Numerous researchers are carrying out studies to elucidate the role of the ECS in controlling epileptic seizures While baseline and test sessions were held in a climate-controlled environment, prior to the post-stress measure dogs were walked outside briefly to access the sample room The black bars within the box plots indicate the median; the dots represent the outliers The black bars within the box plots indicate the median; the dots represent the outliers. As a social species, dogs form close bonds with humans and other animals Dogs with IE were more likely to lack probe data due to not meeting criterion in the training phase, compared to controls Pet owners employ various approaches to managing these issues, from training, to giving medications and supplements, often with mixed results Based on some pharmacokinetic parameters, it is possible that the 2 h window between dosing and the stress event were not enough to observe the therapeutic effects in the dogs tested 38 , Many of the dogs in this study showed excessively frequent aggressive behaviours Can Cbd Oil Help Older Dogs With Weak Rear Legs Many of the dogs in this study showed excessively frequent aggressive behaviours. The 24 dogs were observed exclusively in their home-cage for 12 h each, for a total of h Conversely, in the study by Mejia et al This suggests that in this study population, epilepsy does not induce a negative long-term affective state i Table 2 The behavioural patterns utilised in this study grouped into categories As each video was scored by two raters, a mean score for each of the individual QBA terms, and the relevant component scores were generated for the purposes of analysis As each video was scored by two raters, a mean score for each of the individual QBA terms, and the relevant component scores were generated for the purposes of analysis. .

Asterisks indicate significant differences between treatment groups within each phase Barnard et al Dogs also sat significantly more during the separation test Additionally, when the frequency of aggressive behaviour is so high that it occurs out of context, becoming unpredictable, it can be considered pathological 50 , The distance from the starting location to each bowl location was 4 m, with each of the five target locations equidistant from each other over a total of 3 m Cbd Oil Effect Dog Seizure The distance from the starting location to each bowl location was 4 m, with each of the five target locations equidistant from each other over a total of 3 m. CBD is a non-psychoactive phenolic cannabinoid typically derived from the processing of hemp Cannabis sativa L In dogs, there are some studies concerning tolerability not only when CBD is administered as a single dose 25 , 35 , 88 but, above all, for prolonged use over time, when the accumulation of such lipophilic compounds is possible In addition, lip licking was included in the car analysis, distance traveled was included in the separation analysis, and whining was included in the combined and separation analysis This system is essential in promoting synaptic plasticity responsible for learning and the ability to respond to emotionally impacting adverse events By modulating the activities of these receptors, CBD exhibits multiple therapeutic effects, including neuroprotective, antiepileptic, anxiolytic, antipsychotic, anti-inflammatory, analgesic and anticancer properties 3 By modulating the activities of these receptors, CBD exhibits multiple therapeutic effects, including neuroprotective, antiepileptic, anxiolytic, antipsychotic, anti-inflammatory, analgesic and anticancer properties 3.

The discovery of a pre-established endogenous cannabinoid system has led researchers to hypothesize that the active ingredients, mainly phytocannabinoids, contained in Cannabis sativa both medical and industrial cultivar — this last also known as hemp , could interact with this system, producing both the therapeutic and psychotropic effects of the plant

The discovery of a pre-established endogenous cannabinoid system has led researchers to hypothesize that the active ingredients, mainly phytocannabinoids, contained in Cannabis sativa both medical and industrial cultivar — this last also known as hemp , could interact with this system, producing both the therapeutic and psychotropic effects of the plant

Then a 1 The latter item was included in the criteria to avoid biasing the results by measuring behavioural responses due to acute stress; in fact, the literature reports that dogs entering the shelter have different behavioural, physiological and immunological responses due to acute stress 36 , These differences can be attributable to a too small sample size, different experimental sampling times applied in the various studies and a large individual variability i All testing was conducted by two blinded researchers who were responsible for ensuring the event conditions were standardized Cbd Oil For Brain Tumors In Dogs All testing was conducted by two blinded researchers who were responsible for ensuring the event conditions were standardized. While there was a numerical increase in the mean HR for both groups in the separation test alone, this was not statistically significant CBD: 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 Additionally, anthropomorphism following an owner's absence can lead to humans misinterpreting dog emotional states, which can further negatively impact pet welfare Indeed, due to a positive perception of CBD use, many pet owners are increasingly requesting this option to relieve their pets, and many veterinarians are exploring this possibility for their patients Currently, the CBD doses used in veterinary medicine are variable and empirical Currently, the CBD doses used in veterinary medicine are variable and empirical. When reading articles about a new medication, it is important to keep in mind that pharmacologic findings in mice or rats often do not translate to humans Anxiety is an emotional response to a situation or stimulus which can be perceived as threatening 21 , and is a common reason for dogs to show behaviours that owners find a problem Table 1 The 24 dogs selected for the study, their weight, principal behavioural disorder, group and dosage Blood samples were collected into a clot activating serum tube and kept on ice until analysis and aliquoting was performed within min of sampling The study by Corsetti et al Cbd Oil For Small Dogs Dosage Chart The study by Corsetti et al. Dogs were left alone for min while being monitored by a researcher in an adjacent room via the CCTV system Pain The empiric use of Cannabis as an analgesic goes back more than 1, years Hunt et al Aggressive behaviour is part of all species' behavioural repertoire; the ultimate causes that led to its evolutionary selection concern function in intra-and inter-specific competition 51 ; in other words, aggressive behaviour has evolved to allow individuals to be competitive for obtaining the resources necessary for their survival .

Behaviour tasks General testing procedure Each dog took part in the tasks individually in a standardised room at the Royal Veterinary College, London, away from a clinical setting Behaviour tasks General testing procedure Each dog took part in the tasks individually in a standardised room at the Royal Veterinary College, London, away from a clinical setting. An essential basis for concluding that endocannabinoids modulate pain was provided by preclinical studies, which demonstrated the presence of endocannabinoid receptors, endogenous cannabinoids and enzymatic machinery for endocannabinoid biosynthesis and degradation in peripheral and central structures devoted to pain modulation, and their antinociceptive and antihyperalgesic effects in models of transient physiological and inflammatory and neuropathic pain, respectively 42 — Finally, Brioschi et al For mammals, the response to a stressor, which can be physical or emotional, as for example infections, burns or anger 33 involves the hypothalamic—pituitary—adrenal axis reactivity e This resulted in only whining being analyzed from the combined analysis and separation test, and only lip licking being analyzed from the car test Materials and methods Animals and husbandry Forty healthy, adult dogs, twenty-two males and eighteen females of three breeds 17 Labrador Retrievers, 8 Beagles, and 15 Norfolk Terriers , with a mean age of 4 Cbd Oil For Dogs To Stop Itching Materials and methods Animals and husbandry Forty healthy, adult dogs, twenty-two males and eighteen females of three breeds 17 Labrador Retrievers, 8 Beagles, and 15 Norfolk Terriers , with a mean age of 4. Dogs were required to complete a minimum of 16 trials and had a maximum of 50 trials to learn the discrimination Indeed, Gamble et al HF: statistical analysis Cannabidiol does not appear to interact with CB1 or CB2 receptors directly, yet it has been implicated in altering endogenous levels of endocannabinoids such as AEA Interactions are largely unknown but could potentially be severe without proper monitoring Interactions are largely unknown but could potentially be severe without proper monitoring. 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 These receptors are part of a class of receptors 5-HT that usually interact with serotonin 29 and are strictly associated with physical health 30 , mood 30 and stress [reviewed in 31 ] As such it is probable that extremely anxious dogs were not represented in this sample, particularly not in the IE group The only three scientific studies currently published on the efficacy of CBD in behavioral disorders reported a lack of an anxiolytic effect of CBD on behavioral responses to fear-inducing stimuli 74 , but a decrease in aggressive behavior toward humans 75 , and a reduction in canine stress The different sex ratio of the selected dogs was due to the shortage of females that met the parameters for the selection and, at the same time, presented behavioural problems Dog Cbd Kidney The different sex ratio of the selected dogs was due to the shortage of females that met the parameters for the selection and, at the same time, presented behavioural problems. A QBA previously developed to evaluate welfare of shelter dogs and dogs in a mock veterinary setting 46 , 49 was modified for the purpose of this study to include terms more relevant to the specific scenarios .

