CBD And Sarcoids

Hello Summarians!

How do we know that a particular drug therapy will work? It seems like a simple question. If it cures or controls a particular problem, then it works, right? That may be true for the individual, but how do we apply it to larger populations?

We can look at drug kinetics in larger populations, or how they work in tissue cultures, or even random placebo-controlled studies.

There is no one perfect answer, so we collectively pool the information that we have and try to reach a consensus about safety and efficacy—an important fact to remember when considering the plethora of information available to us.

Respiratory Issues In Equine Athletes

This study investigated the prevalence of respiratory tract abnormalities in a group of apparently healthy, actively competing barrel racing horses in Oklahoma using post-race resting endoscopy. Despite the absence of owner-reported respiratory complaints or poor performance, respiratory abnormalities were common. Pharyngeal lymphoid hyperplasia and recurrent laryngeal neuropathy were particularly prevalent, with pharyngeal lymphoid hyperplasia identified in nearly all horses and recurrent laryngeal neuropathy observed in over 60% of the population. These findings were unexpected, as the authors hypothesized that a clinically normal population would have a lower prevalence of abnormalities than previously reported in horses presenting for respiratory signs or poor performance. The high prevalence may be partially explained by the timing of endoscopy shortly after intense exercise, which may transiently exacerbate inflammatory or functional changes in the upper airway. 

Importantly, most abnormalities detected were mild in severity and were not associated with slower run times. Combined recurrent laryngeal neuropathy scores were generally low and did not correlate with performance, consistent with prior evidence that mild grades of laryngeal dysfunction do not impair athletic output. Dorsal displacement of the soft palate was relatively uncommon, likely underestimated due to the exclusive use of resting rather than dynamic endoscopy, and showed no association with respiratory noise or performance. Exercise-induced pulmonary hemorrhage was identified in approximately 28% of horses, a lower prevalence than previously reported in barrel racers and racehorses of other disciplines. Interestingly, horses with evidence of exercise-induced pulmonary hemorrhage had faster run times, suggesting that, in this short-duration, high-intensity sport, its presence may reflect greater exertional intensity rather than a limiting pathology. 

The study also highlighted age-related trends, with younger horses exhibiting higher pharyngeal lymphoid hyperplasia scores and older horses more likely to show exercise-induced pulmonary hemorrhage. Medication use influenced some findings, as dexamethasone administration was associated with lower pharyngeal lymphoid hyperplasia scores but higher exercise-induced pulmonary hemorrhage scores, though the latter association was unlikely to be causal. Interobserver variability was noted across grading categories, underscoring the subjective nature of endoscopic interpretation, particularly for subtle or transient findings. Overall, the results demonstrate that respiratory abnormalities are common in barrel racing horses considered clinically normal, but most do not appear to negatively affect performance. The authors conclude that dynamic endoscopy may further clarify the true functional significance of these findings and is warranted in future studies.

Williams, M. R., Silverstone, A., Burba, D. J., McCarrel, T., Schoonover, M. J., & Rudra, P. (2026). Barrel racing horses demonstrate a high incidence of nonclinical postrace airway disorders. Journal of the American Veterinary Medical Association https://doi.org/10.2460/javma.25.10.0712 

Bottom line — Common problem with unknown significance

CBD And Sarcoids

Equine sarcoids are the most common skin tumors in horses and are locally invasive, fibroblastic growths associated with bovine papillomavirus infection, genetic susceptibility, and abnormal wound healing. Their unpredictable behavior and resistance to treatment make them a persistent clinical challenge. Cannabidiol (CBD), a non-psychoactive cannabinoid with documented anti-tumor activity in human cancer models, has not previously been studied in equine sarcoid cells. This in vitro study examined whether CBD influences sarcoid cell viability, apoptosis, cytotoxicity, and invasive behavior. The results demonstrated a clear dose- and time-dependent decrease in sarcoid cell viability, with apoptosis emerging as the dominant mechanism of cell death after prolonged exposure. Early cellular responses suggested transient adaptive or repair mechanisms, but sustained CBD exposure led to marked caspase-3/7 activation and apoptotic signaling. Interestingly, equine sarcoid cells showed measurable sensitivity even at low CBD concentrations, which differs from many human tumor models that require higher doses to produce early cytotoxic effects. 

CBD also significantly suppressed the secretion of matrix metalloproteinases MMP-1, MMP-2, and MMP-9, enzymes central to extracellular matrix degradation and local tumor invasiveness. Because sarcoids are characterized by aggressive local tissue infiltration rather than metastasis, modulation of these matrix pathways is biologically meaningful. Although a functional invasion assay showed a trend toward reduced invasion, the decrease did not reach statistical significance at the tested time point, suggesting that biochemical changes may precede measurable behavioral changes in vitro. Importantly, parallel experiments using normal equine dermal fibroblasts revealed no reduction in viability or migration, indicating tumor-specific responsiveness rather than nonspecific toxicity. 

