CBD Oil For Pain In Dogs

ABSTRACT 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 mg/kg and 8 mg/kg) oil. Thereafter, a randomized placebo-controlled, veterinarian and owner blinded, cross-over study was conducted. Dogs received each of two treatments: CBD oil (2 mg/kg) or placebo oil every 12 hours. Each treatment lasted for 4 weeks with a 2-week washout period. Baseline veterinary assessment and owner questionnaires were completed before initiating each treatment and at weeks 2 and 4. Hematology, serum chemistry and physical examinations were performed at each visit. A mixed model analysis was utilized for all variables with a p value of < 0.05 deemed significant. Results Pharmacokinetics revealed an elimination half-life of 4.2 hours at both doses and no observable side effects. Clinically, canine brief pain inventory and Hudson activity scores showed a significant decrease in pain and increase in activity (p < 0.01) with CBD oil. Veterinary assessment showed decreased pain during CBD treatment (p < 0.02). No side effects were reported by owners, however, serum chemistry showed an increase in alkaline phosphatase during CBD treatment (p < 0.01). Clinical significance This pharmacokinetic and clinical study suggests that 2 mg/kg of CBD twice daily can help increase comfort and activity in dogs with OA. Keywords Cannabidiol; CBD oil; hemp; canine; osteoarthritis; pharmacokinetic How much do you know about dog CBD products and their benefits? Here are the basics of CBD for dogs to control pain, anxiety, and cancer. Arthtitis isn’t fun for your furbaby or you. Thankfully these CBD oils for dogs with arthritis can provide some relief.

Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs

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 of two treatments: CBD oil (2 mg/kg) or placebo oil every 12 h. Each treatment lasted for 4 weeks with a 2-week washout period. Baseline veterinary assessment and owner questionnaires were completed before initiating each treatment and at weeks 2 and 4. Hematology, serum chemistry and physical examinations were performed at each visit. A mixed model analysis, analyzing the change from enrollment baseline for all other time points was utilized for all variables of interest, with a p ≤ 0.05 defined as significant.

Results: Pharmacokinetics revealed an elimination half-life of 4.2 h at both doses and no observable side effects. Clinically, canine brief pain inventory and Hudson activity scores showed a significant decrease in pain and increase in activity (p < 0.01) with CBD oil. Veterinary assessment showed decreased pain during CBD treatment (p < 0.02). No side effects were reported by owners, however, serum chemistry showed an increase in alkaline phosphatase during CBD treatment (p < 0.01).

Clinical significance: This pharmacokinetic and clinical study suggests that 2 mg/kg of CBD twice daily can help increase comfort and activity in dogs with OA.

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). In a systematic review of 35 canine models of OA and 29 clinical trials in dogs, treatment with NSAIDs caused adverse effects in 35 of the 64 (55%) studies, most commonly being gastro-intestinal signs (3). Although other pharmacological agents are advocated, such as gabapentin or amantadine, there is little evidence regarding their efficacy in dogs with chronic or neuropathic pain related to OA. Recent medical interest in alternative therapies and modalities for pain relief has led many pet owners to seek hemp related products rich in cannabinoids.

The endocannabinoid receptor system is known to play a role in pain modulation and attenuation of inflammation (5–7). Cannabinoid receptors (CB1 and CB2) are widely distributed throughout the central and peripheral nervous system (8–10) and are also present in the synovium (11). However, the psychotropic effects of certain cannabinoids prevent extensive research into their use as single agents for pain relief (5, 12). The cannabinoids are a group of as many as 60 different compounds that may or may not act at CB receptors. One class of cannabinoids, cannabidiol (CBD), may actually be an allosteric non-competitive antagonist of CB receptors (13). In lower vertebrates, CBD is also reported to have immunomodulatory (14), anti-hyperalgesic (15, 16), antinociceptive (17, 18), and anti-inflammatory actions (5, 19), making it an attractive therapeutic option in dogs with OA. Currently there are several companies distributing nutraceutical derivatives of industrial hemp, rich in cannabinoids for pets, yet little scientific evidence regarding safe and effective oral dosing exists.

The objectives of this study were to determine: (1) single-dose oral pharmacokinetics, (2) short-term safety, and (3) efficacy of this novel CBD-rich extract, as compared to placebo, in alleviating pain in dogs with OA. Our underlying hypotheses were that appropriate dosing of CBD-rich oil would safely diminish perceived pain and increase activity in dogs with OA.

Materials and Methods

CBD Oil and Protocols Approval

The industrial hemp used in this study was a proprietary hemp strain utilizing ethanol and heat extraction with the final desiccated product reconstituted into an olive oil base containing ~10 mg/mL of CBD as an equal mix of CBD and carboxylic acid of CBD (CBDa), 0.24 mg/mL tetrahydrocannabinol (THC), 0.27 mg/mL cannabichromene (CBC), and 0.11 mg/mL cannabigerol (CBG); all other cannabinoids were less than 0.01 mg/mL. Analysis of five different production runs using a commercial analytical laboratory (MCR Laboratories, Framingham, MA) show less than a 9% difference across batches for each of the detected cannabinoids listed above. The study was performed after the Cornell University institutional animal care and use committee (IACUC) approved the study following the guidelines for animal use according to the IACUC. Client owned dogs were enrolled after informed consent in accordance with the Declaration of Helsinki.

