Volume V: Pharmacokinetics, Formulations and Safety

Volume V: Pharmacokinetics, Formulations and Safety

Volume V: Pharmacokinetics, Formulations and Safety

Purpose

Pharmacokinetics describes what the horse’s body does with a substance:

  • Absorption
  • Distribution
  • Metabolism
  • Accumulation
  • Elimination

Most equine cannabinoid research has focused on oral CBD rather than THC or topical treatment.

These studies help researchers understand exposure and safety. They do not automatically prove pain relief.


Study 1: Repeated Oral CBD Doses

Pharmacokinetic Evaluation of a Cannabidiol Supplement in Horses

Published: 2022
Animals: Seven horses
Study design: Randomized crossover
PubMed:
https://pubmed.ncbi.nlm.nih.gov/34923070/

What researchers tested

Horses received repeated oral doses of either:

  • 0.35 mg/kg CBD
  • 2 mg/kg CBD

The doses were given every 24 hours for seven administrations.

Why it matters

The study documented how blood concentrations changed after repeated dosing and showed that dose level affected exposure.

Limitation

This was a pharmacokinetic study, not a pain or arthritis trial.


Study 2: CBD Safety and Joint-Fluid Exposure

Plasma Pharmacokinetics, Short-Term Safety and Synovial Fluid Levels Following Oral CBD Administration

Published: 2022
Study design: Prospective, randomized and controlled
PubMed:
https://pubmed.ncbi.nlm.nih.gov/35307550/

What researchers studied

Horses received oral CBD at different doses. Researchers monitored:

  • Plasma CBD concentrations
  • CBD metabolites
  • Clinical observations
  • Bloodwork
  • Synovial-fluid exposure

Importance

The study confirmed that oral CBD could be measured after administration and investigated whether CBD-related compounds reached the equine joint environment.

Limitation

Presence in synovial fluid does not prove that the concentration was sufficient to treat joint disease.


Study 3: CBD in Senior Horses

Pharmacokinetics of Cannabidiol in a Randomized Crossover Trial in Senior Horses

Published: 2022
Animals: Eight senior horses
PubMed:
https://pubmed.ncbi.nlm.nih.gov/35895770/

What researchers compared

The horses received:

  • A single oral CBD dose
  • A lower intravenous CBD dose

Researchers collected blood samples for up to 264 hours and monitored blood counts and serum chemistry.

Why it matters

Senior horses are often the population targeted by products marketed for stiffness and age-related discomfort. This study provided basic absorption and elimination information but did not establish clinical pain relief.


Study 4: Oil Versus Micellar Formulations

Pharmacokinetics and Oral Bioavailability of Cannabidiol in Horses After Intravenous and Oral Administration With Oil and Micellar Formulations

Published: 2023
Animals: Eight healthy horses
Journal: Equine Veterinary Journal
PubMed:
https://pubmed.ncbi.nlm.nih.gov/36624043/

What researchers compared

CBD was administered through:

  • Intravenous administration
  • Oral sesame-oil formulation
  • Oral micellar formulation

The study estimated oral bioavailability at approximately 14% for both oral formulations under the tested conditions.

Why this matters

A label showing the amount of CBD in a product does not reveal how much will enter the horse’s circulation.

Absorption may depend on:

  • Carrier
  • Formulation
  • Feeding status
  • Dose
  • Frequency
  • Individual metabolism
  • Product quality

Study 5: Exercising Thoroughbreds

Pharmacokinetics and Effects on Arachidonic Acid Metabolism of Oral Cannabidiol in Exercising Thoroughbreds

Published: 2021
PubMed:
https://pubmed.ncbi.nlm.nih.gov/33723919/

What researchers evaluated

The researchers examined:

  • CBD pharmacokinetics
  • Behavior
  • Physiological measurements
  • Selected inflammatory biomarkers

The horses were exercising Thoroughbreds rather than inactive laboratory animals.

Why it matters

Athletic horses may process treatments differently because of exercise, conditioning, feeding and metabolic demands.

