TABLE 2.
Interventional studies investigating the safety (only) of low‐dose CBD
| Citation | Study design | Participant population | CBD dose (mg) | Primary outcome(s) | Side effects (n Incidence) |
|---|---|---|---|---|---|
| Studies involving doses of ≤60 mg CBD | |||||
| Atsmon et al. 64 | Open label (without controls) |
15 M; ~31 years Healthy volunteers |
10 mg; SD | Pharmacokinetic | Headache (reported in 14–24% participants). No SAEs reported. |
| Carlini and Cunha 29 (experiment 4) | DB (PC); BSD |
4 M; NS Healthy volunteers |
10 mg/day; 20‐days | Safety | CBD group: Somnolence (2) |
| Škopek et al. 65 | “Blind” (PC); WSD |
16 M; 23 ± 1 years Healthy volunteers |
11 mg; SD | Cognitive | None reported. No effect of CBD on simple or choice reaction time. |
| Knaub et al. 66 | Open label (without controls) |
16 (8 M); ~28 years Healthy volunteers |
25 mg; SD (2 different formulations) |
Pharmacokinetic | Diarrhea (1). No SAEs reported. |
| Bird et al. 67 | DB (PC); WSD |
161 (122 M); ~21 years Healthy volunteers |
320 μg/kg (~21 mg); SD |
Cognitive | None reported. No effect of CBD on cognitive performance. |
| Belgrave et al. 68 | DB (PC); WSD |
15 (11 M); ~21 years Healthy volunteers |
320 μg/kg (~21 mg); SD |
Cognitive | None reported. No effect of CBD on cognitive performance. |
| Williams et al. 69 | Open label (without controls) |
15 (9 M); 29 ± 11 years Healthy volunteers |
30 mg; SD (5 different formulations) |
Pharmacokinetic | None reported. No effect of the CBD formulations on heart rate variability, heart rate or blood pressure |
| Carlini and Cunha 29 (experiment 1) | Open label (without controls) |
2 (NS) Healthy volunteers |
10 mg; SD | Safety | None reported |
|
2 (NS) Healthy volunteers |
40 mg; SD | ||||
| Patrician et al. 70 | DB (PC); WSD |
12 M; 24 ± 4 years Healthy volunteers |
45 mg; SD (2 different formulations) |
Pharmacokinetic | None reported |
| Devinsky et al. 71 | Open label (without controls) |
11 (9 M); 36 ± 8 years Healthy volunteers |
50 mg; SD | Pharmacokinetic | No “treatment‐emergent” AEs reported |
| Karniol et al. 72 | DB (PC); BSD |
20 M; 21–42 years Healthy volunteers |
15 mg; SD | Subjective effects | None reported. No effect of CBD at any dose on heart rate or time estimation. Low grade psychological impact of CBD on 1 of 5 participants at both 15 and 30 mg |
| 30 mg; SD | |||||
| 60 mg; SD | |||||
| Abbotts et al. 73 | “Blind” (PC); WSD |
14 M; 20–51 years Healthy volunteers |
30 mg; (5 different formulations) |
Pharmacokinetic | None reported. No effect on HR or BP. No effect on liver enzymes. Food increased plasma CBD concentrations |
| Studies involving doses of >60–100 mg CBD | |||||
| Carlini and Cunha 29 (experiment 1) | Open label (without controls) | 2 (NS) | 80 mg; SD | Safety | None reported |
| Izgelov et al. 74 | Open label (without controls) |
12 M; 27–35 years Healthy volunteers |
90 mg; SD (3 different formulations) |
Pharmacokinetic | Somnolence (6) and abdominal pain (2) |
| Patrician et al. 70 | DB (PC); WSD |
12 M; 24 ± 4 years Healthy volunteers |
90 mg; SD (2 different formulations) |
Pharmacokinetic | None reported |
| Spindle, Cone, Goffi et al. 75 | DB (PC); WSD |
19 (8 M); 31 ± 6 years Healthy volunteers |
100 mg; SD | Pharmacokinetic and cognitive | No SAEs reported |
| Spindle et al. 76 | DB (PC); WSD |
6 (3 M); 31 ± 6 years Healthy volunteers |
100 mg; SD | Pharmacokinetic | None reported |
| Atsmon et al. 64 | Open label (without controls) |
15 M; ~31 years Healthy volunteers |
