Related article Even though there is a lot of anecdotal evidence to support that CBD might help with dog seizures, the honest truth is that scientific research is ongoing The epileptic seizure events in this population of dogs ranged from 3 to 14 seizures with a mean of 8 seizures over the week study using placebo, which decreased to a mean of 5 seizures with a range of 0—12 events over the 12 weeks of treatment Research shows that CBD improves seizure control in patients with specific epilepsy syndromes Additionally, she uses Full Spectrum Hemp Extract on all her pets at her rescue farm every day, and has since Additionally, she uses Full Spectrum Hemp Extract on all her pets at her rescue farm every day, and has since . The difference in response between dogs may be related to the utilization of a whole hemp extract rich in CBD, vs The CB1 receptors — centralized in the nervous system and the brain Right now, veterinarians are being inundated with questions, unrealistic expectations, and sketchy information about CBD products for pets In their review article, Franco et al At these time points, blood was drawn to evaluate the complete blood counts, serum biochemistry and serum ASMs, including zonisamide, phenobarbital and bromide between 10 a Dog Health Cbd At these time points, blood was drawn to evaluate the complete blood counts, serum biochemistry and serum ASMs, including zonisamide, phenobarbital and bromide between 10 a. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers Idiopathic epilepsy has no identifiable cause and is often a genetic issue, while symptomatic epilepsy occurs when there is an identifiable underlying brain lesion or metabolic cause, like the ones mentioned above .

The same active product is freely available in the United Kingdom, marketed as a human preparation Ellevance , due to current United Kingdom legislative restrictions on the provision of CBD based products to animals Additionally, the formulation used in our study contains significant amounts of CBDA which has been shown to have anti-convulsant and anti-seizure activity in rodent models when delivered orally once per day 4 ; there is relatively sparse information regarding its use in humans, short of a pharmaceutical company trial suggesting efficacy of CBDA when provided orally once a day . McGrath et al Complete blood counts including white blood cell, red blood cells, hematocrit, hemoglobin, neutrophil, lymphocyte, platelet, eosinophil, and basophil counts were performed at the University of Florida Veterinary Clinical Pathology Department A serum biochemistry including sodium, potassium, chloride, phosphorus, calcium, magnesium, albumin, total protein, globulin, cholesterol, glucose, alanine aminotransferase ALT , aspartate amino transferase AST , alkaline phosphatase ALP , bilirubin, urea nitrogen and creatinine was evaluated at each time point No differences were observed in serum zonisamide, phenobarbital or bromide concentrations while on the treatment across groups Read more about what CBD can do for your dog or cat Benefits Of Cbd Oil In Dogs Read more about what CBD can do for your dog or cat. Randomized controlled canine trials with large sample sizes are needed to determine the range of therapeutic plasma concentrations, develop evidence-based dosing regimens, determine the efficacy of cannabidiol in drug-refractory epilepsy, and explore potential associations between treatment effects and different etiologies, epilepsy types, and drug combinations In a study of quality and labeling, only 10 of 29 products were accurately labeled with regard to CBD, and two products showed unacceptable levels of heavy metals, even though many touted a Certificate of Analysis However, your dog may need more, or less, CBD oil for dog seizures Another group of researchers conducted a similar experiment where three dogs who suffered epileptic seizures were given hemp-derived CBD for eight weeks Treatment consisted of a hemp derived cannabinoid therapy in sesame seed oil Treatment consisted of a hemp derived cannabinoid therapy in sesame seed oil. Some dogs with these kinds of seizures may be weaned off their medications over time if they are treated for the underlying cause There are several different things that cause seizures: Underlying health condition like liver or kidney disease or cancer Electrolyte problems Topical flea and tick products Herbicides and pesticides Head injury CBD Oil For Dogs With Epilepsy If your dog suffers from regular seizures, epilepsy might be the culprit DOI: Written informed consent was obtained from the owners for the participation of their animals in this study Introduction Since the 's or earlier, cannabinoids have been found to have anti-epileptic effects in animal seizure models 1 Can I Give My Dog Cbd Gummy Introduction Since the 's or earlier, cannabinoids have been found to have anti-epileptic effects in animal seizure models 1. Causes of seizures vary from dog to dog .

