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The Use of Cannabidiol-Rich Hemp Oil Extract to Treat Canine Osteoarthritis-Related Pain: A Pilot Study


Abstract and Figures

The objective of this 90-day pilot clinical trial was to assess the impact of a full-spectrum product containing hemp extract and hemp seed oil on dogs with chronic mal-adaptive pain. A total of 37 dogs diagnosed with chronic maladaptive pain primarily as a result of osteoarthritis were enrolled in the study. The dogs were given an initial physical examination that included systematic pain palpa- tion, mapping of pain patterns, informal gait analysis, metabolic profile, and owner interview. The same palpa-tions and mappings were performed during each biweekly assessment to identify trends, chart progress, and inform dose adjustments. The metabolic parameters were repeated at the end of the study. Of the 32 dogs that completed the study, 30 dogs demonstrated improved pain support. Of the 23 dogs in the study that were taking gabapentin at the time of enrollment, 10 dogs were able to discontinue the gabapentin, and an additional 11 dogs were able to have their daily dose reduced with the addition of the cannabi-diol (CBD) oil. Conclusion: The addition of a hemp-derived CBD oil appears to positively affect dogs with chronic maladaptive pain by decreasing their pain, thereby improving their mobility and quality of life. The reduction in gabapentin dose may be the result of changes in analgesia and/or sedation with the addition of the hemp oil extract.
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AHVMA Journal Volume 58 Spring 2020 35
Scientific Report
ADLs Activities of daily living
CBD Cannabidiol
NSAIDs  Nonsteroidalanti-inammatorydrugs
OA Osteoarthritis
THC Tetrahydrocannabinol
The objective of this 90-day pilot clinical trial was to
assess the impact of a full-spectrum product containing
hemp extract and hemp seed oil on dogs with chronic mal-
adaptive pain. A total of 37 dogs diagnosed with chronic
maladaptive pain primarily as a result of osteoarthritis
were enrolled in the study. The dogs were given an initial
physical examination that included systematic pain palpa-
tion, mapping of pain patterns, informal gait analysis,
metabolic prole, and owner interview. The same palpa-
tions and mappings were performed during each biweekly
assessment to identify trends, chart progress, and inform
dose adjustments. The metabolic parameters were repeated
at the end of the study. Of the 32 dogs that completed the
study, 30 dogs demonstrated improved pain support. Of
the 23 dogs in the study that were taking gabapentin at the
time of enrollment, 10 dogs were able to discontinue the
gabapentin, and an additional 11 dogs were able to have
their daily dose reduced with the addition of the cannabi-
diol (CBD) oil. Conclusion: The addition of a hemp-
derived CBD oil appears to positively affect dogs with
chronic maladaptive pain by decreasing their pain, thereby
improving their mobility and quality of life. The reduction
in gabapentin dose may be the result of changes in analgesia
and/or sedation with the addition of the hemp oil extract.
Laws in the United States surrounding cannabis have
undergone tremendous changes over the last several
years. In 2018, the US government enacted the Agriculture
Improvement Act of 2018, which removed hemp from
Schedule I of the federal Controlled Substances Act. Hemp
Author contacts:
Lori Kogan, PhD
Department of Clinical Sciences, College
of Veterinary Medicine and Biomedical
Sciences, Colorado State University
Fort Collins, CO
Peter Hellyer, DVM
Department of Clinical Sciences, College
of Veterinary Medicine and Biomedical
Sciences, Colorado State University
Fort Collins, CO
Robin Downing, DVM, MS
The Downing Center for Animal Pain
Management, LLC
Wi ndso r, CO
The Use of Cannabidiol-Rich
Hemp Oil Extract to Treat
Canine Osteoarthritis-Related Pain:
A Pilot Study
Lori Kogan, PhD, Peter Hellyer, DVM, Robin Downing, DVM, MS
36 AHVMA Journal Volume 58 Spring 2020
is a form of Cannabis sativa L with low levels (<0.3%) of
tetrahydrocannabinol (THC). The federal act authorized
the states to seek approval from the USDA to have primary
regulatory authority over hemp production within the state
by preparing and submitting a state plan of regulation to
the secretary of the USDA (1). Subsequently, the state of
Colorado (the location of the current study) passed a bill
in May 2019 stating that “Colorado leads the nation in
public policy supporting the hemp industry and is poised
to continue that leadership with the passage of the federal
Agricultural [sic] Improvement Act of 2018’” (2).
Due to the myriad of laws concerning cannabis and only
recent changes in the legal status of hemp, there is little
empirical research regarding the veterinary use of cannabis
products (3). Yet many pet owners are increasingly willing to
try cannabis products to help their pets with a wide array of
medical and behavioral issues (4, 5). Some of the benets of
cannabis products reported by pet owners include improved
mobility in animals with osteoarthritis (OA) as well as
reduced anxiety, pain, and occurrence of epileptic seizures
(5, 6). When pet owners were asked to compare cannabis
products to other forms of medication or therapy, the major-
ity (93%) reported that cannabis products work better than
other treatments (only 7% felt that cannabis does not work
as well) (6). When asked about side effects, these pet owners
most frequently reported sedation and overactive appetite.
Despite the interest by pet owners, however, the lack of
scientic studies has made veterinarians reluctant to
initiate cannabis-related conversations with their clients. In
addition, state laws legalizing medicinal and/or recreational
forms of cannabis do not apply to animals. The laws sur-
rounding the use of cannabis products, including hemp prod-
ucts, in veterinary medicine are complex and evolving. One
study found that 85% of veterinarians rarely or never initiate
conversations about cannabis (3). Similarly, very few advise
(73% either never or rarely), recommend (83% either never
or rarely), or prescribe (91% either never or rarely) cannabis
products, with a lack of knowledge being the most common
reason (3). With the changing laws, however, clinical trials
are now permitted. This paper outlines one such study.
Many pet owners and veterinarians working with animals
suffering from OA-related pain desire an alternative to tra-
ditional medications (nonsteroidal anti-inammatory drugs
[NSAIDs], gabapentin, etc). NSAIDs, as well as other drugs
such as gabapentin, are sometimes inadequate in relieving
OA-related pain and come with potential side effects, espe-
cially for geriatric patients (7). The facts that the endocan-
nabinoid receptor system is involved with pain modulation
and cannabis has antihyperalgesic and anti-inammatory
properties have made cannabidiol (CBD) an attractive option
to explore for the reduction of canine pain (8, 9). CBD is a
component of cannabis, which is derived from the hemp plant
and is low in psychoactive THC. One clinical trial conducted
with dogs suffering from OA found that CBD oil increased
the canine subjects’ comfort and activity levels and decreased
their pain without side effects (7). This study emphasized,
however, that different strains of cannabis contain differ-
ent amounts of cannabinoids, including CBD, making the
results difcult to generalize (7). For this reason, the current
study was undertaken to continue the exploration of canna-
bis products’ effects on dogs suffering from OA-related pain.
