Detection of pro-inflammatory cytokines in healthy canine tears using Canine Cytokine SpikeMix™ mass spectrometry via multiple reaction monitoring.

PURPOSE: To evaluate the efficacy of the Canine Cytokine SpikeMix™ and MRM-MS for detecting pro-inflammatory cytokines in canine tears from healthy research Beagles. METHODS: A complete ophthalmic examination was performed on 15 healthy research Beagles to verify no ophthalmic diseases. Tears were collected OU by placing a Weck-Cel® cellulose spear in the ventral conjunctival fornix for 1 min. The Weck-Cel® spear was placed in a 2.0 mL tube with a centrifuge filter forcing tears to flow through the filter into the bottom of the tube. The tears were analyzed using the Canine Cytokine SpikeMix™ and MRM-MS. Descriptive data from this study was reported as the normalized total peak area (nTPA) and median (range) using data imported from the online MRM-MS Skyline program. RESULTS: The level of 16 pro-inflammatory cytokines was successfully detected in all 15 dogs. The four cytokines with the highest median amounts in the samples were IL-2 = 0.1243 (0.019-6.7289), IL-6 = 0.964 (0.0036-16.9365), TNFα = 0.1644 (0.0096-0.7138), and CSF-2 = 0.4022 (0.1475-2.6208). CONCLUSIONS: This study revealed that 16 pro-inflammatory cytokines in canine tears from healthy dogs can be detected with Canine Cytokine SpikeMix™ and MRM-MS.

Long-term effect of oral cannabidiol administration to healthy adult dogs on tear production, intraocular pressure, and tear concentrations.

OBJECTIVE: To determine the chronic effects of oral cannabidiol (CBD) use on tear production, intraocular pressure (IOP), and concentration of CBD in tears of healthy dogs. ANIMALS STUDIED: Eighteen healthy research Beagles. PROCEDURES: This was a masked, placebo-controlled, randomized prospective study. Eighteen dogs were randomly assigned to three groups (six dogs per group) based on daily dosage of oral MCT oil (placebo), CBD 5 mg/kg, and CBD 10 mg/kg. Schirmer tear test (STT-1) and IOP were measured twice daily (7 am and 7 pm) every 4 weeks for 36 weeks. Week 36 tears were collected and analyzed for CBD concentrations (ng/mL) using liquid chromatography/mass spectrometry. A mixed linear model was used as the statistical method and p-value <.05 was considered significant. RESULTS: No significant differences were found between placebo vs. 5 mg/kg vs. 10 mg/kg for STT-1 or IOP (AM and PM). CBD was detected in 10 out of 11 (91%) viable tear samples receiving 5 mg/kg or 10 mg/kg dosages. One sample in the 5 mg/kg group had inadequate tear volume for analysis. The CBD concentration in tears was at or below the lower limit of quantification in placebo group, 4.12-11.2 ng/mL for the 5 mg/kg group, and 6.22-152 ng/mL for the 10 mg/kg group. CONCLUSIONS: Long-term administration of oral CBD in healthy research beagles demonstrates a favorable safety profile regarding ocular tolerability. Oral CBD administration does not appear to affect tear production or IOP over a 36-week period. This is the first canine study positively identifying concentrations of CBD in tears following oral administration.

Flip the Pharmacy's impact on comprehensive medication management performance.

BACKGROUND: Clinically integrated networks of community pharmacies are expanding partnerships with health care payers for sustainable provision of patient care services. The Pennsylvania Pharmacists Care Network (PPCN), a part of CPESN USA, launched its first payer program in 2017 with a Medicaid managed care organization for comprehensive medication management (CMM). Some PPCN pharmacy teams have participated in Flip the Pharmacy, a national practice transformation initiative. OBJECTIVES: This study aimed to determine whether pharmacy participation in Flip the Pharmacy was associated with a greater rate of CMM encounters than in nonparticipating pharmacies within a statewide clinically integrated network. METHODS: This project was a retrospective quantitative study. CMM encounter data including total number of encounters and total number of eligible members were extracted from monthly reports. Generalized estimating equations were used to assess the association between Flip the Pharmacy participation and CMM encounter rates. RESULTS: Of 103 pharmacies that participated in the CMM program in 2019 and 2020, 77.7% of pharmacies (n = 80) were included in analyses. Of these, 31.3% (n = 25) participated in Flip the Pharmacy. Overall, 80 pharmacies documented 8460 patient encounters through the CMM program. On average, pharmacies participating in Flip the Pharmacy recorded 1.67 times the rate of encounters compared with non-Flip the Pharmacy pharmacies (95% CI 1.10-2.54), controlling for single versus multiple pharmacy sites and weekend hours. On average, pharmacies participating in Flip the Pharmacy recorded 1.18 times the rate of initial encounters (95% CI 0.84-1.59) and 2.06 times the rate of follow-up encounters (95% CI 1.22-3.48) compared with non-Flip the Pharmacy pharmacies. CONCLUSION: Participation in Flip the Pharmacy in Pennsylvania was associated with greater engagement and completion of encounters within a payer program for CMM. Continued practice transformation efforts are needed to ensure the sustainability of community pharmacy practice as it continues to expand into payment for patient care services.

