Available via license: CC BY-NC 4.0
Content may be subject to copyright.
American Journal of Veterinary Research 1
Currents in One Health
Leading at the intersection of
animal, human, and environmental health
PK Studies with CBD in Dogs
In domestic animals to the present, the great-
est number of pharmacokinetic (PK) studies with
hemp cannabidiol (CBD) have been conducted in
dogs. Indeed, the correlation between CBD serum
levels and clinical eectiveness in conditions such
as seizure disorders and osteoarthritis is established
in canine patients.1,2 Initial PK studies with CBD in
dogs showed an extremely low bioavailability (0% to
19%) with some dogs showing no serum levels after
oral administration.3 This may be due to rst-pass
hepatic metabolism or the type of formulation uti-
lized (powder in a gelatin capsule).4
Bartner et al studied the PK of oral forms (micro-
encapsulated oil beads, CBD-infused oil) and a topi-
cal preparation (CBD-infused transdermal cream)
in dogs.5 Oral dosage levels of CBD were 10 and
20 mg/kg, which is higher than that used in sub-
sequent oral studies in dogs. The oil preparations
A One Health perspective on comparative cannabidiol
and cannabidiolic acid pharmacokinetics and
biotransformation in humans and domestic animals
Wayne S. Schwark, DVM, MS, PhD1, and Joseph J. Wakshlag, DVM, PhD, DACVIM, DACVSMR2*
1Department of Molecular Medicine, Cornell University College of Veterinary Medicine, Ithaca, NY
2Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY
*Corresponding author: Dr. Wakshlag (drjoesh@gmail.com)
Received February 13, 2023
Accepted March 1, 2023
doi.org/10.2460/ajvr.23.02.0031
resulted in a higher maximal serum concentration
(Cmax) and area under the curve (AUC; see Table 1)
with both oral doses than in the report cited above.3
As a follow-up, the drugs were administered in simi-
lar doses chronically (6 weeks) to determine adverse
eects. The Cmax levels after the 6-week period were
similar to that after a single dose, indicating that
there were no alterations in elimination rate with
chronic administration.
Gamble et al found a dose-dependent absorp-
tion of CBD in a CBD/CBDA-rich hemp mixture. Oral
administration of the mixture in oil (1 and 4 mg/kg
CBD, as the 2 mg/kg and 8 mg/kg dose contained an
equal amount of cannabidiolic acid [CBDA], which
was not assessed pharmacokinetically) resulted in
median Cmax levels of 102 and 591 ng/mL and AUCs
of 376 and 2,658 ng·h/mL.1 This group subsequently
reported a PK study with oral 1 mg/kg CBD in a
CBD/CBDA soft chew preparation and found sub-
stantial CBD absorption (Cmax of 301 ng/mL and
ABSTRACT
The goal of pharmacokinetic (PK) studies is to provide a basis for appropriate dosing regimens with novel therapeu-
tic agents. With a knowledge of the desired serum concentration for optimum pharmacological eect, the amount
and rate of drug administration can be tailored to maintain that concentration based on the 24-hour PK modeling
(eg, every 24 hours, every 12 hours) to achieve therapeutic ranges. This dosing and PK information are tailored to
maintain that concentration. Typically, these optimum serum concentrations pertain across species. Single-dose PK
modeling provides fundamental parameters to suggest dosing regimes. Multiple-dose PK studies provide information
on steady-state serum levels to assure that desired therapeutic levels are maintained during chronic administration.
Clinical trials using dosing suggested by these PK determinations provide proof that the compound is producing the
desired therapeutic eect. A number of PK studies with cannabinoids in humans and domestic animals have been
conducted with the goal of determining appropriate clinical use with these plant-derived products. The following
review will focus on the PK of cannabidiol (CBD) and the lesser-known precursor of CBD, cannabidiolic acid (CBDA).
Although Δ9-tetrahydrocannabinol (THC) has profound pharmacological eects and may be present at variable and
potentially violative concentrations in hemp products, PK studies with THC will not be a major consideration. Because,
in domestic animals, hemp-CBD products are usually administered orally, that route will be a focus. When available,
PK results with CBD administered by other routes will be summarized. In addition, the metabolism of CBD across
species appears to be dierent in carnivorous species compared with omnivorous/herbivorous species (including
humans) based on current information, and the preliminary information related to this will be explained with the
therapeutic implication being addressed in Currents in One Health by Ukai et al, JAVMA, May 2023.
Unauthenticated | Downloaded 03/29/23 05:00 PM UTC
2 AJVR
an AUC of 1,297 ng·h/mL), indicating a somewhat
greater absorption with the soft chew formulation.6
Chicoine et al administered a cannabis herbal
extract containing a 1:20 ratio of Δ9-THC:CBD
orally in doses of 2, 5, and 10 mg/kg CBD to fasted
dogs. There was an apparent dose-dependent
increase in Cmax and AUC (Table 1).7 In contrast to
previous studies, there was an initial rapid elimina-
tion based on a half-life of elimination time (T1/2;
approximately 2 hours) and a slower second phase
of elimination with half-lives of up to 24 hours. The
authors speculated this may be related to a redis-
tribution from tissue depots such as adipose tis-
sue. Particularly in the high-dose group, a number
of neurological side eects were observed, which
may be attributed to the tetrahydrocannabinol
(THC) content.
Wakshlag et al reported the PK of CBD and a
number of other cannabinoid and cannabinoid
metabolites after administration of 1 mg/kg CBD
in 3 formulations (medium-chain triglyceride in
sesame oil; sunower-lecithin in sesame oil and
soft chews).8 There were no signicant dierences
between the formulations in CBD PK (Table 1).
Examination of steady-state serum levels after 1
and 2 weeks of daily q 12 hour administration dem-
onstrated no signicant dierences in CBD levels
between the formulations. In a study to determine
the acceptance of a soft gel vs an oil formulation of
a commercial CBD/CBDA-rich hemp blend in dogs,
no signicant dierences in PK parameters were
found with CBD (1 mg/kg) in a single dose study
or in steady state after q 12 hour administration for
1- or 2-week periods.9 The generally greater palat-
ability and acceptance of the soft gel formulation
and the similar PK results suggested that this may
be a superior formulation for clinical use compared
with the oil formulation.
