Long-term effects of a diet supplement containing Cannabis sativa oil and Boswellia serrata in dogs with osteoarthritis following physiotherapy treatments: a randomised, placebo-controlled and double-blind clinical trial

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“Dogs are commonly affected by Osteoarthritis (OA). Different approaches can be used to alleviate animals’ symptoms. In this randomised, placebo-controlled and double-blind clinical trial, we performed a three months follow-up study assessing the efficacy of a food supplement containing natural ingredients (Cannabis sativa oil, Boswellia serrata Roxb. Phytosome® and Zingiber officinale extract) in dogs with OA after the interruption of physiotherapy that was performed during the previous three months. Inflammation and oxidative stress were reduced in the treated group (higher glutathione (GSH) and lower C-reactive protein [CRP] levels in blood) as well as chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/36067506/

https://www.tandfonline.com/doi/abs/10.1080/14786419.2022.2119967?journalCode=gnpl20

Cannabidiol as a treatment for arthritis and joint pain: an exploratory cross-sectional study

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“Introduction: An estimated 54 million Americans currently suffer from debilitating arthritis. Patients who have exhausted conservative measures can be subject to chronic pain and resort to symptomatic management with anti-inflammatories, acetaminophen, and opioids. Cannabidiol (CBD) is a non-psychoactive cannabinoid that has shown promise in preclinical studies to reduce inflammation and pain associated with arthritis. The purpose of this study was to explore patient perceived effects of cannabidiol on symptoms of arthritis.

Methods: A novel anonymous questionnaire was created to evaluate perceived efficacy of cannabidiol for the treatment of arthritis. A self-selected convenience sample (N=428) was recruited through online methods including social media accounts and newsletters (The Arthritis Foundation and Savvy Cooperative) between May 5, 2020, and November 5, 2020. Statistical analysis was performed to determine differences between types of arthritis and improvements in quality-of-life symptoms. Furthermore, a regression analysis was performed to identify variables associated with decreasing or discontinuing other medications.

Results: CBD use was associated with improvements in pain (83%), physical function (66%), and sleep quality (66%). Subgroup analysis by diagnosis type (osteoarthritis, rheumatoid, or other autoimmune arthritis) found improvements among groups for physical function (P=0.013), favoring the osteoarthritis group. The overall cohort reported a 44% reduction in pain after CBD use (P<0.001). The osteoarthritis group had a greater percentage reduction (P=0.020) and point reduction (P<0.001) in pain compared to rheumatoid arthritis and other autoimmune arthritis. The majority of respondents reported a reduction or cessation of other medications after CBD use (N=259, 60.5%): reductions in anti-inflammatories (N=129, 31.1%), acetaminophen (N=78, 18.2%), opioids (N=36, 8.6%) and discontinuation of anti-inflammatories (N=76, 17.8%), acetaminophen (N=76, 17.8%), and opioids (N=81, 18.9%).

Conclusion: Clinicians and patients should be aware of the various alternative therapeutic options available to treat their symptoms of arthritis, especially in light of the increased accessibility to cannabidiol products. The present study found associations between CBD use and improvements in patient’s arthritis symptoms and reductions in other medications. Future research should focus on exploring the benefits of CBD use in this patient population with clinical trials.”

https://pubmed.ncbi.nlm.nih.gov/35999581/

“The present study, while exploratory in nature, suggests there may be therapeutic benefits to CBD use and highlights the need for research in a field where the science lags behind popular use.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-022-00154-9

Distinctive Therapeutic Effects of Non-Euphorigenic Cannabis Extracts in Osteoarthritis

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“Introduction: Osteoarthritis (OA) is disabling and degenerative disease of the joints that is clinically characterized by pain and loss of function. With no disease-modifying treatment available, current therapies aim at pain management but are of limited efficacy. Cannabis products, specifically cannabinoids, are widely used to control pain and inflammation in many diseases with no scientific evidence demonstrating their efficacy in OA. 

Objective: We investigated the effects of non-euphorigenic cannabis extracts, CBD oil and cannabigerol oil (CBG oil), on pain and disease progression in OA mice. 

Methods and Results: Twelve-week-old male C57BL/6J mice received either sham or destabilization of the medial meniscus (DMM) surgery. DMM mice were treated with vehicle, CBD oil, or CBG oil. The gait of DMM mice was impaired as early as 2 weeks following surgery and continued deteriorating until week 8, which was restored by CBD oil and CBG oil treatments throughout the disease course. Mechanical allodynia developed in DMM mice, however, was not ameliorated by any of the treatments. On the other hand, both CBD oil and CBG oil ameliorated cold allodynia. In open field test, both oil treatments normalized changes in the locomotor activity of DMM mice. CBD oil and CBG oil treatments significantly reduced synovitis in DMM mice. Only CBG oil reduced cartilage degeneration, chondrocyte loss, and matrix metalloproteinase 13 expression, with a significant increase in the number of anabolic chondrocytes. Subchondral bone remodeling found in vehicle-treated DMM mice was not ameliorated by either CBD or CBG oil. 