This pilot study had 4 objectives: (1) to determine if this par-
ticular hemp-derived CBD product could positively inuence
pain relief and overall function in dogs experiencing chronic
maladaptive pain from OA; (2) to determine if it would
be well tolerated and accepted by the enrolled dogs; (3) to
observe any potential effects on the doses of pain-related
medications already in place for the dogs; and (4) to identify
an appropriate dosing range to facilitate improved pain man-
agement in dogs suffering from chronic maladaptive pain.
Materials and Methods
A total of 37 dogs were enrolled in this 90-day pilot study.
All of the enrollees suffered from chronic maladaptive
pain, primarily as a result of OA. All but 5 of the dogs
were patients of a specialty clinic in animal pain manage-
ment in Colorado prior to participating in the study. Of
the 37 enrolled dogs, 32 dogs completed and had their
nal assessment at 90 days, and 5 dogs did not complete
the study due to their medical conditions or their owners’
life/schedule changes. Specically, changes in 1 owner’s
schedule precluded her ability to participate in the
reassessment appointments; 1 dog was diagnosed with a
bleeding splenic tumor and was euthanized; 1 dog devel-
oped an iris mass and the ophthalmologist recommended
withdrawal from the study; 1 dog was diagnosed with
an osteosarcoma and was withdrawn; and 1 dog’s pre-
existing liver and kidney disease progressed, and she was
therefore withdrawn from the study.
AHVMA Journal Volume 58 Spring 2020 37
38 AHVMA Journal Volume 58 Spring 2020
To minimize the potential for inconsistencies among
multiple observers, all enrollments and assessments were
conducted at the same hospital by the same veterinarian
(RD). Independent observations from the owners played
an important role in how these patients were managed,
providing feedback on the efcacy of increasing the hemp
oil extract and decreasing the gabapentin dose. Descrip-
tive statistics and paired t tests were conducted in SPSS
(IBM SPSS version 25) for changes in pain, ALKP, and
ALT. Statistical signicance was set at P < .05.
Eligible canine subjects and their owners met the follow-
ing criteria: dogs with chronic pain from OA for at least
3 months in duration; owners who desired trying a CBD
product to manage their dogs’ pain; owners who could
commit to a 90-day study with dogs’ medical assess-
ments every 2 weeks; owners who were willing to keep an
informal journal of their dogs’ activities of daily living
(ADLs) using the Cincinnati Orthopedic Disability Index
(se e Appendix 1 p. 44) as a guide during the duration of
the study to better understand the impact of the CBD prod-
uct; and owners who agreed not to use any medications or
supplements during the 90-day course of the study unless
approved by the veterinarian performing the assessments.
The owners of the enrolled dogs consented to have the
data generated during the study anonymously aggregated
for evaluation, statistical analysis, and publication at a
future date. Likewise, they consented to a review of
their dogs’ complete medical records to ensure that all
inclusion criteria were met. This study was classied
as exempt by the institutional review board at Colorado
State University.
Several specic pain-directed medications and therapies
were excluded during the 90-day study. With the limited
study population and in order to create as consistent a
“baseline” as possible, the use of NSAIDs was restricted
from all participants. The intention was to have NSAIDs
available only as a “rescue” therapy for individuals whose
pain could not be relieved with the CBD product under
investigation. In addition, none of the patients enrolled
in the study were taking tramadol or amantadine at the
commencement of the study, and to minimize extra-
neous variables, the addition of tramadol or amantadine
during the course of the study was disallowed. Finally,
to limit some of the inherent variability in a study of this
nature, study participants were limited to a single physi-
cal medicine modality. Because several participants were
receiving medical acupuncture for neurologic support
(rather than for pain management) at the time of enroll-
ment, the decision was made to not withdraw acupuncture
support from their treatment protocols in order to avoid
compromising these patients.
Specic pain-directed medications that were permitted
during the 90-day study included gabapentin and poly-
sulfated glycosaminoglycan (a). Most of the dogs enrolled
in this study were under the care of a veterinary pain
management expert and were already taking gabapentin
as part of a multimodal pain management strategy. Taking
into consideration the phenomenon of rebound pain in
response to an abrupt withdrawal of gabapentin, it was
determined that dogs already taking gabapentin would be
able to continue their dosing, but any new prescriptions of
gabapentin were disallowed during the course of the study.
Specic pain-directed therapies that could possibly be
permitted during the 90-day study pending approval
included medical acupuncture, therapeutic laser, and
nutraceuticals. These therapies were evaluated on a case-
by-case basis. Although these therapies can alter the
degree of pain and may have affected the results, the
intent of the study was to determine the role of the hemp oil
extract as an adjunct in the management of chronic pain.
In this group of patients, chronic pain was managed using
a multimodal approach, and the authors were interested
in determining the role of the hemp oil extract in the
presence of other therapeutic modalities.
The initial assessment of the dogs enrolled in this study
included a full physical examination and informal gait
analysis. The physical examination consisted of a sys-
tematic pain palpation and mapping of pain patterns. The
same palpation and mapping were performed during each
biweekly assessment to identify trends, chart progress, and
inform dose adjustments. A metabolic prole, including
a CBC, serum chemistry prole, and a screening thyroid
prole, to evaluate organ system function and to provide
a baseline for future comparison were performed on each
enrollee. These same metabolic parameters were repeated
at the end of the study. The informal gait analysis consisted
AHVMA Journal Volume 58 Spring 2020 39
of observing the dog, with the owner as the handler,
at a slow walk, a fast walk, and a trot. The dogs were
in an inside hallway approximately 40 feet in length,
moving rst away from and then toward the observer
(RD). Lameness was noted as to limb and severity. In
addition to identifying lameness, the purpose was to
gain insight into each patient’s ability and willingness to
move at various speeds and to note any changes over the
course of the study. No force plate or lm analysis was
conducted. Informal assessment of the dogs’ ease and
willingness to move was one aspect of evaluating their
quality of life. Initial assessment also included a detailed
interview with each dog owner to discuss the dog’s ADLs
and quality of life as well as the owner’s desired outcome
goals for the dog.
