Research study: Localisation of cannabinoid and cannabinoid-related receptors in the equine dorsal root ganglia (horses)

Research study: Localisation of cannabinoid and cannabinoid-related receptors in the equine dorsal root ganglia (horses)

We work with the very best researchers and universities around the World to gain valuable knowledge about, how CBD products work in humans and animals and to get detailed information about, how the cannabinoids react with the CB1 and CB2 receptors.

We work with University of Bologna and Professor Roberto Chiocchetti DVM, PhD. and his team from Department of Veterinary Medical Science and are funding a number of research studies on CBD and animals.

Disclaimer: we supported the University of Bologna with financial funds for research. The authors declare they have no conflict of interest.

Research study: Localisation of cannabinoid and cannabinoid-related receptors in the equine dorsal root ganglia (horses)

Growing evidence recognises cannabinoid receptors as potential thera-peutic targets for pain. Consequently, there is increasing interest in developing cannabinoid receptor agonists for treating pain. As a general rule, to better understand the actions of a drug, it would be of extreme importance to know the cellular distribution of its specific receptors. The localisation of cannabinoid receptors in the dorsal root ganglia of the horse has not yet been investigated.
Objectives: To localise the cellular distribution of canonical and putative cannabinoid receptors in the equine cervical dorsal root ganglia.

Even though limited empirical research has been carried out concerning the use of medical marijuana for pain treatment in domestic animals and horses, the use of cannabis products in animals is expanding. Of the cannabis products, cannabidiol (CBD), a non-psychoactive compound found in cannabis sativa, seems to be one of the most promising therapeutic substances. Due to its numerous health-related benefits, CBD has found multiple clinical applications in the medical field, including analgesic, anti-in- flammatory, anti-spasmodic and anti-anxiety uses. For many years, it was assumed that the beneficial effects of the cannabinoids were mediated exclusively by cannabinoid receptors 1 (CB1R) and 2 (CB2R). However, it is currently known that phytocannabinoids may act on multiple targets outside the endocannabinoid system, such as other G-protein-coupled receptors (GPRs), the transient receptors potential (TRPs) channel, nuclear peroxisome proliferator-activated receptors (PPARs), and serotonin receptors. In particular, CBD, which shows indirect interaction with CB1R and CB2R, seems to be involved in the modulation of receptors, such as the serotoninergic 5-HT1a receptor (5-HT1aR), and the transient receptors potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1), the latter two being ex- citatory ion channels expressed by the sensory neurons mediating somatic and visceral pain.

Results: The neurons showed immunoreactivity for CB1R (100%), CB2R (80% ± 13%), PPARα (100%), TRPA1 (74% ± 10%) and 5-HT1aR (84% ± 6%). The neuronal satellite glial cells showed immunoreactivity for CB2R, PPARα, TRPA1 and 5-HT1aR.

As a general rule, to better understand the effects exerted by a drug, it is important to know the cellular distribution of its specific receptors. Currently, only a small number of studies have been pub- lished regarding the expression of cannabinoid receptors in the dorsal root ganglia of animals and no analogous studies have yet been carried out on horses.

Thus, the current study was designed to immunohistochemically localise, two canonical cannabinoid receptors (CB1R and CB2R) and three cannabinoid-related receptors (PPARα, TRPA1 and 5-HT1aR) in the equine dorsal root ganglia.

Conclusions:

Cannabinoid and cannabinoid-related receptors had a wide distribution in the sensory neurons and SGCs of the equine dorsal root ganglia. These findings represented an important anatomical basis upon which it would be possible to continue with other preclinical and clinical studies aimed at investigating and possibly supporting the specific therapeutic uses of non-psychotropic cannabinoid agonists against noxius stimulation in horses.

Read the full 9-page research study here for free.

by Formula Swiss July 06, 2020

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Cannabidiol (CBD) may improve osteoarthritis symptoms in dogs

A 2020 study published in Pain has demonstrated the potential therapeutic benefits of CBD for improving symptoms associated with osteoarthritis in dogs.