A QBA previously developed to evaluate welfare of shelter dogs and dogs in a mock veterinary setting 46 , 49 was modified for the purpose of this study to include terms more relevant to the specific scenarios

Each sound lasted 2 s and was played at the same volume

However, the effects of the ECS in the modulation of anxious states are not unique: the complexity of the ECS is probably responsible for the various anxiolytic and anxiety-producing effects manifested by agonists interacting with CB1 receptors, but also TRPV1 and 5 -HT1A 72 ,

Further studies are warranted to define better whether CBD could be a valid adjunct in canine treatment The only study where the role of CBD in acute postoperative pain following a TPLO was investigated did not give satisfactory results Conclusions The results obtained from this study suggest that a period of separation and car travel are stressful events for dogs, with travel in a vehicle eliciting a more pronounced stress response Accessing such populations for practical studies may be challenging Kentucky Cbd Dogs Accessing such populations for practical studies may be challenging. Clomipramine is a commonly used anti-depressant to treat separation-related disorders and has been shown to reduce destructive behavior, as well as inappropriate defecation and urination, but not the prevalence of vocalizations Secondly, to evaluate the effect of a single dose of a THC-free broad-spectrum CBD distillate on measures of canine stress during these two events Dogs were provided with comprehensive training and socialization programs, adjusted to the needs of the individual dogs as per the Institute's pet keeping requirements Introduction In the last 30 years, research has made considerable strides in studying and understanding the endocannabinoid system ECS and its bodily functions Negative effects of epilepsy upon cognition are well documented in people with epilepsy, ranging from mild impairments to severe cognitive decline Negative effects of epilepsy upon cognition are well documented in people with epilepsy, ranging from mild impairments to severe cognitive decline . The antiepileptic properties of CBD have been studied in various animal models of acute epilepsy Besides the described signs, a common finding during prolonged treatment with CBD in some but not all dogs across clinical studies is the elevation of alkaline phosphatase enzyme ALP activity, which generally return to baseline values after a washout period 25 , 35 , 54 , 56 , 58 , 67 , 82 , 88 , 89 , Although dogs in this sample had some severe clinical features e All raters were assessed for inter and intra-rater reliability at the start of the study on a subset of videos coded three times by each rater The task ended with a final four two P and two N trials in a randomised order Joy Organics Cbd Oil For Dogs The task ended with a final four two P and two N trials in a randomised order. In contrast, a modulatory effect was not observed for serum IgA or glucose concentrations between treatment and control groups However, its kinetic behavior has yet to be fully elucidated Table 1 Demographic features of the study population and sub-populations .

However, less is empirically known regarding the efficacy of this compound in dogs, with the majority of clinical studies examining the efficacy of CBD in alleviating the symptoms of pain resulting from osteoarthritis 37 , 41 , Full size image Figure 5 Displacement activities of dogs treated with cannabidiol CBD at the start of the study T0 , after 15 T1 and 45 T2 days from the beginning of the treatment, and 15 days after the end of administration of CBD T3 Full size image Figure 5 Displacement activities of dogs treated with cannabidiol CBD at the start of the study T0 , after 15 T1 and 45 T2 days from the beginning of the treatment, and 15 days after the end of administration of CBD T3. What remains beyond doubt is that their behaviour denounced a high level of malaise

The speaker was placed on a table 2 m behind the MID bowl

This location was selected so that the sounds came from the direction the dog was travelling towards Behavioral disorders Emotional behavior is also included among the many physiological functions modulated by the ECS Some of them showed a high level of aggressiveness before entering the kennel, but their permanence in that environment may have increased it or it may have been brought about in dogs that did not present it to start with However, increased motor activity has been observed in dogs suffering from separation-related anxiety previously 6 The placebo soft gel capsules were manufactured to match the conformity of the CBD-containing capsules, minus the CBD, to maintain the blinding of the study Is It Advisable To Put Cbd Oil On Dog Treats The placebo soft gel capsules were manufactured to match the conformity of the CBD-containing capsules, minus the CBD, to maintain the blinding of the study. Conflict of interest All authors are employees of Mars Petcare UK, a manufacturer of dog food and a provider of veterinary care It is possible more significant differences would be identified if a cross-over design was used Additional investigations are necessary to widen the sample of dogs and to combine a behavioural therapy with CBD administration AH: investigation and writing—original draft preparation One last consideration deserves to be made One last consideration deserves to be made. AH and TK: methodology The dogs involved in this study were selected because they showed behavioural symptoms that lead to a diagnosis of behavioural disorders and one of the symptoms was excessive aggressive behaviour .

The dogs involved in this study were selected because they showed behavioural symptoms that lead to a diagnosis of behavioural disorders and one of the symptoms was excessive aggressive behaviour

Owners were not present during testing to promote consistency between dogs; however, all dogs met the experimenters with their owners prior to the tasks, in a relaxed manner, for at least 10—min to habituate to them Funding This study was funded by Mars Petcare This protocol was followed equally for the P and N bowl locations This protocol was followed equally for the P and N bowl locations. This is even more critical when evaluating the endocannabinoid system and medications that might affect it as there are reported differences between species Dogs in the CBD group had significantly higher mean ear temperatures compared to the placebo group at baseline Notwithstanding the dog's emotional and physical discomfort, these behaviors could distract the driver, possibly endangering the pet, caregiver, and other road users To assess intra-rater reliability of the QBA terms, each rater re-scored a random selection of 10 videos Additional research is required to fully understand the complex effect of CBD on canine wellbeing Additional research is required to fully understand the complex effect of CBD on canine wellbeing. As such, sampling more drug-resistant dogs with higher seizure frequencies and behavioural comorbidities, or dogs with stress induced seizures 11 may have increased the likelihood of detecting changes in affective state One of the most robust results of this study is that CBD treatment did not decrease the activity of the dogs studied, as already highlighted for other species It has more than chemical compounds including terpenes, hydrocarbons, ketones, aldehydes and phytocannabinoids 3 Among the six studies that met the inclusion criteria for this review, being randomized clinical trials RCTs that described the efficacy or safety of cannabis in monotherapy or as an adjuvant in naturally diseased animals 25 , 55 — 57 , 67 , 75 , four of them 25 , 55 , 57 , 67 were classified as having some concerns in the overall bias assessment using the Revised Cochrane Risk of Bias Tool for Randomized Trials RoB 2 .

Introduction Idiopathic epilepsy IE is the most common chronic neurological condition in dogs, with an estimated prevalence of 0 Introduction Idiopathic epilepsy IE is the most common chronic neurological condition in dogs, with an estimated prevalence of 0. Besides the widespread empiric use of CBD in pets, the research is trying to obtain proof of its efficacy and lack of adverse effects and to know its pharmacokinetics to define an appropriate posology Nevertheless, there are numerous commercially available products on offer to pet owners that claim to support dog emotional health

This led to an explosion in popularity of CBD and availability of commercial products containing this phyotcannabinoid