Coaching strategies for the Flip the Pharmacy practice transformation initiative in Pennsylvania independent community pharmacies.

BACKGROUND: Flip the Pharmacy (FtP) is a nationwide initiative to scale practice transformation in community pharmacies. Participating pharmacies are coached through monthly practice transformation initiatives and document their patient-care activities through Pharmacist electronic Care (eCare) Plans. OBJECTIVES: The objective of this study was to identify peer coaching strategies to facilitate practice transformation in Pennsylvania community pharmacies. METHODS: This was a qualitative study using semistructured interviews with practice transformation coaches and pharmacy champions participating in Pennsylvania's FtP program. The interview guide was informed by the Consolidated Framework for Implementation Research and elicited information using the intervention characteristics, inner setting, characteristics of individuals, and process domains. Interviews were conducted in person or via telephone over a 3-month period. An inductive qualitative thematic analysis was performed to identify coaching strategies. RESULTS: A total of 18 key informants were interviewed: 6 pharmacy champions and 12 practice transformation coaches. The following 5 coaching strategies emerged: (1) learn to use the pharmacy's specific Pharmacist eCare Plan software, (2) build a trusting relationship with the pharmacy, (3) engage all pharmacy team members in practice transformation, (4) adapt communication strategies to the pharmacy's preference, and (5) tailor goals to the pharmacy's stage of practice transformation. CONCLUSION: This study elicited 5 peer coaching strategies to support community pharmacy practice transformation initiatives. These findings can be used to further practice transformation efforts in community pharmacies through FtP and other initiatives aimed at expansion of community pharmacy patient care services.

Pharmacokinetics of escalating single-dose administration of cannabidiol to cats.

This study aimed to assess the single-dose pharmacokinetics and tolerability of a cannabidiol (CBD) isolate in sunflower oil with escalating oral doses in eight healthy, purpose-bred cats. Eight cats were randomized into six dosing groups of four cats each. Cats were administered a single 2.5, 5, 10, 20, 40, or 80 mg/kg dose orally with at least a two-week washout in between doses. Behavior scoring, complete blood count, serum biochemistry analysis, physical examination, and CBD plasma levels were evaluated before and after dosing. All cats successfully completed the study. CBD was measured in the plasma of all cats dosed with CBD oil. The Cmax and AUC increased in a dose-proportional fashion across all dosing groups. There were no major bloodwork or behavioral changes although the BUN and creatinine values decreased after treatment across all doses. No adverse effects were observed, and behavioral changes were limited to head shaking, lip smacking, and hypersalivation immediately following dose administration. Single orally administered CBD doses up to 80 mg/kg were safe and well tolerated in this cohort of cats and display dose-proportional pharmacokinetics across a broad concentration.

Atypical multiple myeloma in 3 young dogs.

Three dogs under 12 months old were diagnosed with atypical multiple myeloma (MM), having an aggressive multifocal anaplastic round cell sarcoma in bone marrow, viscera, and/or peripheral blood, which were confirmed by cytology and immunohistochemistry to be of plasma cell origin. The intramedullary sarcomas caused myelophthisis, osteolysis, and hypercalcemia. Complete or free light chain monoclonal gammopathy in the serum and/or urine was demonstrated by protein electrophoresis and immunofixation. The polymerase chain reaction for antigen receptor rearrangement assay performed on 2 cases identified a clonally rearranged immunoglobulin gene. Neoplastic cells lacked expression of CD45, CD3, CD18, CD21, CD34, and MHCII by flow cytometry. Immunohistochemistry revealed MUM1 immunoreactivity of the neoplastic cells. Combining all data, the diagnosis was MM. An aggressive form of MM in young dogs should be a differential diagnosis for patients with an immunoglobulin-productive, B cell-clonal, CD45-negative, MUM1-positive discrete cell neoplasm arising from the bone marrow.

