Table 3 Summary of findings. GRADE Working Group grades of evidence. High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate

Chronic pain

Dronabinol vs Placebo

1395 (15 RCTs)

53

⨁⨁⨁◯

MODERATE ^c

SMD 0.31 lower

(0.46 lower to 0.15 lower)

Dronabinol vs Active

14 (1 RCT)

SMD 0.73 higher

(0.1 lower to 1.56 higher)

Nabilone vs Placebo

363 (9 RCTs)

70

⨁⨁◯◯

LOW ^c,g

SMD 0.41 lower

(0.76 lower to 0.06 lower)

Nabilone vs Active

262 (3 RCTs)

83

⨁◯◯◯

VERY LOW ^c,e

SMD 0.08 lower

(0.54 lower to 0.38 higher)

Cannabidiol vs Placebo

129 (1 RCT)

SMD 0.01 higher

(0.34 lower to 0.35 higher)

Nabiximols vs Placebo

3238 (21 RCTs)

65

⨁⨁⨁◯

MODERATE ^c

SMD 0.23 lower

(0.34 lower to 0.12 lower)

Spasticity

Dronabinol vs Placebo

704 (6 RCTs)

52

⨁⨁◯◯

LOW ^c,f

SMD 0.08 lower

(0.34 lower to 0.17 higher)

Nabilone vs Placebo

44 (2 RCTs)

68

⨁◯◯◯

VERY LOW ^a,c,g

SMD 0.7 lower

(1.56 lower to 0.16 higher)

Nabiximols vs Placebo

1658 (14 RCTs)

68

⨁⨁⨁◯

MODERATE ^c

SMD 0.36 lower

(0.54 lower to 0.19 lower)

Nausea/vomiting

Dronabinol vs Placebo

495 (8 RCTs)

61

⨁⨁◯◯

LOW ^c,f

SMD 0 .21 lower

(0.49 lower to 0.07 higher)

Dronabinol vs Active

308 (5 RCTs)

0

⨁⨁◯◯

LOW ^a,g

SMD 0.28 lower

(0.47 lower to 0.1 lower)

Nabilone vs Placebo

603 (4 RCTs)

61

⨁⨁◯◯

LOW ^c,f

SMD 0.09 lower

(0.36 lower to 0.18 higher)

Nabilone vs Active

627 (11 RCTs)

46

⨁⨁◯◯

LOW ^b,c

SMD 0.44 lower

(0.62 lower to 0.26 lower)

Nabiximols vs Placebo

393 (6 RCTs)

56

⨁◯◯◯

VERY LOW ^a,e

SMD 0.23 lower

(0.55 lower to 0.08 higher)

Appetite

Dronabinol vs Placebo

599 (10 RCTs)

81

⨁⨁⨁◯

MODERATE ^c

SMD 0.51 lower

(0.87 lower to 0.15 lower)

Dronabinol vs Active

795 (3 RCTs)

86

⨁⨁◯◯

LOW ^c,f

SMD 0.02 lower

(0.39 lower to 0.34 higher)

Nabilone vs Placebo

187 (4 RCTs)

74

⨁◯◯◯

VERY LOW ^c,e

SMD 0.44 lower

(0.98 lower to 0.11 higher)

Nabilone vs Active

130 (3 RCTs)

85

⨁◯◯◯

VERY LOW ^{a,d, g}

SMD 0.24 higher

(0.51 lower to 0.99 higher)

Cannabidiol vs Placebo

27 (1 RCT)

SMD 0.1 higher

(0.66 lower to 0.85 higher)

Nabiximols vs Placebo

430 (6 RCTs)

66

⨁⨁◯◯

LOW ^c,f

SMD 0.25 lower

(0.61 lower to 0.1 higher)

Amyotrophic lateral sclerosis

Dronabinol vs Placebo

22 (1 RCT)

SMD 0.26 higher

(0.17 lower to 0.68 higher)

Nabiximols vs Placebo

59 (1 RCT)

SMD 0.38 higher

(0.13 lower to 0.90 higher)

Chorea Huntington

Nabilone vs Placebo

74 (1 RCT)

SMD 0.45 lower

(0.79 lower to 0.11 lower)

Cannabidiol vs Placebo

30 (1 RCT)

SMD 0.18 higher

(0.33 lower to 0.69 higher)

Nabiximols vs Placebo

50 (1 RCT)

SMD 0.17 higher

(0.23 lower to 0.56 higher)

Dystonia

Dronabinol vs Placebo

14 (1 RCT)

SMD 0.05 higher

(0.69 lower to 0.79 higher)

Nabilone vs Placebo

26 (1 RCT)

SMD 0.49 lower

(1.07 lower to 0.08 higher)

Nabiximols vs Placebo

50 (1 RCT)

SMD 0

(0.39 lower to 0.39 higher)

Epilepsy

Cannabidiol vs Placebo

956 (6 RCTs)

0

⨁⨁⨁⨁

HIGH

SMD 0.5 lower

(0.62 lower to 0.38 lower)

