How Safe is CBD in Horses

Hello, Summarians!

Just because we have the technological ability to change something does that mean we should pursue it? I get it. I am all for innovation and the possibility of improving our animal friends' quality of life, but how do we explore these ethical considerations?

Some studies and innovations beg for a different framework of questions. This is getting more critical as the speed of change could increase rapidly.

One of the studies below should be viewed with that thought in mind.

CBD in Horses.

Cannabidiol (CBD) and its precursor, cannabidiolic acid (CBDA), derived from Cannabis sativa, have shown potential therapeutic applications in veterinary medicine. While CBD is nonintoxicating and interacts with the endocannabinoid system to regulate neuronal development, pain, and inflammation, CBDA has unique properties, including selective inhibition of cyclooxygenase-2 and modulation of various receptors. Despite extensive research on CBD in dogs and cats, data on its effects in horses remain limited. 

Recent studies demonstrate that both CBD and CBDA are safe for short-term and chronic administration in horses. Acute and long-term pharmacokinetic studies reveal that CBDA exhibits superior absorption and retention compared to CBD, with higher peak serum concentrations and bioavailability. However, horses show lower plasma CBD concentrations compared to other species, possibly due to differences in metabolism, absorption pathways, or dietary factors. CBDA also demonstrates unique pharmacokinetic behavior, including higher absorption via certain delivery matrices and potential changes in metabolism over time. 

This study investigated the pharmacokinetics and safety of oral administration of full-spectrum CBD and CBDA oils in horses over six weeks. CBDA consistently exhibited better bioavailability than CBD, maintaining higher serum concentrations. Unlike CBD, whose peak concentrations declined over time, CBDA concentrations fluctuated, suggesting potential metabolic adaptations. No significant adverse effects were observed, and serum liver enzymes remained stable. Histopathological liver analysis confirmed no hepatocellular damage from chronic administration. Minor changes in serum sodium and chloride were attributed to dietary adjustments rather than cannabinoid effects. 

Although both cannabinoids were well-tolerated at 1 mg/kg doses, significant variability in absorption and serum concentrations was observed, potentially influenced by factors such as diet, gastrointestinal conditions, and age. CBDA's higher bioavailability and faster onset compared to CBD suggest it may be a more effective cannabinoid supplement for horses. Further studies are needed to explore the therapeutic benefits, optimal dosages, and mechanisms underlying CBDA’s pharmacokinetics, particularly for long-term use. This research underscores the importance of tailored cannabinoid formulations and delivery methods for improving therapeutic outcomes in equine medicine. 

Wang, T. C., Wakshlag, J. J., Jager, M. C., Schwark, W. S., Trottier, N. L., Chevalier, J. M., Pearson, G., & Cercone, M. (2025). Chronic oral dosing of cannabidiol and cannabidiolic acid full-spectrum hemp oil extracts has no adverse effects in horses: a pharmacokinetic and safety study. American Journal of Veterinary Research  https://doi.org/10.2460/ajvr.24.08.0235 

Bottom line — No adverse effects noted but pay attention to formulations.

Genetic Modification in Horse Embryos

In the past 17 years, horse cloning has primarily been used for commercial purposes to replicate valuable individuals due to its ability to conserve the genome, ensuring cloned foals inherit the original genotype. When combined with gene-editing techniques like CRISPR, cloning becomes a powerful tool for introducing new, desirable traits in one generation. CRISPR, originally identified as an immune system in prokaryotes, has been adapted for gene editing across various species, enabling advancements in disease resistance, bioreactor development, disease modeling, and xenotransplantation. 

