Cannabis and Cannabinoid Research

Volume 7, Number 6, 2022 Open camera or QR reader and

ª Mary Ann Liebert, Inc. scan code to access this article
DOI: 10.1089/can.2021.0172 and other resources online.

Safety and Efficacy of the Therapeutic Use

of Cannabis-Based Products in the Treatment of Dogs:
An Integrative Review
Diego Fontana de Andrade,1,* João Lourenço Hasckel Gewehr,2 and Erik Amazonas de Almeida3

Abstract
The use of cannabis-based products for therapeutic purposes is a reality in the field of animal health. However,
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although cannabis is considered safe when appropriately used by human patients, cannabis-based products can
pose a risk to companion animals such as dogs, depending on their composition or route of administration. Thus,
this article discusses aspects of the safety and efficacy of different cannabis-based products in dogs’ treatment
through an integrative review. The review was systematically performed in Medline (via Pubmed) and Latin
American and Caribbean Health Sciences Literature (LILACS) databases, with period restriction (between 1990
and 2021). The qualified articles (n = 19), which met the previously established inclusion criteria, were critically
evaluated. Based on the literature review, it is possible to infer safety in the administration of cannabis-based
products for the treatment of dogs, especially products rich in cannabidiol (CBD), free or with low concentrations
of tetrahydrocannabinol, under the conditions evaluated. In addition, CBD products potentially promote im-
proved quality of life and reduce pain perception in animals affected by canine osteoarthritis. Finally, owing
to the lack of large-scale and robust clinical research studies, the performance of clinical trials, considering
the individual characteristics of each cannabis-based product (composition, concentration, nature of adjuvants,
dosage form, route of administration), is strongly encouraged.
Keywords: dogs; Cannabis sativa; cannabidiol; integrative review; canine osteoarthritis

Introduction According to the study conducted by Joffe and Joffe,

Cannabis products for companion animals gained pop-
ularity in the mid-1990s after the approval of medical
use of cannabis in some American states, such as Cal-
ifornia.1 Encouraged by the growing knowledge on the
benefits of using cannabis for medicinal purposes in
humans, many owners began to explore the same use
in their companion animals, especially dogs and cats.
In this scenario, cannabis-based products have been
used in substitution for other pharmaceutical products
that were not well tolerated or often ineffective against
the most diverse clinical conditions.2,3
human patients and dog owners report similar motiva-
tions for choosing cannabis-based products for treating
chronic pain. Furthermore, the authors emphasize that
tutors consider these products better than conventional
drugs owing to their natural origin.4
Although cannabis-based products are considered
safe when used adequately by human patients, they
can pose a risk to companion animals. It depends on
their composition or route of administration because
cannabinoids can be metabolized differently in differ-
ent species.4–6 There is evidence, for example, that

1
Laboratório de Controle de Produtos Biológicos, Laboratório Federal de Defesa Agropecuária do Rio Grande do Sul—LFDA/RS, Ministério da Agricultura, Pecuária e
Abastecimento (MAPA), Porto Alegre, Brazil.
2
Red Cannabis Medicinal Veterinária Brasil, Florianópolis, Brazil.
3
Departamento de Biociências e Saúde Única, Centro de Ciências Rurais—Universidade Federal de Santa Catarina, Curitibanos, Brazil.

*Address correspondence to: Diego Fontana de Andrade, PhD, Laboratório de Controle de Produtos Biológicos, Laboratório Federal de Defesa Agropecuária do Rio Grande
do Sul—LFDA/RS, Estrada da Ponta Grossa, Porto Alegre 3036, Brazil, E-mail: diego.andrade@agro.gov.br