At the initial evaluation and enrollment, qualied dogs
received a CBD oil product at a dose of 0.25 mg/kg
delivered on food QD for 3 days and then morning and
night (approximately every 12 hours). The product
given was a certied organic, cold-pressed hemp seed oil
infused with 1,000 mg of full-spectrum hemp extract
derived from organically grown hemp plants, cultivated
in Colorado. Full-spectrum extract includes cannabinoids
(such as cannabidiolic acid, CBD, cannabigerol, canna-
bichromene), avonoids, terpenes, and other constitu-
ents within the cannabis plant (see Cannabinoid Prole
in Appendix 2 p. 45).
Pain assessments of each participant were conducted
every 2 weeks during the 90-day study and consisted of
a systematic pain palpation and pain pattern mapping,
informal gait analysis, and review with each dog’s owner
of the previous week’s ADLs and owner observations as
recorded in the owner’s log. The CBD dose was adjusted
as needed in response to the new assessment. CBD dose
escalations of 0.5 to 0.75 mg/kg approximately every
12 hours were prescribed at each reassessment until the
patient’s pain score on palpation was 0 to 1 on a scale of
10. Each modied dose of the CBD product within that
dose escalation range reected a volume that was easy for
the owner to measure. The primary goal was to achieve
acceptable comfort without inducing sedation. Although
sedation is a known potential side effect of CBD ingestion,
the sedation may be occurring as a result of low levels
of THC in the formula, not the CBD (10).
Each patient’s overall pain severity was scored using a
0 to 10 scale, with 10 representing the worst possible pain.
This overall pain score alongside the pain map was used to
guide CBD oil dose adjustments. The pain map recorded
anatomic locations that were reactive to systematic pal-
pation. This pain palpation technique has been described
in detail (11). In addition, for the dogs taking gabapentin
for chronic maladaptive pain at the time of study enroll-
ment, once their comfort level was stable following
CBD dose escalations, gabapentin dose reductions were
attempted. Gabapentin dosing varied from 10 to 40 mg/kg
delivered every 8 to 12 hours, depending on the needs
of the individual patient to achieve adequate pain
relief without inducing sedation. At times, deescalating
the gabapentin dose changed the dosing interval from
every 8 hours to every 12 hours or from every 12 hours to
every 8 hours, depending on the total dose per day, ease of
achieving the required dose based on currently available
strengths of gabapentin, and ease of dosing with respect to
the owners’ schedules. The gabapentin dose was reduced
by 20% to 40% of the total daily dose based on the reduc-
tion amount that would provide the easiest dose delivery
(for instance, reducing a dog’s dose from 1,200 to 900 mg
per day, which would reduce the daily dose by 300 mg).
The new dose was maintained until the next assessment.
If a dose reduction was too great (dened as increased
pain noted in the following pain reassessment), the dose
would be increased to the previous level. These dose
reductions were a way to assess the ability of the CBD
oil to reduce the required dose of gabapentin to support
the dog’s comfort level.
A total of 32 dogs completed the study, with only 2 dogs
deemed by their owners and supported by the veterinary
assessments to have achieved no measurable improvement
in pain with the addition of the CBD oil. The nal CBD
dose used in the 2 “non-responders” was 2 mg/kg every
12 hours. These dogs’ overall mobility and comfort did not
change during the course of the 90-day study, with their
overall pain scores remaining at 1/10. It is unclear why
they seemed to show no changes with the addition of the
CBD product. The 30 remaining dogs represent a variety
of breeds with an average weight of 23.2 kg (range: 5–50 kg)
and average age of 10.9 years (range: 2–16.6 years)
(Table 1). All 30 dogs demonstrated improved pain
40 AHVMA Journal Volume 58 Spring 2020
support, with their pain scale score decreasing from
an average of 3.2 ± 2.2 (mean ± standard deviation) to
0.97 ± 0.81, or an average change of −2.23 ± 2.3 (Table 2).
Of the patients, 7 patients had no change in their over-
all pain scores, starting and ending the study with pain
scores of 1. These 7 dogs started the study with gabapentin
as a part of their pain management protocols, and their
gabapentin doses were reduced and comfort was retained.
Of the 23 dogs that were taking gabapentin at the time of
enrollment, 10 dogs were able to discontinue taking
gabapentin after the addition of the CBD oil to their pain
management protocols. Of the 13 dogs in the study that
were taking gabapentin when they were enrolled and were
unable to discontinue gabapentin by the end of the study,
11 dogs were able to have their daily dose of gabapentin
reduced with the addition of the CBD oil; 5 enrolled dogs
received no gabapentin during the course of the study.
Of the 30 dogs deemed to benet from the addition of
CBD oil to treat their chronic maladaptive pain, all ended
the study with an overall pain score ranging from 0/10 to
2/10 (Table 2). Of these 30 dogs, 6 dogs experienced an
improvement in their overall pain scores of 5 or better:
2 dogs’ scores reduced from 8/10 to 1/10; 2 dogs’ scores
reduced from 7/10 to 1/10; 1 dog’s score reduced from 6/10
to 1/10; and 1 dog’s score reduced from 5/10 to 0/10.
Among these 30 dogs, the dose of CBD needed to achieve
a positive effect ranged from 0.3 up to 4.12 mg/kg BID.