Glaucoma

Dronabinol vs Placebo

12 (1 RCT)

SMD 1.28 lower

(2.36 lower to 0.2 lower)

Nabiximols vs Placebo

12 (1 RCT)

SMD 0.82 higher

(0.1 lower to 1.75 higher)

IBS

Dronabinol vs Placebo

81 (2 RCTs)

85

⨁◯◯◯

VERY LOW ^c,e

SMD 0

(1.09 lower to 1.09 higher)

MS

Dronabinol vs Placebo

660 (2 RCTs)

74

⨁⨁◯◯

LOW ^c,f

SMD 0.15 lower

(0.51 lower to 0.22 higher)

Nabiximols vs Placebo

863 (5 RCTs)

65

⨁⨁◯◯

LOW ^c,f

SMD 0.14 lower

(0.38 lower to 0.11 higher)

Parkinson

Nabilone vs Placebo

51 (2 RCTs)

46

⨁◯◯◯

VERY LOW ^c,e

SMD 0.38 lower

(1.05 lower to 0.29 higher)

Cannabidiol vs Placebo

101 (3 RCTs)

0

⨁⨁⨁◯

MODERATE ^g

SMD 0.41 lower

(0.75 lower to 0.08 lower)

ADHD

Nabiximols vs Placebo

30 (1 RCT)

SMD 0.83 lower

(1.58 lower to 0.09 lower)

Anorexia nervosa

Dronabinol vs Placebo

48 (1 RCT)

SMD 0.47 lower

(0.89 lower to 0.05 lower)

Dronabinol vs Active

22 (1 RCT)

SMD 0.06 lower

(0.65 lower to 0.53 higher)

Anxiety

Dronabinol vs Placebo

113 (4 RCTs)

49

⨁⨁◯◯

LOW ^e

SMD 0.03 lower

(0.47 lower to 0.41 higher)

Dronabinol vs Active

278 (1 RCT)

SMD 0.14 higher

(0.03 lower to 0.31 higher)

Nabilone vs Placebo

147 (6 RCTs)

84

⨁◯◯◯

VERY LOW ^a,c,e

SMD 0.59 lower

(1.4 lower to 0.22 higher)

Nabilone vs Active

192 (2 RCTs)

11

⨁⨁◯◯

LOW ^e

SMD 0.11 lower

(0.33 lower to 0.11 higher)

Cannabidiol vs Placebo

481 (11 RCTs)

78

⨁◯◯◯

VERY LOW ^c,e

SMD 0.34 lower

(0.73 lower to 0.06 higher)

Nabiximols vs Placebo

258 (6 RCTs)

43

⨁⨁◯◯

LOW ^e

SMD 0.06 higher

(0.23 lower to 0.34 higher)

Dementia

Dronabinol vs Placebo

115 (3 RCTs)

3

⨁⨁◯◯

LOW ^e

SMD 0.27 lower

(0.57 lower to 0.04 higher)

Nabilone vs Placebo

76 (1 RCT)

SMD 0.53 lower

(0.87 lower to 0.19 lower)

Depression

Dronabinol vs Placebo

700 (7 RCTs)

83

⨁⨁◯◯

LOW ^c,f

SMD 0.15 lower

(0.49 lower to 0.19 higher)

Dronabinol vs Active

278 (1 RCT)

SMD 0.14 higher

(0.03 lower to 0.31 higher)

Nabilone vs Placebo

76 (3 RCTs)

0

⨁⨁◯◯

LOW ^e

SMD 0.03 lower

(0.48 lower to 0.43 higher)

Nabilone vs Active

192 (2 RCTs)

0

⨁⨁◯◯

LOW ^e

SMD 0.03 lower

(0.23 lower to 0.17 higher)

Cannabidiol vs Placebo

301 (6 RCTs)

0

⨁⨁◯◯

LOW ^e

SMD 0.12 higher

(0.09 lower to 0.34 higher)

Nabiximols vs Placebo

413 (7 RCTs)

43

⨁⨁⨁◯

MODERATE ^f

SMD 0.12 lower

(0.36 lower to 0.13 higher)

PTSD

Dronabinol vs Placebo

46 (1 RCT)

SMD 0.63 lower

(1.22 lower to 0.03 lower)

Nabilone vs Placebo

18 (1 RCT)

SMD 0.88 lower

(1.65 lower to 0.11 lower)

Schizophrenia

/psychosis

Dronabinol vs Placebo

26 (1 RCT)

SMD 0.89 higher

(0.25 higher to 1.53 higher)

Cannabidiol vs Placebo

152 (3 RCTs)

70

⨁◯◯◯

VERY LOW ^c,f

SMD 0.24 lower

(0.81 lower to 0.33 higher)

Cannabidiol vs Active

39 (1 RCT)

SMD 0.05 higher

(0.58 lower to 0.68 higher)

Sleep

Dronabinol vs Placebo

683 (7 RCTs)