PK Studies with CBD in Cats
Regarding drug therapy, cats are unique in sev-
eral respects. As a species, felines are decient in
the ability to glucuronidate drugs which can lead to
accumulation and toxicity unless dosage regimes are
tailored to account for this characteristic.10 Cats are
discriminating eaters, which may lead to the rejec-
tion of orally administered drugs. These consider-
ations may impact the interpretation of PK studies in
cats. In an initial cat study, Deabold et al compared
the single-dose PK of CBD-rich hemp (50:50 mixture
of CBD:CBDA) in dogs and cats. Fasted animals were
orally administered 2 mg/kg in the form of soft chews
(glycerol/starch/ber base) in dogs and suspended
in sh oil in cats.6 Results indicated that there was an
apparent decrease in the ability of cats to absorb CBD
compared with dogs. The mean Cmax of CBD in dogs
was 7-fold greater than in cats (301 vs 43 ng/mL) and
AUC was 8 times greater in dogs than cats (1,297 vs
164 ng·h/mL) (Table 1). The authors suggested this
may be related to the matrix of drug suspension in
the sh oil form in cats. Because cannabinoids are
highly lipid soluble, interaction with the sh oil may
have diminished systemic absorption. Notably, some
of the cats exhibited head shaking and excessive sal-
ivation that may have indicated rejection of a portion
of the dose. Thus, optimum therapeutic levels may
not be obtained in cats as opposed to dogs utilizing
these specic formulations.
CBD preparations
Kulpa et al studied the safety of 11 escalating
oral doses of cannabinoids in oil (CBD alone, THC
alone, or a combination of CBD/THC) in healthy
cats.11 While the goal of the study was the exami-
nation of adverse eects, measurements of plasma
levels of the CBD, THC, and their metabolites were
Table 1—Averages for single dose oral CBD PK data in small animals.
Reference Species Del. matrix Dose (mg/kg) Cmax (ng/mL) Tmax (h) T1/2 el. (h) AUC (ng·h/mL) MRT (h)
Bartner5* Dog Oil 10 635 ND 3.3 136 3.6
Dog Nano-emulsion 10 346 ND 1.6 98 5.9
Dog Oil 20 846 ND 2.1 298 6.0
Dog Nano-emulsion 20 578 ND 1.9 163 5.5
Gamble1# Dog Oil 1 102 1.5 4.2 367 5.6
Dog Oil 4 591 2 4.2 2,658 5.6
Deabold6Dog Soft chew 1 301 1.4 1.0 1,297 1.4
Chicoine7Dog Herbal extract 2 213 2.1 2.5 692 ND
Dog Herbal extract 5 838 1.9 2.6 2,433 ND
Dog Herbal extract 10 1,868 2.3 2.3 5,883 ND
Wakshlag8Dog MCT + Oil 1 145 1.5 4.1 635 5.2
Dog Lecithin + Oil 1 124 2.0 4.4 683 6.5
Dog Soft chew 1 226 2.5 3.8 826 5.3
Tittle9Dog Soft gel 1 185 1.4 3.4 688 4.4
Dog Oil 1 268 1.1 2.2 693 3.4
Deabold6Cat Oil 1 43 2.0 1.5 164 3.5
Kulpa11 Cat Oil 25 236 ND ND ND ND
Wang12 Cat Paste 1.37 282 2.0 2.1 909 3.8
AUC = area under the serum concentration curve; CBD = cannabidiol; Cmax = maximum serum/plasma concentration;
MCT = medium chain triglyceride; MRT = mean residence time; PK = pharmacokinetics; T1/2 el = elimination half-life; Tmax = time
of maximum serum concentration; ND = not determined.
*AUC expressed as µg-min/mL #data expressed as median values; #data reported as medians.
Unauthenticated | Downloaded 03/29/23 05:00 PM UTC
AJVR 3
undertaken after the 9th dose of the 11-dose esca-
lating study (at that time 25 mg/kg CBD alone).
With regard to CBD, higher Cmax values (236 com-
pared with 43 ng/mL in the Deabold study6) were
attributed to the higher dosage and/or the suspend-
ing oil (medium-chain triglyceride vs sh oil).
Interestingly, the CBD/THC combination resulted
in higher CBD Cmax (483 vs 236 ng/mL), suggesting
that the presence of THC enhanced the absorption
of CBD. Other PK parameters were not reported. The
study found a number of adverse gastrointestinal
and neurological eects with higher dosages.
In a more recent study in cats, Wang et al investi-
gated the 24-hour and 1-week steady-state PK with
a CBD/CBDA rich hemp paste.12 A unique matrix
of palatable drug suspension consisting, in part, of
soy oil, dextrose, and chicken liver was used as the
carrier in this study. Minor amounts of other can-
nabinoids were present in the preparation and were
also assayed for PK analysis. Utilizing this formula-
tion, much better absorption was apparent than
in the feline studies cited above. Similar doses of
CBD/CBDA resulted in a 6-fold higher CBD Cmax than
in the Deabold study6 (282 vs 43 ng/mL) and a simi-
lar Cmax of CBD was achieved (282 vs 256 ng/mL)
with an 18 times lower dose of CBD than in the Kulpa
article (Table 1).11 The absolute steady state achieved
after 1 week of administration was less than that pre-
dicted by PK analysis. The authors speculated that
chronic twice-daily administration may induce cyto-
chrome P-450 systems that enhance the elimination
of CBD and other cannabinoids.
PK Studies with CBD in Horses
Dietary considerations and the unique proper-
ties of the equine gastrointestinal tract (hindgut
fermentation) may impact cannabinoid PK. As in
ruminants (see below), the presence of forage and
pH variations may impact absorption of the canna-
binoids compared with simple stomached animals
like dogs and cats. Turner et al conducted a PK study
with the oral administration of 2 mg/kg CBD (in soy
oil) in senior horses.13 True bioavailability was deter-
mined by comparison of AUC with IV administration
(0.1 mg/kg in DMSO). Bioavailability was found to be
low (8%) which was comparable with that previously
reported in dogs. An average Cmax of 18.5ng/mL was
seen after 2.5 hours. A longer half-life (7.2 hours)
was akin to that in ruminants (see below).
Williams et al administered 2 doses (0.35 and
2 mg/kg daily for 7 days) of a commercially available
equine CBD supplement. PK determinations were
performed after the last day of administration. Serum
levels appeared to increase in a dose-dependent man-
ner (Cmax of 6.6 ng/mL with 0.35 mg/kg vs 51 ng/mL
with the 2 mg/kg/day dose).14 The terminal half-life
was prolonged (10.4 hours) and was in the range sim-
ilar to that with a similar dosage in senior horses.13
The authors did not establish whether long-term
administration may aect PK (eg, by cytochrome
P450 induction) because PK determinations were not
undertaken on day 1 of administration. THC levels
were also measured and were found to be signicant
which may impact drug testing in competition horses.