736
 CANNABIS-BASED PRODUCTS FOR TREATING DOGS
the canine central nervous system (CNS) expresses
more cannabinoid receptors than the human CNS.3,7,8
This fact may contribute to the pronounced sensitivity
of dogs to tetrahydrocannabinol (THC) compared
with other species.
In veterinary products development, like those for
human use, it is mandatory to ensure efficacy, safety,
and quality. Thus, considering the medicinal use of
cannabis in treating dogs’ diseases, it is necessary to
know and consider pharmacokinetic parameters from
the administration of phytocannabinoids, such as can-
nabidiol (CBD) and THC.
This article will present, analyze, and discuss the stud-
ies available in the scientific literature that assess the
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safety and efficacy of different cannabis-based products
for dogs’ treatment. According to the authors’ knowledge,
this is the first integrative review study, performed sys-
tematically, presenting pharmacokinetic parameters and
results of clinical studies of CBD and THC administra-
tion in isolated or combined forms, specifically in dogs.
Methodology
The integrative review was carried out according to the
methodology proposed by Whittemore and Knafl9:
1. The following guiding question was established: ‘‘Is
the use of cannabis-based products for the treat-
ment of health problems in dogs safe and effective?’’
2. The search for scientific articles related to the re-
view’s scope was performed using the guiding
question.
3. The retrieved articles were evaluated according to
established inclusion and exclusion criteria.
4. The selected studies were categorized and ana-
lyzed, enabling the organization and presentation
of this review.
The research was carried out in October 2021. The
electronic databases Medline (Medical Literature Anal-
ysis and Retrieval System Online) and Latin American
and Caribbean Health Sciences Literature (LILACS)
were searched for published studies between 1990
and October 1, 2021.
The following search strategy was used: [(dog AND
cannabis) OR (dog AND cannabidiol) OR (dog AND
THC) OR (dog AND marijuana) OR (dog and canna-
binoid)]. First, the articles were selected through the
screening of studies’ titles and abstracts.
Then, studies found from the electronic searches
were screened for eligibility based on the following in-
clusion criteria: (1) in vivo experimental studies; (2) only
737
pharmacokinetic studies or clinical trials (interventional
studies) in target animal species (dogs); and (3) studies
in any language and fully available. Criteria for studies’
exclusion included the following: (1) expert opinion ar-
ticles; (2) case reports; or (3) literature reviews.
Finally, after the full-text reading, selected studies
were categorized into three groups according to their
objectives and experimental approaches: pharmacoki-
netic aspects, safety, and efficacy. As an integrative
review that does not involve human participants, this
study does not require Institutional Review Board
(IRB) approval.
Results
Electronic searching retrieved 392 studies (Fig. 1). All
article titles and abstracts were screened to determine
those who met inclusion criteria. After duplicate re-
moval (16 articles), 23 articles were selected for full-
text reading. This process led to the exclusion of four
studies according to exclusion criteria. Finally, 19 arti-
cles remained and were included in this integrative re-
view. These studies will be presented and discussed in
the subsequent sections.
Pharmacokinetic aspects
Eight articles (42%) of the included studies presented
pharmacokinetic studies. The studies’ authors deter-
mined pharmacokinetic parameters for products con-
taining CBD alone or combined with THC in dogs
through different routes of administration. Tables 1
and 2 present the products’ description, route, and
dose administered (mg/kg of body weight), as well as
pharmacokinetic parameters based on a single admin-
istration of the cannabis-based products: maximum
plasma concentration (Cmax), half-life (t1/2), and area
under the curve (AUC).
Vaughn et al. present pharmacokinetic parameters
established of a multiple dosage regimen (administered
once a day for 28 days in oral doses ranging from 1 to
12 mg/kg of body weight) of a CBD formulation in
medium-chain triglycerides (MCT).10 Successive ad-
ministrations increased the dog’s total systemic exposure
to CBD by two and three times compared with the val-
ues seen immediately after the first administration.
Safety
Sixteen of the 19 articles included in this review pro-
vided data related to the safety of cannabis-based prod-
ucts. In addition, the studies’ authors discussed aspects
related to the safety of cannabis-based products
 738
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FIG. 1. Flow chart for study’s identification and assessment of eligibility for inclusion in the integrative
review. LILACS, Latin American and Caribbean Health Sciences Literature.
intended for therapeutic use in the treatment of dog ail-
ments. Among the studies, 5 evaluated CBD and THC
products, whereas 11 studied THC-free CBD products.
According to the data published by qebkowska-
Wieruszewska et al., the administration of a single oral
dose of a formulation containing THC (1.5 mg/kg) and
CBD (0.0375 mg/kg) did not cause signs of excitation
or sedation. Furthermore, the authors did not observe
any other adverse effect in dogs that received the formu-
lation regardless of their feeding state (fasting or fed).11
Moreover, the treatment of dogs with a formulation
containing CBD (1.2 mg/kg)/THC (0.04 mg/kg)/can-
nabidiolic acid (CBDA) (1.3 mg/kg)/tetrahydrocanna-
binolic acid (0.03 mg/kg) did not induce changes in
clinical biomarkers when given twice a day for 2
weeks.12 No changes in serum levels of albumin, biliru-
bin, total cholesterol, and hepatic biomarkers (alkaline
phosphatase, aspartate aminotransferase, or alanine
aminotransferase) were observed. Moreover, the dogs
did not show any behavioral changes or health prob-
lems associated with the treatment.
DE ANDRADE ET AL.
Fernández-Trapero et al. did not observe any rele-
vant adverse effects associated with neurological,
body temperature, respiratory function, or hemody-
namic parameters after administration of a cannabis-
based product (CBD: 0.62 mg/kg; THC: 0.67 mg/kg)
once a day, per 14 consecutive days in six dogs.13
Chicoine et al. assessed the oral administration of
cannabis-based products at two different doses: full
(10 mg/kg CBD; 0.5 mg/kg THC) and half (5 mg/kg
CBD; 0.25 mg/kg).14 The authors observed signs such
as hyperesthesia, proprioceptive deficits, ptyalism, uri-
nary incontinence, and vomiting after a single admin-
istration of the full dose. Nevertheless, the animals
did not show clear signs of cannabinoid intoxication.
Mild neurological changes were observed in the half-
dosed dogs, such as pupil dilation, mild ataxia, noise
sensitivity, and delay in reflex responses. However,
after five consecutive administrations of the same
dose (q12h), these adverse effects were reduced.
Hannon et al. administered a semisolid product
(ointment) in the ear of healthy dogs twice a day for
 CANNABIS-BASED PRODUCTS FOR TREATING DOGS 739