Causes of seizures vary from dog to dog

Endocannabinoids are synthesized on demand by the body to maintain homeostasis — a stable internal environment Next, we put her on a natural CBD oil for seizures in dogs regimen and switched her to a fresh and species appropriate raw diet

These are changes that should be monitored or discussed with clients interested in pursuing CBD-rich hemp treatment for epileptic seizure management 16 —

The oil suspension was utilized to make 10, 25, and 50 mg capsules to be dispensed At the end of the week period, the diary was given to the investigators and the owners were provided a second diary to utilize for the next week period of the cross-over design Contrary to popular belief, the question of how much CBD oil to give dogs with seizures has very little to do with the size and weight of your dog Usually, however, an episode can be determined by postictal activities or inappropriate soiling of surroundings, particularly since these were dog owners who were managing chronic epilepsy for over a year and were astute to behavioral changes Can Dogs With Cushings Disease Take Cbd Oil Usually, however, an episode can be determined by postictal activities or inappropriate soiling of surroundings, particularly since these were dog owners who were managing chronic epilepsy for over a year and were astute to behavioral changes. Seeing your beloved dog have a seizure can be a frightening experience For all dogs, no new medications could be added throughout the study period, but alterations in phenobarbital or potassium bromide dosing could occur, based on adverse events reported by the owner i Electronic address: potschka pharmtox They might be over quickly, or they can last for several minutes Additionally, Gaston et al Additionally, Gaston et al. Two types of endocannabinoid receptors have been identified: CB1 receptors, found predominantly in the brain, nervous system, glands, and organs; and CB2 receptors, existing mainly in the regulatory cells of the immune system Vet J Conversely, McGrath et al If you must move the dog, try to move them from their hind legs or hips In a recent study , neurologist Stephanie McGrath assessed the short-term effect of CBD on seizure frequency in 16 dogs Canna Paws For Pain Relief In Dogsbest Cbd For Dogs In a recent study , neurologist Stephanie McGrath assessed the short-term effect of CBD on seizure frequency in 16 dogs. Considering the product being tested contained other cannabinoids namely CBDA we felt that any assessment would be incomplete; therefore serum was not saved for future analysis In this context, it should be noted that the quality of available CBD varies widely, underscoring the importance of pharmaceutical quality and its control Seizures In Dogs Seizures in dogs can manifest as anything from a twitch to uncontrollable shaking J Epilepsy Res All dogs involved in the study could not have endocrine issues or organ dysfunction, other than concomitant osteoarthritis issues and could be on non-steroidal anti-inflammatories and non-hemp based nutraceuticals, but owners were informed that the regimen could not be altered over the 6-month study period All dogs involved in the study could not have endocrine issues or organ dysfunction, other than concomitant osteoarthritis issues and could be on non-steroidal anti-inflammatories and non-hemp based nutraceuticals, but owners were informed that the regimen could not be altered over the 6-month study period. .

All dogs involved in the study could not have endocrine issues or organ dysfunction, other than concomitant osteoarthritis issues and could be on non-steroidal anti-inflammatories and non-hemp based nutraceuticals, but owners were informed that the regimen could not be altered over the 6-month study period

How does CBD work to reduce seizures? All mammals have an endocannabinoid system, a network of numerous receptors that regulates body functions Primary preclinical rodent models have found benefit in providing THCA as a neuroprotective molecule for various degenerative diseases, including models of Parkinson's and Huntington's disease related pathologies 24 , A single seizure should not last more than 5 minutes

All dogs were required to be negative for infectious disease titers including all tick-borne diseases, toxoplasma and neospora, as well as Dirofilaria Immitis

This concurs with Doran et al In line with the ALP rise, there is expected to be some alterations in either induction or inhibition of the CYP enzyme system that is involved in the metabolism of drugs like phenobarbital and zonisamide 12 , 14 , 29 , Published by Elsevier Ltd Serum concentrations of ASMs were measured at each time point throughout the study Goerl et al Cbd Oil For Dogs Locally Goerl et al. Renal parameters creatinine, urea nitrogen showed no significant changes over time or with treatment Table 2 Seizure control assessment Epileptic seizure events as recorded by owners were tallied over each 3-month period of time and the mean and standard deviations were calculated All data were assessed utilizing a Shapiro-Wilk test, and residual plots were examined to determine normality When you buy CBD oil for dogs, shop carefully All of the dogs in the study suffered from seizures All of the dogs in the study suffered from seizures. .