100 mg; SD | Pharmacokinetic | Headache (reported in 14–24% participants). No SAEs reported. |
| Studies involving doses of >100–200 mg CBD | |||||
| Carlini and Cunha 29 (experiment 1) | Open label (without controls) |
2 (NS) Healthy volunteers |
160 mg; SD | Safety | None reported |
| Cunha et al. 77 | DB (PC); BSD |
16 (11 M); 22–35 years Healthy volunteers |
3 mg/kg/day; 30 days (~195 mg/day a ) |
Safety | CBD group: Somnolence (2). No SAEs reported. |
| Carlini and Cunha 29 (experiment 3) | DB (PC); WSD |
10 (6 M); NS Healthy volunteers |
200 mg; SD | Cognitive | No effect of CBD on the cancellation test, differential aptitude test or finger tap test. |
| Tayo et al. 78 | Open label (without controls) |
8 (5 M); 62 ± 11 years Mild renal impairment |
200 mg; SD | Pharmacokinetic | Visual disturbance (1), nausea (1) and drowsiness (1) |
|
8 (5 M); 59 ± 12 years Moderate renal impairment |
200 mg; SD | Pharmacokinetic | None reported | ||
|
8 (3 M); 65 ± 11 years Severe renal impairment |
200 mg; SD | Pharmacokinetic | None reported | ||
|
8 (3 M); 60 ± 12 years Healthy volunteers |
200 mg; SD | Pharmacokinetic | Back pain (1) and hip pain (1) | ||
| Taylor et al. 79 | Open label (without controls) |
8 (4 M); 62 ± 11 years Mild hepatic impairment |
200 mg; SD | Pharmacokinetic | Diarrhea (3) and dizziness (1) |
|
8 (5 M); 59 ± 12 years Moderate hepatic impairment |
200 mg; SD | Pharmacokinetic | Low platelet count (1) | ||
|
8 (3 M); 65 ± 11 years Severe hepatic impairment |
200 mg; SD | Pharmacokinetic | None reported | ||
|
8 (4 M); 60 ± 12 years Healthy volunteers |
200 mg; SD | Pharmacokinetic | None reported | ||
| Studies involving doses of >200–300 mg CBD | |||||
| Crippa et al. 80 | Open label (without controls) |
120 (NS) Healthy volunteers |
300 mg; SD | Pharmacokinetic | None reported |
| Birnbaum et al. 81 | Open label (without controls) |
8 (6 M); ~49 years Localization‐related or intractable epilepsy |
300 mg; SD (fed and fasted) | Pharmacokinetic | None reported |
| Good et al. 82 | Open label (without controls) |
16 (14 M); 58 ± 12 years Advanced cancer |
Median 300 mg/day; 28 days | Tolerability | “…generally well‐tolerated, the major adverse effect being drowsiness that seemed dose‐related and improved with dose reduction” |
| Studies involving oral of >300–400 mg CBD | |||||
| Perkins et al. 83 | DB (PC); BSD |
12 (7 M); ~28 years Healthy volunteers |
5 mg/kg; SD (~310 mg/kg b ) | Pharmacokinetics | CBD group: Hunger (1), dizziness (1), headache (1) and drug eruption (1) |
| Manini et al. 84 | DB (PC); WSD |
17 (9 M); 39 ± 2 years Healthy volunteers |
400 mg; SD (with fentanyl) | Safety and pharmacokinetics of fentanyl | CBD group: Gastrointestinal discomfort (6), dizziness/drowsiness (5), itching/rash (3), headache (2). No SAEs. |
| Haney et al. 85 | DB (PC); WSD |
31 (17 M); 29 ± 9 years Regular cannabis users |
400 mg; SD (with cannabis) | Subjective and physiological effects of cannabis | CBD group: Headache (2), gastrointestinal (1) and blurred vision (1) |
Note: Those that were administered CBD only (i.e., no placebo) were considered “open label” regardless of the design used as participants were aware that they would be receiving CBD.
Abbreviations: AE, adverse event; BP, blood pressure; BSD, between‐subjects design; CBD, cannabidiol; DB, double‐blind; HR, heart rate; M, male; NS, not specified; PC, placebo‐controlled; SAEs, serious adverse events; SD, single dose; WSD, within‐subjects design.
At a reported average body weight of 65 kg.
Assuming an average body weight of 62 kg.