What αs1-casozepine is
αs1-casozepine is a decapeptide — ten amino acids — released when the casein protein in cow's milk is hydrolysed (broken down). It was discovered through a observation every parent knows: milk has a calming effect on nursing infants. Researchers traced part of that effect to this peptide fragment, which binds to the same brain receptor site that anti-anxiety medicines target — the benzodiazepine site on the GABA-A receptor — but far more gently, and without sedation at studied doses.[1]
It is best known by the supplement brand Zylkene, sitting in a useful regulatory niche: a nutraceutical (food-derived) with an actual clinical trial record — a combination almost no other calming supplement can claim.
The dog trials: from anxiety disorders to the vet's table
The landmark dog study dates to 2007: Beata and colleagues ran a controlled trial in dogs diagnosed with anxiety disorders, comparing αs1-casozepine against selegiline — a licensed veterinary anxiolytic drug. Over 56 days, both groups improved meaningfully on anxiety scores, with the peptide showing comparable benefit and an excellent tolerability profile.[1] A supplement matching a registered drug's effect size is rare enough to be worth remembering.
More recent work has focused on a stressor every owner recognizes: the vet visit. In a 2024 randomized placebo-controlled trial published in The Veterinary Journal, Schroers and colleagues gave dogs αs1-casozepine before a veterinary examination and measured stress responses; treated dogs showed reduced signs of stress compared with placebo.[2]
What this means for your dog
If your dog shakes through fireworks season, dreads the vet or unravels when you leave, αs1-casozepine is one of the few calming supplements with placebo-controlled trials behind it — non-sedating and gentle enough for daily use. It is a support tool, not a behavioural cure: pair it with desensitization training, and for severe anxiety (self-injury, destruction, panic) see a vet behaviourist, because prescription options exist and work.
The cat trials: placebo-controlled, stress-hormone measured
Cats actually carry the strongest casozepine record. In a 2020 randomized, placebo-controlled study of 60 cats, Makawey and colleagues tested two dosing schedules around real veterinary checkups, measuring both observed stress signs and faecal cortisol metabolites — an objective, non-invasive readout of stress-hormone activity. Cats on the higher dose (75 mg/kg for three days) showed a significant reduction in stress-linked sweaty paws at the clinic, with a modest downward trend in cortisol metabolites.[3]
Earlier, Landsberg and colleagues tested a therapeutic diet supplemented with αs1-casozepine and L-tryptophan in anxious cats, finding improved fear and anxiety scores on standardized behavioural tests versus control.[4] Across species and study designs, the pattern is consistent: modest, real, non-sedating calming — strongest for situational stress.
Using it sensibly: timing, expectations, limits
The trial protocols teach the practical lesson: αs1-casozepine works best started before the stressor — days ahead for a known event (vet visit, travel, fireworks night), or daily for ongoing generalized anxiety, with effects typically building over the first one to two weeks. It does not sedate, so it will not knock out a panicking dog at 9pm on New Year's Eve; it lowers the background volume so training and coping have a chance.
Know the limits: severe noise phobia and separation anxiety are medical-grade behavioural conditions. A supplement can be one leg of the plan — alongside desensitization, management and, when a vet behaviourist advises it, prescription medication. Red flags for professional help: self-injury, property destruction, escape attempts, or anxiety that is getting worse.
How it compares to selank-type peptides in development
Beyond casozepine sit the "designer" calming peptides — selank being the most discussed. Selank is a synthetic heptapeptide (a tuftsin analog) developed in Russia as an anxiolytic, with small human studies abroad suggesting anti-anxiety and nootropic effects. What it does not have is what casozepine has: placebo-controlled trials in dogs and cats. For pets, selank-type compounds remain investigational — no veterinary pharmacokinetics, no efficacy trials, no established dosing.
That gap is exactly why the PSA PETS Calm formula is in development rather than on the shelf: the mechanism is promising, the pet evidence is not there yet, and we would rather launch late with data than early with adjectives. When it arrives, it will carry the same honesty label as everything else we make.
What this means for South African pet owners
South African dogs face a uniquely noisy calendar: Guy Fawkes, New Year's Eve, summer Highveld thunderstorms, and — for rescue dogs in particular — histories that make every bang a memory. Behavioural euthanasia and shelter surrenders spike around fireworks season; this is not a trivial market.
The practical local advice: start situational calming support at least a few days before known events, build a safe den space, and talk to your vet early — not on the night itself. Our calming formula is in development; αs1-casozepine-class products are the evidence benchmark we hold it to, and the waitlist hears launch news first.
Honest answers.
What is αs1-casozepine and how does it calm dogs?
It is a ten-amino-acid peptide from hydrolysed milk casein that binds gently to the benzodiazepine site on the GABA-A receptor — the same calming pathway targeted by anti-anxiety medicines, but without sedation at studied doses. It is best known from the supplement Zylkene.
Does αs1-casozepine actually work? What trials exist?
It has placebo-controlled trials in both species: dogs with anxiety disorders improved comparably to the licensed drug selegiline over 56 days (Beata 2007); a 2024 randomized placebo-controlled trial showed reduced stress during veterinary examinations; and in cats, a 60-animal placebo-controlled study found reduced stress signs and a cortisol trend around vet visits (Makawey 2020).
Will it sedate my dog?
No — that is the point. Trials show calming without sedation at studied doses, which makes it suitable before vet visits, travel and fireworks, and for daily use. It lowers baseline arousal rather than knocking the animal out.
How far in advance should I start it before fireworks?
Trial protocols dosed for days before the stressor — start at least 2–3 days ahead of a known event, longer for ongoing anxiety. Combine it with management (safe den, curtains, white noise) and, for severe phobia, a vet behaviour plan.
Is selank proven for anxious dogs?
No. Selank is an investigational synthetic peptide with no placebo-controlled trials in dogs or cats, no veterinary dosing data and no regulatory approval. It should be considered experimental — which is why our own calming formula remains in development with an honesty label attached.
When is anxiety a vet problem rather than a supplement problem?
When there is self-injury, destruction, escape behaviour, house-soiling panic, or worsening fear — or any time anxiety is costing your dog quality of life. Vet behaviourists have effective prescription options; supplements are the gentle first rung, not the whole ladder.
References
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[1]
Beata C, Beaumont-Graff E, Coll V, et al.. “Effects of alpha-casozepine (Zylkene) versus selegiline hydrochloride (Selgian, Anipryl) on anxiety disorders in dogs.” Journal of Veterinary Behavior, 2007.
https://doi.org/10.1016/j.jveb.2007.08.001 -
[2]
Schroers M, et al.. “Effect of casozepine administration on stress in dogs during a veterinary examination — a randomized placebo-controlled trial.” The Veterinary Journal, 2024.
https://pubmed.ncbi.nlm.nih.gov/38838768/ -
[3]
Makawey A, Iben C, Palme R. “Cats at the Vet: The Effect of Alpha-s1 Casozepin.” Animals, 2020.
https://pubmed.ncbi.nlm.nih.gov/33167443/ -
[4]
Landsberg GM, Milgram B, de Rivera C, et al.. “Therapeutic effects of an alpha-casozepine and L-tryptophan supplemented diet on fear and anxiety in the cat.” Journal of Feline Medicine and Surgery, 2017.
https://pubmed.ncbi.nlm.nih.gov/27677831/