All of the dogs in the study suffered from seizures

Give your pet CBD regularly to reduce the severity and frequency of seizures Cannabidiol CBD is a non-psychotropic component of the Cannabis sativa plant, which has been shown to have anticonvulsant properties The seizure frequency observed from diaries were likely influenced by recall bias, which is a factor that cannot be controlled in survey research Alterations in medications were allowed during the protocol, yet few were observed This was due to lack of serum for one dog; the second dog's serum was lost on shipment to the diagnostic laboratory Dog Cancer Cbd Thc This was due to lack of serum for one dog; the second dog's serum was lost on shipment to the diagnostic laboratory. The research found that 89 percent of dogs who received CBD in the clinical trial had a reduction in the frequency of seizures This must be done very gradually under the supervision of a veterinarian because some dogs will not be able to be safely weaned off without their seizures returning The ability to shorten a seizure, and therefore reduce the damage from a seizure, is an incredible finding in scientific research Of these 11 candidates originally enrolled, only 1 dog discontinued from protocol within the first week, due to compliance issues dog resistant to medicating while initially taking the treatment medication However, these medications may have negative side effects and can cause further liver damage, which is why many pet parents are turning to holistic alternatives, including full spectrum hemp extract CBD for seizures in dogs However, these medications may have negative side effects and can cause further liver damage, which is why many pet parents are turning to holistic alternatives, including full spectrum hemp extract CBD for seizures in dogs. One of the dogs receiving a lower dose during the treatment phase was maintained on the lower dose during the placebo phase .

Serum chemistry, complete blood counts, serum anti-seizure medication ASM concentrations and epileptic seizure frequency were followed over both arms of the cross-over trial When measuring both phenobarbital and zonisamide concentrations over the week period, there were no differences when compared to placebo treatment for 12 weeks International Publication Date—February 16th, J Clin Pharmacol Lazy Dog Elicksors Cbd 7oz Dog Treats Honey Sweet Potato J Clin Pharmacol. We asked three veterinarians to weigh in on natural remedies that show promise Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher Epileptic seizure frequency decreased across the population from a mean of 8 And one of the most important uses of CBD oil for dogs is in the management of seizures THCA is the carboxylic acid form of THC which is found in the Cannabis sativa and is retained during extraction of the product used in this study THCA is the carboxylic acid form of THC which is found in the Cannabis sativa and is retained during extraction of the product used in this study. Furthermore, McGrath et al .

Furthermore, McGrath et al

In most of these cases, the dogs will not need long-term seizure medications if they make a full recovery from their underlying medical problem

Data availability statement The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation

All placebo bottles were lined with a thin layer of cannabinoid depleted terpenes, to provide the same odor upon opening the bottle to aid in blinding owners to the treatment vs CBD can provide multiple additional benefits Based on the current state of knowledge it is not possible to provide clear-cut recommendations for the use of CBD in canine epilepsy Based on the current state of knowledge it is not possible to provide clear-cut recommendations for the use of CBD in canine epilepsy. Kat Helgeson Kat Helgeson comes from a ten year career in social media marketing and content creation Typically, relief will be best achieved by dosing twice a day The legal environment can be confusing, but generally cannabis products are not legal for veterinary use, and therefore remain unregulated For some reason, pet owners have unfailing positive views of cannabis products, believing them to be safe and scientifically proven effective, despite a lack of evidence We cannot provide veterinary advice Please note we cannot provide health recommendations for individual animals, and we are not veterinarians We cannot provide veterinary advice Please note we cannot provide health recommendations for individual animals, and we are not veterinarians. Of course, unlike humans where precise accounts are likely, for dogs there may be seizures missed and unaccounted for The mean number of epileptic seizures during the placebo phase was 8 Randomized blinded controlled clinical trial to assess the effect of oral cannabidiol administration in addition to conventional antiepileptic treatment on seizure frequency in dogs with intractable idiopathic epilepsy Published Dec The good news is that those studies are happening The good news is that those studies are happening. She had powered through so many other issues and her happy, curious spirit remained After initial enrolment, the enrolment criteria was modified to increase dog numbers as there were patients identified that had been on ASM for long duration over 1 year and showed no bloodwork or urinalysis abnormalities indicating metabolic issues, yet the owners were resistant to general anesthesia for MRI and CSF assessment and were enrolled based on level 1 confidence of the International Veterinary Epilepsy Task Force .