Use of a telovelar approach for complete resection of a choroid plexus tumor in a dog.

OBJECTIVE: To describe a telovelar approach to the fourth ventricle for excision of a choroid plexus tumor within the ventricle. ANIMAL: A 3-year-old entire male Chihuahua. STUDY DESIGN: Case report METHODS: A 3-year-old dog with two-month history of progressive vestibular signs and subdued mentation was diagnosed with a fourth ventricle tumor. Gross total resection of the tumor was achieved through a telovelar approach to the fourth ventricle. RESULTS: Complete removal of the tumor was confirmed on immediate postoperative MRI. The dog recovered from the surgical procedure without complications, displaying some neurological deficits as preoperatively. His neurological examination was normal 2 weeks after surgery and remained so until the time of writing this case report (28 months) without additional treatment. CONCLUSION: The telovelar approach allowed complete excision of a choroid plexus tumor located in the fourth ventricle of the dog reported here.

Plasma and joint tissue pharmacokinetics of two doses of oral cannabidiol oil in guinea pigs (Cavia porcellus).

Cannabidiol (CBD) has gained widespread popularity as a treatment for osteoarthritis (OA) in pets; however, there is minimal scientific evidence regarding safe and effective dosing. This study determined plasma and tissue pharmacokinetics after oral CBD oil suspension administration in Hartley guinea pigs (Cavia porcellus), which spontaneously develop OA at 3 months of age. Ten, 5-month-old, male guinea pigs were randomly assigned to receive 25 (n = 5) or 50 mg/kg (n = 5) CBD oil once orally. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 h timepoints. Open-field enclosure monitoring revealed no adverse effects. After euthanasia, stifle cartilage and infrapatellar fat pads were collected to quantitate CBD. CBD concentrations were determined using a validated liquid chromatography-mass spectrometry method, and pharmacokinetic parameters were calculated using noncompartmental analysis. The area under the plasma concentration-versus-time curve was 379.5 and 873.7 h*ng/mL, maximum plasma concentration was 42 and 96.8 ng/mL, time to maximum plasma concentration was 1.6 and 4.8 h, and terminal phase half-life was 8.1 and 10.8 h for the 25 and 50 mg/kg doses, respectively. CBD was detected in joint tissues of all animals. Further studies, including work in female guinea pigs, are needed to determine the efficacy of CBD for OA.

Evaluation of the Effect of Cannabidiol on Naturally Occurring Osteoarthritis-Associated Pain: A Pilot Study in Dogs.

The objective of this study was to provide preliminary data describing the safety and effect of cannabidiol (CBD) for symptom relief of canine osteoarthritis-associated pain in a clinical setting using objective outcome measures. Twenty-three client-owned dogs with naturally occurring osteoarthritis of appendicular joints completed this prospective, double-blinded, crossover, placebo-controlled study. Baseline data were acquired for 4 wk, followed by random allocation to either placebo or CBD treatment for 6 wk, followed by 6 wk with the opposite treatment. Outcome measures included objective gait analysis, activity counts (via accelerometry) and clinical metrology instruments. There were no differences noted between groups at any time point for any of the recorded outcome measures. Adverse events associated with CBD administration included elevation in liver enzymes (n = 14) and vomiting (n = 2).

Onscreen-guided resection of extra-axial and intra-axial forebrain masses through registration of a variable-suction tissue resection device with a neuronavigation system.