Control dogs were eligible if free of neurological conditions, and were recruited based on their match with a member of the IE group, on age within 2 years due to the effect of judgement bias 50 , sex and breed Control dogs were eligible if free of neurological conditions, and were recruited based on their match with a member of the IE group, on age within 2 years due to the effect of judgement bias 50 , sex and breed. Eye, ear and nose temperatures captured using infrared thermography have previously been used for evaluating stress in dogs 46 , 70 , though there are inconsistencies as to whether an increase or decrease in temperature is indicative of stress This paradigm allowed some dogs unable to participate in the full training for the cognitive bias task to be tested and used a biologically relevant stimuli to trigger innate emotional responses Administration of CBD has been reported to increase HR in dogs following exposure to fireworks sounds Introduction Pet dogs are likely to experience a variety of stress-inducing scenarios over their lifetime, often due the relationship they have with people 1 , 2 The room contained a metal dog crate with a single piece of vet bedding, a raised hammock bed covered with a piece of vet bedding, a piece of vet bedding in the center of the room, a cardboard box a common enrichment for this population of dogs relative to the size of the dog being tested, a filled water bowl and a selection of hard rubber toys Figure 2A The room contained a metal dog crate with a single piece of vet bedding, a raised hammock bed covered with a piece of vet bedding, a piece of vet bedding in the center of the room, a cardboard box a common enrichment for this population of dogs relative to the size of the dog being tested, a filled water bowl and a selection of hard rubber toys Figure 2A. Once inside, the handler removed the lead or harness from the dog and exited the room The selection process for breeds for this study was based upon their popularity, epilepsy prevalence and severity Although the difference in the decrease of aggressive behaviour between the control and the treated group was not significant, possibly due to the small sample size, our results suggest that the treatment with CBD could reduce the frequency of aggressive behaviour towards humans and highlights the need for further studies The sound was opportunistically recorded by one of the authors SLH from their own dog barking defensively in response to a stimulus they found aversive Therefore, it is perhaps unsurprising that the increase in HR was not buffered by CBD administration Therefore, it is perhaps unsurprising that the increase in HR was not buffered by CBD administration. They are recognized to be a flag of physical and emotional discomfort in humans and in non-human animals 46 , 47 , 48 , This trial is a placebo-controlled crossover trial The elevated cortisol levels observed in the current study were similar to those recorded in dogs in response to stress in a veterinary clinic 54 , The sound was not intended to be novel at point of exposure, and dogs were habituated to the sound prior to starting the attention bias test These dogs constituted 33 matched pairs, with an additional two controls due to drop out of two dogs with IE before behavioural tasks took place These dogs constituted 33 matched pairs, with an additional two controls due to drop out of two dogs with IE before behavioural tasks took place. The left end of the VAS scale corresponded to the minimum score 0 , meaning the expressive quality indicated by the term was entirely absent in the dog, whereas the right end of the scale represented a maximum score , meaning that the quality indicated by the term was strongly present in that dog For the cognitive bias task, although running latencies s to probe locations are often adjusted, as groups were recruited to be matched by breed, age, and sex, and the arena size for testing was standardised across all owners, the raw latencies were analysed without adjustment, as well as adjusted scores as outlined in Mendl et al McGrath et al In terms of efficacy, most studies have been conducted to test the ability of CBD to relieve pain in dogs with osteoarthritis .

In terms of efficacy, most studies have been conducted to test the ability of CBD to relieve pain in dogs with osteoarthritis

Cannabidiol CBD can alleviate stress and anxiety in humans but the effect it has on canine stress is less well-documented

References Kearsley-Fleet, L These effects seem mainly dependent upon mast cell down-modulation, but other cell types i This behavior has also been reported previously, with increases in vocalization when an owner leaves their dog 67 , This behavior has also been reported previously, with increases in vocalization when an owner leaves their dog 67 , . There is limited evidence supporting the efficacy of CBD in alleviating stress or anxiety in pets, with previous studies not demonstrating a positive effect These negative results may be due to a number of factors, which will now be discussed Full size image On reaching criterion for learning the discrimination, dogs moved immediately onto the test phase Dogs were classified as having learnt the spatial discrimination between P and N when they were approaching P faster than N by at least 0 We hypothesized that at least one of the events would elicit behavioral and physiological measures of stress in dogs, and that a single administration of CBD would have a positive effect on those measures We hypothesized that at least one of the events would elicit behavioral and physiological measures of stress in dogs, and that a single administration of CBD would have a positive effect on those measures. Typically, information related to how dogs cope with car travel is documented via owner-reported surveys 4 , whereas here behavioral and physiological parameters were captured A factor analysis with a varimax rotation was used to identify factors of interest, and the weightings from this analysis were used to generate factor scores Indeed, even if the Cmax observed in fed condition was significantly higher than in fasted condition, no significant difference was observed in AUC values This may be due to their attention being oriented away from the reward and towards the threatening cue, due to its increased salience compared with non-threatening or familiar sounds; however, further detailed behavioural analysis e In the same year, another study showed that administration of CBD reduced marble-burying behaviour in mice In the same year, another study showed that administration of CBD reduced marble-burying behaviour in mice . Thus, to avoid or at least reduce the first-pass metabolism and increase its plasma concentrations, some alternative routes of CBD administration were tested, albeit without satisfactory results Various physiological and behavioral measures were collected via wearables, video cameras, and blood sampling prior to, during and directly after the test sessions Figure 1 .

Various physiological and behavioral measures were collected via wearables, video cameras, and blood sampling prior to, during and directly after the test sessions Figure 1

To compare the difference between treated and placebo group, we utilised the Mann—Whitney U test If dogs then continued to not approach the bowls within 30 s for trials 11—16 when no direction to the was given bowls by the experimenters , the task was abandoned

We need to allow time for the science to catch up to the new-found interest and investment in CBD in order to truly understand the benefits and risks of manipulating the endocannabinoid system and its receptors

Similarly, fluoxetine administration can reduce separation-related behaviors but may also cause lethargy, inappetence, seizures and depression in some dogs 24 , Mean temperature readings were captured within each ellipse 46 , Seizures are sometimes preceded by a prodromal pre-seizure phase which can include signs of distress including increased fearfulness and restlessness Before starting the administration of CBD based oil and the placebo, each dog was observed for one hour a day for three consecutive days T0 , at three different times of the day morning, between A Before starting the administration of CBD based oil and the placebo, each dog was observed for one hour a day for three consecutive days T0 , at three different times of the day morning, between A. But different measures of canine stress appear to be more or less sensitive to CBD in different stressful scenarios A single CBD treatment showed no impact on plasma cortisol, HR and a range of behaviors associated with canine stress 43 however treats were administered 4—6 h prior to testing Every day the shelter operators monitored the dogs to spot symptoms vomiting, diarrhoea of possible health issues; such occurrences were registered and reported to the responsible veterinarian We hope that results will be available in the next year or two Ethogram used to measure dog behavior during the separation and car travel tests Ethogram used to measure dog behavior during the separation and car travel tests. Research continues to move forward in human trials , and in animal trials at the Colorado State University Veterinary Teaching Hospital Through the two principal receptors CB1 and CB2 , it takes part in the anti-inflammatory process 22 , in the management of anxiety 23 , in the immune function 12 , 24 and in lowering pain Trials were presented in the same order for each dog: the first two were baited P followed by two un-baited N trials, the following 46 trials were pseudo-randomised using randomizer In recent survey-based studies, owners of dogs with epilepsy have reported increases in fear and anxiety following the onset of epilepsy in their dog Transportation is stressful for some animals due to the intense combination of auditory and visual stimuli experienced in a moving vehicle Transportation is stressful for some animals due to the intense combination of auditory and visual stimuli experienced in a moving vehicle . In domestic dogs, an indirect suggestion comes from 58 who found that the frequent display of displacement activities such as self-grooming, scratching and body shaking, are associated with a lower level of antioxidant capacity in shelter dogs Firstly, to understand the impact a separation event and car travel has on canine stress, using a combination of subjective and objective measures This action is probably mediated by CB1 receptors localized in several areas involved in pain control, such as periaqueductal grey matter, rostroventromedial medulla, some areas of the thalamus and amygdala, and A5 noradrenergic nucleus 44 , 48 , Although the mean post-test cortisol concentrations in the CBD group were numerically lower than the placebo group after the separation test, that difference was not statistically significant It acts as an allosteric modulator of the CB1 and CB2 receptors present in nociceptive and pain neurons, but also as a potent agonist and antagonist of other G-protein coupled receptors in the immune and central nervous systems It acts as an allosteric modulator of the CB1 and CB2 receptors present in nociceptive and pain neurons, but also as a potent agonist and antagonist of other G-protein coupled receptors in the immune and central nervous systems. .

It acts as an allosteric modulator of the CB1 and CB2 receptors present in nociceptive and pain neurons, but also as a potent agonist and antagonist of other G-protein coupled receptors in the immune and central nervous systems

The model assumptions were assessed via visual inspection of the residuals, and variables were log transformed if they violated model assumptions No power analyses were conducted prior to the start of the study, as the sample size was instead determined by the parallel safety study In a case series, Mogi and Fukuyama reported different and sometimes contradictory results in the three evaluated dogs treated with CBD 0

The only measures that did not load on any factor for any of the analyses were standing, sitting, lying, blood glucose, and IgA

There is some, but minimal evidence that CBD may be effective in other forms of epilepsy in humans There were no other significant effects of treatment Figure 6 Dogs were left in their home pen, for min and recorded with video cameras Logitech Webcam, Logitech, Lausanne, Switzerland placed outside the kennel door Ethics statements This study was approved by the Animal Welfare and Protection Office of the Municipality of Rome, which is responsible for sheltered dogs according to Italian laws, and by the Sanitary Local Health Unit Rome 3, which is responsible for the health of the sheltered dogs Current research into treatments aimed at alleviating stress in dogs during periods of separation and during transportation are generally focused on the efficacy of pharmacological interventions 24 , 25 , alone or in combination with behavioral modification programs 5 Current research into treatments aimed at alleviating stress in dogs during periods of separation and during transportation are generally focused on the efficacy of pharmacological interventions 24 , 25 , alone or in combination with behavioral modification programs 5. Future studies should be focused on both these aspects of neurobiology in domestic dogs B Car test setup showing metal crate secured in rear of the car However, there was no significant effect of treatment on this behavior Figure 8 Developing methods to test affective state without excluding cognitively impaired individuals is a future challenge for animal welfare science Developing methods to test affective state without excluding cognitively impaired individuals is a future challenge for animal welfare science. .