Table 1. Pharmacokinetic Parameters from a Single Administration of Cannabis-Based Products Formulated

with Cannabidiol Isolated, Purified, and/or with Low Levels of Tetrahydrocannabinol

Dose
Route of (mg/kg body AUC1-t
Product description administration weight) Cmax (ng/mL) T1/2 (h) (h$ng/mL) References

Purified Cannabis extract, rich in CBD, Oral 1 30 – 7 5.6 – 1 183 – 43 Vaughn et al.10
incorporated into an oily matrix. (MCT)
Purified Cannabis extract, rich in CBD, Oral 2 46 – 23 9.3 – 6.6 287 – 168 Vaughn et al.10
incorporated into an oily matrix. (MCT)
Cannabis extract containing CBD, THC, CBC, Oral 2 102 (61–132)a 4.2 (3.8–6.8)a 367 (183–437)a Gamble et al.16
and CBG incorporated in an oily
matrix (olive oil)
Soft chews containing purified Cannabis Oral 2 301 – 63 1 – 0.2 1297 – 210 Deabold et al.17
extract, rich in CBD
Purified Cannabis extract, rich in CBD, Oral 4 130 – 47 5.4 – 1.4 859 – 475 Vaughn et al.10
incorporated into an oily matrix. (MCT)
Cannabis extract containing CBD, THC, CBC, Oral 8 591 (389–905)a 4.2 (3.8–4.8)a 2658 (1753–3048)a Gamble et al.16
and CBG incorporated in an oily
matrix (olive oil)
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Transdermal cream containing purified Transdermal 10 74.3 – 127.2 ND 195 – 315 Bartner et al.27
Cannabis extract, rich in CBD
Purified Cannabis extract, rich in CBD, Oral 10 346.3 – 158.7 1.6 – 0.5 1633.3 – 721.7 Bartner et al.27
incorporated into an oily matrix and
microencapsulated
Purified Cannabis extract, rich in CBD, Oral 10 625.3 – 164.3 3.3 – 0.9 2260 – 771.7 Bartner et al.27
incorporated into an oily matrix
Purified Cannabis extract, rich in CBD, Oral 12 201 – 55 ND 1430 – 610 Vaughn et al.10
incorporated into an oily matrix. (MCT)
Transdermal cream containing purified Transdermal 20 277.6 – 476 ND 495 – 493.3 Bartner et al.27
Cannabis extract, rich in CBD
Purified Cannabis extract, rich in CBD, Oral 20 578.1 – 287.1 1.9 – 1.5 2713.3 – 1023.3 Bartner et al.27
incorporated into an oily matrix and
microencapsulated
Purified Cannabis extract, rich in CBD, Oral 20 845.5 – 262.2 2.1 – 0.5 4960 – 1880 Bartner et al.27
incorporated into an oily matrix
a
Data are expressed as median (range) and mean – standard deviation.
AUC1-t, area under the plasma concentration–time curve, from time zero to t; Cmax, maximum plasma concentration; CBC, cannabichromene; CBD,
cannabidiol; CBG, cannabigerol; MCT, medium-chain triglycerides; t1/2, half-life time; THC, tetrahydrocannabinol.