The authors found no adverse eects with these
2 levels of CBD and suggested that higher dosages of
CBD may be required to elicit clinical responses.
Yocom et al explored the single dose 24-hour
PK, safety, and synovial uid concentrations of CBD,
utilizing a sunower oil-lecithin based suspension
of CBD.15 Dosages of 1 and 3 mg/kg were adminis-
tered orally after feeding a small meal. Horses were
then treated twice daily with either 0.5 or 1.5 mg/
kg for 6 weeks and steady-state plasma levels were
determined. There was a dose-dependent increase
in plasma levels (Cmax of 4.3 and 19.9 ng/mL with
the 0.5 and 3 mg/kg dose, respectively). Elimination
half-lives ranged from 8.8 to 14.3 hours. Steady-state
Cmax levels after 6-week treatment were compared
with those with single-dose CBD administration,
indicating no apparent alteration in PK. Synovial
uid levels of CBD up to 7 to 8 ng/mL were detected
but this was not consistently observed in all horses.
This may have implications for the use of CBD for the
management of osteoarthritic pain in horses.
Ryan et al administered 3 doses of CBD (0.5, 1,
and 2 mg/kg) in sesame oil to exercising thorough-
bred horses.16 Levels of CBD were detected for up to
48 hours but Cmax values were low.
Elimination half-lives were comparable with the
3 doses (9.9 to 10.7 hours). Although the results
were inconsistent, there was evidence that eico-
sanoid metabolites (COX-1, COX-2, and LOX) were
aected by these levels of CBD. The results of these
studies in horses are summarized (Table 2).
Table 2—Averages for single-dose oral CBD PKs of CBD in large animals.
Reference Species Del. matrix Dose (mg/kg) Cmax (ng/mL) Tmax (h) T1/2 el. (h) AUC (ng·h/mL) MRT (h)
Meyer18 Calves Oil 5 50 7.5 23 950 35
Kleinhenz19 Calves Hemp 0.5 4 ND ND ND ND
Turner13 Horse Oil 2 18 2.5 7 132 ND
Williams14 Horse Hemp pellets 0.35 7 1.8 ND 42 156
Horse Hemp pellets 2 51 2.4 10 330 153
Yocum15 Horse Lecithin-oil 1 4.3 4.1 14.8 73 13.5
Horse Lecithin-oil 3 19.9 5 8.5 186 10.5
Ryan16 Horse Oil 0.5 1.2 10.7 ND ND ND
Horse Oil 1 2.9 10.6 ND ND ND
Horse Oil 2 6.1 9.9 ND ND ND
See Table 1 for key.
Unauthenticated | Downloaded 03/29/23 05:00 PM UTC
4 AJVR
PK Studies with CBD in Cattle
In cattle and other ruminants, dierent com-
partments of the forestomach have unique epithe-
lial absorptive characteristics and pH properties that
aect drug absorption. The presence of an abundant
microora, particularly in the rumen, may degrade
drugs. Thus, age could have a profound eect on PK
results because pre-ruminant calves lack this ora
until post-weaning.17 Meyer et al studied the plasma
PK of CBD in 19-day-old (pre-ruminant) calves after
oral administration of 5 mg/kg of an oil formulation.
CBD was absorbed, reaching a Cmax of 50 ng/mL with
an average Tmax of 7 hours.18 The absorption was sus-
tained and the average half-life of elimination was
23 hours, which represents a much slower elimina-
tion rate than in simple-stomached animals. The level
of plasma CBD was still appreciable at 48 hours, the
last point of plasma collection. This may have impli-
cations for withdrawal times in edible tissues.
Kleinhenz et al administered CBDA (an acidic
precursor of CBD) rich hemp to 10-month-old calves
at a dosage of 5 mg/kg.19 CBD content in this prod-
uct was very low (delivering a dosage of 0.6 mg/
kg). While CBDA absorption was adequate to allow
PK calculations (Cmax of 73 ng/mL), CBD levels were
only detectable in 2 of 8 calves and in those the aver-
age concentration of CBD was 4 ng/mL, a reection
of the lower dose of CBD compared with the Meyer
study cited above.18 Regarding CBDA, the elimina-
tion half-life was 14 hours, comparable with that
of CBD in Meyer et al18 and suggests cannabinoids
per se may be eliminated slowly in cattle. Notably,
these animals were considerably older than the CBD
study cited above and this may impact cannabinoid
absorption. Feeding of this CBDA-rich preparation
for a 2-week period was found to induce behavioral
changes (increased recumbency) and a reduction of
circulating inammatory biomarkers (cortisol, pros-
taglandin E2).20 This was correlated with measurable
levels of acidic forms of the cannabinoids (especially
CBDA) but a lack of signicant CBD serum levels.
The results of these PK studies and comparison with
data in horses are shown in Table 2.
PK Studies with CBD in Humans
Data on the PK of oral CBD in people have
recently been reviewed. Reports include those where
CBD was administered alone or in a combination of
CBD/THC.21–23 A wide diversity of oral formulations
were used in these studies (capsules, drops, and
solutions) and in a wide range of doses. For the most
part, studies were conducted in healthy adult male
and female volunteers but gender-related dierences
in PK were not explored. As in animals (see above),
bioavailability after oral administration of CBD in
people is low. Amounts varying from 6%24 to 13% to
16% were reported.25 Generally, dose-dependent PK
(Cmax and AUC) was found after oral administration
of CBD in adult humans (see below). Tmax was found
to occur 1–4 hours after administration and half-
lives of elimination varied widely but were typically
within the 2–4 hour range reported in dogs and cats
(see Table 1).22,26,27
Administration of oral CBD doses lower than
those examined in animals cited above (5–60 mg/
adult that would be equivalent to less than 1 mg/
kg for a 70 kg adult) resulted in plasma Cmax levels
below 5 ng/mL and AUCs below 50 ng·hr/mL).28,29
When dosages comparable with those reported in
animal studies (400–800 mg total dose or 5–10 mg/
kg for a 70 kg individual), Cmax values ranged from
80–220 ng/mL, which is in the range of that found
in dogs and cats administered similar oral doses.30,31
As reported in animals, CBD administration with
food increased the rate of absorption and the ulti-
mate Cmax of CBD.8,32 Bioavailability increased 4-fold
between fasted individuals and those administered
CBD in conjunction with a high-fat meal. Thus, feed-
ing itself and the nature of the food can profoundly
aect CBD PK.