Pharmacokinetics

An initial investigation into single-dose oral pharmacokinetics was performed with 4 beagles (3.5–7 years, male castrated, 10.7–11.9 kg). Each dog received a 2 mg/kg and an 8 mg/kg oral dosage of CBD oil, with a 2-week washout period between each experiment. The dogs were fed 2 h after dosing. Physical examination was performed at 0, 4, 8, and 24 h after dosing. Attitude, behavior, proprioception, and gait were subjectively evaluated at each time point during free running/walking and navigation around standard traffic cones (weaving). Five milliliters of blood was collected at time 0, 0.5, 1, 2, 4, 8, 12, and 24 h after oil administration. Blood samples were obtained via jugular venipuncture and transferred to a coagulation tube for 20 min. Samples were centrifuged with a clinical centrifuge at 3,600 × g for 10 min; serum was removed and stored at −80°C until analysis using liquid chromatography-mass spectrometry (LC-MS) at Colorado State University Core Mass Spectrometry facility.

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). Briefly, 0.05 mL of canine serum was subjected to protein precipitation in the presence of ice-cold acetonitrile (80% final concentration), spiked with deuterated CBD as the internal standard (0.06 mg/mL, CDB-d3 Cerilliant, Round Rock, TX, USA). 0.2 mL of water was added to each sample prior to the addition of 1.0 mL of hexane to enhance liquid-liquid phase separation. Hexane extract was removed and concentrated to dryness under laboratory nitrogen. Prior to LC-MS analysis, samples were resuspended in 0.06 mL of 100% acetonitrile. A standard curve using the CBD analytical standard was prepared in canine serum non-exposed to CBD and extracted as above. Cannabidiol concentration in serum was quantified using a chromatographically coupled triple-quadropole mass spectrometer (UHPLC-QQQ-MS) using similar methods as previously described (21).

CDB Serum Concentration Data Analysis

From the UHPLC-QQQ-MS data, peak areas were extracted for CBD detected in biological samples and normalized to the peak area of the internal standard CBD-d3, in each sample using Skyline (22) as well as an in-house R Script (www.r-project.org). CBD concentrations were calculated to nanograms per mL of serum as determined by the line of regression of the standard curve (r 2 = 0.9994, 0–1,000 ng/mL). 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, 24). Pharmacokinetic variables were estimated by means of non-compartmental analysis, utilizing a pharmacokinetic software package (PK Solution, version 2.0, Montrose, CO, USA).

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. 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. Each dog had an initial complete blood count ([CBC] Bayer Advia 120, Siemens Corp., New York, NY, USA) and serum chemistry analysis (Hitachi 911, Roche Diagnostics, Indianapolis, IN, USA) performed to rule out any underlying disease that might preclude enrolment. 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.e., lytic lesions).

During the trial, dogs were only allowed to receive NSAIDs, fish oil, and/or glucosamine/chondroitin sulfate without any change in these medications for 4 weeks prior to or during the 10-week study period as standard of care for the disease process. 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.

Clinical 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): CBD, 2 mg/kg every 12 h, or placebo (an equivalent volume of olive oil with 10 parts per thousands of anise oil and 5 parts per thousands of peppermint oil to provide a similar herbal smell) every 12 h. 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 (26–28).

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 0.80 and alpha of 0.05 using prior data suggesting a baseline CBPI or Hudson score change of ~15 points (two tailed) with a standard deviation of 20. When calculated it was assumed that 14 dogs would be necessary to find differences in outcomes of interest (29).

Statistical analysis was performed with a commercially available software package (JMP 12.0, Cary, NC, USA). All continuous data were assessed utilizing a Shapiro–Wilk test for normality. Considering a majority of our blood, serum and scoring data were normally distributed a mixed model analysis was used to analyze these outcomes, including the fixed effects of treatment, time, sequence of treatment assignment, gender, age, NSAID usage, treatment × time; as well as random effects of observation period, period nested within dog, time point nested within period nested within dog to account for the hierarchical nature of data in a cross-over design as well as repeated measurements for each dog. 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. This statistical modeling approach allowed for adequate control of hierarchical data structure necessary in a cross-over design, as well as for the performance of easily interpretable time × treatment Tukey post-hoc comparisons that were our main interest, as compared to an ordinal logistical regression (30, 31). 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 0.05 was defined as the significance cut-off.