2 weeks. The applied amount corresponds to *19 mg
of CBD and 0.8 mg of THC. The authors described
an occurrence of aural erythema probably owing to
the ointment formulation.15
No clinically relevant adverse events were observed
in studies that evaluated THC-free CBD products in
dogs at doses ranging from 1.2 to 5.0 mg/kg in a single
daily dose or half of that dosage twice a day, by
oral16–21 or oral-transmucosal22 routes spanning from
7 to 84 days.
Deabold et al. reported the evacuation of loose stools as
the most observed adverse event after two daily oral CBD
(2 mg/kg) intakes for 84 days (3.3% of total observations).
Furthermore, no abnormalities or changes in the dogs’
behavior were observed during the study period.17
Mcgrath et al. observed an increase in serum alkaline
phosphatase levels in animals after 12 weeks of oral
treatment with a cannabis-based product containing
CBD (2.5 mg/kg) given twice a day.18 Similarly,
Vaughn et al. observed increased serum alkaline phos-
phatase concentration in animals treated with CBD at
doses of 2, 4, or 12 mg/kg of body weight, once a day,
in the first 2 weeks of the study.6 Conversely, only
the group of animals on the highest dose of CBD
(12 mg/kg) showed a statistical difference for the pa-
rameter compared with the placebo group after 28
days of treatment. Furthermore, the authors reported
no clinical signs associated with increased serum levels
of biomarkers of liver injury.
Finally, Morris et al. demonstrated that 3 weeks of
CBD (4.5 mg/kg/day) supplementation altered the ca-
nine metabolome of healthy animals.23 However, feed-
ing CBD-containing treats did not affect animals’ daily
voluntary activity.24
Efficacy
Seven retrieved studies assessed the effectiveness of
cannabis-based products’ administration in treating
different dogs’ clinical and behavioral conditions.
Table 3 summarizes the characteristics of the evaluated
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Table 2. Pharmacokinetic Parameters from a Single Administration of Cannabis-Based Products Formulated with Cannabidiol and Tetrahydrocannabinol

Dose (mg/kg body weight) Cmax (ng/mL) T1/2 (h) AUC1-t (h$ng/mL)
Route of
Product description administration CBD THC CBD THC CBD THC CBD THC References
a a b b b b
Purified Cannabis extract Sublingual 0.62 0.67 10.5 18.5 ND ND 60.4 94.9 Fernández-Trapero et al.13
into a vehicle containing
ethanol, propylene glycol
and vegetable oil
Purified Cannabis extract Oral (fasted animals) 0.0375 1.5 NDT 24.34 (9.2–77.1)c ND ND ND 74.25 (22.05–100.18)c qebkowska-
incorporated into Wieruszewska et al.11
an oily matrix
Purified Cannabis extract Oral (fed animals) 0.0375 1.5 NDT 7.10 (3.6–11.4)c ND ND ND 29.74 (8.6–61.23)c qebkowska-
incorporated into Wieruszewska et al.11
an oily matrix
Purified Cannabis extract Oral 1.2a 0.04a 145 – 69 ND 4.1 – 0.7 ND 635 – 399 ND Wakshlag et al.12
containing CBD, CBDA,
THC, THCA, CBC, and
CBGA incorporated in
an oily matrix
(MCT + sesame oil)
Purified Cannabis extract Oral 1.2a 0.04a 124 – 62 6–3 4.4 – 1.4 4.0 – 3.9 683 – 145 22 – 9 Wakshlag et al.12
containing CBD, CBDA,
THC, THCA, CBC, and
CBGA incorporated in