This study aimed to determine the therapeutic potential of CBD on osteoarthritis in dogs. The study compared both naked and liposomal-encapsulated CBD to determine the potential benefits in dogs with spontaneous osteoarthritis.

Methods

Dogs were selected for the study if they presented to Sunset Animal Hospital (Houston, TX) with osteoarthritis-related conditions, including lameness. Owners completed a questionnaire to outline the affected limbs, lameness, and any medications the dogs was on.

Dogs were selected if they were diagnosed with osteoarthritis and demonstrated pain, lameness, joint pain, and gait issues, as assessed by their owners. Dogs were also ruled out if they had an underlying disease, outlined by a blood test.

The 20 selected dogs were then randomly assigned to one of four treatment groups: placebo, 30 mg/day naked CBD, 50 mg/day naked CBD, or 20 mg/day liposomal CBD. Blood samples were collected at the start of the treatment, and after 30 days for chemical analysis. As well as this, veterinarians assessed each dog’s locomotion for walking, running, and standing. Owners were also asked to assess their dog’s pain using an assessment called the Helsinki Chronic Pain Index.

Together, these methods were used to determine pain levels before, and after 30 days of treatment with CBD.

Results

There was a range of veterinarian and owner assessed outcomes to determine whether CBD had a therapeutic impact on dogs with osteoarthritis.

Owner assessment

There was no significant change to pain levels for dogs in the placebo and 20 mg/day naked CBD group when assessed by the owners. However, owners reported significant pain reduction in dogs receiving both 50 mg/day naked CBD and 20 mg/day liposomal CBD. These pain reductions were also found to be significant for at least 15 days after finishing treatment.

Veterinary assessment

As with the owner assessment, veterinary assessment observed very little change in the groups that received the placebo or 20 mg/day naked CBD. However, consistent with the owner assessment, there were evident improvements in all categories of veterinary assessment for dogs receiving 50 mg/day naked CBD and 20 mg/day liposomal CBD.

Together, these results demonstrated an overall decrease in pain, and an increase in locomotion, as assessed by both owners and veterinarians.

Discussion of results and implications

This study was assessing the therapeutic potential of CBD on osteoarthritis in dogs. Dogs with confirmed osteoarthritis were randomly assigned to treatment groups, and all researchers and participants were blinded to which group they were in.

CBD appears to reduce pain and improve locomotion

The results from the owner assessment questionnaire, as well as the veterinary assessments, both demonstrate the potential therapeutic benefits of CBD. The overall decrease in pain for two of the treatment groups compared to the placebo indicates that using CBD could be beneficial in reducing osteoarthritis-associated pain in dogs.

Additionally, the same two groups showed improved performance in locomotion, indicating that CBD could be important in not only reducing pain but also improving the quality of life for dogs with osteoarthritis. Their increased ability to perform daily activities, such as walking or standing up, demonstrated the role CBD could be playing in improving arthritis-related symptoms alongside the pain.

CBD has the potential to be beneficial for managing arthritis in dogs and this study provides an excellent foundation for future research exploring CBD use for pets.

Observed therapeutic benefits of CBD appear to be dose-dependent

One very interesting aspect of this study is that CBD may be more effective at a higher dose. The dogs receiving the 20 mg/day of naked CBD showed little to no improvements, with many scoring similar to those in the placebo group.

However, the group that was given 50 mg/day of naked CBD consistently showed a significant decrease in pain as well as a decrease in arthritis-related symptoms. This indicates that the higher daily dose may be crucial in gaining the apparent benefits associated with CBD.

As well as this, dogs receiving liposomal CBD showed significant improvements compared to both the placebo and 20 mg/day naked CBD groups. Even though the dose for liposomal CBD was also 20 mg/day, it demonstrated significant improvements compared to the naked CBD.

This is likely due to the capsule increasing the bioavailability of the CBD, meaning more of it is available for the body to digest. This demonstrates the potential for the use of a capsulated CBD supplement to provide an optimal response at a relatively low dose, reducing the need to take high-dose CBD to gain the same effect.