In horses, genetic modifications have primarily focused on reversing genetic diseases and improving disease resistance. Recent efforts used CRISPR/Cas9 to correct mutations causing glycogen branching enzyme deficiency and skin disease in horse fibroblasts, with the intention of cloning these corrected cells. However, no prior studies targeted gene edits for improving sport performance in horses. The myostatin (MSTN) gene, a negative regulator of muscle growth, is a promising target. Mutations in MSTN can enhance muscle mass, as seen in certain cattle and dog breeds. Although MSTN mutations have not been described in horses, a specific SNP linked to racing performance has been identified. This study aimed to edit the MSTN gene in horse embryos using CRISPR/Cas9 and somatic cell nuclear transfer (SCNT), marking the first reported generation of edited horse embryos. 

Two gRNAs targeting MSTN's first exon demonstrated high editing efficiency. Editing outcomes depended on plasmid concentration, with lower concentrations favoring monoallelic edits and higher concentrations yielding biallelic edits but increasing off-target effects. Cloning was preferred over other embryo-generation methods due to its ability to ensure accurate edits before embryo development, avoiding the inefficiencies and risks of mosaicism associated with techniques like zygote microinjection. 

Despite its advantages, cloning requires clonal cell line generation, which can reduce efficiency due to increased cell passages. Alternative nuclear donors, such as mesenchymal stem cells (MSCs), may improve outcomes but face limitations like early senescence. Edited embryos generated in this study showed lower developmental rates than controls, likely due to these challenges. 

This study successfully edited fibroblasts and generated genetically modified horse embryos, enabling future corrections of genetic defects and precision breeding strategies. Long-term goals include introducing advantageous alleles, such as the MSTN promoter SINE insertion, to enhance traits like speed and muscle fiber composition, achieving desired characteristics in a single generation. 

Moro, Lucia & Viale, Diego & Bastón, Juan & Arnold, Victoria & Suvá, Mariana & Wiedenmann, Elisabet & Olguín, Martín & Miriuka, Santiago & Vichera, Gabriel. (2020). Generation of myostatin edited horse embryos using CRISPR/Cas9 technology and somatic cell nuclear transfer. Scientific Reports. 10. 15587. 10.1038/s41598-020-72040-4. 

Bottom line — Hmm… not sure this is a road we want to pursue.

Bacterial Fermentation as a Protein Source

The pilot study explores the use of a novel, greenhouse gas-derived fermented protein as a sustainable alternative in canine diets. The study highlights the growing demand for environmentally sustainable protein sources due to increasing concerns about the ecological impact of animal-based proteins in pet foods. This fermented protein source optimizes land and water usage, reduces carbon footprint, and offers a balanced amino acid profile. 

Three diet groups, including a control and diets with 5% and 10% fermented protein inclusion, were tested on Beagle dogs. Results showed the protein source was palatable and well-accepted, with no significant differences in alertness, clinical symptoms, water consumption, or social behavior among the groups. Faecal scoring and microbiome analysis revealed no adverse effects on gut health or microbial diversity, though slight shifts in specific bacterial genera were observed. 

Fermented proteins showed potential advantages over conventional animal-based and plant-based proteins, such as sustainability, nutritional balance, and reduced environmental impact. The protein diet had no negative effects on digestive health or weight maintenance. The findings suggest fermented protein is a viable option for enhancing canine diets while reducing greenhouse gas emissions and supporting sustainable practices. 

Although the study's short duration and small sample size are limitations, the findings provide a foundation for further research. Long-term, multicenter studies are recommended to confirm the nutritional and ecological benefits of this alternative protein. With advancements in fermentation technology and process engineering, integrating such proteins into commercial pet foods may significantly contribute to sustainability and carbon footprint reduction in the pet food industry. 

Babu Ravindra , Padmanabhan Sreedevi , Ganesan Ravikumar , Subbian Ezhil , Van Thi Thu Hao , Eri Rajaraman Sustainable, greenhouse gas derived fermented protein in canine diets—a pilot study Frontiers in Veterinary Science VOLUME11 YEAR 2025 URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets. 2024.1477182 DOI=10.3389/fvets.2024.1477182 

Bottom line — Interesting work.

Just putting things in perspective …