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Randomized, placebo-controlled, 28-day safety and pharmacokinetics evaluation of repeated oral cannabidiol administration in healthy dogs

OBJECTIVE To determine the safety and pharmacokinetics of various doses of plant- derived cannabidiol (CBD) versus placebo following repeated oral administration. ANIMALS 20 healthy adult Beagles. PROCEDURES In a randomized, blinded, placebo-controlled trial, dogs were randomized to 5 groups balanced in body weight and sex (n = 4 dogs/group) and received a CBD (1, 2, 4, or 12 mg/kg; from cannabis extract) or placebo oil formulation PO once daily for 28 days. Outcome variables were assessed through daily health observations, veterinary examinations, CBC, and serum biochemical analysis. Blood samples were collected at various time points to estimate 24- hour pharmacokinetic profiles of CBD and...
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Preliminary Investigation of the Safety of Escalating Cannabinoid Doses in Healthy Dogs

Objective: To determine the safety and tolerability of escalating doses of three cannabis oil formulations, containing predominantly CBD, THC, or CBD and THC (1.5:1) vs. placebo in dogs. Design: Randomized, placebo-controlled, blinded, parallel study. Animals: Twenty healthy Beagle dogs (10 males, 10 females). Methods: Dogs were randomly assigned to one of five treatment groups (n = 4 dogs per group balanced by sex): CBD-predominant oil, THC-predominant oil, CBD/THC-predominant oil (1.5:1), sunflower oil placebo, medium-chain triglyceride oil placebo. Up to 10 escalating doses of the oils were planned for administration via oral gavage, with at least 3 days separating doses. Clinical observations, physical examinations, complete blood counts, clinical chemistry, and...
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Safety and tolerability of escalating cannabinoid doses in healthy cats

Abstract 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...
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US Veterinarians’ Knowledge, Experience, and Perception Regarding the Use of Cannabidiol for Canine Medical Conditions

Due to the myriad of laws concerning cannabis, there is little empirical research regarding the veterinary use of cannabidiol (CBD). This study used the Veterinary Information Network (VIN) to gauge US veterinarians' knowledge level, views and experiences related to the use of cannabinoids in the medical treatment of dogs. Participants (n = 2130) completed an anonymous, online survey. Results were analyzed based on legal status of recreational marijuana in the participants' state of practice, and year of graduation from veterinary school. Participants felt comfortable in their knowledge of the differences between Δ9-tetrahydrocannabinol (THC) and marijuana, as well as the toxic effects of marijuana in...
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Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs

Osteoarthritis (OA) is the most common chronic condition that dogs face. If diagnosed, it is important to focus on managing the symptoms versus find a cure. This study shows that cannabidiol (CBD) can help increase comfort and activity levels in dogs with OA. Objectives: The objectives of this study were to determine basic oral pharmacokinetics, and assess safety and analgesic efficacy of a cannabidiol (CBD) based oil in dogs with osteoarthritis (OA). Methods: Single-dose pharmacokinetics was performed using two different doses of CBD enriched (2 and 8 mg/kg) oil. Thereafter, a randomized placebo-controlled, veterinarian, and owner blinded, cross-over study was conducted. Dogs received each...
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Use of CBD-Rich Hemp Nutraceutical in Healthy Dogs and Cats

The use of cannabidiol (CBD)-rich hemp-based nutraceuticals is increasing in dogs and cats for disorders related to anxiety, seizures, cancer and pain. To date, there is little information related to appropriate dosing or long-term effects on serum chemistry or complete blood counts (CBC), and little data on the pharmacokinetics of single- or long-term dosing in dogs and cats. Single-dose pharmacokinetics and preliminary 12-week serum chemistry and complete blood counts are reported here showing short pharmacokinetic half-lives of cannabidiol in dogs and cats, with cats showing far lower oral absorption kinetics or rapid elimination suggesting dosing may differ between the two species. Fortunately, there were...
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The Endocannabinoid System of Animals

Our understanding of the Endocannabinoid System of animals, and its ubiquitous presence in nearly all members of Animalia, has opened the door to novel approaches targeting pain management, cancer therapeutics, modulation of neurologic disorders, stress reduction, anxiety management, and inflammatory diseases. Both endogenous and exogenous endocannabinoid-related molecules are able to function as direct ligands or, otherwise, influence the EndoCannabinoid System (ECS). This review article introduces the reader to the ECS in animals, and documents its potential as a source for emerging therapeutics.
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Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors

In this study, we report the isolation from canine intestines of 2-arachidonyl glycerol (2-Ara-Gl). Its structure was determined by mass spectrometry and by direct comparison with a synthetic sample. 2-Ara-Gl bound to membranes from cells transiently transfected with expression plasmids carrying DNA of either CB1 or CB2--the two cannabinoid receptors identified thus far--with Ki values of 472 +/- 55 and 1400 +/- 172 nM, respectively. In the presence of forskolin, 2-Ara-Gl inhibited adenylate cyclase in isolated mouse spleen cells, at the potency level of delta 9-tetrahydrocannabinol (delta 9-THC). Upon intravenous administration to mice, 2-Ara-Gl caused the typical tetrad of effects produced by THC: antinociception,...
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