Pharmacokinetics of a single oral administration of two cannabidiol formulations in fed and fasted horses DOI Creative Commons
Alessandra Di Salvo, Marilena Bazzano, Giorgia Della Rocca

et al.

Frontiers in Veterinary Science, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 19, 2025

Pain management in horses plays a pivotal role the therapeutic approach to several diseases. Horses have cannabinoid receptors at level of dorsal root ganglia, blood vessels, and synoviocytes that can be up or down- regulated by inflammatory conditions, justifying possible efficacy exogenous cannabinoids (i.e., phytocannabinoids) managing painful pathologies this animal species. However, current use supplements containing cannabidiol (CBD) equines is based on anecdotal evidence, without support sufficient pharmacokinetic studies. In humans, concentration peak CBD area under concentration-time curve (AUC) are both strongly influenced food administration. Also, equids, oral bioavailability some drugs meal but no information available about CBD. This study investigated pharmacokinetics following single administration two different formulations pure (oil paste), dosed 1 mg/kg, times oil paste were administered orally mg/kg eight healthy according cross over design, samples taken pre-fixed time-points for analyses. The obtained data did not allow statistically significant differences between (paste oil) feeding time (fed fasted status). treatment with paste, Cmax was achieved shorter range compared oily formulation, indicating it could better formulation consider future equine

Language: Английский

Editorial: Use of cannabis derivatives in veterinary medicine DOI Creative Commons
Robin Temmerman

