Table 6.
Studies on tolerability of CBD-based products.
| Formulation and dose of CBD, route of administration and treatment’ duration | Dogs (n°) | Side effects (n° of involved dogs/recruited dogs) | References |
|---|---|---|---|
| 1 mg/kg CBD + 1 mg/kg CDBA hemp oil twice a day orally for 4 weeks | 16 | Increase in ALP activity (9/16, CBD group) | (25) |
| CBD oil, CBD microencapsulated and CBD cream, 10 mg/kg or 20 mg/kg twice daily orally or transdermally for 6 weeks | 30 | Diarrhea (30/30), vomiting (6/30), erythematous pinnae (11/30). Other signs: nasal discharge, salivary staining, lameness, prolapsed nictitans, hyperthermia. Transient isosthenuria, hyposthenuria or proteinuria (15/30). Increased ALP activity (11/30). | (93) |
| CBD hemp oil, 0.51–5 mg/kg/day for 8 weeks | 3 | Somnolence (2/3) | (69) |
| 1 mg/kg of CBD +1 mg/kg of CBDA oil in soft chew, orally twice daily for 12 weeks | 8 | Loose stool, vomiting (food or bile products) | (29) |
| CBD-industrial hemp extract oil, Casperome® and powdered melon fruit pulp and juice extract, 2,4 mg/per 15 kg of BW for 4 weeks | 8 | None | (94) |
| CBD-infused oil, 2.5 mg/kg orally twice daily for 12 weeks | 16 | Increased ALP activity | (67) |
| CBD oil, 2 mg/kg twice daily orally transmucosally (OTM) for 12 weeks | 24 | Minimal ptyalism (2/24, only in CBD group), somnolence and mild ataxia (3/24, 1 dog of CBD group, 2 dogs of control group). No relevant changes in the blood cell count and serum biochemical analysis. | (56) |
| CBD hemp oil, 0.3–4.12 mg/kg daily twice for 12 weeks | 30 | Increase in ALP activity | (54) |
| CBD oil and CBD oil liposomally encapsulated, 20 mg/day of naked CBD oil, 50 mg/day of naked CBD oil, 20 mg/day of liposomal CBD oil or placebo orally for 4 weeks | 20 | No relevant changes in cell blood counts and biochemical profile | (55) |
| CBD hemp oil, 1 drop/2 kg (~1.25 mg/kg) orally once a day for 45 days | 24 | One-day duration diarrhea (1/24) | (75) |
| CBD hemp oil, 2.5 mg/kg orally twice daily for 6 weeks | 24 | Vomiting (1/24), mild elevation in liver enzymes (14/24) | (57) |
| CBD hemp oil, 1, 2, 4, or 12 mg CBD/kg once daily for 4 weeks | 20 | Mild and self-limiting gastrointestinal signs (mainly hypersalivation), more incident at the dosage of 12 mg/kg. Transient increase of ALP | (88) |
| CBD hemp oil, 4 mg/kg PO daily for 26 weeks | 40 | Increased ALP activity | (89) |
| CBD-CBDA hemp oil, 2 mg/kg PO twice daily for 12 weeks | 10 | Mild and self-limiting gastrointestinal signs (2/10), somnolence (3/10) and mild worsening of ataxia (4/10) | (68) |
| CBD/CBDA in sesame oil, 2 mg/kg twice daily for 4 weeks | 29 | Lethargy (2/29), somnolence and sleepiness (2/29), decreased aggression (1/29) and increased calmness (3/29), regurgitation (1/29), increased flatulence (1/29), loss of appetite (1/29), increased energy/mobility (2/29). Elevation of ALP activity. Placebo group: diarrhea and regurgitation (1/29). 1 dog excluded for lethargy and behavioral changes. |
(82) |
| CBD/CBDA-rich soft gel and hemp oil, 2 mg/kg daily twice orally for 4 weeks | 8 | Soft gel: vomiting (2/8), loose stools (6/8) Oil: vomiting (1/8) and occasional episodes of licking, grimacing and chomping |
(33) |
| 5, 10 or 20 mg/kg of pure CBD in (MCT) oil twice daily for 2 weeks | 9 (3x dosage) | Vomiting, hyporexia, anorexia (5/9) and an increase in serum ALP activity | (30) |
| CBD/CBDA rich hemp oil, 2–2.5 mg/kg twice daily for 4 weeks | 44 | Increased ALP activity | (58) |
| Purified CBD (Epidiolex™) 0 mg/kg/day (control group, C), 10 mg/kg/day (Low dose, LD), 50 mg/kg/day (Medium dose, MD), 100 mg/kg/day (High Dose, HD) over 39 weeks |
4/sex/group +2/sex for C and HD |
|
(92) |