Together, these results demonstrate that, without the aid of a capsule, increasing the dose of CBD appears to result in a better response. However, adding a lipophilic capsule allows for the same impact at a lower dose. This could help to inform further therapeutic studies looking at the best dosage to implement for safe and effective results.

Future research

This study provides excellent preliminary data and foundations for further research into the potential role of CBD in the treatment of osteoarthritis.

Ideally, the next first step would be to increase the overall sample size. While this study demonstrated the potential of CBD for therapeutic use, it did only have a sample size of 20. To further develop our understanding of the therapeutic potential and safety of CBD, further studies incorporating large populations would need to be done.

It would also be beneficial to do a study that follows up the participants for longer than 4 weeks to develop the long term benefits and harms of CBD use for osteoarthritis. This would need to be done before it could be considered as a regular treatment option.

Broadening the population used would also help to make the results from this study more generalizable to a population as a whole. This could include incorporating a wide range of dog breeds and the severity of arthritis.

Lastly, specific dose-response studies should be done to determine the optimal dose for therapeutic use. This would help to maximize the outcomes while also minimizing the potential harms that high-dose administration can cause.

There are therefore several future options that can be explored to further our understanding of the therapeutic potential of CBD for osteoarthritis.

The bottom line

This study demonstrated the clear potential therapeutic benefits of CBD for osteoarthritis in dogs. The preliminary data from this study demonstrated that, at the right dose or in the right form, CBD appears to reduce pain and improve the quality of life for dogs suffering from osteoarthritis.

The results suggest that CBD may be an excellent candidate for osteoarthritis management, warranting further studies into its potential therapeutic uses.

References:

Verrico, C. D., Wesson, S., Konduri, V., Hofferek, C. J., Vazquez-Perez, J., Blair, E., … Halpert, M. M. (2020). A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain. Pain, 1. DOI: 10.1097/j.pain.0000000000001896

This article was written by an independent and third-party author specialising in CBD, hemp and cannabis research. Any opinion, advice or recommendation expressed in the article does not reflect the opinion of Formula Swiss AG or any of our employees. We do not make any claims about any of our products and refer to our disclaimer for more information.

by Formula Swiss May 19, 2020

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Cannabidiol (CBD) may help reduce pain in dogs with osteoarthritis

Cannabidiol (CBD) may help reduce pain in dogs with osteoarthritis

A 2020 study published in Veterinary Record has demonstrated the potential for CBD to be used alongside current drug treatments to reduce pain in dogs with osteoarthritis.

This study aimed to assess the potential role of cannabidiol (CBD) in reducing osteoarthritis-associated pain in dogs. The overall aim of the study was to determine if CBD can reduce pain associated with osteoarthritis in dogs if it is given alongside current treatments.

Methods

The researchers carried out a literature search and found one paper that met the search parameters and was relevant to the aim.

The paper assessed the pain, lameness, and weight of 16 dogs with confirmed osteoarthritis. The dogs were assigned to either receiving CBD or a placebo alongside their regular medication for 4 weeks. The groups then swapped treatments for a further 4 weeks following a 2 week period where the dogs received no intervention.

Outcomes were measured by an owner questionnaire as well as veterinary assessments that included hematology, serum chemistry, and physical examinations. Outcomes were measured before treatment, at week 2, and the end of the treatment intervention.

Results

Due to there being several potential outcomes to report on, the study reported a range of results consisting of owner and veterinary assessments.

Owner-assessed outcomes

Following CBD treatment, owners reported an overall decrease in pain and a subsequent increase in activity at both 2 and 4 weeks after treatment began. There were also no side effects reported by owners.

Vet-assessed outcomes

Following CBD treatment, there was an overall decrease in pain. Based on veterinary assessment palpitation scores, pain levels significantly decreased at both 2 and 4 weeks following CBD treatment compared to the baseline scores. Additionally, pain decreased in the CBD-treated group compared to the placebo group.

However, there were no significant changes in vet-assessed lameness or weight-bearing scores.