Human PK studies have explored routes of
administration other than orally (e.g., intravenous,
oromucosal spray, sublingually, nebulization, aero-
sol inhalation, and smoking).22 Vaporization seems
to be an especially eective approach to achieving
systemic absorption of CBD.33 Cannabinoid admin-
istration by inhalation exhibits a similar PK to that
attained after IV administration.25 Inhaled CBD was
found to have a bioavailability several-fold higher
than after oral administration.21 The apparent
increased bioavailability of CBD by inhalation has led
to the development of products that deliver vapor-
ized Cannabis products by this route.34
Alternate Routes of CBD
Administration in Animals
Because oral bioavailability of CBD is low (0%
to 19%) in dogs,3 the PK of routes of administra-
tion other than oral have been explored in animals.
Because rst-pass hepatic metabolism may be a
major contributor to decreasing oral bioavailability,
routes of administration that bypass this site have
particular interest. In their PK study in dogs, Bartner
et al also examined a group wherein CBD was applied
topically to the ear pinnae.5 This transdermal appli-
cation resulted in Cmax levels that were only about
one-tenth of that achieved by the oral dosage forms.
Similarly, Hannon found minimal blood concentra-
tions of CBD and CBDA after topical application of
4 mg/kg q 12 hour of a CBD/CBDA-rich extract for
periods of up to 2 weeks.35 The hydrophobic nature
of the cannabinoids apparently limits diusion across
the aqueous layer of the skin, making this route of
administration seemingly ineective for routine sys-
temic clinical use.
Fernandez-Trapero et al studied the PK of a com-
mercial preparation of phytocannabinoids (Sativex,
GW Pharmaceuticals) administered via a sublingual
spray in adult dogs.36 Peak plasma levels (Cmax =
15 ng/mL) were attained 2 hours after administra-
tion but were low compared with that after oral
administration. No neurological or other pharma-
cological eects were noted with this treatment
Unauthenticated | Downloaded 03/29/23 05:00 PM UTC
AJVR 5
protocol. Higher plasma levels were found after mul-
tiple than single sublingual doses which, the authors
speculated could be due to an accumulation in and
subsequent release from fat depots.
Although no PK determinations were under-
taken, Brioschi et al found that an oral transmuco-
sal CBD preparation (2 mg/kg q 12 hour) enhanced
the analgesic eects of other drugs used to treat
osteoarthritic pain (non-steroidal anti-inammatory
drugs, amitryptyline, and gabapentin) in canine
patients. However, this transmucosal application is
suspect because dogs will naturally swallow orally
applied products.37 Polidoro et al performed a com-
parative PK study in dogs after intranasal, rectal, and
oral administration.38 Plasma concentrations after
rectal administration were undetectable. No signi-
cant dierences in Cmax or AUC values were detected
between the oral or intranasal routes but the authors
concluded that oral administration was preferable
based on the convenience of administration. Studies
such as these indicate that, to date, there is no ideal
alternative route to oral administration to achieve
signicant systemic levels of CBD or other canna-
binoids in animals. While administration by inhala-
tion holds promise, as demonstrated in humans, this
route is impractical for routine clinical use in animals.
CBD vs CBDA PKs
As summarized (Table 3), CBDA, the precursor
of CBD in hemp, is generally absorbed to a greater
extent after oral administration. This is seen across
species and with dierent oral formulations. Because
CBDA itself has pharmacological activity, prepara-
tions containing CBDA may reinforce the actions of
CBD.39 Furthermore, there is evidence that CBDA
may enhance the gastrointestinal absorption of
CBD.40 Thus, the presence of acidic precursor prod-
ucts in hemp preparations must be taken into con-
sideration when designing dosing regimens because
acidic cannabinoids appear to be absorbed better
than their decarboxylated neutral counterparts glob-
ally.8,12,41–43 This examination of CBDA absorption
across many domestic species is being established
and has yet to be examined in the human literature to
any appreciable degree. These novel ndings across
dogs, cats, horses, and cattle suggest that CBDA
may be preferably absorbed and suggests that ther-
apeutic dosing of CBDA may be more achievable
than CBD when using the oral route.
Metabolism and
Elimination of CBD/CBDA
The elimination of all drugs takes place primar-
ily through the phase 1 enteric or hepatic metabo-
lism that often includes the cytochrome p450 system
(CYP) leading to hydroxylation and carboxylation to
the increased polarization of compounds for renal
excretion. In conjunction, this initial phase 1 reac-
tion provides a polar group to increase the poten-
tial for phase II glucuronidation that occurs through
UDP glucuronidation pathways resulting in primarily
hepatobiliary elimination of many compounds from
foods to pharmacological agents consumed daily.44
The hepatic metabolism of cannabinoids is relatively
well deciphered in rodents and humans; whereby,
the CYP2 (CYP2B6, CYP2C19, and CYP2D6) and
CYP3 (CYP3A4, CYP3A5) isoenzymes appear to
metabolize CBD to 7-OH-CBD (and lesser degree
6-OH CBD) and eventually 7-COOH-CBD with serum
levels increasing to very high concentrations in the
bloodstream in the range often well over 1,000 ng/
mL during chronic use, with smaller amounts of 6
and 4 hydroxylation occurring in these species.45–48
This has been found to be renally excreted while
7-COOH-CBD undergoes glucuronidation leading
to the primarily hepatobiliary excretion of cannabi-
noids, in general.49,50
In horses this appears to be a primary means of
metabolism which may be why serum concentrations
of CBD in horses appear to be similar to humans at
typical dosing regimens between 1–3 mg/kg, leading
to lower than expected serum CBD concentrations.
Thus far, in dogs and cats, the serum concentrations
of 7-COOH CBD are signicantly lower during single
and multiple day-dosing assessments suggesting dif-
ferent primary metabolic pathways.8,12,51 Dog ex vivo
microsomal assays examining metabolites of CBD
show signicant hydroxylation of the 6 carbon that
suggests fundamental dierences in CYP metabolism
that is thought to undergo carboxylation as well.52
Table 3—Comparison of PK parameters with oral CBD and CBDA
Reference Species Del. matrix CBD dose
(mg/kg) CBDA dose
(mg/kg) CBD Cmax
(ng/mL) CBD AUC
(ng·h/mL) CBDA Cmax
(ng/mL) CBDA AUC
(ng·h /mL)
Wakshlag8Dog MCT + Oil 1 1 145 635 383 1,018
Dog Lecithin + Oil 1 1 124 683 386 1,619
Dog Soft chew 1 1 226 826 510 1,407
Tittle9Dog Soft gel 1 1 268 688 1826 2,786
Dog Oil 1 1 184 693 923 2,161
Wang12 Cat Paste 1.37 1.13 282 909 1,011 2,639
Thomson41 Horse Oil 1 1 6 37 46 425
Kleinhenz19 Bovine Hemp 0.6 5 4 ND 73 ND
Rooney42 Rabbit Oil 15 16.4 30 180 2,573 12,286
CBDA = cannabidiolic acid.