Results

Pharmacokinetics

Pharmacokinetics demonstrated that CBD half-life of elimination median was 4.2 h (3.8–6.8 h) for the 2 mg/kg dose, and 4.2 h (3.8–4.8 h) for the 8 mg/kg dose (Table 1). Median maximal concentration of CBD oil was 102.3 ng/mL (60.7–132.0 ng/mL; 180 nM) and 590.8 ng/mL (389.5–904.5 ng/mL; 1.2 uM) and was reached after 1.5 and 2 h, respectively, for 2 and 8 mg/kg doses. No obvious psychoactive properties were observed on evaluation at any time point during the 2 and 8 mg/kg doses over 24 h. These results led to dosing during the clinical trial at 2 mg/kg body weight every 12 h, due the cost prohibitive nature of 8 mg/kg dosing for most larger patients, the impractical nature of more frequent dosing, the volume of oil necessary and anecdotal reports surrounding 0.5-2 mg/kg dosing recommended by other vendors.

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Table 1. Serum pharmacokinetic of single oral dosing (2 mg and 8 mg/kg) of CBD oil in dogs.

Dogs Included in the Clinical Trial

Twenty-two client-owned dogs with clinically and radiographically confirmed evidence of osteoarthritis were recruited. Sixteen of these dogs completed the trial and were included in the analyses; their breed, weight, age, sex, worse affected limb, radiographic findings, use of NSAIDs and sequence of treatments are summarized in Table 2. Dogs were removed due to osteosarcoma at the time of enrolment, gastric torsion (placebo oil), prior aggression issues (CBD oil), pyelonephritis/kidney insufficiency (CBD oil), recurrent pododermatitis (placebo oil), and diarrhea (placebo oil).

Table 2. Characteristics of dogs enrolled in a placebo-controlled study investigating the effects of CBD on osteoarthritis.

Clinical Trial

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.

Figure 1. 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. *Indicates a significant difference (p < 0.05) from week 0 CBD treatment.

Discussion

To date, an objective evaluation of the pharmacokinetics of a commercially available industrial hemp product after oral dosing in dogs is absent. This study showed that the terminal half-life of oral CBD, as the most abundant cannabinoid in this specific preparation when in an oil base, was between 4 and 5 h, suggesting it was bioavailable with a dosing schedule of 2 mg/kg at least twice daily. This half-life was shorter than a previous report after intravenous (1.88–2.81 and 3.75–5.63 mg/kg) and oral (7.5–11.25 mg/kg) administration (32). In the intravenous study, CBD distribution was rapid, followed by prolonged elimination with a terminal half-life of 9 h. When examining prior oral CBD bioavailability it was determined to be low and highly variable (0–19% of dose) with three dogs showing no absorption. 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 (32). After initially seeing no neurological effects at the 2 mg/kg dose a 8 mg/kg dose was chosen to assess the potential neurological effects since mistaken overdosing can occur clinically, and a higher dose might have been necessary since the prior study showed poor absorption. 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, 33). As previously demonstrated, CBD biotransformation in dogs involves hydroxylation, carboxylation and conjugation, leading to relatively rapid elimination suggesting a more frequent dosing schedule (34). 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. Despite our small sample size, short study duration and heterogeneity of OA signs, CBPI and Hudson scores showed that CBD oil increase comfort and activity in the home environment for dogs with 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. the placebo oil, while NSAID treatment resulted in a higher creatinine concentration. 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 p450 mediated oxidative metabolism of the liver (reported previously with prolonged exposure to cannabis) (36–38). 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 (39). Some of the conditions thought to be relieved by hemp consumption were: pain, inflammation, anxiety and phobia, digestive system issue, and pruritus (39). 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 (41). The apparent analgesic effect of the industrial hemp based oil observed in the present study may be attributable to downregulation of cylooxygenase enzymes, glycine interneuron potentiation, transient receptor potential cation receptor subfamily V1 receptor agonism (peripheral nerves), and/or g-protein receptor 55 activation (immune cells), influencing nociceptive signaling and/or inflammation (14, 42, 43).

The industrial hemp product used in this study is a proprietary strain-specific extract of the cannabinoids outlined in the methods with relatively high concentrations of CBD and lesser quantities of other cannabinoids as well as small amounts of terpenes that may have synergistic effects often termed the “entourage effect.” This brings to light that fact that different strains of cannabis produce differing amounts of CBD and other related cannabinoids making the results of this study specific to this industrial hemp extract that may not translate to other available products due to differing cannabinoid concentrations in this largely unregulated market.

In conclusion, this particular product was shown to be bioavailable across the small number of dogs examined in the PK portion of the study, and dogs with OA receiving this industrial hemp extract high in CBD (2 mg/kg of CBD) were perceived to be more comfortable and active. There appear to be no observed side effects of the treatment in either the dogs utilized in the PK study at 2 and 8 mg/kg, or dogs undergoing OA treatment for a month duration. 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.

Author Contributions

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.

Funding

Ellevet LLC supported this research with a grant to Cornell University to study this product.