Discussion of results and implications

This study was assessing whether CBD can reduce pain levels in dogs with osteoarthritis, alongside their current treatments. The study did a literature search and found one paper that assessed this.

CBD appears to reduce pain

The initial findings of this study indicate that CBD does aid in overall pain reduction in dogs with arthritis. The owner-assessed questionnaire determined that, from the perspective of the owner, there was an overall increase in their dog’s comfort levels following the use of CBD.

These results were reinforced by the veterinary-assessed outcomes, which also found a significant decrease in pain following palpitation testing. The fact that this was found when comparing baseline to treatment, as well as a placebo to treatment, further confirms the pain-reduction potential of CBD for dogs with osteoarthritis.

Potential weaknesses

While these findings are promising, several things would have to be improved in the study to reinforce their clinical significance.

1. Sample population

This study had a relatively small sample size of only 16 dogs in total. Additionally, there was no consistency in the breed, age, or severity of arthritis. As well as this, there was no controlling for the type or dose of the medication that the dogs were already on for their osteoarthritis. All of these factors could impact the ability to make a conclusive call from the results obtained from this study.

2. Timelines

There is no explanation as to where the 2 and 4 week periods came from. The half-lives of CBD or any other medications the dogs did not appear to be taken into account, therefore, it is uncertain whether the timeline of this study is sufficient enough to conclude whether CBD reduces pain long-term. As well as this, it is unclear whether 2 weeks is sufficient enough to clear the drug from the dog’s system before swapping the treatment groups over.

3. CBD composition

The study used a very specific cannabinoid product that consisted of high concentrations of CBD. Not all strains of cannabinoids have the same proportion of CBD to other products, and so these results won't necessarily apply to other strains.

Regardless of this, these results are an excellent foundation for further studies to take place the potential use of CBD as a pain reliever in dogs with osteoarthritis. The researchers have demonstrated a clear potential for CBD that, with further research, could change the way osteoarthritis pain is treated in the veterinary clinic.

Future research

Several things could be done to further understand whether the addition of cannabidiol alongside current drug treatments reduces pain in dogs with osteoarthritis.

Firstly, a study with a much larger sample size would need to be conducted. An increased sample size, as well as the incorporation of a variety of dog breeds, would help to form the conclusion that is more representative of the entire population as a whole. As well as this, it would be beneficial to control for factors such as age, breed, current medication, and severity of arthritis to reduce the possibility that the findings are due to an unrelated reason.

To understand the impact of CBD on pain long-term, future research would need to include studies that involved a longer period. This will help to understand whether CBD can relieve pain long-term, as well as any possible side effects that could arise from long-term use of the substance.

Further down the line, it would also be beneficial to do a number of tests comparing an array of CBD products. CBD can vary in purity and consistency, meaning that one company’s product could produce different results than another. It would, therefore, be useful to test several CBD products to determine any possible differences in their results.

Future research opportunities will help to further develop an understanding of the potential benefits of CBD on pain reduction in dogs with osteoarthritis.

The bottom line

This study provides a good foundation for the potential benefits of CBD on pain reduction for dogs with osteoarthritis. The preliminary data from this study demonstrate that CBD appears to aid in pain reduction for dogs with osteoarthritis.

While the initial findings are promising, further studies will allow for an increased understanding of the benefits of CBD for dogs with osteoarthritis.

References:

Morrow, L., & Belshaw, Z. (2020). Does the addition of cannabidiol alongside current drug treatments reduce pain in dogs with osteoarthritis? Veterinary Record, 186(15), 493–494. DOI: 10.1136/vr.m1594

This article was written by an independent and third-party author specialising in CBD, hemp and cannabis research. Any opinion, advice or recommendation expressed in the article does not reflect the opinion of Formula Swiss AG or any of our employees. We do not make any claims about any of our products and refer to our disclaimer for more information.

by Formula Swiss May 19, 2020

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Research study: Localization of cannabinoid and cannabinoid related receptors in the cat gastrointestinal tract

Research study: Localization of cannabinoid and cannabinoid related receptors in the cat gastrointestinal tract

We work with the very best researchers and universities around the World to gain valuable knowledge about, how CBD products work in humans and animals and to get detailed information about, how the cannabinoids react with the CB1 and CB2 receptors.

