Dr. Shadi Ireifej explains the science behind Separation Anxiety Disorder in dogs. He also discusses how to diagnose and several possible treatments (including increasingly popular CBD treatments).
By Pet Pro Supply Co. Featured Veterinarian,
Dr. Shadi Ireifej DVM DACVS
Co-founder and Chief Medical Officer at VetTriage
What is Separation Anxiety Disorder in Dogs?
Separation anxiety disorder is a disease involving psychological, emotional, behavioral, and physiological aspects. This disorder has been reported in birds, dogs, cat, horse, pig, sheep, goat, cattle, cetaceans (whale, dolphin, or porpoise), and human and nonhuman primates. This discussion will be focused on the canine companion population.
Canine separation anxiety disorder occurs when a given dog is forced to remain at a physical distance from their owner. Dogs affected by separation anxiety disorder can exhibit psychogenic grooming ("over-grooming") and secondary self-inflicted injury. This disease may be similar to phobic disorders and panic attacks in people. Dogs may show over-exaggeration and overreact to ambiguous or unpredictable situations. Similar to bipolar disorders in people, dogs can fluctuate between manic or agitated states and depressive or subdued states. These clinical signs may be more overt in more severe cases.
How Common is Separation Anxiety in Dogs?
Approximately 14% to 20% of canine patients from general veterinary practices show signs of separation anxiety disorder in their owners’ absence.
However, as with other anxiety disorders in veterinary patients, underdiagnosis of anxiety-dependent separation problems has been previously reported due to misinterpretation of normal and pathological anxiety and the lack of recognition of mild clinical signs by pet owners.
As such, it is suspected that up to 50% to 56% of the overall canine population may actually display clinical signs of anxiety at some point in their life.
To quantify it: out of the total population of approximately 160 million dogs in the United States and Europe, this disease may affect approximately 85 million dogs. Also, separation-related problems are one of the primary cited reasons for the relinquishment of dogs to animal shelters.
Physiological Changes from Separation Anxiety Disorder in Dogs
The more psychological aspects of this disorder are obvious, but also prone to interpretation and subjectivity. The definition of this disorder from within the lens of physiological changes has proven interesting from both an understanding of the disease as well as in aiding veterinarians to diagnose the disease with increased clarity.
There are numerous physiological changes that have been reported in studies of dogs and other animals to be associated with various psychosocial stresses. These include: increased glucocorticoids, increased adrenocorticotropic hormone (ACTH), altered cardiovascular parameters, altered immune parameters, and increased nerve growth factor. Additionally, the neuropeptide oxytocin has been found to attenuate anxiety, central fear responses, and neuroendocrine reactivity. Conversely, the neuropeptide vasopressin has been associated with augmented anxiety and fear expression and increased neuroendocrine stress response.
These two neuropeptides are not only a focus of research because of their direct involvement with affecting behavior as it relates to the stress-response and their seemingly polar opposite effects on the body, but also because they are synthesized in the brain. Oxytocin and vasopressin are synthesized in the hypothalamus, primarily in large magnocellular neurons situated in the supraoptic and paraventricular nuclei, and secreted from their axons, which are projected to the neurohypophysis, into the general circulation.
Diagnosing Separation Anxiety Disorder in Dogs
Physiological biomarkers can be measured from any numbers of bodily fluids and are helpful objective measures of a specific disease. Because the diagnosis of behavior disorders carry a large element of subjectiveness, such behavior biomarkers would be incredibly valuable.
In a 2019 veterinary research study, dogs with separation anxiety have been shown to depict exploratory behavior at a rate that is significantly less than normal dogs. Additionally, those dogs with anxiety were significantly more persistent in expressing passive stress-coping strategies aimed at seeking proximity to their pet owners. Upon reuniting with their owners, those dogs with separation distress spent significantly more time jumping up on the strangers than normal dogs did.