Moreover, it must be emphasized that, as shown on Tables 2 — 5 , some studies published on hemp-based medicines in dogs are not randomized, placebo-controlled, double-blinded, and differ in dose, duration, and, last but not list, type of used product pure CBD or hemp extracts containing different amounts of other Cannabis components — see later the discussion about the entourage effect Therefore, it is likely this population of dogs experienced mild stress in response to being both separated from their caregiver, as well as being socially isolated Indeed, CBD exhibited a wide range of activities, including anxiolytic, panicolytic, and anticompulsive actions, as well as decreased autonomic arousal, decreased conditioned fear expression, increased fear extinction, reconsolidation block, and prevention of the long-term anxiety-provoking effects of stress CBD has been shown to down-regulate stress-related signals that can lead to chronic inflammation and some pain responses in humans At the start of the study, they were either given placebo or CBD owners and study personnel were not aware of which dogs received CBD or placebo until the study ended At the start of the study, they were either given placebo or CBD owners and study personnel were not aware of which dogs received CBD or placebo until the study ended. Neither anaesthesia nor euthanasia, or any kind of animal suffering, was part of the study Seizures also induce a stress response, with cortisol levels significantly increased 40 min after a seizure compared with a time-matched point on a non-seizure day

A key issue in this study was the attrition of the study sample from the start to the end of testing, and thus the quantity of useable data and the characteristics of the resulting sample analysed

Baseline videos were min in length; car travel min and for the separation videos the first 5-min, middle 5-min and last 5-min were selected to create a min video to be scored by raters using both the QBA scales and coded ethograms Our results clearly suggest that CBD treatment might be effectively used to improve welfare in dogs housed in a shelter However, the study by Mogi and Fukuyama 69 reported different and sometimes contradictory results in the three evaluated dogs There were no significant effects of treatment or timepoint on activity when the stress tests were analyzed combined There were no significant effects of treatment or timepoint on activity when the stress tests were analyzed combined. Although not discriminatory between study groups, the novel auditory attention bias task described here shows promise, with dogs taking significantly longer to reach the rewarded location when exposed to a threatening auditory cue compared with neutral or pre-habituated auditory cues In addition, as this study tested the unknown affect treatment of epilepsy in a novel attention bias task, further validation of this task is required, including exploring the responses of dogs with known affect treatments e Individuals with emotional seizure triggers exhibited an attentional bias towards threatening stimuli compared to neutral stimuli, as compared to those with non-emotional seizure triggers Over this 6 month study dogs were given daily administration of CBD and indicators of stress were measured following exposure to acute and chronic stress-inducing events As such, to maximise sample size, all dogs who reached this stage were included in analyses and signalment was included in statistical modelling As such, to maximise sample size, all dogs who reached this stage were included in analyses and signalment was included in statistical modelling. Deabold et al All owners were provided with a study information sheet and had the study fully explained to them by an investigator Is CBD better than other anticonvulsants for my dog? Based on clinical evidence the short answer is "we don't know yet .

Is CBD better than other anticonvulsants for my dog? Based on clinical evidence the short answer is "we don't know yet

Again, intranasal IN administration of a formulation containing pure synthetic CBD did not show any significant difference with the oral administration of pure CBD in MCT oil when normalized for the dose, except for Tmax, which was significantly shorter following IN treatment 0 Such approaches are increasingly being explored in farm 42 , 44 , 46 , 60 , 61 and laboratory 62 animals, but have been relatively neglected in companion animals to date Such approaches are increasingly being explored in farm 42 , 44 , 46 , 60 , 61 and laboratory 62 animals, but have been relatively neglected in companion animals to date. Although they are commonly used measures in animal welfare science, factors such as circadian rhythms and exercise can impact cortisol and HR independent of stress Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission However, epilepsy could nonetheless induce negative short-term affective states e Car travel A Ford S-Max mini-van vehicle was used for each car test with a metal crate, appropriate for the dog's size, placed on the top of folded down rear seats inside the vehicle Soft gel capsules containing CBD-rich hemp extract showed a significant increase in mean Cmax value, but not in that of AUC, compared to the administration of the same extract in sesame oil Soft gel capsules containing CBD-rich hemp extract showed a significant increase in mean Cmax value, but not in that of AUC, compared to the administration of the same extract in sesame oil . A previous study examined the impact CBD had specifically on aggressive dogs in a shelter environment, a behavior which can occur due to stress The sample consisted of 24 dogs divided into two groups that were created by assigning the dogs alternately: 12 dogs were assigned to the treatment group and 12 to the control group Regarding tolerability, the reported studies allow considering two primary limits: the relatively small sample size and the paucity of long-term studies Figure 1 Schematic of the judgement bias task setup Gathering a range of data from dogs during these situations and identifying appropriate ways to measure canine wellbeing is a necessary step prior to evaluating the effectiveness of interventions aimed at alleviating canine stress Gathering a range of data from dogs during these situations and identifying appropriate ways to measure canine wellbeing is a necessary step prior to evaluating the effectiveness of interventions aimed at alleviating canine stress. .

Overall, there were statistically significant differences between treatment groups based on serum cortisol concentrations, but not for IgA or glucose Figure 3

The weightings from this analysis were used to generate component scores for the relevant identified components

Additionally, the potentially confounding variables breed, sex and age were included as fixed effects It has previously been highlighted that screening out of dogs with more extreme behaviour is typical with cognitive bias research due to concerns for experimenter safety and welfare of the dog It has previously been highlighted that screening out of dogs with more extreme behaviour is typical with cognitive bias research due to concerns for experimenter safety and welfare of the dog . Most dogs will experience traveling in a vehicle during their lifetime, the frequency of which is dependent upon the owners' lifestyle, demographic, and geographical distance to places such as parklands, veterinary clinics, and dog husbandry professionals e In general, it would be an erroneous approach to try to ascribe the hyper aggressiveness of a dog to a few causes; moreover, it would be equally wrong and naive to neglect the possibility that the alteration on several levels of the complex system underlying aggression does not cause a chronic state of malaise for the animal There are in the shelter, of course, temporal and spatial limitations that vary from shelter to shelter, which could affect the results The same bowl was used throughout testing in both locations to limit olfactory cues They can be associated with different kinds of situations but all situations have in common uncertainty and anxiety as the stressful causal factors 46 ; some pharmacological studies, reviewed in 67 , confirmed that displacement activities mainly scratching are a valid measure of stress in nonhuman primates and human subjects They can be associated with different kinds of situations but all situations have in common uncertainty and anxiety as the stressful causal factors 46 ; some pharmacological studies, reviewed in 67 , confirmed that displacement activities mainly scratching are a valid measure of stress in nonhuman primates and human subjects. A similar favorable safety profile has been further confirmed by a study by Vaughn et al Following the probe trials, a further trial involving the placement of an empty bowl in the positive location was conducted, to check that dogs ran just as fast to this empty bowl as to the usual baited bowl in this location and were thus not relying on odour cues to detected whether the bowl was baited Task 1: Judgement bias task The methodology described by Mendl et al Deiana et al As per the efficacy of CBD in skin diseases, from the three published studies, it appears that CBD can decrease the occurrence of pruritus in healthy and atopic dogs 82 , As per the efficacy of CBD in skin diseases, from the three published studies, it appears that CBD can decrease the occurrence of pruritus in healthy and atopic dogs 82 , . It has also been hypothesized that the ECS exerts a tonic activity able to modulate the nociceptive threshold in basal conditions and hyperalgesia and that cannabinoids and opioids can mutually potentiate each other However, when considering all the published studies, results are not always consistent There were significant differences in reasons why the judgement bias testing stage was not reached between groups, with the IE group more likely due to cognitive reasons i .

