Dogs received each of two treatments: CBD oil (2 mg/kg) or placebo oil every 12 h. (IACUC) approved the study following the guidelines for animal use An initial investigation into single-dose oral pharmacokinetics was. Dogs received either CBD oil at 2 mg/kg every 12 hours or they received First of all, hemp plants contain less than percent Neither was I, so I asked my own lawyer to do some research for me on CBD oil use in pets. beneficial use in other animal species (ferrets, cats, dogs, monkeys) that have been reported in the scientific lit- erature. out and the results of these studies have led to the approval of manner the text will first be focused on the classifi-.
in of Veterinary on Studies CBD The Medicine First Use
Blood was collected to repeat complete blood counts and chemistry analysis at weeks 2 and 4 for each treatment. At each visit, each dog was evaluated by a veterinarian based on a scoring system previously reported 25 as well as by its owner canine brief pain inventory [CBPI], Hudson activity scale before treatment initiation and at weeks 2 and 4 thereafter 26 — Initial power analysis was performed to assess number of dogs needed for this study as a cross over design with a power set 0.
When calculated it was assumed that 14 dogs would be necessary to find differences in outcomes of interest Statistical analysis was performed with a commercially available software package JMP All continuous data were assessed utilizing a Shapiro—Wilk test for normality. For ordinal veterinary scoring data a similar linear mixed model was used, but differences from baseline were first calculated to approximate a normal distribution to meet assumptions for a mixed model analysis.
Residual diagnostics of all final models showed that residuals were normally distributed and fulfilled the assumption of homoscedasticity, and assumptions where therefore met. To control for baseline differences and therefore the possible difference in relative change in CBPI pain, and activity interference assessments and Hudson scoring across dogs, the initial CPBI or Hudson Scores were included for these analyses as a covariate.
Pairwise comparisons between all-time points of both groups were corrected for multiple comparisons with Tukey's post-hoc tests to examine the interaction of time and treatment variables, and to assess differences between change from baseline at any time point as they related to treatment.
A p -value of less than 0. Pharmacokinetics demonstrated that CBD half-life of elimination median was 4. Median maximal concentration of CBD oil was Twenty-two client-owned dogs with clinically and radiographically confirmed evidence of osteoarthritis were recruited. Characteristics of dogs enrolled in a placebo-controlled study investigating the effects of CBD on osteoarthritis.
No other veterinary pain comparisons were statistically significant. Canine Brief Pain Inventory Pain and Activity questions and Hudson Scale mean and standard deviation; lameness, weight-bearing and pain scores median and ranges at each time for cannabidiol CBD and placebo oils.
Chemistry analysis and CBC were performed at each visit. No significant change in the measured CBC values was noted in either the CBD oil or placebo treated dogs data not shown. Other notable significances in serum chemistry values were associated with primarily age or NSAID use.
Box-and-whisker plot of serum alkaline phosphatase ALP activity at each time for treatment and placebo oils. Box represents the mean and 25th and 75th percentile and the whiskers represent the 99th and 1st percentiles.
To date, an objective evaluation of the pharmacokinetics of a commercially available industrial hemp product after oral dosing in dogs is absent. This half-life was shorter than a previous report after intravenous 1. In the intravenous study, CBD distribution was rapid, followed by prolonged elimination with a terminal half-life of 9 h. This may be due to the first pass effect in the liver, and the product was not in an oil base, but a powder within a gelatin capsule being a different delivery vehicle Although our dogs were fasted the delivery vehicle was olive oil which is a food item.
The absorption may be greater and more consistent because of the oil-based vehicle which may be due to the lipophilic nature of CBD, hence delivery with food may be preferable 32 , As previously demonstrated, CBD biotransformation in dogs involves hydroxylation, carboxylation and conjugation, leading to relatively rapid elimination suggesting a more frequent dosing schedule The dosing schedule of twice per day was chosen due to the practical nature of this dosing regimen even though the elimination is well within a three or four time a day dosing regimen.
Our hope was that the lipophilic nature of CBD would allow for a steady state over time, and future studies examining 24 h pharmacokinetics with different dosing regimens with larger numbers of dogs, and steady state serum pharmacokinetics after extended treatment in a clinical population are sorely needed. The main objective of this study was to perform an owner and veterinary double-blinded, placebo-controlled, cross-over study to determine the efficacy of CBD oil in dogs affected by OA.