The researchers in this study also found that the concentrations of oxytocin and vasopressin hormones collected from the salivary glands of anxious dogs did not differ between samples taken before the separation. However, vasopressin concentrations immediately after separation were significantly higher. These results indicated that dogs with separation distress became more anxious than normal dogs when separated from their owner in an unfamiliar environment and provided preliminary support for the use of salivary vasopressin as a possible biomarker for anxiety-related responses in dogs.
Many antidepressants exert their positive clinical effects by inhibiting serotonin reuptake, norepinephrine reuptake, or the reuptake of both. The selective serotonin reuptake inhibitor class of antidepressants act specifically on synaptic serotonin concentrations by blocking its reuptake in the presynapse and increasing levels in the presynaptic membrane. Thus, the concentration of available serotonin, and therefore its effects, is increased.
The selective serotonin reuptake inhibitor class of antidepressants includes citalopram, escitalopram (the active enantiomer of citalopram), fluoxetine, fluvoxamine, paroxetine, and sertraline. Both clomipramine (Anafranil is the common brand name) and fluoxetine (Prozac is the common brand name) are currently approved for the treatment of canine separation distress. This class of drugs are as effective as tricyclic antidepressants in treatment of major depression with less significant side effects. They are also used to treat obsessive-compulsive disorder, panic disorders, alcoholism, obesity, migraines, and chronic pain in human beings.
As with any medication, behavior modifying drugs contain potential side effects and toxicities. Clinical signs of selective serotonin reuptake inhibitor antidepressant medication toxicosis are the result of excessive amounts of serotonin in the central nervous system, termed serotonin syndrome. These signs include nausea, vomiting, mydriasis, hypersalivation, and hyperthermia. These clinical signs are dose dependent and higher dosages may result in the serotonin syndrome that manifests itself as ataxia, tremors, muscle rigidity, hyperthermia, diarrhea, and seizures.
Diagnosis of toxicosis is based on history, clinical signs, and response to therapy. No single clinical test is currently available to confirm toxicosis. The goals of treatment in this intoxication are to support the animal, prevent further absorption of the drug, support the central nervous system, control hyperthermia, and halt any seizure activity. The prognosis in animals that receive treatment for toxicosis is excellent. In one retrospective study, there were no deaths in 313 dogs experiencing toxicosis. Differential diagnoses for overdose or toxicosis includes ingestions of other serotonergic medications such as phenylpiperidine opioids (fentanyl and tramadol), mirtazapine, buspirone, amitraz, and chlorpheniramine.
Cannabidiol (CBD) treatment for canine anxiety
Overall, the medical research on the role cannabidiol (CBD) and related therapies currently play in treating and managing canine separation anxiety is still severely limited.
An informative 2019 veterinary research study regarding the collection of anecdotal veterinary use of CBD was performed. It was concluded in that study that CBD was most frequently discussed as a potential treatment for pain management, anxiety and seizures. The most commonly used CBD formulations were oil/extract and edibles. These were also stated to be the most helpful in providing analgesia for chronic and acute pain, relieving anxiety and decreasing seizure frequency/severity. The most commonly reported side-effect was sedation.
For pet owners, a 400 mg CBD hemp oil product by The Anxious Pet is available, used specifically for dogs weighing 15 pounds or less. For those dogs without known peanut allergies and who are not prone to pancreatitis, a 5 mg CBD chew is also available for those dogs suffering from anxiety. Simply follow the directions on the product!
At this time the ability to discuss and the quality of discussion with a veterinarian regarding the use of cannabidiol to treat or manage canine conditions varies widely state by state and individual by individual. Placing federal and state legal limitations aside, the safety margins and appropriate doings of cannabidiol still need to be determined.