The 2 dogs in the study requiring the highest dose of the
CBD product were both Cavalier King Charles spaniels
(not related to one another), and neither of these dogs
experienced any changes/elevations in liver enzymes. It
is unclear why some patients responded to a very small
dose of the CBD product (0.3 mg/kg per dose), whereas
the majority required dosing in the range of 1 to 2 mg/kg
per dose. This wide dosing range suggests that practi-
tioners must approach CBD use for chronic pain in dogs
with the intention of following these patients carefully
during their initial treatment in order to ne-tune the CBD
dose to meet the needs of the individual. As an analogy,
it is a well-known phenomenon in human pain manage-
ment that individuals can have very different requirements
of opioids to control pain. Further studies of CBD use
in dogs for chronic pain may facilitate a better understand-
ing of variable needs among individuals. The majority,
Table 1. Patient Characteristics of Dogs
With Chronic Pain Enrolled in CBD Trial
Patient # Breed Age (years) Sex Weight (kg)
Existing patients
1Border collie 8.9 FS 25
2 German shepherd 8.2 FS 31
3Rhodesian Ridgeback 11.9 FS 38.6
4Rhodesian Ridgeback 2FI 38
5Labrador retriever 12.8 MN 34
6Labrador retriever 12.8 FS 25
7Maltese 13.3 FS 5
8Labrador retriever 13.5 MN 40
9American pit bull terrier 10.3 MN 28.5
10 Australian shepherd 13.3 MN 10.4
11 French bulldog 5.75 MN 13.6
12 Bichon frise/cocker spaniel 14 FS 9
13 Scottish terrier 16.6 MN 11.8
14 German shepherd 12.9 MN 43.2
15 Shepherd/chow 12.1 FS 21
16 Great Dane 9 FS 50
17 King Charles spaniel 8.1 FI 8
18 Beagle 13.25 MN 10.2
19 King Charles spaniel 8.8 MN 10
20 American pit bull terrier 6.3 FS 27.3
21 Australian shepherd 11.4 FS 2 7.6
22 Peke-a-poo 15.5 MN 8.2
23 Beagle 9.8 FS 10.5
24 Labrador retriever 8.4 MN 41
25 Border collie X 13.7 FS 27
26 Dachshund (standard) 10.2 FS 5.5
New patients
27 Shiba Inu mix 14.25 FS 11
28 Pit bull 5.25 FS 27
29 Australian shepherd 13.25 FS 26
30 Labrador retriever 11.6 FS 33
Patients were either existing or new patients to the clinic for the treatment
of chronic pain.
Abbreviations: FI, intact female; FS, spayed female; MN, neutered male.
AHVMA Journal Volume 58 Spring 2020 41
or 19, of these dogs ended the study with a dose ranging
between 1.2 and 2 mg/kg BID.
Among the study’s dogs taking gabapentin that expe-
rienced a dose reduction (but not a withdrawal of gaba-
pentin), the nal doses varied from 20% to 60% of the
original dose. The dogs taking gabapentin at the time of
enrollment had been taking gabapentin for a time that
ranged from 3 months to 10 years.
The only clinically meaningful change in blood param-
eters obtained was an increase in ALKP (Table 3). Inter-
estingly, there was a slight decrease in ALT between the
beginning and end of the study, but it was not statistically
signicant (Table 4).
During the course of the study, the dog owners shared their
subjective impressions of their dogs’ responses to the CBD
oil. These impressions included observations of increased
energy and stamina for daily activities. Quotes from clients
include: “She’s more like a puppy”; “He is acting like a
much younger dog”; and “I haven’t seen him play like this
for a long time.” Additionally, several of the dog owners
reported noticing that their dogs were more attentive, ani-
mated, and mentally engaged after starting the CBD oil.
During the study, gabapentin was decreased (n = 11) or
eliminated (n = 10) for 21 dogs. Many of these dog own-
ers reported that their dogs subsequently slept less, which
translated into more interaction time with the family. Our
results could not differentiate the reason for less sleep in
these patients: a reduction in gabapentin-induced sedation,
improved analgesia from the hemp oil extract, or both.
Overall feedback from 94% of the owners (n = 30)
indicated they felt their dogs’ quality of life had improved
after starting the CBD product.
Increasing interest in hemp-derived CBD products for
pain relief in dogs, coupled with minimal research dem-
onstrating safety and efcacy to date, prompted this
pilot study to examine the potential role of a CBD oil as a
strategy for managing chronic maladaptive pain in dogs
with OA. Of the 32 dogs that completed the study, 30 dogs
demonstrated benets from the addition of this hemp-derived
Table 2. Starting and Ending Numeric Rating Score, CBD Dose, and Gabapentin Doses in a Clinical Trial
of Dogs Receiving CBD for the Treatment of Chronic Pain
Pre Post Change
Numeric Rating Score* 3.2 ± 2.2 0.97 ± 0.81 −2.23 ± 2.3
CBD dose (mg/kg) 0.31 ± 0.04 1.67 ± 0.09 1.36 ± 0.88
Gabapentin dose (mg/day)** 1,846 ± 1,756 710 ± 1,112 −1,263 ± 1,314
*NRS (t = 5.35, df = 29, P <.001); **Gabapentin (t = 5.12, df = 29, P = .001).
Data are presented as mean ± standard deviation.
Abbreviations: df, degrees of freedom; NRS, Numeric Rating Scale.
Table 3. Changes in Liver Enzymes (ALKP)
in Dogs With Chronic Pain Receiving CBD
in a 90- Day Trial
Starting ALKP (U/L) Ending ALKP (U/L) Change in ALKP (U/L)*
133.3 ± 118 264 ± 233.2 130. 8 ± 135
*ALKP (t = −5.22, df = 28, P = .001).
Biochemistry values were obtained before beginning the clinical trial
and at 90 days.
Abbreviation: df, degrees of freedom.
Table 4. Changes in Liver Enzymes (ALT)
in Dogs With Chronic Pain Receiving CBD
in a 90- Day Trial
Starting ALT (U/L) Ending ALT (U/L) Change in ALT (U/L)*
93.5 ± 69.3 91 ± 60.4 −2.5 ± 43
*ALT (t = .31, df = 29, P = .76).
Biochemistry values were obtained before beginning the clinical trial
and at 90 days.
Abbreviation: df, degrees of freedom.
42 AHVMA Journal Volume 58 Spring 2020
CBD oil. Outcome benets included decreased pain scores,
improvements in mobility, and improved quality of life
as dened by their owners.
A total of 23 dogs in the study were taking gaba-
pentin as part of a multimodal pain management proto-
col. Of the total, 10 dogs (43.5%) were able to discontinue
their reliance on gabapentin with the addition of CBD
oil. Of the 13 dogs who continued to take gabapentin,
11 dogs were able to reduce the gabapentin dose neces-
sary to retain comfort to 20% to 60% of the original
dose. These results strongly suggest that a CBD prod-
uct, at an appropriate therapeutic dose, may provide a
gabapentin-sparing effect for dogs experiencing chronic
maladaptive pain.
The dosing range for hemp-derived CBD oil suggested
by this study reects a similar range to that articulated
by Gamble et al (study doses of 2 and 8 mg/kg, with anec-
dotal evidence suggesting efcacy as low as 0.5 mg/kg),
implying that any potential variability among different
hemp plant genetics may be overcome by demonstrating,
via independent analysis, the presence and concentration
of the active CBD molecule (7). Due to the variation in
concentration from product to product of CBD content
and constituents such as terpenes, cannabinoids, and a-
vonoids, it is essential to publish an analysis of the product
being tested in order to describe that specic cultivar.