In a prior study examining the ALP activity over 12 weeks in dogs treated with a CBD-rich hemp extract for refractory epilepsy, a 2—4-fold increase in ALP serum enzyme activity was shown, suggesting potential alterations to hepatic drug metabolism This facilitated dispensing for the next few weeks, where owners did suggest that they were nearly out of capsules, allowing us to assume relatively regular twice daily dosing All rights reserved All rights reserved. Following the approval of a highly purified CBD formulation, licensed in humans 1 specifically for the treatment of seizures associated with Dravet Syndrome, Lennox-Gastaut Syndrome and more recently Tuberous Sclerosis Complex, there has been a resurgent interest in the use of CBD for various forms of epileptic activity in various species 3 — 5

Studies suggest that the endocannabinoid system is altered by seizures and epilepsy

In fact, in , the U Demand has surpassed research as the public is progressively gaining access to these products and, on the advice of a friend or internet article, using them on their dogs Three dogs had phenobarbital decreased during the treatment phase, with one dog increasing the dose during the placebo phase, and one dog decreasing the dose during the placebo phase Watching your pet suffer a seizure can make you feel helpless If he feels any side effects at all, it will most probably take the form of mild drowsiness Daisy experienced a drastic reduction in the number and duration of her seizures within the very first week Prior to enrolment, all clients were provided with a client consent form outlining the study and the expectations during the research protocol In these cases, the brain is normal but is being affected by other problems in the body Results demonstrated that besides a mild increase in alkaline phosphatase, there were no alterations observed on routine bloodwork at 2, 6, and 12 weeks during either arm of the study Endocannabinoids are found throughout the body Two of nine dogs in the treatment group showed a fifty percent or greater reduction in epileptic seizure events No dogs receiving zonisamide or levetiracetam had alterations in dosing throughout the week study Release of bowel or bladder What Causes Seizures in Dogs? Individual seizures can be caused by a number of things, including ingesting poison, liver disease, fluctuating blood sugar, fever, strokes, brain cancer, anemia, electrolyte problems, or head injury CBD has been shown to have anticonvulsant properties that may reduce the frequency and severity of seizures in dogs McGrath S et al Four of the 5 dogs were recruited and completed the study .

Four of the 5 dogs were recruited and completed the study

Seizures are basically caused by the abnormal firing of neurons in the brain Dogs had complete blood counts, serum chemistry, pre and post-feeding bile acids, thyroid hormone assessment and urinalysis to rule out other metabolic issues as defined by the International Veterinary Task Force level II confidence When the nervous system has been impacted by an illness or injury, CBD supplements can restore homeostasis Hepatic parameters AST, ALP, bilirubin, cholesterol, glucose, albumin, and total protein showed no significant alterations over time with treatment Angela has seven dogs, Odie a year-old mini-schnauzer, Nina an 8-year-old Doberman When normality was rejected, the data was log transformed before analysis utilizing a mixed model analysis of variance According to our Chief Veterinary Officer, Dr CBD reaches a peak concentration at about 2 hours and is absent after approximately 6 to 8 hours

Split the daily CBD dosage into several doses throughout the day microdosing , to maintain bloodstream concentration

Smaller dogs require lower dosages, of course, and larger dogs will need more to see an effect CBD stands for Cannabidiol These findings are very similar to the pilot study performed by McGrath et al As ordinal data, the 3-month owner survey questions related to severity, frequency and overall seizure management for placebo vs Traditional Medications For Seizures in Dogs Seizures are traditionally treated with anti-seizure drugs with a goal of reducing the frequency and severity of the seizures Additionally, the National Institute of Health has published CBD research demonstrating strong reductions in epileptic seizures in rodents and shows CBD to be an effective therapeutic anti-convulsant Perucca E Kogan L et al The CB2 receptors — mainly in the immune system Greenwich Biosciences Inc Kat is also the author of numerous books for young adults Mean epileptic seizure days in the control group over the week period were 5 .

