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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®
          
      
         
        
US veterinarians’ knowledge, experience, and perception
regarding the use of cannabidiol for canine medical conditions.
Front Vet Sci
             
for pets: gaps in our knowledge. Toxicol Commun
          
Cannabis in veterinar y medicine: cannabinoid therapies for
animals. In: Gupta RC, Srivastava A, Lall R, eds. Nutraceuticals
in veterinar y medicine. Switzerland: Springer International
        
use and perceptions of cannabis produc ts. J Am Holist Vet Med
         
        
osteoarthritic dogs. Front Vet Sci
          
      
effect of the nonpsychoactive cannabinoid, cannabidiol,
       Br J Pharmacol.
9. Nagarkatti P, Pandey R, Rieder SA, Hegde VL, Nagarkatti M.
      Future Med
       
synthetic cannabinoids, and cannabidiol in dogs and cats.
Vet Clin North Am Small Anim Pract
      
NAVC Clinician’s Brief. 
         
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
... At present, only a limited number of studies have evaluated the efficacy and safety of CBD in dogs with OA. These prior studies unanimously reported a few adverse events, which were not serious ones (18, [22][23][24][25][26][27]. The literature contains several review articles; however, those previous reviews did not perform meta-analysis (9,28,29). ...
... A total of 73 articles were identified from the search. Five studies investigating the efficacy and safety of CBD products were included (18, 22,24,26,27). The study selection flow is presented in Figure 1. ...
... Two studies were parallel RCTs (22,27), while the other two were cross-over RCTs (18, 26). One study was a single-arm study (24). Participating dogs were client-owned dogs with OA, of which three studies specifically included only dogs with radiographic-confirmed OA (18, 22,26). ...
Full-text available
Introduction Canine osteoarthritis (OA) is a degenerative disease with chronic inflammation of internal and external joint structures in dogs. Cannabis spp. contains cannabidiol (CBD), a substance known for various potential indications, such as pain relief and anti-inflammatory in various types of animals, including dogs with OA. As CBD is increasingly in the spotlight for medical use, we aimed to perform a systematic review and meta-analysis to evaluate the efficacy and safety of CBD in treating canine OA. Methods We searched PubMed, Embase, Scopus, and CAB Direct for animal intervention studies investigating the effects of CBD for canine OA from database inception until February 28, 2023. Study characteristics and findings were summarized. A risk of bias in the included studies was assessed. Meta-analyses were performed using a random-effects model to estimate the effects of CBD on pain scores (0–10), expressed as mean difference (MD) and 95% confidence interval (95% CI). Certainty of evidence was assessed using GRADE. Results Five articles were included, which investigated the effects of CBD in 117 dogs with OA. All studies were rated as having a high risk of bias. CBD products varied substantially, i.e., oral full-spectrum CBD oil in four studies, and isolated CBD oil and liposomal CBD oil in another study. Treatment duration varied from 4–12 weeks. Meta-analyses of three studies found that, in dogs with OA, treatment with oral full-spectrum CBD oil may reduce pain severity scores (MD; −0.60, 95% CI; −1.51 to 0.31, I ² = 45.64%, p = 0.19) and pain interference scores (MD; −1.52, 95% CI; −3.84 to 0.80, I ² = 89.59%, p = 0.20) but the certainty of evidence was very low. CBD is generally considered safe and well-tolerated in the short-run, with few mild adverse events observed, such as vomiting and asymptomatic increase in alkaline phosphatase level. Conclusion CBD is considered safe for treating canine OA. CBD may reduce pain scores, but the evidence is very uncertain to conclude its clinical efficacy. High-quality clinical trials are needed to further evaluate the roles of CBD in canine OA.
... Besides the described signs, a common finding during prolonged treatment with CBD in some but not all dogs across clinical studies is the elevation of alkaline phosphatase enzyme (ALP) activity, which generally return to baseline values after a washout period (25, 35,54,56,58,67,82,88,89,93). This alteration is usually attributed to a reversible upregulation of cytochrome p450-mediated oxidative metabolism of the liver (97,98). ...
... In terms of efficacy, most studies have been conducted to test the ability of CBD to relieve pain in dogs with osteoarthritis. Albeit in one study no differences were noted between groups for any of the recorded outcome measures (57), from results obtained in all other studies CBD seemed able to significantly reduce pain and increase the activity of dogs, thus improving their quality of life (24, 25, [54][55][56]. The only study where the role of CBD in acute postoperative pain following a TPLO was investigated did not give satisfactory results (58). ...
