Table 5.
Effect estimates, event rates, and NNHs of meta-analyses examining medical cannabinoids versus placebo for adverse events
| TYPE OF ADVERSE EVENT | STUDY | NO. OF RCTS (NO. OF PARTICIPANTS) | RELATIVE EFFECT ESTIMATE (95% CI), HETEROGENEITY | RE-ANALYSIS EFFECT ESTIMATE (95% CI), HETEROGENEITY | CANNABINOID EVENT RATE | PLACEBO EVENT RATE | NNH |
|---|---|---|---|---|---|---|---|
| Overall | Lobos Urbina and Peña Duran, 201617 | NR | OR = 3.03 (2.42 to 3.80), I2 = 44% | NA | 92% | 78% | 8 |
| Meza et al, 201729 | 4 (1025) | RR = 1.18 (1.10 to 1.27), I2 = NR | NA | NR | NR | NA | |
| Wade et al, 201028 | 3 (666) | NR | RR = 1.42 (1.27 to 1.59),* NA | 79% | 56% | 5 | |
| Wang et al, 200830 | 23 (2068) | Rate ratio of 1.86 (1.57 to 2.21), I2 = 87% | NA | 10.4 per patient-year | 6.9 per patient-year | NA | |
| Whiting et al, 20152 | 29 (3714) | OR = 3.03 (2.42 to 3.80), I2 = 31% | RR = 1.30 (1.21 to 1.39), I2 = 53% | 81% | 62% | 6 | |
| Serious | Mücke et al, 201619 | 6 (1031) | RR = 1.15 (0.88 to 1.49), I2 = NR | NA | 26% | 17% | NS |
| Petzke et al, 201616 | 11 (1568) | RD = 1% (−1% to 3%), I2 = NR | NA | 6.3% | 17% | NS | |
| Wang et al, 200830 | 23 (2068) | Rate ratio 1.04 (0.78 to 1.39), I2 = NR | NA | 0.37 per patient-year | 0.25 per patient-year | NA | |
| Whiting et al, 20152 | 34 (3248) | OR = 1.41 (1.04 to 1.92), I2 = 0% | NA | NR | NR | NA | |
| Withdrawal | Smith et al, 201525 | 2 (276) | RR = 6.85 (1.96 to 23.99), I2 = 0% | NA | 14% | 1% | 8 |
| Tramèr et al, 200127 | 19 (1111) | RelR = 4.67 (3.07 to 7.09), I2 = NR | NA | 11% | 2% | 11 | |
| Mücke et al, 201619 | 6 (1031) | RR = 1.20 (0.85 to 1.71), I2 = NR | NA | 15% | 11% | NS | |
| Petzke et al, 201616 | 11 (1574) | RD = 0.04 (0.01 to 0.07), I2 = 22% | RR = 2.03 (1.43 to 2.88), I2 = 0% | 11% | 5% | 19 | |
| Iskedjian et al, 200718 | 7 (508 observations) | NA | NA | 4.3% | 3.6% | NA | |
| Koppel et al, 201431 | 24 (2737) | NR | NA | 7% | 2% | 22 | |
| Wade et al, 201028 | 3 (666) | NR | RR = 3.04 (1.59 to 5.81),* NA | 11% | 4% | 14 | |
| Whiting et al, 20152 | 23 (2755) | OR = 2.94 (2.18 to 3.96), I2 = 2% | NA | NR | NR | NA | |
| Sedation | Smith et al, 201525 | 2 (139) | RR = 4.47 (0.35 to 57.81), I2 = 72% | NA | 59% | 25% | NS |
| Tramèr et al, 200127 | 15 (1373) | RelR = 1.66 (1.46 to 1.89), I2 = NR | NA | 50% | 30% | 5 | |
| Whiting et al, 20152 | 26 (3168) | OR = 2.83 (2.05 to 3.91) I2 = 27% | NA | NR | NR | NA | |