OBJECTIVES: To describe a novel surgical technique in which neuronavigation is used to guide a tissue resection device during excision of forebrain masses in locations difficult to visualize optically. STUDY DESIGN: Short case series. ANIMALS: Six dogs and one cat with forebrain masses (five neoplastic, two nonneoplastic) undergoing excision with a novel tissue resection device and veterinary neuronavigation system. METHODS: The animals and resection instrument were coregistered to the neuronavigation system. Surgery was guided by real-time onscreen visualization of the resection instrument position relative to the preoperative MR images. Surgical outcome was evaluated by calculating residual tumor volume according to postoperative MRI. RESULTS: The technique was technically simple and led to the collection of diagnostic tissue samples in all cases. Postoperative MRI was available in six cases, two with gross-total resection, three with near-total resection, and one with subtotal resection. CONCLUSION: Neuronavigation-guided resection of intra-axial and extra-axial brain masses with the resection device resulted in gross-total or near-total resection in five of six animals with tumors otherwise difficult to visualize. Risk of brain shift limited absolute reliance on navigation images. CLINICAL SIGNIFICANCE: Real-time neuronavigation assistance is a feasible method for guidance and successful resection of brain masses that are poorly visualized because of intra-axial or deep location, tumor appearance, or hemorrhage.

Community pharmacists' educational needs for implementing clinical pharmacogenomic services.

OBJECTIVES: Pharmacist leadership and knowledge of pharmacogenomics is critical to the acceleration and enhancement of clinical pharmacogenomic services. This study aims for a qualitative description of community pharmacists' pharmacogenomic educational needs when implementing clinical pharmacogenomic services at community pharmacies. METHODS: Pharmacists practicing at Rite Aid Pharmacy locations in the Greater Pittsburgh Area were recruited to participate in this qualitative analysis. Pharmacists from pharmacy locations offering pharmacogenomic testing and robust patient care services were eligible to participate in a semistructured, audio-recorded interview. The semistructured interview covered 4 domains crafted by the investigative team: (1) previous knowledge of pharmacogenomics; (2) implementation resources; (3) workflow adaptation; and (4) learning preferences. Interviews were transcribed verbatim and independently coded by 2 researchers. A thematic analysis by the investigative team followed. Supporting quotes were selected to illustrate each theme. RESULTS: Eleven pharmacists from 9 unique pharmacy locations participated in this study. The average length of practice as a community pharmacist was 12 years (range, 1.5-31 years). Pharmacist's pharmacogenomic educational needs were categorized into 5 key themes: (1) enriched pharmacogenomic education and training; (2) active learning to build confidence in using pharmacogenomic data in practice; (3) robust and reputable clinical resources to effectively implement pharmacogenomic services; (4) team-based approach throughout implementation; (5) readily accessible network of pharmacogenomic experts. CONCLUSION: This study describes the educational needs and preferences of community pharmacists for the successful provision of clinical pharmacogenomic services in community pharmacies. Pharmacists recognized their needs for enriched knowledge and instruction, practice applying pharmacogenomic principles with team-based approaches, robust clinical resources, and access to pharmacogenomic experts. This deeper understanding of pharmacist needs for pharmacogenomic education could help to accelerate and enhance the clinical implementation of pharmacogenomic services led by community pharmacists.

The pharmacokinetics of cytarabine administered at three distinct subcutaneous dosing protocols in dogs with meningoencephalomyelitis of unknown origin.

The objective of this study was to evaluate the pharmacokinetics of the standard cytarabine (Ara-C) protocol (50 mg/m2 subcutaneously every 12 hr for 2 days) used for dogs with neuroinflammatory disease and compare it to two more practical protocols (a single 200 mg/m2 subcutaneous dose and two 100 mg/m2 subcutaneous doses every 12 hr). Four client-owned dogs previously diagnosed with meningoencephalomyelitis of unknown origin were administered three distinct Ara-C protocols with a 21-day washout between each protocol. A complete blood count was performed seven days after each dosing protocol to assess for clinically relevant myelosuppression. No adverse events were observed. Plasma Ara-C concentrations were measured using a validated liquid chromatography coupled to tandem mass spectrometry assay. The mean maximal concentrations in this study were 4,230, 9,293, and 16,675 ng/ml for a single dose of 50, 100, and 200 mg/m2 , respectively. There was a linear relationship between dose and drug exposure. Drug exposure was similar regardless of the dosing protocol when the total dose was analyzed, with an area under the concentration versus time curve of 37,026, 38,465, and 32,510 ng × hr/ml for 50, 100, and 200 mg/m2 , respectively.

Activity of hypothiocyanite and lactoferrin (ALX-009) against respiratory cystic fibrosis pathogens in sputum.