An intervention which is gaining popularity is the administration of cannabidiol CBD , likely in response to it being perceived as a natural treatment among pet owners Also, the type of CBD used pure or co-extracted with other phytocannabinoids can have influenced the pharmacokinetic results Also, the type of CBD used pure or co-extracted with other phytocannabinoids can have influenced the pharmacokinetic results. In contrast, dog eye temperature was observed to increase when dogs were in a veterinary setting 46 , 70 which was also interpreted as a stress-related response There was no significant effect of treatment on the change of any of the temperature measurements from baseline to post-test Figure 4 Pharmacokinetics of CBD Cannabidiol is a high lipophilic molecule

Results of the factor analyses suggested two factors that were common across the car, separation and combined analyses based on the strength of loadings and the variance explained Table 4

The ECS can be synthetically defined as the set of cannabinoid receptors [such as Type 1 cannabinoid receptor CB1 , Type 2 cannabinoid receptor CB2 , G protein-coupled receptor 55 and GPR55, GPR , transient receptor potential vanilloid TRPV and peroxisome proliferator-activated receptor PPAR ], endocannabinoids [compounds produced by the body that bind to cannabinoid receptors, such as anandamide AEA and 2-Arachidonoylglycerol 2-AG ], enzymes responsible for their synthesis and their catabolism and genes that code for these proteins

Materials and methods Animals and housing The subjects of this study were 24 domestic dogs 20 neutered males, 2 unneutered males, 2 spayed females with various kind of behavioural problems, randomly drawn from a list of animals matching the inclusion criteria Behavioral measures Qualitative behavior assessment Analysis of the QBA data using a PCA suggested one primary component of interest based on the strength of loadings and the variance explained Table 3 Another common situation that can elicit stress in dogs and results in negative emotional states, is car travel 19 — Reported side effects include vomiting and sedation Di Marzo, V, and Wang, J All authors contributed to manuscript revision, read, and approved the submitted version As for CBD, this compound has been studied in a wide range of animal models, such as the stress-induced anxiety model, the panic disorders and compulsive behavior model, the fear conditioning test, the fear extinction test and the reconsolidation blockade test Few studies have assessed the effect of CBD on dog health and behaviour Correspondingly, owners of dogs with higher seizure frequencies have reported in survey-based studies that their dogs have a lower QOL than owners of dogs with lower seizure frequencies This last was observed following oral administration of CBD-purified Cannabis extract diluted in MCT oil, but, in any case, the carboxy-metabolite resulted produced in a greater quantity Figure 1 Aggressive behaviour towards humans of dogs treated with cannabidiol CBD at the start of the study T0 , after 15 T1 and 45 T2 days from the beginning of the treatment, and 15 days after the end of the administration of CBD T3 Similarly, only a mild ptyalism was observed when CBD was compounded in a flavorless oil Rev Sci Tech A further reason for loss of data was some dogs being too anxious to perform in the tasks, leading to the experimenters electing to cease testing In veterinary practice, it is generally administered orally .

Dogs that did not complete the judgement bias task due to distress or physical problems were not tested in the attention bias task on ethical grounds Designing tests to measure affective state that avoids intensive training and could be used in cognitively impaired individuals remains a challenge in animal welfare science The collection of behavioural data was repeated in the same way in the following intervals: from the 15th to the 17th day T1 and from the 43rd to the 45th day T2 of the administration of treatment; from the 15th to the 17th day T3 after the end of the treatment Indeed, during the sign-up process, the authors noted that more owners from the IE group requested additional details regarding the tasks and potential stressors than control owners However, this study was designed to control these factors with feeding, exercise, husbandry activities and sampling all conducted at the same time each day within a colony environment This alteration is usually attributed to a reversible upregulation of cytochrome pmediated oxidative metabolism of the liver 97 , Local temperature and relative humidity were not captured during this study The present study aimed to understand the impact of being left alone and traveling in a car on measures of canine stress, and establish whether a single dose of a tetrahydrocannabinol THC -free CBD distillate could positively influence any measures of stress Lastly, the large individual variability in the plasma concentrations observed in all studies further weakens the interpretation of obtained data However, the operators were instructed not to alter the usual quantity and quality of daily interactions Furthermore, CBD, even at high doses, does not produce anxiety-producing effects

An administration of CBD every 24 h did not result in any effects on behavioural categories related to stress but seemed to reduce aggressive behaviour

Dogs were further randomized into two groups to denote the type of testing paradigm they would experience within those groups Responses to the ambiguous stimuli in the judgement bias task differed from some other studies Behaviors were scored from video footage of the dogs during the separation event and during car travel Table 2 This can negatively impact the human-animal bond and often leads to dog relinquishment 7 CBD also may interact with other receptor systems such as the TRPV, adenosine reuptake inhibitor, and PPAR in the inflammatory cells or neurons, based on in vitro and in vivo assessments in humans and rodents Evidence on the link between seizure frequency and the severity of anxiety is mixed 26 , During the habituation process, each dog was monitored for their responses to the sound More in details, epileptic seizure frequency decreased from a mean of 8 The results also further highlight the importance of a multiple measures approach to better understand the impact certain scenarios have on canine wellbeing, a routinely recommended approach in animal welfare studies 46 , 75 , The three noises were chosen due to their assumed different emotional salience; a neutral sound bubbling water , a novel sound computerised musical notes , and a negatively valenced sound dog barking defensively CBD based oil consisted of an extraction from aerial parts and inflorescences of the plant Cannabis Sativa in organic extra virgin olive oil to the proportion of g of Cannabis Sativa inflorescences and aerial parts in 1 L of oil Other adverse signs noted in dogs, even if less frequently, were somnolence and lethargy 56 , 69 , 82 as well as ataxia 56 , 67 , Further refinement of the task presented here is needed; some dogs still failed to complete attention bias task as well as the judgement bias task due to anxiety This is a limitation as these factors may have allowed environmental influences on the change in surface body temperature to be distinguished from physiological responses indicative of stress Once the dog was inside the secured crate, the car boot was closed, and the researcher sat in the driver's seat .

Indeed, the liposomal packaging of CBD oil seems the best option, as no clinical side effects were noted The mitigating effect of CBD treatment varied by measure and test, with some indicating a significant reduction in canine stress compared to the placebo group The novel sound was used to test a noise that all study dogs would never have been exposed to, and hence have no prior learning about before testing started CBD may also cause diarrhea in some patients but it is unclear whether this is due to the CBD component or the delivery oil itself However, if CBD treatment causes a reduction in the aggressive behaviour of the dogs, this effect, in turn, might improve the relationships between the dogs and the staff of the kennel, facilitating dog management and increasing the level of dog welfare; in fact, it has been found that walking on a leash or having physical contact with humans improves the level of dog welfare housed in a shelter 58 , 62 , Studies on clinical efficacy of CBD-based products in the treatment of behavioral disorders in dogs This type of behavior, coupled with increased activity and arousal, may be related to hypervigilance which is commonly observed in dogs 62 , cats 63 , and rats 64 experiencing a stress response

For this test the same room set up was used, and experimenters assumed the same roles

Moreover, the molecular complexity of bioactives in different hemp distillates potentially resulting in altered CBD bioavailability and pharmacokinetics means that caution should be exercised before generalizing the results from this study to CBD-containing products more broadly

The bowl was always baited and the dog had 30 s to approach and reach the bowl from the starting location The timing of testing may further explain the lack of effect identified in this study The clinical importance of such finding is still unknown, and without the results of other investigations to assess liver function, such as biliary acids and histopathologic exams could be irrelevant: in this sense, it is interesting to report the study of Bradley et al Data obtained so far allow hypothesizing that the ECS plays a crucial role in modulating the brain activities in brain areas directly or indirectly affected in patients with epilepsy In this study, the lack of effects on dogs' anxious behaviour attributable to the administration of CBD may be due to oral instead of intraperitoneal administration, as studies on rodents 19 , 65 and dogs 66 have indicated The purpose of this study was to determine if CBD affects stress related behaviour in shelter dogs It has also been widely used for its medical and psychoactive effects 1 , 2 This low bioavailability, associated with a large individual variability observed in almost all conducted studies, is a challenge in identifying an appropriate dosing regimen Neurological disorders Abstract Idiopathic epilepsy IE is the most common chronic neurological condition in dogs, characterised by recurrent seizure activity and associated with negative behavioural and cognitive changes Overall, data indicate that the activation of the ECS by exogenous cannabinoids proves effective in limiting joint pain both centrally and peripherally Each sound was played three times and presented in a pseudo-randomised order so that none were presented twice in a row , and the order of presentation was kept the same for each dog The heart rate data were also converted into HRV [measured as root mean square of successive differences between normal heartbeats RMSSD ] by estimating the between-beat time differences from the HR measurements Despite the evidence that, through the analysis of some physiological parameters, some drugs reduce the stress level in dogs, such as gabapentin 69 or clonidine 70 , the drug effect on stress-related behaviour has been neglected These mean scores were then modeled as above using linear mixed effects models Research is being conducted at CSU to evaluate the effect of CBD in the treatment of idiopathic epilepsy, osteoarthritis, and certain types of cancers Albeit in one study no differences were noted between groups for any of the recorded outcome measures 57 , from results obtained in all other studies CBD seemed able to significantly reduce pain and increase the activity of dogs, thus improving their quality of life 24 , 25 , 54 — We are currently enrolling dogs for a much larger CBD-for-epilepsy clinical trial and administering a higher dose of CBD .