| “Feeling high” | Smith et al, 201525 | 3 (137) | RR = 31.10 (6.37 to 151.85), I2 = 0% | NA | 70% | 0% | 2 |
| Tramèr et al, 200127 | 8 (1032) | RelR = 10.6 (6.86 to 16.5), I2 = NR | NA | 35% | 3% | 4 | |
| Dysphoria | Smith et al, 201525 | 2 (96) | RR = 9.00 (0.50 to 160.59), I2 = NA | NA | 8% | 0% | NS |
| Tramèr et al, 200127 | 10 (690) | RelR = 8.06 (3.38 to −19.2), I2 = NR | NA | 13% | 0.3% | 8 | |
| Martin-Sanchez et al, 200914 | 4 (343) | OR = 2.56 (0.66 to 9.92), I2 = 0% | RR = 2.85 (0.74 to 10.93), I2 = 0% | 4% | 1% | NS | |
| Euphoria | Martin-Sanchez et al, 200914 | 4 (202) | OR = 4.11 (1.33 to 12.72), I2 = 0% | RR = 3.67 (1.02 to 13.13), I2 = 0% | 15% | 2% | 9 |
| Whiting et al, 20152 | 27 (2420) | OR = 4.08 (2.18 to 7.64), I2 = 49% | NA | NR | NR | NA | |
| Blurred vision or visual hallucination | Tramèr et al, 200127 | 10 (859) | RelR = 6.10 (2.41 to 15.4), I2 = NR | NA | 6% | 0% | 17 |
| Martin-Sanchez et al, 200914 | 5 (296) | OR = 8.34 (4.63 to 15.03), I2 = 0% | RR = 4.93 (2.54 to 9.58), I2 = 0% | 44% | 8% | 3 | |
| Whiting et al, 20152 | 10 (898) | OR = 2.19 (1.02 to 4.68), I2 = 0% | NA | NR | NR | NA | |
| Tinnitus | Martin-Sanchez et al, 200914 | 2 (152) | OR = 2.18 (0.93 to 5.11), I2 = 0% | RR = 2.11 (0.69 to 6.41), I2 = 0% | 16% | 7% | NS |
| Disorientation or confusion | Martin-Sanchez et al, 200914 | 5 (508) | OR = 3.24 (1.51 to 6.97), I2 = 0% | RR = 2.85 (1.25 to 6.47), I2 = 0% | 9% | 2% | 15 |
| Whiting et al, 20152 | 12 (1736) | OR = 5.41 (2.61 to 11.19), I2 = 0% | NA | NR | NR | NA | |
| Dissociation or acute psychosis | Tramèr et al, 200127 | 6 (571) | RelR = 8.58 (6.38 to 11.5), I2 = NR | NA | 5% | 0% | 20 |
| Martin-Sanchez et al, 200914 | 4 (277) | OR = 3.18 (0.89 to 11.33), I2 = 0% | RR = 3.96 (0.90 to 17.40), I2 = 0% | 5% | 0% | NS (20)† | |
| Whiting et al, 20152 | 2 (37) | OR = 1.09 (0.07 to 16.35), I2 = 25% | NA | NR | NR | NA | |
| Speech disorders | Martin-Sanchez et al, 200914 | 3 (200) | OR = 4.13 (2.08 to 8.20), I2 = 0% | RR = 2.91 (1.28 to 6.64), I2 = 0% | 32% | 7% | 5 |
| Ataxia or muscle twitching | Martin-Sanchez et al, 200914 | 6 (540) | OR = 3.84 (2.49 to 5.92), I2 = 39% | RR = 2.43 (1.61 to 3.67), I2 = 0% | 30% | 11% | 6 |
| Whiting et al, 20152 | 6 (920) | OR = 2.62 (1.12 to 6.13), I2 = 0% | NA | NR | NR | NA | |
| Numbness | Martin-Sanchez et al, 200914 | 4 (226) | OR = 3.98 (1.87 to 8.49), I2 = NR | RR = 3.47 (1.34 to 9.00), I2 = 0% | 21% | 4% | 6 |