... One last consideration deserves to be made. In the studies cited in this review, the CBD formulations used were all different and described either as CBD hemp oil (88,89), CBD-predominant full-spectrum hemp oil (54,69), hemp-derived CBD oil (55), CBD-purified hemp oil (24), CBD-purified Cannabis extract (35), CBD-infused hemp oil (26, 67), CBD enriched Cannabis extract (27), CBD based oil (75), CBD-containing broad-spectrum hemp oil (83), galenic CBD (29, 30,56), CBD/CBDA-predominant hemp oil (25, 34, 57), CBD/CBDA rich hemp product (58,68), CBD industrial hemp extract incorporated into treats (74,84), CBD/CBDA oil in soft chew (28), CBD/CBDA-rich hemp extract in gelatine capsules (33, 82), pure CBD in capsules (31), microencapsulated CBD oil beads (26), CBD-infused oil cream (26). Besides the large variability of formulations, in some cases the presence of trace amounts of other cannabinoids was specified, while most studies did not report whether other phytocannabinoids (such as cannabichromene, cannabigerol, and cannabinol, among others) or other chemical components of hemp (such as terpenes, triterpenes, and flavonoids) were present. ...
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In the last 5 years, interest has grown in using phytocannabinoids, particularly cannabidiol (CBD), in veterinary medicine to treat several pathologies, including pain, epilepsy, anxiety, nausea, anorexia, skin lesions, and even some types of cancer, among others. Indeed, due to a positive perception of CBD use, many pet owners are increasingly requesting this option to relieve their pets, and many veterinarians are exploring this possibility for their patients. Besides the widespread empiric use of CBD in pets, the research is trying to obtain proof of its efficacy and lack of adverse effects and to know its pharmacokinetics to define an appropriate posology. This review summarizes all data published so far about the canine pharmacokinetics, efficacy, and tolerability of CBD and cannabidiolic acid (CBDA). Despite a certain number of available pharmacokinetic studies, the kinetic profile of CBD has yet to be fully known, probably because of the very different experimental conditions. In terms of efficacy, most studies have tested CBD’ ability to relieve osteoarthritic pain. In contrast, few studies have evaluated its role in epilepsy, behavioral disorders, and skin lesions. From obtained results, some evidence exists supporting the beneficial role of CBD. Nevertheless, the limited number of published studies and the occurrence of bias in almost all require caution in interpreting findings. From tolerability studies, CBD’ side effects can be classified as mild or unremarkable. However, studies were prevalently focused on short- to medium-term treatment, while CBD is usually employed for long-term treatment. Further studies are warranted to define better whether CBD could be a valid adjunct in canine treatment.
... Se concluyó que la adición de un aceite de CBD derivado de cáñamo parece afectar positivamente a los perros con dolor crónico desadaptativo al disminuir su dolor, mejorando así su movilidad y calidad de vida. La reducción de la dosis de gabapentina puede ser el resultado de cambios en la analgesia y/o sedación con la adición del extracto de aceite de cáñamo [19]. ...
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Introducción: la marihuana (Cannabis sativa L.)es una planta originaria de Asia cada vez más reconocida por su valor terapéutico en la medicina humana y veteri-naria.Contiene una gran cantidad de componentes entre los que destacan los fito-cannabinoides, de los cuales los más representativos son el delta-9-tetrahidrocanna-binol (THC) y Cannabidiol (CBD) que se acoplan respectivamente a los receptores CB1 y CB2 en el sistema endocannabinoide que es un sistema neurotransmisor entre células que regula varios procesos en los vertebrados como memoria, dolor, inflamación, apetito y procesos inmunológicos entre otros. Objetivo: realizar una síntesis narrativa del sistema endocannabinoide y cannabidiol en el manejo del dolor en perros, a partir de la búsqueda de publicaciones en bases de datos electrónica PubMed, NCBI, SciELO, Science Direct, Dialnet, Google y Google Académico. Resultados: el CBD es el principal cannabinoide utilizado en la terapia del manejo del dolor en perros por sus propiedades analgésicas y carencia de efectos psicoactivos. Conclusión: se evidencia la necesidad de realizar más investigaciones con ensayos clínicos controlados sobre el uso terapéutico del cannabidiol, que tengan validez interna y externa, con poblaciones más significativas en la especie de interés.
... Additionally, a cannabinoid-rich hemp oil made from hemp seems to have a favorable impact on dogs with chronic maladaptive pain by reducing their pain and enhancing their mobility and quality of life. The inclusion of the hemp oil extract may alter analgesia and/or sedation, which could explain why the gabapentin dosage was decreased (Kogan, Hellyer, and Downing 2020) ...