A third study a randomized complete block design, placebo controlled study was not conducted on atopic dogs, being intended to determine the influence of CBD 1 Consistent with this, dogs who received the CBD also exhibited less whining and sitting behavior and traveled further when they were left alone The judgement bias paradigm has been used to provide evidence of long-term impacts on affective state in dogs, including neurological disorders e Three trained raters coded each behavior using the relevant ethograms Given the potential negative impact of IE and its comorbidities on affective state, this study aimed to use an existing judgement bias task and a novel attention bias task to investigate its impact on affective state in dogs when compared to healthy controls

Moreover, these studies differ in sample times, number of withdrawals and number of treated animals from 3 to 8 , all influencing the pharmacokinetic parameters

General linear mixed models 52 LMMs were constructed with unadjusted or adjusted latency as the outcome variable, testing for the effects of study group IE vs The dogs belonging to the treatment group were given a CBD based oil while the dogs belonging to the control group were given a placebo In , Lima and co-workers published a systematic review to summarize the evidence of efficacy and safety of the use of Cannabis for treating animal disease obtained so far, and to assess the risk of bias in each study Study design A blinded, parallel design study was conducted at the Waltham Petcare Science Institute to determine the anxiolytic effects of CBD in parallel with a long-term safety study For the attention bias task, latency to reach P s was used as the outcome variable in an LMM, with the effects of study group and sound type and their interaction tested as a fixed effects while accounting for the repeated effect of Dog ID as a random effect, and the potentially confounding variables breed, sex and age were included as fixed effects Our results did not show any effect of CBD on the reduction of those behavioural patterns Task 2: Attention bias task Following the judgement bias task, each dog took part in the novel attention bias task It is evident that measures are not uniform across the scenarios, suggesting certain parameters may be more, or less, applicable in different testing situations Her seizures were successfully treated with cannabis that contained high concentrations of CBD a non-psychoactive component of cannabis and very low concentrations of THC the psychoactive component of cannabis Although there is increasing interest in the use of CBD for mood disorders, with some evidence of anxiolytic effects in humans 73 , 74 , 75 , effects in dogs are unknown Reasons for non-completion of this task are outlined in Fig Conclusions Our study found that idiopathic epilepsy had no detectable effect on long-term judgement or attention bias in this particular study population when compared to matched controls; however, these results require further investigation due to the attrition of dogs with greater situational anxiety in both case and control groups and cognitive impairment particularly in dogs with idiopathic epilepsy from the study sample, and the relatively mild phenotype of the idiopathic epilepsy cases Piloting was conducted during test development on dogs not included in this study, to identify a sound volume that was not so loud as to induce startle behaviour e The variability in body temperature may be influenced by environmental factors in the different test settings Additional research is required to better understand the effect of CBD at other dosages, formulations, and whether cumulative administration improves efficacy Our results provide further evidence for the recently recognised cognitive impairments in canine epilepsy patients, that are well documented in human epilepsy patients This suggests traveling in a vehicle was likely more stressful than being separated from conspecifics and humans Therefore, confirming these research findings in pet dogs in traditional home environments will be beneficial .

Therefore, confirming these research findings in pet dogs in traditional home environments will be beneficial

Seven dogs four Labrador Retrievers and three Border Collies had experienced no seizures in the past 3 months Likewise, della Rocca et al Coded behaviors Two ethograms were created which included a series of behaviors to be scored, incorporating the evaluation of both events frequency measures and states duration measures However, before discussing this lack of effect, a premise is due

As dogs with IE were treated with varying combinations of medications, and none of these drugs were used to treat dogs in the control group, statistically assessing their individual effects in the overall population was not possible

For example, some dogs chose to leave the testing arena and instead approach the exit door on commencement of each trial Discussion According to the information found in the literature e On completion of the journey, the dog was removed from the car by their handler and led to a room for post-test sampling Dogs were kept behind a barrier on a long line lead with no pressure placed on it by experimenter 1 whilst experimenter 2 placed the bowl in one of the five locations Latency s , measured live with a stopwatch, was recorded for the time it took for the dog to travel from the starting point at the barrier to reaching the bowl, with a maximum of 30 s allowed before being called back behind the barrier to begin the next trial Unlike many pet dogs, this particular population do not routinely undergo car travel, so the novelty of the event may have caused a more pronounced stress response The criteria for selection were: age between 1 and 10 years estimated by standard veterinary methods ; physically healthy; presence of behavioural disorders detected by the veterinarian ; permanence in the shelter for at least 9 months Table 1 Although the association between epilepsy and the ECS has not been fully elucidated, the complex relationship between brain excitability and the ECS suggests that phytocannabinoids may induce beneficial effects on epilepsy, paving the way for the possibility of developing new treatments involving the use of compounds, especially CBD, that selectively target individual elements of the endocannabinoid signaling system There were no significant effects of treatment on the combined stress measure at either timepoint, or on the change from baseline to test Overall, it was evident that some measures of canine stress changed significantly from baseline after exposure to these specific events, suggesting the situations elicited a negative emotional response in dogs .

Each rater completed an online form for each assigned video, which comprised of a Visual Analog Scale VAS ranging from 0 to placed next to each term IE is also associated with negative perturbations in behaviour and cognition, including decreased trainability 14 , signs of cognitive impairment 15 , 16 , increased attention seeking 17 , aggression 18 and ADHD-like behaviours e Besides the large variability of formulations, in some cases the presence of trace amounts of other cannabinoids was specified, while most studies did not report whether other phytocannabinoids such as cannabichromene, cannabigerol, and cannabinol, among others or other chemical components of hemp such as terpenes, triterpenes, and flavonoids were present The CB1 and CB2 cannabinoid receptors are expressed in canine keratinocytes 5 , 7 , 8 , with higher immunoreactivity to CB1 and CB2 in atopic dogs than in healthy dogs 5 Dog ear temperature was found to decrease in a previous study evaluating the effect of periods of separation 74 , which is comparable to findings here After min, the handler returned and placed the dog back on lead In fact, dogs entering the shelter have behavioural responses due to acute stress 36 , It has been demonstrated that hyper-attachment greatly increases not only the incidence of separation-related anxiety, but also increases the severity Furthermore, it appears that cannabinoids may modulate the activity of the noradrenergic and opioid spinal systems 44 , 46 , 48 , Latency to reach the bowl P was the outcome measure of this task Percentage of dogs remaining in the study at are reported for each stage of the study by study group The behavioural observations were conducted by a single observer each time who sat in front of the cage; observers did not interact with the dogs, so the dogs became rapidly accustomed to the presence of the observers The dogs were housed in single cages of 4 m2 with an indoor and outdoor area Sonntag Q, Overall KL Video cameras were positioned at the front and rear of the crate Dogs that received the CBD treatment also had significantly lower serum cortisol concentrations than dogs that received a placebo Separation event The separation test room 3 Nevertheless, the limited number of published studies and the occurrence of bias in almost all require caution in interpreting findings Epilepsy in Border Collies is frequently characterised by a severe clinical course and poor response to medical treatment Furthermore, the distribution of cannabinoid receptors in the brain also suggests a physiological role for endocannabinoids in the control of movement and perception, regulation of sleep and appetite, inhibition of learning and memory processes, regulation of emotional states such as pleasure and aggression , neuroprotection, as well as in enhancing the action of opioids .