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. Staffeld and Danny Sack for data entry. The present study was financially supported by ElleVet Sciences, Portland, Maine.

Abbreviations

CBD, cannabidiol; CB, cannabinoid; CBDa, carboxylic acid of CBD; THC, tetrahydrocannabinol; CBC, cannabichromene; CBG, cannabigerol; CBPI, Canine Brief Pain Inventory.

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33. Garrett ER, Hunt CA. Physicochemical properties, solubility, and protein binding of delta9-tetrahydrocannabinol. J Pharm Sci. (1974) 63:1056–64. doi: 10.1002/jps.2600630705

34. Harvey DJ, Samara E, Mechoulam R. Comparative metabolism of cannabidiol in dog, rat and man. Pharmacol Biochem Behav. (1991) 40:523–32.

35. Conzemius mg, Evans RB. Caregiver placebo effect for dogs with lameness from osteoarthritis. J Am Vet Med Assoc. (2012) 241:1314–9. doi: 10.2460/javma.241.10.1314

36. Bornheim LM, Correia MA. Effect of cannabidiol on cytochrome P-450 isozymes. Biochem Pharmacol. (1989) 38:2789–94. doi: 10.1016/0006-2952(89)90432-2

37. Khanna P, Gupta MB, Gupta GP, Sanwal GG, Ali B. Influence of chronic oral intake of cannabis extract on oxidative and hydrolytic metabolism of xenobiotics in rat. Biochem Pharmacol. (1991) 41:109–13. doi: 10.1016/0006-2952(91)90017-Y

38. Yamamoto I, Watanabe K, Narimatsu S, Yoshimura H. Recent advances in the metabolism of cannabinoids. Int J Biochem Cell Biol. (1995) 27:741–6. doi: 10.1016/1357-2725(95)00043-O

39. Kogan LR, Hellyer PW, Robinson NG. Consumers’ perceptions of hemp products for animals. J Am Holist Vet Med Assoc. (2016) 42:40–8.

40. Campora L, Miragliotta V, Ricci E, Cristino L, Di Marzo V, Albanese F, et al. Cannabinoid receptor type 1 and 2 expression in the skin of healthy dogs and dogs with atopic dermatitis. Am J Vet Res. (2012) 73:988–95. doi: 10.2460/ajvr.73.7.988

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42. Kathmann M, Flau K, Redmer A, Trankle C, Schlicker E. Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors. Naunyn Schmiedebergs Arch Pharmacol. (2006) 372:354–61. doi: 10.1007/s00210-006-0033-x

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Keywords: cannabidiol, CBD oil, hemp, canine, osteoarthritis, pharmacokinetic

Citation: Gamble L-J, Boesch JM, Frye CW, Schwark WS, Mann S, Wolfe L, Brown H, Berthelsen ES and Wakshlag JJ (2018) Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs. Front. Vet. Sci. 5:165. doi: 10.3389/fvets.2018.00165

Received: 25 February 2018; Accepted: 02 July 2018;
Published: 23 July 2018.

Troy N. Trumble, University of Minnesota Twin Cities, United States

Gareth Edward Zeiler, University of Pretoria, South Africa
Joao Henrique Neves Soares, Virginia Tech, United States

Copyright © 2018 Gamble, Boesch, Frye, Schwark, Mann, Wolfe, Brown, Berthelsen and Wakshlag. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). 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.

How Can CBD Help A Dog In Pain

Cannabidiol (CBD) has exploded in popularity in the last two years among dog owners looking to relieve pain and anxiety for their beloved pets.

If you have a mobility-impaired or older dog suffering from arthritis or hip dysplasia, you might be thinking, “Is this just another passing trend, or is there any science to back it up?” Of course, you want to do everything possible to help keep your pet safe.

Naturally, you also don’t want to waste your money or jeopardize the health of your lovely companion, which is why picking out the right product is essential.

This article will provide a general overview of CBD oil, including what it is, how it works, and what benefits it may provide for your dog with joint discomfort, arthritis, chronic inflammation, and other mobility concerns.

CBD Oil For Dogs

CBD is a cannabinoid molecule found naturally in cannabis plants. CBD oil has reportedly undergone extensive testing, commonly known as cannabidiol or hemp oil. Nowadays, CBD oil is a widely used natural remedy for various physical and mental ailments.

CBD oil is a natural combination of CBD extract and carrier oil, such as hemp oil or coconut oil, which can be applied topically or consumed sublingually. High-quality CBD oil could be a vital part of a vet-approved treatment program for dogs.

Canines with mobility challenges, chronic pain, inflammation, or age-related illnesses, such as arthritis or hip dysplasia, may benefit from CBD. Let’s glance at some of the science in more detail.

CBD & Pain

Pain management and relief are essential parts of treatment for many disabled and elderly dogs. Dog owners should know that the underlying cause of the pain can be complicated due to multiple factors. Your dog’s pain levels can range from mild to severe and can be short-term or long-term.