740
an oily matrix
(MCT + sesame oil +
sunflower lecithin)
Chewable treat formulated Oral 1.2a 0.04a 226 – 89 ND 3.8 – 0.3 ND 826 – 74 ND Wakshlag et al.12
with purified Cannabis
extract containing CBD,
CBDA, THC, THCA, CBC,
and CBGA
Purified Cannabis extract Oral 2 0.1 213 – 49 17.5 – 5.5 2.5 – 0.5 1.6 – 1.5 692 – 292 43.5 – 16 Chicoine et al.14
containing CBD, THC, and
CBC incorporated into
an oily matrix
Purified Cannabis extract Oral 5 0.25 838 – 304 67.6 – 20.3 2.6 – 0.4 1.9 – 0.5 2433 – 911 203.9 – 73.3 Chicoine et al.14
containing CBD, THC,
and CBC incorporated
into an oily matrix
Purified Cannabis extract Oral 10 0.5 1868 – 698 138.3 – 56.4 2.3 – 0.2 1.9 – 0.2 5883 – 2181 451.5 – 178.8 Chicoine et al.14
containing CBD, THC, and
CBC incorporated into
an oily matrix
a
Approximate dose, considering the total administered product and the average weight of the animals in the study, according to the protocols described by the studies’ authors.
b
Standard deviations not reported by studies’ authors.
c
Data are expressed in terms as median, minimum and maximum.
CBDA, cannabidiolic acid; CBGA, cannabigerolic acid; ND, not determined; NDT, not detectable; THCA, tetrahydrocannabinolic acid.
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Table 3. Main Findings of Efficacy Studies of Cannabis-Based Products in the Treatment of Dogs

Medical Route of Dosage Experimental No. of

Product description conditions administration regimen design participants Main results References

Cannabis extract containing Osteoarthritis Oral 2 mg of CBD/kg of Randomized, 16 Y pain and [ dogs’ activity Gamble et al.16
CBD, THC, CBC, and CBG body weight, double-blinded
incorporated in an oily every 12 h, (veterinarian
matrix (olive oil) for 4 weeks and tutor),
crossover and
placebo-
controlled
Purified Cannabis extract Intractable Oral 2.5 mg/kg of Randomized, 16 Y frequency of seizures, McGrath et al.18
containing CBD idiopathic body weight, double-blinded but no difference was
epilepsy twice a day, (veterinarian observed in the proportion
for 12 weeks and tutor), of respondents between
placebo-controlled the test and placebo groups
Purified Cannabis extract Osteoarthritis Oral transmucosal 2 mg/kg of Randomized, 21 Y pain perception and Brioschi et al.22
containing CBD incorporated body weight, placebo-controlled improvement in the animals’
into an oily matrix (MCT) every 12 h, quality of life
for 12 weeks