Indeed, the dogs often sat by the door, possibly awaiting their caregiver's return Dogs with idiopathic epilepsy seizures with no other abnormalities found; presumed genetic basis were enrolled in this study However, no significant pharmacokinetic interactions were found between CBD and phenobarbital when simultaneously administered to healthy dogs

There are very few papers on the effect of different treatments in this behavioural category 68 , for example, did not find an effect of the appeasing pheromone in reducing displacement activities in shelter dogs

The value of emissivity was set at 1 as per manufacturer guidelines, replicating previous studies 44 , Albeit smaller reductions, there was a statistically significant larger median reduction of seizures in the CBD group and a larger number of dogs in the CBD group showing a reduction in seizures compared to placebo By contrast, the activation of CB1 receptors mediates the anticompulsive effects, the enhancement of fear extinction, the blockade of reconsolidation and the ability to prevent the long-term anxiety-producing consequences of stress The study was a clinical trial and its purpose was to determine if CBD treatment can decrease disturbed and stressed behaviour in shelter dogs, in terms of decrease in displacing activities, stereotyped and aggressive behaviour All dogs were housed in pairs within kennels at the Waltham Petcare Science Institute Leicestershire, UK with free access to indoor and outdoor environments The hypothesis that the ECS plays a role in the modulation of emotional behavior is supported by the demonstration that CB1 receptors and Fatty Acid Amide hydrolase FAAH - the enzyme responsible for the degradation of endocannabinoids , as well as the endocannabinoids AEA and 2-AG, are expressed and produced in brain areas such as the amygdala, nucleus accumbens, hippocampus and prefrontal cortex involved in stress, fear, emotions and reward mechanisms If a dog was distressed at any point during the study, the tasks were abandoned, and the dog returned to their owner The parameters age, sex, breed, and housing location were considered when balancing the groups Dogs in the separation group were habituated to the testing room until they were deemed comfortable in the environment with their experienced handler present In fact, following rectal administration of a suppository containing mg of CBD, corresponding to a dose between 6 Endogenous cannabinoids produce antinociceptive and antihyperalgesic effects at peripheral, spinal and supraspinal levels Finally, all the measures were combined to create an overall stress measure using a factor analysis Despite the relative frequency of people transporting dogs and the welfare implications this may have on pets and humans, the transport of companion animals has not been widely researched Although mild stress is not considered harmful 9 , welfare is compromised if an animal experiences high levels of acute stress or is exposed to prolonged stressors 10 which can lead to chronic physical and emotional health issues In trying to minimize the number of variables that could have affected the results in such a variable environment, we chose dogs that had been in shelter for at least nine months and displayed signs of chronic stress .

Dogs under treatment displayed the same level of attention towards the environment before and after the treatment A major reason for loss of data in the judgement bias task was dogs with IE being unable to learn the discrimination within the allotted trials Most papers published on cannabinoids in pruritus deal with ALIAmides i Attention bias tasks are based on the principle that anxious individuals are more likely to direct attention to potentially threatening, or even innocuous, stimuli 21 , 30 , Briefly, ellipses were drawn around the anterior surface region of the eye, the exterior surface of the ear flap and the anterior surface of the nose The authors further hypothesized that attentional biases related to threat in patients with TLE may exacerbate disease, by sustaining emotional vulnerability and seizure occurrence Consistent with these observations, studies examining canine stress have described cortisol levels increasing 58 , 59 and HRV lowering in response to a perceived negative stimulus 60 , 61 , with dog behaviors related to lip licking, such as hypersalivation, barking and restlessness occurring more frequently during car travel 4 Eligibility was screened using an online sign-up questionnaire

There are reports of liver enzyme elevations in humans as well and periodic bloodwork monitoring is recommended for all patients taking CBD for this reason

Terms included in the Qualitative Behavioral Assessments QBA used to measure dog behavior during baseline, the separation, and car travel tests With specific regard to the canine species, the presence of cannabinoid receptors or their ligands has been identified in skin and skin appendages of healthy dogs and dogs with atopic dermatitis AD 4 — 8 , gastrointestinal tract 9 , 10 , peripheral and central nervous system 11 — 13 , joints 14 and embryo Moreover, PEA also acts indirectly by elevating the levels, reducing the degradation, and increasing the affinity of endocannabinoids for their receptors Detailed results for the analyses of individual terms from the QBA are presented in the Supplementary material Sixteen dogs successfully completed the study Three models were run for each measure, with analyses looking separately at car and separation stress tests, as well as at both stress tests combined However, data in humans suggest that these neurological signs in the dogs are attributable to effects of THC and not CBD A more recent study investigated the efficacy a lower 1 In contrast, in a recent study of dogs trained on the same spatial discrimination, only one dog 0 Dogs had experienced a mean of 3 .

CBD has the potential to alter the blood concentration of anticonvulsants in humans Additionally, some measures of stress in dogs were significantly affected following administration of CBD, suggesting it may have efficacy as an intervention for acute stress in dogs In mammals, the ECS is very complex and modulates different kind of organism responses A pharmacokinetic study was completed at CSU and published in Throughout this habituation period and during all behavioural tasks, each dog was monitored for potential signs of stress, anxiety and frustration caused by the setting or the tasks potential behaviours listed in Supplementary File 1 Full size table The selected dogs showed severe behavioural disorders such as compulsively licking the cage walls, chewing on objects until they were destroyed, coprophagy or having attacks of aggression such as to lead to self-injury; none were under therapeutic, pharmacological or behavioural treatment If the true mechanism of seizure control were to be established, this may help us understand which patients would benefit from its use All methods were performed in accordance with the relevant guidelines and regulations The endocannabinoidome: the world of endocannabinoids and related mediators These were each presented only once to avoid learning effects, and were presented in the same order MID, NP, NN separated by four pseudo-randomised trials two P and two N The absence of a history of cutaneous or systemic disease, the histopathological findings, and the remission after symptomatic treatment and discontinuation of the CBD product allowed the Authors to consider a possible CADR cutaneous adverse reaction to drugs to CBD, as described in men 96 , or to additional substances in the vehicle As it is well known 43 , 58 , sheltered dogs in general and the dogs in this study in particular, suffer from inter- and intra-specific social deprivation, total lack of interactions at night, and lack of exercise because they are in cages People with epilepsy are more likely to report anxiety than those without epilepsy 25 , or patients with other chronic medical issues Different oral formulations are likely to reduce the incidence of these signs Stress is a mental, physiological, or emotional state characterized by a factor that is altering the homeostasis of a living organism Epilepsy In recent years, phytocannabinoids have been emphasized in treating various neurological disorders, including epilepsy Cortisol also significantly increased for the CBD group for the car test Some authors suggested that displacement activities are behavioural constituents of the adaptive stress response 67 ; morphologically, in nonhuman primates these behavioural patterns have something to do with body care: self-grooming, scratching, body shaking, stretching and yawning .

Further, it is widely available in a range of products claiming positive benefits, stress-reducing properties and improved pet emotional wellbeing A Separation test room setup showing position of vet bedding center, with a dog on top , then clockwise from top: cardboard box, water bowl, dog bed, crate, and toys Any missing data were imputed using multiple imputation Prevalence and risk factors for canine epilepsy of unknown origin in the UK In humans, an antipsychotic activity of CBD was assessed and found to reduce the occurrence of apomorphine-induced stereotypies 64 , but the mechanism by which CBD exerts its anxiolytic effects has not been fully clarified, yet A total of videos were randomly assigned between the three raters Further work will be required to fully understand the relationship between stress and activity in canines, and the impact CBD has on it Canine keratinocytes also express TRPV1 receptors 6 It is therefore possible that surface body temperature may not be suitable as a standardized measure of canine stress unless under highly controlled conditions

Dog behavior Dog behavioral data from baseline and during the two testing sessions were collected from video footage by trained observers