Experts describe chronic pain as lasting longer than six months, even though the cause (disease or injury) is no longer present. Injury, surgery, and chronic and progressive conditions, including IVDD, hip dysplasia, and arthritis, can cause pain.

All pet owners know how essential it is to improve a special needs dog’s quality of life by reducing pain. Vets and many non-specialist dog owners commonly use prescription medicines such as opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) to treat pain.

These drugs are pretty effective, but they also have serious side effects. Chemical dependence, long-term liver damage, and the risk of a fatal overdose are all possible side effects.

The natural substance cannabidiol, on the other hand, has been shown in several studies to help relieve pain with few side effects. Note that CBD doesn’t produce the same euphoric “high” like THC, but its complex effects can aid the body in utilizing its endocannabinoids.

Science Behind CBD Pain Management Properties

CBD may be a viable alternative for dogs, cats, and people who suffer from chronic pain and rely on drugs like opioids, which can be addictive and have multiple adverse effects.

The endocannabinoid system (ECS) is a complex cell-signaling system. Researchers believe CBD interacts with endocannabinoid receptors in the brain and immune system, which are key components of the ECS.

The ECS system regulates immunological responses in mammals, including humans, dogs, and cats. Receptors are tiny proteins found on cell surfaces.

They receive chemical messages from various stimuli and assist cells in responding. This reaction produces pain-relieving and anti-inflammatory properties, which aid in pain management.

CBD oil binds with a dog’s CB1 & CB2 receptors, acting as a natural neuroprotective agent with various possible medical advantages. After that, the oil’s cannabinoids allow for two-way communication between endocannabinoid receptors, enabling the body to adjust its immunological response as needed.

CBD oil is a natural technique to regulate the body’s systems and keep them perfectly balanced.

You may find it interesting to know that many dogs are lacking in cannabinoids. This causes CBD to help manage moderate pain more effectively in them. Supplementing pets with CBD increases cannabinoids in the muscle and restores balance to the ECS system.

CBD Research

Research on CBD products and pain management has indeed proved promising. And as cannabis becomes legal, a more in-depth and long-term study involving human volunteers is likely to occur.

According to a 2015 study, CBD can affect receptor systems in our bodies and the ECS associated with other cannabinoids. Research shows that CBD also raises anandamide levels in the body. Individuals link this chemical to lower pain perception and enhanced mood.

According to new research, CBD doesn’t ultimately lessen pain intensity, but it does make it feel less unpleasant. Academics examined the effects of cannabis medications on pain in early 2021 by safely creating experimental thermal pain and analyzing how the neurological system reacts and responds to it. By applying pure CBD isolate oil, researchers discovered that while CBD didn’t lower pain severity, it did make it less annoying.

Moreover, according to an investigation published in July 2018 by Cornell University researchers, CBD boosted the comfort and activity of dogs suffering from arthritis. This clinical trial revealed that administering dogs with osteoarthritis 2 mg of CBD twice per day can make them feel more comfortable and active.

Effects Of CBD On Dogs

If your dog is suffering from joint pain, your veterinarian may prescribe NSAIDs or other pain relievers like Gabapentin and Meloxicam. However, NSAIDs can induce joint and soft tissue degeneration on their own. They can also harm your dog’s liver in the future. Meds like Gabapentin can potentially damage kidneys.

Furthermore, most of these drugs prove ineffective in the long run. But CBD is natural and anti-inflammatory with none of the adverse side effects of pharmaceuticals.

Keep reading to learn about all of the potential benefits of CBD oils and other CBD pain meds for dogs.

Controlling Arthritis Pain

Arthritis pain is excruciating for many older dogs. CBD oil is a newer medication that has shown some promise for dogs suffering from arthritic symptoms. Animal medicine follows human medical trends, with testing and approval of veterinary medications typically taking years.

The FDA hasn’t approved a veterinary medicine based on CBD or hemp-derived chemicals to treat arthritis. However, that isn’t to suggest there isn’t evidence that CBD is impactful for dogs with arthritis.

Several promising studies demonstrate that cannabidiol reduces inflammation.

In one study, CBD was found to help reduce inflammation and slow the progression of degeneration in rats.

Managing Anxiety

Stress is among the most common reasons dog owners seek CBD for dogs. Anxiety can manifest itself in a variety of ways, including:

  • Fear of noise
  • Separation anxiety
  • Violence

Of course, the human version of anti-anxiety medications is accessible for dogs as well. Moreover, researchers are hailing CBD as a natural anxiety-management drug with no harmful side effects.

For your information, CBD oil treats pain, anxiety, and depression in humans. More than a third of consumers have reported that CBD works “extremely effectively by itself.” CBD even helps children with post-traumatic stress disorder (PTSD) or those who can’t control their anxiety and insomnia. The good news for dog owners is that animal studies reveal that its antidepressant effects aren’t just for people.

