Table 2.

Summary of studies on the efficacy of Cannabis derivatives in dogs

Study design, formulation, dose, treatment duration and n. of recruited dogs	Efficacy	Tolerability	Reference
Cannabis derivatives in chronic pain from osteoarthritis (OA)
Randomized, placebo-controlled, double-blind, crossover clinical trial to evaluate the analgesic efficacy of a CBD-dominant hemp oil (equal mix of CBD and CBDA, 2 mg/kg orally twice daily for four weeks) on OA-related pain relief in 16 dogs.	CBD produced a significant decrease in pain scores measured by the Canine Brief Pain Inventory (CBPI) and increased activity levels measured by the Hudson activity scale at weeks 2 and 4 during CBD treatment compared to baseline (week 0) and placebo.	Owners reported no side effects; however, serum chemistry showed an increase in alkaline phosphatase (ALP) activity during CBD treatment in 9 out of 16 treated dogs.	Gamble et al. 2018
Randomized, placebo-controlled, double-blind clinical trial to evaluate the analgesic potential of different doses and formulations of hemp-derived CBD oil on OA-related pain in 20 dogs. Dogs received 20 or 50 mg/day of naked CBD, or 20 mg/day of liposomal CBD, or placebo, orally, for four weeks.	CBD significantly increased mobility and reduced pain scores measured by the Helsinki Chronic Pain Index (HCPI) in a dose-dependent manner, with liposomal CBD being as effective as the higher dose of non-liposomal CBD in improving clinical outcomes.	No relevant changes in cell blood counts and biochemical profile were reported following treatments.	Verrico et al. 2020
Randomized placebo-controlled study to evaluate the efficacy of a pure CBD oil formulation in relieving OA-related pain in 9 dogs. CBD was given by oral transmucosal route (OTM, 2 mg/kg CBD twice daily for 12 weeks), within a multimodal analgesic drug regimen.	The OTM CBD improved owner-reported pain scores and quality of life of CBD treated dogs as measured by the CBPI.	Minimal ptyalism, somnolence and mild ataxia were recorded in 2 and 3 dogs in the CBD-treated group, respectively. No relevant changes in the blood cell count and serum biochemical analysis were noted.	Brioschi et al. 2020
Double-blind, randomized, placebo-controlled, crossover clinical study to evaluate the efficacy of a CBD-dominant hemp oil (2.5 mg/kg of CBD orally twice daily for six weeks) on OA-related pain in 23 dogs.	No differences were observed between groups at any time point for any of the outcomes (objective gait analysis, activity counts and pain scores measured by the Liverpool Osteoarthritis in Dogs– LOAD– and the CBPI).	Vomiting in 1/24 dogs, and mild elevation in liver enzymes in 14/24 were recorded.	Mejia et al. 2021
Pilot clinical study to evaluate the efficacy of a dietary supplement containing CBD, Boswellia serrata and Cucumis melo on OA-related pain in 8 dogs. The daily quantity of CBD was about 2.4 mg/15 kg BW for 30 days.	A significant reduction in pain scores measured by the HCPI at the end of the study was recorded.	No adverse effects were observed.	Martello et al. 2019
Pilot clinical study to evaluate the therapeutic efficacy of a single subcutaneous injection of liposomal-CBD (5 mg/kg) on OA-related pain in 6 dogs. Dogs were monitored for six weeks after treatment.	Dogs showed significantly improved CBPI pain severity scores compared with baseline at weeks 2 and 3, improved CBPI pain interference scores at weeks 2 and 6, improved CBPI total scores at weeks 2 and 3 and borderline improvement at week 6, and improved CBPI quality of life at weeks 2 and 3. Collar activity scores were significantly increased on weeks 5 and 6.	The main adverse effect was minor local swelling for several days in 5/6 dogs.	Shilo-Benjamini et al. 2023
Non-blinded observational study to evaluate the efficacy of a CBD-dominant full-spectrum hemp oil-based product (0.3–4.12 mg/kg of CBD orally twice daily for 90 days) as adjunctive therapy (dogs were under multimodal analgesic therapy - acupuncture, laser, nutraceuticals, polysulfated glycosaminoglycan, and/or gabapentin) on OA-related pain in 32 dogs.	Thirty out of 32 dogs showed pain relief (as measured on a 0 to 10 scale, with 0 representing no pain and 10 the worst possible pain), and 21/23 dogs could reduce or discontinue gabapentin.	An increase in ALP activity was the only detected adverse effect.	Kogan et al., 2020
Case report on one dog with chronic OA treated with a CBD-purified hemp oil (1 mg/kg orally twice daily for 30 days).	CBD treatment produced analgesia with consequent improvement in mobility and quality of life of the dog.	N.R.	Coelho et al. 2021
Case report on a dog subcutaneously injected with a liposomal cannabidiol formulation (5 mg/kg) for pain management as compassion care. The dog was cachectic, presented general muscle atrophy, suffered from bilateral hip and elbow osteoarthritis and severe cervical pain, and had a suspected testicular neoplasia. Notwithstanding a multimodal analgesic treatment on board, the dog deteriorated rapidly, with increased pain, and decreased function.	After the CBD injection, the dog showed improved CBPI and Interactive Visual Analog Scale (iVAS) pain scores, and increased collar activity scores (compared to his activity before the injection) up to 3 weeks following injection.	N.R.	Shilo-Benjamini et al. 2022