741
Chewable treat formulated with Anxiety Oral 0.7 mg/kg of Randomized, 16 There was no evidence of Morris et al.19
purified Cannabis extract body weight, placebo-controlled anxiolytic effect associated
containing CBD twice a day, with the administration of CBD
for 7 days
Isolated CBD incorporated into Osteoarthritis Oral 0.5 or 1.2 mg/kg Randomized, 16 Improvement in the animals’ Verrico et al.20
an oily matrix (vegetable oil) of body weight double-blinded quality of life (only to
once a day (veterinarian the test group treated
for 6 weeks and tutor), with the highest dose)
placebo
controlled
Purified Cannabis extract Aggressive behavior Oral Approximately Randomized, 24 There was no evidence Corsetti et al.21
containing CBD 1.25 mg/kg blinded of reduction in animals’
body weight (dog behavior aggressive behavior
once daily observers),
for 45 days placebo
controlled
Purified Cannabis extract Osteoarthritis Oral 2.5 mg/kg of Randomized, 23 There were no differences Mejia et al.25
containing CBD body weight, double-blinded, between groups on activity
every 12 h, crossover and count, clinical metrology
for 6 weeks placebo-controlled instrument, and objective
gait analysis
 742
phytocannabinoid products, the addressed clinical con-
dition, the route, dose, administration regimen, the
type of study, and a brief description of the main results
presented by the authors.
All seven studies were randomized placebo-
controlled clinical trials. Cannabis-based products
with attributes significantly different from each other,
produced either by purified cannabis extract (THC-
free or not) or formulated from isolated CBD, were
evaluated. The daily dose for clinical studies, expressed
in terms of the amount of CBD administered per kilo-
gram of animal weight, did not exceed 5 mg/kg/day in
any of the studies. Except for the study conducted by
Brioschi et al., which proposed administering the
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cannabis-based product through the oral mucosa
(oral transmucosal), all other clinical trials used the
oral route for formulations administration.22
The outcomes of studies addressing the efficacy of
cannabis-based products in the treatment of pain and
improvement in the quality of life of dogs with osteoar-
thritis were positive in three of seven clinical trials in
different experimental designs.16,20,22 On the contrary,
Mejia et al. reported no differences between groups at
any time point for any of the recorded outcome mea-
sures (objective gait analysis, activity counts, and clin-
ical metrology instrument) on naturally occurring
osteoarthritis-associated pain treatment.25
Intractable idiopathic epilepsy showed inconclusive
results on CBD administration (2.5 mg/kg, q12h).18
The evaluated formulation reduced the frequency of
seizures in treated animals compared with the placebo
group. Still, there was no difference in the proportion of
responding animals between the two groups.
There were no differences between the treatment
and placebo groups in the other two clinical trials in-
cluded in this integrative review to treat behavioral
signs associated with anxiety and aggression.
Discussion
Pharmacokinetics is one of the priority areas for medic-
inal cannabis-related research.26 To enable the incor-
poration of cannabis-based products into the clinical
practice of veterinarians, understanding the pharmaco-
kinetic properties of these substances, particularly CBD
and THC, is essential to recommend the best route of
administration and dosage regimen for each case.
When comparing identical formulations containing
CBD, differing only the dose administered by oral
route to animals, such as in the studies conducted by
Bartner et al., Gamble et al., and Vaughn et al., the sys-
DE ANDRADE ET AL.
temic exposure to phytocannabinoid, described by
the AUC parameter, increases in a dose-dependent
manner.10,16,27 In addition, in the study conducted by
Bartner et al., it is also possible to evidence a dose-
dependent relationship in systemic exposure to CBD
when administered through the transdermal route.
Although less evident, the Cmax of CBD also seems to
follow the same behavior.27
However, under the same circumstances, when eval-
uating the t1/2 described by several authors, which
range from 1 to 9 h, it is impossible to clearly show a
direct incremental relationship between the parameter
values and the dose administered to dogs in the differ-
ent studies.10–14,16,17,27
The study conducted by Chicoine et al. similarly re-
veals the dependence of the AUC and Cmax parameters
on the administered dose of CBD and THC and the ev-
ident lack of relationship between the dose of phyto-
cannabinoids administered and the t1/2.14
It is critical to consider the influence of formulation’s
characteristics such as dosage form and excipients and
the animal’s feeding state (fasting or fed) in the absorp-
tion of phytocannabinoids. Deabold et al. highlighted the
influence on the CBD absorption process, reporting a
2.5-fold increase in AUC when administering CBD in
a soft chew treat containing glycerol, starch, and fibers
compared with CBD reconstituted in olive oil.16,17 In ad-
dition, Wakshlag et al. showed that the presence of soy
lecithin promoted an increase in CBDA AUC compared
with a formulation without the adjuvant.12 qebkowska-
Wieruszewska et al. observed an increase in AUC from
the plasma concentration of THC in dogs in the fasted
state compared with animals in the fed state.11