Objectives: To determine the antimicrobial activity of ALX-009, a combination of bovine lactoferrin and hypothiocyanite, in sputum against Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc), key pathogens causing infection in the lungs of cystic fibrosis (CF) patients. Methods: The antimicrobial activity of ALX-009 against clinical respiratory P. aeruginosa isolates was determined by time-kill assay. Sputum from CF patients was treated with ALX-009, either alone or in combination with tobramycin, and the effect on P. aeruginosa, Bcc and total sputum density was determined. Results: Time-kill assay indicated that ALX-009 was bactericidal at 24 h against 4/4 P. aeruginosa isolates under aerobic conditions, and against 3/4 isolates under anaerobic conditions. ALX-009 was also bactericidal against P. aeruginosa in sputum samples at 6 h (n = 22/24 samples) and 24 h (n = 14/24 samples), and demonstrated significantly greater activity than tobramycin at both timepoints. Activity against Bcc in sputum samples (n = 9) was also demonstrated, but the magnitude of change in Bcc density was less than for P. aeruginosa. To determine the effect of treating sputum with two doses of ALX-009, similar to current regimens for inhaled antibiotics, aliquots of a further 10 sputum samples positive for P. aeruginosa were treated with one (t = 0 h) or two doses (t = 0 h, t = 12 h) of ALX-009; treatment with two doses resulted in bactericidal activity in 7/10 samples at 34 h compared with only 3/10 samples when treatment was with one dose. Conclusions: ALX-009 demonstrates promise as a novel antimicrobial that could be used to decrease P. aeruginosa density in the lungs of people with CF.

Clinical and imaging findings, treatments, and outcomes in 27 dogs with imaging diagnosed trigeminal nerve sheath tumors: A multi-center study.

The clinical behavior of canine trigeminal nerve sheath tumors and benefits of previously reported treatments are incompletely defined. Aims of this retrospective, multicenter, observational study were to describe clinical signs, tumor localization characteristics, treatments, and clinical outcomes in a group of dogs with this neoplasm. Databases at four hospitals were reviewed for dogs with a trigeminal nerve sheath tumor diagnosis, magnetic resonance imaging (MRI) studies, and presentation between 2004 and 2014. A single observer recorded medical record findings and two observers recorded MRI characteristics by consensus. A total of 27 dogs met inclusion criteria (15 treated with stereotactic radiation therapy and 12 unirradiated). Two unirradiated dogs were excluded from outcome analyses. The most common presenting signs were masticatory muscle atrophy (26 dogs), neurologic signs referable to intracranial disease (13), and ocular disease (12). Based on MRI findings, all dogs had disease extending centrally at the level of the brainstem. The most commonly affected trigeminal nerve branches were the mandibular (26 dogs), maxillary (22), and ophthalmic (10). Of 15 dogs treated with stereotactic radiation therapy, one had improved muscle atrophy, and six had poor ocular health after treatment. Neurologic signs improved in 4/5 dogs with intracranial signs. Overall median survival time for the 10 unirradiated dogs with available follow-up was 12 days and 441 days for the 15 stereotactic radiation therapy dogs. Mean survival times between these groups were not significantly different (mean 95% CI for unirradiated dogs was 44-424 days and mean 95% CI for stereotactic radiation therapy dogs was 260-518 days).

Implementation of targeted medication adherence interventions within a community chain pharmacy practice: The Pennsylvania Project.

OBJECTIVE: To identify facilitators and barriers to implementing targeted medication adherence interventions in community chain pharmacies, and describe adaptations of the targeted intervention and organizational structure within each individual pharmacy practice. DESIGN: Qualitative study. SETTING: Central and western Pennsylvania from February to April 2012. PARTICIPANTS: Rite Aid pharmacists staffed at the 118 Pennsylvania Project intervention sites. MAIN OUTCOME MEASURES: Qualitative analysis of pharmacists' perceptions of facilitators and barriers experienced, targeted intervention and organizational structure adaptations implemented, and training and preparation prior to implementation. RESULTS: A total of 15 key informant interviews were conducted from February to April 2012. Ten pharmacists from "early adopter" practices and five pharmacists from "traditionalist" practices were interviewed. Five themes emerged regarding the implementation of targeted interventions, including all pharmacists' need to understand the relationship of patient care programs to their corporation's vision; providing individualized, continual support and mentoring to pharmacists; anticipating barriers before implementation of patient care programs; encouraging active patient engagement; and establishing best practices regarding implementation of patient care services. CONCLUSION: This qualitative analysis revealed that there are a series of key steps that can be taken before the execution of targeted interventions that may promote successful implementation of medication therapy management in community chain pharmacies.

