Use of CBD in pain
management, arthritis etc
Literature review:
Yu CHJ, Rupasinghe HPV 2021, ‘Cannabidiol-based natural health products for companion animals: Recent advances in the management of anxiety, pain, and inflammation’, Research in Veterinary Science, vol. 140, pp.38-46
There is preliminary evidence to support the analgesic properties of CBD in treating chronic canine osteoarthritis & managing pain
How does CBD help with pain?
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Endogenous endocannabinoids AEA and 2-AG are one group of the body’s first responders to tissue injury, where these molecules activate cannabinoid receptors, which regulate neuroimmune interactions and modulate pain by various methods.
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AEA suppresses pain by 1) activating CB1 for inhibition of pain signals at the synapse, 2) becoming directly transformed by COX-2 enzyme into pain-relieving prostamides, and 3) activating CB2 and other receptors for the interference of inflammation
(Hill et al., 2017; Silver, 2019)
To date, there are multiple studies on CBD supplementation in managing chronic pain in dogs. There are no studies in CBD and feline pain, whether acute or chronic.
Studies on dogs (see summaries below)
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Gamble et al., 2018
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Kogan et al., 2020
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Martello et al., 2019
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Mejia et al., 2021
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Verrico et al., 2020
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Brioschi et al, 2020
Anti-inflammatory action
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CB2 receptors are present on the surface of many immune cells, and various experimental models have demonstrated the immunomodulatory effects of the endocannabinoid system.
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CBD attenuates inflammation by (1) suppressing pro-inflammatory cytokines and chemokines such as TNF-alpha, GM-CSF, IFN-gamma, IL-10, and IL-6, etc., (2) limiting immune cell infiltration, (3) inducing T-cell apoptosis, (4) inhibiting T-effector cell proliferation, and (5) promoting T-regulatory cell proliferation
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There are currently no canine or feline data available on CBD use and treatment of inflammation. Extrapolating from rodent studies.
References:
Hill, KP, Palastro, MD, Johnson, B & Ditre, JW 2017, ‘Cannabis and pain: a clinical review, Cannabis Cannabinoid Research, vol. 2, pp. 96–104.
Silver RJ 2019, ‘The Endocannabinoid System of Animals’, Animals (Basel), vol. 16, no. 9, pp. 686
N= 6 studies reviewed
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Gamble et al, 2018 - OA (see below)
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Brioschi et al, 2020 - OA (see below)
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Verrico et al, 2020 - OA (see below)
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Mejia et al, 2020 - OA (see below)
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McGrath et al, 2019 - epilepsy (see Epilepsy page)
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Corsetti et al, 2021 - behaviour (see Behaviour page)
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All studies used cannabidiol (CBD) oil in monotherapy or in combination with other drugs.
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Studies used CBD at 2 or 2.5 mg/kg BID PO during 4 or 6 weeks, and compared CBD with placebo (n = 5).
Findings:
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CBD significantly reduced pain and increased activity in dogs with osteoarthritis (n = 3).
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CBD significantly reduced the frequency of seizures in dogs with epilepsy (n = 1)
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CBD significantly reduced the aggressive behavior of dogs (n = 1).
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CBD was well tolerated with mild adverse effects.
Studies on dogs:
Design: randomized, placebo-controlled, owner and veterinarian double-blind, cross-over trial.
Aim: to determine basic oral pharmacokinetics, and assess safety and analgesic efficacy of a CBD based oil in dogs with OA.
Sample: 16 client-owned dogs with clinically and radiographically confirmed evidence of osteoarthritis were used
Intervention: During the trial, dogs were only allowed to receive NSAIDs, fish oil, and/or glucosamine/chondroitin sulfate without any change in these medications for 4 weeks prior to or during the 10-week study period as standard of care for the disease process. Other analgesic medications used, such as gabapentin and tramadol, were discontinued at least 2 weeks prior to enrolment.
Method:
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Single-dose pharmacokinetics was performed using two different doses of CBD enriched (2 and 8mg/kg) oil.
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Then a randomized placebo-controlled, veterinarian, and owner blinded, cross-over study was conducted. Dogs received each of two treatments: CBD oil (2mg/kg) or placebo oil every 12 h. Each treatment lasted for 4 weeks with a 2-week washout period.
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Baseline veterinary assessment and owner questionnaires were completed before initiating each treatment and at weeks 2 and 4.
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Hematology, serum chemistry and physical examinations were performed at each visit.
Results:
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Pharmacokinetics revealed an elimination half-life of 4.2 h at both doses and no observable side effects.
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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.
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Veterinary assessment showed decreased pain during CBD treatment (p < 0.02).
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No side effects were reported by owners, however, serum chemistry showed an increase in alkaline phosphatase during CBD treatment (p < 0.01).
Clinical relevance: This pharmacokinetic and clinical study suggests that 2mg/kg of CBD twice daily can help increase comfort and activity in dogs with OA.
Kogan, L, Hellyer, P & Downing, R 2020, ‘The use of Cannabidiol-rich hemp oil extract to treat canine osteoarthritis-related pain: a pilot study’, Journal of the American Holistic Veterinary Medical Association, vol. 58, pp. 35-45
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CBD doses of 0.3-4.12 mg/kg alleviated osteoarthritic (OA) pain in client-owned dogs and improved quality of life
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in dogs on gabapentin, 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.