See Table 1 for remainder of key.
Unauthenticated | Downloaded 03/29/23 05:00 PM UTC
6 AJVR
In cats, a single cat’s hepatic microsomes were
assessed in a comparative study showing the CBD CYP
metabolism occurs at both the 6 and 4 sites in hepatic
microsomal preparations further suggesting inter-
species dierences.53 Considering the lack of inter-
est in veterinary species the quantication of these
metabolites is dicult because standards for 4 and
6 hydroxylation and carboxylation metabolites are not
available commercially to perform standard curves for
PK studies; therefore, the extent of this metabolism as
major metabolites is currently unknown.
In human medicine, it has been established
that the major 7 carboxylated metabolite of CBD
appears to be inactive.49 Currently, it is unknown as
to whether the metabolites of CBD in dogs are phar-
macologically active, and further research is neces-
sary to fully understand CBD metabolites in dogs
and cats (Figure 1). These minor dierences in met-
abolic byproducts suggest there may be dierential
CYP metabolism in dogs with preliminary informa-
tion suggesting that CYP1A metabolism may be a
primary means of CBD metabolism in dogs, while
CYP2 isoenzyme metabolism may be a secondary
pathway for metabolism at relatively high concentra-
tions (Michael Court, DVM PhD, College of Veterinary
Medicine, Washington State University, email report,
January 7, 2023). The metabolic fate of CBDA is rela-
tively unknown across all species. It has been postu-
lated that the native 3' carboxylation may make CBDA
a good substrate for direct glucuronidation similar to
THC glucuronidation found at high concentrations in
human serum after oral cannabis decoction, yet has
not been examined regarding CBDA metabolism.50,54
CBD and its metabolites are lipophilic and there
is evidence of bioaccumulation, particularly in adi-
pose and brain tissues to some extent while the acids
such as CBDA appear to undergo less bioaccumu-
lation in brain tissue, yet are still present, albeit at
lower concentrations than CBD.55,56 Recent work in
Guinea pigs examining adipose and cartilage tissues
shows that the bioaccumulation of CBD does occur
primarily in the patellar fat pad and much less so in
cartilage.57 Work in beef cows examining contami-
nated hempseed cake also shows CBD and CBDA in
liver and kidney tissue at low concentrations lower
than what was found in plasma, suggesting similarly
to people that organs do not show signicant bioac-
cumulation while adipose can be a modest reposi-
tory for cannabinoids to some extent.58
Potential CYP Inhibition
and Drug Interactions
There is extensive work performed in humans
and rodents to better understand if CBD and its
metabolites have the ability to inhibit specic CYP
isoenzymes including CYP1A, CYP2B, CYP2D, and
CYP3A isoenzymes that are the major CYPs involved
in the metabolism of drugs.49 This has been exten-
sively studied in human clinical neurology as it is the
primary area of investigation in human medicine pro-
viding some evidence that drugs like clonazepam,
valproate, and levetiracetam are all aected by CBD
administration.56,59,60 That said, recent work assessing
the metabolism of phenobarbital in clinical and pre-
clinical studies suggests that this anti-epileptic drug
is not aected when dogs are administered between
1–20 mg/kg body weight of CBD once or twice a
day.61,62 Another recent study suggests that potas-
sium bromide and zonesimide serum concentrations
were not aected by doses of 2 mg/kg of CBD/CBDA
equal mix provided twice a day for 12 weeks.63
Although CBD has the potential to inhibit CYP
drug metabolism in many of the liver microsomal
systems examined the concentrations necessary
to signicantly inhibit CYP activity would be in the
1 uM and above range, while serum Cmax concentra-
tions observed in most studies suggest that serum
CBD is usually below or near this threshold.62,64,65
Therefore, the current dosing recommendations
observed in many studies are unlikely to heavily
inuence CYP metabolism; however, further studies
are necessary with commonly used veterinary phar-
maceuticals to fully understand compatibility, partic-
ularly those heavily metabolized by CYP1A, CYP2B,
CYP2D, and CYP3A isoenzymes.
Conclusions
A few concepts surrounding PKs from a One
Health perspective are becoming increasingly clear.
Firstly, CBD absorption and retention appear to be
superior in dogs and cats as they can often achieve
over 100 ng/mL as a Cmax while humans and horses
are often 10-fold lower when utilizing similar dos-
ing. This may be due to inherent CYP450 enzymatic
dierences between species and it is becoming
increasingly evident that the typical metabolite
7 COOH-CBD found in humans and horses appears to
be a secondary metabolite in dogs and cats. Second,
in veterinary species, the absorption of CBDA, and
generally all of the acidic forms of cannabinoids,
appears to be absorbed and retained at a higher
Figure 1—Basic phase 1 and 2 metabolism of cannabi-
diol by species showing probable hydroxylation, car-
boxylation, and glucuronidation sites in the molecule
depending on species.
Unauthenticated | Downloaded 03/29/23 05:00 PM UTC
AJVR 7
level than CBD suggesting that further work in this
area is warranted because it may be easier to reach
therapeutic levels and there is a dearth of information
regarding CBDA in the human literature. There is still a
tremendous amount of research to be done surround-
ing long-term PKs and optimization of therapeutic
levels across all species making this a “One Health”
initiative that will benet humans and animals alike.
Acknowledgments
Dr. Wayne Schwark and Dr. Joseph Wakshlag are both
paid consultants for Ellevet Sciences
References
1. Gamble L-J, Boesch JM, Frye CW, Schwark WS, Mann S,
et al. Pharmacokinetics, safety, and clinical ecacy of
cannabidiol treatment in osteoarthritic dogs. Front Vet
Sci. 2018;5:165.
2. Potschka H, Bhatti SFM, Tipold A, McGrath S. Cannabidiol
in canine epilepsy. Vet J. 2022;6:105913. doi:10.1016/
j.tvjl.2022.105913
3. Samara E, Bialer M, Mechoulam R. Pharmacokinetics of
cannabidiol in dogs. Drug Metab Disp. 1988;16:469–473.