Tolerability of long-term cannabidiol supplementation to healthy adult dogs.

BACKGROUND: Cannabidiol (CBD) has therapeutic potential in companion animals. Shorter-term studies have determined that CBD is well tolerated in dogs with mild adverse effects and an increase in alkaline phosphatase (ALP) activity. There is need to assess CBD's long-term tolerability. HYPOTHESIS: Determine the long-term tolerability of CBD administered PO to healthy dogs for 36 weeks at dosages of 5 and 10 mg/kg body weight (BW)/day. Our hypothesis was that CBD would be well tolerated by dogs. METHODS: Eighteen healthy adult beagle dogs were randomly assigned to 3 groups of 6 each that received 0, 5, or 10 mg/kg BW/day CBD PO. Dogs were adapted to their housing for 3 weeks and received treatment for 36 weeks once daily with food. Adverse events (AEs) were recorded daily. Blood biochemistry profiles were monitored every 4 weeks. Data were analyzed as repeated measures over time using a mixed model, with significance at α = 0.05. RESULTS: The 0 and 5 mg/kg treatment groups had similar fecal scores, and the 10 mg/kg treatment group had higher frequency of soft feces. No other significant AEs were noted. An increase (P < .0001) in ALP activity occurred in groups that received CBD. Remaining blood variables were within reference range. CONCLUSIONS AND CLINICAL IMPORTANCE: Chronic administration of CBD in healthy dogs at 5 mg/kg was better tolerated than 10 mg/kg, and both dosages caused an increase in ALP activity. Although our data does not indicate hepatic damage, it is recommended to monitor liver function in dogs receiving CBD chronically.

Targeting Neuroinflammation by Pharmacologic Downregulation of Inflammatory Pathways Is Neuroprotective in Protein Misfolding Disorders.

Neuroinflammation plays a crucial role in the development of neurodegenerative protein misfolding disorders. This category of progressive diseases includes, but is not limited to, Alzheimer's disease, Parkinson's disease, and prion diseases. Shared pathogenesis involves the accumulation of misfolded proteins, chronic neuroinflammation, and synaptic dysfunction, ultimately leading to irreversible neuronal loss, measurable cognitive deficits, and death. Presently, there are few to no effective treatments to halt the advancement of neurodegenerative diseases. We hypothesized that directly targeting neuroinflammation by downregulating the transcription factor, NF-κB, and the inflammasome protein, NLRP3, would be neuroprotective. To achieve this, we used a cocktail of RNA targeting therapeutics (SB_NI_112) shown to be brain-penetrant, nontoxic, and effective inhibitors of both NF-κB and NLRP3. We utilized a mouse-adapted prion strain as a model for neurodegenerative diseases to assess the aggregation of misfolded proteins, glial inflammation, neuronal loss, cognitive deficits, and lifespan. Prion-diseased mice were treated either intraperitoneally or intranasally with SB_NI_112. Behavioral and cognitive deficits were significantly protected by this combination of NF-κB and NLRP3 downregulators. Treatment reduced glial inflammation, protected against neuronal loss, prevented spongiotic change, rescued cognitive deficits, and significantly lengthened the lifespan of prion-diseased mice. We have identified a nontoxic, systemic pharmacologic that downregulates NF-κB and NLRP3, prevents neuronal death, and slows the progression of neurodegenerative diseases. Though mouse models do not always predict human patient success and the study was limited due to sample size and number of dosing methods utilized, these findings serve as a proof of principle for continued translation of the therapeutic SB_NI_112 for prion disease and other neurodegenerative diseases. Based on the success in a murine prion model, we will continue testing SB_NI_112 in a variety of neurodegenerative disease models, including Alzheimer's disease and Parkinson's disease.

The clinical use of cannabidiol and cannabidiolic acid-rich hemp in veterinary medicine and lessons from human medicine.