Limitation

Changes in laboratory biomarkers do not necessarily mean meaningful pain relief or improved athletic performance.


Study 6: Long-Term CBD and CBDA Administration

Chronic Oral Dosing of Cannabidiol and Cannabidiolic Acid Full-Spectrum Hemp Oil Extracts Has No Adverse Effects in Horses

Published: 2025
PubMed:
https://pubmed.ncbi.nlm.nih.gov/39787699/

What researchers examined

Researchers administered CBD-rich or CBDA-rich hemp extracts over a longer period and monitored:

  • Blood concentrations
  • Clinical health
  • Laboratory safety variables
  • Accumulation and retention

At the studied dose of 1 mg/kg, the researchers reported that both treatments appeared well tolerated. CBDA produced higher or more persistent serum exposure than CBD.

Important limitation

This does not prove that:

  • Higher doses are safe
  • THC-containing products are equally safe
  • Every commercial hemp oil is safe
  • Long-term use is safe in sick horses
  • Cannabinoids are safe with every medication

Study 7: CBD and CBDA Exposure

Differences in Plasma Exposure of Cannabidiol and Cannabidiolic Acid in Horses

Published: 2026
Study design: Crossover
PubMed:
https://pubmed.ncbi.nlm.nih.gov/41017237/

What researchers compared

Horses received:

  • CBD
  • CBDA
  • Placebo

The study showed that CBD and CBDA have different plasma-exposure patterns and should not be treated as interchangeable compounds.


Study 8: Additional CBD Metabolism Research

Pharmacokinetics of Cannabidiol and Its Major Metabolites in Horses

Published: 2025
PubMed:
https://pubmed.ncbi.nlm.nih.gov/40654508/

Researchers evaluated CBD and major phase-I metabolites. CBD oil was reported as well tolerated under the study conditions, although measurable physiological changes and prolonged detectability were observed.

Why metabolites matter

A horse may no longer have a high concentration of the original compound while still carrying detectable metabolites.

This matters for:

  • Safety interpretation
  • Repeated dosing
  • Accumulation
  • Competition testing
  • Withdrawal recommendations

Study 9: CBD and Equine Metabolic Syndrome Concerns

Metabolic Effects and Pharmacokinetics of Oral Cannabidiol in Horses

Published: 2026
PubMed:
https://pubmed.ncbi.nlm.nih.gov/42221961/

What researchers examined

The researchers measured:

  • Glucose
  • Insulin
  • Triglycerides
  • CBD concentrations
  • CBD metabolites
  • Safety observations

CBD did not improve the measured metabolic variables. It was associated with an altered insulin response during oral-sugar testing, and the clinical meaning remains uncertain. The authors noted that this deserves attention in horses predisposed to equine metabolic syndrome.

Why this matters

A product that appears well tolerated in healthy horses may not have the same risk profile in horses with:

  • Insulin dysregulation
  • Equine metabolic syndrome
  • Laminitis risk
  • Liver disease
  • Multiple medications

    Overall Safety Conclusions

    What the equine studies suggest

    Oral CBD has generally been described as well tolerated under several controlled research protocols. Researchers have nevertheless documented changes or uncertainties involving:

    • Liver-associated laboratory values
    • Heart rate
    • Metabolism
    • Insulin response
    • Accumulation
    • Long elimination periods
    • Detectable metabolites

    What remains uncertain

    • Long-term THC safety
    • CBD and THC drug interactions
    • Safety in pregnant mares
    • Safety in foals
    • Safety in liver or kidney disease
    • Safety in metabolically compromised horses
    • Effects of chronic high doses
    • Effects of mislabeled products
    • Safety of licking topical products
    • Full-spectrum products containing unlisted THC

    Evidence-based statement

    Controlled equine research suggests that certain oral CBD formulations can be tolerated at studied doses, but formulation, dose, duration and the horse’s health status all matter. Safety findings from CBD should not automatically be applied to THC-rich products.