Interestingly, ALKP, but not ALT, increased signicantly
during the 90-day trial. In a study to investigate CBD
hepatoxicity, 8-week-old male B6C3F1 mice were gavaged
with CBD in an acute and subacute toxicity model. In
both models, mice developed signs of hepatoxicity with
evidence of cholestatic changes (12). The doses used in
that study were signicantly different from doses used
in the current study. Nevertheless, it is worthwhile to note
the potential for hepatotoxicity as a result of an accidental
overdose. There was no evidence of clinical hepatic dis-
ease in dogs in this study that received CBD; however, the
changes in ALKP suggest the need for longer-term safety
studies. The dog who was withdrawn from the study due
to progressing systemic disease was determined via
abdominal ultrasound to have a very advanced liver tumor
that clearly predated the start of this 90-day study. His rapid
decline in activity and quality of life prompted the ultra-
sound, which revealed the terminal neoplastic disease.
This study had several limitations. It was an open study
with no placebo control group, and because a single
individual assessed all patients in the absence of a con-
trol group, there was a potential for bias. In addition,
the sample size was relatively small. Although the study
subjects were understood to be similar in that they were
all suffering from OA, OA and its resultant pain create
individualized experiences among patients. In addition,
the pain assessment and scoring of canine pain are sub-
jective by nature. The investigators attempted to limit the
subjectivity by having the study dogs evaluated and the
owners interviewed by a single individual (RD) through-
out the study. Future studies incorporating more objec-
tive assessments of pain, such as force plate analysis, are
needed to quantify the amount of functional improve-
ment associated with CBD products. Longer-term studies
are needed to determine if CBD, in combination with
other analgesics used to treat chronic pain, has deleterious
effects on liver function.
In summary, this study provides the foundation for
future research into the benecial use of CBD products,
delivered at therapeutically relevant doses, to mitigate
chronic maladaptive pain in dogs with OA.
AHVMA Journal Volume 58 Spring 2020 43
               
communicating with dog owners and manuscript formatting.
a. Adequan®
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Front Vet Sci
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synthetic cannabinoids, and cannabidiol in dogs and cats.
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of a cannabidiol-rich cannabis ext ract in the mouse model.
44 AHVMA Journal Volume 58 Spring 2020
Appendix 1
AHVMA Journal Volume 58 Spring 2020 45
Cannabidiolic acid (CBD-A)
Cannabidiol (CBD)
(–)-trans-∆⁹-tetrahydrocannabinol (THC)
∆9-Tetrahydrocannabinolic acid A (THC-A) ∆8-Tetrahydrocannabidol
Tetrahydrocannabivarin (THCV)
Cannabidivarin (CBDV)
Cannabigerolic acid (CBG-A)
Cannabichromene (CBC)
Cannabinol (CBN)
Cannabigerol (CBG)
Appendix 2
... However, in another randomised, double-blinded, crossover study involving 23 dogs, Mejia et al. (2021) found no significant difference between CBD oil treatment and placebo over the course of 6 weeks, based on CMI outcomes and objective pressure gait analysis. Two other published studies have suggested an improvement in clinical signs of OA in dogs treated with CBD oil as part of a multi-modal analgesic plan (Brioschi et al. 2020), and with gabapentin (Kogan et al. 2020). However, both studies have limitations. ...
... However, both studies have limitations. The latter study had no control group, and did not use validated pain scoring systems to subjectively measure outcomes (Kogan et al. 2020), and the former involved dogs already receiving an NSAID, gabapentin and amitriptyline (Brioschi et al. 2020). Both also involved small numbers of dogs, with sample sizes of 32 and 23, respectively. ...
Full-text available
Canine osteoarthritis is a significant cause of pain in many dogs and can therefore compromise animal welfare. As the understanding of the biology and pain mechanisms underpinning osteoarthritis grows, so do the number of treatments available to manage it. Over the last decade, there have been a number of advances in the pharmaceutical treatment options available for dogs with osteoarthritis, as well as an increasing number of clinical trials investigating the efficacy of pre‐existing treatments. This review aims to examine the current evidence behind pharmaceutical treatment options for canine osteoarthritis, including non‐steroidal anti‐inflammatory drugs, piprants, monoclonal antibodies, adjunctive analgesics, structure modifying osteoarthritis drugs and regenerative therapies.
... To date, there are a total of five studies on CBD supplementation in managing chronic canine pain (Gamble et al., 2018;Kogan et al., 2020;Martello et al., 2019;Mejia et al., 2021;Verrico et al., 2020), and none in feline pain, whether acute or chronic. CBD supplementation is delivered by oral administration of CBD oil (Gamble et al., 2018), ingestion of CBD-enriched tablets (Martello et al., 2019), CBD-enriched hemp oil delivered on food and ingestion of naked and liposomally-encapsulated CBD (Verrico et al., 2020) at doses of 0.3-4.12 ...
... mg/kg body weight alleviated osteoarthritic (OA) pain in client-owned dogs and improved quality of life. Kogan et al. (2020) even reported that in dogs on gabapentin, a drug used for treating neuropathic pain, the additional CBD supplementation allowed a third of the dogs to wean off the drug, and another one-third of the dogs were able to have their doses reduced. In addition, it was reported that a wide range of doses (0.3-4.12 mg/kg body weight) was needed to achieve the analgesic effects in chronic canine OA pain, where some responded to small doses of CBD while others required larger doses for the same effect , suggesting different pain tolerance in dogs and different dosage requirements (Allweiler, 2013). ...
Recent advances in cannabidiol (CBD) use in canines and felines for anxiety management, pain management, and anti-inflammatory effects were reviewed using a literature search conducted with the following keywords: CBD, anxiety, inflammation, pain, dogs, cats, and companion animals. For decades, research on CBD has been hindered due to the status of cannabis (C. sativa L.) as an illicit drug. Limited safety data show that CBD is well-tolerated in dogs, with insufficient information on the safety profile of CBD in cats. Upon oral supplementation of CBD, elevation in liver enzymes was observed for both dogs and cats, and pharmacokinetics of CBD are different in the two species. There is a significant gap in the literature on the therapeutic use of CBD in cats, with no feline data on anxiety, pain, and inflammation management. There is evidence that chronic osteoarthritic pain in dogs can be reduced by supplementation with CBD. Furthermore, experiments are required to better understand whether CBD has an influence on noise-induced fear and anxiolytic response. Preliminary evidence exists to support the analgesic properties of CBD in treating chronic canine osteoarthritis; however, there are inter- and intra-species differences in pharmacokinetics, tolerance, dosage, and safety of CBD. Therefore, to validate the anxiety management, pain management, and anti-inflammatory efficacy of CBD, it is essential to conduct systematic, randomized, and controlled trials. Further, the safety and efficacious dose of CBD in companion animals warrants investigation.