64

⨁⨁◯◯

LOW ^c,f

SMD 0.13 lower

(0.39 lower to 0.12 higher)

Dronabinol vs Active

22 (1 RCT)

SMD 1.12 higher

(0.37 higher to 1.87 higher)

Nabilone vs Placebo

175 (6 RCTs)

77

⨁◯◯◯

VERY LOW ^c,g

SMD 0.58 lower

(1.14 lower to 0.01 lower)

Nabilone vs Active

200 (2 RCTs)

91

⨁◯◯◯

VERY LOW ^d,e

SMD 0.21 lower

(0.97 lower to 0.55 higher)

Cannabidiol vs Placebo

961 (8 RCTs)

46

⨁⨁◯◯

LOW ^a,c

SMD 0.06 lower

(0.23 lower to 0.11 higher)

Nabiximols vs Placebo

3659 (23 RCTs)

61

⨁⨁⨁◯

MODERATE ^c

SMD 0.24 lower

(0.35 lower to 0.14 lower)

SUDs

Dronabinol vs Placebo

196 (3 RCTs)

0

⨁⨁◯◯

LOW ^a,g

SMD 0.47 lower

(0.73 lower to 0.2 lower)

Dronabinol vs Active

60 (1 RCT)

SMD 0.85 lower

(1.41 lower to 0.29 lower)

Nabilone vs Placebo

70 (3 RCTs)

0

⨁⨁◯◯

LOW ^a,g

SMD 0.55 lower

(0.93 lower to 0.18 lower)

Cannabidiol vs Placebo

353 (7 RCTs)

81

⨁◯◯◯

VERY LOW ^c,e

SMD 0.2 lower

(0.63 lower to 0.24 higher)

Nabiximols vs Placebo

237 (4 RCTs)

59

⨁⨁⨁◯

MODERATE ^g

SMD 0.48 lower

(0.92 lower to 0.04 lower)

Tourette

Dronabinol vs Placebo

41 (2 RCTs)

0

⨁⨁⨁◯

MODERATE ^g

SMD 1.01 lower

(1.58 lower to 0.44 lower)

Retention

Dronabinol vs Placebo

3285 (37 RCTs)

65

⨁⨁◯◯

LOW ^c,f

OR 1.11

(0.80 to 1.53)

194 per 1.000

17 more per 1.000

(33 fewer to 75 more)

Dronabinol vs Active

1079 (8 RCTs)

32

⨁◯◯◯

VERY LOW ^a,e

OR 1.03

(0.76 to 1.40)

422 per 1.000

7 more per 1.000

(65 fewer to 83 more)

Nabilone vs Placebo

1070 (16 RCTs)

0

⨁◯◯◯

VERY LOW ^a,e

OR 0.99

(0.76 to 1.29)

143 per 1.000

1 fewer per 1.000

(30 fewer to 34 more)

Nabilone vs Active

1004 (13 RCTs)

0

⨁◯◯◯

VERY LOW ^a,e

OR 0.99

(0.79 to 1.25)

205 per 1.000

2 fewer per 1.000

(36 fewer to 39 more)

Cannabidiol vs Placebo

1775 (22 RCTs)

41

⨁◯◯◯

VERY LOW ^c,g

OR 1.38

(0.77 to 2.47)

71 per 1.000

24 more per 1.000

(15 fewer to 88 more)

Nabiximols vs Placebo

4643 (33 RCTs)

44

⨁⨁◯◯

LOW ^c,f

OR 1.17

(0.92 to 1.49)

170 per 1.000

23 more per 1.000

(11 fewer to 64 more)

Adverse events

Dronabinol vs Placebo

2707 (37 RCTs)

56

⨁⨁◯◯

LOW ^c

OR 2.16

(1.59 to 2.94)

320 per 1.000

184 more per 1.000

(108 more to 260 more)

Dronabinol vs Active

925 (8 RCTs)

67

⨁⨁◯◯

LOW ^a,c

OR 2.75

(1.43 to 5.26)

466 per 1.000

240 more per 1.000

(89 more to 355 more)

Nabilone vs Placebo

996 (16 RCTs)

76

⨁⨁⨁◯

MODERATE ^c

OR 3.12

(1.52 to 6.42)

226 per 1.000

251 more per 1.000

(81 more to 426 more)

Nabilone vs Active

909 (13 RCTs)

71

⨁⨁◯◯

LOW ^a,c

OR 2.47

(1.45 to 4.20)

223 per 1.000

192 more per 1.000

(71 more to 324 more)

Cannabidiol vs Placebo

1736 (22 RCTs)

58

⨁⨁⨁◯

MODERATE ^c

OR 1.82

(1.08 to 3.07)

482 per 1.000

147 more per 1.000

(19 more to 259 more)

Nabiximols vs Placebo

4404 (33 RCTs)

74

⨁⨁⨁◯

MODERATE ^c

OR 1.97

(1.48 to 2.64)

536 per 1.000

159 more per 1.000

(95 more to 217 more)