Additionally, veterinary assessments of pain were also favorable. Although a caregiver placebo effect should be considered with subjective evaluations by owners and veterinarians 35 , the cross-over design limits confounding covariates since each dog serves as its own control. Our statistical model controlled for the possible effect of treatment sequence.
The lack of a placebo effect in our study may be due to nine of the 16 owners being intimately involved in veterinary medical care, all of whom have an understanding of the placebo effect making them more cognizant of improvements when providing feedback.
In addition, there was a noticeable decrease in Hudson scores and rise in CBPI scores during the initiation placebo treatment suggesting a potential carry over effect of CBD treatment indicating that a longer washout period might be indicated in future studies.
This carry over effect may have resulted in some improved perceptions at the initiation of the placebo treatment which were eliminated by week 4 of placebo treatment, underscoring the importance of longer term steady state PK studies in dogs.
There was no significant difference in subjective veterinary lameness score and weight-bearing capacity throughout the study. Kinetic data was obtained from these dogs data not shown , however 11 of the 16 dogs had significant bilateral disease stifle, coxofemoral, or elbow making evaluation of peak vertical force or symmetry tenuous at best.
Unilateral disease in any of the aforementioned joints would be ideal to study the kinetic effects of this or similar extracts for pain relief leading to better objective outcomes.
The population we used in our investigation was representative of dogs presenting in a clinical setting for management of OA and represents the typical OA patient. Currently, NSAIDs are the primary treatment for OA and are associated with negative effects on the gastrointestinal tract and glomerular filtration 2. In the current study, no significant difference was noted in BUN, creatinine, or phosphorus between dogs treated with the CBD oil vs. A mild rise in creatinine from baseline was noted in both groups at weeks 2 and 4, the hydration status of the dogs was unknown; however changes in albumin sodium, and chloride were unchanged suggesting euhydration, and all creatinine values remained within the reference interval.
Increased ALP activity is fairly sensitive for hepatobiliary changes in this age group, but not specific. Increased ALP activity noted in nine dogs in the CBD treatment group may be an effect of the hemp extract attributed to the induction of cytochrome p mediated oxidative metabolism of the liver reported previously with prolonged exposure to cannabis 36 — Other causes of cholestasis, increased endogenous corticosteroid release from stress, or a progression of regenerative nodular hyperplasia of the liver cannot be ruled out.
Without concurrent significant rise in ALT in the CBD treatment to support hepatocellular damage, or biopsy for further clarification, the significance is uncertain. As such, it may be prudent to monitor liver enzyme values especially ALP while dogs are receiving industrial hemp products until controlled long term safety studies are published.
A recent survey reported that pet owners endorse hemp based treats and products because of perceived improvement in numerous ailments, as hemp products were moderately to very helpful medicinally Some of the conditions thought to be relieved by hemp consumption were: One immunohistochemical study suggested that cannabinoids could protect against the effects of immune-mediated and inflammatory allergic disorders in dogs 40 whereas another uncontrolled study suggested that CBD has anticonvulsant and anti-epileptic properties in dogs There were some dogs with incidental rises in alkaline phosphatase that could be related to the treatment.
Further long-term studies with larger populations are needed to identify long-term effects of CBD rich industrial hemp treatment, however short term effects appear to be positive. L-JG was responsible for data analysis and interpretation, drafting of the manuscript and approval of the submitted manuscript.
JB was responsible for the conception of the study and manuscript writing and revisions. CF was responsible for acquisition of data and manuscript revision. WS was responsible for pharmacokinetic evaluation and revision of the manuscript. SM was responsible for statistical analysis, data analysis and revision of the manuscript. LW was responsible for laboratory work including liquid chromatography-mass spectrometry.
HB was responsible for interpretation of the blood work and manuscript revision. EB was responsible for acquisition of data, and data analysis. JW was responsible for the conception of study, supervised data collection, statistical analysis, and manuscript editing. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The authors would like to thank Renee C. Staffeld and Danny Sack for data entry. National Center for Biotechnology Information , U. Journal List Front Vet Sci v. Published online Jul Lauri-Jo Gamble , 1 Jordyn M. Boesch , 1 Christopher W. Frye , 1 Wayne S. Berthelsen , 1 and Joseph J. Author information Article notes Copyright and License information Disclaimer. This article was submitted to Veterinary Surgery and Anesthesiology, a section of the journal Frontiers in Veterinary Science.
Received Feb 25; Accepted Jul 2. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.