... Areas of interest include use for osteoarthritis pain [88,[96][97][98], other types of pain (oncologic, neuropathic) [99], immune-mediated and inflammatory allergic disorders [100], cardio-vascular and respiratory conditions [101], and epilepsy [102,103]. According to the scientific literature review, cannabinoids are mainly used in the treatment of pain, especially osteoarthritis pain. ...
... Kogan et al., (2020) [96] Dogs (16) CBD oil (2 and 8 mg/kg) or placebo oil every 12 h. ...
Full-text available
As cannabis-derived products have become more available, veterinarians are seeing more cases of toxicosis. In addition, animal owners are having an increasing interest in using these products for their pets. This review looks at the situation in Europe and North America, the different types of cannabis and cannabis-derived products with historical examples of use in animals, and the cannabis industry. The existing regulatory framework for use in humans and animals as medicines and/or supplements was examined. Finally, a review of the clinical indications for which medicinal cannabis is authorised, a discussion of toxicosis, and recommendations and warnings around medical cannabis use are presented.
... Cannabinoids have been shown to play a role in neurogenic and inflammatory pain by a variety of mechanism of actions on various receptors and pathways (104). The use of cannabinoids in veterinary medicine is still relatively new, nevertheless there have been multiple clinical trials published that show promising results for its efficacy for pain relief of OA (70,(105)(106)(107)(108)(109)(110). The existing studies conducted have been product specific, in that the researched product has a specific cannabinoid and terpenoid profile. ...
Full-text available
The Canadian consensus guidelines on OA treatment were created from a diverse group of experts, with a strong clinical and/or academic background in treating OA in dogs. The document is a summary of the treatment recommendations made by the group, with treatments being divided into either a core or secondary recommendation. Each treatment or modality is then summarized in the context of available research based support and clinical experience, as the treatment of OA continues to be a multimodal and commonly a multidisciplinary as well as individualized approach. The guidelines aim to help clinicians by providing clear and clinically relevant information about treatment options based on COAST defined OA stages 1–4.
... The rapidly growing market for cannabis-based products and the widespread acceptance of these products as an effective treatment for pets have challenged veterinarians to gather as much scientific data as possible on the use of CBDs (21)(22)(23). Moreover, emerging scientific evidence supports the use of CBDs in dogs and cats (33)(34)(35)(36)(37)(38)(39)(40). ...
Full-text available
The aim of this study was to assess the personal experience and attitudes of Slovenian pet owners regarding cannabinoid (CBD) use and to identify the predictors of the first use and reuse of CBDs in dogs and cats. We hypothesized that positive attitudes toward CBDs, postmodern health values, and personal experience would be significant predictors of CBD use in animals. An open online survey targeted randomly selected Slovenian dog and cat owners, regardless of their experience with cannabis products. The questionnaire consisted of six sections related to demographic data and personal experience with CBD use, information about the participant's animal, experience with CBD use in the participant's animal, reasons for not using CBDs in their animal, attitudes toward CBD use in dogs and cats, and postmodern health values. Descriptive statistics were performed to analyze demographics, personal experience with CBD use, and experience with CBD use in dogs and cats. Hierarchical multiple regression using the enter method was performed to analyze the important predictors of CBD use. A total of 408 completed questionnaires were included in the statistical analysis. A substantial proportion (38.5%) of owners had already used CBDs to treat their animal. Positive attitudes and previous personal experience were significant ( p < 0.05) predictors of first use and reuse of CBDs in pets, while postmodern health values were not. In conclusion, the decision to use CBDs for medicinal purposes is based on acquired information and personal experience. Veterinarians should be informed and familiar with CBDs as a treatment option. However, further research is essential to establish the use of CBDs in veterinary medicine. Improved laws and regulations are also needed to ensure that only high-quality medications are prescribed to dogs and cats.
Background: Cannabidiol (CBD) and cannabidiolic acid (CBDA) are reported to have antinociceptive, immunomodulatory and anti-inflammatory actions. Objectives: To determine if CBD/CBDA is an effective therapy for canine atopic dermatitis (cAD). Animals: Thirty-two privately owned dogs with cAD. Materials and methods: Prospective, randomised, double-blinded, placebo-controlled study. Concurrent therapies were allowed if remained unchanged. Dogs were randomly assigned to receive either 2 mg/kg of an equal mix of CBD/CBDA (n = 17) or placebo for 4 weeks. On Day (D)0, D14 and D28, Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) and pruritus Visual Analog Scale (pVAS) scores were determined by investigators and owners, respectively. Complete blood count, serum biochemistry profiles and cytokine bioassays were performed on serum collected on D0 and D28. Results: There was no significant difference in CADESI-04 from D0 to D14 (p = 0.42) or D28 (p = 0.51) in either group. pVAS scores were significantly lower for the treatment group at D14 (p = 0.04) and D28 (p = 0.01) and a significant change in pVAS from baseline was seen at D14 (p = 0.04) and not D28 (p = 0.054) between groups. There was no significant difference in serum levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein - 1, IL-31 or IL-34 between groups at D0 or D28. Elevated alkaline phosphatase was observed in four of 17 treatment group dogs. Conclusions and clinical relevance: CBD/CBDA as an adjunct therapy decreased pruritus, and not skin lesions associated with cAD in dogs.
Cannabidiol (CBD) products have gained popularity among horse owners despite limited evidence regarding pharmacokinetics. The purpose of this study was to describe the pharmacokinetic profile of multiple doses of an orally administered cannabidiol product formulated specifically for horses. A randomized 2-way crossover design was used. Seven horses received 0.35 or 2.0 mg/kg CBD per os every 24h for 7 total doses, separated by a 2-week washout. Plasma CBD and delta-9-tetrahydrocannabinol (THC) were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) daily through day 10, then on day 14 after beginning CBD administration. On the final day of CDB administration, plasma CBD and THC were quantified at multiple times. After administration of 0.35 mg/kg of CDB, the Cmax of CBD was 6.6 ± 2.1 ng/mL while Tmax was 1.8 ± 1.2 h, whereas the Cmax for THC was 0.7 ± 0.6 ng/mL with a Tmax of 2.5 ± 1 h. After administration of 2.0 mg/kg of CBD, the Cmax of CBD was 51 ± 14 ng/mL with a mean Tmax of 2.4 ± 1.1 h and terminal phase half-life of 10.4 ± 6 h, whereas the Cmax of THC was 7.5 ± 2.2 ng/mL with a Tmax of 2.9 ± 1.1 h. Oral administration of a cannabidiol product at 0.35 mg/kg or 2.0 mg/kg once daily for 7 days was well-tolerated. Based on plasma CBD levels obtained, dose escalation trials in the horse evaluating clinical efficacy at higher mg/kg dose rates are indicated.
