)-298.6(5-HT1A)-308.9(receptors)-307.8(in)-296.4(the)]TJ
0 -1.2064 TD
[(dorsal)-302.2(raphe)-309(nucleus.)-308.4(Addict)-301.5(Biol.)-304.1(2013;18:286)-16.3(296.)]TJ
-1.7224 -1.1988 TD
[(75.)-505.4(Karagianni)-305.6(A,)-299.2(Malamat)-11.5(ari)-297.8(M,)-306.1(Kachrimanis)-306.5(K.)-301.5(Pharmaceu)-12.8(tical)-304.7(cocrystals:)]TJ
1.7224 -1.1988 TD
[(new)-298(soli)-9.7(d)-295.4(phase)-304.3(modicat)-12.6(ion)-301.8(approaches)-305.5(for)-302.8(the)-302.9(formul)-12.5(ation)-297.5(of)-306.1(APIs.)]TJ
T*
[(Pharmaceutics.)-312.2(2018;10.)]TJ
-1.7224 -1.1988 TD
[(76.)-505.4(Lee)-299.9(B,)-301.5(Shim)-302.3(I,)-302.4(Lee)-307.5(H,)-296.1(et)-308.6(al.)-301.4(Tetramethylpyrazine)-315.1(reverses)-305(anxiety-li)-10.7(ke)]TJ
1.7224 -1.1988 TD
[(behaviors)-303.9(in)-304(a)-302.5(rat)-303.5(model)-301.8(of)-298.6(post-trau)-15.5(matic)-300.2(stress)-311.5(disorder.)-308(Korean)-305(J)]TJ
0 -1.2064 TD
[(Physiol)-302.5(Pharmaco)-12(l.)-302.4(2018;22:525538.)]TJ
/F4 1 Tf
-.7891 -5.1975 TD
[(Cite)-256.1(this)-245.3(article)-253.9(as:)]TJ
/F9 1 Tf
8.3615 0 TD
[(OSullivan)-251.9(SE,)-251.5(Steven)-11(son)-249.6(CW,)-247(Laviolett)-12.4(e)-243.6(S)0(R)-247.1(\(2021\))]TJ
-8.3615 -1.1988 TD
[(Could)-309.3(cannabidiol)-306.3(be)-303.8(a)-294.9(treatment)-309.6(for)-302.8(coronavirus)-311.7(disease-19)-11.3(-related)]TJ
T*
[(anxiety)-307.8(disorders?)]TJ
/F11 1 Tf
7.8455 0 TD
[(Cannabis)-311(and)-303.2(Cannabinoid)-312.5(Research)]TJ
/F9 1 Tf
15.2965 0 TD
[(6:1,)-308.4(718,)]TJ
-23.142 -1.1988 TD
[(DOI:)-302.4(10.1089/ca)-13.9(n.2020.0102.)]TJ
/F4 1 Tf
8.9663 0 0 8.9663 393.1652 691.4266 Tm
[(Abbreviations)-336.5(Used)]TJ
/F9 1 Tf
7.4718 0 0 7.4718 344.5227 679.1243 Tm
(5HT)Tj
5.6038 0 0 4.9805 356.8251 677.877 Tm
(1A)Tj
/F12 1 Tf
7.4718 0 0 7.4718 364.2519 679.1243 Tm
()Tj
/F9 1 Tf
.9409 0 TD
[(serotoni)-12.5(n)-328.2(1)0(A)]TJ
-2.5949 -1.1988 TD
(AEs)Tj
/F12 1 Tf
1.6541 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(adverse)-336.8(effects)]TJ
-2.1776 -1.1988 TD
(BP)Tj
/F12 1 Tf
1.2368 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(blood)-342.1(pressure)]TJ
-2.6025 -1.1988 TD
(CB)Tj
5.6038 0 0 4.9805 360.17 651.0045 Tm
(1)Tj
/F12 1 Tf
7.4718 0 0 7.4718 364.2519 652.2518 Tm
()Tj
/F9 1 Tf
.9409 0 TD
[(cannab)-9.6(inoid)-330.2(receptor)-346.1(type)-333.3(1)]TJ
-2.6025 -1.2064 TD
(CB)Tj
5.6038 0 0 4.9805 360.17 641.9904 Tm
(2)Tj
/F12 1 Tf
7.4718 0 0 7.4718 364.2519 643.2377 Tm
()Tj
/F9 1 Tf
.9409 0 TD
[(cannab)-9.6(inoid)-330.2(receptor)-346.1(type)-333.3(2)]TJ
-2.8757 -1.1988 TD
(CBD)Tj
/F12 1 Tf
1.9348 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(cannab)-9.6(idiol)]TJ
-3.6875 -1.1988 TD
(CHR-P)Tj
/F12 1 Tf
2.7467 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(clinical)-338.3(high)-338.2(risk)-338.7(for)-333.2(psychosis)]TJ
-5.1292 -1.1988 TD
(COVID-19)Tj
/F12 1 Tf
4.1883 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(coronavirus)-342(diseas)-12.2(e-19)]TJ
-2.7391 -1.1988 TD
(CYP)Tj
/F12 1 Tf
1.7982 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(cytochrome)-346(P450)]TJ
-2.3673 -1.1988 TD
(DA)Tj
/F12 1 Tf
1.4265 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(decrease)-339.3(dopami)-11.2(ne)]TJ
-3.4372 -1.2064 TD
(FAAH)Tj
/F12 1 Tf
2.4963 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(fatty)-341.2(acid)-331.7(am)-8.2(ide)-332.8(hydrolase)]TJ
-3.2626 -1.1988 TD
(FABP)Tj
/F12 1 Tf
2.3218 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(fatty)-341.2(acid)-331.7(binding)-343.4(protein)]TJ
-2.815 -1.1988 TD
(GPR)Tj