Conclusions: Our results show evidence for the therapeutic efficacy of CBD oil and CBG oil, where both oils ameliorate pain and inflammation, and improve gait and locomotor activity in OA mice, representing clinical pain and function. Importantly, only CBG oil is chondroprotective, which may provide superior efficacy in future studies in OA patients.”

https://pubmed.ncbi.nlm.nih.gov/35994012/

https://www.liebertpub.com/doi/10.1089/can.2021.0244

Safety and Efficacy of the Therapeutic Use of Cannabis-Based Products in the Treatment of Dogs: An Integrative Review

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

https://pubmed.ncbi.nlm.nih.gov/35512739/

https://www.liebertpub.com/doi/10.1089/can.2021.0172

Medical Cannabis Use Reduces Opioid Prescriptions in Patients With Osteoarthritis

“Osteoarthritis (OA) can result in significant pain, requiring pain management with opioids. Medical cannabis (MC) has the potential to be an alternative to opioids for chronic pain conditions. This study investigates whether MC used in the management of OA-related chronic pain can reduce opioid utilization.

Results

Average MME/day decreased from 18.2 to 9.8 (n=40, p<0.05). The percentage of patients who dropped to 0 MME/day was 37.5%. VAS scores decreased significantly at three and six months, and Global Physical Health score increased significantly by three months.

Conclusions

MC reduces opioid prescription for patients with chronic OA pain and improves pain and quality of life.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8873278/

Cannabinoid-based therapy as a future for joint degeneration. Focus on the role of CB 2 receptor in the arthritis progression and pain: an updated review

“Over the last several decades, the percentage of patients suffering from different forms of arthritis has increased due to the ageing population and the increasing risk of civilization diseases, e.g. obesity, which contributes to arthritis development. Osteoarthritis and rheumatoid arthritis are estimated to affect 50-60% of people over 65 years old and cause serious health and economic problems. Currently, therapeutic strategies are limited and focus mainly on pain attenuation and maintaining joint functionality. First-line therapies are nonsteroidal anti-inflammatory drugs; in more advanced stages, stronger analgesics, such as opioids, are required, and in the most severe cases, joint arthroplasty is the only option to ensure joint mobility.

Cannabinoids, both endocannabinoids and synthetic cannabinoid receptor (CB) agonists, are novel therapeutic options for the treatment of arthritis-associated pain. CB1 receptors are mainly located in the nervous system; thus, CB1 agonists induce many side effects, which limit their therapeutic efficacy. On the other hand, CB2 receptors are mainly located in the periphery on immune cells, and CB2 modulators exert analgesic and anti-inflammatory effects in vitro and in vivo. In the current review, novel research on the cannabinoid-mediated analgesic effect on arthritis is presented, with particular emphasis on the role of the CB2 receptor in arthritis-related pain and the suppression of inflammation.”

https://pubmed.ncbi.nlm.nih.gov/34050525/

“Cannabinoids not only alleviate joint hyperalgesia but also may help to prevent joint damage, chronic pain development and disease progression.”

Cannabinoid Receptors and Their Relationship With Chronic Pain: A Narrative Review

CB1-versus-CB2-receptors “The burden of chronic pain has affected many individuals leading to distress and discomfort, alongside numerous side effects with conventional therapeutic approaches.

Cannabinoid receptors are naturally found in the human body and have long been an interest in antinociception. These include CB1 and CB2 receptors, which are promising candidates for the treatment of chronic inflammatory pain.

The mechanism of action of the receptors and how they approach pain control in inflammatory conditions show that it can be an adjunctive approach towards controlling these symptoms. Numerous studies have shown how the targeted approach towards these receptors has activated them promoting a release in cytokines, all leading to anti-inflammatory effects and immune system regulation.

Cannabinoid activation of glycine and gamma-aminobutyric acid (GABA) models also showed efficacy in pain management. Chronic conditions such as osteoarthritis were shown to also benefit from this considerable treatment. However, it is unclear how the cannabinoid system works in relation with the pain pathway. Therefore, in this review we aim to analyse the role of the cannabinoid system in chronic inflammatory pain.”

https://pubmed.ncbi.nlm.nih.gov/33072446/

https://www.cureus.com/articles/39887-cannabinoid-receptors-and-their-relationship-with-chronic-pain-a-narrative-review

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-logo “The aim of this study was to evaluate the efficacy of oral transmucosal (OTM) cannabidiol (CBD), in addition to a multimodal pharmacological treatment for chronic osteoarthritis-related pain in dogs.