Cannabidiol (CBD) has gained widespread popularity as a treatment for osteoarthritis (OA) in pets; however, there is minimal scientific evidence regarding safe and effective dosing. This study determined plasma and tissue pharmacokinetics after oral CBD oil suspension administration in Hartley guinea pigs (Cavia porcellus), which spontaneously develop OA at 3 months of age. Ten, 5-month-old, male guinea pigs were randomly assigned to receive 25 (n = 5) or 50 mg/kg (n = 5) CBD oil once orally. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 h timepoints. Open-field enclosure monitoring revealed no adverse effects. After euthanasia, stifle cartilage and infrapatellar fat pads were collected to quantitate CBD. CBD concentrations were determined using a validated liquid chromatography-mass spectrometry method, and pharmacokinetic parameters were calculated using noncompartmental analysis. The area under the plasma concentration-versus-time curve was 379.5 and 873.7 h*ng/mL, maximum plasma concentration was 42 and 96.8 ng/mL, time to maximum plasma concentration was 1.6 and 4.8 h, and terminal phase half-life was 8.1 and 10.8 h for the 25 and 50 mg/kg doses, respectively. CBD was detected in joint tissues of all animals. Further studies, including work in female guinea pigs, are needed to determine the efficacy of CBD for OA.
Medical use of Cannabis (or hemp) began thousands of years ago. In the 20th century, mechanisms of action were demonstrated with the discovery of its active substances, the phytocannabinoids, and its pharmacological targets, the endocannabinoid system. This system is composed of receptors, endogenous substances, and enzymes, and it participates in the modulation of physiological mechanisms in several species, including dogs. Studies indicate that changes in this system may contribute to the genesis of some diseases. Therefore, the use of substances that act on its components may help in the treatment of these diseases. The main phytocannabinoids described are Δ9−tetrahydrocannabinol (THC) and cannabidiol (CBD). In humans, the benefits of using CBD in several diseases have been demonstrated. The popularization of this type of treatment has also reached veterinary medicine, which on one hand was related to an increase in adverse event records, but on the other also allowed reports of anecdotal evidences of its effectiveness and safety in animals. Clinical studies published so far indicate that the use of CBD in dogs can be safe at given doses and can contribute to osteoarthritis and idiopathic epilepsy treatments. Clinical and pre-clinical studies and case reports were reviewed in this report to identify the main characteristics of hemp-based therapies in dogs, including its pharmacokinetics, pharmacodynamics, safety, and efficacy in the treatment of diseases.
The endocannabinoid system (ECS) is involved in all aspects of the pathophysiological processes of pain. The nociceptive pathway includes transduction, transmission, modulation and perception, with the ECS playing an essential role in both afferent and efferent pain stimuli. Interest in using cannabinoid products for pain is of continued research and clinical interest. Data in human, lab animals and now companion animals does show efficacy for use especially for chronic pain states. The relative therapeutic index appears favorable and the addition of these compounds at least gives veterinary practitioners another tool to consider for pain management. Careful consideration is important for product selection, not only quality but cannabinoid and terpene profiles that may best fit a patient’s pain state. The clinically relevant science of medical cannabinoids for veterinary patients is in its infancy but is very encouraging. We now have our first well conducted clinical trials with more underway. The future looks promising for medical cannabinoids, specifically CBD, for the treatment of pain conditions in our patients. Given the numerous nuances of products and the ECS dosing for pain, both acute and chronic, dosing should be done in an escalating manner. Reasonable considerations for CBD dominant or isolate products can start as low as 0.5 mg/kg by mouth twice to three times a day and increase significantly until the therapeutic benefit is appreciated.
Full-text available
The use of cannabis for animal species is an area of growing interest, largely due to the therapeutic benefits being observed for humans and animals in the era of cannabis legalization. The close relationship humans have with their pets and other veterinary species has led to a renewed interest in the possibility and promise of cannabis to treat similar health issues in the animal community. This chapter explores the literature available on cannabis, its interactions with the endocannabinoid system, and how animal species interact with various formulations and cannabis treatments. A brief overview of the biology, chemistry, and history of cannabis is discussed with the relevance to veterinary species in mind. The pharmacologically active components are discussed with both anecdotal and objective, evidence-based, and clinical data.
Full-text available
Due to the myriad of laws concerning cannabis, there is little empirical research regarding the veterinary use of cannabidiol (CBD). This study used the Veterinary Information Network (VIN) to gauge US veterinarians' knowledge level, views and experiences related to the use of cannabinoids in the medical treatment of dogs. Participants (n = 2130) completed an anonymous, online survey. Results were analyzed based on legal status of recreational marijuana in the participants' state of practice, and year of graduation from veterinary school. Participants felt comfortable in their knowledge of the differences between Δ9-tetrahydrocannabinol (THC) and marijuana, as well as the toxic effects of marijuana in dogs. Most veterinarians (61.5%) felt comfortable discussing the use of CBD with their colleagues, but only 45.5% felt comfortable discussing this topic with clients. No differences were found based on state of practice, but recent graduates were less comfortable discussing the topic. Veterinarians and clients in states with legalized recreational marijuana were more likely to talk about the use of CBD products to treat canine ailments than those in other states. Overall, CBD was most frequently discussed as a potential treatment for pain management, anxiety and seizures. Veterinarians practicing in states with legalized recreational marijuana were more likely to advise their clients and recommend the use of CBD, while there was no difference in the likelihood of prescribing CBD products. Recent veterinary graduates were less likely to recommend or prescribe CBD. The most commonly used CBD formulations were oil/extract and edibles. These were most helpful in providing analgesia for chronic and acute pain, relieving anxiety and decreasing seizure frequency/severity. The most commonly reported side-effect was sedation. Participants felt their state veterinary associations and veterinary boards did not provide sufficient guidance for them to practice within applicable laws. Recent graduates and those practicing in states with legalized recreational marijuana were more likely to agree that research regarding the use of CBD in dogs is needed. These same groups also felt that marijuana and CBD should not remain classified as Schedule I drugs. Most participants agreed that both marijuana and CBD products offer benefits for humans and expressed support for use of CBD products for animals.