Regarding safety, the studies suggest that the admin-
istration of CBD products, free or with a minimal con-
tent of THC traces, does not trigger clinically relevant
adverse events in dogs, either from a single product ad-
ministration or by successive administrations, espe-
cially by oral route, in the different doses evaluated.
Moreover, the oral administration of CBD products
in combination with THC showed no apparent signs
of cannabinoid intoxication at the different doses stud-
ied by several authors.6,11,13–15,17,18,24
Moreover, concerning the longest safety assessment of
a CBD-containing product (84 days), Deabold et al.
reported occasional episodes of loose stool as a noted
side effect. However, the authors also stated that the inci-
dence follows the typical occurrence of diarrhea observed
by the laboratory (close to 3%). Hence it is unlikely to be
an effect induced by the CBD-containing product.
 CANNABIS-BASED PRODUCTS FOR TREATING DOGS
It is well-known that the canine brain has a greater
density of cannabinoid receptors than the human
brain.3,8 Moreover, concerning the spatial distribution
of CB1 receptors in the canine CNS, Freundt-Revilla
et al. reported that the high receptors’ expression in
the cerebral and cerebellar cortex, Cornu Ammonis
and dentate gyrus of the hippocampus, globus pallidus,
and substantia nigra spinal cord and dorsal root ganglia
might be related to effects of cannabinoids on motor
functions, which may represent a potential risk.7
Regarding the effectiveness of the therapeutic use of
cannabis-based products for the treatment of dogs,
products containing CBD and THC or rich in CBD
and with low levels of THC can promote an improve-
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ment in the quality of life and perception of pain in an-
imals affected by canine osteoarthritis.
It is important to highlight that the conflicting re-
sults presented by Mejia et al. compared with the re-
sults from the other three studies that assessed the
efficacy of Cannabis-based products for the canine os-
teoarthritis treatment could be attributed to several
limitations of the study protocol (lack of a washout pe-
riod, potential difficulties with the blinding process, use
of hemp oil as the base for the placebo group). The au-
thors reported the use of hemp oil as the base for the
placebo group, which may have resulted in positive
clinical effects even in this group of animals owing to
the product’s composition.
Polyunsaturated fatty acids or low levels of cannabi-
noids contained in the placebo product could act as a
confounding factor impairing the distinction between
test and control groups, resulting in a lack of evidence
of CBD-containing product efficacy.
Nonetheless, it was impossible to state the benefits of
cannabis-based products for the other studied condi-
tions (intractable idiopathic epilepsy, anxiety, and ag-
gressiveness). However, owing to the apparent
studies’ limitations, for example, CBD and/or THC ad-
ministered in low doses, experimental design, and the
heterogeneity of the population evaluated, it is
unthinkable to rule out the possibility that cannabis-
based products can contribute to treating these clinical
conditions. Therefore, more clinical research studies
are needed, and high standardization and scientific
rigor levels are strongly recommended.
Conclusion
Given the studies included in this integrative review, it
is possible to infer the safety of cannabis-based prod-
ucts for the treatment of dogs. This is especially true
743
for CBD-rich, low-THC, or THC-free products. Fur-
thermore, oral administration of CBD is an alternative
for improving quality of life and reducing the percep-
tion of pain in animals affected by canine osteoarthritis.
It is necessary to highlight that owing to the inherent
characteristics of each cannabis-based formulation, it is
not possible to predict the safety and efficacy of all
products containing CBD, THC, or their several com-
binations. For example, phytocannabinoids’ absorp-
tion, distribution, metabolism, and excretion are
influenced by the dosage form, the adjuvants’ nature,
and the route of administration. In this scenario, new
clinical research studies are strongly encouraged. How-
ever, their results must be interpreted in light of each
cannabis-based products’ pharmaceutical, biopharma-
ceutical, and pharmacokinetic properties.
Authors’ Contributions
D.F.d.A.: conceptualization; data curation; formal anal-
ysis; investigation; methodology; writing—original
draft; writing—review and editing. J.L.H.G.: investiga-
tion; methodology; writing—original draft; writing—re-
view and editing. E.A.d.A.: investigation; methodology;
writing—original draft; writing—review and editing.
Author Disclosure Statement
No competing financial interests exist.
Funding Information
No funding was received for this article.
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Cite this article as: de Andrade DF, Gewehr JLH, de Almeida EA
(2022) Safety and efficacy of the therapeutic use of cannabis-based
products in the treatment of dogs: an integrative review, Cannabis
and Cannabinoid Research 7:6, 736–744, DOI: 10.1089/can.2021.0172.
Abbreviations Used
AUC ¼ area under the curve
Cmax ¼ maximum plasma concentration
CBD ¼ cannabidiol
CBDA ¼ cannabidiolic acid
CNS ¼ central nervous system
LILACS ¼ Latin American and Caribbean Health Sciences Literature
MCT ¼ medium-chain triglycerides
t1/2 ¼ half-life
THC ¼ tetrahydrocannabinol
THCA ¼ tetrahydrocannabinolic acid