4. Huestis MA. Human cannabinoid pharmacokinetics. Chem
Biodivers. 2007;4:1770–1777. doi:10.1002/cbdv.200790152
5. Bartner LR, McGrath S, Rao S, Hyatt LK, Wittenburg LA.
Pharmacokinetics of cannabidiol administered by 3 deliv-
ery methods at 2 dierent dosages to healthy dogs. Can J
Vet Res. 2018;82:178–183.
6. Deabold KA, Schwark WS, Wolf L, Wakshlag JJ. Single-
dose pharmacokinetics and preliminary safety assessment
with use of CBD-rich hemp nutraceutical in healthy dogs
and cats. Animals. 2019;9:832. doi:10.3390/ani9100832
7. Chicoine A, Illing K, Vuong S, Pinto KR, Alcorn J, et al.
Pharmacokinetic and safety evaluation of various oral
doses of a novel 1:20 THC:CBD cannabis herbal extract in
dogs. Front Vet Sci. 2020;7:583404.
8. Wakshlag JJ, Schwark WS, Deabold KA, Talsma BN,
Cital S, et al. Pharmacokinetics of cannabidiol, cannabi-
diolic acid, Δ-9 tetrahydrocannabinol, tetrahydrocannabi-
nolic acid and related metabolites in canine serum after
dosing with three oral forms of hemp extract. Front Vet
Sci. 2020;7:505.
9. Tittle DJ, Wakshlag JJ, Schwark WS, Lyubimov A,
Zakharov A, et al. Twenty-four hour and one-week steady
state pharmacokinetics of cannabinoids in two formula-
tions of cannabidiol and cannabidiolic acid rich hemp in
dogs. Med Rec Arch. 2022;10:2907.
10. Lascelles BD, Court MH, Hardie EM, Robertson SA.
Nonsteroidal anti-inammatory drugs in cats: a review.
Vet Anesthes Analg. 2007;34:228–250. doi:10.1111/
j.1467-2995.2006.00322.x
11. Kulpa JE, Paulionis IJ, Eglit GM, Vaughn DM. Safety and
tolerability of escalating cannabinoid doses in healthy
cats. J Fel Med Surg. 2021;23:1162–1175. doi:10.1177/1
098612X211004215
12. Wang T, Zakharov A, Gomez B, Lyubimov A, Trottier NL,
et al. Serum cannabinoid 24h and 1 week steady state
pharmacokinetic assessment in cats using a CBD/CBDA
rich hemp paste. Front Vet Sci. 2022;9:895368.
13. Turner SE, Knych HJ, Adams AA. Pharmacokinetics of can-
nabidiol in a randomized crossover trial in senior horses.
Amer J Vet Res. 2022;83:ajvr.22.02.0028. doi:10.2460/
ajvr.22.02.0028
14. Williams MR, Holbrook TC, Maxwell L, Croft CH, Intile MM,
et al. Pharmacokinetic evaluation of a cannabidiol sup-
plement in horses. J Equine Vet Sci. 2022;110:103842.
doi:10.1016/j.jevs.2021.103842
15. Yocum AF, O’Fallon ES, Gustafson DL, Contino EK.
Pharmacokinetics, safety, and synovial uid concentra-
tions of single- and multiple-dose oral administration of
1 and 3 mg/kg cannabidiol in horses. J Equine Vet Sci.
2022;113:103933. doi:10.1016/j.jevs.2022.103933
16. Ryan D, McKemie DS, Kass PH, Puschner B.
Pharmacokinetics and eects on arachidonic metabo-
lism of low doses of cannabidiol following oral adminis-
tration to horses. Drug Test Anal. 2021;13:1305–1317.
doi:10.1002/dta.3028
17. Schwark WS. Factors that aect drug disposition in
food-producing animals during maturation. J Anim Sci.
1992;70:3635–3644. doi:10.2527/1992.70113635x
18. Meyer K, Hayman K, Baumgartner J, Gorden PJ. Plasma
pharmacokinetics of cannabidiol following oral adminis-
tration of cannabidiol oil to dairy calves. Front Vet Sci.
2022;24:789495.
19. Kleinhenz MD, Magnin G, Lin Z, Grin J, Kleinhenz KE,
et al. Plasma concentrations of eleven cannabinoids in
cattle following oral administration of industrial hemp
(Cannabis sativa). Sci Rep. 2020;10:12753. doi:10.1038/
s41598-020-69768-4
20. Kleinhenz MD, Weederntgomery M, Martin M, Curtis A,
Magnin G, et al. Short term feeding of industrial hemp
with high cannabidiolic acid (CBDA) content increases
lying behavior and reduces biomarkers of stress in
inammation in Holstein steers. Sci Rep. 2022;12:3683.
doi:10.1038/s41598-022-07795-z
21. Lucas CJ, Galettas P, Schneider J. The pharmacokinet-
ics and pharmacodynamics of cannabinoids. Br J Clin
Pharmacol. 2018;84:2477–2482. doi:10.1111/bcp.13710
22. Millar SA, Stone NL, Yates AS, O’Sullivan SE. A systematic
review of the pharmacokinetics of cannabidiol in humans.
Front Pharmacol. 2018;9:1365.
23. Britch SC, Babalonis S, Walsh SL. Cannabidiol pharma-
cology and therapeutic targets. Psychopharmacology.
2021;238:9–28. doi:10.1007/s00213-020-05712-8
24. Hawksworth G, McArdle K. Metabolism ad pharmacokinet-
ics of cannabinoids. In: Guy GW, Whittle BA, Robson PJ,
eds. The Medicinal Uses of Cannabis and Cannabinoids.
Pharmaceutical Press; 2004:205–228.
25. Grotenhermen F. Pharmacokinetics and pharmacodynam-
ics of cannabinoids. Clin Pharmacokinet. 2003;42:327–360.