Improving Mobility

As our dogs become older, they lose interest in the activities they used to like. A dog in pain may find that daily walks and a swim in the pool are too much for them to endure. It’s sad to see the process unfold because we all want to keep our pets mobile for as long as possible.

Dog CBD oil may aid your older dog’s movement by addressing pain and inflammation. In one dog research, 2mg of CBD administered twice a day enhanced movement in dogs with osteoarthritis.

Managing Hip Dysplasia Symptoms

Another typical joint problem starting in puppyhood is hip dysplasia. Similar to arthritis, hip dysplasia is characterized by joint pain and inflammation.

Hip dysplasia is a genetic condition where the hip joints grow unevenly. Hip arthritis commonly develops at an early age as a result. Hip dysplasia causes joint pain, loss of movement, and chronic inflammation in dogs, just like arthritis. Hip dysplasia also causes the following symptoms:

  • Reluctance to get up from a sleeping or sitting position
  • Difficulty jumping or climbing stairs
  • Leg pain in the back legs
  • Hips with a restricted range of motion
  • Muscle mass loss in the lower limbs

CBD oil for dogs has been shown to help with pain and inflammation. Many veterinarians and pet owners are turning to CBD oil for dogs to aid with hip dysplasia symptoms. This eliminates canine pain and improves the quality of life for pets by reducing discomfort and increasing movement.

Fighting Cancer

Unfortunately, cancer affects 50% of mature dogs. Cancer poses a significant health risk to dogs, particularly if subjected to chemotherapy or radiation.

Cancer experts are constantly searching for new ways to treat cancer and alleviate the pain and nausea that it can cause. And CBD oils have been extensively studied as a cancer-fighting chemical.

CBD was found to decrease the growth of breast cancer cells in mice research. In 2018, their team discovered that CBD helped mice with pancreatic cancer live longer. Other animal research has also shown that CBD oil has cancer-fighting properties and can slow the growth of cancer cells.

See also  How To Use CBD Massage Oil

Is CBD Safe?

CBD has no documented side effects, and most topical CBD products don’t enter the bloodstream. However, there are some probable adverse effects, such as:

  • Weariness
  • Diarrhea
  • Changes in appetite
  • Changes in weight

CBD may interact with the following substances:

  • Prescription medicines and some over-the-counter (OTC) drugs
  • Nutritional supplements

CBD products may be able to provide treatment for many pets suffering from normal or chronic pain without producing intoxication or addiction.

Considerations to Find the Right Product

Dog CBD products aren’t all made equal. The active ingredient in many CBD oils, pills, and dog treats is insufficient to deliver these advantages. Moreover, some products don’t meet quality standards the way others (like Wiggles & Paws CBD Pet Oil ) do.

Learn how to recognize low-quality items that aren’t worth the money and how to find CBD oil for dogs that do help with the pain.

Animal Welfare Commitment

Make a financial investment. Try supporting companies that prioritize animal welfare through service and contributions to rescue pets in need. Remember that CBD oils like “The Wiggles & Paws CBD Pet Oil” can also benefit other animals!

Tested By A Third-Party Lab

Before purchasing hemp oil, make sure to check purity and dosage. To ensure you’re obtaining a high-quality CBD product evaluated for quality and potency, look for a product that has recently been tested and approved by a third-party lab.

The amount of CBD in the product should be specified on the label. Make sure the product you’re purchasing is THC-free.

Check to see if your dog’s CBD comes from CO2 extraction.

CO2 extraction is a method of extracting oil from plants using carbon dioxide. Oils with a greater concentration of CBD are produced utilizing this extraction method. Consequently, your dog’s supplement will be more effective. Naturally, this increases the product’s price, but it’s worth it.

No Contaminants Present

You must understand where and how the hemp used to create CBD oil is farmed. This significantly impacts the test results you see in the COA. To limit the risk of environmental toxins, always choose an organic product. You want to know that the soil and water in which it was grown are as pure as possible.

Caution Before Using CBD Oil

This website’s content does not replace a one-on-one relationship with your veterinarian. Don’t hesitate to contact your vet before making any changes to your dog’s medication regimen.

CBD oil for dogs is available ‘over the counter,’ but speaking with your vet before introducing any prescription or supplement is very important because CBD oil can interact with the metabolism of other medications your dog may need.

With that in mind, here you’ll find five tips to remember for keeping your beloved canine companion safe.

Drug Interferences

You may have been warned (or at least heard) not to consume grapefruit while taking medications. Grapefruit compounds can temporarily suppress the cytochrome P450 enzymes in the liver, requisite for the metabolization of certain drugs.

Because cannabidiol has a similar inhibitory function, timing your dosing is recommended.

First-Time Side Effects

The consumption of CBD oil products causes minimal adverse effects in certain pets. When your pet is using the product for the first time, it may experience mild drowsiness, feeling drowsy or “out of it,” vomiting, or diarrhea.

If any of these adverse effects occur, or if you have any other questions or concerns regarding CBD oil for dogs, stop utilizing the oil and seek guidance from your vet.