This was not the only study to find CBD for seizures in dogs to be a successful anti-epileptic supplement This lack of influence on serum ASMs concentrations is further corroborated in a recent publication by Doran et al MeSH terms Moreover, social media and public pressure has sparked a renewed awareness of cannabinoids, which have been used for epilepsy since ancient times How effective is CBD at treating seizures in dogs? Anecdotal feedback is highly encouraging First things first, we safely weaned her off of Phenobarbital and other pharmaceutical medications CBD also interacts with these endocannabinoid receptors Seizures themselves can cause irreversible brain damage if they go untreated Dose-related somnolence and sedation is a commonly reported side effect of CBD administration 10 , 14 and is of greater magnitude in human patients receiving the ASM, clobazam Complete blood counts, serum chemistry, and ASM concentrations Dogs were re-evaluated at 2, 6, and 12 weeks of each arm of the cross-over study .

Complete blood counts, serum chemistry, and ASM concentrations Dogs were re-evaluated at 2, 6, and 12 weeks of each arm of the cross-over study

Common causes include congenital abnormalities, brain tumors, or damage from a head injury The Likert scores were then compared between the two treatment phases for 13 of the 14 dogs enrolled One theory is that CBD affects the receptors that calm the neurons that fire during a seizure There is mounting evidence that constituent compounds within CBD-rich hemp extracts have efficacy as anti-epileptics and that dosing can be significantly decreased from CBD isolates 26 , Surprisingly, owners did not find any improvement in frequency but did feel that the severity of seizures was improved on treatment So … how does CBD oil work? Earlier I mentioned those endocannabinoid receptors Typically, seizures only last a few minutes and the dog will resume their normal activity afterward This rise can also be observed with ASMs like phenobarbital in dogs 28 , hence examination of hepatic parameters are of utmost importance when using any ASM It can also be mixed into food, and fatty foods can aid in the absorption of CBD, however the CBD will take longer minutes to enter the bloodstream as it passes through the digestive system, and may be less effective A similar scale was used related to seizure severity, seizure frequency and overall control of seizures during both week periods of placebo and treatment see Supplementary material

Discussion The major finding of our study is the statistically significant reduction in epileptic seizure frequency, as well as number of epileptic seizure days, as assessed through diaries kept by owners

The results have not been analyzed yet, but they hope to have some preliminary results to share this year and a publication out by next year ! All things considered, advances in technology, science, and medicine are happening faster every year, so rest assured that we will have an answer very soon Similarly, there is an interest in using CBD, cannabidiolic acid CBDA or cannabinoid-rich hemp products in the treatment of idiopathic epilepsy in dogs The examination of CBDA as an anticonvulsant is in its infancy and further studies are necessary, yet it does seem to provide similar efficacy in dogs, to primary CBD-rich hemp treatment alone Statistical analysis was performed with a commercially available software package JMP Hypnotic and antiepileptic effects of cannabidiol All of these dogs had partial response to ASM for over 1-year duration, without confirmation by MRI and CSF, and no alterations in treatment protocols within the prior 3 months of treatment No other treatment effects were observed across serum chemistry or complete blood count assessment during the week trial when compared to placebo The average Likert score for owner perceived improvement in frequency of seizures was a median of 3 no change; range 2—5 during the treatment phase The remaining dog completed the study, but it was later found that phenobarbital was instituted at the initiation of the study, so the data were removed from the analysis Additionally, these alterations were within 2 weeks of initiating treatment and remained static for the 3 months of treatment Angela Ardolino Angela Ardolino is a holistic pet expert who has been caring for animals for over 20 years and operates a rescue farm, Fire Flake Farm, in Florida Seizures can have profound effects on the endocannabinoid system Owner adverse event and epileptic seizure diary At the initial visit, owners were provided with a epileptic seizure diary to log events and cluster activity i CBD treatment has been well studied in both humans and rodents, showing reductions in seizure activity, particularly in various childhood conditions including Dravet's syndrome and Lennox- Gastaut syndrome 16 — The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest Serum zonisamide concentrations were not significantly different based on treatment or time, and no alterations due to treatment over time Table 3 The highest concentration is in the brain, spinal column, and nervous system Serum phenobarbital concentrations were not significantly different based on treatment, or over time and no alterations due to treatment over time Table 3 Rosenberg EC, et al They can also be distressingly severe, resulting in uncontrollable fits, tremors, and even loss of consciousness .