Cannabis derivatives in chronic pain (origin not detailed)
Double-blind placebo-controlled study to evaluate the efficacy of a hemp oil (containing 15 mg/ml total cannabinoids) in organic extra virgin olive oil (2 mg phytocannabinoids/kg orally twice a day for 8 weeks, and placebo for the previous or the following 8 weeks, depending on group allocation of dogs) in 40 dogs living with pain.	The intervention was positively associated with a decrease in pain scores (based on CBPI), increased ability to walk up and down the stairs, and improved daily activity. Decreases in plasma levels of proinflammatory cytokines TNF-α, IL-6, and IL-8 were also observed.	No major adverse effects attributable to the intervention were reported during the study. The incidence of vomiting or diarrhea were rare and equally distributed between the intervention and placebo groups. Blood work showed no significant changes in most of the parameters tested.	Panda et al. 2024
Cannabis derivatives in epilepsy
Randomized placebo-controlled, double-blinded clinical trial to assess the efficacy of a CBD-infused hemp oil (2.5 mg/kg orally twice daily for 12 weeks) in addition to conventional antiepileptic treatment on seizure frequency in 26 dogs with idiopathic epilepsy.	Compared to the placebo group, the CBD-treated group exhibited a significant reduction in seizure frequency (median change, 33%). However, there were no differences between groups in the proportion of dogs considered responders to treatment (≥ 50% decrease in seizure activity).	The only adverse effect was increased ALP activity.	McGrath et al. 2019
Randomized, controlled-placebo, crossover study to evaluate the efficacy of a CBD and CBDA-rich hemp product (2 mg/kg orally twice daily for 12 weeks) for the treatment of refractory epileptic seizures in 14 dogs.	The CBD treatment produced a statistically significant reduction in epileptic seizure frequency and number of epileptic seizure days compared to the placebo group.	Mild adverse events included vomit/diarrhea, somnolence, anxiety, and mild worsening of ataxia, occurring in 2, 3, 2 and 4 treated subjects, respectively.	Garcia et al. 2022
Double-blinded placebo-controlled crossover study to evaluate the efficacy of a CBD-infused hemp seed oil on total seizures and seizure days in 51 dogs with at least two seizures per month while receiving at least one antiseizure drug (ASD), with phenobarbital, potassium bromide, zonisamide and levetiracetam being the most used ASD. As the initial tested 5 mg/kg/day dose did not produce any change in 12 dogs, a dosage of 9 mg/kg/day (orally for three months) was used in the following 39 dogs.	At the lower CBD dose, no significant changes to total seizures or seizure days were observed. At the higher dose, a slight increase in the percentage change (3.31%) of total seizures from baseline was recorded, which was significantly lower compared to the placebo group (30.72%). Conversely, the percentage change of seizure days in the CBD group decreased significantly by 24.1%, whereas dogs on placebo had a 5.81% increase. A percentage change ≥ 50% (responders) was observed in 9 subjects in the CBD group and 8 in the placebo group for total seizures, and in 13 versus 8 subjects for seizure days. These differences were not significant.	Significant increase in mean serum ALP and alanine aminotransferase (ALT) activity in the CBD group. Owners reported various adverse effects, including decreased or increased appetite, vomiting, soft feces or diarrhea, anxiety, increased or decreased activity, ataxia, and aggression. Among these, decreased appetite and vomiting were more frequently reported in the CBD group.	Rozental et al. 2023b
Case series to evaluate the efficacy of a CBD-predominant full-spectrum hemp oil in 3 dogs with suspected epilepsy. Dogs were treated respectively with different doses of CBD (0.51 mg/kg, 1.24–1.25 mg/kg and 5 mg/kg, respectively), given orally twice daily for eight weeks.	Results varied among dogs, with one experiencing a considerable reduction in epileptic seizure frequency and improvement of other signs (i.e., aggression behavior), another showing slight improvement of seizure intensity, and the third showing no response to therapy, as reported by the owners.	Somnolence in 2/3 dogs was the only reported adverse effect.	Mogi and Fukuyama 2019
Cannabis derivatives in behavioral disorders