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Objectives: The objectives of this study were to determine basic oral pharmacokinetics, and assess safety and analgesic efficacy of a cannabidiol (CBD) based oil in dogs with osteoarthritis (OA). Methods: Single-dose pharmacokinetics was performed using two different doses of CBD enriched (2 and 8 mg/kg) oil. Thereafter, a randomized placebo-controlled, veterinarian, and owner blinded, cross-over study was conducted. Dogs received each of two treatments: CBD oil (2 mg/kg) or placebo oil every 12 h. Each treatment lasted for 4 weeks with a 2-week washout period. Baseline veterinary assessment and owner questionnaires were completed before initiating each treatment and at weeks 2 and 4. Hematology, serum chemistry and physical examinations were performed at each visit. A mixed model analysis, analyzing the change from enrollment baseline for all other time points was utilized for all variables of interest, with a p ≤ 0.05 defined as significant. Results: Pharmacokinetics revealed an elimination half-life of 4.2 h at both doses and no observable side effects. Clinically, canine brief pain inventory and Hudson activity scores showed a significant decrease in pain and increase in activity (p < 0.01) with CBD oil. Veterinary assessment showed decreased pain during CBD treatment (p < 0.02). No side effects were reported by owners, however, serum chemistry showed an increase in alkaline phosphatase during CBD treatment (p < 0.01). Clinical significance: This pharmacokinetic and clinical study suggests that 2 mg/kg of CBD twice daily can help increase comfort and activity in dogs with OA.
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Cannabidiol (CBD)-infused pet treats are becoming a huge market for pet owners as they turn to this supplement for a non-traditional therapeutic option. However, CBD's short-term or long-term effects on companion animals remain largely unknown. We conducted a targeted literature search about the mechanism, efficacy, and safety of these treats in order to highlight the gaps in knowledge of CBD products. This communication elucidates some of the common misperceptions regarding CBD pet treats, and proposes suggestions for further research based on the status of knowledge in this field. With the emergence of these treats and identified gaps in knowledge, the veterinary research community needs to determine the pharmacokinetic parameters for short- and long-term duration and conduct rigorous clinical trials to assess CBD's and other cannabinoids' impact on various diseases.
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Cannabinoids are a group of compounds that mediate their effects through cannabinoid receptors. The discovery of Δ9-tetrahydrocannabinol (THC) as the major psychoactive principle in marijuana, as well as the identification of cannabinoid receptors and their endogenous ligands, has led to a significant growth in research aimed at understanding the physiological functions of cannabinoids. Cannabinoid receptors include CB1, which is predominantly expressed in the brain, and CB2, which is primarily found on the cells of the immune system. The fact that both CB1 and CB2 receptors have been found on immune cells suggests that cannabinoids play an important role in the regulation of the immune system. Recent studies demonstrated that administration of THC into mice triggered marked apoptosis in T cells and dendritic cells, resulting in immunosuppression. In addition, several studies showed that cannabinoids downregulate cytokine and chemokine production and, in some models, upregulate T-regulatory cells (Tregs) as a mechanism to suppress inflammatory responses. The endocannabinoid system is also involved in immunoregulation. For example, administration of endocannabinoids or use of inhibitors of enzymes that break down the endocannabinoids, led to immunosuppression and recovery from immune-mediated injury to organs such as the liver. Manipulation of endocannabinoids and/or use of exogenous cannabinoids in vivo can constitute a potent treatment modality against inflammatory disorders. This review will focus on the potential use of cannabinoids as a new class of anti-inflammatory agents against a number of inflammatory and autoimmune diseases that are primarily triggered by activated T cells or other cellular immune components.
The legal market for recreational and medicinal cannabis for human consumption is growing worldwide. At the same time, marketing of cannabis products for use in pets is expanding. Yet, there is little research exploring the effects of cannabis use in veterinary medicine. This study used an anonymous, online survey to assess Canadian pet owners' reasons for purchasing cannabis products for their dogs, and their perceptions regarding efficacy of these treatments. Owners purchased cannabis products for treatment of pain, inflammation, and anxiety in dogs, and perceived these preparations to be equally or more effective than conventional medications. Most owners reported only minimal side effects in their dogs. Despite indicating comfort in discussing canine cannabis administration with their veterinarian, most owners relied on commercial websites for product information. The main reasons for choosing cannabis products were the ability to use as an adjuvant to other therapies, and the perception of it being a natural substance. Given this information, it is incumbent upon veterinarians to appropriately counsel their clients, and also to advocate for evidence-based studies to evaluate the efficacy of cannabis use in non-human species.
Pet exposure to marijuana-containing products—both recreational and medicinal—along with exposure to extracts such as cannabidiol is increasing in conjunction with greater accessibility. Cannabis products are even sold for use in pets. In addition, exposure to illegal synthetic cannabinoids remains concerning. Veterinarians need to be able to recognize associated clinical signs and understand when cases have the potential for severity. This article provides a brief history of cannabis along with a review of the endocannabinoid system, common cannabis products, expected clinical signs, and medical treatment approaches associated with cannabis exposure in pets.
Cannabidiol (CBD), a nonpsychoactive marijuana constituent, was recently shown as an oral antihyperalgesic compound in a rat model of acute inflammation. We examined whether the CBD antihyperalgesic effect could be mediated by cannabinoid receptor type 1 (CB1) or cannabinoid receptor type 2 (CB2) and/or by transient receptor potential vanilloid type 1 (TRPV1). Rats received CBD (10 mg kg−1) and the selective antagonists: SR141716 (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) for CB1, SR144528 (N-[(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3 carboxamide) for CB2 and capsazepine (CPZ) for TRPV1 receptors. The intraplantar injection of carrageenan in rats induced a time-dependent thermal hyperalgesia, which peaked at 3 h and decreased at the following times. CBD, administered 2 h after carrageenan, abolished the hyperalgesia to the thermal stimulus evaluated by plantar test. Neither SR141716 (0.5 mg kg−1) nor SR144528 (3 and 10 mg kg−1) modified the CBD-induced antihyperalgesia; CPZ partially at the lowest dose (2 mg kg−1) and fully at the highest dose (10 mg kg−1) reversed this effect. These results demonstrate that TRPV1 receptor could be a molecular target of the CBD antihyperalgesic action. British Journal of Pharmacology (2004) 143, 247–250. doi:10.1038/sj.bjp.0705920