The endocannabinoid system (ECS) is an integral neuromodulatory system involved in neuronal development, synaptic plasticity, and homeostasis regarding immunity, as well as brain and other physiological functions such as anxiety, pain, metabolic regulation, and bone growth. Cannabis is a plant that contains exogenous cannabinoids, which have the potential for profound interplay within the ECS as enzymatic inhibitors or receptor-mediated interactions. Activation of cannabinoid receptors leads to various intracellular signaling processes that are involved in cellular functions, but those interactions are diverse due to different affinities of each cannabinoid with relevant receptors. Among the exogenous cannabinoids, cannabidiol (CBD) has drawn attention due to its potential anticancer, antiangiogenic, anti-inflammatory, and antiseizure properties using in vitro and in vivo models. Although scientific evidence is limited in dogs, there appears to be cautious optimism regarding the utilization of CBD in conjunction with other therapeutics for a range of disorders. This review will primarily focus on current scientific research on the efficacy of CBD on seizure, anxiety, osteoarthritis, and atopic dermatitis, following a brief discussion of endo- and exogenous cannabinoids, ECS, their molecular mechanism, and potential side effects in veterinary medicine. Cannabinoid pharmacology and pharmacokinetics will be addressed in the companion Currents in One Health by Schwark and Wakshlag, AJVR, May 2023.

Scientific Validation of Cannabidiol for Management of Dog and Cat Diseases.

Cannabidiol (CBD) is a non-psychotropic phytocannabinoid of the plant Cannabis sativa L. CBD is increasingly being explored as an alternative to conventional therapies to treat health disorders in dogs and cats. Mechanisms of action of CBD have been investigated mostly in rodents and in vitro and include modulation of CB1, CB2, 5-HT, GPR, and opioid receptors. In companion animals, CBD appears to have good bioavailability and safety profile with few side effects at physiological doses. Some dog studies have found CBD to improve clinical signs associated with osteoarthritis, pruritus, and epilepsy. However, further studies are needed to conclude a therapeutic action of CBD for each of these conditions, as well as for decreasing anxiety and aggression in dogs and cats. Herein, we summarize the available scientific evidence associated with the mechanisms of action of CBD, including pharmacokinetics, safety, regulation, and efficacy in ameliorating various health conditions in dogs and cats.

Cannabidiol plasma determination and pharmacokinetics conducted at beginning, middle and end of long-term supplementation of a broad-spectrum hemp oil to healthy adult dogs.

Introduction: Veterinary hemp products containing cannabidiol (CBD) and negligible psychoactive (THC) have increased popularity since hemp (with <0.3% THC) was removed from schedule 1 substances under the Controlled Substances Act in 2018. This was accompanied by increased CBD research, mostly on the short-term safety and efficacy for inflammatory and neurological conditions. It is imperative to understand how CBD is metabolized or accumulated in the body long-term, thus the goal of the present work was to determine monthly plasma CBD concentrations, as well as changes in pharmacokinetic (PK) parameters in chronically dosed dogs. Methods: The study was a masked, placebo-controlled, randomized design. Six adult beagles were assigned to placebo, 5 and 10 mg/kg/day CBD treatment groups. Dogs received oral oil treatment once daily for 36 weeks. Blood was collected once every 4 weeks pre- and postprandially for CBD plasma determination (at 0 and 2 h). Pharmacokinetics were conducted at 0, 18 and 36 weeks. Pharmacokinetics and monthly CBD plasma data of dogs who received CBD were analyzed as repeated measures over time using a mixed model, with significance at α = 0.05. Results: Average plasma CBD at 5 and 10 mg/kg were 97.3 ng/mL and 236.8 ng/mL pre-prandial, 341 ng/mL and 1,068 ng/mL postprandial, respectively. PK parameters suggested CBD accumulation over time, with significant increases in Cmax and AUC at both the 18 and 36-week timepoints. Cmax and AUC were dose proportional. Half-life demonstrated large inter-individual variations and increased (p < 0.05) at weeks 18 and 36 compared to baseline. Volume of distribution was not affected by time or treatment, while MRT increased, and clearance decreased over time (p < 0.05). Conclusions and clinical importance: Chronic administration of CBD to healthy adult dogs led to a dose-proportional accumulation in the body for 36 weeks, which was confirmed by an increased half-life, total exposure, mean residence time and plasma peak. Our data also suggests that CBD plasma levels may have less daily variation if administered twice daily.