Ellevet Sciences was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication This would be defined as a partial response to an ASM 15 , and is considered clinically significant After getting her certificate in Medical Cannabis Biology and Therapeutic use from the University of Vermont School of Medicine, she founded CBD Dog Health to provide high quality, all-natural medical cannabis products designed specifically for pets Thirteen dogs were receiving potassium bromide; 11 dogs, zonisamide; 9 dogs were on phenobarbital; 13 on levetiracetam and one dog, topiramate Supplementary Table 1 All dogs from this cohort had been treated for over a year and remained only partially responsive to common highest tolerable doses of ASM yet still having at least one epileptic event per month as criteria for enrolment Owners were surveyed at the end of each week phase of the study for improvements in severity, frequency and overall management of seizures At the time of initiating the study, there were no laboratories performing serum analysis of any cannabinoid other than CBD Drug-to-drug interactions between various ASM and CBD have been explored in numerous studies and review articles in both humans and animals 3 , 6 , 10 — Nevertheless, cannabis products continue to explode in popularity and profitability Through the study, McGrath found that 89 percent of dogs who received CBD in the clinical trial had a reduction in the frequency of seizures Plus get new recipes delivered right to your inbox These dogs must have the underlying cause treated and are usually quite sick in general Serum bromide concentrations were not significantly different based on treatment, or over time and no alterations due to treatment over time Table 3 Unfortunately, at this moment veterinarians and veterinary neurologists have difficulty prescribing cannabinoids because of the paucity of sound scientific studies Researchers randomly assigned a placebo or hemp-derived CBD to dogs in the trial for 12 weeks .

Researchers randomly assigned a placebo or hemp-derived CBD to dogs in the trial for 12 weeks

Serum chemistry evaluations showed no significant changes for any serum electrolyte sodium, potassium, chloride, phosphorus, calcium, or magnesium over time or treatment data not shown

Cannabinoids and Epilepsy Yes, evidence from humans and lab animals does suggest that CBD may prove useful in veterinary medicine, but to date, there have been no in-depth studies of CBD in dogs to prove this All 10 remaining dogs completed the protocol by the summer of Measuring serum cannabinoids at intervals would have allowed for better assessment of this factor and would have allowed for regression statistics to be run on the CBD serum concentrations to clinical response Hence, 14 dogs completed the protocols with adequate data for analysis All authors contributed to the article and approved the submitted version DT and JW were involved in data analysis and manuscript review All other time points were evaluated in the mixed model analysis of variance For these reasons, it is very important to control seizures as much as possible There was control to some extent by dispensing the initial 6 weeks of treatment or placebo and then asking about relative needs to complete the trial Microdosing helps maintain the CBD in the bloodstream, which aids in reducing seizures in dogs Furthermore, the serum chemistry and complete blood count profiles across the week trial period on treatment were no different than the placebo treatment phase, with the exception of a mild rise in serum alkaline phosphatase She takes pride in her ability to communicate the culture and values of an organization via the written word Do not try to move the dog unless they are in an unsafe area for example, if they are laying on the edge of a dock over water or are near a fire Secondary Seizures Secondary seizures are those that have a clearly diagnosed brain abnormality as the cause of the seizure The recent pandemic has however, prevented adequate enrolment, alongside client hesitance to perform anesthesia for MRI and CSF collection This is because of the way CBD is structured However, the seizures were pulling her away from spending her twilight years playing and resting peacefully CBD is an extract of the cannabis plant marijuana , but unlike the other major active ingredient, deltatetrahydrocannabinol THC , it does not cause psychoactive effects .

These enzymes are also involved in the metabolism of many ASMs, and so some interaction or inhibition of metabolism could be anticipated

The ability of THCA to reach the central nervous system has yet to be reported, but THCA appears to have variable effects on rodent seizure models and improvements in Huntington's disease models, as well as potent anti-inflammatory activity; this may be due to its interaction with the peroxisomal proliferation receptor system that modulates the inflammatory response 24 ,