No use, distribution or reproduction is permitted which does not comply with these terms. Introduction Routine nonsteroidal anti-inflammatory drug NSAID treatments, though efficacious, may not provide adequate relief of pain due to osteoarthritis OA and might have potential side effects that preclude its use, particularly in geriatric patients with certain comorbidities, such as kidney or gastrointestinal pathologies 1 — 4.
Pharmacokinetics An initial investigation into single-dose oral pharmacokinetics was performed with 4 beagles 3. Extraction of CBD from canine serum and mass spectrometry analysis CBD was extracted from canine serum using a combination of protein precipitation and liquid-liquid extraction using n-hexane as previously described 20 , with minor modifications for microflow ultra-high pressure liquid chromatography UHPLC. Inclusion and exclusion criteria for the clinical trial The study population consisted of client-owned dogs presenting to Cornell University Hospital for Animals for evaluation and treatment of a lameness due to OA.
Clinical trial The study was a randomized, placebo-controlled, owner and veterinarian double-blind, cross-over trial. Statistical analysis Initial power analysis was performed to assess number of dogs needed for this study as a cross over design with a power set 0. Results Pharmacokinetics Pharmacokinetics demonstrated that CBD half-life of elimination median was 4. Open in a separate window. Dogs included in the clinical trial Twenty-two client-owned dogs with clinically and radiographically confirmed evidence of osteoarthritis were recruited.
Table 2 Characteristics of dogs enrolled in a placebo-controlled study investigating the effects of CBD on osteoarthritis. Table 3 Canine Brief Pain Inventory Pain and Activity questions and Hudson Scale mean and standard deviation; lameness, weight-bearing and pain scores median and ranges at each time for cannabidiol CBD and placebo oils.
Table 4 Serum chemistry values of dogs receiving CBD or placebo oils. Discussion To date, an objective evaluation of the pharmacokinetics of a commercially available industrial hemp product after oral dosing in dogs is absent.
Author contributions L-JG was responsible for data analysis and interpretation, drafting of the manuscript and approval of the submitted manuscript. Conflict of interest statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Acknowledgments The authors would like to thank Renee C. Clinical pharmacology of nonsteroidal anti-inflammatory drugs in dogs. Owl Rides Segway on the Street. Grandpa Mason's New Batch of Kittens. View All Pet Videos. This information is for educational purposes only and is not intended to replace the advice of your own veterinarian or doctor. Karen Becker cannot answer specific questions about your pet's medical issues or make medical recommendations for your pet without first establishing a veterinarian-client-patient relationship.
In addition, the laws regulating the cultivation and sale of hemp products appear to be loosening up. Stephanie McGrath, who specializes in treating seizure disorders and inflammatory brain diseases in animals, recently completed a study of CBD for the treatment of osteoarthritis in dogs, and is currently running an epilepsy study.
That, along with this drug becoming legalized [in Colorado], prompted a lot more questions from clients and veterinarians. And [with] me being unable to answer their questions, that really bothered me. So the more I started looking, the more I realized what a void there was in cannabis research.
Her osteoarthritis study required that participating dogs have arthritis affecting one or more joints and a visible lameness that had been present for at least four weeks. Each dog in the study received either the CBD oil or a placebo for six weeks, after which the CBD group received a placebo and the placebo group received CBD for another six weeks. During the week period, each dog received X-rays, bloodwork, 15 minutes of walking per day and a daily pain assessment.
In the current epilepsy trial, study dogs must experience at least two seizures a month and be receiving conventional anticonvulsant medications. The trial is set up similar to the arthritis trial, except that each phase runs 12 weeks for a total of 24 weeks. A total of 27 dogs are participating in the two studies, and researchers are logging dosage, oil application, side effects and how to counteract those side effects.
I look forward to seeing the published results of Dr. Veterinary assessments, the pain inventory and the activity score showed a significant reduction in pain and an increase in activity in the dogs who received CBD treatment.
The research team is currently conducting a similar trial with cats, and there are additional studies planned to evaluate the use of CBD oil in treating acute pain, behavior issues and during chemotherapy for pets with cancer. My personal go-to authority on cannabidiol for pets is Dr.
Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs
distinguished by initial capital letters. The World .. There is unsanctioned medical use of CBD based products with oils, supplements, gums, and .. Neuroimaging studies in humans and animals have shown that CBD has. Her first study sponsored by Applied Basic Science examined the "But those who used it for personal medical use, that was correlated, which makes College of Veterinary Medicine, tested the pharmacokinetics of CBD oil. sort of research behind the use of CBD in animals that he was turning needed to get approval to conduct the first-ever cannabis clinical trials.