Fortunately, a 2020 veterinary research study tested three cannabis oil formulations containing either cannabidiol, tetrahydrocannabinol (a crystalline compound that is the main active ingredient of cannabis), or a combination of the two in healthy dogs. These dogs were exposed to increasing doses of these products with the goal of establishing types and incidences of adverse events. In summary, the study showed that dose escalation of the cannabidiol-predominant oil formulation was shown to be as safe as the placebo and safer than dose escalation of oils containing tetrahydrocannabinol. Adverse events were reported in all dogs across the groups and 94.9% of these events were deemed mild.
Dogs are not the only species whom CBD has been studied in. A 2019 study published in the Animals Journal (Basel, Switzerland) studied the pharmacokinetics of a CBD-rich hemp nutraceutical in otherwise healthy dogs and casts. Eight of each species were provided a 2 mg/kg total CBD concentration orally twice daily for 12 weeks with vigorous blood panel screening and measurements. Cats do appear to absorb or eliminate CBD differently than dogs, showing lower serum concentrations and adverse effects of excessive licking and head-shaking during oil administration.
There are a number of older studies that have also evaluated various dosages, routes of administration, formulations, effects, and toxicoses of such products in the canine and feline population.
For more information regarding the most current, up-to-date statutes governing the prescribing, dispensing, and use of medical marijuana and CBD in animals, we urge you to visit the following sites:
- American Veterinary Medical Association (AVMA):
- Food & Drug Administration (FDA):
Certainly, there is more to learn about canine separation anxiety disorder and ways to treat it. Novel therapies are still being evaluated and we can anticipate more research in the future.
A 2017 veterinary research paper explains that the hormone oxytocin plays an important role in attachment formation and bonding between humans and domestic dogs. As such, intranasally administered oxytocin affects on social cognition and social bonding in dogs has been researched and could potentially be a treatment option of separation anxiety.
Likewise, future drugs targeting the vasopressinergic system may also offer treatment options for canine separation distress therapy.
Deabold KA, Schwark WS, Wolf L, Wakshlag JJ. Single-Dose Pharmacokinetics and Preliminary Safety Assessment with Use of CBD-Rich Hemp Nutraceutical in Healthy Dogs and Cats.Animals (Basel). 2019 Oct 19;9(10):832. PMID: 31635105
Fitzgerald KT, Bronstein AC. Selective serotonin reuptake inhibitor exposure. Top Companion Anim Med. 2013 Feb;28(1):13-7. PMID: 23796482
Kogan L, Schoenfeld-Tacher R, Hellyer P, Rishniw M. US Veterinarians' Knowledge, Experience, and Perception Regarding the Use of Cannabidiol for Canine Medical Conditions. Front Vet Sci. 2019 Jan 10;5:338. PMID: 30687726
Thielke LE, Udell MA. The role of oxytocin in relationships between dogs and humans and potential applications for the treatment of separation anxiety in dogs. Biol Rev Camb Philos Soc. 2017 Feb;92(1):378-388. PMID: 26548910
Pirrone F, Pierantoni L, Bossetti A, Uccheddu S, Albertini M. Salivary Vasopressin as A Potential Non-Invasive Biomarker of Anxiety in Dogs Diagnosed with Separation-Related Problems. Animals (Basel). 2019 Nov 26;9(12):1033. PMID: 31779267
Vaughn D, Kulpa J, Paulionis L. Preliminary Investigation of the Safety of Escalating Cannabinoid Doses in Healthy Dogs. Front Vet Sci. 2020 Feb 11;7:51. PMID: 32118071
About Dr. Shadi Ireifej:
Dr. Shadi Ireifej DVM DACVS is the Chief Medical Officer at VetTriage. He holds degrees from SUNY Binghamton and Cornell University and has practiced as a veterinary surgeon all across the United States. Follow him on Instagram @dr.shadi.ireifej and subscribe to his YouTube channel (Dr. Shadi Ireifej).
VetTriage is the world’s foremost provider of veterinary telehealth services. With VetTriage, pet owners have immediate access to triage advice from licensed veterinarians. Follow them on Instagram @vettriage and Facebook (facebook.com/televeterinarian).