By Brennen McKenzie, MA, MSc, VMD, cVMA

Pheromones are chemical compounds produced by an animal that have predictable physiologic and behavioral effects on other animals of the same species.¹ They are a form of social signaling that can influence behavior related to reproduction, aggression, feeding, social coordination, and many other areas.¹ The chemical nature and effects of specific pheromones have been well characterized in some species, particularly insects.² In other species, such as humans, there is great debate about whether pheromones exist or, if they do, how significant their effects may be.³

In small animal veterinary medicine, there has been considerable interest over the last couple of decades in the therapeutic use of pheromones.⁴ Several companies have produced products based on purported dog and cat pheromones and marketed them to address some behavioral problems, including various forms of fear and anxiety, aggression, stress-related illness, and undesirable urine marking, and destructive behaviors.

An evidence-based assessment of the potential therapeutic uses for dog and cat pheromones begins with characterizing the basic science and biologic plausibility of the claims, followed by an evaluation of the published research literature and its strengths and weaknesses. Given the marketing and widespread use of pheromone products, it might be assumed that there is a robust evidence base for the plausibility and clinical benefits of these products. However, as is often the case in veterinary medicine, the market is well ahead of the science, and there is surprisingly little data characterizing the composition, physiologic and behavioral effects, and clinical benefits of dog and cat pheromone products.

Pre-clinical research evidence

One challenge in evaluating most veterinary products, other than pharmaceuticals, is that there are no regulatory guidelines requiring manufacturers to generate and publish basic and clinical research evidence supporting the safety and efficacy of these products. It is often difficult to access and critically evaluate what evidence there is, which is often proprietary or unpublished.

For example, several of the most widely used pheromone products are marketed as containing dog appeasing pheromone (DAP), identified as "the synthetic equivalent of the pheromone secreted by bitches to reassure their pups on contact."⁵ Feline pheromones are identified as containing synthetic analogues of various feline pheromones, including the F3 fraction of the facial pheromone, cat appeasing pheromones (CAP) produced in the mammary region, and "feline interdigital semiochemical," produced on the feet.⁶

The exact composition of these cat and dog pheromones, and the composition of the analogues used in commercial products, is difficult to determine from published sources. There is virtually no published peer-reviewed research characterizing the discovery, composition, variability, and physiologic effects of dog and cat pheromones. It turns out that patents filed by some companies marketing pheromone products, or by some private researchers licensing their discoveries to such companies, make up most of the published information on the composition of the original pheromones and the associated synthetic analogues.^7-10

Unlike scientific research reports, there is little methodological information in these patent documents describing how these pheromones were discovered and characterized. Therefore, this evidence is difficult to evaluate.

The lack of peer-reviewed published data on the composition of dog and cat pheromones and how these vary with age, sex, breed, and many other potentially relevant factors, along with the proprietary nature of the composition and manufacture of most pheromone products, makes the biologic plausibility of these interventions impossible to fully assess. The general principle that mammalian pheromones can affect behavior is well supported by basic science. However, the claims made for the composition and actions of specific dog and cat pheromones, and their synthetic analogues, do not have robust preclinical research literature to support them.

Clinical research evidence

There is a moderate amount of published clinical research evidence concerning dog and cat pheromone products. A systematic review of clinical studies prior to 2010 has been conducted.¹¹ After eliminating studies that did not meet minimum quality criteria, the authors analyzed seven pheromone studies in dogs and seven in cats involving a variety of products and behavioral problems. None of the cat studies provided convincing evidence of a benefit; one study in dogs found some benefit in reducing anxiety in puppies during training.¹¹

Since this review was published, several additional clinical studies of pheromone products in dogs and cats have appeared. Each has its own strengths and limitations. Most evaluate numerous variables and find that only a few differ between treated animals and the control group. Strong, consistent evidence of clinically significant benefits has not been found, though some small positive effects are sometimes seen for some variables.

Siracusa (2010) - An evaluation of physiologic and behavioral markers of stress in 46 dogs undergoing elective surgery. Some effect of DAP on prolactin and a few behaviors, no effect on any other variables.¹²

Conti (2015) - An evaluation of physiologic and behavioral markers of stress in 30 cats examined at home and in the vet clinic. No effect of Feliway on measured variables.¹³

Landsberg (2015) - An evaluation of passive and active stress behaviors and hide box use in 24 lab beagles with thunderstorm phobia. No effect on passive anxiety, some effect on active anxiety, and some potentially paradoxical effect on hide box use that is difficult to interpret.¹⁴

Chadwin (2017) - An evaluation of behavioral markers of stress and occurrence of upper respiratory infections in several hundred shelter cats. No apparent effect of Feliway, though study was underpowered.¹⁵

Contrera (2017) - An evaluation of behavioral and physiologic markers of stress and clinical signs of FHV-1 resurgence in 12 5-month old kittens inoculated with FHV-1. No difference from placebo for most measures; possible decrease in sneezing and increase in sleeping
with Feliway.¹⁶

Conclusions

It is clear that pheromones play an important role in the regulation of mammalian behavior, so it is plausible that they might have therapeutic value in managing problematic or pathologic behaviors. However, there is little published preclinical evidence on the composition or effects of natural pheromones or synthetic analogues, and what is available comes from proprietary or commercial sources.