| Impaired memory | Martin-Sanchez et al, 200914 | 2 (227) | OR = 3.45 (1.19 to 9.98), I2 = NR | RR = 3.41 (0.95 to 12.27), I2 = 0% | 11% | 2% | NS (12)† |
| Disturbance in attention or disconnected thoughts | Martin-Sanchez et al, 200914 | 5 (381) | OR = 5.12 (2.34 to 11.21), I2 = NR | RR = 4.29 (1.75 to 10.53), I2 = 0% | 17% | 2% | 7 |
| Dizziness | Mücke et al, 201619 | 4 (823) | RD = 3% (−2% to 8%), I2 = NR | NA | 14% | 11% | NS |
| Wade et al, 201028 | 3 (666) | NR | RR = 2.87 (2.02 to 4.08),* NA | 32% | 11% | 5 | |
| Whiting et al, 20152 | 41 (4243) | OR = 5.09 (4.10 to 6.32), I2 = 18% | NA | NR | NR | NA | |
| Nausea | Whiting et al, 20152 | 30 (3579) | OR = 2.08 (1.63 to 2.65), I2 = 0% | NA | NR | NR | NA |
| Diarrhea | Whiting et al, 20152 | 17 (2077) | OR = 1.65 (1.04 to 2.62), I2 = 15% | NA | NR | NR | NA |
| Fatigue | Whiting et al, 20152 | 20 (2171) | OR = 2.00 (1.54 to 2.62), I2 = 0% | NA | NR | NR | NA |
| Central nervous system | Petzke et al, 201616 | 9 (1304) | RD = 36% (14% to 59%), I2 = NR | NA | 60% | 27% | 4 |
| Psychiatric | Mücke et al, 201619 | 5 (763) | RD = 1% (−2% to 4%), I2 = NR | NA | 4% | 3% | NS |
| Petzke et al, 201616 | 9 (1304) | RD = 11% (6% to 16%), I2 = NR | NA | 17% | 5% | 9 | |
| Wade et al, 201028 | 3 (666) | NR | RR = 3.29 (1.98 to 5.48),* NA | 19% | 6% | 8 | |
| Dry mouth | Whiting et al, 20152 | 36 (4181) | OR = 3.50 (2.58 to 4.75), I2 = 28% | NA | NR | NR | NA |
| Depression | Whiting et al, 20152 | 15 (2353) | OR = 1.32 (0.87 to 2.01), I2 = 0% | NA | NR | NR | NA |
| Anxiety | Whiting et al, 20152 | 12 (1242) | OR = 1.98 (0.73 to 5.35), I2 = 54% | NA | NR | NR | NA |
| Vomiting | Whiting et al, 20152 | 17 (2191) | OR = 1.67 (1.13 to 2.47), I2 = 0% | NA | NR | NR | NA |
| Asthenia or weakness | Whiting et al, 20152 | 15 (1717) | OR = 2.03 (1.35 to 3.06), I2 = 0% | NA | NR | NR | NA |
| Dyspnea | Whiting et al, 20152 | 4 (375) | OR = 0.83 (0.26 to 2.63), I2 = 0% | NA | NR | NR | NA |
| Hypotension | Tramèr et al, 200127 | 13 (982) | RelR = 2.23 (1.75 to 2.83), I2 = NR | NA | 25% | 11% | 8 |
NA—not applicable, NNH—number needed to harm, NR—not reported, NS—not significant, OR—odds ratio, RCT—randomized controlled trial, RD—risk difference, RelR—relative risk, RR—risk ratio, RCT—randomized controlled trial.
*
Preplanned pooling of 3 studies. Combined data available, so RR was calculated without formal meta-analysis.
†
Confidence intervals suggest that benefit is likely, so estimated NNH provided.