Pain Severity Score was significantly lower in CBD than in C group at T1 (p = 0.0002), T2 (p = 0.0043) and T3 (p = 0.016). Pain Interference Score was significantly lower in CBD than in C group at T1 (p = 0.0002), T2 (p = 0.0007) and T4 (p = 0.004). Quality of Life Index was significantly higher in CBD group at T1 (p = 0.003). The addition of OTM CBD showed promising results. Further pharmacokinetics and long-term studies in larger populations are needed to encourage its inclusion into a multimodal pharmacological approach for canine osteoarthritis-related pain.”

https://pubmed.ncbi.nlm.nih.gov/32858828/

“Osteoarthritis is a progressive and degenerative condition that affects dog populations, causing pain. The pain associated with osteoarthritis is considered to be chronic, owing to both active inflammation and to a maladaptive component caused by central sensitization. Chronic pain in dogs is being increasingly recognised as a significant problem, and finding successful treatments against canine osteoarthritis-related pain is challenging. The aim of this study was to assess the efficacy in pain management over a twelve-week period of oral transmucosal cannabidiol, in combination with a multimodal pharmacological protocol, in dogs affected by spontaneous osteoarthritis. Dogs receiving oral transmucosal cannabidiol in addition to an anti-inflammatory drug, gabapentin and amitriptyline showed a meaningful improvement in Canine Brief Pain Inventory scores, in comparison with dogs that did not receive cannabidiol. The present study suggests that the addition of oral transmucosal cannabidiol to a multimodal pharmacological treatment for canine osteoarthritis improves owner reported pain scores and quality of life of dogs, without severe adverse effects.”

https://www.mdpi.com/2076-2615/10/9/1505

A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain.

PAIN Impact Factor Increase to 6.029 - IASP“Over the last two decades, affirmative diagnoses of osteoarthritis in the United States have tripled due to increasing rates of obesity and an aging population.

Hemp-derived cannabidiol (CBD) is the major non-THC component of cannabis and has been promoted as a potential treatment for a wide variety of disparate inflammatory conditions.

Here we evaluated CBD for its ability to modulate the production of pro-inflammatory cytokines in vitro and in murine models of induced inflammation and further validated the ability of a liposomal formulation to increase bioavailability in mice and in humans.

Subsequently, the therapeutic potential of both naked and liposomally-encapsulated CBD was explored in a 4-week, randomized placebo-controlled, double-blinded study in a spontaneous canine model of osteoarthritis.

In vitro and in mouse models, CBD significantly attenuated the production of pro-inflammatory cytokines IL-6 and TNF-α while elevating levels of anti-inflammatory IL-10. In the veterinary study, CBD significantly decreased pain and increased mobility in a dose-dependent fashion among animals with an affirmative diagnosis of osteoarthritis.

Liposomal CBD (20 mg/day) was as effective as the highest dose of non-liposomal CBD (50 mg/day) in improving clinical outcomes. Hematocrit, comprehensive metabolic profile, and clinical chemistry indicated no significant detrimental impact of CBD administration over the four-week analysis period.

This study supports the safety and therapeutic potential of hemp-derived CBD for relieving arthritic pain and suggests follow-up investigations in humans is warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/32345916

https://journals.lww.com/pain/Abstract/9000/A_randomized,_double_blind,_placebo_controlled.98420.aspx

Cannabinoids CB2 Receptors, One New Promising Drug Target for Chronic and Degenerative Pain Conditions in Equine Veterinary Patients.

Journal of Equine Veterinary Science“Osteoarticular equine disease is a common cause of malady; in general, its therapy is supported on steroids and nonsteroidal anti-inflammatories. Nevertheless, many side effects may develop when these drugs are administered. Nowadays, the use of new alternatives for this pathology attention is demanded; in that sense, cannabinoid CB2 agonists may represent a novel alternative.

Cannabinoid belongs to a group of molecules known by their psychoactive properties; they are synthetized by the Cannabis sativa plant, better known as marijuana.

The aim of this study was to contribute to understand the pharmacology of cannabinoid CB2 receptors and its potential utilization on equine veterinary patients with a chronic degenerative painful condition. In animals, two main receptors for cannabinoids are recognized, the cannabinoid receptor type 1 and the cannabinoid receptor type 2. Once they are activated, both receptors exert a wide range of physiological responses, as nociception modulation.

Recently, it has been proposed the use of synthetic cannabinoid type 2 receptor agonists; those receptors looks to confer antinociceptive properties but without the undesired psychoactive side effects; for that reason, veterinary patients, whit chronical degenerative diseases as osteoarthritis may alleviate one of the most common symptom, the pain, which in some cases for several reasons, as patient individualities, or side effects produced for more conventional treatments cannot be attended in the best way.”

https://www.ncbi.nlm.nih.gov/pubmed/31952645

https://www.sciencedirect.com/science/article/abs/pii/S073708061930629X?via%3Dihub