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a wide range of CBD 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
Martello, E, Bigliati, M, Bisanzio, D, Biasibetti, E, Dosio, F, Pastorino, D, De-Nardi, M & Bruni, N, 2019, ‘Effects on pain and mobility of a new diet supplement in dogs with osteoarthritis: a pilot study’, Annals of Clinical Laboratory Research, vol. 7, pp. 1-5.
Sample:
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8 client-owned dogs suffering from OA were recruited in the pilot study.
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Inclusion criteria: confirmed radiographic and clinical signs of OA by a veterinarian orthopedic on at least one joint.
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Exclusion criteria are listed here: evidence of other diseases based on clinical history and blood test results, acute pain, recent trauma or surgery on any joint in the previous 6 months, neurological conditions, medications or diet supplements given in the two weeks before the enrolment in the study.
Method:
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Tablets containing a preparation of natural ingredients were administered for 30 days
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Active ingredients: Cannabidiol (CBD)-rich fraction (99.9%), hempseed oil, Boswellia serrata Roxb. in a Phytosome® delivery form and Cucumis melo L. extract)
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Veterinary evaluations were performed and owners filled questionnaires on chronic pain (Helsinki chronic pain indexHCPI) three times during the study.
Findings:
The product was well tolerated and owners reported a good palatability and ease of administration. Found a significant reduction of pain scores at the end of the study.
Mejia, S, Duerr, FM, Griffenhagen, G & McGrath, S 2021, ‘Evaluation of the effect of Cannabidiol on naturally occurring osteoarthritis-associated pain: a pilot study in dogs, Journal of the American Animal Hospital Association, vol. 57, pp. 81-90.
Design: prospective, double-blinded, crossover, placebo-controlled study
Aim: to provide preliminary data describing the safety and effect of CBD for symptom relief of canine osteoarthritis-associated pain in a clinical setting
Sample: 23 client-owned dogs with naturally occurring osteoarthritis of appendicular joints
Method: Baseline data were acquired for 4 wk, followed by random allocation to either placebo or CBD treatment for 6 wk, followed by 6 wk with the opposite treatment.
Outcome measures included objective gait analysis, activity counts (via accelerometry) and clinical metrology instruments.
Relevant findings:
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There were no differences noted between groups at any time point for any of the recorded outcome measures.
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Adverse events associated with CBD administration included elevation in liver enzymes (n = 14) and vomiting (n = 2).
Verrico, CD, Wesson, S, Konduri, V, Hofferek, CJ, Vazquez-Perez, J, Blair, E, Dunner, KJ, Salimpour, P, Decker, WK & Halpert, MM 2020, ‘A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain’, Pain, vol. 161, pp. 2191–2202.
Design: 4-week randomized, double-blind, placebo-controlled study
Aim: evaluate the safety and efficacy of CBD isolate (99.9% CBD) in dogs
Sample: 20 large (> 20 kg, mean 41 +/− 15 kg) client-owned dogs
Inclusion criteria: dogs that 1) received an affirmative diagnosed of OA by a veterinarian and 2) demonstrated signs of pain according to assessment by their owners, detectable lameness on visual gait assessment, and painful joint(s) upon palpation.
Exclusion: No cases of OA were related to trauma, and no animals with end-stage disease were enrolled.
Intervention:
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All other medications were discontinued at least 2 weeks prior to enrolment and dogs were not allowed to receive any medications during the 4-week study period except the study medication.
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4 groups: 1) placebo, 2) 20 mg/day (0.5 mg/kg) naked CBD, 3) 50 mg/day (1.2 mg/kg) naked CBD, or 4) 20 mg/day liposomal CBD.
Relevant findings:
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neither animals given placebo nor animals given a low daily dose of naked CBD responded to therapy in any significant fashion.
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Conversely, animals given a high dose of naked CBD or a low dose of liposomally-encapsulated CBD experienced significant improvements in quality of life scores as documented by both owner and veterinarian assessments.
administration of CBD was not associated with any significant alterations to circulating lymphocyte subsets, clinical chemistry values, or assessed metabolic parameters.
Brioschi FA, Di Cesare F, Gioeni D, Rabbogliatti V, Ferrari F, D’Urso ES, Amari M & Ravasio G 2020, ‘Oral transmucosal cannabidiol oil formulation as part of a multimodal analgesic regimen: effects on pain relief and quality of life improvement in dogs affected by spontaneous osteoarthritis’, Animals (Basel), vol. 10, pp. 1505.
Design: random controlled trial
The aim of this study was to evaluate the efficacy of oral transmucosal CBD in addition to a multimodal pharmacological treatment for chronic osteoarthritis-related pain in dogs.
Method:
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21 dogs randomly divided into two groups:
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Treatment (n = 9) group given CBD @ 2 mg/kg q 12 h + pharmaceuticals (NSAID, gabapentin, amitriptyline)
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Control – pharmaceuticals only, no CBD
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Dogs were evaluated by owners using the Canine Brief Pain Inventory scoring system before treatment initiation (T0), and one (T1), two (T2), four (T3) and twelve (T4) weeks thereafter.
Findings:
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Pain Severity Score was significantly lower in CBD vs control group
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Pain Interference Score was significantly lower in CBD vs control group
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Quality of Life Index was significantly higher in CBD group