Osteoarthritis (OA) is a common joint disease and has been studied extensively in recent years as no promising therapy available so far for its treatment and remains a great challenge for health care specialists. Although the identification of some major mechanisms that contribute to this disease suggests a plethora of bioactive agents in tackling the associated complications yet OA's pathophysiology is still poorly understood owing to complex mechanistic changes observed. Experimental research is now exploring a wide range of therapeutically effective agents in an effort to find a way to repair OA-related joint degeneration and halt it from getting worse. Data was acquired and reviewed from most relevant and recent studies. This review summarizes the studies that are currently available and focuses on how various unconventional functional oils affect osteoarthritis and the affected joint tissues. An analysis of the recent scientific literature allowed us to highlight the potential anti-arthritic properties of edible oils and their main constituents, which seems to suggest an interesting new potential therapeutic application. Due to eccentric nature of OA, it is necessary to concentrate initially on the management of symptoms. The evidence supporting functional oils chondroprotective potential is still accumulating, underpinning a global need for more sustainable natural sources of treatment. More clinical research that focuses on the consequences of long-term treatment, possible negative effects, and epigenetic implications is necessary to get optimistic results. However, different animal or clinical studies suggest that linolenic and linoleic fatty acids decreased chondrocyte oxidative stress, cartilage breakdown, and expression of inflammatory markers. Distinct fatty acids along with minor components of oils also reduced the generation of prostaglandins and decreased oxidative stress. Furthermore, the potential roles of the main components of edible oils and possible negative results (if any) are also reported. While no severe side effects have been reported for any edible oils. Overall, these studies identify and support the use of functional oils as an adjuvant therapy for the management of OA and as a means of symptomatic alleviation for OA patients. However, to prove the effectiveness or to draw precise conclusions, high-quality clinical trials are required.
... For this reason and due to the involvement of the endocannabinoid system in the pain pathways, several clinical studies investigated the efficacy of cannabis derivatives, in particular cannabidiol (CBD), on osteoarthritic chronic pain in dog. The oral administration of different CBD oils (as a sole treatment or as add-on to other analgesic drugs), generally at doses ranging between 1 and 2 mg/kg every 12 h for at least 4 weeks, resulted in a significant reduction of pain scores, an improvement of mobility and of quality of life as well as a decrease of inflammatory serum biomarkers (4)(5)(6)(7). ...
Full-text available
Introduction In the last few years, different formulations containing cannabidiol (CBD) were tested with regard to its efficacy on chronic pain, refractory epilepsy, anxiety, aggressive behavior and atopic dermatitis in dogs. CBD is generally administered orally, but its low bioavailability, probably due to a first-pass metabolism, represents a great limitation. The aim of this study was to evaluate if CBD bioavailability increases after oral transmucosal administration (OTM) compared to oral treatment. Methods Twelve dogs diagnosed with mild chronic pain were enrolled in the study and treated once orally or OTM (6 dogs/group) with a pure CBD in oil formulation at a dosing rate of 1 mg/kg b.w. At prefixed time points, blood samples were collected to define CBD plasma concentrations vs. time profiles, and the main pharmacokinetics parameters were obtained by non-compartmental model. Results CBD Cmax, Tmax, terminal half-life and AUC 0 − t were 206.77 ± 167 and 200.33 ± 158.33 ng/mL, 2.17 ± 0.98 and 1.92 ± 1.11 h, 2.67 ± 0.53 and 2.62 ± 0.64 h, 647.51 ± 453.17, and 536.05 ± 370.21 h * ng/mL, following oral and OTM administration, respectively. No significant difference in pharmacokinetic parameters were observed between treatments. Discussion The OTM administration did not increase cannabidiol bioavailability compared to oral treatment. The almost perfectly superimposable mean plasma concentrations of cannabidiol following the two treatments suggests that CBD is not able to be adsorbed by the oral mucosa or that its absorption is very scarce, and that CBD is swallowed and absorbed in the gastrointestinal tract.