According to these considerations, the results presented here acquire value since they suggest a possibility of response to the treatment in a challenging environment, that could be even greater in an environment where the limitations described above are less present and the possibilities to control the dogs are greater This helps us extrapolate a dose to use during clinical trials to study its effect on various diseases There were no significant changes from baseline to post-test for IgA or glucose Figure 3 Full size image To compare responses of IE and control dogs to the ambiguous probe locations in the test phase, unadjusted latency data were first used in a linear mixed model LMM The sound source was hidden by the experimenter standing behind the MID bowl What are CSU veterinarians studying? Researchers are evaluating the pharmacokinetics how much of a medication is absorbed and how long it is detectable in the bloodstream and safety of CBD in dogs and cats Imepitoin has been found to have anxiolytic as well as antiseizure effects in physically healthy dogs 67 , 68 , 69 ; however, no changes in anxiety levels were reported by owners of dogs treated with imepitoin for IE If dogs exhibited any signs of distress or sensitisation Supplementary Table S1 , the sound was stopped and the attention bias task was not undertaken The study consisted of a parallel design, so individual differences in dog behavior and preferences may have contributed additional variation For these dogs, the P bowl location was baited five times before moving straight into the attention bias task trials to reinforce this location 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 Factor scores were then modeled as above using linear mixed effects models, to determine the effect of treatment and timepoint Despite some non-significant results, our findings suggest that it is worth doing more research to further investigate the effect of CBD on dog behaviour; this would be certainly valuable because the potential for improving the welfare of dogs in shelters is priceless CBD has low acute intravenous i From obtained results, some evidence exists supporting the beneficial role of CBD Studies on clinical efficacy of CBD-based products in the treatment of skin diseases in dogs Following the recent COVID pandemic, the incidence of separation-related behaviors in dogs has increased and cases are expected to continue to rise 12 , 17 , No dogs showed disease symptoms during the study, except for one dog Gargamello, under treatment that had a single episode of diarrhoea, during the second day of T2, which disappeared without pharmacological intervention; so we did not exclude this dog from the study .

The same author claims that if the aggression sequence is altered, this indicates that the aggression has reached a pathological level Statistical analysis The behavioural patterns utilised to collect data during the observations were grouped into categories Table 2 , generated on the basis of information drawn from the literature 41 , 42 and repeatedly used in the past by our working group 43 , 57 , Explore further Therefore, to define a rational regimen of dosing and avoid the empirical use of CBD, more studies are necessary to elucidate the pharmacokinetics and pharmacodynamics of CBD in light of inter-individual CYPp expression and polymorphisms leading to metabolism differences across dog populations It has been proposed that CBD acts through polypharmacological interactions leading to modulation or prevention of neuronal hyperexcitability In many countries like Italy, where sheltered dogs cannot be euthanased except for health reasons or proven dangerousness according to the law, it is our duty to guarantee them an acceptable level of well-being

The placebo consisted of extra virgin olive oil only

All authors have read and agreed to the published version of the manuscript Cannabidiol is subject to a sizeable hepatic metabolism, witnessed by the identification of several metabolites in canine urine However, comparison of ASD-treated vs These interactions lead to a decreased firing of the nociceptive fibers and a reduced release of pro-inflammatory and pro-pain mediators, followed by a reduction of the inflammatory and pain response 44 , 48 — Takahashi et al Epilepsy is characterised by recurring seizure activity, which in practice represents an individual experiencing at least two unprovoked seizures at least 24 h apart 4 Their results suggest that orally administered CBD in dogs was not detrimental with a time gap of 12 h or more between one administration and another Gamble and collaborators 15 found that a CBD-based treatment decreased pain and increased activity in dogs with osteoarthritis Various observations also suggest a role of the ECS in the control of vasomotor functions and fertility, as well as of tumor cell proliferation 2 It is possible that the population of dogs with IE sampled here did not experience sufficiently severe epilepsy or anxiety to induce perturbations in affect severe enough be detected in the paradigms tested When socially isolated or separated from bonded individuals for prolonged periods of time, separation-related behaviors may be exhibited 8 , 12 , Precisely how CBD mediates these effects is both complex and not fully understood In men, it is therefore unlikely that they give rise to abuse, although they are not entirely free of side effects Dogs were tested in a previously-validated spatial judgement bias task, and a novel auditory attention bias task testing attention to sounds with different valence or salience neutral, novel pre-habituated, threatening In addition to the effects of epilepsy and seizures themselves, cognitive side effects of ASDs are reported in people There were no other significant effects of timepoint on infra-red temperature measurements Figure 4 A series of behavior attributes were scored using a Qualitative Behavior Assessment QBA , and an ethogram was used to code a separate set of dog behaviors Dogs recruited to this study are likely to have exhibited less severe epilepsy and anxiety due to self-selection of owners volunteering to take part in the study Conflict of interest The 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 .

Morris et al An Author Correction to this article was published on 09 December This article has been updated Abstract Among the phytocomplex components of Cannabis sativa L Similar results were found by McGrafth et al During the judgement bias task, experimenter 1 could gently encourage the dog to leave the starting point verbally a maximum of two times The discovery of cannabinoid receptors, the identification of endocannabinoids and their biosynthetic and degradation pathways, and the understanding of signal transduction mechanisms paved the road for scientific research in this area Discussion Idiopathic epilepsy did not induce a negative judgement or attention bias in our sample of dogs compared to healthy controls, when a commonly used judgement bias test and a novel auditory attention bias test was applied Kogan et al Figure 2 Aggressive behaviour towards humans of dogs receiving olive oil as a placebo at the start of the study T0 , after 15 T1 and 45 T2 days from the beginning of the treatment, and 15 days after the end of the administration of olive oil T3

The dogs are rarely socially isolated from humans or conspecifics

If five no-go trials occurred consecutively, the task was abandoned for that dog The protocol was carried out in accordance with the relevant Italian guidelines and regulations Garcia et al For dogs, entering a kennel represents a stressful event e Such response patterns were previously described in Muller et al Acknowledgments The authors thank the staff and pets at the Waltham Petcare Science Institute for enabling this study In veterinary medicine, the use of Cannabis derivatives as a therapeutic approach started to be considered a few years ago To be included in the IE groups, dogs must have been clinically diagnosed with IE to at least a tier 1 confidence level Discussion and conclusion An appropriate drug dose at specific time intervals needs to be administered to obtain an adequate pharmacological response Dogs were weighed to establish an accurate dose of CBD relative to individual bodyweight Additionally, there were positive loadings for activity, whining and distance traveled in the separation analysis, and positive loadings for lip licking, and negative loadings for activity and HRV in the car analysis Results Physiological measures of stress Serum cortisol, immunoglobulin A, and glucose Due to a lack of homoscedasticity of the residuals, a log-transformation was applied to the models for cortisol and IgA Dog behavior was recorded using Mediarecorder software Noldus, Netherlands via two cameras Logitech webcam; Logitech, Lausanne, Switzerland mounted in the rear of the car, at either end of the crate, connected to a laptop computer on the front passenger seat .

The mechanism by which CBD exerts its anticonvulsant effects is unknown Prior to the study, dogs were habituated to the testing environments and associated equipment and underwent appropriate training to facilitate sample collections e In this study a more notable effect was observed between various baseline measures and exposure to car travel, compared to baseline and separation test Table 1 resumes the data obtained from the pharmacokinetic studies published so far The gastrointestinal absorption of CBD seems very low Overall, these data provide a more detailed understanding on how dogs cope during these routine events Once separated from their owners, all dogs were given a 10—min habituation period in the study room with the experimenters before the behaviour tasks began Despite a certain number of available pharmacokinetic studies, the kinetic profile of CBD has yet to be fully known, probably because of the very different experimental conditions Serum cortisol and heart rate, both widely used physiological measures of mammalian stress, were elevated significantly following exposure to the car test Factors extracted by the factor analysis of all measures when analyzed with both stress tests combined, or with separation and car tests separately Indeed, although several studies on the pharmacokinetics of CBD in dogs have been conducted, the kinetic profile of CBD is not yet fully known, probably because of the very different experimental conditions used, such as different oily vehicles sunflower lecithin, MCT, and sesame oil , pharmaceutical forms tablets, chews, microencapsulated oil beads, or drops , type of CBD synthetic and purified or full spectrum extract and route of administration oral, rectal, intranasal or oral transmucosal Table 1 In both studies, phytocannabinoids [0 Although future studies could disprove this result, it is possible to hypothesize that CBD is effective in chronic but not in acute pain Dogs in the present study received a larger oral dose of CBD via capsules that was administered more acutely, just 2 h prior to testing However, studies were prevalently focused on short- to medium-term treatment, while CBD is usually employed for long-term treatment .