The study is limited by the small number of sarcoid cell lines, the restricted range of CBD doses and exposure times, and the inherent constraints of in vitro systems that lack immune and microenvironmental influences. Nevertheless, the findings provide preliminary evidence that CBD modulates proliferative and matrix-remodeling pathways in equine sarcoid cells through apoptotic and invasion-associated mechanisms. These results support further investigation into cannabinoid signaling in veterinary oncology and highlight CBD as a biologically active compound capable of selectively altering tumor cell behavior without damaging normal equine dermal cells. 

Stewart, S. D., Allen, S., Eisenberg, B., Sakakeeny, K., Hammond, T. N., Schneider, B., Mochel, J., & Zhou, T. (2023). Comparison of the pharmacokinetics of continuous and intermittent infusions of ampicillin-sulbactam in dogs with septic peritonitis, American Journal of Veterinary Research, 84(2), ajvr.22.08.0139. Retrieved Feb 7, 2023, from https://avmajournals.avma.org/view/journals/ajvr/84/2/ajvr.22.08.0139.xml 

Bottom line — It seems to alter cell behavior without hurting normal tissue.

Zonisamide For Seizures In Dogs

Zonisamide (ZNS) is an FDA-approved sulfonamide antiseizure medication in human medicine that has gained widespread extra-label use in dogs with epilepsy, both as monotherapy and as an add-on drug. Its multifactorial mechanism of action—blocking sodium and T-type calcium channels and inhibiting carbonic anhydrase—differs from many other antiseizure medications, contributing to its growing popularity in veterinary neurology. Surveys and laboratory submission data over the past decade demonstrate a substantial increase in ZNS use, reflecting clinician confidence in its efficacy and tolerability. Pharmacokinetically, ZNS has favorable properties for long-term use in dogs, including good oral bioavailability, a relatively long elimination half-life, and minimal fluctuation in plasma concentrations over a dosing interval, making twice-daily dosing practical and therapeutic drug monitoring (TDM) more flexible. 

This retrospective study evaluated the effectiveness of ZNS as monotherapy in dogs with non-structural epilepsy and sought to define a canine-specific reference interval (RI) for plasma ZNS concentrations. Using stringent inclusion criteria, 123 dogs were analyzed, of which 59% were classified as responders after at least three months of treatment, and 30% achieved seizure freedom. These outcomes are comparable to previously reported efficacy rates for other first-line antiseizure medications such as phenobarbital and potassium bromide, supporting ZNS as a clinically valid first-line option. Although response rates were slightly lower than those reported in a prior prospective study, differences in study design and retrospective data limitations likely contributed to this discrepancy. 

Based on responders in this cohort, the study proposes a plasma ZNS RI of approximately 10–55 μg/mL, which is broader than the commonly cited human-derived range of 10–40 μg/mL that is frequently applied in veterinary practice. Importantly, dogs demonstrated therapeutic responses both below and above the traditional human RI, underscoring that strict adherence to human reference values may be inappropriate for canine patients. The findings emphasize that the RI should be interpreted as a population-based guide rather than a rigid therapeutic target. Clinical response and tolerability must remain central to dose adjustment decisions, as some dogs achieved seizure control at concentrations below 10 μg/mL, while others tolerated concentrations exceeding 40 μg/mL without adverse effects. 

The study also highlighted substantial interindividual variability in ZNS response, with no significant differences in dose or plasma concentration across IVETF response categories. This suggests that pharmacodynamic factors, seizure etiology, genetic influences, and concurrent conditions likely play a major role in determining clinical outcomes. A modest linear relationship between dose and plasma concentration was observed, but a large proportion of variability was attributable to factors beyond dose alone. At higher doses, nonlinear pharmacokinetics may further contribute to unpredictable concentration changes, reinforcing the value of TDM in guiding individualized therapy. 

Adverse effects, particularly elevations in liver enzymes, were reported across a range of plasma concentrations, including relatively low levels, indicating that toxicity is not strictly dose-dependent. While causality cannot be established from retrospective, spontaneous reporting data, these findings support careful clinical monitoring regardless of measured concentration. Overall, this study supports ZNS as an effective monotherapy for canine epilepsy and provides evidence for a broader, canine-specific plasma concentration RI. Integrating TDM with individualized clinical assessment, rather than relying solely on predefined concentration thresholds, may optimize seizure control, minimize adverse effects, and improve long-term treatment success in dogs with epilepsy. 

Kamoltip Thungrat, Tom Jukier, Dawn Merton Boothe, Efficacy of monotherapy with zonisamide and proposed reference interval in dogs with epilepsy: a cohort of 207 dogs (2011-2021), Journal of Veterinary Internal Medicine, Volume 40, Issue 1, January-February 2026, aalaf026, https://doi.org/10.1093/jvimsj/aalaf026

Bottom line — Monotherapy is useful in dogs.

Just putting things in perspective …