Check CBD Product Quality

If you intend to administer CBD oil to your beloved dog to help with arthritis or movement concerns, show the product to your doctor first. Your veterinarian will want to make sure the product has been third-party lab tested, is THC-free, and has a proper amount of CBD.

Some CBD pet products fail to meet these safety and efficacy criteria. To help you find the best CBD products, ask your veterinarian for suggestions, or check out our CBD-infused dog treats and shop with your mind at ease.

Is CBD Legal?

CBD products derived from hemp plants (with less than 0.3 percent THC) are technically legal in the United States and Canada. However, some dog CBD oil products are still banned in several US states. CBD products produced from marijuana are prohibited on the federal level, although legal in several states.

Check your city’s website or read the laws of your state. It’s important to remember that nonprescription CBD products aren’t FDA-approved and may be mislabeled.

Final Thoughts

We can now extract CBD oil for dogs and other animals from the cannabis plant and utilize them in various ways to help our dogs fight cancer, feel calmer, deal with joint pain, etc. In this beginner’s tutorial, we went through how CBD can help with canine pain management. We also discussed CBD’s safety and legality and what scientific studies have revealed about its effectiveness in treating pets.

We hope this blog helps you better understand how CBD oils could benefit your canine companion if your dog deals with arthritis pain, hip dysplasia, or other chronic pain and inflammation problems.

Best CBD oil for dogs with arthritis

Arthtitis isn’t fun for your furbaby or you. Thankfully these CBD oils for dogs with arthritis can provide some relief.

By Davies Media | Published Aug 12, 2021 5:59 AM

Humans use CBD oil for everything from pain to anxiety to relaxation and beyond. This naturally occurring chemical compound is extracted from industrial hemp, which is a strain of the Cannabis plant, containing 0.3% or less of the psychoactive compound THC.

CBD is used all over the world, and, in fact, has become one of the most popular personal care products on the market today. Experts predict the CBD industry can generate around $20 billion in revenue by 2025, but why all the hype? What good is CBD, and what does it do for pets?

How CBD helps arthritis in dogs

Arthritis is a common medical condition, especially in larger dog breeds. As dogs age, the cartilage between their joints wears away, causing bones to rub against one another and create painful inflammation in the joints. This causes discomfort, reduced mobility, and exhaustion.

CBD interacts directly with the dog’s endocannabinoid system, which helps mitigate pain. CBD itself is a natural painkiller and anti-inflammatory compound; the perfect mix for addressing the painful and often debilitating symptoms of a condition such as arthritis.

Is CBD right for your dog?

Before you start giving your dog CBD, it’s important to discuss the options with your veterinarian to determine if CBD is the right fit. Some pet owners want a natural alternative to painkillers while others want something that addresses all of the symptoms of arthritis instead of just pain or inflammation.

Whatever the case may be, it’s important to consult with your vet and keep them updated on changing doses or brands so they can monitor your dog’s reaction.

Is it dangerous?

So far, no research or anecdotal evidence has shown us any major negative side effects from using CBD products. CBD isn’t dangerous, and side effects include mild inconveniences like drowsiness, diarrhea, and headaches.

1. Verma Farms Salmon-Flavored CBD Oil 300mg

Price

$49.99 per bottle

Dose

300mg per bottle/10mg per serving

Why buy?

When it comes to CBD products, Verma Farms takes the cake, so to speak. With 100% organic, USA-grown hemp, no GMOs or artificial ingredients, and a customer care team armed with knowledge and compassion, you just won’t find a better deal in the CBD space.

This delicious, (no, we didn’t try it ourselves, we asked the dogs!) potent, and affordable canine CBD oil offers the savory taste of salmon with the potency of organic hemp extract and the Verma quality promise. Curb your pup’s arthritis symptoms with some of the best CBD in the business without spending a fortune. There’s a reason this one made the top of the list!

2. Penguin Natural Flavor CBD Oil 600mg

Price

Dose

600mg per bottle/20mg per serving

Why buy?

Penguin CBD’s natural flavored CBD oil takes the number two spot on our list with flying colors. This 600mg, $75 bottle of high-potency CBD can conquer arthritis and so much more, leaving your pup feeling happy, healthy, and active. Penguin is renowned in publications like Maxim, Healthline, and Rolling Stone for its potency, quality, and transparency.

The blend contains no THC, so you don’t have to worry about your dog becoming intoxicated, but still takes advantage of the full-spectrum of cannabinoids found in Cannabis. Get your bottle today to learn why Penguin is so loved by customers across the country.

3. Evn CBD Natural Flavor CBD Oil 500mg

Price

Dose

500mg per bottle/16.6mg per serving

Why buy?

If you were looking for all-natural, affordable, THC-free CBD oil for your dog’s arthritis pain, you’ve found it. Evn CBD is one of the country’s favorite brands, but not because it’s affordable; because it’s incredible. With only natural ingredients, premium hemp, and no THC, this is the perfect option for pets and humans alike.

