Oral Transmucosal Cannabidiol Oil Formulation as Part of a Multimodal Analgesic Regimen: Effects on Pain Relief and Quality of Life Improvement in Dogs Affected by Spontaneous Osteoarthritis

Brioschi, Federica Alessandra; Cesare, Federica Di; Gioeni, Daniela; Rabbogliatti, Vanessa; Ferrari, Francesco; D'Urso, Elisa Silvia; Amari, Martina; Ravasio, Giuliano

doi:10.3390/ani10091505

Cited by 63 publications

(138 citation statements)

References 49 publications

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“…There are no published studies on the efficacy of cannabinoids in cats. In dogs with osteoarthritis, CBD has been shown to reduce pain and increase mobility when administered at 1.2 mg/kg daily for 4 weeks, 3 and to reduce pain and improve quality of life when administered at 2 mg/kg q24h for 12 weeks 4 or q12h (1:1 CBD:CBDA) for 4 weeks. 5 CBD (2.5 mg/kg q12h for 12 weeks) has also been shown to decrease seizure frequency in dogs with intractable idiopathic epilepsy.…”

Section: Introductionmentioning

confidence: 99%

Safety and tolerability of escalating cannabinoid doses in healthy cats

Kulpa¹,

Paulionis²,

Eglit³

et al. 2021

Journal of Feline Medicine and Surgery

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Objectives The aim of this study was to determine the safety and tolerability of escalating doses of orally delivered cannabis oils predominant in cannabidiol (CBD), tetrahydrocannabinol (THC), or both CBD and THC in healthy cats. Methods In this placebo-controlled, blinded study, 20 healthy adult cats were randomized to one of five treatment groups (n = 4 per group): two placebo groups (sunflower oil [SF] or medium-chain triglyceride oil [MCT]), or three plant-derived cannabinoid oil groups (CBD in MCT, THC in MCT or CBD/THC [1.5:1] in SF). Up to 11 escalating doses of each formulation were delivered orally via syringe to fasted subjects, with at least 3 days separating doses. Safety and tolerability were determined from clinical observations, complete blood counts (CBCs) and clinical chemistry. Plasma cannabinoids (CBD, THC) and metabolites (7-COOH-CBD, 11-OH-THC) were assessed. Results Titration to maximum doses of 30.5 mg/kg CBD (CBD oil), 41.5 mg/kg THC (THC oil) or 13.0:8.4 mg/kg CBD:THC (CBD/THC oil) was safely achieved in all subjects. All observed adverse events (AEs) were mild, transient and resolved without medical intervention. Gastrointestinal AEs were more common with formulations containing MCT. Constitutional (lethargy, hypothermia), neurologic (ataxia) and ocular (protrusion membrana nictitans) AEs were more common with oils containing THC (CBD/THC and THC oils). There were no clinically significant changes in CBC or clinical chemistry across treatment groups. Higher plasma levels of the cannabinoids and their metabolites following administration of the CBD/THC combination product are suggestive of a pharmacokinetic interaction. Conclusions and relevance This is the first feline study to explore the safety and tolerability of CBD and THC, alone and in combination, in a controlled research setting. These findings will inform veterinarians of the safety profile of cannabinoids, particularly when considering the potential therapeutic use of CBD in cats or recognizing clinical signs associated with accidental exposure to THC-containing products.

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Section: Introductionmentioning

confidence: 99%

Safety and tolerability of escalating cannabinoid doses in healthy cats

Kulpa¹,

Paulionis²,

Eglit³

et al. 2021

Journal of Feline Medicine and Surgery

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“…There has been considerable interest in the use of CBD for both humans and companion animals due to its reported benefits, such as analgesia, anti-inflammatory, anxiolytic, and sedative effects ( 28 – 30 ). The analgesic effect of CBD has been documented in rodent and human models ( 31 – 33 ), and the use of oral and transmucosal CBD oil formulations increased the Canine Brief Pain Inventory (CBPI) and Hudson scores in dogs with osteoarthritis, suggesting an increase in activity and comfort with CBD use ( 34 , 35 ). However, despite evidence of an anxiolytic effect of CBD in both rodents and humans with doses ranging from 2.5 to 10 mg/kg ( 36 – 38 ), a recent report failed to demonstrate an anxiolytic effect of treats containing 1.4 mg CBD/kg body weight (BW) in dogs exposed to a noise-induced fear response test ( 39 ).…”

