Clinical Trial Pharmacokinetics, Safety and Clinical Efficacy of CBD Treatment

Pharmacokinetics, Safety and Clinical Efficacy of Cannabidiol Treatment of Osteoarthritic Dogs. July 2018

1-The objectives of the study were to determine basic oral pharmacokinetics and assess safety and analgesic of a cannabidiol (CBD) based oil in dogs with osteoarthritis (OA).

2- Single-dose administrations were performed using two different doses of CBD enriched (2 mg and 8 mg/kg) oil. The CBD extraction was reconstituted into an olive oil base. A randomized placebo controlled, veterinarian and owner blinded cross over study was conducted. Each dog received each of the two treatments with a 2-week wash-out period.

3- Twenty-two client owned dogs with clinically and radiographically confirmed evidence of osteoarthritis were recruited for the study. Sixteen of these dogs completed the study. Dogs were removed due to osteosarcoma (placebo oil), gastric torsion (placebo oil), prior aggression issues (CBE oil), kidney insufficiency (CBD oil), reoccurring pododermatitis (placebo oil) and diarrhea (placebo oil).

3- At each visit each dog was evaluated by a veterinarian based on a scoring system as well by its owner (canine brief pain inventory and Hudson activity scale) and blood was collected to repeat complete blood counts and chemistry analysis at weeks 2 and 4 for each treatment.

4- Pharmacokinetics demonstrated that CBD half-life of elimination median was 4.2 hours for the 2 mg dose and 4.2 hours for the 8 mg dose.

5- There were no significant difference in subjective veterinary lameness and weightbearing capacity. There were no observed side effects.

To view this clinical trial: www.frontierin.org/articles/10.3389/fvets.2018.00165/full

Clinical Trial Baylor MedTerra 2020

A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain - 2020

Chris D. Verricoa, Shonda Wessonc , Vanaja Kondurid , Colby J. Hofferekd , Jonathan Vazquez-Perezd , Emek Blaire, Kenneth Dunner, Pedram Salimpourg , William K. Deckerd, Matthew M. Halpertd

Method: Cannabidiol, provided by MedterraCBD (Irvine, CA), was isolated solely from hemp grown and extracted under the strict guidelines of the Kentucky Department of Agricultural Industrial Hemp pilot program. Subsequent analysis by third party (ProVerde Laboratories, Milford, MA) mass spectrometry confirmed the absence of D9-THC, other cannabinoid derivatives, and contaminants while further HPLC testing demonstrated CBD isolate purity of 99.9%. For all assays, CBD was solubilized in fractionated coconut oil.

Canine Study: Osteoarthritis veterinary trial design Canine veterinary studies were performed with oversight as stipulated by Baylor College of Medicine IACUC protocol AN7705. The study population consisted of client-owned dogs presenting to Sunset Animal Hospital (Houston, TX) for evaluation and treatment of lameness due to OA. Owners completed a brief questionnaire to define the affected limb(s), duration of lameness, and duration of analgesic or other medications taken. Dogs were considered for inclusion in the study if they (1) received an affirmative diagnosed of OA by a veterinarian and (2) demonstrated signs of pain according to assessment by their owners, detectable lameness on visual gait assessment, and painful joint(s) upon palpation. Complete blood count (CBC) and serum chemistry were performed at presentation to rule out other underlying disease. Dogs were excluded by the attending study veterinarian if they exhibited evidence of uncontrolled renal, endocrine, neurologic, or neoplastic disease or were undergoing physical therapy. No cases of OA were related to trauma, and no animals with end-stage disease were enrolled. All other medications were discontinued at least 2 weeks before enrollment.

Results: In this study, neither animals given placebo nor animals given a low daily dose of naked CBD responded to therapy in any significant fashion. Conversely, animals given a high dose of naked CBD or a low dose of liposomally encapsulated CBD experienced significant improvements in quality of life scores as documented by both owner and veterinarian assessments. CBD significantly attenuated the production of pro-inflammatory cytokines IL-6 and TNF-α while elevating levels of anti-inflammatory IL-10. In addition, CBD significantly decreased pain and increased mobility in a dose-dependent fashion among animals with an affirmative diagnosis of osteoarthritis. In summary, we demonstrate here that the widely available supplement CBD exerts robust and quantifiable anti-inflammatory properties in experimental systems. These experimental results were translatable in a randomized, double-blind, placebo-controlled trial in a spontaneous canine model of OA.

Citation: April 2020 Pain DOI: 10.1097/ j.pain. 0000000000001896

http://dx.doi.org/10.1097/j.pain.0000000000001896

A Report of Adverse Effects Associated with the Administration of Cannabidiol in Healthy Dogs

Journal of the American Holistic Veterinary Medical Association (JAHVMA). Article first appeared in Volume 52, Fall Issue, 2018.

1) The purpose of this study was to determine the tolerability of cannabidiol (CBD) by healthy dogs. The scientists hypothesized that CBD would be tolerated in a healthy population of dogs. A group of 30 healthy Beagle dogs were randomly assigned to receive CBD in the form of microencapsulated oil beads (capsule), CBD-infused oil, or CBD-infused transdermal cream at a dose of 10 mg/kg/day or 20 mg/ kg/day for 6 weeks. Complete blood counts, chemistry panels, urinalysis, and bile acids were performed at 0, 2, 4, and 6 weeks.

2) Clinically significant results were recorded as binary data indicating the presence or absence of the clinical outcome. Contingency tables were constructed for each of the analyses; and the Fisher's exact test was used to evaluate the significance of association between the formulations at each time point, and between the time points within each formulation for both doses of CBD. A P value of 0.05 was used to determine statistical significance.

3) Throughout the 6-week study period, gastrointestinal upset was the most frequently recorded adverse clinical sign. All of the dogs in the study developed diarrhea, and 6/30 (20%) dogs had single episodes of vomiting. The dogs that vomited were in the groups that received CBD orally in the form of capsules.

4) Erythematous pinnae was the second most common adverse clinical sign reported at week 2 and 4. A mild erythematous reaction of the pinnae occurred in 11 dogs (36%), 9 of whom belonged to the group that received the transdermal cream.

5) Limitations of this study include the lack of a control group and the short duration of the study period. Each dog served as its own control but an actual control group would have helped to confirm if adverse effects were secondary to CBD versus other causes, such as being housed in an unfamiliar setting or eating unfamiliar food especially with regard to the diarrhea.

Reference

https://www.ahvma.org/wp-content/uploads/AHVMA-2018-V52-CannabisAdverseEffects.pdf