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Our underlying hypotheses were that appropriate dosing of CBD-rich oil would safely diminish perceived pain and increase activity in dogs with OA.
Client owned dogs were enrolled after informed consent in accordance with the Declaration of Helsinki. An initial investigation into single-dose oral pharmacokinetics was performed with 4 beagles 3. The dogs were fed 2 h after dosing. Physical examination was performed at 0, 4, 8, and 24 h after dosing.
Five milliliters of blood was collected at time 0, 0. Blood samples were obtained via jugular venipuncture and transferred to a coagulation tube for 20 min. 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.
Hexane extract was removed and concentrated to dryness under laboratory nitrogen. Prior to LC-MS analysis, samples were resuspended in 0. A standard curve using the CBD analytical standard was prepared in canine serum non-exposed to CBD and extracted as above. For this assay, the limits of detection LOD and limits of quantification LOQ represent the lower limits of detection and quantification for each compound in the matrix of this study 23 , Pharmacokinetic variables were estimated by means of non-compartmental analysis, utilizing a pharmacokinetic software package PK Solution, version 2.
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.
Dogs were considered for inclusion in the study if they had radiographic evidence of OA, signs of pain according to assessment by their owners, detectable lameness on visual gait assessment and painful joint s on palpation.
Elevations in alkaline phosphatase ALP , alanine aminotransferase ALT , and aspartate aminotransferase AST were allowed if prior hepatic ultrasound was deemed within normal limits except for potential non-progressive nodules possible hepatic nodular hyperplasia.
All owners completed a brief questionnaire to define the affected limb s , duration of lameness, and duration of analgesic or other medications taken. All dogs underwent radiographic examination of affected joints and a radiologist confirmed the presence or absence of OA, and excluded the presence of concomitant disease that might preclude them from enrolment i. Other analgesic medications used, such as gabapentin and tramadol, were discontinued at least 2 weeks prior to enrolment.
Dogs were excluded if they had evidence of renal, uncontrolled endocrine, neurologic, or neoplastic disease, or were undergoing physical therapy. Every dog was fed its regular diet with no change allowed during the trial.
The study was a randomized, placebo-controlled, owner and veterinarian double-blind, cross-over trial. Dogs received each of two treatments in random order Randomizer iPhone Application: Each treatment was administered for 4 weeks with a 2-week washout period in between treatments. 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. When I started The Cannabis Pet, there were terms such as Hemp oil, CBD oil, cannabis oil, marijuana oil all referring to oil from the cannabis plant that made it quite confusing not to mention trying to understand what the difference is between hemp and marijuana.
First, Hemp pertains to the strain of the Cannabis Sativa plant that is grown for its fiber and seed oils without representing flowering buds at any stage of the growing cycle. It is the seed and fiber of the stalk that produces more CBD cannabinoids than its counterpart having only traces of THC less than 0.
Hemp requires a different growing condition which results in low concentrations of THC and hemp comes from the stalk, not the flowering buds or leaves. If the idea is to maximize the concentration of THC, then we move to talking about marijuana drug. The resin is the gooey, sticky part of the flowering bud containing higher levels of THC. Hemp is the stalk of the Cannabis Sativa. Leafly put out this video about 3 minutes which explains the difference between CBD vs.
However, CBD products sold at dispensaries means it uses the full flower. THC can be harmful if you do not know how much to give your pet. Make sure you consult with your veterinarian first!
Although the results from clinical research are promising, it is still relatively new. And because of their licensing restrictions, they can get into a lot of trouble with the Veterinary Medical Board. Another way is research on your own, talk with other dog owners, get their feedback.
Remember, trying CBD oil made by hemp has hardly any side effects, so it will not hurt to try for yourself. Products containing CBD have opened a new world for pet care and those who believe in natural remedies. Early research and anecdotal testimonials show that CBD has helped pets in many ways.
Gary Richter and Robert Silver, both vets and both understand the benefits of conventional and holistic treatments.
Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs
With the appropriate dose of CBD oil, dogs can safely reap the benefits of feeling like CBD oil works to reduce pain-related symptoms by. Hemp CBD dog treats or oil can be a great natural calming aid. I can help . Using Hemp CBD oil, there are several ways you can make your own dog treats. CBD guaranteed *safe* for use on PETS | See more ideas about Pets, Hemp and Hemp oil.