26. Guy GW, Flint ME. A single centre, placebo-controlled, four
period, crossover, tolerability study assessing, pharma-
codynamic eects, pharmacokinetic characteristics and
cognitive proles of a single dose of three formulations of
Cannabis Based Medicine Extracts (CBMEs) (GWPD9901),
plus a two period tolerability study comparing pharmaco-
dynamic eects and pharmacokinetic characteristics of a
single dose of a cannabis based medicine extract given via
two administration routes (GWPD9901 EXT). J. Cannabis
Ther. 2004:3:35–77. doi:10.1300/J175v03n03_03
27. Atsmon J, Heetz D, Deutsch L, Deutsch F, Sacks H.
Single-dose pharmacokinetics of oral cannabidiol follow-
ing administration of PTL101: a new formulation based
on gelatin matrix pellets technology. Clin Pharmacol Drug
Dev. 2017;7:751–758. doi:10.10.1002/cpdd.408
28. Sellers EM, Schoedel K, Bartlett C, Romach M, Russo EB,
et al. A multiple-dose, randomized, double-blind,
placebo-controlled, parallel-group QT/QTc study to evalu-
ate the electrophysiologic eects of THC/CBD spray. Clin
Pharmacol Drug. 2017;2:285–294. doi:10.1002/cpdd.36
29. Nadulski T, Pragst F, Weinberg G, Roser P, Schnelle M,
et al. Randomized, double-blind, placebo-controlled
study about the eects of cannabidiol (CBD) on the phar-
macokinetics of D9-tetrahydrocannabinol (THC) after oral
application of THC verses standardized cannabis extract.
Ther Drug Monit. 2005:27:799–810.
30. Manini AF, Yiannoulos G, Bergamaschi MM, Hernandez S,
Olmedo R, et al. Safety and pharmacokinetics of oral can-
nabidiol when administered concomitantly with intrave-
nous fentanyl in humans. J Addict Med. 2015:9:204–210.
doi:10.1097/ADM.0000000000000118
Unauthenticated | Downloaded 03/29/23 05:00 PM UTC
8 AJVR
31. Haney M, Malcolm RJ, Babalonis S, Nuzzo PA,
Cooper ZD, et al. Oral cannabidiol does not alter the subjec-
tive, reinforcing or cardiovascular eects of smoked can-
nabis. Neuropsychopharmacology. 2016;41:1974–1982.
doi:10.1038/npp.2015.367
32. Silmore LH, Willmer AR, Capparelli EV, GR Rosania.
Food eects on the formulation, dosing, and administra-
tion of cannabidiol (CBD) in humans: a systemic review
of clinical studies. Pharmacotherapy. 2021:41:405–420.
doi:10.1002/phar.2512
33. Beregia CL, Spindle TR, Cone EJ, Sholler D, Go E,
et al. Pharmacokinetic prole of Δ9-tetrahydrocannabinol,
cannabidiol and metabolites in blood following vaporiza-
tion and oral ingestion of cannabidiol products. J Analyt
Toxicol. 2022;46: 583–591. doi:10.1093/jat/bkab124
34. Spindle TR, Cone EJ, Kuntz D, Mitchell JM, Bigelow GE,
et al. Urinary pharmacokinetic prole of cannabinoids fol-
lowing administration of vaporized and oral cannabidiol
and vaporized CBD-dominant cannabis. J Analyt Toxicol.
2020;44:109–125. doi:10.1093/jat/bkz080
35. Hannon MB, Deabold KA, Talsma BN, Lyubimov A, Iqbal A,
et al. Serum cannabidiol, tetrahydrocannabinol (THC),
and their native acid derivatives after transdermal appli-
cation of a low-THC Cannabis sativa extract in beagles.
J Vet Pharmacol Ther. 2020;43(5):508–511. doi:10.1111/
jvp.12896.
36. Fernandez-Trapero M, Perez-Diaz C, Espejo-Porra F,
de Lago E, Fernandez-Ruiz J. Pharmacokinetics of Sativex
in dogs: towards a potential cannabidiol-based therapy
for canine disorders. Biomolecules. 2020;10:279.
37. Brioschi FA, Di Cesare F, Gioeni D, Rabbogliatti V, Ferrari F,
et al. Oral transmucosal cannabidiol oil formulation as
part of a multimodal analgesic regimen eects on pain
relief and quality of life improvement in dogs aected by
spontaneous osteoarthritis. Animals. 2020;10(9):1505.
doi:10.3390/ani10091505
38. Polidoro D, Temmerman R, Devreese M, Charalambous M,
Ham LV, et al. Pharmacokinetics of cannabidiol following
intranasal, intrarectal, and oral administration in healthy
dogs. Front Vet Sci. 2022;9:899940. doi:10.3389/
fvets.2022.899940
39. Formato M, Crescente G, Scognamiglio M, Fiorentino A,
Pecoraro MT. S(-)-Cannabidiolic acid, a still overlooked
bioactive compound: an introductory review and pre-
liminary research. Molecules. 2020;25:2638. doi:10.3390/
molecules25112638
40. Eichler M, Spinedi L, Unfer-Grauwiler S, Bodmer M,
Surber C, et al. Heat exposure of Cannabis sativa extracts
aects the pharmacokinetic and metabolic prole in
healthy male subjects. Planta Med. 2012;78:686–691.
doi:10.1055/s-0031-1298334
41. Thomson ACS, McCarrel TM, Lyubimov A, Schwark WS,
Mallicote MF, et al. Pharmacokinetics and pharmaco-
dynamics of single-dose enteral cannabidiol in horses
(Equus caballus). J Vet Pharmcol Ther. [Submitted for
publication]
42. Rooney TA, Carpenter JW, KuKanich B, Gardhouse SM,
Magnin GC, et al. Feeding decreases the oral bioavailabil-
ity of cannabidiol and cannabidiolic acid in hemp oil in
New Zealand White rabbits (Oryctolagus cuniculus). Amer
J Vet Res. 2002;83(10):ajvr.2022.01.0006. doi:10.2460/
ajvr.22.01.0006
43. Amstutz K, Schwark WS, Zakharov A, Gomez B,
Lyubimov A, Ellis K, et al. Single dose and chronic oral
administration of cannabigerol and cannabigerolic acid-
rich hemp extract in fed and fasted dogs: physiological
eect and pharmacokinetic evaluation. J Vet Pharmacol
Ther. 2022;45:245–254. doi:10.1111/jvp.13048
44. Riviere JE. Absorption, distribution, metabolism and
elimination. In: Reviere J, Papich M, eds. Veterinary
Pharmacology and Therapeutics. 10th ed. Wiley Blackwell;
2018:8–40.