Replicated 4 × 4 Latin square design experiment to evaluate the influence of a CBD industrial hemp extract incorporated into treats on behavioral responses (such as cowering, shaking, vocalization, destructiveness, and tucking tail upon the start of the fireworks track) to fear-inducing stimuli in 16 dogs. CBD was dosed at 1.4 mg/kg orally 4–6 h prior to the test.	The obtained results did not provide strong support for the anxiolytic effect of CBD in dogs.	N.R.	Morris et al. 2020
Placebo-controlled study to determine if a 5% CBD-based oil (dosed at ~ 1.25 mg/kg orally once a day for 45 days) could affect stress related behavior in 12 shelter dogs.	Aggressive behaviour towards humans decreased significantly over time in the CBD treatment group. However, only the T0-T2 (baseline - 45th day) comparison was significant in the pairwise comparisons.	One-day duration diarrhea (1/24) was the only reported side effect.	Corsetti et al. 2021
Blinded, placebo-controlled, parallel-design study to determine the anxiolytic effect of a CBD based hemp derived distillate incorporated into soft gel capsules (~ 4 mg/kg of CBD orally 2 h prior to the test) in dogs experiencing a separation event (n=21) or a car travel (n=19).	The mitigating effect of CBD treatment varied by outcome. measures and tests, with some indicating a significant reduction in canine stress compared to the placebo group.	N.R.	Hunt et al. 2023
Blinded, parallel study design to determine whether multiple doses of a tetrahydrocannabinol-free CBD distillate (4 mg/kg of CBD orally 2 h prior the tests) over a period of 6 months could positively influence measures of stress due to a series of short car journeys (test) in 19 dogs.	The mitigating effect of CBD treatment varied by measure, with cortisol, whining, lip licking, and qualitative behavioral ratings indicating a significant reduction in canine stress compared to the placebo group for at least one time point. The effect of CBD decreased over time following 6 months of daily treatment.	N.R.	Flint et al. 2024
Pilot study to evaluate the effects of CBD administration (2.0 mg/kg/day orally over a 2-week-period) compared to placebo on the vocal activity of 10 healthy domestic dogs upon their temporary separation from caregivers.	All dogs vocalized more often when being left alone, regardless they had received CBD or placebo, but the degree of such increase was significantly less robust following the CBD administration, probably due to an anxiolytic effect of CBD.	N.R.	Masataka 2024
Cannabis derivatives in skin diseases
Randomised, double-blinded and placebo-controlled trial to determine if the administration of gelatin capsules containing a CBD/CBDA-rich hemp extract (2 mg/kg orally twice daily for 28 days) as an adjunct therapy decreased pruritus and cutaneous lesions in 17 dogs with atopic dermatitis.	Lesion severity was not affected by CBD/CBDA; however, the treatment did have a positive effect on pruritus, as scored with the Pruritus Visual Analog Scale (PVAS, a 0 to10 scale, with 0 representing a complete absence of pruritus and 10 the most severe form of pruritus), in some dogs.)	Adverse effects were lethargy (2/17), somnolence and sleepiness (2/17), decreased aggression (1/17) and increased calmness (3/17), regurgitation (1/17), increased flatulence (1/17), loss of appetite (1/17), increased energy/mobility (2/17). While not significant, ALP was elevated outside the reference range in six of 17 treatment group dogs on the 28th day.	Loewinger et al. 2022
Double-blinded and placebo-controlled trial to evaluate the effectiveness of a full-spectrum cannabis oil rich in CBD (2.5 mg/kg orally twice daily for 60 days) in 14 dogs with atopic dermatitis.	No differences regarding lesions’ severity and pruritus in pre- and post-treatment were obtained.	N.R.	Mariga et al. 2023
Retrospective case series examining the effect of a 10% CBD-containing broad-spectrum hemp oil as a supplemental treatment for canine atopic dermatitis in 8 dogs. CBD treatment started with an initial dose of approximately 0.07 to 0.25 mg/kg orally twice daily; then, the dose was increased up to 0.72 mg/kg if no apparent change was observed with the previous dose. Administration was performed for at least eight weeks.	While there was relatively little change in lesion severity, CBD decreased the occurrence of pruritus, as scored with a PVAS, in 6/8 dogs.	No adverse events were reported following the ingestion of the CBD oil.	Mogi et al. 2022
Case report of a dog with discoid lupus erythematosus (DLE) resistant to conventional treatment. The dog was treated orally as follow: initial dose 1 drop/day (0.08 mg/kg) of a full-spectrum oil containing a 2:1 THC: CBD ratio (40 mg/ml); the dose was then modified (increased and decreased), up to a final dose of 3 drops once daily (0.24 mg/kg total cannabinoids) and the adjunct of 10 drops of a full-spectrum CBD-rich oil (50 mg/mL) twice daily (1.96 mg/kg/day total cannabinoids).	Significant improvement in skin lesions within a few weeks was observed, and after 1 year the dog remained clinically stable on a low dose of full-spectrum CBD-rich oil.	No evidence of DLE recurrence was observed.	Da Silva et al. 2024

N.R.: Not reported