Results of clinical studies of these products are mixed. Consistent, replicable evidence of clinically significant effects is not available. No evidence of any harm from pheromone products has been published, and while adverse events seem unlikely, no study has been conducted specifically to look for them.

Available pheromone products are likely safe, but it is unclear what, if any, clinical benefits they may provide for any of the variety of indications for which they are commonly recommended.

References

1. Liberles SD. Mammalian Pheromones. Annual review of physiology. 2014;76:151-175.
2. Yew JY. Chung H. Insect pheromones: An overview of function, form, and discovery. Prog Lipid Res. 2015;59:88-105.
3. Wyatt TD. The search for human pheromones: the lost decades and the necessity of returning to first principles. Proc Biol Sci. 2015;282(1804):20142994.
4. Pageat, P. Gaultier E. Current research in canine and feline pheromones. Veterinary Clinics of North America: Small Anim Pract. 2003;33(2):187-211.
5. CEVA Santé Animale. Available at: https://www.ceva.com/Products/Companion-animals/Behaviour. Accessed on 12/27/2017.
6. CEVA Animal Health. Available at: https://www.feliway.com/us/FELIWAY/The-Science-Behind-Feliway. Accessed on 12/27/2017.
7. Pageat P. (1995) U.S. Patent No. 5709863 A. U.S. Patent and Trademark Office. Available at: https://www.google.com/patents/US5709863. Accessed on 12/27/2017.
8. Beck A. CEVA Santé Animale. (2015) European Patent No. EP2954886 A1. Available at: https://www.google.com/patents/EP2954886A1?cl=en. Accessed on 12/27/2017.
9. Nouvel L. McGlone J. Sargeant's Pet Care Products, Inc. (2014). U.S. Patent No. 8741965 B2. U.S. Patent and Trademark Office. Available at: https://www.google.com/patents/US8741965. Accessed on 12/27/2017.
10. Pageat P. Institut de Recherche en Semiochimie et Ethologie Appliquee. (2014) Patent No. WO2014001836 A1. Available at: https://www.google.com/patents/WO2014001836A1?cl=en. Accessed on 12/28/2017.
11. Frank D. Beauchamp G. Palestrini C. Systematic review of the use of pheromones for treatment of undesirable behavior in cats and dogs. J Am Vet Med Assoc. 2010;36(12):1308-1316.
12. Siracusa C, Manteca X, Cuenca R, del Mar Alcala M, Alba A, et al. Effect of a synthetic appeasing pheromone on behavioral, neuroendocrine, immune, and acute-phase perioperative stress response in dogs. J Am Vet Med Assoc. 2010;237(6):p. 673-81.
13. Conti, LMC. Champion, T. Guberman, UC. et al. Evaluation of environment and a feline facial pheromone analogue on physiologic and behavioral measures in cats. J of Feline Med and Surg. 2015;19(2):165-70.
14. Chadwin RM. Bain MJ. Kass PH. Effect of a synthetic feline facial pheromone product on stress scores and incidence of upper respiratory tract infection in shelter cats. J Am Vet Med Assoc. 2017 Aug 15;251(4):413-420.
15. Landsberg GM. Beck A. Lopez A. et al. Dog-appeasing pheromone collars reduce sound-induced fear and anxiety in beagle dogs: a placebo-controlled study. Vet Rec. 2015 Sep 12;177(10):260.
16. Contreras ET. Hodgkins E. Tynes V. et al. Effect of a pheromone on stress-associated reactivation of feline herpesvirus-1 in experimentally inoculated kittens. J Vet Intern Med. 2017 Dec 8. 

Dr. McKenzie discovered evidence-based veterinary medicine after attending the University of Pennsylvania School of Veterinary Medicine and working as a small animal general practice veterinarian. He has served as president of the Evidence-Based Veterinary Medicine Association and reaches out to the public through his SkeptVet blog, the Science-Based Medicine blog, and more. He is certified in medical acupuncture for veterinarians. Columnists' opinions do not necessarily reflect those of Veterinary Practice News.