/F12 1 Tf
1.8741 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(g-protein)-344.4(coupled)]TJ
-2.3218 -1.1988 TD
(HC)Tj
/F12 1 Tf
1.3809 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(healthy)-342.8(controls)]TJ
-2.2839 -1.1988 TD
(HR)Tj
/F12 1 Tf
1.343 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(heart)-336.5(rate)]TJ
-2.815 -1.1988 TD
(NAc)Tj
/F12 1 Tf
1.8741 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(nucleus)-338.5(accumbens)]TJ
-2.8529 -1.2064 TD
(OTC)Tj
/F12 1 Tf
1.9121 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(over-the-c)-12.5(ounter)]TJ
-3.4903 -1.1988 TD
(PCL-5)Tj
/F12 1 Tf
2.5494 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(PTSD)-338.9(Checklist)-337.8(for)-340.8(DSM-5)]TJ
-3.2702 -1.1988 TD
(PTSD)Tj
/F12 1 Tf
2.3294 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(post-trauma)-16.1(tic)-329.8(stress)-341.9(disorder)]TJ
-3.1033 -1.1988 TD
(PTSS)Tj
/F12 1 Tf
2.1624 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(post-trauma)-16.1(tic)-329.8(stress)-341.9(symptoms)]TJ
-3.0957 -1.1988 TD
(RCTs)Tj
/F12 1 Tf
2.1549 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(randomized)-342.4(controlle)-12.2(d)-333.3(trials)]TJ
-3.0881 -1.1988 TD
(SAEs)Tj
/F12 1 Tf
2.1473 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(serious)-339.7(adverse)-344.4(effects)]TJ
-6.0017 -1.1988 TD
(SARS-CoV-2)Tj
/F12 1 Tf
5.0609 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(severe)-339.1(acute)-336.3(respiratory)-348.6(syndrome)-341.7(coronavirus)-342(2)]TJ
-3.4068 -1.2064 TD
(SNRIs)Tj
/F12 1 Tf
2.466 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(selective)-344.6(noradrenaline)-342.2(reuptake)-335.1(in)-8.1(hibitors)]TJ
-3.2399 -1.1988 TD
(SSRIs)Tj
/F12 1 Tf
2.299 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(selective)-344.6(serotonin)-340.6(reuptake)-335.1(in)-8.1(hibitors)]TJ
-2.815 -1.1988 TD
(THC)Tj
/F12 1 Tf
1.8741 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(tetrahydr)-13.2(ocannabinol)]TJ
-3.4599 -1.1988 TD
(TRPM)Tj
/F12 1 Tf
2.5191 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(melasta)-10.5(tin-related)-339.9(transient)-340.9(receptor)-338.6(potential)-338.6(cati)-10.2(on)]TJ
1.4947 -1.1988 TD
[(cha)-9.2(nnels)]TJ
-5.2126 -1.1988 TD
(TRPV1)Tj
/F12 1 Tf
2.777 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(transient)-340.9(receptor)-346.2(potential)-338.6(cation)-336.1(channel)]TJ
1.4947 -1.2064 TD
[(subfamily)-343.5(V)-335.7(member)]TJ
-5.0154 -1.1988 TD
(vHIPP)Tj
/F12 1 Tf
2.5798 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(ventral)-341.8(hippocampus)]TJ
-3.2854 -1.1988 TD
(WHO)Tj
/F12 1 Tf
2.3446 0 TD
()Tj
/F9 1 Tf
.9409 0 TD
[(World)-340.8(Health)-338.4(Organization)]TJ
/F4 1 Tf
9.9626 0 0 9.9626 62.022 754.3557 Tm
(18)Tj
40.6704 0 TD
[(OSULLIVA)-10.2(N)-303.2(E)0(T)-299.4(AL.)]TJ
ET
endstream
endobj
100 0 obj
<>stream
8;X]O>EqN@%''O_@%e@?J;%+8(9e>X=MR6S?i^YgA3=].HDXF.R$lIL@"pJ+EP(%0
b]6ajmNZn*!='OQZeQ^Y*,=]?C.B+\Ulg9dhD*"iC[;*=3`oP1[!S^)?1)IZ4dup`
E1r!/,*0[*9.aFIR2&b-C#soRZ7Dl%MLY\.?d>Mn
6%Q2oYfNRF$$+ON<+]RUJmC0InDZ4OTs0S!saG>GGKUlQ*Q?45:CI&4J'_2j$XKrcYp0n+Xl_nU*O(
l[$6Nn+Z_Nq0]s7hs]`XX1nZ8&94a\~>
endstream
endobj
103 0 obj
<>stream
hT=o w~ō:`N%%m%Pf'pvj0ˇppw>F{nzQiqጃ6JPZ5Ke8sB?6/w@ߝB #:-CM
{B¾&<^,Br~=)^W
QH^~G(ALq8HUbAT2#x`ϋ˵ X_ۭW8ƐfmjƮ" |U
endstream
endobj
104 0 obj
<>stream
h\SiPSW~ Wbm](;ECA$,A*K K D\,e*XQup8[{t~vqΙ}`\
* 3~a7wSRb(~g_ Fr8vRX^B7!ťBIJ-OQ RcӔijyPPI jP)WɕKPeZօlaͰݩl6786`;YcA,I1[VfŚ?89*0׆+qUjzuub2z9&GPhK+r˱tm浼\:E&OEh