We work with University of Bologna and Professor Roberto Chiocchetti DVM, PhD. and his team from Department of Veterinary Medical Science and are funding a number of research studies on CBD and animals.

Disclaimer: we supported the University of Bologna with financial funds for research. The authors declare they have no conflict of interest.

Research study: Localization of cannabinoid and cannabinoid related receptors in the cat gastrointestinal tract

An increasing amount of literature indicates that activation of cannabinoid receptors may exert beneficial effects on gastroin-testinal inflammation and visceral hypersensitivity.

The present study aimed to immunohistochemically investigate the distribution of the canonical cannabinoid receptors CB1 and CB2 and other key receptors in tissue samples of the gastrointestinal tract of the cat.

Abstract: Cannabinoid receptors showed a wide distribution in the feline gastrointestinal tract layers. Although not yet confirmed/supported by functional evidences, the present research might represent an anatomical substrate potentially useful to support, in feline species, the therapeutic use of cannabinoids during gastrointestinal inflammatory diseases.

Cannabinoid receptors regulate gastrointestinal tract (GIT) motility and secretion, sensation, emesis, satiety, and inflammation. Several evidences indicate that substances acting on GIT cannabinoid receptors may be beneficial for gut discomfort and pain.

The primary and most studied cannabinoid receptors are two G protein-coupled receptors: cannabinoid receptors type 1 (CB1R) and type 2 (CB2R). CB1R is mostly expressed in the central and peripheral nervous system, while CB2R is mainly expressed in immune cells.

Several studies suggest that CB1R or CB2R might have a protective role in inflammatory bowel disease (IBD), and support the possible value of targeting these pathways with pharmacological agents, such as phytocannabinoids or synthetic cannabinoid agonists, for therapeutic gain.

Cannabidiol (CBD) is currently one of the most studied cannabinoids and its use is spreading throughout human and veterinary medical practice. Notably, CBD also is a non-psychoactive compound with proved anti-inflammatory, analgesic, anti-anxiety and anti-tumoral properties.

CBD seems to act preferentially on cannabinoid-related receptors, such as GPR3 (inverse agonist), GPR6 (inverse agonist), GPR12 (inverse agonist), GPR55 (antagonist), TRPA1 (agonist), TRPV1 (agonist), and serotoninergic receptors 5-HT1a (agonist), 5-HT2a (partial agonist), and 5-HT3 (antagonist)

Read the full 18-page research study here for free.

by Formula Swiss February 27, 2020

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How to use CBD to calm your pets

How to use CBD to calm your pets

Like humans, pets also suffer from anxiety, fear, and nervousness. Their senses are very sensitive; they can feel all changes that happen in the atmosphere. Especially on events and parties when fireworks start and the sky is filled with countless light, mostly pets feel anxious or afraid. But they can't tell what they feel but only a few symptoms can express their situation. Pets are of many kinds but here we discuss common pets (dogs and cats).

Symptoms of fear or anxiety:

  • Hide themselves
  • Urinate
  • Scratching things
  • Vomit and shaking
  • Discomfort (running here and there)
  • Offensive Actions

CBD helps to calm pets

There are many individuals who use CBD oil to deal with anxiety in their pets on parties. During the events, loud noise causes disturbance among them because normally they are not used to it. There are also many people who like to use CBD products to fight with their own issues. 

A recent study shows that the effect of hemp has been controlled. New research discovered that it also changes the range of hydroxytryptamine. The main cause of low levels of hydro-oxytryptamin is both anxiety and depression.

How to give CBD to pets?

The best way to keep your pet out of anxiety is to give CBD several hours before fireworks because CBD takes some time to go through the pet's digestive system and after it starts working. 