Section: Introductionmentioning

confidence: 99%

Feeding Cannabidiol (CBD)-Containing Treats Did Not Affect Canine Daily Voluntary Activity

et al. 2021

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Growing public interest in the use of cannabidiol (CBD) for companion animals has amplified the need to elucidate potential impacts. The purpose of this investigation was to determine the influence of CBD on the daily activity of adult dogs. Twenty-four dogs (18.0 ± 3.4 kg, 9 months−4 years old) of various mixed breeds were utilized in a randomized complete block design with treatments targeted at 0 and 2.5 mg (LOW) and at 5.0 mg (HIGH) CBD/kg body weight (BW) per day split between two treats administered after twice-daily exercise (0700–0900 and 1,700–1,900 h). Four hours each day [1,000–1,200 h (a.m.) and 1,330–1,530 h (p.m.)] were designated as times when no people entered the kennels, with 2 h designated as Quiet time and the other 2 h as Music time, when calming music played over speakers. Quiet and Music sessions were randomly allotted to daily a.m. or p.m. times. Activity monitors were fitted to dogs' collars for continuous collection of activity data. Data were collected over a 14-day baseline period to establish the activity patterns and block dogs by activity level (high or low) before randomly assigning dogs within each block to treatments. After 7 days of treatment acclimation, activity data were collected for 14 days. Data were examined for differences using the MIXED procedure in SAS including effects of treatment, day, session (Quiet or Music), time of day (a.m. or p.m.), and accompanying interactions. CBD (LOW and HIGH) did not alter the total daily activity points (P = 0.985) or activity duration (P = 0.882). CBD tended (P = 0.071) to reduce total daily scratching compared with the control. Dogs were more active in p.m. sessions than in a.m. sessions (P < 0.001). During the p.m. session, dogs receiving HIGH tended (P = 0.091) to be less active than the control (CON). During the a.m. and p.m. sessions, CBD reduced scratching compared with CON (P = 0.030). CBD did not affect the activity duration during exercise periods (P = 0.143). These results indicate that, when supplemented with up to 4.5 mg CBD/kg BW/day, CBD does not impact the daily activity of adult dogs, but may exert an antipruritic effect.

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“…Pain Severity Score (PSS), Pain Interference Score (PIS), and Quality of Life Index (QoL), in comparison with dogs that did not receive CBD (Brioschi et al, 2020). When considering individual results, treatment success (reduction of >1 in PSS and >2 in PIS) was obtained in more dogs in the CBD group compared with the comparator group (Brioschi et al, 2020). Verrico et al (2020) reported that owner assessment of animal symptomatology by Helsinki Chronic Pain Index (HCPI) was not significantly altered by administration of placebo or 20 mg day −1 naked CBD; however, administration of 50 mg day −1 naked CBD or 20 mg day −1 liposomal CBD generated statistically significant reductions in pain symptomatology (P < 0.01), an effect that remained statistically significant for at least 15 days after cessation of therapy (P < 0.05).…”

Section: Results With Osteoarthritismentioning

confidence: 99%

Use of cannabis in the treatment of animals: a systematic review of randomized clinical trials

Lima

Santiago

Alves

et al. 2022

Anim. Health. Res. Rev.

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Cannabis is used in the treatment of several human conditions; however, its use is still less explored in veterinary medicine. This systematic review aims to summarize the evidence of efficacy and safety of the use of cannabis for the treatment of animal disease. A literature search was performed for studies published until 16 March 2021 in five databases. Randomized clinical trials (RCTs) that reported the efficacy or safety of cannabis in the treatment of animal disease were included. The RoB 2 Tool was used to assess the risk of bias. A total of 2427 records were identified, of which six studies fully met the eligibility criteria. RCTs were conducted in dogs with osteoarthritis (n = 4), with epilepsy (n = 1), and with behavioral disorders (n = 1). All studies used cannabidiol (CBD) oil in monotherapy or in combination with other drugs. Studies used CBD at 2 or 2.5 mg kg−1 twice daily (n = 4), orally (n = 5), during 4 or 6 weeks (n = 3), and compared CBD with placebo (n = 5). CBD significantly reduced pain and increased activity in dogs with osteoarthritis (n = 3). Moreover, CBD significantly reduced the frequency of seizures in dogs with epilepsy (n = 1) and the aggressive behavior of dogs (n = 1). Although promising results were identified, studies were heterogeneous and presented risks of bias that required caution in the interpretation of findings. Therefore, there was some evidence to support the use of CBD in dogs with osteoarthritis to reduce pain and increased activity, but limited evidence against epilepsy and behavioral problems. In addition, CBD was well tolerated with mild adverse effects. More RCTs with high quality of evidence are needed, including greater numbers of animal subjects, additional species, and clear readout measures to confirm these findings.

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Oral Transmucosal Cannabidiol Oil Formulation as Part of a Multimodal Analgesic Regimen: Effects on Pain Relief and Quality of Life Improvement in Dogs Affected by Spontaneous Osteoarthritis

Cited by 63 publications

References 49 publications

Safety and tolerability of escalating cannabinoid doses in healthy cats

Safety and tolerability of escalating cannabinoid doses in healthy cats

Feeding Cannabidiol (CBD)-Containing Treats Did Not Affect Canine Daily Voluntary Activity

Use of cannabis in the treatment of animals: a systematic review of randomized clinical trials

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