Frontiers in Veterinary Science, Journal Year: 2025, Volume and Issue: 12

Published: March 7, 2025

Editorial: Use of Cannabis Derivatives in Veterinary MedicineIntroductionCannabis species (Cannabis spp.) are pharmacologically diverse plants containing myriad distinct compounds, with the phytocannabinoids (pCBs) tetrahydrocannabinolic acid (THCA) and cannabidiolic (CBDA) their derivatives Δ9-tetrahydrocannabinol (THC) cannabidiol (CBD) as prime examples. The main pharmacodynamic target these compounds is endocannabinoid system (ECS), which comprises endocannabinoids (eCBs) such anandamide (AEA) 2-Arachidonoylglycerol (2-AG), cannabinoid receptors (CB) 1 2 anabolic/catabolic enzymes (Di Salvo, Conti, Della Rocca 2023; Di Salvo et al. 2024; Marzo 2020; Lutz 2020). Inclusion several eCB-like lipid mediators, metabolic molecular targets forms endocannabinoidome 2020).In human medicine, use cannabis-derived products increasing globally for a variety indications, post-injury back pain, chronic neuropathic sleeping disorders, multiple sclerosis, epilepsy others (Klatzkow 2022; Levinsohn Hill Leinen 2023). medicine dovetailing this trend growing interest from clients veterinarians treating medical conditions animals molecules. In general, CBD primary entity veterinary but other molecules being investigated, exemplified Research Topic (e.g. studies CBDA) Johns Thomson 2024).While cannabinoids show considerable therapeutic potential management osteoarthritis, epilepsy, pain conditions, there currently paucity adequately controlled data to confirm safe effective indications. Considering current knowledge research gap, goal was consolidate recent findings results high-quality on pharmacokinetics safety efficacy cannabis-derivatives animal species. This turn will serve basis further discussions investigations area. editorial synthesizes sixteen studies, published special e-collection, highlighting applications benefits cannabis practice.Pharmacokinetics BioavailabilityUnderstanding (PK) crucial determining appropriate dosing regimens ensuring efficacy. Several have focused different formulations species: Dogs: comparing four preparations (3 liquid ones: oil-based, nanoemulsion-based water-soluble semi-solid formulation) dogs revealed that provided higher bioavailability faster absorption compared (Limsuwan 2024). concentration-time profiles were comparable between oil- water-based formulations. all reached maximum plasma concentration within 3 h post-dose, an average range 92–314 μg/L, aligns well Cmax values reported PK using same or similar dose levels 2023).Another study demonstrated no difference parameters when administered either orally transmucosally, indicating not readily adsorbed by oral mucosa probably swallowed absorbed gastrointestinal tract (Della 2022).In addition, subcutaneous injection liposomal-CBD formulation produced detectableCBD concentrations 6 weeks following (median range): 45.2 (17.8–72.5) ng/mL, Tmax 4 (2–14) days half-life12.4 (7.7–42.6) (Shilo-Benjamini long-acting properties could offer advantage patient owner compliance. Finally, Corsato Alvarenga shows long-term supplementation broad-spectrum hemp oil leads dose-proportional accumulation canine body (Corsato 2023). Cats: A administration 1:20 THC:CBD herbal extract cats has shown THC quickly absorbed, peak occurring 2-3 hours post-dose (Lyons also increased dose-proportionally. Importantly, appears be lower than (Chicoine 2020), suggesting potentially species-specific differences metabolism. Another explanation more general issue difficulty 2024). Horses: horses cross-over design nasogastric tube (2 mg/kg 8 mg/kg) CBD/CBDA-rich product indicated CBDA therefore showed (Thomson Additionally, it biphasic pattern. Reported were: - 5.2 36.95 ng/mL; 40.35 353.56 ng/mL. elimination half-life found relatively short possible calculate due lack quantifiable timepoints, need frequent maintain levels. Also, did appear impact neurological, behavioral (see below). Eichler mean 12.17 ng/ml dosed at mg/kg. study, leveraging single escalation (also discussed below), 3-compartmental population pharmacokinetic (popPK) built describe predict metabolite profiles. urine samples analysed, (7-OH-CBD) plasma. extensively metabolized high volumes tissue distribution (not corrected bioavailability) resulting extended phase (Eichler, Pozniak, Cynomolgus macaques (nonhuman primate): investigated (CBD/ArHO), two (4 cynomolgus macaques, nonhuman primates. Mean around 30 times (456.75 vs. 15.98 ng/ml). suggests once daily chosen insufficient maintaining serum (Johns 2023).Therapeutic ApplicationsCBD promise managing various patients, including inflammation, anxiety, although strength scientific evidence indications can fluctuate: Pain Inflammation: Klatzkow post-operative tibial plateau leveling osteotomy (TPLO) CBD/CBDA (dosed 2–2.5mg/kg PO every 12 weeks) randomized, placebo controlled, blinded clinical trial client-owned 2022). Variables included biochemistry, standardized assessments score, weight-bearing, lameness Canine Brief Inventory. significant early bone healing. CBA/CBDA associated increase alkaline phosphatase (ALP) decrease eosinophils association reduced anxiety. Shilo-Benjamini (liposomal) alleviating improving quality life osteoarthritis 2023) minimal adverse events. However, should interpreted cautiously non-blinding placebo.  Epilepsy: Clinical trials reduce frequency severity seizures intractable idiopathic These suggest valuable adjunctive treatment patients. Dermatological Conditions: case-report 2-year old mixed breed dog CBD-rich full spectrum autoimmune skin disorder discoid lupus erythematosus (DLE) (da Silva been used manage pruritus atopic dermatitis dogs. Mariga evaluated effectiveness full-spectrum (CAD) negative control (olive oil) based degree pruritus, dermatological evaluation (CADESI-4 scoring) histopathology. however olive group (Mariga Behavioral Disorders: explored anxiety stress-related behaviors dogs, some positive outcomes 2023).Safety TolerabilityThe profile critical consideration its medicine. Most well-tolerated animals, few effects: TPLO result blood ALP warrants caution serious events single-dose Bookout healthy beagle non-blinded, negatively-controlled, parallel 90-day repeat additional 14-day recovery period (Bookout authors report somnolence, (AE) (SAE). There changes pathology ALT, GGT), considered clinically relevant. It noted Klatzow highlight low AE SAE incidence US National Animal Supplement Council (NASC) Adverse Event Reporting System (NAERS). No effects observed 5 Coltherd conducted (6 month) tolerance THC-free, distillate (placebo) (Coltherd tolerated biochemistry haematology data. horses, neurologic, behavioral, Moreover, paste (TAMACAN XL 55%®) events-free Ehrle, Machnik, Eichler, Jensen, both (0.2, 1.0 3.0 (CBD 15 days) significantly heart rate, sedation level, behavioural observations morning cortisol placebo.Future DirectionsWhile research, e-collection specifically, provides insights into pharmacokinetics, areas warrant investigation: Long-term Safety: More needed assess cumulative levels. Dosing regimen optimization: Future focus optimizing (posology duration) maximize exposure subsequently while minimizing effects. Mechanisms Action: Understanding pharmacodynamics mode action exert (off-target) help developing targeted treatments specific conditions. Comparative Studies: across provide clearer understanding interspecies inherent underlying physiological mechanisms efficacy.In conclusion, highlights versatile agent claimed supported robustly showing intra- variability. Subsequently, medicalization presents opportunities challenges professionals, making continued essential fully elucidate ensure health care.

Language: Английский

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Pharmacokinetics of a single oral administration of two cannabidiol formulations in fed and fasted horses DOI Creative Commons
Alessandra Di Salvo, Marilena Bazzano, Giorgia Della Rocca

et al.

Frontiers in Veterinary Science, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 19, 2025

Pain management in horses plays a pivotal role the therapeutic approach to several diseases. Horses have cannabinoid receptors at level of dorsal root ganglia, blood vessels, and synoviocytes that can be up or down- regulated by inflammatory conditions, justifying possible efficacy exogenous cannabinoids (i.e., phytocannabinoids) managing painful pathologies this animal species. However, current use supplements containing cannabidiol (CBD) equines is based on anecdotal evidence, without support sufficient pharmacokinetic studies. In humans, concentration peak CBD area under concentration-time curve (AUC) are both strongly influenced food administration. Also, equids, oral bioavailability some drugs meal but no information available about CBD. This study investigated pharmacokinetics following single administration two different formulations pure (oil paste), dosed 1 mg/kg, times oil paste were administered orally mg/kg eight healthy according cross over design, samples taken pre-fixed time-points for analyses. The obtained data did not allow statistically significant differences between (paste oil) feeding time (fed fasted status). treatment with paste, Cmax was achieved shorter range compared oily formulation, indicating it could better formulation consider future equine

Language: Английский

Citations

0