There are many CBD products that can be used to reduce fear and anxiety, but here are the two most effective products for pets:

  • Oil drops
  • CBD pet treats

The efficiency of CBD products for cats has been confirmed only by the research and proof that is given by many cat owners. Same results are noticed in dogs.

The choice between CBD oil and pet procedure depends on how your dog takes the medicine.

CBD oil drops:

These are given by pulling a few drops in the mouth of the dog. You can also add this oil in the food if your dog is not taking it in his mouth. 

CBD dog treats:

This product looks like other dogs treats. It also has the same taste as other favourite treats. Surely your dog will love to eat it.

The quantity of CBD oil that you have to give to your pet to calm him during fireworks will depend on many factors. These are:

  • Size of your pet
  • Level of fear or anxiety

It also depends on the quantity of CBD you buy. The fine quality of CBD comes with guidelines of how much you have to give it to your pet. Excessive use of oil and other product may cause other negative effects. Be careful and get fully aware of these products.

Other remedies to help calm your dog:

  • Keep your pet indoors while firework started.
  • Keep your pet busy
  • Play soft music to make them comfortable.

Make sure that you give the right dosage of CBD to your pet to assure that they can get the positive effects. You will notice a positive change in the healthy and attitude of your pet.

This article was written by an independent and third-party author specialising in CBD, hemp and cannabis research. Any opinion, advice or recommendation expressed in the article does not reflect the opinion of Formula Swiss AG or any of our employees. We do not make any claims about any of our products and refer to our disclaimer for more information.

by Formula Swiss September 25, 2019

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CBD has profound antidepressant effect in animals

CBD has profound antidepressant effect in animals

You will be surprised to know that stress is not only a problem in humans. There are many animals and pets that are suffering from serious depression only because they do not get the time of their human friends or they do not get the attention that they need. Due to depression, there are various other health problems that animals have to suffer from. However, recently the positive effects of CBD in humans are the reasons that scientists are interested in finding out whether it will be effective for animals or not. Here are some of the reasons how CBD might prove to be effective for animals that are suffering from depression.

Increase BDNF signaling

A recent study conducted on rodents showed the positive effects of CBD. It was acting just like any other antidepressant. It was found that the CBD increase the BDNF signals in the brain. They affected the cells of mPFC and hippocampus. It also had increased the density of the spine after 30 minutes of the application. That is why due to increase in such signals the rodents felt relaxed and their overall condition was improved. These are the same effects that are induced by antidepressants in the animals.

Improve mood

There are various chemical changes that are happening in the mind of the animals just like humans. In order to control depression, it is important to control and improve all such reactions. CBD can help improve the mood of the animals just like it does in humans. It can calm their senses that will help them fight against the cause of depression and improve the overall condition of the pets.

Relax mind and reduce stress

It has been proved in the research that CBD can help relax the mind of the pets. The biggest cause of depression is anxiety and stress. CBD can help to relieve this condition of stress due to which most pets feel uncomfortable. It can bring a positive change in the behaviour. The rodents that were behaving badly before they were given CBD, had a very calm behaviour after the induction of CBD into their body. They showed positive results in terms of different tests that were conducted on the rodents.

It demonstrated that little dosage of CBD permitted the impact of little portions of serotonergic antidepressants, for example, fluoxetine, to be viable. This demonstrates co-directing CBD with serotonergic antidepressants may add to the utilization of littler dosages of the last mentioned, in this way diminishing their symptoms, without trading off the energizer impact. This is a procedure to be additionally investigated in different examinations and in the clinical setting.

However, there are no effective results given yet that can show that CBD is really very effective for pets and animals. It might act as an antidepressant but the experts still have to work on their research to find out whether it will show any long term benefits in the animals just like it is doing in humans.

This article was written by an independent and third-party author specialising in CBD, hemp and cannabis research. Any opinion, advice or recommendation expressed in the article does not reflect the opinion of Formula Swiss AG or any of our employees. We do not make any claims about any of our products and refer to our disclaimer for more information.

by Formula Swiss May 13, 2019

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