Objective To determine the chronic effects of oral cannabidiol (CBD) use on tear production, intraocular pressure (IOP), and concentration of CBD in tears of healthy dogs. Animals Studied Eighteen healthy research Beagles. Procedures This was a masked, placebo‐controlled, randomized prospective study. Eighteen dogs were randomly assigned to three groups (six dogs per group) based on daily dosage of oral MCT oil (placebo), CBD 5 mg/kg, and CBD 10 mg/kg. Schirmer tear test (STT‐1) and IOP were measured twice daily (7 am and 7 pm) every 4 weeks for 36 weeks. Week 36 tears were collected and analyzed for CBD concentrations (ng/mL) using liquid chromatography/mass spectrometry. A mixed linear model was used as the statistical method and p ‐value <.05 was considered significant. Results No significant differences were found between placebo vs. 5 mg/kg vs. 10 mg/kg for STT‐1 or IOP (AM and PM). CBD was detected in 10 out of 11 (91%) viable tear samples receiving 5 mg/kg or 10 mg/kg dosages. One sample in the 5 mg/kg group had inadequate tear volume for analysis. The CBD concentration in tears was at or below the lower limit of quantification in placebo group, 4.12–11.2 ng/mL for the 5 mg/kg group, and 6.22–152 ng/mL for the 10 mg/kg group. Conclusions Long‐term administration of oral CBD in healthy research beagles demonstrates a favorable safety profile regarding ocular tolerability. Oral CBD administration does not appear to affect tear production or IOP over a 36‐week period. This is the first canine study positively identifying concentrations of CBD in tears following oral administration.
Fossil fuel supplies are becoming scarce as a result of the growing world’s population. The increasing use of fossil fuels also pose a threat to ecosystem. Renewable energy sources should be revived in order to meet future energy demands, and minimize the adverse effects on environment. Biofuels and biochemicals can be made from a wide variety of lignocellulosic biomass, which has been studied for decades. Several useful bioproducts can now be made from hemp's lignocellulosic biomass (cellulose, hemicellulose, lignin, protein, and others). Hemp has considerable commercial potential as it can be used in biorefinery applications for the production of bioethanol, biodiesel, biohydrogen, biogas, organic acids, biomaterials, bio-oil and various pharmaceutical and nutraceuticals compounds. Effective conversion of lignocellulosic biomass to value-added bioproducts for biorefinery and other potential applications relies on a wide range of pretreatment processes. This article aims to highlight recent developments in hemp lignocellulosic conversion technologies for biorefinery applications and other value-added products development with the goal of bolstering future industries in a manner that is more environmentally friendly and secure.
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Objective: To determine the pharmacokinetics of 8 cannabinoids and 5 metabolites after oral administration of single and multiple doses of a cannabidiol (CBD)-cannabidiolic acid (CBDA)-rich hemp extract to orange-winged Amazon parrots (Amazona amazonica) as well as to evaluate the extract's adverse effects. Animals: 12 birds. Procedures: Based on pilot studies, a single-dose study based on 30/32.5 mg/kg of cannabidiol/cannabidiolic acid of a hemp extract was administered orally to 8 fasted parrots, and 10 blood samples were collected over 24 hours after administration. After a 4-week washout period, the hemp extract was administered orally to 7 birds at the previous dose every 12 hours for 7 days, and blood samples were collected at the previous time points. Cannabidiol, Δ9-tetrahydrocannabinol, cannabinol, cannabichromene, cannabigerol, cannabidiolic acid, cannabigerolic acid, Δ9-tetrahydrocannabinolic acid, and 5 specific metabolites were measured by liquid chromatography-tandem/mass-spectrometry, and pharmacokinetic parameters were calculated. Adverse effects and changes in the plasma biochemistry and lipid panels were evaluated. Results: Pharmacokinetic parameters for cannabidiol, cannabidiolic acid, Δ9-tetrahydrocannabinol, Δ9-tetrahydrocannabinolic acid, and the metabolite 11-hydroxy-9-tetrahydrocannabinol were established. For the multiple-dose study, cannabidiol/cannabidiolic acid mean Cmax was 337.4/602.1 ng/mL with a tmax of 30 minutes and a terminal half-life of 8.6/6.29 hours, respectively. No adverse effects were detected during the multidose study. The predominant metabolite was 11-hydroxy-9-tetrahydrocannabinol. Clinical relevance: Twice daily oral administration of the hemp extract based on 30 mg/kg/32.5 mg/kg of cannabidiol/cannabidiolic acid was well tolerated and maintained plasma concentrations considered to be therapeutic in dogs with osteoarthritis. Findings suggest different cannabinoid metabolism from mammals.
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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.
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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