Every one of Evn CBD’s products is lab-tested to ensure maximum quality, because why pay for anything else? Evn comes with some excellent reviews as well, both from its paying customers and industry critics at Forbes, Discover, and Thrillist.

4. PureKana Bacon Flavor CBD Oil for Pets 500mg

Price

Dose

500mg per bottle/10mg per serving

Why buy?

If you can keep your dog away from the bottle long enough, you might manage to get a few drops of this delicious bacon-flavored CBD oil on their food. But dogs love it, and so do we. Why? Because it’s organic, natural, and made by PureKana; one of the best and most well-respected CBD brands in the industry today.

Crush your dog’s arthritis symptoms with 10mg of potent CBD per serving. With 500mg in each bottle and a price tag of just under $50, you can’t beat the quality and consistency this brand has to offer.

5. Charlotte’s Web Full-Spectrum Hemp Extract CBD Oil for Dogs 30mL

Price

$59.99 per bottle

Dose

500mg per bottle/17mg per serving

Why buy?

Charlotte’s Web is one of our favorite CBD providers because the brand always brings something new to the table. This chicken-flavored CBD oil for dogs is a perfect example. Where many brands don’t offer any flavors for their pet blends, Charlotte’s Web offers delicious chicken flavor alongside pure, potent CBD for an effect your dog will feel right away.

Conquer those stiff, achy joints with some of the best CBD in the industry.

6. MedTerra Beef Flavor CBD Tincture for Dogs 300mg

Price

$24.99 per bottle

Dose

300mg per bottle/10mg per serving

Why buy?

MedTerra is one of the country’s premier CBD brands, with gummies, oils, and plenty of other products for humans and pets alike. This particular pet blend is designed for dogs of every size, featuring 300mg of potent CBD and a delicious beef flavor that even the pickiest doggos simply can’t ignore.

7. CBD Distillery CBD Pet Tincture 150mg

Price

$20 per bottle (normally $30)

Dose

150mg per bottle/5mg per serving

Why buy?

CBD Distillery is another one of our preferred CBD brands, simply because of a commitment to quality we think you can appreciate. If you’re looking for something that won’t break the bank and is versatile enough for both large and small dog breeds, this 150mg bottle of premium CBD oil from CBD Distillery is just what you need.

Made with premium CBD extracted from high-quality hemp, this blend offers relief for even the worst arthritis pains in manageable doses. Keep your pup comfortable and happy and your mind at ease with CBD Distillery’s entry in our top ten.

8. HolistaPets Unflavored Full-Spectrum (NO THC) CBD Oil for Pets 300mg

Price

$64.95 per bottle

Dose

300mg per bottle/5mg per serving

Why buy?

Sometimes, a more holistic approach is the better approach, especially for ailments like arthritis. Mother Nature offers a full bounty of effective products for treating canine arthritis, and few reach the staggering potential that Holistapet’s unflavored, full-spectrum CBD oil for pets does. With all-natural ingredients, no THC, and a name you can trust, this is the perfect option for doggos who need a little extra relief from their worst symptoms.

9. Holistic Hound Mighty Mojo CBD and Mushroom Oil for Dogs 250mg

Price

$59.97 per bottle

Dose

250mg per bottle

Why buy?

Holistic Hound might be a newcomer on our list, but don’t let that fool you. This Mighty Mojo CBD and mushroom extract blend contains only premium, naturally sourced ingredients to support your doggo’s health. Leave arthritis symptoms behind with natural CBD and conquer other health complications with wild mushroom extract in a convenient format.

Each bottle contains 250mg of CBD and mushroom extract for easy dosing, and while the full spectrum of cannabinoids is included in the there is no THC present. Try some today for something a bit different.

10. CBDFx Small Breed CBD Oil Tincture for Dogs 250mg

Price

$29.99 per bottle

Dose

250mg per bottle

Why buy?

CBDFx is next with its premium small breed CBD oil tincture. Perfect for pain, inflammation, and other arthritis symptoms, this simple blend combines quality, affordability, and consistency from a brand trusted by critics and customers alike. Every ingredient is organic and non-GMO, so you’re giving your pup only the best in CBD oils.

11. Innovet Pet Organic Full-Spectrum CBD Oil for Dogs 125mg

Price

$21.45 per bottle

Dose

125mg per bottle/5mg per serving

Why buy?

Why buy Innovet’s CBD oil for pets? If you’re looking for USDA-certified organic hemp extract, you just can’t do better. With the seal of approval from the USDA, Innovet brings potent, effective CBD oil to pets everywhere with this 125mg bottle. The smaller dose size is perfect for dogs who are new to CBD or for smaller dog breeds with less of a tolerance to cannabinoids.

Get yours today and pay a fraction of the cost of other brands with the same quality. Innovet also sends all of its CBD to a lab for third-party testing, so you know you’re getting only the best product for your money.