45. Zendulka O, Dovretelova G, Noskova K, Turjap M,
Sulcova A, et al. Cannabinoids and cytochrome p450
interactions. Current Drug Metab. 2016;17:206–216.
doi:10.2174/1389200217666151210142051
46. Jiang R, Yamaori S, Takeda S, Yammamoto I, Watanabe
Z. Identication of cytochrome p450 enzymes respon-
sible for metabolism of cannabidiol by human liver
microsomes. Life Sci. 2011;89:165–170. doi:10.1016/j.
lfs.2011.05.018
47. Stout SM, Cimino NM. Exogenous cannabinioids as sub-
strates, inhibitors and inducers of human drug metaboliz-
ing enzymes: a systematic review. Drug Metab Reviews.
2014;46(1):86–95. doi:10.3109/03602532.2013.849268
48. Bansal S, Paine MF, Unadkat JD. Comprehensive predic-
tions of cytochrome p450-mediated in vivo cannabinoid-
drug interactions based on reversible and time
dependent p450 inhibition in human liver microsomes.
Drug Metab Dispos. 2022;50(4):351–360. doi:10.1124/
dmd.121.000734
49. Taylor L, Gidal B, Blakey, G, Tayo B, Morrison G.
A phase 1, randomized, double blinded, placebo con-
trolled, single ascending dose, multiple dose and food
eect triol on the safety and tolerability and pharmaco-
kinetics of highly puried cannabidiol in healthy subjects.
CNS Drugs. 2018;32:1053–1067. doi:10.1007/s40263-
018-0578-5
50. Fabritius M, Staub C, Mangin P, Giroud C. Distribution of
free and conjucated cannabinoids in human bile samples.
Forens Sci Internat. 2012; 223:114–118. doi:10.1016/
j.forsciint.2012.08.013
51. Whalley BJ, Lin H, Bell L, Hill T, Patel A, Gray RA, Elizabeth
Roberts C, Devinsky O, Bazelot M, Williams CM, Stephens
GJ. Species-specic susceptibility to cannabis-induced
convulsions. Br J Pharmacol. 2019;176(10):1506–1523.
doi:10.1111/bph.14165
52. Harvey DJ, Samara E, Mechoulam R. Comparative
metabolism of cannabidiol in dog, rat and human.
Pharm Biochem Behav. 1991;40:523–532. doi:10.1016/
0091-3057(91)90358-9
53. Harvey DJ, Brown NK. Comparative in vitro metabolism
of the cannabinoids. Pharm Biochem Behav. 1991;40:
533–540. doi:10.1016/0091-3057(91)90359-A
54. Pichini S, Mannocchi G, Gottardi M, Pérez-Acevedo AP,
Poyatos L, et al. Fast and sensitive UHPLC-MS/MS analysis
of cannabinoids and their acid precursors in pharmaceuti-
cal preparations of medical cannabis and their metabo-
lites in conventional and non-conventional biological
matrices of treated individual. Talanta. 2020;209:120537.
doi:10.1016/j.talanta.2019.120537
55. Spittler AP, Helbling JE, McGrath S, Gustafson DL,
Santangelo KS, Sadar MJ. Plasma and joint tissue phar-
macokinetics of two doses of oral cannabidiol oil in
guinea pigs (Cavia porcellus). J Vet Pharmacol Ther.
2021;44(6):967–974. doi:10.1111/jvp.13026
56. Bardhi K, Coates S, Watson CJW, Lazarus P. Cannabinoids
and drug metabolizing enzymes: potential for drug-drug
interactions and implications for drug safely and ecacy.
Exp Rev Clin Pharm. 2022;15(12):1443–1460. doi:10.108
0/17512433.2022.2148655
57. Anderson LL, Low IK, Banister SD, McGregor IS, Arnold
JC. Pharmacokinetics of phytocannabinoid acids and anti-
convulsant eect of cannabidiolic acid in a mouse model
of Dravet syndrome. J Nat Prod. 2019;82(11):3047–3055.
doi:10.1021/acs.jnatprod.9b00600
58. Chakrabarty S, Serum EM, Winders TM, Neville B,
Kleinhenz MD, Magnin G, Coetzee JF, Dahlen CR,
Swanson KC, Smith DJ. Rapid quantication of can-
nabinoids in beef tissues and bodily uids using direct-
delivery electrospray ionization mass spectrometry.
Food Addit Contam Part A Chem Anal Control Expo Risk
Assess. 2022;39(10):1705–1717. doi:10.1080/19440049.
2022.2107711
59. Ujvary I, Hanus L. Human metabolites of cannabidiol: a
review on their formation, biological activity and rel-
evance in therapy. Cannabis Cannabin Res. 2016;1.1:
90–107. doi:10.1089/can2015.0012
Unauthenticated | Downloaded 03/29/23 05:00 PM UTC
AJVR 9
60. Gilmartin CGS, Dowd Z, Parker APJ, Harijan P. Interaction
of cannabidiol with other antiseizure medications: a nar-
rative review. Seizure Eur J Epilep. 2021;86:189–196.
doi:10.1016/j.seizure.2020.09.010
61. Doran CE, McGrath S, Bartner LR, Thomas B, Cribb AE,
et al. Drug-drug interaction between cannabidiol and
phenobarbital in healthy dogs. Am J Vet Res. 2021;83(1):
86–94. doi:10.2460/ajvr.21.08.0120
62. McGrath S, Bartner LR, Rao S, Packer RA, Gustafson DL.
Randomized blinded controlled clinical trial to assess
the eect of oral cannabidiol administration in addition
to conventional antiepileptic treatment on seizure fre-
quency in dogs with intractable idiopathic epilepsy. J Am
Vet Med Assoc. 2019;254(11):1301–1308. doi:10.2460/
javma.254.11.1301
63. Garcia GA, Kube S, Carrera-Justiz S, Tittle D, Wakshlag JJ.
Safety and ecacy of cannabidiol-cannabidiolic acid rich
hemp extract in the treatment of refractory epileptic sei-
zures in dogs. Front Vet Sci. 2022;9:939966. doi:10.3389/
fvets.2022.939966
64. Mejia S, Duerr FM, Grienhagen G, McGrath S. Evaluation
of the eect of cannabidiol on naturally occurring
osteoarthritis-associated pain: a pilot study in dogs.
J Am Anim Hosp Assoc. 2021;57:81–90. doi:10.5326/
JAAHA-MS-7119
65. Loewinger M, Wakshlag JJ, Bowden D, Peters-Kennedy J,
Rosenberg A. The eect of a mixed cannabidiol and can-
nabidiolic acid based oil on client-owned dogs with atopic
dermatitis. Vet Dermatol. 2022;33:329–e77. doi:10.1111/
vde.13077
Unauthenticated | Downloaded 03/29/23 05:00 PM UTC
